Shen W-K, et al.2017 ACC/AHA/HRS Syncope Guideline 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society Developed in Collaboration With the American College of Emergency Physicians and Society for Academic Emergency Medicine Endorsed by the Pediatric and Congenital Electrophysiology Society WRITING COMMITTEE MEMBERS* Win-Kuang Shen, MD, FACC, FAHA, FHRS, Chair† Downloaded from http://circ.ahajournals.org/ by guest on November 16, 2017 Robert S. Sheldon, MD, PhD, FHRS, Vice Chair David G. Benditt, MD, FACC, FHRS*‡ Mark S. Link, MD, FACC‡ Mitchell I. Cohen, MD, FACC, FHRS‡ Brian Olshansky, MD, FACC, FAHA, FHRS*‡ Daniel E. Forman, MD, FACC, FAHA‡ Satish R. Raj, MD, MSc, FACC, FHRS*§ Zachary D. Goldberger, MD, MS, FACC, FAHA, FHRS‡ Roopinder Kaur Sandhu, MD, MPH‡ Blair P. Grubb, MD, FACC§ Dan Sorajja, MD‡ Mohamed H. Hamdan, MD, MBA, FACC, FHRS*‡ Benjamin C. Sun, MD, MPP, FACEP║ Andrew D. Krahn, MD, FHRS*§ Clyde W. Yancy, MD, MSc, FACC, FAHA‡¶ ACC/AHA TASK FORCE MEMBERS Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, FACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair# Sana M. Al-Khatib, MD, MHS, FACC, FAHA Federico Gentile, MD, FACC Kim K. Birtcher, MS, PharmD, AACC Samuel Gidding, MD, FAHA Biykem Bozkurt, MD, PhD, FACC, FAHA Mark A. Hlatky, MD, FACC Ralph G. Brindis, MD, MPH, MACC# John Ikonomidis, MD, PhD, FAHA Joaquin E. Cigarroa, MD, FACC José Joglar, MD, FACC, FAHA Lesley H. Curtis, PhD, FAHA Susan J. Pressler, PhD, RN, FAHA Lee A. Fleisher, MD, FACC, FAHA Duminda N. Wijeysundera, MD, PhD *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. †ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ‡ACC/AHA Representative. §HRS Representative. ║ACEP and SAEM Joint Representative. ¶ACC/AHA Task Force on Performance Measures Liaison. #Former Task Force member; current member during the writing effort. This document was approved by the American College of Cardiology Clinical Policy Approval Committee on behalf of the Board of Trustees, the American Heart Association Science Advisory and Coordinating Committee, the American Heart Association Executive Committee, and the Heart Rhythm Society Board of Trustees in January 2017. The online Comprehensive RWI Data Supplement table is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000499/-/DC1. The online Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000499/-/DC2. © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society 1 Shen W-K, et al. 2017 ACC/AHA/HRS Syncope Guideline The American Heart Association requests that this document be cited as follows: Shen W-K, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD, Grubb BP, Hamdan MH, Krahn AD, Link MS, Olshansky B, Raj SR, Sandhu RK, Sorajja D, Sun BC, Yancy CW. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. Circulation. 2017;:–. DOI: 10.1161/CIR.0000000000000499. This article has been copublished in the Journal of the American College of Cardiology and Heart Rhythm. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org), the American Heart Association (professional.heart.org), and the Heart Rhythm Society (www.hrsonline.org). A copy of the document is available at http://professional.heart.org/statements by using either “Search for Guidelines & Statements” or the “Browse by Topic” area. To purchase additional reprints, call 843-216-2533 or e-mail
[email protected]. Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements. Select the “Guidelines & Statements” drop-down menu, then click “Publication Development.” Downloaded from http://circ.ahajournals.org/ by guest on November 16, 2017 Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright-Permission-Guidelines_UCM_300404_Article.jsp. A link to the “Copyright Permissions Request Form” appears on the right side of the page. (Circulation. 2017;000:e000–e000. DOI: 10.1161/CIR.0000000000000499.) © 2017 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Rhythm Society. Circulation is available at http://circ.ahajournals.org © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society 2 Shen W-K, et al. 2017 ACC/AHA/HRS Syncope Guideline Table of Contents Preamble .................................................................................................................................................................. 5 1. Introduction......................................................................................................................................................... 8 1.1. Methodology and Evidence Review ......................................................................................................... 8 1.2. Organization of the Writing Committee ................................................................................................... 8 1.3. Document Review and Approval .............................................................................................................. 8 1.4. Scope of the Guideline.............................................................................................................................. 9 2. General Principles ............................................................................................................................................. 11 2.1. Definitions: Terms and Classification .................................................................................................... 11 2.2. Epidemiology and Demographics ........................................................................................................... 12 2.3. Initial Evaluation of Patients With Syncope ........................................................................................... 13 History and Physical Examination: Recommendation....................................................................... 14 Electrocardiography: Recommendation............................................................................................. 15 Risk Assessment: Recommendations................................................................................................. 16 Downloaded from http://circ.ahajournals.org/ by guest on November 16, 2017 Disposition After Initial Evaluation: Recommendations ................................................................... 19 3. Additional Evaluation and Diagnosis ............................................................................................................... 21 3.1. Blood Testing: Recommendations .......................................................................................................... 22 3.2. Cardiovascular Testing ........................................................................................................................... 23 Cardiac Imaging: Recommendations ................................................................................................. 24 Stress Testing: Recommendation ....................................................................................................... 25 Cardiac Monitoring: Recommendations ............................................................................................ 25 In-Hospital Telemetry: Recommendation.......................................................................................... 28 Electrophysiological Study: Recommendations ................................................................................ 29 Tilt-Table Testing: Recommendations .............................................................................................. 30 3.3. Neurological Testing............................................................................................................................... 32 Autonomic Evaluation: Recommendation ......................................................................................... 32 Neurological and Imaging Diagnostics: Recommendations .............................................................. 33 4. Management of Cardiovascular Conditions...................................................................................................... 34 4.1. Arrhythmic Conditions ........................................................................................................................... 34 Bradycardia: Recommendation.......................................................................................................... 35 Supraventricular Tachycardia: Recommendation .............................................................................. 35 Ventricular Arrhythmia: Recommendation ....................................................................................... 36 4.2. Structural Conditions .............................................................................................................................. 36 Ischemic and Nonischemic Cardiomyopathy: Recommendation ...................................................... 37 Valvular Heart Disease: Recommendation ........................................................................................ 37 Hypertrophic Cardiomyopathy: Recommendation ............................................................................ 37 Arrhythmogenic Right Ventricular Cardiomyopathy: Recommendation .......................................... 38 Cardiac Sarcoidosis: Recommendations ............................................................................................ 38 4.3. Inheritable Arrhythmic Conditions ......................................................................................................... 39 Brugada Syndrome: Recommendations ............................................................................................. 39 Short-QT Syndrome: Recommendation............................................................................................. 40 Long-QT Syndrome: Recommendations ........................................................................................... 41 Catecholaminergic Polymorphic Ventricular Tachycardia: Recommendations ................................ 42 Early Repolarization Pattern: Recommendations .............................................................................. 43 5. Reflex Conditions ............................................................................................................................................. 44 5.1. Vasovagal Syncope: Recommendations ................................................................................................. 44 5.2. Pacemakers in Vasovagal Syncope: Recommendation .......................................................................... 46 5.3. Carotid Sinus Syndrome: Recommendations ......................................................................................... 47 5.4. Other Reflex Conditions ......................................................................................................................... 48 6. Orthostatic Hypotension ................................................................................................................................... 48 6.1. Neurogenic Orthostatic Hypotension: Recommendations ...................................................................... 48 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society 3 Shen W-K, et al. 2017 ACC/AHA/HRS Syncope Guideline 6.2. Dehydration and Drugs: Recommendations ........................................................................................... 50 7. Orthostatic Intolerance...................................................................................................................................... 52 8. Pseudosyncope: Recommendations .................................................................................................................. 53 9. Uncommon Conditions Associated With Syncope ........................................................................................... 54 10. Age, Lifestyle, and Special Populations.......................................................................................................... 56 10.1. Pediatric Syncope: Recommendations.................................................................................................... 56 10.2. Adult Congenital Heart Disease: Recommendations .............................................................................. 59 10.3. Geriatric Patients: Recommendations ..................................................................................................... 60 10.4. Driving and Syncope: Recommendation ................................................................................................ 61 10.5. Athletes: Recommendations ................................................................................................................... 63 11. Quality of Life and Healthcare Cost of Syncope ............................................................................................ 65 11.1. Impact of Syncope on Quality of Life .................................................................................................... 65 11.2. Healthcare Costs Associated With Syncope ........................................................................................... 65 12. Emerging Technology, Evidence Gaps, and Future Directions ...................................................................... 66 12.1. Definition, Classification, and Epidemiology ......................................................................................... 66 12.2. Risk Stratification and Clinical Outcomes.............................................................................................. 66 Downloaded from http://circ.ahajournals.org/ by guest on November 16, 2017 12.3. Evaluation and Diagnosis ....................................................................................................................... 67 12.4. Management of Specific Conditions....................................................................................................... 67 12.5. Special Populations ................................................................................................................................. 68 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) ................................................. 70 Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive)................................... 74 Appendix 3. Abbreviations .................................................................................................................................... 81 References.............................................................................................................................................................. 82 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society 4 Shen W-K, et al. 2017 ACC/AHA/HRS Syncope Guideline Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a cornerstone for quality cardiovascular care. The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each organization volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA. Intended Use Practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but guidelines developed in collaboration with other organizations may have a global impact. Although guidelines may be used to inform regulatory or payer decisions, their intent is to improve patients’ quality of care and align with patients’ interests. Guidelines are Downloaded from http://circ.ahajournals.org/ by guest on November 16, 2017 intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment. Clinical Implementation Guideline recommended management is effective only when followed by healthcare providers and patients. Adherence to recommendations can be enhanced by shared decision making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities. Methodology and Modernization The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations including the Institute of Medicine (1,2) and on the basis of internal reevaluation. Similarly, the presentation and delivery of guidelines are reevaluated and modified on the basis of evolving technologies and other factors to facilitate optimal dissemination of information at the point of care to healthcare professionals. Given time constraints of busy healthcare providers and the need to limit text, the current guideline format delineates that each recommendation be supported by limited text (ideally, <250 words) and hyperlinks to supportive evidence summary tables. Ongoing efforts to further limit text are underway. Recognizing the importance of cost–value considerations in certain guidelines, when appropriate and feasible, an analysis of the value of a drug, device, or intervention may be performed in accordance with the ACC/AHA methodology (3). To ensure that guideline recommendations remain current, new data are reviewed on an ongoing basis, with full guideline revisions commissioned in approximately 6-year cycles. Publication of new, potentially practice-changing study results that are relevant to an existing or new drug, device, or management strategy will prompt evaluation by the Task Force, in consultation with the relevant guideline writing committee, to determine whether a focused update should be commissioned. For additional information and policies regarding guideline development, we encourage readers to consult the ACC/AHA guideline methodology manual (4) and other methodology articles (5-8). Selection of Writing Committee Members The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds. Writing committee members represent different geographic regions, sexes, ethnicities, races, intellectual perspectives/biases, and © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society 5 Inc. 2017 When developing recommendations. An independent evidence review committee (ERC) is commissioned when there are 1 or more questions deemed of utmost clinical importance that merit formal systematic review. MD. and biostatisticians. The recommendations are limited to drugs. c) the relevance to a substantial number of patients. The Level of Evidence (LOE) rates the quality of scientific evidence that supports the intervention on the basis of the type. Appendix 1 of the current document lists writing committee members’ relevant RWI.acc. the writing committee uses evidence-based methodologies that are based on all available data (4-7). diagnostic testing. Only key references are cited. or endorsers.acc. Literature searches focus on randomized controlled trials (RCTs) but also include registries.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy. The Task Force may also invite organizations and professional societies with related interests and expertise to participate as partners. and pharmacological and procedural treatments. devices. Glenn N. ERC members may include methodologists. healthcare providers. Class of Recommendation and Level of Evidence The Class of Recommendation (COR) indicates the strength of the recommendation. quantity.org/guidelines/about-guidelines-and- clinical-documents/guidelines-and-documents-task-forces. The recommendations developed by the writing committee on the basis of the systematic review are marked with “SR”. et al.ahajournals. encompassing the estimated magnitude and certainty of benefit in proportion to risk. cohort studies.0000000000000499/-/DC1). For the purposes of full transparency.org/lookup/suppl/doi:10. This systematic review will determine which patients are most likely to benefit from a drug. American Heart Association. Evidence Review and Evidence Review Committees Downloaded from http://circ. Criteria for commissioning an ERC and formal systematic review include: a) the absence of a current authoritative systematic review. case series.org/ by guest on November 16. collaborators. and treatments approved for clinical use in the United States. ACC/AHA Task Force on Clinical Practice Guidelines © 2017 by the American College of Cardiology Foundation. nonrandomized comparative and descriptive studies. and Heart Rhythm Society 6 . and consistency of data from clinical trials and other sources (Table 1) (4-6). b) the feasibility of defining the benefit and risk in a time frame consistent with the writing of a guideline. or treatment strategy and to what degree. Guideline-Directed Management and Therapy The term guideline-directed management and therapy (GDMT) encompasses clinical evaluation. device. systematic reviews. epidemiologists. and d) the likelihood that the findings can be translated into actionable recommendations.ahajournals. Relationships With Industry and Other Entities The ACC and AHA have rigorous policies and methods to ensure that guidelines are developed without bias or improper influence. writing committee members’ comprehensive disclosure information is available online (http://circ.1161/CIR. FACC. FAHA Chair.. 2017 ACC/AHA/HRS Syncope Guideline scopes of clinical practice. and expert opinion. The complete relationships with industry and other entities (RWI) policy can be found at http://www. Levine. For these and all recommended drug treatment regimens. Shen W-K. the reader should confirm the dosage by reviewing product insert material and evaluate the treatment regimen for contraindications and interactions. Comprehensive disclosure information for the Task Force is available at http://www. 2017 © 2017 by the American College of Cardiology Foundation. Inc. and Heart Rhythm Society 7 . Shen W-K. American Heart Association. et al.. 2017 ACC/AHA/HRS Syncope Guideline Table 1. Interventions.ahajournals. Applying Class of Recommendation and Level of Evidence to Clinical Strategies. or Diagnostic Testing in Patient Care* (Updated August 2015) Downloaded from http://circ. Treatments.org/ by guest on November 16. published in English. The finalized evidence tables. Inc. tilt-table test. risk stratification. AHA. electrophysiologists. An independent ERC was commissioned to perform a systematic review of clinical questions. 1. orthostatic hypotension. summarize the evidence used by the writing committee to formulate recommendations. American College of Emergency Physicians. the writing committee reviewed documents related to syncope previously published by the ACC and AHA and other organizations and societies. dehydration. the Agency for Healthcare Research and Quality. Lastly. were also considered by the writing committee and added to the evidence tables when appropriate. Additional relevant studies published through October 2016. An initial extensive evidence review. implantable loop recorder. carotid sinus hypersensitivity. and ventricular arrhythmia. Organization of the Writing Committee The writing committee was composed of clinicians with expertise in caring for patients with syncope. American College of Emergency Physicians and Society for © 2017 by the American College of Cardiology Foundation. EMBASE.org/ by guest on November 16. was conducted from July to October 2015. death. falls. during the guideline writing process. a neurologist. syncope.ahajournals. electrophysiological study. 2017 ACC/AHA/HRS Syncope Guideline 1.. or Carotid Sinus Hypersensitivity) Syncope” is published in conjunction with this guideline (9). evidence based. psychogenic pseudosyncope. and Society for Academic Emergency Medicine. older populations. and indexed in MEDLINE (through PubMed). et al. 1. which included literature derived from research involving human subjects. electrocardiogram. syncope unit. The writing committee included representatives from the ACC.3. Introduction 1. 1 reviewer each from the American Academy of Neurology. autonomic neuropathy. epidemiology.1161/CIR. and other selected databases relevant to this guideline. supraventricular tachycardia.ahajournals. 2017 diagnosis. Downloaded from http://circ.org/lookup/suppl/doi:10. recurrent syncope. American Heart Association. References selected and published in this document are representative and not all inclusive. carotid sinus syndrome. Shen W-K. Document Review and Approval This document was reviewed by 2 official reviewers each nominated by the ACC. driving.1. vasovagal syncope. and a pediatric cardiologist. bradycardia. children. Situational. Key search words included but were not limited to the following: athletes.2. Heart Rhythm Society (HRS). and Heart Rhythm Society 8 . AHA. and HRS. mortality. pediatrics. included in the Online Data Supplement (http://circ. the results of which were considered by the writing committee for incorporation into this guideline. Methodology and Evidence Review The recommendations listed in this guideline are. American Academy of Neurology. The systematic review report “Pacing as a Treatment for Reflex-Mediated (Vasovagal. the Cochrane Library. including cardiologists. an emergency physician. whenever possible.0000000000000499/-/DC2). which is often required during the evaluation and management of patients with syncope. sports medicine specialists. adult congenital heart disease (ACHD). such as syncope management units. It is not a review of physiology. the relevant age is noted in those specific cases. Inc. The definition of older populations has been evolving. in different populations and circumstances. a lay/patient representative. geriatric specialists. and Pediatric and Congenital Electrophysiology Society. with different causes. or mechanisms of underlying conditions associated with syncope. the writing committee agreed to make Class IIa recommendations because of the paucity of outcome data. Scope of the Guideline The purpose of this ACC/AHA/HRS guideline is to provide contemporary. this document discusses risk stratification and prevention of SCD when appropriate. the guideline addresses the management of syncope with the patient as a focus. In developing this guideline. pathophysiology. unless otherwise specified. The goals of the present guideline are: • To define syncope as a symptom. rather than larger aspects of health services. neurologists. arrhythmia specialists. AHA. • To identify key areas in which knowledge is lacking. and 25 individual content reviewers.org/ by guest on November 16. and HRS and was endorsed by the Pediatric and Congenital Electrophysiology Society. thus obviating the need to repeat existing guideline © 2017 by the American College of Cardiology Foundation. This guideline is intended to be a practical document for cardiologists. This document was approved for publication by the governing bodies of the ACC. and Heart Rhythm Society 9 . Age >75 years is used to define older populations or older adults in this document. we have addressed the involvement of syncope only as a presenting symptom. or selected circumstances. specific causes. and other healthcare professionals involved in the care Downloaded from http://circ.. et al. 2017 ACC/AHA/HRS Syncope Guideline Academic Emergency Medicine. Because of the plausible association of syncope and sudden cardiac death (SCD) in selected populations. to foster future collaborative research opportunities and efforts. or athletes. The nature of syncope as a symptom required that the writing committee consider numerous conditions for which it can be a symptom.ahajournals. Shen W-K. and succinct guidance on the management of adult and pediatric patients with suspected syncope. 2017 of this very large and heterogeneous population.4. and as much as possible. Finally. The use of the terms selected populations and selected patients in this document is intended to direct healthcare providers to exercise clinical judgment. accessible. older populations. Reviewers’ RWI information was distributed to the writing committee and is published in this document (Appendix 2). general internists. 1. If a study has defined older adults by a different age cutoff. emergency physicians. • To provide guidance and recommendations on the evaluation and management of patients with suspected syncope in the context of different clinical settings. When a recommendation is made to refer a patient to a specialist with expertise for further evaluation. such as in the case of autonomic neurology. American Heart Association. the writing committee reviewed the evidence to support recommendations in the relevant ACC/AHA guidelines noted in Table 2 and affirms the ongoing validity of the related recommendations in the context of syncope. ahajournals. EHRA. Relevant ACC/AHA Guidelines Publication Year Title Organization (Reference) ACC/AHA guideline policy relevant to the management of syncope Supraventricular tachycardia ACC/AHA/HRS 2015 (10) Valvular heart disease AHA/ACC 2014 (11) Device-based therapies for cardiac rhythm abnormalities ACCF/AHA/HRS 2012 (12) Ventricular arrhythmias and sudden cardiac death ACC/AHA/ESC 2006 (13)* Other ACC/AHA guidelines of interest Hypertension* ACC/AHA --- Stable ischemic heart disease ACC/AHA/ACP/ 2012 and 2014 AATS/PCNA/SCAI/STS (14. European Society of Cardiology.26) Expert consensus statement on the recognition and PACES/HRS 2014 (27) management of arrhythmias in adult congenital heart disease Expert consensus statement on the use of implantable HRS/ACC/AHA 2014 (28) cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials Expert consensus statement on ventricular arrhythmias EHRA/HRS/APHRS 2014 (29) Expert consensus statement on the diagnosis and HRS/EHRA/APHRS 2013 (25) management of patients with inherited primary arrhythmia syndromes Guidelines for the diagnosis and management of syncope ESC 2009 (30) *Revisions to the current documents are being prepared. Heart Rhythm Society.15) Downloaded from http://circ. American Heart Association.. 2017 Atrial fibrillation AHA/ACC/HRS 2014 (16) Non–ST-elevation acute coronary syndromes AHA/ACC 2014 (17) Assessment of cardiovascular risk ACC/AHA 2013 (18) Heart failure ACC/AHA 2013 (19)* Hypertrophic cardiomyopathy ACC/AHA 2011 (20) Assessment of cardiovascular risk in asymptomatic adults ACC/AHA 2010 (21) Adult congenital heart disease ACC/AHA 2008 (22)* Other related references Scientific statement on electrocardiographic early AHA 2016 (23) repolarization Expert consensus statement on the diagnosis and treatment HRS 2015 (24) of postural tachycardia syndrome. Preventive Cardiovascular Nurses Association. American College of Physicians. and vasovagal syncope Guidelines for the management of patients with ventricular ESC 2015 and 2013 arrhythmias and the prevention of sudden cardiac death (25. ACCF. SCAI. Table 2. AATS indicates American Association for Thoracic Surgery. with publication expected in 2017. HRS. Pediatric and Congenital Electrophysiology Society. ESC. Society for Cardiovascular Angiography and Interventions. inappropriate sinus tachycardia. Inc. American College of Cardiology Foundation. et al. and Heart Rhythm Society 10 . 2017 ACC/AHA/HRS Syncope Guideline recommendations in the present guideline when applicable or when appropriate. AHA. European Heart Rhythm Association.org/ by guest on November 16. ACC. Table 2 also contains a list of other statements that may be of interest to the reader. © 2017 by the American College of Cardiology Foundation. and STS. Society of Thoracic Surgery. APHRS. ACP. American College of Cardiology. PCNA. American Heart Association. PACES. Shen W-K. Asia Pacific Heart Rhythm Society. e.30). The presumed mechanism is cerebral hypoperfusion (24. palpitations.. generalized weakness. Neurogenic OH is due to lesions involving the central or peripheral autonomic nerves..36). tremulousness. syncope Noncardiac syncope Syncope due to noncardiac causes which include reflex syncope. exercise intolerance. or persistent lightheadedness. 2017 Transient loss of Self-limited loss of consciousness (30) can be divided into syncope and nonsyncope consciousness conditions. pseudosyncope) (24. or acute vascular dissection (35. recurrent. antecedent head trauma. • Delayed OH A sustained reduction of systolic BP of ≥20 mm Hg (or 30 mm Hg in patients with supine hypertension) or diastolic BP of ≥10 mm Hg that takes >3 min of upright posture to develop. such as “tunnel vision” or “graying out”. with presyncope or syncope (31. Individuals with orthostatic intolerance have ≥1 of these symptoms associated with reduced ability to maintain upright posture.34). and fatigue upon standing. and variable degrees of altered consciousness without complete loss of consciousness. or it could abort without syncope. The initial evaluation includes but is undetermined etiology) not limited to a thorough history. transient.ahajournals. OH • Classic OH A sustained reduction of systolic BP of ≥20 mm Hg or diastolic BP of ≥10 mm Hg within 3 min of assuming upright posture (31). Unexplained syncope Syncope for which a cause is undetermined after an initial evaluation that is deemed (syncope of appropriate by the experienced healthcare provider. whereas nonsyncope conditions are attributed to different mechanisms.. volume depletion. Table 3.1. Downloaded from http://circ. associated with inability to maintain postural tone. OH. Presyncope The symptoms before syncope. and ECG. These symptoms could include extreme lightheadedness. The fall in BP is usually gradual until reaching the threshold (31). • Initial (immediate) A transient BP decrease within 15 s after standing. or hypotension due to low cardiac index.30). There should not be clinical features of other nonsyncope causes of loss of consciousness. physical examination. and concussion due to head trauma. (cardiovascular) blood flow obstruction. metabolic conditions. Cardiac Syncope caused by bradycardia. Orthostatic A drop in systolic BP of ≥20 mm Hg or diastolic BP of ≥10 mm Hg with assumption of an hypotension (OH) upright posture (31). with rapid and spontaneous recovery. definitions of syncope and relevant terms are provided in Table 3.30.org/ by guest on November 16. American Heart Association. OH. and blood loss (35).32). or apparent loss of consciousness (i. Definitions: Terms and Classification For the purpose of this guideline. Relevant Terms and Definitions* Term Definition/Comments and References Syncope A symptom that presents with an abrupt. vasodilatation. Presyncope could progress to syncope. Loss of consciousness A cognitive state in which one lacks awareness of oneself and one’s situation. or syncope (24). (near-syncope) visual sensations. Orthostatic A sustained increase in heart rate of ≥30 bpm within 10 min of moving from a recumbent tachycardia to a quiet (nonexertional) standing position (or ≥40 bpm in individuals 12–19 y of age) (24. Nonsyncope conditions include but are not limited to seizures. • Neurogenic OH A subtype of OH that is due to dysfunction of the autonomic nervous system and not solely due to environmental triggers (e. such as seizure. hypoglycemia. Orthostatic intolerance A syndrome consisting of a constellation of symptoms that include frequent. with an inability to respond to stimuli. drug or alcohol intoxication. © 2017 by the American College of Cardiology Foundation. The underlying mechanism of syncope is presumed to be cerebral hypoperfusion. 2017 ACC/AHA/HRS Syncope Guideline 2. Inc.g. General Principles 2. blurred vision. Shen W-K. dehydration or drugs) (33. dehydration. tachycardia. and Heart Rhythm Society 11 . These symptoms can occur with or without orthostatic tachycardia.31). complete loss of consciousness. et al. such as coughing. In a cross section of 1. Studies of syncope report prevalence rates as high as 41%.. 364 reported an episode of syncope in their lifetime. 2017 ACC/AHA/HRS Syncope Guideline Reflex (neurally Syncope due to a reflex that causes vasodilation. lightheadedness.. orthostatic hypotension. Carotid sinus syndrome hypersensitivity is present when a pause ≥3 s and/or a decrease of systolic pressure ≥50 mm Hg occurs upon stimulation of the carotid sinus. and 4) is often followed by fatigue. generalized (POTS) weakness. VVS is often preceded by identifiable triggers and/or by a characteristic prodrome. guidelines. and pallor. diarrhea. 60. exercise intolerance. The incidence follows a trimodal distribution in both sexes. electrocardiogram. mediated) syncope • Vasovagal syncope The most common form of reflex syncope mediated by the vasovagal reflex. observers. pain.. or metabolic causes (30). Psychogenic A syndrome of apparent but not true loss of consciousness that may occur in the absence pseudosyncope of identifiable cardiac. palpitations. atrioventricular (AV) or left bundle-branch block. bloating.org/ by guest on November 16. 2017 micturition.. Typical features may be absent in older patients (24).ahajournals. the estimated prevalence of syncope was 19%.925 randomly selected residents of Olmsted County. The standing heart rate is often >120 bpm (31. *These definitions are derived from previously published definitions from scientific investigations. POTS. fatigue. neurological. • Situational syncope Reflex syncope associated with a specific action. • Carotid sinus Reflex syncope associated with carotid sinus hypersensitivity (30). or both (24. and healthcare providers. Interpretation of the symptoms varies among the patients. swallowing. nausea. The diagnosis is made primarily on the basis of a thorough history. bradycardia. postural tachycardia syndrome. Carotid sinus hypersensitivity can be associated with varying degrees of symptoms. tremulousness. or medical settings. Females reported a higher prevalence of syncope (22% versus 15%. the incidence depends on the population being evaluated. p<0. impaired renal function.38- 42). with a median age of 62 years (all age >45 years). and those that are systemic (e. Epidemiology and Demographics Syncope has many causes and clinical presentations. physical examination. vasovagal syncope. reflex.001) (44). blurred vision. Inc. et al. It occurs more frequently in older patients. and fatigue). Postural (orthostatic) A clinical syndrome usually characterized by all of the following: 1) frequent symptoms tachycardia syndrome that occur with standing (e. or 80 years of age and the third peak occurring 5 to 7 years earlier in males (45). and Heart Rhythm Society 12 . Carotid sinus syndrome is defined when syncope occurs in the presence of carotid sinus hypersensitivity. VVS 1) may (VVS) occur with upright posture (standing or seated or with exposure to emotional stress. Shen W-K. warmth. those not associated with particular postures (e.g. abdominal pain). with the first episode common around 20. ECG.5% (43). 2) typically is characterized by diaphoresis. or defecation. Symptoms associated with POTS include those that occur with standing (e. and 2) an increase in heart rate of ≥30 bpm during a positional change from supine to standing (or ≥40 bpm in those 12–19 y of age). These syncope events are closely associated with specific physical functions. The evaluation is further obscured by inaccuracy of data collection and by improper diagnosis.31).2. Predictors of recurrent syncope in older adults are aortic stenosis. 2. male sex. laughing. sleep disturbance. lightheadedness. and eyewitness observation.g. © 2017 by the American College of Cardiology Foundation. MN. migraine headaches) (37). nausea. with recurrent syncope occurring in 13.g. and 3) the absence of OH (>20 mm Hg reduction in systolic BP).30. and VVS. expert consensus statements. American Heart Association. Estimates of isolated or recurrent syncope may be inaccurate and underestimated because epidemiological data have not been collected in a consistent fashion or because a consistent definition has not been used.g. Downloaded from http://circ.. if available. palpitations). OH. 3) is associated with vasodepressor hypotension and/or inappropriate bradycardia. and Webster dictionary after obtaining consensus from the WC BP indicates blood pressure. 8% to 2. The National Hospital Ambulatory Medical Care Survey reported 6. with the cause of syncope unknown in 37% (35).4% in multiple studies in both academic and community settings (49-55). Shen W-K. Initial Evaluation of Patients With Syncope The time interval between the index syncopal event and the initial evaluation can vary significantly according to the medical necessity for evaluation and the patient’s effort in seeking evaluation. 2017 ACC/AHA/HRS Syncope Guideline chronic obstructive pulmonary disorder.47). 2017 30% 2-year recurrence rate (56). 58% were admitted to hospital (48). Inc. atrial fibrillation (AF). The recommendations in the present section are intended for consideration under the general principles of what constitutes GDMT during initial evaluation.7 million episodes of syncope in the emergency department (ED). The patient could seek evaluation in an outpatient setting with a generalist or a specialist or in the ED at a hospital. a 23% overall prevalence. The incidence of syncope in older adults may overlap with falls. Older institutionalized patients have a 7% annual incidence of syncope. followed by cardiac syncope (9%) and orthostatic hypotension (OH) (9%). The prevalence of syncope as a presenting symptom to the ED ranged from 0. Among patients >80 years of age. heart failure (HF). with a sharp increase in incidence after 70 years of age (35). The clinical setting in which the initial evaluation takes place also varies.. so it may be difficult to distinguish one from the other.ahajournals. In patients with New York Heart Association class III–IV HF. In older adults. Additional evaluation is discussed in subsequent sections according to the outcomes of initial evaluation or in the presence of specific disease conditions. and a Downloaded from http://circ. and orthostatic medications (45).org/ by guest on November 16. or 0.3% among nonfainters (57). and Heart Rhythm Society 13 .3. advancing age. there is a greater risk of hospitalization and death related to syncope.77% of all ED patients. American Heart Association. These general principles for the initial evaluation are shown in Figure 1. syncope is present in 12% to 14% of patients (46. 2. © 2017 by the American College of Cardiology Foundation. Older adults are predisposed to falls when syncope occurs. with a 1- year fall rate of 38% among fainters versus 18. et al. regardless of the clinical setting. Reflex syncope was most common (21%). This figure shows the general principles for initial evaluation of all patients after an episode of syncope. provide physiological insight. The history should aim to identify the prognosis.3. medication use.ahajournals. et al. diagnosis.org/ by guest on November 16.. Prognostic factors generally separate neurally mediated from cardiac syncope and are described in Section 2. Syncope Initial Evaluation Transient loss of consciousness* Suspected Evaluation as clinically No syncope indicated Yes Initial evaluation: history. comorbidities. reversible or ameliorable factors.3. Time relationship to meals and physical activities and duration of the prodrome are helpful in differentiating neurally mediated syncope from cardiac syncope. American Heart Association. Video recordings are helpful when available. and patient and family needs. Downloaded from http://circ. prodromal symptoms that Supplement 1. Shen W-K. 2017 ACC/AHA/HRS Syncope Guideline Figure 1. Comorbidities and medication use are particularly important © 2017 by the American College of Cardiology Foundation. History and Physical Examination: Recommendation Recommendation for History and Physical Examination COR LOE Recommendation A detailed history and physical examination should be performed in patients I B-NR with syncope (58-66). bystander observations of the event and vital signs. Cardiac syncope carries a significantly worse prognosis than does neurally mediated syncope. and post-event symptoms. patient’s self-report. and Heart Rhythm Society 14 . Inc. physical examination. The diagnostic history See Online Data focuses on the situations in which syncope occurs. ECG indicates electrocardiogram. 2017 and ECG (Class I) Cause of syncope Cause of syncope Risk assessment certain uncertain Treatment Further evaluation *See relevant terms and definitions in Table 3. Colors correspond to Class of Recommendation in Table 1. A basic neurological examination should be performed. or rubs that would indicate the presence of structural heart disease. particularly with regard to the existence of preexisting cardiovascular disease (58-66).org/ by guest on November 16. The physical examination should include determination of orthostatic blood pressure and heart rate changes in lying and sitting positions. A family history should be obtained. a resting 12-lead I B-NR electrocardiogram (ECG) is useful (76). gallops. A history of past medical conditions should be obtained. medical environment • Situational triggers: cough.. et al. Historical Characteristics Associated With Increased Probability of Cardiac and Noncardiac Causes of Syncope (60.67-75) More Often Associated With Cardiac Causes of Syncope • Older age (>60 y) • Male sex • Presence of known ischemic heart disease. sinus pauses or high-grade conduction block. distressful stimulus.g. defecation. and Heart Rhythm Society 15 . bradyarrhythmia with Supplement 2. micturition. cardiac and noncardiac syncope are summarized in Table 4. though not diagnostic of. 2017 Table 4. ECG is widely available and inexpensive and can provide information about the See Online Data potential and specific cause of the syncope episode (e. with particular emphasis on histories of syncope or sudden unexplained death (or drowning). It may © 2017 by the American College of Cardiology Foundation. Careful attention should be paid to heart rate and rhythm. on immediate standing. ventricular tachyarrhythmia). Historical characteristics associated with. Electrocardiography: Recommendation Recommendation for Electrocardiography COR LOE Recommendation In the initial evaluation of patients with syncope. Inc. vomiting. Downloaded from http://circ. pain. 2017 ACC/AHA/HRS Syncope Guideline factors in older patients. or reduced ventricular function • Brief prodrome. feeling warmth • Presence of specific triggers: dehydration. deglutition • Frequent recurrence and prolonged history of syncope with similar characteristics SCD indicates sudden cardiac death. laugh. American Heart Association. looking for focal defects or other abnormalities that would suggest need for further neurological evaluation or referral.ahajournals. structural heart disease. or sudden loss of consciousness without prodrome • Syncope during exertion • Syncope in the supine position • Low number of syncope episodes (1 or 2) • Abnormal cardiac examination • Family history of inheritable conditions or premature SCD (<50 y of age) • Presence of known congenital heart disease More Often Associated With Noncardiac Causes of Syncope • Younger age • No known cardiac disease • Syncope only in the standing position • Positional change from supine or sitting to standing • Presence of prodrome: nausea. as well the presence of murmurs. such as palpitations. Shen W-K.. previous arrhythmias. and after 3 minutes of upright posture (31). Although having precise definitions for high-. heart block with preserved ejection fraction. risk stratification schemes for short. outcomes would not be expected to be similar for patients with vasovagal syncope (VVS). observational study (76) concluded that the presence of AF.67-70. Subsets of patients with Wolff-Parkinson-White syndrome. The types of events. as well (69. long-QT syndrome (LQTS). 2017 Risk Assessment: Recommendations Syncope is a symptom that can be due to various causes. advanced cardiomyopathy and HF. and ventricular pacing were associated with increased risk of death from all causes at 1 year. For example. voltage criteria for left ventricular (LV) hypertrophy.83. long-term prognosis is related to the effectiveness of therapy and the severity and progression of underlying diseases. study endpoints.81). acute gastric bleeding. Shen W-K. or arrhythmogenic right ventricular cardiomyopathy (ARVC) have characteristic ECG features.89. Despite the benefit of identifying a likely cause or potential clue about the cause of syncope from the ECG. The prognostic value of an abnormal ECG in patients with syncope has been questioned.77-80). Brugada syndrome.82..92.and long-term I B-NR morbidity and mortality risk of syncope are recommended (Table 5) (68. Inc.99). ranging from benign to life-threatening conditions.65.and long-term clinical outcomes are limited by the inclusion of all patients with syncope. Risk markers are summarized in Table 5 (64. However. event rates. hypertrophic cardiomyopathy (HCM). prospective. prospective studies did not conclude that ECG findings significantly affected subsequent management (73.100).87. and study durations from investigations that estimated risk scores are summarized in Table 6 (64.97. Downloaded from http://circ. 2017 ACC/AHA/HRS Syncope Guideline demonstrate an underlying arrhythmogenic substrate for syncope or SCD. The short-term prognosis of patients presenting with syncope is mainly related to the cause of syncope and the acute reversibility of the underlying condition.82-98). intraventricular conduction disturbances. American Heart Association. without regard to the presence or absence of underlying medical conditions associated with syncope. and low-risk patient groups after an episode of syncope would be useful for managing these patients. and time intervals between these events are variable from study to study. which can prompt the decision to pursue further evaluation. et al.76. intermediate-. or aortic dissection.72-75. evidence from current clinical studies renders this proposal challenging because of a large number of confounders. especially cardiac or terminal illnesses.org/ by guest on November 16. Recommendations for Risk Assessment COR LOE Recommendations Evaluation of the cause and assessment for the short.81. adverse event rates. However. Current data are best grouped into short-term risk (associated with outcomes in the ED and up to 30 days after syncope) and long-term risk (up to 12 months of follow-up). Risk markers from history. and Heart Rhythm Society 16 . Risk stratification during initial evaluation is important for guiding the treatment and preventing long-term morbidity and mortality. laboratory investigations. © 2017 by the American College of Cardiology Foundation. a multicenter. physical examination.ahajournals. Potential predictors of increased short-term risk of death and serious outcomes are listed in Table 5.85. and laboratory studies associated with adverse outcomes from selected studies. 2017 ACC/AHA/HRS Syncope Guideline Syncope may be an acute result of major hemodynamic abnormalities or a manifestation of serious underlying disease.103) HF (74. Table 5.93) Evidence of bleeding (83) Lower GFR Persistent abnormal vital signs (70) Abnormal ECG (68. inclusion of patients with serious outcomes already identified in Supplements 3 and the ED. including inconsistent definitions of syncope. Inc. This table includes individual risk predictors from history. small samples that limited model reliability. assessment of the cause of syncope and underlying comorbidities is necessary.102) Male sex (68. including those listed in Table 5 (69. Shen W-K.67-75.and Long-Term Risk Factors* Short-Term Risk Factors (≤30 d) Long-Term Risk Factors (>30 d) History: Outpatient Clinic or ED Evaluation Male sex (74. Thus. © 2017 by the American College of Cardiology Foundation. The evaluation of patients with syncope should include a full assessment of the long-term risk factors.90.89. Long-term adverse events and deaths are more likely determined by the underlying medical comorbidities.101.74. which biases risk scores toward identifying “obvious” events. The specific endpoints for the individual studies in this table are defined in Data Supplements 3 and 4 and summarized in Table 6 for selected studies.97).68. 4.90) Exertional syncope (83) Cancer (68) Structural heart disease (70.70. outcomes.98).83.75. Investigators have reported numerous risk scores to predict adverse outcomes after syncope (examples in Table 6).95. In patients without a See Online Data presumptive cause of syncope. and Heart Rhythm Society 17 . This literature has important limitations. risk stratification for potential short-term Supplements 3 and outcomes is necessary for immediate decision making in the acute setting.88) HF (90) Cerebrovascular disease (70) Cerebrovascular disease (68) Family history of SCD (70) Diabetes mellitus (104) Trauma (68.101) High CHADS-2 score (95) Physical Examination or Laboratory Investigation Abnormal ECG (84.85. Use of risk stratification scores may be reasonable in the management of Downloaded from http://circ.101). and limited external validation. et al. 2017 IIb B-NR patients with syncope (67.73. many of which are cardiac.96.org/ by guest on November 16..88.84-93. Short-term adverse events and deaths are determined largely by the cause of syncope and the effectiveness of the treatment. outcome time frames.90) Older age (>60 y) (88) Older age (90) No prodrome (68) Absence of nausea/vomiting preceding syncopal event (93) Palpitations preceding loss of consciousness (83) VA (68.72.103) Structural heart disease (68.83. Short. physical examination.72-74.105) Positive troponin (75) *Definitions for clinical endpoints or serious outcomes vary by study. American Heart Association. composite outcomes that combine events with different pathophysiologies. See Online Data and predictors.ahajournals.72. Risk scores have not performed better than unstructured clinical judgment (64. the use of 4.87.101.100.75. ST abnormalities. or readmission.584 173 30-d serious No Abnormal ECG#. emergency department. pulmonary embolism. N/A. Examples of Syncope Risk Scores Sample Events Outcome ED NPV Study/Reference Year N N Definition Events* Predictors (%)† Martin (90) 1997 252 104 1-y death/ Yes Abnormal ECG#. negative predictive value. 100 (11%) no prodrome. Osservatorio Epidemiologico sulla Sincope nel Lazio. BP. family history of SCD. OESIL. MI. NPV. and Heart Rhythm Society 18 . AVB indicates atrioventricular block. supine. sudden cardiac death. MI. Shen W-K. VHD. blood pressure. history of arrhythmia. bundle-branch block. ECG. ventricular arrhythmias. persistent abnormal vital signs. or significant anemia requiring blood transfusion. stroke. 2017 mm Hg. type-2 second-degree AVB or third-degree AVB). GFR. HF Sarasin (74) 2003 175 30 Inpatient Yes Abnormal ECG#. an abnormal ECG is any rhythm other than normal sinus rhythm. and VA. no --- (6%) events║ prodrome. hypertension. 93 (41%) arrhythmia VA. hemorrhage. hemorrhage. BBB. systolic BP >160 mm Hg. exertional. conduction delays (BBB. stroke. HF. worrisome cardiac history. O2Sat. aortic dissection. et al. glomerular filtration rate. and stroke or transient ischemic attack. §Events: death. HF Boston Syncope Rule 2007 293 68 30-d serious Yes Symptoms of acute coronary 100 (70) (23%) events‡ syndrome.. new diagnosis of severe structural heart disease. presence of Q waves. ECG. arrhythmia. pulmonary embolism. pulmonary embolism. palpitations. trauma. >90 y of age. cardiac history SFSR (72) 2004 684 79 7-d serious Yes Abnormal ECG#. >45 y of age. ‡Events: death. Inc. O2Sat. or prolonged QT interval. ║Events: death. precipitant (low-risk factor). primary central nervous event Del Rosso (69) 2008 260 44 Cardiac N/A Abnormal ECG#/cardiac 99 (17%) etiology history. myocardial infarction. systolic BP <90 Downloaded from http://circ. electrocardiogram.ahajournals. ROSE. MI. arrhythmia. major therapeutic procedure. Table 6. 99 (12%) events§ hematocrit. or readmission. or life- threatening sequelae of syncope.org/ by guest on November 16. emergency department. heart failure. heart failure. age ≥75 years. oxygen saturation. hemoglobin. #Abnormal ECG is defined variably in these studies. HF. dyspnea. autonomic prodrome (low-risk factors) STePS (68) 2008 676 41 10-d serious Yes Abnormal ECG#. electrocardiogram. B-natriuretic 98 (7%) events¶ peptide. MI. positive troponin. SCD. ED. arrhythmia. stroke/TIA. diabetes mellitus. ED. >65 y of age. signs of conduction disease. >65 y of age. male sex Syncope Risk Score 2009 2. volume depletion. not available. American Heart Association. In the context of syncope evaluation. major therapeutic procedure. Risk Stratification of © 2017 by the American College of Cardiology Foundation. near-syncope (a low-risk factor) ROSE (73) 2010 550 40 30-d serious Yes Abnormal ECG#. 97 (75) (7%) events¶ male sex. fecal occult blood *Did the study include events diagnosed during the ED evaluation? †NPV: negative predictive value for lowest risk group for the specific events defined by the study. cerebral hemorrhage. sepsis. 98 (17%) arrhythmia HF OESIL (67) 2003 270 31 1-y death N/A Abnormal ECG#. ¶Events: death. 2017 ACC/AHA/HRS Syncope Guideline CHADS-2 indicates congestive heart failure. © 2017 by the American College of Cardiology Foundation.106. severe anemia from a gastrointestinal bleed).98). In this setting. Finally. and the lack of data demonstrating that hospital-based evaluation improves outcomes. and VHD. In patients with a presumptive cause of reflex-mediated syncope and no other dangerous medical conditions Downloaded from http://circ.120). Short-Term Prognosis of Syncope Study. Decision support algorithms may reduce health service use in the evaluation of syncope (Figures 1 and 2) (105.106). hospital-based evaluation is unlikely to provide benefit (35). medication management and consideration of surgical intervention for critical aortic stenosis).. Individual risk factors (Table 5) and risk scores (Table 6) are correlated with short. SCD.ahajournals.. American Heart Association. Disposition After Initial Evaluation: Recommendations The evaluating provider must decide whether further workup can continue in an outpatient setting or whether hospital-based evaluation is required. Presence of ≥1 serious medical condition. sudden cardiac death. VA.and long-term clinical outcomes.org/ by guest on November 16. a lack of consensus on acceptable short-term risk of serious outcomes. a large spectrum of noncardiac serious conditions may be associated with syncope and require management of the underlying problem (e. 2017 identified. varying availability and expertise of outpatient diagnostic clinics. but they are not primary determinants for admission to hospital.g. 2017 ACC/AHA/HRS Syncope Guideline Syncope in the ED.” Arrhythmic causes may require consideration of pacemaker / implantable cardioverter-defibrillator (ICD) placement or revision See Online Data and/or medication modification.g. SFSR. the logistical and financial feasibility of specialized syncope units in North American settings is unknown. the healthcare provider may recommend a hospital-based evaluation. Recommendations for Disposition After Initial Evaluation COR LOE Recommendations Hospital evaluation and treatment are recommended for patients presenting I B-NR with syncope who have a serious medical condition potentially relevant to the cause of syncope identified during initial evaluation (105. STePS. ventricular arrhythmias. underlying condition (e. summarized in Table 7. In patients with perceived higher risk. a structured ED protocol can be effective as an alternative to inpatient admission (107-110). San Francisco Syncope Rule. However. A wider acceptance of syncope units requires further evidence of improvement in clinical outcomes. although there are currently insufficient data to advocate the use of specific decision support algorithms for making disposition decisions..111-113). transient ischemic attack. Cardiac causes require treatment of the Supplements 5 and 6. The disposition decision is complicated by varying resources available for immediate testing. The purpose of hospital-based evaluation is to expedite the treatment of identified serious conditions or to continue the diagnostic evaluation in the absence of a presumptive cause of syncope (105. et al. Shen W-K. and Heart Rhythm Society 19 . is the key determinant for further in-hospital management of patients after syncope (90. Table 7 provides examples of serious conditions associated with syncope that may require inpatient evaluation and “treatment. valvular heart disease. TIA. Specialized syncope evaluation units may lead to reduced health service use and increased diagnostic rates (114-119). Inc. “Intermediate” risk factors Downloaded from http://circ. has not demonstrated an improvement in patient-relevant outcomes. device without evidence of dysfunction. concerning ECG findings. as an alternative to extended hospital-based evaluation. exceptions that might require hospital-based evaluation include frequent recurrent syncope with risk of injury or identified injury related to syncope. use of a IIa B-R structured ED observation protocol can be effective in reducing hospital admission (107-110). Two small RCTs suggest that structured ED-based protocols. and Heart Rhythm Society 20 . Patients evaluated for See Online Data suspected cardiac syncope in outpatient settings are seldom admitted for Supplements 5 and 6. Patients with presumptive VVS have a long-term risk of death similar to that of risk-matched patients without syncope (35). In intermediate-risk patients with an unclear cause of syncope. prior history of cardiac disease. It may be reasonable to manage selected patients with suspected cardiac IIb C-LD syncope in the outpatient setting in the absence of serious medical conditions (106.org/ by guest on November 16. result in reduced health service use without adverse impact on clinical outcomes when compared with unstructured hospital admission. Hospital-based evaluation of syncope of unclear cause. consisting of time- limited observation and expedited access to cardiac testing/consultation. Possible Supplements 5 and 6. Hospital-based evaluation for See Online Data presumptive VVS is unlikely to improve long-term outcomes. 2017 See Online Data included the following: ≥50 years of age. cardiac Supplements 5 and 6. and it may be reasonable to extend a similar approach to EDs after initial evaluation is completed in the ED. 2017 ACC/AHA/HRS Syncope Guideline It is reasonable to manage patients with presumptive reflex-mediated IIa C-LD syncope in the outpatient setting in the absence of serious medical conditions (35). Shen W-K.121-123). or family history of early SCD. Both trials also allowed unstructured physician judgment to identify intermediate-risk patients (107-110). Inc. © 2017 by the American College of Cardiology Foundation. American Heart Association. as indicated by availability of resources and provider’s assessment of short-term risk of serious outcomes. in the absence of other serious identified medical conditions. Primary providers can consider expedited referral to specialists with expertise in syncope. Several observational studies suggest modest diagnostic yield of hospital admission (121-123). et al.ahajournals. and symptoms not consistent with reflex-mediated syncope. diagnostic purposes.. risk stratification. after the initial history.ahajournals. SVT. is a clinical decision based on the patient’s clinical presentation. See Figure 3 for the algorithm for additional evaluation and diagnosis for syncope. 3. A broad-based use of additional testing is costly and often ineffective. HF. © 2017 by the American College of Cardiology Foundation. left ventricular. Examples of Serious Medical Conditions That Might Warrant Consideration of Further Evaluation and Therapy in a Hospital Setting Cardiac or Vascular Cardiac Arrhythmic Conditions Noncardiac Conditions Nonarrhythmic Conditions • Sustained or symptomatic VT • Cardiac ischemia • Severe • Symptomatic conduction system • Severe aortic stenosis anemia/gastrointestinal disease or Mobitz II or third-degree • Cardiac tamponade bleeding heart block • HCM • Major traumatic injury due • Symptomatic bradycardia or sinus • Severe prosthetic valve dysfunction to syncope pauses not related to neurally mediated • Pulmonary embolism • Persistent vital sign syncope • Aortic dissection abnormalities • Symptomatic SVT • Acute HF • Pacemaker/ICD malfunction • Moderate-to-severe LV dysfunction • Inheritable cardiovascular conditions predisposing to arrhythmias HCM indicates hypertrophic cardiomyopathy. and a clear understanding of diagnostic and prognostic value of any further testing. Patient Disposition After Initial Evaluation for Syncope Syncope initial evaluation Serious medical conditions present? (Table 7) Yes No Downloaded from http://circ. and VT. heart failure. Additional Evaluation and Diagnosis The selection of a given diagnostic test. implantable cardioverter-defibrillator. 2017 ACC/AHA/HRS Syncope Guideline Figure 2. and Heart Rhythm Society 21 . ICD. patients. 2017 Manage presumptive Structured ED Manage selected pts reflex-mediated observation protocol with suspected Inpatient evaluation syncope in for intermediate. physical examination. Shen W-K. ED indicates emergency department. pts. et al. American Heart Association. ventricular tachycardia. cardiac syncope in (Class I) outpatient setting risk pts outpatient setting (Class IIa) (Class IIa) (Class IIb) Colors correspond to Class of Recommendation in Table 1.org/ by guest on November 16. This section provides recommendations for the most appropriate use of additional testing for syncope evaluation. and baseline ECG.. LV. supraventricular tachycardia. Table 7. Inc. This section reviews circulating biomarkers. orthostatic hypotension. cardiovascular. CV. and Heart Rhythm Society 22 .. ECG (Class I) Initial evaluation Initial evaluation Stress testing clear unclear (Class IIa)† TTE Initial Initial Initial (Class IIa)† No additional Targeted blood evaluation evaluation evaluation evaluation testing Options suggests suggests reflex suggests CV needed* (Class IIa)† EPS neurogenic OH syncope abnormalities (Class IIa)† Downloaded from http://circ. American Heart Association. 3. Inc. Although broad-panel testing is common in clinical practice at the point of triage. © 2017 by the American College of Cardiology Foundation. †In selected patients (see Section 1. Blood Testing: Recommendations The availability of simple and accurate biomarkers might streamline risk stratification and diagnosis of the cause of syncope. Recommendations for Blood Testing COR LOE Recommendations Targeted blood tests are reasonable in the evaluation of selected patients IIa B-NR with syncope identified on the basis of clinical assessment from history. CT indicates computed tomography. Shen W-K. electrocardiogram. magnetic resonance imaging. 2017 ACC/AHA/HRS Syncope Guideline Figure 3.org/ by guest on November 16. which are being evaluated as markers either of hypotension or underlying disease processes. Data to support specific See Online Data blood testing are largely descriptive data from case series and registries. Supplements 7 and 8. there are no data on the utility of this approach. MRI. OH. Additional Evaluation and Diagnosis for Syncope Syncope additional evaluation and diagnosis Initial evaluation: history.ahajournals. 2017 Referral for Cardiac monitor MRI or CT Tilt-table autonomic selected based (Class Ilb)† testing evaluation on frequency (Class IIa)† (Class IIa)† and nature (Class I) Options Ambulatory Implantable external cardiac cardiac monitor monitor (Class IIa)† (Class IIa)† Colors correspond to Class of Recommendation in Table 1. et al. physical exam. *Applies to patients after a normal initial evaluation without significant injury or cardiovascular morbidities. and ECG (124). and TTE.1.4). electrophysiological study. ECG. EPS. Complete blood count and electrolyte panel are frequently obtained during syncope evaluation. transthoracic echocardiography. None have met with strong success. patients followed up by primary care physician as needed. physical examination. The diagnostic yield is low when these are used routinely. Determining the significance of such abnormalities. specific testing should stem from the assessment by history and physical examination when the nature of the syncope presentation or associated comorbidities suggests a diagnostic or more likely prognostic role for laboratory testing. et al.131). portends a poor prognosis (35. Inc. The presence of significant cardiovascular diseases. 3. Supplements 7 and 8. there are sufficient data to suggest that natriuretic peptide is elevated in patients whose subsequent cause for syncope is determined to be cardiac.g.2. Thus. and whether subsequent treatment is merited requires clinical judgment and appropriate selection of cardiovascular testing. As such. cardiovascular testing can be a critical element in the evaluation and management of selected patients with syncope. © 2017 by the American College of Cardiology Foundation. Results have not been linked to clinical decision making or outcomes (125-128). Specific cardiac biomarkers may play a See Online Data limited role when directed by clinical suspicion from the baseline assessment. It is important also to recognize that the abnormalities found during cardiovascular testing may not have a causal relationship to syncope itself. or tarry stools associated with OH on physical examination). when these blood tests are conducted in patients with a suspected related diagnosis (e. Although data to support biomarker testing are in general relatively weak.org/ by guest on November 16. There are no data on the utility of a standardized broad panel of laboratory testing in patients with syncope. test results can be diagnostic and useful for guiding therapy. their causality.130). 2017 ACC/AHA/HRS Syncope Guideline however. Usefulness of brain natriuretic peptide and high-sensitivity troponin IIb C-LD measurement is uncertain in patients for whom a cardiac cause of syncope is suspected (125. history of peptic ulcer disease. A Downloaded from http://circ. 2017 systematic review of biomarkers found little value in contemporary troponin See Online Data measurement unless acute myocardial infarction is suspected. Cardiovascular Testing Cardiovascular causes of syncope are common.. American Heart Association.129. often associated with the cardiovascular causes of syncope.132).127. and Heart Rhythm Society 23 . III: No B-NR Routine and comprehensive laboratory testing is not useful in the Benefit evaluation of patients with syncope (126. The ability of troponin and natriuretic peptide measurement to influence clinical decision making or patient outcome is unknown (129). There is little biological plausibility linking the remaining elements of broad- panel laboratory testing to the presentation or mechanism of syncope. modest predictive value for high-sensitivity troponin and natriuretic peptides for major adverse cardiovascular events.ahajournals. Shen W-K. and there is Supplements 7 and 8.. g.138). American Heart Association.141).136). physical examination. and imaging with transthoracic echocardiography is widely used for this purpose because it is noninvasive and low risk.133). Although some investigators have advocated for cardiac imaging—particularly See Online Data transthoracic echocardiography—as a routine screening examination for patients Supplement 9. including CT and MRI. HCM. and Heart Rhythm Society 24 . 2017 Supplement 9. are usually reserved for selected patients presenting with syncope. The use of CT and MRI in contemporary cardiology is increasing (137. These modalities offer superior spatial resolution in delineating cardiovascular anatomy (e. especially when other noninvasive means are inadequate or inconclusive. 88 patients had an abnormal history or ECG. in the ED (134). Cardiac imaging is often used to identify a structural cardiac abnormality. in patients with structural. Inc.. or ECG. clinical evidence does not support such practice. Imaging modalities. the echocardiogram See Online Data suggested a diagnosis of cardiac syncope in 48% of the study cohort (99).99). or ECG (77. CT or MRI may not provide answers about the cause of syncope. Unexpected findings on © 2017 by the American College of Cardiology Foundation.ahajournals. or congenital heart disease [CHD]) (135. aortic stenosis). MRI is useful when there is a suspicion of ARVC or cardiac sarcoidosis (140. 2017 ACC/AHA/HRS Syncope Guideline Cardiac Imaging: Recommendations Recommendations for Cardiac Imaging COR LOE Recommendations Transthoracic echocardiography can be useful in selected patients IIa B-NR presenting with syncope if structural heart disease is suspected (80.. The use of CT or MRI increased from 21% See Online Data in 2001 to 45% in 2010. Shen W-K. incidental abnormalities (p<0. Their role in the evaluation of syncope has been investigated (139). In a retrospective study of patients presenting with syncope and suspected cardiac disease after history. an echocardiogram showed systolic dysfunction (LV ejection fraction ≤40%) in 24 patients (80).g.. In a Downloaded from http://circ. infiltrative. physical examination.01).124). or LV dysfunction (124. prospective evaluation of 650 patients referred for syncope of unknown origin. including history. They provide information on the structural disease substrate relevant to the overall diagnosis and subsequent evaluation and follow-up in selected patients presenting with syncope. and 50% of patients with LV systolic dysfunction had manifest arrhythmias. compared with 9% with minor. CT can confirm the diagnosis in selected patients (128).99. it provides information for a potential disease substrate related to prognosis. Transthoracic echocardiography can be useful when healthcare providers are concerned about the presence of valvular disease (e. Although an echocardiogram may not be able to establish the immediate cause of syncope. et al. Routine cardiac imaging is not useful in the evaluation of patients with III: No B-NR syncope unless cardiac etiology is suspected on the basis of an initial Benefit evaluation. as reported in a series of patients evaluated for syncope Supplement 9. Computed tomography (CT) or magnetic resonance imaging (MRI) may be IIb B-NR useful in selected patients presenting with syncope of suspected cardiac etiology (134).org/ by guest on November 16. with syncope who lack clear signs or symptoms of cardiovascular disease (133). When pulmonary embolism is suspected in patients presenting with syncope to the hospital. an ECG stress evaluation was felt to be the sole test useful in identifying a presumptive cause of syncope in only 2 patients. echocardiography. hypotension) must be done with extreme caution and in an environment See Online Data with proper advanced life support. a “screening” echocardiogram is of low utility (142). In rare instances. radionuclide imaging and cardiac catheterization have little role in the evaluation of syncope. The choice of monitoring system and duration should be appropriate to the likelihood that a spontaneous event will be detected and the patient may be incapacitated and unable to voluntarily trigger the recording system. it was found that echocardiograms in patients with no clinical evidence of heart disease according to history.143). contributed to the diagnosis or management in <5% of cases and helped determine the etiology of syncope <2% of the time (77). including structural lesions. interarterial anomalous coronary artery and pulmonary arterial hypertension. In a prospective evaluation of 433 patients in which tachyarrhythmia was studied as the etiology for exertional syncope (132). physical examination. CT scans. exercise-induced ischemia (143-146) or coronary vasospasm (147) may lead to high grade/infranodal AV block in patients with underlying coronary disease. a battery of testing. Subjecting a patient to a treadmill exercise test to reproduce the symptoms or evaluate the hemodynamic response to exertion (e. Similarly. in another retrospective series of 128 inpatients with syncope. such as LQTS (type 1) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Inc. or ECG either were normal (63%) or provided no useful additional information for arriving at a diagnosis (37%) (99). and channelopathies. Shen W-K. In 1 evaluation of 2.g. Finally. Supplement 10. bradyarrhythmia may ultimately be responsible for exertional syncope as well. Exertion can result in syncope in a variety of conditions. American Heart Association. carotid ultrasonography.ahajournals. Cardiac Monitoring: Recommendations Although cardiac monitoring is often used in the evaluation of palpitations or intermittent arrhythmias. 2017 ACC/AHA/HRS Syncope Guideline echocardiograms to explain syncope are uncommon.. et al. © 2017 by the American College of Cardiology Foundation. and electroencephalography. Stress Testing: Recommendation Downloaded from http://circ. 2017 Recommendation for Stress Testing COR LOE Recommendation Exercise stress testing can be useful to establish the cause of syncope in IIa C-LD selected patients who experience syncope or presyncope during exertion (132..106 inpatients with syncope. and may only be elicited during stress testing. However. including cardiac enzymes. such as hypertrophic obstructive cardiomyopathy and aortic stenosis. and Heart Rhythm Society 25 .org/ by guest on November 16. the following recommendations and discussion are focused primarily on the use of monitoring for the evaluation of patients with syncope. and suddenness of incapacitation. External loop recorders are also limited by infrequent syncopal events.150. To evaluate selected ambulatory patients with syncope of suspected IIa B-R arrhythmic etiology. multicenter study of 392 patients (28% with syncope) reported a Supplements 11 and 4-week diagnostic yield of 24. some external loop recorders are of limited use in patients who are temporarily incapacitated around the time of syncope. Although the diagnostic yield of an external loop recorder may be lower than that of an implantable cardiac monitor (ICM).ahajournals. To evaluate selected ambulatory patients with syncope of suspected arrhythmic etiology.. Inc.154-156) Downloaded from http://circ. The advances of new patch-based devices offer another and often less cumbersome means of identifying an arrhythmic cause for syncope (157-159). Transtelephonic monitor (150. The technology of cardiac rhythm monitoring is dynamic and advancing at rapid speed. there was a similar result in the subgroup of patients presenting with syncope or presyncope. © 2017 by the American College of Cardiology Foundation.org/ by guest on November 16. duration of prodrome. supraventricular arrhythmias being strong predictors of diagnostic events (156). Holter monitor (149-153) IIa B-NR 2.008). the following external cardiac monitoring approaches can be useful: 1. which provide real-time arrhythmia monitoring and analysis.153. the noninvasive strategy is reasonable as a first approach. 2017 ACC/AHA/HRS Syncope Guideline Recommendations for Cardiac Monitoring COR LOE Recommendation The choice of a specific cardiac monitor should be determined on the basis of I C-EO the frequency and nature of syncope events. External loop recorder (150. with a significantly higher diagnostic yield in the mobile continuous outpatient telemetry group (89% versus 69%.161). and Heart Rhythm Society 26 .153) and may offer a diagnosis after a negative Holter evaluation (150). The types of external monitoring devices are summarized in Table 8. an ICM can be useful (149. The advantage of an external loop recorder over Holter monitoring stems from a longer monitoring period. however.5%. American Heart Association.155) 3. Importantly. allows for symptom rhythm correlation. Several types of ambulatory cardiac rhythm monitoring are summarized in N/A Table 8. p=0. The duration of monitoring (2 to 14 days) is often shorter than for the external loop recorder or mobile continuous outpatient telemetry.008). continuous versus intermittent monitoring. frequency of syncope. The patient activation. An RCT (161) of 266 patients with suspected intermittent arrhythmias demonstrated that an arrhythmia was diagnosed in 88% of mobile continuous outpatient telemetry patients versus 75% of external loop recorder patients (p=0. before or after an event.154. Patch recorder (157-159) 5. Some practices offer mobile continuous outpatient telemetry devices. Mobile cardiac outpatient telemetry (160. Their selection and usefulness are highly dependent on patient characteristics with regard to the frequency of syncope and the likelihood of an arrhythmic cause of syncope (148). with recurrent events and previous history of 12. The effectiveness of any external cardiac monitoring device for syncope evaluation is related to the duration of monitoring. See Online Data One prospective. 2017 4.161-175). which confers a higher yield than Holter monitoring (149. et al. Shen W-K. which transmits triggered data automatically over a wireless network to a remote monitoring system External patch • Patch device that continuously records and • Can be considered as an alternative to recorders stores rhythm data. which generally have shown that patients who Supplements 11 and underwent the ICM approach experienced higher rates of diagnosis than those of 12. up to 2 detected within a short period (24–72 wk with newer models h) of monitoring* • Symptom rhythm correlation can be achieved through a patient event diary and patient- activated annotations Patient-activated. and Heart Rhythm Society 27 .org/ by guest on November 16. spontaneous symptoms transtelephonic activated data (live or stored) via an analog likely to recur within 2–6 wk monitor (event phone line to a central remote monitoring • Limited use in patients with frank monitor) station (e.155) record asymptomatic arrhythmias) to provide a recording of events antecedent to (3–14 min). and after the triggered event © 2017 by the American College of Cardiology Foundation.177). 2017 ACC/AHA/HRS Syncope Guideline Several RCTs and observational studies have demonstrated a benefit of the ICM in establishing a diagnosis in syncope of unclear etiology. and is largely • No leads or wires. Cardiac Rhythm Monitors Types of Monitor Device Description Patient Selection Holter monitor • A portable..154. and adhesive to chest water resistant. Inc. American Heart Association. These findings See Online Data are consistent with other studies. to within 2–6 wk (150.176. In a prospective study of 60 patients with syncope of unknown origin. Downloaded from http://circ.g.. spontaneous symptoms (patient or auto rhythm data over weeks to months related to syncope.ahajournals.154. likely to recur triggered)† • Patient activated. et al.. heterogeneity of patient populations. • Symptoms frequent enough to be (151-153) • Continuous recording for 24–72 h. Table 8. Shen W-K. during. to external monitors. physician office) syncope associated with sudden (150..164. • Frequent. compared with a 19% diagnostic yield with conventional testing (external loop recorder. or auto triggered (e.0014) (162). or auto triggered (e. it offers only 1- record asymptomatic arrhythmias) to provide lead recording a recording of events antecedent to. during. 2017 and changing technology.g. followed by tilt-table testing and electrophysiological study [EPS]) (p=0. the diagnosis (primarily bradyarrhythmia) was made in 55% with ICM.178). patients who underwent the conventional approach (164. A study on cost-effectiveness of the ICM strategy reported that the mean cost per participant was higher but the cost per diagnosis was lower in patients who received ICM than in patients who underwent conventional approaches (162. with patient-trigger external loop recorder (157-159) capability to allow for symptom-rhythm • Given that it is leadless. battery-operated device. • A recording device that transmits patient.g. • Offers accurate means of assessing burden of potentially improving compliance atrial fibrillation • Unlike Holter monitors and other • Patient activated. Key confounders in cost assessment include differences in healthcare settings. pricing of devices and healthcare delivery. can be correlation accurately self-applied. and after (1–4 min) the triggered event • Newer models are equipped with a cellular phone.155) incapacitation External loop recorder • A device that continuously records and stores • Frequent. it may be more wall/sternum comfortable and less cumbersome • Various models record from 2–14 d than an external loop recorder. 182.183). physical examination. the monitor automatically transmits the patient’s ECG data through a wireless network to the central monitoring station.106 patients admitted with syncope demonstrated high telemetry use (95%) but a diagnostic yield of only 5% (77). No arrhythmias or interventions occurred in the 7% of patients who were assigned to telemetry because of syncope. A large. Continuous telemetry in the hospital for patients presenting with syncope not suspected of a cardiac etiology is not cost-effective (186. Furthermore. However.8±2. prospective evaluation of 2.ahajournals. unexplained monitor (162. The yield was highest in older patients with HF. significant arrhythmias were seen in only 12 patients with known or suspected coronary artery disease or in those with previously documented arrhythmias (183). 2017 transmission. †Higher yield in patients who are able to record a diary to correlate with possible arrhythmia. may include nondiagnostic tilt-table test or electrophysiological study. In-Hospital Telemetry: Recommendation Recommendation for In-Hospital Telemetry COR LOE Recommendation Continuous ECG monitoring is useful for hospitalized patients admitted I B-NR for syncope evaluation with suspected cardiac etiology (77.240 patients admitted to a See Online Data telemetry unit. © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society 28 . One study of 172 patients with syncope presenting to the ED and admitted to a telemetry unit revealed a diagnostic yield in 18% of patients. Shen W-K. In 1 prospective study of 2.167. in another prospective evaluation of 205 patients admitted to telemetry. ECG indicates electrocardiogram.org/ by guest on November 16. the diagnostic yield of inpatient telemetry is low in the absence of high suspicion about an arrhythmic cause (183). patients admitted for syncope (10%) had low rates of Supplement 13. inpatient telemetry could be a valuable diagnostic modality.161) patient activation to a communication hub at • In high-risk patients whose rhythm the patient’s home requires real-time monitoring • Significant arrhythmias are detected. with or without structural Downloaded from http://circ. with 15% demonstrating bradyarrhythmias (182). as well as automatic detection heart disease of significant arrhythmias with remote monitoring *Includes history. Given that patients with syncope and structural heart disease are at high risk of death or significant arrhythmia (184). and most were unrelated to arrhythmic conditions (185). and 12-lead ECG.. et al. No deaths occurred within an average monitoring time of 4. which is attended by trained technicians 24 h/d • This offers the potential for real-time. American Heart Association. with a • Recurrent. Inc. infrequent. battery life of 2–3 y syncope (or suspected atypical reflex 181) • Triggered by the patient (or often family syncope) of suspected arrhythmic member witness) to store the event cause after a nondiagnostic initial • Models allow for transtelephonic workup. immediate feedback to a healthcare provider for evaluation Implantable cardiac • Subcutaneously implanted device.7 days. 2017 ACC/AHA/HRS Syncope Guideline Mobile cardiac • Device that records and transmits data (up to • Spontaneous symptoms related to outpatient telemetry 30 d) from preprogrammed arrhythmias or syncope and rhythm correlation (160. unexpected intensive care transfer.187).179. depending on patient selection and pretest probability of a bradycardia substrate (189-191).ahajournals. Recommendations for EPS COR LOE Recommendations EPS can be useful for evaluation of selected patients with syncope of IIa B-NR suspected arrhythmic etiology (91. Shen W-K. 2017 monomorphic VT predicts lower risk of spontaneous VT and better prognosis (192). and Heart Rhythm Society 29 . and valvular heart disease). Of 219 patients without evidence of heart disease. the diagnostic yield of EPS was approximately 50% and 10% in patients with and without structural heart disease. conduction system delay.7%) and that the diagnostic yield was low in patients with a normal © 2017 by the American College of Cardiology Foundation..188). Most of the literature evaluating EPS as a means to diagnose syncope is relatively old. EPS is not recommended for syncope evaluation in patients with a normal III: No B-NR ECG and normal cardiac structure and function. respectively.187. This is primarily due to the use of ICD as a Class I indication for the primary prevention of SCD in patients with ischemic or nonischemic cardiomyopathy and significant LV dysfunction (ejection fraction ≤35%).151. et al. EPS has a limited role in the evaluation of syncope. Diagnostic results detected during EPS occur predominantly in patients who have cardiac disease (e. they may not prevent syncope. The lack of an inducible sustained Downloaded from http://circ. American Heart Association. cardiomyopathy. The overall role of EPS in the evaluation of ventricular arrhythmias (VA) in patients with syncope has diminished in the past 2 decades.. See Online Data Eight of these small retrospective studies (91.199-205). unless an arrhythmic Benefit etiology is suspected (205-207). The role of EPS in patients with syncope suspected to be due to VA and acquired nonischemic heart disease is unproven (193-198).199-205) (total n=625) found that. Supplement 14. The causal relationship between the inducible VT during EPS and syncope requires clinical correlation. Overall. only 5% had a positive result (1% with VT and 10% with evidence of substrate for symptomatic bradycardia). of the 406 patients with cardiac disease or an abnormal ECG. Despite these purported benefits. However. 21% had VT and 34% had a bradycardia) (151). although ICDs may reduce risk of death.g. Inducible ventricular tachycardia (VT) in patients with syncope. 2017 ACC/AHA/HRS Syncope Guideline Electrophysiological Study: Recommendations The EPS can identify a substrate for clinical bradyarrhythmia or tachyarrhythmia as a potential cause of syncope after a nondiagnostic initial evaluation. One prospective evaluation of 247 patients with syncope of undetermined See Online Data etiology who underwent EPS found that the diagnostic yield was significantly Supplement 14. The sensitivity and specificity of EPS to assess sinus node dysfunction and AV conduction disease in patients with syncope are variable.org/ by guest on November 16. higher in patients with an abnormal ECG than in those with a normal ECG (22% versus 3. 41% had a positive result (of these. Inc. and the data were obtained in referral centers where there was a high pretest probability of an arrhythmia. An EPS is no longer required in patients with syncope before consideration of ICD therapy. especially in patients without known heart disease or with low suspicion of an arrhythmic etiology (117. ischemic heart disease. and a prior history of myocardial infarction is predictive of spontaneous VT and prognosis. coronary artery disease. with or without bradycardia (less commonly asystole). may improve sensitivity but See Online Data decrease specificity (210. specificity.213. Correlation of tilt-table–induced findings to patients’ clinical presentation is critically important to prevent consequences of false-positive results from tilt-table testing.212. such as a low dose of isoproterenol infusion or sublingual nitrates. and reproducibility of tilt-table testing. The hemodynamic response to the tilt maneuver determines whether there is a cardioinhibitory.215). only 46% had OH within 3 minutes of head-up tilt. A positive response is defined as inducible presyncope or syncope associated with hypotension. a normal ECG and ambulatory monitor were associated with a lower risk of EPS abnormalities than were an abnormal ECG and ambulatory monitor (9% versus 82% ) (207). tendency or predisposition to VVS induced in the laboratory. the increasing recognition of VVS from a structured history taking. American Heart Association.. and Heart Rhythm Society 30 .211. There is general consensus that a tilt-table angle of 70 degrees for 30 to 40 minutes would provide optimal yield (211.219).213). It is an orthostatic stress test to assess the susceptibility of a vasovagal response to a postural change from a supine to an upright position. 15% had OH between 3 and 10 © 2017 by the American College of Cardiology Foundation. Tilt-Table Testing: Recommendations Recommendations for Tilt-Table Testing COR LOE Recommendations If the diagnosis is unclear after initial evaluation. the results were abnormal but not diagnostic in 2 patients and were normal in the remaining 28 patients. is distinct from delayed OH. tilt-table testing can be Downloaded from http://circ. and the availability of long-term cardiac monitoring (24. Shen W-K.217). or a similar fall in blood pressure within 3 minutes of upright tilt-table testing to 60 degrees (220). OH with standing. Inc.216. 2017 IIa B-R useful for patients with suspected VVS (208-213). In another evaluation of 421 patients with undiagnosed syncope who underwent noninvasive testing as a means of predicting abnormal EPS findings. et al. Several factors have reduced the role of tilt-table testing in the evaluation of syncope: the overall moderate sensitivity. Delayed OH may be responsible Supplement 15. A positive tilt-table test suggests a Supplement 15. Tilt-table testing can be useful for patients with syncope and suspected IIa B-NR delayed OH when initial evaluation is not diagnostic (218. 2017 ACC/AHA/HRS Syncope Guideline ECG and without cardiac disease (2. In 1 retrospective study of 230 patients with OH. the results were diagnostic in only 4 patients. This observation during tilt-table testing cannot necessarily define a causal etiology or be entirely conclusive of a reflex mechanism for syncope in the clinical setting. characterized by a sustained decrease in blood pressure occurring beyond 3 minutes of See Online Data standing or upright tilt-table testing (220. The utility of tilt-table testing is highest in patients with a suspected VVS when syncope is recurrent.ahajournals. Tilt-table testing has been used to evaluate patients with syncope for nearly 3 decades (208). for syncopal episodes or symptoms of orthostatic intolerance only after prolonged standing.org/ by guest on November 16. In another small series of 34 patients with unexplained syncope who had normal ECGs and normal testing otherwise and who underwent EPS (205). or mixed response (214). vasodepressor. Adjunctive agents. the presence of false-positive response in controls.6%) (206).221). Psychogenic pseudosyncope should be suspected when patients present with frequent (even daily) symptoms that mimic VVS (and. rules out true See Online Data syncope and most forms of epilepsy (227-229). In another study of 74 patients with a questionable diagnosis of epilepsy (because of drug-refractory seizures or clinically suspected not to be true epilepsy). Shen W-K. with >25% developing profound hypotension or bradycardia during the head-up tilt-table test. and 39% had OH only after 10 minutes of tilt-table testing (218).g. 54% of individuals with delayed OH progressed to classic OH (219). III: No Tilt-table testing is not recommended to predict a response to medical B-R Benefit treatments for VVS (230. In 10-year follow-up data from 165 of these patients. confirming the diagnosis of VVS (225). Taken together. antiepileptic therapy (223). Inc. the apparent unconsciousness with loss of motor control. it can be estimated from these studies that approximately 50% of patients with either questionable or drug-refractory epilepsy have positive tilt-table tests suggestive of a vasovagal etiology (226). underwent tilt-table testing. Convulsive syncope is a term that can be used to describe any form of syncope manifesting with convulsive movements (e. in some cases. One study of 21 patients with suspected pseudosyncope who were subjected to tilt-table testing with continuous monitoring of the ECG. a cardiac diagnosis was established in 42% of patients. 2017 ACC/AHA/HRS Syncope Guideline minutes. It is often challenging to differentiate psychogenic syncope from true syncope. Prolonged convulsions and marked postictal confusion are uncommon in patients with syncope associated with convulsive movements (226). combined with normal blood pressure and heart rate (and a normal electroencephalogram [EEG] if such a recording is obtained). Tilt-table testing has been shown to be of value in this clinical setting when a detailed history cannot clearly determine whether the convulsive movements were Downloaded from http://circ. © 2017 by the American College of Cardiology Foundation. and increased heart rate and blood pressure are highly specific for pseudosyncope.org/ by guest on November 16. tilt-table testing may help to elucidate the diagnosis. Tilt-table testing is reasonable to distinguish convulsive syncope from IIa B-NR epilepsy in selected patients (222-225). respectively.. In a prospective study of 15 patients with See Online Data recurrent unexplained seizure-like episodes who were unresponsive to Supplement 15. with a history of true VVS). eye closure during the event. American Heart Association.ahajournals. However.. compared with 64% and 9% in individuals with baseline OH and controls. In 1 study of 800 patients who Supplement 15. approximately 5% were diagnosed with pseudosyncope. and fatigue is frequent after reflex syncope and may be confused with a postictal state (226). Compared with patients with VVS. Tilt-table testing is reasonable to establish a diagnosis of pseudosyncope IIa B-NR (227-229). et al. and blood pressure revealed 17 patients with non-epileptiform limb shaking without significant changes on an EEG or hemodynamic changes (227). long periods of apparent transient loss of consciousness.231). and Heart Rhythm Society 31 . The 10-year death rate in individuals with delayed OH was 29%. EEG. 67% had convulsive movements associated with hypotension and bradycardia during tilt-table testing. myoclonus). given the need for objective evidence to help distinguish this entity from true epileptic seizures. During tilt-table testing. 2017 secondary to syncope. 231). The care of patients with neurogenic OH is complex. such as neuropathies due to diabetes amyloidosis. Many symptomatic treatments for neurodegenerative disease will increase the risk of syncope due to worsening OH.3.ahajournals. Confirmation of specific neurogenic OH conditions causing syncope often requires additional autonomic evaluation. Such care may be provided by a neurologist.org/ by guest on November 16. prolonged standing. in addition to suggesting a diagnosis of VVS. internist. and cardiac and reflex syncope. known as pure autonomic failure (243).236-239). Recommendation for Autonomic Evaluation COR LOE Recommendation Referral for autonomic evaluation can be useful to improve diagnostic and IIa C-LD prognostic accuracy in selected patients with syncope and known or suspected neurodegenerative disease (219. selection of these treatments needs to be balanced against the increased morbidity of not treating the symptoms of the neurodegenerative disease. hereditary sensory and autonomic neuropathies. 2017 management. or See Online Data other physician who has sufficient training to treat these complicated patients. cardiologist. and the “coat hanger” headache (a triangular headache at the base of the neck due to trapezius ischemia). American Heart Association. Some symptoms of neurogenic OH may differ from those due to dehydration. Supplement 16. cognitive slowing.240). accurate.. Inc. meals. Parkinson’s disease (242). but these data were limited by the lack of reproducibility of tilt-table testing (232-235). these include persistent and often progressive generalized weakness. 3. Its causes should be sought so as to provide efficient. immune- mediated neuropathies. leg buckling. the effectiveness of a therapy during repeated testing (230. or increased ambient temperature. Neurological Testing Autonomic Evaluation: Recommendation Syncope due to neurogenic OH is common in patients with central or peripheral autonomic nervous system damage or dysfunction. Several small studies suggested a possible benefit. especially in individuals with neurodegenerative disease. Peripheral autonomic dysfunction may be due to a selective degeneration of peripheral autonomic neurons. Care providers must be knowledgeable in the pathophysiology of the autonomic nervous system and the pharmacology of treatments for neurodegenerative disease (33. and effective Downloaded from http://circ. drugs. 2017 ACC/AHA/HRS Syncope Guideline One of the purported advantages of tilt-table testing. is the ability to assess the efficacy of pharmacological See Online Data therapeutics in suppressing a vasovagal response to postural stress by evaluating Supplement 15. et al. and inflammatory neuropathies. Central autonomic degenerative disorders include multiple system atrophy (241). and Lewy Body dementia (238). or may accompany autonomic peripheral neuropathies. Peripheral neuropathies due to vitamin B12 © 2017 by the American College of Cardiology Foundation. visual blurring. and Heart Rhythm Society 32 . Shen W-K. These symptoms may be provoked or exacerbated by exertion. fatigue. Syncope due to neurogenic OH is caused by either central or peripheral autonomic nervous system damage or dysfunction. 24%. during syncope.248). In 5 studies investigating patients with syncope. infrequently helpful. the diagnostic yield is low. an EEG is particularly important when a diagnosis cannot be established after a thorough initial evaluation.261-263). American Heart Association. and pseudosyncope. Although a thoughtful and detailed history usually suffices to distinguish among convulsive syncope. Autonomic evaluation may 1) determine the underlying cause of neurogenic OH. Nonetheless. epileptic convulsions. despite the absence of neurological features on history or examination. The evidence suggests that routine neurological testing is of very limited value in the context of syncope evaluation and management. Inc. MRI. 2017 ACC/AHA/HRS Syncope Guideline deficiency. MRI and CT are frequently used and Supplement 16.251-260). It can be useful to consider referring patients with the following characteristics for autonomic evaluation: Parkinsonism (241. during epileptic convulsions whereas.78.260). Recommendations for Neurological Diagnostics COR LOE Recommendations Simultaneous monitoring of an EEG and hemodynamic parameters during IIa C-LD tilt-table testing can be useful to distinguish among syncope. and 3) have therapeutic implications.248). and known or suspected neuropathic postural tachycardia syndrome (POTS) (37.248. HIV and other infections. Epileptiform discharges are recorded Supplement 16. and epilepsy (229. MRI was used in 11% of 397 patients and established a diagnosis in only 0. Downloaded from http://circ.249). Pseudosyncope and psychogenic nonepileptic seizures are associated with a normal EEG (229). progressive autonomic dysfunction without central or peripheral nervous system features (243.org/ by guest on November 16.. and brain structural See Online Data abnormalities are rare.244-246) or other central nervous system features (247. 2017 Neurological and Imaging Diagnostics: Recommendations Many patients undergo extensive neurological investigation after an uncomplicated syncope event. ECG findings are characteristic if an episode can be induced See Online Data during the tilt-table testing (261-263). neurotoxic exposure. and Heart Rhythm Society 33 .77. et al. 2) provide prognostic information. underlying diseases known to be associated with a peripheral neuropathy (240. with very high cost per diagnosis (36. and porphyria are less common causes of neurogenic OH (240). The recommendations pertain to the use of these investigations in patients with syncope and not in patients in the wider category of transient loss of consciousness. Syncope is due to global cerebral hypoperfusion.ahajournals. CT. peripheral neuropathies (240). and carotid ultrasound were ordered in 11% to 58% of patients with a presentation of syncope (78).248).250). III: No MRI and CT of the head are not recommended in the routine evaluation of B-NR patients with syncope in the absence of focal neurological findings or head Benefit injury that support further evaluation (78. A systematic review found that EEG. pseudosyncope. © 2017 by the American College of Cardiology Foundation. postprandial hypotension (248. Shen W-K. an EEG generally shows diffuse brainwave slowing with delta waves and a flat line pattern (263). Similarly. org/ by guest on November 16.256. A review of 7 studies See Online Data of use of an EEG in patients with syncope found that it was used in 52% of 2.257.4. except for the specific cardiac conditions in Sections 4. 4. Although there is general concern about potential radiation-mediated harm from CT.78. The relevant guidelines are noted in Table 2. CT was used in 57% of 2.1. indirectly related. thus obviating the need to repeat existing guideline recommendations in the present guideline.7% (36.77. III: No Carotid artery imaging is not recommended in the routine evaluation of B-NR patients with syncope in the absence of focal neurological findings that Benefit support further evaluation (77.256. EEGs should not be routinely used in the assessment of syncope.728 patients and established a diagnosis in only 1% (77.260). Carotid artery Downloaded from http://circ. Given the cost and impact on health service facilities.254-258).084 Supplement 16. and the prompt identification of an arrhythmic etiology has diagnostic and prognostic implications. patients and established a diagnosis in 0. EEGs are ordered frequently for the evaluation of syncope. 4. 2017 ACC/AHA/HRS Syncope Guideline in 10 studies of investigation of syncope. The recommendations stated in this section focus on syncope relevant to and within the context of the specific stated cardiac condition.2.260). III: No Routine recording of an EEG is not recommended in the evaluation of B-NR patients with syncope in the absence of specific neurological features Benefit suggestive of a seizure (36. Inc. and 4. 2017 ultrasound should not be routinely used in the assessment of syncope. Arrhythmic Conditions Cardiac arrhythmia is a common cause of syncope. A review of 5 studies of carotid artery ultrasound and Doppler use in See Online Data patients with syncope found that these modalities were used in 58% of 551 Supplement 16.256.5. A thorough history. Management of patients with syncope and heart disease would include treating the immediate cause of syncope and further assessing long-term management strategies to improve prognosis. MRI and CT should not be routinely used in the assessment of syncope. The determination of the immediate cause of syncope may be related.78.3 for which ACC/AHA guidelines are not available. It is pertinent to note that the principles of evaluation and management of syncope in patients with various cardiac conditions are the same as for other noncardiac conditions.257.5% (77. Neurological imaging may be indicated if significant head injury as a result of syncope is suspected. or unrelated to the underlying cardiac condition. there are very limited data on the actual harm from CT for syncope evaluation. Management of Cardiovascular Conditions The writing committee reviewed the evidence to support recommendations in the relevant ACC/AHA guidelines and affirms the ongoing validity of the related recommendations in the context of syncope. physical examination.78..260).2. patients and established a diagnosis in 0. and baseline ECG are recommended in all patients. Shen W-K. 4.254-258).257. When bradyarrhythmias and tachyarrhythmias are discovered in patients © 2017 by the American College of Cardiology Foundation. et al.77. American Heart Association.ahajournals. and Heart Rhythm Society 34 . Syncope is due to global cerebral hypoperfusion and therefore not to unilateral ischemia. The baseline presence of an arrhythmia does not necessarily represent the etiology of syncope (e.268).ahajournals. supraventricular arrhythmias (including AF). The writing committee supports the previous recommendations pertaining to syncope in patients with sinus node dysfunction and AV conduction diseases. the notion that permanent pacemaker implantation is reasonable for syncope in N/A patients with chronic bifascicular block when other causes have been excluded. GDMT is recommended (10). which is generally slower in older adult patients than in younger patients (267. Supraventricular Tachycardia: Recommendation Recommendations for Supraventricular Tachycardia (SVT) COR LOE Recommendation I C-EO In patients with syncope and SVT. single-blind trial of older patients (mean age 75 years) randomized to active pacing or back-up pacing with documented adenosine triphosphate–sensitive sinoatrial or AV block. 2017 ACC/AHA/HRS Syncope Guideline with syncope. there was a 75% risk reduction in syncope recurrence with dual-chamber pacing (266). and Heart Rhythm Society 35 .org/ by guest on November 16. The use of adenosine triphosphate in the evaluation of syncope in older patients continues to evolve.. for whom other causes have been excluded. A search and review of papers on syncope and bradycardia has been performed since the last guidelines were published in 2008 and 2012 (12. an RCT (265) showed that a dual-chamber pacemaker reduced recurrent syncope.g. determining their causal relationship to syncope often poses challenges for the practitioner. The evidence continues to support. Bradycardia: Recommendation Recommendation for Bradycardia COR LOE Recommendation Downloaded from http://circ. In a small. Shen W-K. Furthermore. these symptoms N/A appear to be independent of the rate of tachycardia. Of note. et al. 2017 In patients with syncope associated with bradycardia.2). older patients with paroxysmal SVT are more prone to syncope or near-syncope than are younger patients.264). Inc. syncope is uncommon. The writing committee has reached a consensus not to make a new recommendation on its use for syncope evaluation because of the limited data at this time. Although patients with SVT frequently manifest palpitations and lightheadedness. American Heart Association. Adenosine triphosphate is not available in the United States.1 broadly outlines strategies to guide the practitioner when evaluating patients with bradycardia. Younger patients with SVT causing syncope generally have a very rapid tachycardia.. determining the significance of atrial tachyarrhythmias and VT—which are often paroxysmal and occult on initial evaluation—poses additional challenges and may warrant a more extensive evaluation (Section 3. Evaluation of syncope in patients with Wolff-Parkinson-White syndrome with preexcitation on ECG © 2017 by the American College of Cardiology Foundation. GDMT is I C-EO recommended (12. marked resting bradycardia in a young patient with syncope). Section 4. without change from the previous recommendation. and VT.264). In adult patients presenting with syncope and chronic bifascicular block but without documented high-degree AV block. 2017 trigger VVS (270). Indications for ICDs in patients with syncope and suspected VA are predicated on the documentation of or the risk of developing lethal VA (12). abrupt change in rate. Of the patients with VA ≥200 bpm.2. One study of 113 patients with sustained VA showed that patients who had a mean VA rate of N/A ≥200 bpm had a 65% incidence of syncope or near-syncope. Patients with VA (monomorphic or polymorphic) can present with syncope.13. et al. EPS may be useful to distinguish a VT from an SVT responsible for syncope associated with these antecedent symptoms. When a patient with syncope reports antecedent palpitations and lightheadedness. including: rapid rate. Patients with paroxysmal AF are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. and then a comprehensive review of literature published since publication of these disease-specific guidelines was performed to ensure that prior recommendations about © 2017 by the American College of Cardiology Foundation.271). syncope could occur upon termination of AF when prolonged pauses are present. The risk of recurrent syncope and the overall long-term prognosis of patients with VA depend on the severity of the underlying cardiac disease substrates. GDMT is recommended I C-EO (12. As with other forms of SVT. GDMT is recommended (16).ahajournals. 34% did not experience syncope or presyncope. I C-EO In patients with AF. 4. Comprehensive guidelines exist for diagnosis and management of many of these diseases. It should be noted that palpitations can also precede vasovagal faints due to sinus tachycardia. including sections on syncope. in younger patients (269). dyssynchrony of ventricular activation. In patients with sinus node dysfunction. such as VVS. VT should be more strongly suspected than SVT. and the onset of AF may Downloaded from http://circ. In this section. whether it is nonsustained or sustained.org/ by guest on November 16. Shen W-K.. Patients with chronic AF merit control of the ventricular response or maintenance of sinus rhythm with appropriate antiarrhythmic therapy (in carefully selected N/A patients) (16). management of syncope is discussed in patients with underlying structural heart disease. abnormal atrial and ventricular activation relationships. changes in autonomic tone. Ventricular Arrhythmia: Recommendation Recommendation for VA COR LOE Recommendation In patients with syncope and VA. syncope from a rapid ventricular response (in the absence of preexcitation) is relatively unusual.264. The disease-specific ACC/AHA guidelines were assessed first. AF can be associated with syncope. and Heart Rhythm Society 36 . Structural Conditions Syncope occurs not infrequently in patients with underlying heart diseases.220. American Heart Association. so not all palpitations are necessarily due to paroxysmal SVT or VT. The mechanism of syncope from VA is multifactorial. compared with only 15% among patients with a rate <200 bpm (273). and body position during the VA (272). 2017 ACC/AHA/HRS Syncope Guideline requires a thorough history to differentiate an arrhythmic syncope from a nonarrhythmic syncope. Inc. Patients with aortic stenosis may experience syncope during exertion. Treatment of syncope is based on the specific cause of syncope. Inc. aortic valve replacement is recommended in patients with severe aortic stenosis and syncope after other causes of syncope are also considered and excluded. because of inability to augment and sustain cardiac output. 2017 underlying cardiomyopathy. Shen W-K. Specifically. There are no new data that would alter the 2011 recommendations. A review of evidence supports previously N/A published recommendations for patients with syncope in the presence of Downloaded from http://circ. GDMT is recommended (12. whereas treatment for the underlying cardiomyopathy impacts the long-term prognosis. GDMT is recommended I C-EO (20).ahajournals. the writing committee N/A supports the previous recommendations pertaining to syncope in patients with HCM. The mechanism is often hemodynamic. data from registries have shown consistently that unexplained syncope is an independent predictor for SCD and © 2017 by the American College of Cardiology Foundation. they were incorporated into the present document.13). GDMT is I C-EO recommended (11). 2017 ACC/AHA/HRS Syncope Guideline syncope remained current. Although there are no randomized trials. and Heart Rhythm Society 37 . Hypertrophic Cardiomyopathy: Recommendation Recommendation for HCM COR LOE Recommendation In patients with syncope associated with HCM. ICD therapy is also reasonable for patients with unexplained syncope and nonischemic dilated cardiomyopathy with significant LV dysfunction (12. Valvular Heart Disease: Recommendation Recommendation for Valvular Heart Disease COR LOE Recommendation In patients with syncope associated with valvular heart disease. Thus.28). A MEDLINE search and review of papers on syncope and HCM has been performed since the last guideline was published in 2011 (20). as opposed to arrhythmic.13..org/ by guest on November 16. An ICD is recommended in patients with syncope of undetermined origin with clinically relevant and significant VA induced at the time of an EPS (28). In patients with valvular heart disease N/A causing syncope. Ischemic and Nonischemic Cardiomyopathy: Recommendation Recommendation for Ischemic and Nonischemic Cardiomyopathy COR LOE Recommendation In patients with syncope associated with ischemic and nonischemic I C-EO cardiomyopathy. et al. If new published data were available. American Heart Association. Evaluation of syncope in patients with ischemic and nonischemic cardiomyopathy encompasses diagnosis and prognosis. treatment is recommended by the latest guidelines (11). 280-286). © 2017 by the American College of Cardiology Foundation.285). GDMT is recommended (12. 2017 Unexplained or arrhythmic-appearing syncope in patients with ARVC has See Online Data consistently been associated with increased risk of SCD or appropriate therapy Supplement 17. (12). however. particularly with LV dysfunction or pacing indication (290-293). Some studies have shown improvement with immunosuppression (283). ICD indications in patients with ARVC and sustained VA are no different than See Online Data guidelines-based indications for secondary prevention of SCD in other diseases Supplement 17. and Heart Rhythm Society 38 . Unlike AV block. See Online Data Other mechanisms include triggered activity and abnormal automaticity due to Supplement 18. Arrhythmogenic Right Ventricular Cardiomyopathy: Recommendation Recommendation for ARVC COR LOE Recommendations ICD implantation is recommended in patients with ARVC who present I B-NR with syncope and have a documented sustained VA (274-278). Cardiac Sarcoidosis: Recommendations Recommendations for Cardiac Sarcoidosis COR LOE Recommendations ICD implantation is recommended in patients with cardiac sarcoidosis I B-NR presenting with syncope and documented spontaneous sustained VA (12. the results of immunosuppression in patients with VA are controversial.. The present writing committee concurs that ICD implantation is reasonable in patients with HCM presenting with ≥1 recent episodes of syncope suspected to be of arrhythmic nature. the reversibility is unpredictable (287-289). myocardial inflammation (282). ICD implantation is reasonable in patients with ARVC who present with IIa B-NR syncope of suspected arrhythmic etiology (274. ICD implantation is reasonable in patients with cardiac sarcoidosis and IIa B-NR syncope of suspected arrhythmic origin.ahajournals. after ICD implantation in multiple observational studies (274-279).or consensus-based indications for secondary prevention of SCD (12.277-279). As such. whereas others have shown no benefit and even harm due to worsening VA and aneurysm formation (284.287).281). Patients with cardiac sarcoidosis and conduction abnormalities have a worse prognosis than See Online Data that of patients with idiopathic AV block (286. Immunosuppression can Supplement 18. ICD indications in patients with cardiac sarcoidosis and sustained VA are no different than guidelines. et al. it is recommended to proceed with pacing according the most recent guidelines regardless of AV block reversibility. 2017 ACC/AHA/HRS Syncope Guideline appropriate ICD discharges. Downloaded from http://circ. Inc. result in transient reversal of AV block. Patients with cardiac sarcoidosis and conduction abnormalities should be treated according to the most recent guidelines for cardiac pacing (12).org/ by guest on November 16. American Heart Association.275. Shen W-K. Macroreentry around the granulomas is the most common mechanism of VA in patients with cardiac sarcoidosis (280. In patients with cardiac sarcoidosis presenting with syncope and I C-EO conduction abnormalities.286-289).286). 4.ahajournals. In a multicenter study including 235 patients with cardiac sarcoidosis who received ICD therapy for primary or secondary prevention. cardiac arrest. Downloaded from http://circ. versus 1 of 68 in the noninducible group (294). Syncope of suspected arrhythmic cause has been correlated with increased risk of SCD. Recommendations for Brugada ECG Pattern and Syncope COR LOE Recommendations ICD implantation is reasonable in patients with Brugada ECG pattern and IIa B-NR syncope of suspected arrhythmic etiology (296-300). 6 of 8 had VA or died. Patients with cardiac sarcoidosis and mild-to-moderate LV dysfunction have a substantial risk of developing VA (290-293). with a significant male predominance (295). including patients with See Online Data syncope. et al. programmed electrical stimulation may help identify patients at risk of having VA. In patients with cardiac sarcoidosis. According to a study of 76 patients See Online Data with cardiac sarcoidosis and no cardiac symptoms. Inheritable Arrhythmic Conditions The prevalence of inherited arrhythmic conditions is low. or overall cardiac death.220). given the presence of a substrate for VA in patients with cardiac sarcoidosis. received appropriate ICD therapies were more likely to be male and to have a history of syncope. Inc. 36% of patients received appropriate ICD therapy.3. such as cardiac arrest and death.org/ by guest on November 16. ventricular pacing on baseline ECG. and a secondary prevention indication than were those who did not receive appropriate ICD therapies (292). 2017 EPS is reasonable in patients with cardiac sarcoidosis and syncope of IIa B-NR suspected arrhythmic etiology (294). sustained VA. American Heart Association. ranging from 0. Therefore. Brugada Syndrome: Recommendations Brugada syndrome is defined as a genetic disease characterized by an increased risk of SCD and ST elevation with type 1 morphology ≥2 mm in ≥1 lead among the right precordial leads V1 and V2. and Heart Rhythm Society 39 . Shen W-K. Few syncope-specific studies exist.. either at enrollment or as an outcome. During a median follow-up of 5 years. 8 (11%) had inducible Supplement 18. © 2017 by the American College of Cardiology Foundation. Most studies of patients with inherited arrhythmias are open label or not randomized and often are uncontrolled. its impact on syncope recurrence is unknown (25. Although ICD is effective in aborting cardiac arrest and presumably reducing risk of death in the patients with inheritable rhythm disorders.01% to 1%. lower LV ejection fraction.26. particularly in the presence of LV dysfunction. The prevalence is higher in Asian countries than in North America or Western Europe. occurring either spontaneously or after intravenous administration of Class I antiarrhythmic drugs. Most of the publications included other cardiac events. Patients who Supplement 18. ICD implantation is reasonable in patients presenting with syncope suspected to be of arrhythmic origin. 2017 ACC/AHA/HRS Syncope Guideline The presence of myocardial noncaseating granulomas and inflammation puts patients at risk of having both AV block and VA. rendering the clinical significance of an abnormal test a challenge. 304).304). Inc. In a retrospective multicenter study.302). Patients with syncope consistent with a reflex-mediated mechanism should not undergo the implantation of an ICD.. however. syncope. It is a rare condition. The value of EPS in assessing the mechanism of syncope in patients with Brugada is unknown. The role of inducibility of VA in identifying high-risk patients remains controversial (301. and increased risk of SCD.301. the relative risk of cardiac events (SCD. and Heart Rhythm Society 40 . Downloaded from http://circ. Invasive EPS has shown increased vulnerability to VF induction in most patients. inducibility of VA was higher among patients with a prior history of syncope or SCD. 3 times higher than among patients without a prior history of syncope or SCD (296). In large registries of patients with Brugada (PRELUDE and FINGER) (297. and 0. However. Quinidine therapy might provide some protection against VA.ahajournals.7% in patients with aborted SCD. appropriate ICD therapy was limited to survivors of cardiac arrest. particularly in the absence of documented VA. yet the clinical significance of this finding remains unknown (305). associated with a QTc interval ≤340 ms (25. syncope. there are insufficient data to make any recommendations (305.306). In a meta-analysis. or See Online Data ICD shock) among patients with a history of syncope or SCD was approximately Supplement 19.5% in asymptomatic patients (297). the value of EPS in predicting See Online Data prognosis in patients with Brugada is essentially unknown in patients with Supplement 19. ICD implantation is not recommended when the syncope mechanism is believed to be reflex mediated.301). Given the lack of benefit of ICD therapy in patients with reflex Supplement 19.297).org/ by guest on November 16. syncope. 2017 ACC/AHA/HRS Syncope Guideline Syncope is a risk factor for cardiac arrhythmic events in patients with Brugada syndrome (296.5% per year. ICD implantation is reasonable in these patients. Therefore. VA occurred only in patients with syncope suspected to be arrhythmic in origin. 1. Limited data are available about its prognostic significance. © 2017 by the American College of Cardiology Foundation.9% in patients with syncope. the benefit seems to be limited to patients with suspected arrhythmic syncope (298). American Heart Association.26). et al. ICD implantation is not recommended in patients with Brugada ECG III: No B-NR pattern and reflex-mediated syncope in the absence of other risk factors Benefit (303.302). No SCD occurred in patients with nonarrhythmic syncope or with syncope of doubtful origin (298). Data from an international registry showed that the cardiac event rate per year was 7. Short-QT Syndrome: Recommendation Short-QT syndrome is a genetic disease characterized by palpitations. In a cohort including 203 patients with Brugada. whereas none of the other patients with syncope and/or inducible ventricular fibrillation (VF) suffered an arrhythmic event See Online Data (303. 2017 Invasive EPS may be considered in patients with Brugada ECG pattern and IIb B-NR syncope of suspected arrhythmic etiology (297. Shen W-K. syncope and the known rate of inappropriate shocks and ICD complications in patients who receive an ICD (51). at a rate of 5. EPS may be considered only in patients with syncope suspected to be due to an arrhythmia and is not recommended in patients with reflex syncope. however. where significant overlap exists in the clinical presentation of patients with VVS and arrhythmic syncope (313. which affect presentation and response to therapy. See Online Data Many patients who appear to not respond to beta blockers are poorly compliant Supplement 21. Therefore. independent of QTc duration. early recognition and treatment are needed to avoid recurrences. Therefore. In the International Long QT Registry. including avoidance of strenuous activity in LQT1. 2017 ACC/AHA/HRS Syncope Guideline Recommendation for Short-QT Syncope COR LOE Recommendation ICD implantation may be considered in patients with short-QT pattern and IIb C-EO syncope of suspected arrhythmic etiology. et al. Shen W-K.317).org/ by guest on November 16. which could present as cardiac arrest or SCD.319). Patients with LQT1 appear to respond better than patients with LQTS2 and LQTS3 (316. Inc. or do not tolerate the medication (317)..to 12-fold increase in the risk of subsequent fatal/near-fatal events.02% to 1. Recommendations for LQTS COR LOE Recommendations Beta-blocker therapy.63% (305. and not all beta blockers are the same (316.314). This is particularly true in the pediatric population. There are several genetic forms of LQTS. ICD implantation may be limited to patients with suspected arrhythmic syncope. particularly in the presence of a family history of SCD (306).5 when secondary causes have been excluded or in the presence of a pathogenic mutation in 1 of the LQTS genes. Long-QT Syndrome: Recommendations LQTS is diagnosed in the presence of QTc ≥500 ms or LQTS risk score ≥3. is indicated as a I B-NR first-line therapy in patients with LQTS and suspected arrhythmic syncope (316-318). Attention to the triggers and presence of palpitations preceding syncope onset have been helpful in diagnosing an arrhythmic etiology (315). fatal events. Given that syncope is often the result of an arrhythmic event in patients with LQTS. In a study © 2017 by the American College of Cardiology Foundation. in the absence of contraindications. and Heart Rhythm Society 41 .ahajournals. Beta-blocker therapy was associated with a See Online Data significant reduction in the risk of recurrent syncope and subsequent fatal/near- Supplement 21. It can also be diagnosed when the Downloaded from http://circ. Patients with LQTS and syncope should adhere to the lifestyle changes previously published. The response to beta blockers depends on the genotype. Supplement 20.320). depending on the genotype (316. ranging from 0. Cardiac events can occur in patients receiving beta-blocker therapy. 2017 QTc is 480 to 499 ms in a patient presenting with syncope (25).320-324). American Heart Association.307-312). ICD implantation is reasonable in patients with LQTS who continue to have syncope despite beta- blocker therapy and in those who cannot tolerate beta-blocker therapy. patients who experienced ≥1 episode of syncope had a 6. There is no evidence that syncope in patients with short-QT See Online Data pattern is a risk factor for cardiac arrest in the absence of documented VT or VF. with a prevalence ranging from 10% to 32%. The prevalence of short-QT syndrome is very low. and drugs known to prolong QT interval in all patients with LQTS (25). ICD implantation is reasonable in patients with LQTS and suspected IIa B-NR arrhythmic syncope who are on beta-blocker therapy or are intolerant to beta-blocker therapy (317. 326).1 per 1. The prevalence of the disease is estimated to be around 0.. Patients usually present in the first or second decade of life with stress-induced syncope (25). Shen W-K. The variability in outcome with Supplements 22 and beta-blocker therapy is due to multiple factors. breakthrough arrhythmias occur in patients with Supplements 22 and CPVT because of treatment failure. of heavy exercise and competitive sports. American Heart Association. However. Therefore. Inc. In patients with CPVT.334.334. The addition of flecainide to conventional therapy has been shown to partly or © 2017 by the American College of Cardiology Foundation. and in those with frequent shocks from their ICD.000 patients. highlighting the role of the sympathetic nervous system in Supplements 22 and arrhythmogenesis (328. exercise restriction. Flecainide is reasonable in patients with CPVT who continue to have IIa C-LD syncope of suspected VA despite beta-blocker therapy (319. LCSD alone does not completely prevent cardiac events. Therefore. The presence of VA in patients with CPVT has been shown to correlate with See Online Data increases in heart rate. et al. Repeat exercise testing and cardiac monitoring to document arrhythmia suppression can be reassuring (334. (337. 60% have a mutation in either the gene encoding the cardiac ryanodine receptor (RyR2) (autosomal dominant) or in the cardiac calsequestrin gene (CASQ2) (autosomal recessive) (330-333). LCSD can be Supplement 21. Left cardiac sympathetic denervation (LCSD) is reasonable in patients with LQTS and recurrent syncope of suspected arrhythmic mechanism who are IIa C-LD intolerant to beta-blocker therapy or for whom beta-blocker therapy has failed (325-327).329). See Online Data Despite beta-blocker therapy. beneficial in patients with recurrent syncope despite beta blockade. Beta blockers should be first-line therapy in patients with CPVT.334.338). is recommended in all patients with CPVT (335). Recommendations for CPVT COR LOE Recommendations Exercise restriction is recommended in patients with CPVT presenting with I C-LD syncope of suspected arrhythmic etiology (328.336).339).334). and Heart Rhythm Society 42 .336-339). LCSD also reduces shocks in See Online Data patients with an ICD during arrhythmia storms.org/ by guest on November 16. they are not See Online Data always completely protective (329.320).335). 23. noncompliance. LCSD has been shown to be associated with a large and significant clinical benefit in patients with symptomatic LQTS who are either refractory or intolerant to beta-blocker therapy (325. syncope was a predictor of appropriate therapy (322). 2017 Catecholaminergic Polymorphic Ventricular Tachycardia: Recommendations CPVT is characterized by the presence of catecholamine-induced (often exertional) bidirectional VT or polymorphic VT in the setting of a structurally normal heart and normal resting ECG (328. as they have been shown to suppress exercise-induced arrhythmias. including dosing and compliance 23. during long-term follow-up. Downloaded from http://circ. including avoidance 23. including SCD. However. in those who cannot tolerate beta-blocker therapy. Beta blockers lacking intrinsic sympathomimetic activity are recommended I C-LD in patients with CPVT and stress-induced syncope (329. 2017 ACC/AHA/HRS Syncope Guideline of 459 patients with genetically confirmed LQTS who received an ICD. and subtherapeutic dosing.ahajournals. and Heart Rhythm Society 43 .347). Furthermore.347). ICD implantation should be performed in conjunction with beta blocker therapy or LCSD when available (342). One study showed that the presence of a J wave increased the risk of VF from 3. In patients intolerant of beta- blocker therapy. © 2017 by the American College of Cardiology Foundation.4/100.353. including delaying the onset of 23.org/ by guest on November 16. When syncope occurs despite optimal medical therapy. In a worldwide cohort study. 68% after LCSD (349). LCSD may be reasonable in patients with CPVT.342.000 (353). including long detection intervals with high cutoff rate. with 70% of the subjects being male (351). the clinical significance of the early repolarization pattern is unknown. VT storms in patients with CPVT may not always respond to ICD shocks (344). it has been shown in population-based studies to be associated with increased risk of cardiac death (352.000 to 11/100. ICD therapy appears to reduce mortality rate in patients with CPVT and syncope or VA refractory to medical therapy.343). Early repolarization ECG pattern (>1 mm) in the inferior/lateral leads occurs in 1% to 13% of the general population and in 15% to 70% of idiopathic VF cases (352-354). is recommended to decrease the Downloaded from http://circ. LCSD may be a See Online Data reasonable therapy (348-350). syncope. American Heart Association. Furthermore. the effectiveness of ICD shock therapy in CPVT depends on Supplements 22 and the mechanism of the VA. flecainide is useful as monotherapy (341).ahajournals. the absolute risk in patients with early repolarization remains low. In patients with CPVT who continue to experience syncope or VA. However. particularly African Americans. given the low incidence of VF in the general population. 2017 ACC/AHA/HRS Syncope Guideline completely suppress exercise-induced VA (340). In patients with syncope. IIb C-LD verapamil with or without beta-blocker therapy may be considered (346. Early Repolarization Pattern: Recommendations Early repolarization pattern is characterized by a distinct J point and ST elevation in the lateral or inferolateral leads. The pattern is more prevalent in young athletes. Inc. the percentage of Supplements 22 and patients with major cardiac events despite optimal medical therapy was reduced 23. However. Careful programming. ICD therapy is reasonable in patients with CPVT and a history of exercise- IIa B-NR or stress-induced syncope despite use of optimal medical therapy or LCSD (271. for VF (345).. with greater success noted when shocks are delivered 23.343). See Online Data Verapamil alone or in combination with beta blockers helps suppress Supplements 22 and arrhythmias in patients with CPVT (347).355-357). et al. exercise-induced ventricular ectopy (346. Shen W-K. Recommendations for Early Repolarization Pattern COR LOE Recommendations ICD implantation may be considered in patients with early repolarization IIb C-EO pattern and suspected arrhythmic syncope in the presence of a family history of early repolarization pattern with cardiac arrest. and symptomatic IIb C-LD VA despite optimal medical therapy (348-350). 2017 prevalence of inappropriate shocks (342. and shocks may precipitate early recurrence of arrhythmia because of their painful nature with resultant adrenergic See Online Data state. Reflex Conditions 5. N/A VF. reassurance about the benign nature of the condition should be provided. VF was inducible in only 22% of cases. An episode of VVS is typically associated with a prodrome of diaphoresis. Preliminary data from cardiac ganglia plexi ablation in treating selected patients with VVS are encouraging but still insufficient to make recommendations at this time (370-372). triggered by prolonged standing or exposure to emotional stress. or medical procedures (361-365).1. et al.. The underlying pathophysiology of VVS results from a reflex causing hypotension and bradycardia. Downloaded from http://circ. and Heart Rhythm Society 44 . © 2017 by the American College of Cardiology Foundation. there are limited evidence-based therapeutic options (369).353. as syncopal events may result in injury and an impaired quality of life (QoL) (366-368). Physical counter-pressure maneuvers can be useful in patients with VVS who IIa B-R have a sufficiently long prodromal period (373-375). Given the benign nature of VVS and its frequent remissions. or polymorphic VT with documented early repolarization pattern in the affected family member (358. In all patients with the common faint or VVS. Recommendations for VVS COR LOE Recommendations I C-EO Patient education on the diagnosis and prognosis of VVS is recommended. In a multicenter study including 81 patients with early repolarization syndrome and aborted SCD who underwent EPS.359). Given the high prevalence of early repolarization. Inc. American Heart Association. Shen W-K. The VF recurrence rate was similar in patients who were inducible and in those See Online Data who were noninducible (359). pain. Supplement 24. warm environments. effective treatment is needed. medical treatment is usually not required unless conservative measures are unsatisfactory. with fatigue after the event. See Online Data education targeting awareness of and possible avoidance of triggers (e.360).org/ by guest on November 16. an explanation of the diagnosis. EPS is not recommended in patients with early repolarization and syncope in the absence of other cardiac indications (352. the possibility of inducing VF in healthy individuals.. III: EPS should not be performed in patients with early repolarization pattern B-NR Harm and history of syncope in the absence of other indications (359).ahajournals. Vasovagal Syncope: Recommendations VVS is the most common cause of syncope and a frequent reason for ED visits (66). In some patients. 2017 5. and pallor.g. 2017 ACC/AHA/HRS Syncope Guideline ICD implantation may be considered in patients with early repolarization pattern and suspected cardiac syncope if they have a family history of unexplained SCD. prolonged Supplements 25 and standing. See Figure 4 for the algorithm for treatment of VVS. Despite the need and substantial efforts by investigators. coping with dental and medical settings). warmth. and 26. and the limited value of ventricular programmed stimulation in risk stratification. In patients with a sufficiently long prodrome. Serum potassium level should be monitored because of potential 26.. POST II (Prevention of Syncope Trial II) reported a marginally insignificant 31% risk reduction in adults with moderately frequent VVS. physical counter-maneuvers (e.387). or urinary retention (376-380). in a meta-analysis of a prespecified. HF. There are 2 main methods of orthostatic training. fluid. in patients with recurrent VVS and no clear contraindication. et al. midodrine was associated with a 43% reduction in syncope recurrence Downloaded from http://circ. an age-dependent 26. which was significant in patients after a 2-week dose stabilization period (388). compared with those of younger age (394.390-393).383.379. Midodrine is a prodrug that is metabolized to desglymidodrine. The usefulness of orthostatic training is uncertain in patients with frequent VVS IIb B-R (382-386).. Nonetheless. 2017 (318. Encouraging increased salt and fluid intake may be reasonable in selected patients IIb C-LD with VVS. Studies on the Supplements 25 and efficacy of midodrine support its use. American Heart Association. which is a peripherally active alpha-agonist used to ameliorate the reduction in peripheral sympathetic neural See Online Data outflow responsible for venous pooling and vasodepression in VVS.376. unless contraindicated (388. parallel.g. unless contraindicated (396-399). Evidence for the effectiveness of salt and fluid intake for patients with VVS is limited. and avoidance) was superior to conventional therapy in preventing syncope recurrence (375). an RCT found more recurrent symptoms in the fludrocortisone arm than in Supplements 25 and the placebo arm (389). or cardiac dysfunction. label trial.e. not shown a sustained benefit in reducing episodes of syncope recurrence with either option (382.org/ by guest on November 16. it may be reasonable to encourage ingestion of 2 to 3 L of fluid per day and a total of 6 to 9 g (100 to 150 © 2017 by the American College of Cardiology Foundation.395). Midodrine is reasonable in patients with recurrent VVS with no history of IIa B-R hypertension. However. drug-induced hypokalemia. HF. 2017 ACC/AHA/HRS Syncope Guideline Patients with a syncope prodrome should be instructed to assume a supine position to prevent a faint and minimize possible injury. such as a N/A history of hypertension. counseling. and Heart Rhythm Society 45 . which results in increased blood volume.385. Inc. Shen W-K. leg crossing with conventional therapy (i. children. Fludrocortisone has mineralocorticoid activity resulting in sodium and water retention and potassium excretion. open- Supplements 25 and 26. Patients undergo repetitive tilt-table tests in a monitored setting until a negative tilt-table test occurs and then are See Online Data encouraged to stand quietly against a wall for 30 to 60 minutes daily. In a randomized. Supplements 25 and prestratified substudy of POST I and a large observational study. squatting) are a core management strategy. In a pediatric See Online Data population. benefit of beta blockers among patients ≥42 years of age was found. Beta blockers might be reasonable in patients 42 years of age or older with IIb B-NR recurrent VVS (390-393). renal disease.ahajournals. Fludrocortisone might be reasonable for patients with recurrent VVS and IIb B-R inadequate response to salt and fluid intake. or patients simply Supplements 25 and standing quietly against a wall at home for a prolonged period of time daily. limb and/or abdominal See Online Data contraction.389).381)..378. RCTs on the efficacy and effectiveness of beta blockers for the prevention of syncope See Online Data have been negative (64. RCTs have 26. In a meta-analysis of 5 RCTs in adults and 26. leg crossing. salt intake. VVS indicates vasovagal syncope.. Care should be taken to withdraw N/A or reduce medications only where safe to do so and in conjunction with the prescribing healthcare provider. Three small RCTs on selective Supplements 25 and serotonin reuptake inhibitors have been conducted on the effectiveness of fluoxetine 26. Serotonin has central neurophysiological effects on blood pressure and heart rate and See Online Data acutely induces syncope during tilt-table testing (403). A careful examination of the patient’s history for medications that may lower blood pressure (hypotensive agents) should be performed. Figure 4. The long-term balance of risks and benefits of a strategy of increasing salt and water intake is unknown. Pacemakers in Vasovagal Syncope: Recommendation Pacemakers might seem to be an obvious therapy for VVS. with contradictory evidence of effectiveness Downloaded from http://circ. It is becoming clear that strict patient selection on the basis of documented © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society 46 . 5. and paroxetine in preventing syncope.401. Numerous observational studies and RCTs have assessed whether pacemakers are efficacious in preventing syncope (404-409).402). Vasovagal Syncope VVS Education on diagnosis and prognosis (Class I) Options Counter pressure Salt and fluid maneuvers intake (Class IIa) (Class IIb) VVS recurs Options Beta blocker Selected serotonin Dual-chamber Midodrine Fludrocortisone Orthostatic training (in patients >42 y) reuptake inhibitors pacemaker therapy (Class IIa) (Class IIb) (Class IIb) (Class IIb) (Class IIb) (Class IIb) Colors correspond to Class of Recommendation in Table 1. or about 1 to 2 heaping teaspoonfuls.org/ by guest on November 16. a selective serotonin reuptake inhibitor might be IIb C-LD considered (393. Shen W-K. it may be reasonable to reduce or withdraw IIb C-LD medications that cause hypotension when appropriate (400).2. 2017 ACC/AHA/HRS Syncope Guideline mmol) of salt per day. In selected patients with VVS. Inc. In patients with recurrent VVS.ahajournals. 2017 (393. American Heart Association. et al.402). given that bradycardia and asystole are present during some spells.401. 419-426). Among patients with a positive tilt-table test. in a select population of patients >40 years of age with recurrent and 28. the results of which were used to frame our decision making. Shen W-K. or myocardial infarction within the prior 3 months. Supplements 27 However. 2017 ACC/AHA/HRS Syncope Guideline asystole during clinical syncope is important. stroke.410). In 2 RCTs. Full details are provided in the ERC’s systematic review report (9).org/ by guest on November 16. Carotid sinus massage should be performed sequentially over the right and left carotid artery sinus in both the supine and upright positions for 5 seconds each. Contraindications to performing carotid sinus massage include auscultation of carotid bruit and transient ischemic attack.404.ahajournals. 2017 of recurrent syncope was evident as compared with medical or no therapy in open-label trials (52. or a significant vasodepressor response if there is ≥50 mm Hg drop in systolic blood pressure. © 2017 by the American College of Cardiology Foundation.414) and is due to an abnormal reflex attributed to baroreceptor and possibly medulla dysfunction (415. syncope and documented spontaneous pauses ≥3 seconds correlated with syncope or an asymptomatic pause ≥6 seconds. There was less benefit in patients with a positive tilt-table test that induced a vasodepressor response (405). either spontaneously or with carotid sinus massage. American Heart Association. a benefit of pacing for treatment Downloaded from http://circ.1. with continuous beat-to-beat heart rate monitoring and blood pressure measurement (417). See Online Data there was no statistically significant benefit seen with active pacing (407. dual-chamber pacing reduced syncope recurrence. Recommendations for Carotid Sinus Syndrome COR LOE Recommendations Permanent cardiac pacing is reasonable in patients with carotid sinus IIa B-R syndrome that is cardioinhibitory or mixed (413. Recommendation for Pacemakers in VVS COR LOE Recommendation Dual-chamber pacing might be reasonable in a select population of IIb B-R SR patients 40 years of age or older with recurrent VVS and prolonged spontaneous pauses (404-408. and Heart Rhythm Society 47 .408). Carotid Sinus Syndrome: Recommendations Carotid sinus syndrome is associated with mechanical manipulation of the carotid sinus. with a cardioinhibitory response if asystole is >3 seconds or if there is AV block. It is diagnosed by the reproduction of clinical syncope during carotid sinus massage. the recommendation in this section was based on a separately commissioned systematic review of the available evidence. but this result must be interpreted with caution because of the possibility of outcome ascertainment bias. SR indicates systematic review.406.3. As noted in Section 1. Inc.. et al. It occurs more commonly in men >40 years of age (413.416). and that observation combined with a tilt-table test that induces minimal or no vasodepressor response may increase the likelihood of a response to pacing. 5. or a mixed cardioinhibitory and vasodepressor response. except if carotid Doppler excludes significant stenosis (418).410-412). This is because a positive tilt-table test might identify patients who are likely to also have a vasodepressor response during VVS and therefore not respond as well to permanent pacing. Neurogenic OH may present clinically as classic or delayed OH. Normally. Other Reflex Conditions Downloaded from http://circ. Neurogenic Orthostatic Hypotension: Recommendations OH involves excessive pooling of blood volume in the splanchnic and leg circulations.433-436). Appropriate investigations should be undertaken to determine an underlying etiology. cough syncope.. such as multiple system atrophy. the relative risk reduction of syncope recurrence with pacemaker implantation was 76% (409. with a resultant decrease in cardiac output (31). including micturition syncope. such as diuretics and vasodilators. small case series. so increased fluid and salt consumption and reduction or removal of hypotensive drugs and diuretics are encouraged where appropriate and safe (436).427-429). the vasoconstrictor mechanisms of vascular tone may be inadequate because of neurodegenerative disorders. such as those due to diabetes mellitus and other systemic diseases (31).418.1. Syncope caused by OH conditions occurs in the upright position. 2017 ACC/AHA/HRS Syncope Guideline Syncope recurred in fewer patients treated with pacing than in untreated patients. Evidence for dual-chamber pacing versus single-chamber pacing in carotid sinus hypersensitivity is limited to a few small RCTs and limited observational data See Online Data (409. Inc. laugh syncope. Recommendations for Neurogenic OH COR LOE Recommendations © 2017 by the American College of Cardiology Foundation. Evidence for treatment is limited mainly to case reports. It may be reasonable to implant a dual-chamber pacemaker in patients with IIb B-R carotid sinus syndrome who require permanent pacing (427-430). Treatment of most types of situational syncope relies heavily on avoidance or elimination of a triggering event. Although mixed. With standing. venous return to the heart drops. and autonomic peripheral neuropathies. See Online Data with observation periods up to 5 years (420. Parkinson’s disease.ahajournals. This may not always be possible.423). In some individuals. Most commonly. and Heart Rhythm Society 48 . and swallow syncope (431-437). heart rate. including causes that may be reversible (431. 2017 Situational syncope is defined as syncope occurring only in certain distinct and usually memorable circumstances. trials. et al. OH is due to dehydration or medications.427-429).4. In neurogenic OH. prevent hemodynamic compromise and improve symptom recurrence in older adults who may have concomitant sinus node dysfunction or conduction system disease. 6.433-436). and cardiac contractility. In 3 controlled. See Figure 5 for the algorithm for treatment of OH. the autonomic nervous system provides compensatory changes in vascular tone. defecation syncope. and small observational studies (431. 5. pure autonomic failure.org/ by guest on November 16. Orthostatic Hypotension 6. this response may be defective or inadequate (31). Shen W-K. open-label Supplements 29–32. There are no large RCTs. the data suggest dual-chamber pacing may Supplements 29–32. American Heart Association. 467). Fludrocortisone can be beneficial in patients with syncope due to neurogenic IIa C-LD OH (473-476).469).460.445-450).468. at least in astronauts after space flight (476). respectively (397.470-472). other medications should be used before fludrocortisone. Use of carbidopa in patients Supplements 33 and with Parkinson disease may decrease the effectiveness of droxidopa (380). pure autonomic failure. can increase blood pressure. and nausea (468. piloerection. Other side effects commonly seen include © 2017 by the American College of Cardiology Foundation. The benefit is limited to patients with sufficient prodrome and the ability to perform these maneuvers adequately and safely (449). salt may reduce this effect by splanchnic vasodilatation or a decreased osmopressor response.463. IIa C-LD Compression garments can be beneficial in patients with syncope and OH (451-455). and other common side effects include scalp tingling.441.ahajournals. The pressor effect of water is most likely sympathetically See Online Data driven. Use and 34. Droxidopa improves symptoms of neurogenic OH due to Parkinson disease. with a resultant improvement in See Online Data symptoms of OH (473. Midodrine improves symptoms of OH in patients with neurogenic OH (458-467). Supine hypertension 34. Downloaded from http://circ.477. lower body muscle tensing. headache. with the largest effect See Online Data occurring with squatting versus other counter-pressure maneuvers (374.462.439). thigh high and preferably include the abdomen. hypertension. and multiple system atrophy (380. may be a limiting factor. et al.439). such as by leg crossing. temporary relief (438.468-471).470.460. Its use may be limited by supine 34. with the peak effect occurring 30 minutes after ingestion of ≥240 mL and Supplements 33 and additional benefit seen with ≥480 mL (398. Fludrocortisone increases plasma volume.445-450). When taken regularly.467). titration of droxidopa may be limited by supine hypertension (380. Similar or larger benefit would be expected with squatting and other isometric contraction (449). dizziness. usually corresponding to an increase in standing Supplements 33 and blood pressure (459. Shen W-K.466. including older adult patients and those with neurogenic See Online Data etiologies.478). 2017 ACC/AHA/HRS Syncope Guideline Acute water ingestion is recommended in patients with syncope caused by I B-R neurogenic OH for occasional. according to small studies (472). The garments should be at least 34. Acute water ingestion for temporary relief of OH is not intended for routine or long-term use (24). The presence of glucose or 34.442).org/ by guest on November 16.471). and maximal force handgrip.463. IIa C-LD Physical counter-pressure maneuvers can be beneficial in patients with neurogenic OH with syncope (374. Isometric contraction. In neurogenic OH. (447). Midodrine can be beneficial in patients with syncope due to neurogenic OH IIa B-R (458-467). When supine hypertension is present. See Online Data There is a dose-dependent effect. In patients with OH. American Heart Association.. fludrocortisone may Supplements 33 and prevent OH. as shorter garments have not been proved to be beneficial (457). and urinary retention (459. and Heart Rhythm Society 49 . Droxidopa See Online Data might reduce falls. 2017 Supplements 33 and Leg crossing increases cardiac output in patients with neurogenic hypotension 34. compression garments can improve orthostatic symptoms and blunt Supplements 33 and associated decreases in blood pressure (451-456). Droxidopa can be beneficial in patients with syncope due to neurogenic OH IIa B-R (380. acute water ingestion can temporarily restore orthostatic tolerance (438-444). Inc. 482).441-443).398. Rehydration. Salt supplementation (e. such as adrenal suppression and immunosuppression. most likely mediated by 34.439.481. which promotes vasodilation (495-497).org/ by guest on November 16. whether by intravenous or oral formulation. Octreotide may be beneficial in patients with syncope and refractory IIb C-LD recurrent postprandial or neurogenic OH (484-487). depending on whether a person has compensated or uncompensated hypovolemia (494). renal disease. and Heart Rhythm Society 50 . pyridostigmine is able to See Online Data improve orthostatic tolerance through increases in peripheral vascular resistance Supplements 33 and and blood pressure (481.. or cardiac Downloaded from http://circ.480). © 2017 by the American College of Cardiology Foundation. vomiting.499.444). and urinary incontinence (483). salivation. 2017 dysfunction. including the benefits and risks. 6 to 9 g [100 to 150 mmol.439-444). and the long-term effects of these treatments. increases 34. should include sodium supplementation for more rapid recovery (21. Orthostatic tolerance worsens with dehydration and is exacerbated by heat stress.501-504). but often feasibility of cessation of medications is limited by the necessity of the treatments (491-493). Dehydration and Drugs: Recommendations Syncope related to medication becomes prevalent particularly in older adults.482). these 2 treatments may improve blood pressure while decreasing symptoms from OH (396. with a peak effect approximately 30 minutes after ingestion (398. Dehydration may manifest along a spectrum of symptoms. about 1 to 2 teaspoons] of salt per day) increases plasma volume. sweating. can also occur with doses >0.3 mg daily (479. Encouraging increased salt and fluid intake may be reasonable in selected IIb C-LD patients with neurogenic OH (396.g.. and headache. hypokalemia. who frequently have multiple comorbidities requiring treatment and are prone to polypharmacy effects (488-490). sympathetic activation.2. American Heart Association.398. blood pressure. is unknown. with See Online Data limited benefit in patients with already high salt intake (396). which prevents postprandial hypotension. Pyridostigmine may be beneficial in patients with syncope due to neurogenic IIb C-LD OH who are refractory to other treatments (466.443. This additional salt and fluid intake may not be beneficial in patients with history of hypertension. Although the data are limited for salt and fluid supplementation in patients with OH. Side effects include nausea. cramping. HF. abdominal 34. et al.441. Water ingestion Supplements 33 and increases the blood pressure via a pressor effect. Octreotide reduces splanchnic blood flow by Supplements 33 and approximately 20% (486). and this pooling can worsen See Online Data in the postprandial period (484-487). and improves orthostatic tolerance (484-487). 2017 ACC/AHA/HRS Syncope Guideline edema.ahajournals. Splanchnic circulation pooling can contribute to OH. ranging from tachycardia to shock. Cessation of offending medications is usually key for symptomatic improvement. Shen W-K. In patients with autonomic failure and neurogenic OH. but more serious adverse reactions. 6.498-501). Inc. Recommendations for Dehydration and Drugs COR LOE Recommendations Fluid resuscitation via oral or intravenous bolus is recommended in I C-LD patients with syncope due to acute dehydration (438. and the use of a large number of medications causing adverse effects because of drug-drug interactions (488.507.502).org/ by guest on November 16. Beverages with increased sodium concentration (closer to normal body osmolality) rehydrate faster than beverages with lower sodium concentration or increased osmolality (e. Several drug classes have Downloaded from http://circ.492.492. or chronic kidney disease (19). vasodilators. effect because oral fluid loading has a pressor effect (398. American Heart Association. and Heart Rhythm Society 51 .506). Oral fluid bolus may Supplements 35 require less volume than intravenous fluid infusion to have a similar treatment and 36. 2017 ACC/AHA/HRS Syncope Guideline Fluid resuscitation is recommended for syncope secondary to both dehydration and exercise-associated hypotension.507-510).. venodilators..504. and sedatives (488-490. Close Supplements 35 supervision during adjustment of medications is frequently required because of and 36. In patients with dehydration. uncontrolled hypertension. because of glucose content) (498-501. et al. often resulting in hospital admission (488. The latter is likely due to peripheral vasodilation and vasovagal physiology (438. Higher-sodium-content beverages with Supplements 35 osmolality comparable to normal body osmolality may rehydrate faster than and 36.507.503). Inc. Other factors to consider include frailty. including diuretics.492.g.507-510).438.489).498-500. The prevalence of medication-related syncope appears higher in older patients (491. HF and/or cardiac dysfunction. it is reasonable to IIa C-LD encourage increased salt and fluid intake (396. See Online Data negative chronotropes. Syncope is a commonly reported adverse drug reaction. potential worsening of preexisting supine hypertension or cardiac arrhythmias (491-493. This additional dietary sodium may be provided as sodium tablets or sodium already dissolved See Online Data in beverages (396.499. In selected patients with syncope due to dehydration. Both dehydration See Online Data and heat stress worsen orthostatic tolerance (495-497).511).503).510).503).505). lower-sodium-content beverages (498-501.ahajournals.498-501.511-513). 2017 been implicated in syncope.503. sodium supplementation improves plasma volume and improves orthostatic tolerance (396. Shen W-K.503).495. © 2017 by the American College of Cardiology Foundation.440-444. This treatment option is not appropriate for patients with cardiac dysfunction or HF. Reducing or withdrawing medications that may cause hypotension can be IIa B-NR beneficial in selected patients with syncope (488-490. Shen W-K. Inc.ahajournals. recurrent. exercise intolerance. Most commonly. including blood pressure decrease. American Heart Association. 2017 ingestion medications ingestion (Class I) (Class IIa) (Class I) Therapy options in selected patients Compression garments Reduce or withdraw Increase salt and Increase salt (Class IIa) and fluid intake medications fluid intake Counter-pressure (Class IIb) (Class IIa) (Class IIa) maneuvers (Class IIa) Octreotide (Class IIb) Midodrine (Class IIa) Pydridostigmine (Class IIb) Droxidopa (Class IIa) Fludrocortisone (Class IIa) Colors correspond to Class of Recommendation in Table 1. in which upright posture results in an apparently inappropriate tachycardia. generalized weakness. BP indicates blood pressure. blurred vision.org/ by guest on November 16. which may or may not meet criteria for OH. 2017 ACC/AHA/HRS Syncope Guideline Figure 5. the symptoms include lightheadedness. These symptoms may be accompanied by hemodynamic disturbances. et al. One condition of note is POTS. and Heart Rhythm Society 52 . and fatigue.. and heart rate increase. Orthostatic Hypotension Syncope of suspected OH origin Postural decrease in Continue to No BP ≥20/10 mm Hg evaluate Options Neurogenic OH Drugs Dehydration Acute water Reduce or withdraw Acute water Downloaded from http://circ. The pathophysiology is quite varied. OH. orthostatic hypotension. 7. © 2017 by the American College of Cardiology Foundation. which may be inadequate or compensatory (38). or persistent symptoms that develop upon standing (usually with a change in position from sitting or lying to an upright position) and are relieved by sitting or lying (38). Orthostatic Intolerance Orthostatic intolerance is a general term referring to frequent. tremulousness. usually with heart rates >120 bpm (24). palpitations. or EEG during a psychogenic pseudosyncope episode can be documented (229). Pseudosyncope: Recommendations Psychogenic pseudosyncope is a syndrome of apparent loss of consciousness occurring in the absence of impaired cerebral perfusion or function. the patient is likely to be referred for evaluation of syncope (30. but it is included in the present document because patients appear to exhibit syncope and therefore are referred for evaluation of syncope. we refer readers to the HRS consensus statement (24). 8. may be beneficial in conversion disorders (530-532). occasionally tilt-table testing with or without transcranial Doppler and monitoring of an EEG is helpful. significant trend toward improvement in pseudosyncope at 3 months (530). The clinical distinction between the 2 is based on whether prominent jerky muscle movements simulating seizure activity are reported by witnesses. Recommendations for the Treatment of Pseudosyncope COR LOE Recommendations In patients with suspected pseudosyncope. A normal pulse.527. et al. involuntary nature of the attacks (30. and episodes are frequent (525). Patients with psychogenic pseudosyncope are often young females with a higher prevalence of preexisting VVS or a history of physical and/or sexual abuse (229.org/ by guest on November 16.ahajournals. See Online Data Some reports suggest that patients benefit from being informed of the suspected Supplements 37 and diagnosis in a clear but sympathetic manner that also acknowledges the 38. None alone. and Heart Rhythm Society 53 .. a candid discussion with the IIb C-LD patient about the diagnosis may be reasonable (30. American Heart Association. Shen W-K. and usually little physical harm (526). Although many patients with pseudosyncope can be diagnosed with a careful history. however. lack of pallor and diaphoresis. 2017 and pseudoseizures may be the same condition.527-529). blood pressure.514). There are no data that support significant benefit from pharmacotherapy (529). The apparent duration of loss of consciousness is often long (5 to 20 minutes). One Supplements 37 and RCT reported that cognitive behavioral therapy provided a non–statistically 38. provides a definitive diagnosis. particularly cognitive See Online Data behavioral therapy. Psychogenic pseudosyncope is believed to be a conversion disorder—in essence. Cognitive behavioral therapy may be beneficial in patients with IIb C-LD pseudosyncope (530-532). although this is unknown (24. Several key clinical features are suggestive of the diagnosis of psychogenic pseudosyncope. Inc.514-523). Some common characteristics include closed eyes. Psychogenic pseudosyncope does not result in a true loss of consciousness.229. and there is little evidence that the syncope is due to POTS (24. In the absence of associated jerky movements. © 2017 by the American College of Cardiology Foundation. an external somatic manifestation or response to internal psychological stresses. Treatments that improve symptoms of POTS might decrease the occurrence of syncope.524). Uncontrolled studies suggest that psychotherapy.528). Psychogenic pseudosyncope Downloaded from http://circ. it is relatively infrequent. 2017 ACC/AHA/HRS Syncope Guideline Although syncope occurs in patients with POTS. It is an involuntary response and should not be confused with malingering or Munchausen syndrome.525). For further guidance on the management of POTS. 547) deposition. Chest pain and ECG changes consistent with ischemia are commonly seen. Further confirmation of this finding in the older populations is warranted. impaired the kidneys. and peripheral and cardiac output from restrictive autonomic nervous systems. may shock. orthopnea. specific conditions may predispose the patient to various types of syncope. cardiogenic Often tachycardia and hypotension. American Heart Association. Amyloidosis Systemic disease due to amyloid Syncope may be due to conduction (546. Table 9. and conduction disease. cardiomyopathy. hypotension and Syncope due to bradycardia and/or (128. it is not necessary to fully evaluate for all these causes when the etiology remains elusive. It is not intended as a reference for differential diagnosis or a complete synopsis of all conditions associated with syncope. followed by vasodilatation. Most of these presentations rarely cause syncope. May be associated with cough syncope. activity cardiac arrest in severe cases. arrhythmias. Infiltrative Fabry’s disease Lysosomal storage disorder with Syncope usually due to AV block.ahajournals. If the cause for syncope is unclear. 2017 ACC/AHA/HRS Syncope Guideline 9. arthropathy. tachycardia. impotence. or neurological involvement. be hypotensive and bradycardic acutely. often due to stress. according to case reports. Hemochromatosis Systemic iron deposition causing liver Myocardial involvement more common (548) disease. these conditions could be included in the differential diagnosis on the basis of other clinical characteristics and/or historical features. However. Conditions Uncommonly Associated With Syncope Condition Clinical Characteristics Notes Downloaded from http://circ. Table 9 provides a list of less common conditions associated with syncope. © 2017 by the American College of Cardiology Foundation. (533-535) exertional dyspnea.org/ by guest on November 16. Furthermore.543) shock leading to pulseless electrical hypotension. renal failure concentric LVH. Pulmonary embolus Hypoxemia. et al. Light chain amyloidosis affects system disease. tachycardia. and HF. skin pigmentation. diabetes than sick sinus syndrome and AV mellitus. although VA may occur with myocardial involvement. Pulmonary arterial Occurs more often during exertion in Syncope due to inability to augment or hypertension younger patients. The intertrabecular recesses. (544. including edema. Shen W-K.541) hypercontractility. 2017 Cardiovascular and Cardiopulmonary Cardiac tamponade Hypotension. and data are sparse. and Heart Rhythm Society 54 .545) neuropathic pain. Takotsubo cardiomyopathy Apical ballooning and basal Syncope is uncommon and may be (540. Constrictive pericarditis Severe HF symptoms. Inc. heart. One study showed higher prevalence of pulmonary embolus in older patients with first episode of syncope after admission to the hospital.542. LV noncompaction Cardiomyopathy characterized by Syncope reported in 5%–9% of both (536-539) prominent LV trabeculae and deep adult and pediatric patients. embryologic perturbation. multifactorial. due to mechanism may be a tachyarrhythmia. AV block is the likely cause. sustain cardiac output during exertion.. Uncommon Conditions Associated With Syncope Syncope has been reported in many uncommon diseases. dilated cardiomyopathy. Hemodynamic of syncope. dilated (566) manifesting as scapulohymeral and/or cardiomyopathy. American Heart Association. alopecia. Chagas disease Chagasic cardiomyopathy caused by Syncope and sudden death associated (556-559) trypanosomiasis. bladder dysfunction.561) multiple organ systems affected. Chronic Many patients develop significant His (564.555). including erythema many patients manifest VVS (554. daytime somnolence. (567-571) cardiac skeleton. or profound LV VT and AV block are the likely causes (413. syncope alone does not appear to increase the risk of death. AV conduction disease. Cardiac tumors Triad of obstruction. Anomalous coronary artery Common cause of exertional syncope or Syncope can be due to Bezold Jarisch (576-579) SCD. sympathetic fibers in the thoracic spinal Chiari malformation cord is a rare mechanism of syncope (598) (599). hemodynamically significant stenosis of the subclavian artery. and HF. Neuromuscular Myotonic dystrophy Autosomal dominant inheritance with Both bradyarrhythmia and (12. Rheumatoid arthritis Chronic.565) progressive external ophthalmoplegia. with a high risk of embolic phenomenon and obstruction. Syncope can occur in patients with syncope. et al.563) and gait ataxia.org/ by guest on November 16. with ventricular tachyarrhythmias. Severe cases resulting in vertebrobasilar ischemia may rarely result in syncope. including the aortic and mitral rings. Prosthetic valve thrombosis Ranges from asymptomatic to profound May have similar presentation to a (573-575) HF. Erb dystrophy Limb girdle muscular dystrophy. AV block also occurs. and Heart Rhythm Society 55 . as many as 13% of aortic dissections. Inc. may be considered with syncope. myotonia. pigmentary retinopathy. collapse is possible. classically in young athletes..ahajournals. Syringomyelia Arnold Chiari malformations are the most Syringomyelia-induced disruption of (590-597) common form of syringomyelia. 2017 ACC/AHA/HRS Syncope Guideline Infectious Myocarditis Chest pain. including the AV block. Coarctation of the aorta If severe. © 2017 by the American College of Cardiology Foundation.560. pelvifemoral weakness and atrophy. and Syncope is often due to obstruction to (572) systemic signs and symptoms. Anatomic Lev’s and Lenegre’s Progressive fibrosis and sclerosis of Syncope is usually due to high-grade diseases cardiac conduction system. block and syncope. it can result in HF or aortic Associated bicuspid aortic valve stenosis (588) dissection. and daytime somnolence. SCD is known to occur. but (554) of Lyme disease. temporal wasting. hypotension. Otherwise. cataracts. weakness. Grip tachyarrhythmias. myocardial and neurological deficits is higher in infarction. Lyme disease Lyme myocarditis with classical features Syncope may be due to AV block.549-553) systolic dysfunction. Subclavian steal The phenomenon of flow reversal in a Syncope is generally associated with (583-587) vertebral artery ipsilateral to a upper-extremity activity. arrhythmias. Friedreich ataxia Autosomal recessive inheritance with limb Syncope can be bradycardic or Downloaded from http://circ. transient hemodynamic collapse may occur. 2017 (562. Shen W-K. tamponade. Kearns Sayre Mitochondrial myopathy. VT. cardiac tumor. glucose intolerance. Purkinje disease. reflex. embolic. autoimmune inflammatory Rarely associated with complete heart (589) disorder with systemic manifestations. Diffuse interstitial fibrosis and HCM. (580-582) neurological symptoms. or AV block. migraines and neurological manifestations. and tachycardic. Aortic dissection Aortic dissection may manifest with The risk of in-hospital death. blood flow. ahajournals.and second-degree relatives and the manner in which those © 2017 by the American College of Cardiology Foundation. A detailed family history. SCD. Pediatric cardiac syncope may result from obstruction to blood flow (HCM. Mastocytosis (602-609) Vasoactive intestinal peptide tumor Hematologic Beta thalassemia major Severe anemia. ventricular tachycardia. 2017 (611-614) lobe or limbic system. it is estimated that 30% to 50% of children experience at least 1 fainting episode.org/ by guest on November 16. and Syncope may be arrhythmic. vasovagal syncope.. HRS.1. left ventricular hypertrophy. ARVC.616) associated with syncope. CPVT. Cyanotic breath-holding spells typically occur from age 6 months to age 5 years and may be due to desaturation caused by forced expiration during crying. multiple organ failure. myocardial dysfunction (myocarditis. ventricular arrhythmias. 10. Brugada syndrome. Age. and syncope accounts for 3% of all pediatric ED visits (617-622). et al. 2017 ACC/AHA/HRS Syncope Guideline Neck/vagal tumor Recurrent syncope is an uncommon The mechanism may be invasion of the (600. and VVS. By 18 years of age. Neurally mediated syncope accounts for 75% of pediatric syncope. left ventricular. Endocrine Carcinoid syndrome (602) These tumors can release vasoactive Syncope is usually due to transient Pheochromocytoma peptides and cause vasodilation. pulmonary hypertension). (610) dilated cardiomyopathy due to iron overload. LVH. A detailed history with careful attention to the events leading up to the syncope and a complete physical examination can guide practitioners in differentiating the life-threatening causes of syncope (with potential for injury or SCD) from the more common and benign neurally mediated syncope. American Heart Association. Heart Rhythm Society. Pallid breath-holding spells are seen in the first 1 to 2 years of age and may be an early form of VVS. sudden cardiac death. Shen W-K. ACC indicates American College of Cardiology. congenital coronary anomaly. VT. Inc. followed by psychogenic or unexplained syncope in 8% to 15% of cases (623). heart failure. and gastrointestinal symptoms. Lifestyle.601) complication of neck malignancy. Breath-holding spells are a form of syncope unique to the pediatric population. Neurological disorders Seizure induced Generally due to temporal lobe epilepsy. or Wolff-Parkinson-White syndrome). VA. The incidence is higher in females and peaks between 15 to 19 years of age (617). LV. and Heart Rhythm Society 56 . Postictal bradyarrhythmia is uncommon bradycardia/hypotension and likely originates from the temporal Downloaded from http://circ. AV. HCM. and Special Populations 10. hypertrophic cardiomyopathy. Pediatric Syncope: Recommendations Syncope is common in the pediatric population. electrocardiogram. carotid sinus or the afferent nerve fibers of the glossopharyngeal nerve. ECG. Migraine Migraine headaches are statistically Syncope may be vasovagal or due to (615. hypotension. with particular attention to premature SCD among first. or post–Kawasaki disease) or a primary arrhythmic etiology (LQTS. cardiomyopathy. (602. The latter episodes are associated with significant bradycardia and prolonged asystole.603) pruritus. orthostatic intolerance. atrioventricular. AHA. HF. aortic stenosis. flushing. American Heart Association. Prolonged Supplement 40. interventions recommended for adults with similar conditions presenting with syncope can be applied in children. family history of SCD. Exertional syncope has been associated with LQTS and CPVT (315. and ARVC).618. Bradyarrhythmias and high-grade AV block or asystole.627.337.633).634.630. Inc.630.629. is helpful. Brugada.625.630. such as LQTS and CPVT. The types of monitoring devices. A family history of VVS and early SCD should be sought.620.630. although the specificity is modest (618. especially mid-exertional syncope. They may be associated with a family history of SCD. as well as tachyarrhythmias. Characteristics of presenting signs and Downloaded from http://circ. abnormal physical examination. Given that many of the causes of non-CHD cardiac syncope in children who do not have a form of CHD are similar to those experienced in an adult cohort (LQTS. were documented (636-640).634). lack of a prolonged upright posture. Wolff-Parkinson-White. American Heart Association. © 2017 by the American College of Cardiology Foundation. Regardless of symptoms. Exercise stress testing may be helpful in the diagnosis of channelopathies. Shen W-K.639. of consciousness.627). and abnormal ECG (626.337. Recommendations for Pediatric Syncope COR LOE Recommendations VVS evaluation. In 5 retrospective studies of prolonged monitoring in 87 children with either syncope or presyncope.318. including a detailed medical history. I C-LD family history. Channelopathies are major causes of cardiac-related syncope in young people.632.org/ by guest on November 16. should result in a high index of suspicion for a cardiac etiology (633). which have adrenergically mediated arrhythmias. and their limitations are available in Table 8.631. VVS occurs in 33% to 80% of children with syncope (624. HCM. syncope during exercise or in response to auditory or emotional triggers. It should be remembered that children may not be able to clearly communicate specific symptoms. SVT.618.624-630). or primary rhythm disorder (315. 2017 symptoms differentiating VVS from cardiac causes of syncope are generally similar to those in adults.635). Although VVS is the most common cause of pediatric syncope. the mean diagnostic yield was 43% (636- 640). presence of preceding palpitations within seconds of loss Supplement 40. and Heart Rhythm Society 57 . and a 12-lead ECG. cardiac syncope does represent 1..619. Risk factors that raise suspicion of a cardiac etiology include the absence of See Online Data prodromal symptoms. The diagnostic yield of an ICM is higher if the clinical indication was exertional syncope or the patient had underlying CHD (637.628).640). exertional syncope. Noninvasive diagnostic testing should be performed in pediatric patients I C-LD presenting with syncope and suspected CHD. should be performed in all pediatric patients presenting with syncope (315.5% to 6% of pediatric cases (usually defined as up to 18 years of age) (617. heart rhythm monitoring can often provide a correlation between symptoms and an arrhythmia.633). Extended monitoring is reasonable when an arrhythmia diagnosis is suspected. and they increase the risk of SCD in these patients (315.318. cardiomyopathy. 2017 ACC/AHA/HRS Syncope Guideline deaths occurred. physical examination. See Online Data their clinical utility. et al. Education on symptom awareness of prodromes and reassurance are I C-EO indicated in pediatric patients with VVS.632). and polymorphic VT.ahajournals.627.620. exhibited cardiac asystole with pauses >3 seconds (645).651. In the Supplement 40. pallid breath-holding spells. et al. versus 39% in the placebo arm Supplement 40. Tilt-table testing can be useful for pediatric patients with suspected VVS IIa C-LD when the diagnosis is unclear (624. 83% of See Online Data subjects demonstrated improvement or resolution of symptoms (654. Pediatric patients with episodes of VVS may exhibit convulsive movements during loss of consciousness that mimic epileptic See Online Data seizures.org/ by guest on November 16. and the specificity ranges from 83% to 100% (624. Encouraging increased salt and fluid intake may be reasonable in selected IIb B-R pediatric patients with VVS (642). 64% Supplement 40.655). Supplement 40.642).643. In See Online Data an RCT comparing patients receiving conventional therapy (health education.643. In pediatric patients with VVS not responding to lifestyle measures. 86% had either complete resolution or a significant reduction in See Online Data the number of syncopal events with pacing (656. American Heart Association. In children with syncope and convulsions on tilt-table testing. The effectiveness of fludrocortisone is uncertain in pediatric patients with IIb C-LD OH associated with syncope (389. not powered to address the specifics of pacing programming. Although the studies were Supplement 40. (p<0. hot crowded environments. Treatment should emphasize See Online Data symptom awareness and avoidance of precipitating factors that might worsen the Supplement 40. In a single-center prospective case series. A combined cardiology and neurology evaluation may be warranted in this group of patients with syncope and seizure-like activity. standing for prolonged periods of time. it is IIa B-R reasonable to prescribe midodrine (381. and Heart Rhythm Society 58 .648. tilt-table training. children with recurrent syncope did better on placebo than on fludrocortisone (389).657).05) (642). Inc. pseudoephedrine reduced clinical symptoms in 94% of children with recurrent neurally mediated syncope (653). In 2 single-center prospective case series of 0.652).644. and documented prolonged asystole (pauses >4 s).1 mg of fludrocortisone. and salt) and midodrine with patients receiving conventional therapy alone.649). such as dehydration.647. In an RCT.653). Shen W-K.629.657). Upright tilt-table testing Downloaded from http://circ. side effects from midodrine were rare (381. conventional therapy and oral rehydration salts resulted in no further See Online Data recurrence of syncope in 56% of patients. 2017 ACC/AHA/HRS Syncope Guideline Management of children with VVS should include reassurance about the generally benign nature of this condition (641.ahajournals. In 2 prospective studies. only pediatric RCT. the recurrence rate of syncope decreased from 80% to 22% (381). either single. Single-chamber pacing with © 2017 by the American College of Cardiology Foundation. IIb B-NR Cardiac pacing may be considered in pediatric patients with severe neurally mediated syncope secondary to pallid breath-holding spells (656.629.653). In 2 separate studies of 22 predominantly infants and toddlers with reflex anoxic seizures. and diuretic intake.620.655).643-650).. Tilt-table testing has a diminishing role in the diagnosis of children with unexplained syncope.654. condition.652).or dual-chamber pacing significantly reduced the number of syncopal episodes compared with a sensing-only strategy (656. The sensitivity of tilt-table testing ranges from 20% to 90% (624.657). 2017 combined with a graded isoproterenol infusion identified 42% to 67% of patients previously thought to have a primary seizure disorder (223. although some patients do present again at a later age with classic VVS. The long-term outcome with pacing in this population has not been reported. care in a specialized referral center for ACHD care. referral to a specialist with expertise in ACHD can be beneficial. Finally. and VA. III: No Beta blockers are not beneficial in pediatric patients with VVS (655. The prevalence of VT after tetralogy of Fallot repair is 3% to 14% (661. Unexplained syncope Supplement 40. Inc.2. This should be balanced against the known complications of permanent cardiac pacing. Downloaded from http://circ. In a population-based retrospective study of 71. By age 50. and have a deep understanding of noncardiac comorbidities.467 patients with ACHD from Quebec. Recommendations for ACHD COR LOE Recommendations IIa C-EO For evaluation of patients with ACHD and syncope. Canada.659). American Heart Association. 2017 10. especially in patients with moderate-to-severe ACHD. however. Care by a physician with experience in management of CHD can be beneficial. and Heart Rhythm Society 59 . arrhythmias. atrial arrhythmias.662). In a cohort of 252 patients with repaired tetralogy of Fallot © 2017 by the American College of Cardiology Foundation. The beneficial response to pacing in these studies cannot exclude a placebo effect from pacemaker implantation itself. EPS is reasonable in patients with moderate or severe ACHD and IIa B-NR unexplained syncope (664. approximately 38% of patients with ACHD will develop an atrial arrhythmia. is a concerning event.658). the young age of the patients with pallid breath-holding spells makes placebo effect less likely. particularly in those with severe ACHD (663). but also as a result of a previous palliative or corrective surgery. was independently associated with reduced mortality rate. Delivery of ACHD care in highly N/A specialized centers has been shown to reduce mortality rate (663). the treatment group See Online Data actually had a higher recurrence rate. These patients may present with syncope of both hemodynamic and either bradycardic or tachycardic origin. B-R Benefit In an RCT comparing metoprolol and conventional therapy.665). Shen W-K.. it is important to remember that pallid breath- holding syncope does end. Adult Congenital Heart Disease: Recommendations Patients with ACHD are at risk for syncope as a result not only of the underlying structural disease. See Online Data SCD is a leading cause of death in the patient with ACHD. frequently in children (655. and pulmonary hypertension. The entire spectrum of arrhythmias may be seen in adults with CHD. >50% of patients with severe CHD will develop atrial arrhythmias (660). et al. Side effects of beta blockers occur Supplement 40. between 1990 and 2005. 2017 ACC/AHA/HRS Syncope Guideline hysteresis appears as effective as dual-chamber pacing with rate drop response for the prevention of syncope and seizures.org/ by guest on November 16. compared with other care.ahajournals. Care providers must be knowledgeable in the anatomy and repair. The care of the expanding population of ACHD survivors is complex. including bradyarrhythmias secondary to sinus or AV nodal disease. and by age 65. be vigilant in the recognition and management of HF. 9%) than were those without inducible VT (13. and secondary morbidity is high because of comorbidities.45. and tetralogy of Fallot) (665).681. decreased fluid conservation (45.188. The goal is N/A to make management decisions in which older patients are well informed. Recommendations for Geriatric Patients COR LOE Recommendations For the assessment and management of older adults with syncope. the diagnosis is imprecise because of amnesia. and by the physical injuries associated with falls. and an increased probability of developing multiple concurrent morbidities (with their associated pharmacological treatments) that can overwhelm homeostasis.ahajournals. lack of witnesses. physical injury. Furthermore. and frailty (35. which more commonly result from syncope in old age (670).. et al. Mustard. The vulnerability of older adults to syncope increases because of age-associated cardiovascular and autonomic changes. Older patients (>75 years of age) who present with syncope tend to have poor outcomes. both fatal and nonfatal (109. Shen W-K. Geriatric Patients: Recommendations Downloaded from http://circ. with many predisposing factors present simultaneously. collisions.4%) (664). Fontan.. In 50% of patients receiving appropriate ICD shocks. American Heart Association. recurrent syncope can lead to nursing home admission and a devastating loss of independence (683). 2017 ACC/AHA/HRS Syncope Guideline undergoing risk stratification with programmed ventricular stimulation.3. atrial tachyarrhythmias preceded or coexisted with VT (665). among older adults such risks are usually compounded by multiple morbidities and frailty. Given the multifactorial etiologies and high risks associated with syncope. A thorough history and physical examination. which add to age-related vulnerability to syncope (671. falls. and polypharmacy.680). a comprehensive and multidisciplinary approach is often necessary to assess for multiple morbidities.671. Senning. trauma. Ebstein anomaly. A multidisciplinary approach helps to facilitate diagnosis of frailty and other factors that predispose to syncope and poor outcome in older adults.679. It is reasonable to exclude atrial arrhythmias in patients with syncope and a CHD substrate at risk of atrial arrhythmias (e. In a cohort study of ICD recipients with transposition of the great arteries after an atrial baffle procedure. 10. is particularly important in older patients (77). Although some of the risk is attributable to the aspects of syncope described in this guideline. the differential diagnosis is broad.676-678).org/ by guest on November 16. In many instances.684. a syncopal event in an older adult is multifactorial. including orthostatic vital signs. Inc. or trauma.685). Patients with tetralogy of Fallot and inducible monomorphic or polymorphic VT were more likely to have a history of syncope (42. 35% of patients with primary-prevention ICDs presented with syncope.g. induction of either monomorphic or polymorphic VT predicted future clinical VT and SCD (664). a IIa C-EO comprehensive approach in collaboration with an expert in geriatric care can be beneficial. 2017 The management of syncope in older adults is particularly challenging: The incidence is high. frailty.682). therapeutic choices are tailored to each patient’s needs and goals of care.666-675). and other dimensions of health (including cognition and medications) pertinent to diagnosis and management (77. and © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society 60 . the risk of causing harm may be higher than for patients with VVS. Inc.686). Society recognizes that certain groups. United Kingdom. exhaustion. Cognitive impairment is also frequently present in older adults. 2017 Approximately 30% of older adults who present with nonaccidental falls may have had syncope (687). The 418 patients in POST I and POST II had a median of 3 vasovagal faints in 1 year but had no serious injuries or deaths and only 2 minor accidents in the subsequent year (694). polypharmacy. and severity of symptoms. Although untreated syncope may disqualify patients from driving. The acceptable level of risk then becomes a societal decision. the yearly risk of serious injury and death is 0. However. In the general population.ahajournals. et al. laws. and this too can reduce the accuracy of recall of the clinical event (666-669.686). reduced physical activity. It is reasonable to consider syncope as a cause of nonaccidental falls in older IIa B-NR adults (666-669. and cognitive decline. less than the Risk of Harm formula predicted (692). and providers caring for patients with syncope should be aware of pertinent local driving laws and restrictions. Public policies. which diminishes the effectiveness of the history. 10. Downloaded from http://circ. the potential to reduce medications that might lower blood pressure. American Heart Association. Balancing the need to minimize risk from drivers fainting is the need for patients to drive to meet the demands of family and work. weakness. age-related reduction in hepatic and renal clearance). and circumstantial factors.org/ by guest on November 16. This provides an estimated yearly risk of serious injury and death in the VVS population of <0. Characteristics of frailty include weight loss. physical slowing. or fever. such as younger and older adults. infection.4. Consideration of frailty is particularly relevant. and regulations have not been adapted to these results. patient preferences. Supplement 41. and Heart Rhythm Society 61 . even in those without a formal diagnosis of dementia (688-690)..g. physical and cognitive functions. comorbid illness. drug-drug interaction. The main concern is the risk of causing injury or death to the driver or others as a result of recurrent syncope (691).. Assessment is required of underlying cardiovascular and noncardiovascular diseases. Factors to consider in assessing the risk of syncope while driving are summarized in a formula developed by the Canadian Cardiovascular Society 25 years ago (692) that estimates the risk that a driver will suddenly become incapacitated. 2017 ACC/AHA/HRS Syncope Guideline decision making is successfully shared between patients and providers.673. such as dehydration. Amnesia is commonly associated with both falls and See Online Data loss of consciousness. Driving and Syncope: Recommendation The assessment of medical fitness to drive is a common issue for practitioners caring for patients with syncope. with cumulative severity and impact that typically vary between patients and even in 1 patient over time. and Canada (694). use of medications (e. Shen W-K. are allowed to drive despite their higher risk of causing harm for reasons other than syncope (693). for patients with other etiologies of syncope or those in whom syncope occurred without prodrome or warning.500 (694).0017%. effective treatment reduces the © 2017 by the American College of Cardiology Foundation.The societally acceptable risk of injury and death due to motor vehicle accidents has been quantified from an analysis of accident data collected in the United States. Diagnostic and therapeutic approaches to syncope should incorporate considerations of age.067%. or 1 in 1. but not necessarily for commercial drivers because of the higher risk of harm. The Risk of Harm formula simply estimates risk and does not supersede local driving regulations (692). untreated (698) Not fit to drive Syncope due to nonreflex bradycardia.698) Not fit to drive until symptoms resolved Situational syncope other than cough syncope 1 month Cough syncope. 2017 ACC/AHA/HRS Syncope Guideline risk enough to permit driving after a period of observation has elapsed without recurrent syncope. et al. Avoidance of Private Driving After an Episode of Syncope: Suggested Symptom-Free Waiting Times for Various Conditions Condition Symptom-Free Waiting Time* OH 1 month VVS. Table 10. treated with cough suppression 1 month Carotid sinus syncope. as well as the duty of drivers or physicians to report inability of an individual to drive a motor vehicle. then this information should be reported as specific laws require. untreated Not fit to drive Cough syncope. Department of Transportation policy (695).g. Shen W-K. Commercial driving in the United States is governed by federal law and administered by the U. Department of Transportation commercial driver’s license is federally regulated.ahajournals. states or provinces). The writing committee encourages healthcare providers who care for patients with syncope to know pertinent driving laws and restrictions in their region (e.697). untreated (698) Not fit to drive Carotid sinus syncope. As the risk of recurrent syncope decreases with treatment or with the natural history of a disease process.. The suggestions in Table 10 provide general guidance for private drivers. Although physicians have an obligation to maintain confidentiality. Individual states may require reporting of drivers who faint. if a patient’s condition poses a significant risk to others. Inc. Department of Transportation (695). private driving is state regulated.org/ by guest on November 16. and Heart Rhythm Society 62 . untreated (698) Not fit to drive © 2017 by the American College of Cardiology Foundation. Physicians providing care to commercial drivers should be familiar with U. treated with permanent pacemaker (698) 1 week Syncope due to nonreflex bradycardia. commercial drivers typically operate vehicles heavier than private automobiles). >6 syncope per year (694. Regulatory agencies are more likely to disqualify commercial drivers than private drivers because of the amount of driving and the impact of accidents (i. but commercial driving requiring a U.S.. Many patients do not stop driving despite advice to do so. no syncope in prior year (698) No restriction VVS.698) Syncope due to SVT. Recommendations about commercial driving are more a N/A legal than a medical matter. regardless of the duration of restriction (696. American Heart Association. Most suggestions are based on expert opinion and supported by limited data. the risk of harm may become low enough for private drivers to resuming driving. Recommendation for Driving and Syncope COR LOE Recommendation It can be beneficial for healthcare providers managing patients with Downloaded from http://circ.S.. treated with permanent 1 week pacemaker (12.e.S. 2017 IIa C-EO syncope to know the driving laws and restrictions in their regions and discuss implications with the patient. and are not within the purview of this guideline. 1–6 syncope per year (694) 1 month VVS. In the United States. but athlete can be defined as someone who engages in routine vigorous training (e. treated with an 3 months ICD or guideline-directed drug therapy Syncope presumed due to a nonstructural heart disease VT. have been associated with syncopal episodes (708). agility. but current strategies are largely inadequate (706). and Not fit to drive LVEF ≥35%. left ventricular ejection fraction. pharmacologically suppressed (698) 1 month Syncope due to SVT. cardiac adaptations to high levels of exercise may lead to the “athlete’s heart” and thus alter the myocardial substrate (705). such as somatotrophic compounds and amphetamine-like stimulants. Recommendations for Athletes © 2017 by the American College of Cardiology Foundation. and mortality in at-risk athletes is a major consideration. ICD indicates implantable cardioverter-defibrillator. morbidity. right ventricular outflow tract. supraventricular tachycardia. treated with an ICD and guideline-directed drug therapy (701. especially macrolide antibiotics and antihistamines/decongestants. LVOT. et al. More importantly.700) Syncope with LVEF <35% and presumed arrhythmic etiology 3 months with an ICD (701.org/ by guest on November 16. structural heart disease. or games requiring physical strength. RVOT.702) Syncope presumed due to VT/VF. with typical characteristics of dehydration or VVS. untreated Syncope presumed due to VT/VF. is critically important during initial evaluation. orthostatic hypotension. SVT. untreated Not fit to drive Syncope presumed due to VT with a genetic cause. Inc. before drugs are prescribed to highly competitive athletes. VF. OH. The definition of an athlete is imprecise.707). 2017 ACC/AHA/HRS Syncope Guideline Syncope due to SVT. Performance-enhancing agents. are associated with precipitous collapse. A thorough history. The current evidence base is insufficient to support general screening with ECG or echocardiography at baseline (706. untreated Syncope presumed due to a nonstructural heart disease VT. structural heart disease. ventricular fibrillation. LVEF. American Heart Association. treated successfully with ablation or suppressed pharmacologically (698) Syncope of undetermined etiology 1 month *It may be prudent to wait and observe for this time without a syncope spell before resuming driving. and 3 months LVEF ≥35%. Athletes: Recommendations Syncope occurring in the athlete is predominantly of vasovagal origin. or stamina (704). such 3 months Downloaded from http://circ. left ventricular outflow tract.g. Several approved therapeutics. Similarly. but underlying cardiac conditions may place athletes at undue risk for adverse events (703). such Not fit to drive as RVOT or LVOT.ahajournals.. Primary or secondary prevention of syncope. it is prudent to determine whether the drug or its metabolites are on lists of banned substances. sports. 2017 as RVOT or LVOT. 10. ventricular tachycardia. Shen W-K.702) Syncope presumed due to VT with a genetic cause.. vasovagal syncope.5. differentiating syncope occurring during exercise from syncope occurring after exercise or at other times. and Heart Rhythm Society 63 . Syncope during exercise is associated with increased probability of cardiac causes of syncope (Table 4). treated with ablation (698) 1 week Syncope with LVEF <35% and a presumed arrhythmic etiology Not fit to drive without an ICD (699. >150 minutes per week) and is skilled in exercises. VT. and VVS. A careful history is required in the athlete with syncope to rule out exposure to any of these agents (709). 2017 Assessment by a specialist with disease-specific expertise is reasonable for IIa C-LD athletes with syncope and high-risk markers (706. Extended monitoring can be beneficial for athletes with unexplained IIa C-LD exertional syncope after an initial cardiovascular evaluation (717. Cardiovascular causes account for 75% of sport-related deaths in young athletes (709. particularly volume depletion and vasovagal activity. with no firm data on the best device and optimum monitoring period (720). VA in patients with HCM.709. as appropriate. See Online Data or ARVC is catecholamine sensitive. tilt-table testing. unless contraindicated. Downloaded from http://circ. Exercise N/A stress testing.714). Concomitant illnesses. and Heart Rhythm Society 64 .715. Participation in competitive sports in that Supplement 42.710). Imaging may include echocardiography or MRI as required. Syncopal episodes first require a personal and family history to evaluate precipitating causes and benign conditions. Syncope in the competitive athlete requires an evaluation for potentially fatal causes of syncope.. This is a rapidly evolving field. CPVT. Wolff-Parkinson- White syndrome. et al. especially viral infections. and family counseling and/or genetic testing is advised for those conditions with a known familial tendency. LQTS1. For persistent unexplained syncope. 2017 ACC/AHA/HRS Syncope Guideline COR LOE Recommendations Cardiovascular assessment by a care provider experienced in treating I C-EO athletes with syncope is recommended prior to resuming competitive sports.716). Any suspected cardiovascular pathology requires further evaluation. symptomatic mitral valve N/A prolapse. Syncope that occurs after exercise is often of benign origin and may be due to abdominal venous N/A pooling.713). ventricular noncompaction. can be helpful. especially when evidence of HCM. ARVC. circumstance in these patients is not recommended (704. and imaging as clinically indicated (Figure 3) (719). © 2017 by the American College of Cardiology Foundation. or ARVC before Harm evaluation by a specialist (704. Participation in competitive sports is not recommended for athletes with III: B-NR syncope and phenotype-positive HCM. should be investigated and an ECG obtained (709.718).721-724). Inc. CPVT. For those with a suspected cardiovascular etiology of syncope.715. LQTS. American Heart Association. Marfan syndrome. However. syncope during exercise is a much more compelling symptom and can be a harbinger of SCD (712. Shen W-K.710).org/ by guest on November 16. A thorough history and physical examination should be completed by an experienced provider. an evaluation includes an ECG. extended arrhythmia monitoring can be used. congenital coronary anomalies. or other at-risk conditions is present (706.716). LQTS1.ahajournals. including an assessment for OH and evidence of underlying cardiovascular disease (709-711). In the absence of vagal mechanisms. 730. general and syncope-specific QoL improved over a 1-year period. and structural heart disease (725). including Austria.738).6 billion and $7. Impact of Syncope on Quality of Life QoL is reduced with recurrent syncope (725-733). and impairment in activities of daily living. somatization. pediatric patients with recurrent syncope reported worse QoL than individuals with diabetes mellitus and equivalent QoL to individuals with asthma. In 1 study.732). depression.731). with a mean cost of $9. 11. Total costs and costs per admission for presumptive undiagnosed syncope were $1. tertiary referral hospital after an episode of syncope (77). neurological or psychogenic reason for syncope.1.. and anxiety (725. working. There is Downloaded from http://circ. the United Kingdom.728. QoL impairments associated with syncope improve over time (733).ahajournals. Costs are defined as the resources needed to produce a set of services and are distinct from charges billed by facilities and healthcare providers (735).731. including increased fear.S. reduced syncope recurrence. and greater comorbidity at baseline (733).734). Similarly.200. The cost per informative diagnosis (as ordered in routine practice) © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society 65 . 33% reported syncope-related functional impairments with daily activities.729. use of an implantable loop recorder increased diagnostic rate. American Heart Association.400 per admission (736). perception of mental health. These high costs have been estimated both in the United States and abroad. such as driving. and attending school.org/ by guest on November 16.S. Physician reviewers determined whether the results of a diagnostic test affected clinical management at a U.727. such as perceptions of low overall physical health (725. end- stage renal disease. respectively (736). recurrent syncope.730. QoL associated with recurrent syncope was equivalent to severe rheumatoid arthritis and chronic low-back pain in an adult population (728). total annual hospital costs exceeded $4. In the U. Inc. Those with more frequent syncope have reported poorer QoL (726. such as driving or working (732). Syncope-related QoL can be improved through effective diagnosis and treatment. and Spain. Shen W-K. Several investigators have estimated the costs per clinically meaningful test result. 2017 consistent evidence that syncope is associated with worse function on multiple domains of QoL. Quality of Life and Healthcare Cost of Syncope 11. Most studies have focused on facility costs and excluded professional fees and patient copays. et al.734). In a hospital-based cohort of patients with a prior episode of syncope. In the Fainting Assessment Study (733). 2017 ACC/AHA/HRS Syncope Guideline 11. and improved QoL as compared with patients who received a conventional diagnostic workup (164). as demonstrated in studies that compared patients with and without syncope (727. Healthcare Costs Associated With Syncope High healthcare costs are associated with the evaluation and management of syncope. nonpharmacological treatment of recurrent syncope was associated with reductions in recurrent syncope and improvements in QoL (729). Healthcare Utilization Project.1 billion in 2014 dollars. Israel. In a second study. confirm similarly high costs associated with the hospital evaluation of syncope (122. Predictors of worse QoL over time include advanced age.2.737. Single-center studies from multiple countries. inform driving policies.org/ by guest on November 16.900) specialty clinic for unexplained recurrent syncope (163). and functional capacity as additional clinical endpoints.and long-term clinical outcomes? What are the key outcomes relevant to patients with syncope. These knowledge gaps present opportunities for future research to ultimately improve clinical outcomes and effectiveness of healthcare delivery. Evidence Gaps. 2017 ACC/AHA/HRS Syncope Guideline affecting clinical management varied widely by specific diagnostic test. and Heart Rhythm Society 66 . improve patient outcomes. and improve and streamline health service delivery. diminished health care–related QoL. Definition. 2017 Reported incidence and prevalence of syncope vary significantly because of several confounders: variable definitions for syncope versus transient loss of consciousness. what is the standard of care for this group of patients? • Studies are needed to determine whether syncope is an independent predictor of nonfatal or fatal outcomes in selected patient populations. including recurrent syncope? When the cause of syncope is unknown. nonfatal outcomes such as injury. and Future Directions The writing committee created a list of key areas in which knowledge gaps are present in the evaluation and management of patients presenting with syncope. Shen W-K. • Prospective and well-designed studies are needed to define relevant clinical outcomes with regard to recurrent syncope. 12.and long-term follow-up. Classification. © 2017 by the American College of Cardiology Foundation.2. several key questions follow: What is the likely cause of syncope? Does the patient have significant underlying heart disease and/or comorbid medical illnesses? If the cause of syncope is determined.100) to EEG ($32. and different study methodologies. from postural blood pressure ($50) through telemetry ($1. 12. 12. Finally.1. et al. work loss. prevent syncope-related nonfatal outcomes (injury. Emerging Technology. Definition and classification of syncope provided in this document will set the standard for future research. • Studies are needed to develop risk scores to be prospectively validated in a given clinical setting with predefined endpoints from short. different clinical settings. Standardized national registries and large sample databases are needed to gather data on a continuous basis to understand the true incidence and prevalence of syncope. American Heart Association. Risk Stratification and Clinical Outcomes At a patient’s presentation. Similar high costs per actionable diagnosis occur in children admitted for new-onset syncope. Inc. understand patient risk. or improve survival? What are the predictors of short. and fatal outcomes.ahajournals. different populations. mean costs per diagnostic result were also high in an outpatient ($19. Future studies should incorporate QoL. is there an effective therapy to prevent recurrent syncope. lost workdays). and Epidemiology Downloaded from http://circ.973) (77).. 2017 symptom of syncope. Evaluation and Diagnosis Because of the concerns that patients presenting with syncope are at higher risk for an impending catastrophic event. and Heart Rhythm Society 67 . overuse and inappropriate use of testing and hospital admission are common. Studies are needed to differentiate “arrhythmic syncope” versus “nonarrhythmic syncope” versus “aborted SCD” in patients with inheritable arrhythmic conditions • Prospectively designed multicenter or national registries are needed to gather clinical information from patients with reflex syncope to better our understanding on other associated conditions. studies are needed to determine short.and long-term outcomes to guide the overall management of these patients. • RCTs are needed to determine the features of syncope-specialized facilities that are necessary to achieve beneficial outcomes for patient care and to improve efficiency and effectiveness of healthcare delivery. • Among patients without identifiable causes of syncope. plausible © 2017 by the American College of Cardiology Foundation. the cause of syncope. Management of Specific Conditions • Although potential causes of syncope are multiple. studies are needed to determine the value of new technology in the evaluation and management of patients with syncope. • As technology advances. 12.4. Vasovagal syncope is the most common cause of syncope in the general population. a treatment decision is usually fairly straightforward for patients with cardiac causes of syncope or orthostatic causes. • RCTs are needed to develop structured protocols to evaluate patients with syncope who are at intermediate risk without an immediate presumptive diagnosis. Shen W-K. 12. Inc. In addition to the endpoints of diagnostic yield and healthcare utilization.org/ by guest on November 16. Treatment remains challenging in patients who have recurrences despite conservative therapy..3. relevant clinical endpoints of nonfatal and fatal outcomes and recurrence of syncope are to be included. Answers to the following question will improve the effectiveness of patient evaluation: How should the initial evaluation and subsequent follow-up vary by risk (low. 2017 ACC/AHA/HRS Syncope Guideline • Prospective studies are needed to differentiate cardiac and noncardiac clinical outcomes in different clinical settings and with different follow-up durations. • Investigations are needed to understand the key components of clinical characteristics during the initial evaluation and to develop standardization tools to guide the evaluation by healthcare team. the underlying disease condition. American Heart Association.ahajournals. et al. or high) to assess clinical outcomes? • Studies are needed to better understand the interaction and relationships among the presenting Downloaded from http://circ. and their effect on clinical outcomes. intermediate. • RCTs are needed to continue the identification of effective treatment approaches to patients with recurrent reflex syncope. © 2017 by the American College of Cardiology Foundation. geriatric population. 12. • Prospective and randomized studies are needed to assess the usefulness of specialized syncope units in different clinical settings.. and Heart Rhythm Society 68 . and within each of them we identified several key areas that are important for future research considerations. American Heart Association. and natural history of these uncommon conditions. Shen W-K. Inc. • Prospective national registries and big databases are needed to determine risk associated with driving Downloaded from http://circ.ahajournals. 2017 among different populations with syncope. 2017 ACC/AHA/HRS Syncope Guideline mechanisms. and management outlined above for the adult population are needed in the pediatric population. evaluation. et al.5. Special Populations Each population in Section 6 is unique with regard to syncope. and athletes. effectiveness of therapeutic interventions. • Questions and research about risk stratification.org/ by guest on November 16. Science. Guideline Methodology and Policy Abdul R. Science and Clinical Policy Allison Rabinowitz. Chief Executive Officer Rose Marie Robertson. Chief Science and Medicine Officer Gayle R. Education. MD. PhD. Chief Executive Officer William J. Science and Clinical Policy American Heart Association Downloaded from http://circ.org/ by guest on November 16. PhD. Oetgen. Project Manager. FAHA. Project Manager. Inc. Director. Senior Vice President. Education. FACC. CAE. MD. and Heart Rhythm Society 69 . et al. and Publishing American College of Cardiology/American Heart Association Katherine Sheehan. Executive Vice President. MBA. Quality. and Publishing Amelia Scholtz. 2017 Steven R. Publications Manager. Guideline Strategy and Operations Lisa Bradfield.. Office of Science Operations Jody Hundley. President Nancy Brown. MPH. President Shalom Jacobovitz. Associate Science and Medicine Advisor Clara Fitzgerald. PhD. FAAN. Chazal. FACC. Houser.ahajournals. Director. Quality. RN. Abdullah. MD. 2017 ACC/AHA/HRS Syncope Guideline Presidents and Staff American College of Cardiology Richard A. PhD. Office of Science Operations Key Words: AHA Scientific Statements ■ syncope ■ risk assessment ■ diagnosis ■ prognosis ■ cardiac syncope ■ reflex syncope ■ vasovagal syncope ■ orthostatic hypotension ■ neurogenic syncope ■ dehydration ■ pediatrics ■ adult congenital heart disease ■ geriatrics ■ driving ■ athletes © 2017 by the American College of Cardiology Foundation. Whitman. Scientific Publications. FAHA. Shen W-K. American Heart Association. Production Manager. MD. FAHA. Science. 3.1.2.3. 10. 4. Medical School. 12 Mitchell I. 2017 Guideline for the Evaluation and Management of Patients With Syncope (March 2015) Committee Employment Consultant Speakers Ownership/ Personal Institutional. Mayo Clinic College of Medicine—Chair. 10. • St. Sheldon University of Calgary None None None None None None None (Vice Chair) Department of Medicine— Professor David G. Jude 3. Benditt University of Minnesota • Medtronic† None None None None None 3.5.1– Cardiovascular Division— Medical† 4. 10. Phoenix Children’s Heart Center— Co-Director. Expert Voting Member Bureau Partnership/ Research Organizational. or Witness Recusals by Principal Other Financial Section* Benefit Win-Kuang Shen Mayo Clinic Arizona— None None None None None None None (Chair) Professor of Medicine.2.2. Forman University of Pittsburgh— None None None None None None None Professor of Medicine. Geriatric Cardiology Section.1. Cohen University of Arizona None None None None None None None School of Medicine- Phoenix—Clinical Professor of Child Health.5. 2017 ACC/AHA/HRS Syncope Guideline Appendix 1. 4..2.5. Department of Cardiovascular Diseases Robert S.3. 5.2.3. Author Relationships With Industry and Other Entities (Relevant)—2017 ACC/AHA/HRS Downloaded from http://circ.1– 4. et al. 3. Shen W-K.3.org/ by guest on November 16.5. University of Pittsburgh Medical Center—Chair.1.1– Professor of Medicine 4. Pediatric Cardiology— Chief Daniel E. 4. Cardiac Rehabilitation © 2017 by the American College of Cardiology Foundation. American Heart Association. VA Pittsburg Healthcare Systems— Director. 10.1–5. Inc.2. and Heart Rhythm Society 70 .3. Phoenix Children’s Hospital.ahajournals. 5.1.3.4.2.1– Medicine and Head of 4. 10. Professor of Medicine Brian Olshansky University of Iowa Carver • Lundbeck† None None None None None None College of Medicine.5. 12 Mohamed H. 10.5.5. 4.3. 10. Department of Medicine.1. Shen W-K. 4.2.2. 4.1– and Pediatrics—Professor 4. 12 Hamdan School of Medicine.5.3.org/ by guest on November 16. 3.2. Medicine • Medtronic 3.1–5. Cardiovascular Medicine— © 2017 by the American College of Cardiology Foundation. 10. et al.2.2. American Heart Association. 5.1. University of Wisconsin None None • F2 None None None 2. 5.1– Cardiology—Professor of 4. and Heart Rhythm Society 71 . 10.2.. 4.2.1–5. 10.5.1– 4. 2.3. Inc. Center for Autonomic and Peripheral Nerve Disorders—Director Zachary D. Harborview Medical Center Division of Cardiology— Assistant Professor of Medicine Blair P.3.3. 12 Medical Center. Grubb University of Toledo • Biotronik None None None None None 3. Columbia. 3.3. University of Washington None None None None None None None Goldberger School of Medicine. Downloaded from http://circ.5.3.5.2. 12 Mark S.1.3. Cardiac Electrophysiology. 10. 6.1.3.3.2. Division of • Medtronic† 3. 2017 Beth Israel Deaconess 10.3.3.3.1–4. 10.1. 4.3.ahajournals. 10. Solutions Cardiovascular Medicine— Professor and Chief of Cardiovascular Medicine Andrew D. 10.2.2. Medical Center.1. 2017 ACC/AHA/HRS Syncope Guideline Roy Freeman§ Harvard Medical School— • Lundbeck† None None None None None 4. Krahn The University of British • Medtronic None None None • Boston Scientific† None 3.3. 5. Professor of Neurology.5. Link University of Texas None None None None None None None Southwestern Medical Center.1. Division of Cardiology—Director.5.1– Division 4.3.1.1– 4. 4.3. None None None None None None None Sandhu Medical Division of Cardiology—Assistant Professor of Medicine Dan Sorajja Mayo Clinic Arizona.3.1– 4. has a reasonable potential for financial.4.1.5. None None None None None None None Cardiovascular Diseases— Assistant Professor of medicine Benjamin C.1–5. 4.3. Associate Professor 3.3.3.2.5. • GE Healthcare None None • Medtronic None None 2.2. Relationships that exist with no financial benefit are also included for the purpose of transparency. Mercy Downloaded from http://circ. According to the ACC/AHA. professional or other personal gain or loss as a result of the issues/content addressed in the document. 4. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity. or c) the person or a member of the person’s household. The table does not necessarily reflect relationships with industry at the time of publication. 7. or makes a competing drug or device addressed in the document. Diversity & Inclusion— Vice Dean This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document.2–3. and Heart Rhythm Society 72 .2. 10. Sun Oregon Health & Science None None None None None None None University—Associate Professor Clyde W. et al. Raj University of Calgary.3. or b) the company/entity (with whom the relationship exists) makes a drug. topic. 2017 Hospital North Iowa— Electrophysiologist Satish R. or ownership of ≥$5. 4. 10.1– 10. Shen W-K. Relationships in this table are modest unless otherwise noted. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process.1. 2.3. drug class.5. or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year.1– 4.3.5. or issue addressed in the document. or device addressed in the document. American Heart Association.000 of the fair market value of the business entity.1– 4.2. a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter.1.2.. intellectual property or asset.org/ by guest on November 16. Inc. 5. © 2017 by the American College of Cardiology Foundation.ahajournals. 6. Cardiac Sciences— • Lundbeck† 3. 12 Roopinder Kaur University of Alberta.3. Division of Cardiology—Professor of Medicine and Chief. Yancy Northwestern University None None None None None None None Feinberg School of Medicine. 2017 ACC/AHA/HRS Syncope Guideline Emeritus Professor of Internal Medicine. et al. 2017 ‡No financial benefit. and Heart Rhythm Society 73 .. the official representative of the American Academy of Neurology. Roy Freeman. © 2017 by the American College of Cardiology Foundation. before the final balloting process. resigned from the writing committee in November 2016. Downloaded from http://circ. American Heart Association.org/ by guest on November 16. Inc. We thank him for his contributions. Shen W-K. §Dr.ahajournals. 2017 ACC/AHA/HRS Syncope Guideline *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply †Significant relationship. recusals noted are from the initial round of balloting. and Heart Rhythm Society 74 . 2015 • Pfizer* • Sanofi-aventis • Sentra Heart • St. Reviewer Relationships With Industry and Other Entities (Comprehensive)—2017 Downloaded from http://circ.ahajournals. • HRS* • Medtronic • HRS Lead • Janssen • NIH • JCE extraction Pharmaceuticals • Sanofi-aventis • Medtronic* complication • Medtronic* • PACE . Ellenbogen Reviewer—AHA Center—Director..org/ by guest on November 16. Jude Medical* Rakesh Official University of • Boston Scientific • AHA None None None None Gopinathannair Reviewer—HRS Louisville School of • Health Trust PG © 2017 by the American College of Cardiology Foundation. 2017 ACC/AHA/HRS Syncope Guideline Appendix 2. • Atricure* • Boston Science • American Heart Catheter Clinical EP • Biosense • Biosense Webster Journal ablation Laboratory Webster* • Daiichi-Sankyo* • Biosense complication • Biotronik* • Medtronic Webster* . Inc. et al. Official Oregon Health & None None None None • NIH† None Cigarroa Reviewer— Science University— • AHA† ACC/AHA Task Clinical Professor of • SCAI† Force on Clinical Medicine • ASA† Practice • Catheterization Guidelines and Cardiovascular Intervention† Kenneth A. 2015 • Boston Science* (DSMB) • Boston Science* • Plantiff. Official VCU Medical • AHA None None • Atricure* • AHA • Defendant. Witness Principal or Other Financial Benefit Italo Biaggioni Official Vanderbilt University • Lundbeck* None None • Astellas Pharma None None Reviewer—AHA School of Medicine— • Shire (DSMB) Professor of Medicine Pharmaceuticals* • AstraZeneca* • Theravance* • Forest Pharmaceuticals* • Janssen Pharmaceuticals (DSMB) • Lundbeck* • Theravance* Joaquin E. Expert Bureau Partnership/ Organizational. Shen W-K. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (June 2016) Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional. American Heart Association. Witness Downloaded from http://circ. Inc. and Heart Rhythm Society 75 . Jude Medical Medicine. Assistant Professor of Radiology Dhanunjaya Official University of Kansas • Biosense Webster • Boehringer None None None None Lakkireddy Reviewer—ACC Medical Center— • St. Reviewer— Los Angeles— PACES © 2017 by the American College of Cardiology Foundation. Organizational The Mount Sinai None None None None None None Shah Reviewer— Hospital—Associate ACEP/SAEM Professor of Emergency Medicine Mike Silka Organizational Children’s Hospital None None None None None • Defendant. American Heart Association.ahajournals. Jude Medical Ingleheim Board of Professor of Medicine. et al.org/ by guest on November 16. Jude Medical* • Bristol- Hospital Division of Myers Cardiovascular Squibb Medicine—Associate • Pfizer* Professor of Medicine. • Bristol- Governors Center for Excellence Meyer in AF and Complex Squibb Arrhythmias— • Janssen Director Pharmaceutic als • Pfizer Thad Waites Official Forrest General None None None None None None Reviewer—ACC Hospital—Director of Board of Trustees Catheterization Laboratory Christopher Organizational Beth Israel Deaconess • Lundbeck None None • Astellas Pharma None None Gibbons Reviewer—AAN Medical Center (DSMB) Neuropathy Clinic— • Janssen Director Pharmaceuticals (DSMB) Kaushal H. • Zoll Medical Director of Cardiac EP Robert Helm Official Boston University None None None None • Boston None Reviewer—HRS School of Medicine— Scientific Assistant Professor of • St. 2017 Principal or Other Financial Benefit Medicine and Jewish • St. 2017 ACC/AHA/HRS Syncope Guideline Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional.. Expert Bureau Partnership/ Organizational. Shen W-K. 2017 Principal or Other Financial Benefit Professor of SCD in Pediatrics. and Heart Rhythm Society 76 . 2017 ACC/AHA/HRS Syncope Guideline Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional. Jude Medical* Leadership EP Ingelheim* Council • Medtronic* Coletta Barrett Content Our Lady of the Lake None None None None None None Reviewer—Lay Regional Medical Reviewer Center—Vice President Lin Yee Chen Content Reviewer University of None None None None • NIH* None Minnesota Medical School—Associate Professor of Medicine Andrew Epstein Content Reviewer University of None None None • Biosense None None Pennsylvania Hospital Webster* and the Veteran’s • Biotronik* Administration © 2017 by the American College of Cardiology Foundation. Al. Ospedali del Solutions† Tigullio—Head of Cardiology Hugh Calkins Content Johns Hopkins • Abbott None None • Boehringer • Abbott • Defendant. Reviewer—ACC Hospital—Professor of • Atricure Ingelheim† Laboratories SCD. et al.ahajournals. Content Duke Clinical None None None • FDA* • Elsevier* None Khatib Reviewer— Research Institute— • NHLBI* • AHA ACC/AHA Task Professor of Medicine • PCORI* Force on Clinical • VA Health Practice System (DSMB) Guidelines Kim K. Birtcher Content University of Houston • Jones & Bartlett None None None None None Reviewer— College of Learning ACC/AHA Task Pharmacy—Clinical Force on Clinical Professor Practice Guidelines Michele Content Reviewer Arrhythmologic None None • F2 None None None Brignole Centre. Cardiology CPVT patient. Inc. American Heart Association. 2015 EP Section Medicine. Director of • Boehringer • St.org/ by guest on November 16.. 2016 Sana M. Witness Downloaded from http://circ. Expert Bureau Partnership/ Organizational. Shen W-K. Jude Medical* (DSMB) • St.R. and Heart Rhythm Society 77 . Shen W-K. Cardiology Nurse Practitioner. 2017 Principal or Other Financial Benefit Medical Center— • Boston Professor of Medicine Scientific* (DSMB) • Boston Scientific* • C. Bard* • Medtronic (DSMB) • Medtronic* • St.ahajournals. • FH Foundation† Force on Clinical Division of Pediatric Practice Cardiology Guidelines Bulent Gorenek Content Eskisehir Osmangazi None None None None None None Reviewer— ACC University Cardiology EP Section Department—Chair Leadership Council Paul LeLorier Content LSU Health Sciences None None None • Medtronic* • Medtronic* None Reviewer—ACC Center—Associate Heart Failure and Professor of Medicine © 2017 by the American College of Cardiology Foundation. Fellowship Samuel S. Content Nemours/Alfred I. • FH Foundation† None None • FH Foundation† None None Gidding Reviewer— duPont Hospital for International • NIH* ACC/AHA Task Children—Chief. American Heart Association. Witness Downloaded from http://circ. Inc. Expert Bureau Partnership/ Organizational. Jude Medical Susan Etheridge Content University of Utah— None None None • SADS • Up-to-Date† None Reviewer—ACC Training Program Foundation EP Section Director • PACES† Leadership Council Marci Content Reviewer Mayo Clinic School of None None None None None None Farquhar-Snow Health Sciences— Program Director.. 2017 ACC/AHA/HRS Syncope Guideline Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional. et al.org/ by guest on November 16. Jude Medical Institute Rick Nishimura Content Reviewer Mayo Clinic Division None None None None None None of Cardiovascular Disease—Professor of Medicine Richard Page Content Reviewer University of None None None None • FDA None Wisconsin School of Medicine & Public Health—Chair. and Heart Rhythm Society 78 . Prevention Cardiology— Associate Director Carlos Morillo Content Reviewer Cumming School of • Bayer Healthcare None None • Biosense Webster • Biotronik None Medicine—Professor • Boston Scientific • Canadian • Pfizer Department of Cardiac • Boehringer Institutes for Sciences. Expert Bureau Partnership/ Organizational. University Ingelheim Health Research† of Calgary—Section • Boston Scientific • Medtronic† Chief Division of • Merck Cardiology. 2017 Principal or Other Financial Benefit Transplant and Neurology. Witness Downloaded from http://circ. 2017 ACC/AHA/HRS Syncope Guideline Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional. Libin • Pfizer Cardiovascular • St.. Shen W-K. EP Section Service—Director Leadership Council Patrick Content Reviewer University of None None None None None None McBride Wisconsin School of Medicine & Public Health—Professor of Medicine and Family Medicine. Dean for Faculty Affairs— Associate.ahajournals.org/ by guest on November 16. American Heart Association. Inc. Department of Medicine Antonio Content Reviewer Alliance to Fight None None None None None None Raviele Atrial Fibrillation— President. Venice © 2017 by the American College of Cardiology Foundation. et al. Lung Institute.org/ by guest on November 16. Milano—Senior Physician Richard Sutton Content Reviewer National Heart & • Medtronic* • St. Expert Bureau Partnership/ Organizational. Practice Chair of Neurology Colette Seifer Content Reviewer University of None None None None None None Manitoba—Associate Professor. Jude • Boston • Medtronic* None • Defendant. Inc. Director. 2017 Principal or Other Financial Benefit Arrhythmias— President Marwan Refaat Content American University None None None None None None Reviewer—ACC of Beirut—Faculty of EP Section Medicine and Medical Leadership Center Council Melissa Content Reviewer University of • Medtronic* None None None None None Robinson Washington— Assistant Professor of Medicine. Witness Downloaded from http://circ. et al. Ventricular Arrhythmia Program Paola Sandroni Content Reviewer Mayo Clinic— None None None None None None Professor of Neurology. Medical* Scientific* Fatal car Imperial College— • Edwards accident Emeritus Professor Lifesciences caused by * VVS patient. • Shire 3 trials in Pharma 2016* • AstraZenec a © 2017 by the American College of Cardiology Foundation. 2017 ACC/AHA/HRS Syncope Guideline Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional. Section of Cardiology.ahajournals. Shen W-K. and Heart Rhythm Society 79 . Monica Solbiati Content Reviewer Fondazione IRCCS None None None None None None CA' Granda.. Ospedale Maggiore Policlinico. American Heart Association. CPVT. sudden cardiac death. or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year. National Heart. American College of Emergency Physicians. 2017 ACC/AHA/HRS Syncope Guideline Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional. VCU. Relationships in this table are modest unless otherwise noted.. Veterans Affairs. Witness Downloaded from http://circ. SADS. Virginia Commonwealth University. American College of Cardiology. Jude Medical • Zoll Medical Paul Varosy Content Reviewer University of None None None • AHA† None None Colorado Hospital. at the time this document was under review. American Stroke Association. Names are listed in alphabetical order within each category of review. catecholaminergic polymorphic ventricular tachycardia. • VA Office of Clinical Cardiac EP Health Services Training program— Research and Associate Program Development Director. PI. Society for Academic Emergency Medicine. ICD. VA. Please refer to http://www. vasovagal syncope. Expert Bureau Partnership/ Organizational. and Heart Rhythm Society 80 . AHA. Shen W-K. PACE. Patient-Centered Outcomes Research Institute. VA Eastern (PI)* Colorado Healthcare System—Director of Cardiovascular EP This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review. Partners in Advanced Cardiac Evaluation. Society for Cardiovascular Angiography and Interventions. 2017 Principal or Other Financial Benefit Gaurav Content University of • Biosense Webster None None • Biotronik* None None Upadhyay Reviewer—ACC Chicago—Assistant • Biotronik • Medtronic* EP Section Professor of Medicine • Boston Scientific • Biosense Webster Leadership • Medtronic Council • St. AAN indicates American Academy of Neurology.000 of the fair market value of the business entity. Inc. LSU. © 2017 by the American College of Cardiology Foundation. ASA. including those not deemed to be relevant to this document. ACC. data safety monitoring board.org/ by guest on November 16. principal investigator. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity. Lung.S. Pediatric and Congenital Electrophysiology Society. and Blood Institute. DSMB. American Heart Association. HRS. Sudden Arrhythmia Death Syndromes Foundation. et al. The table does not necessarily reflect relationships with industry at the time of publication.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees. SCAI. Food and Drug Administration. American Heart Association. SAEM. ACEP. electrophysiology. familial hypercholesterolemia. PCORI.ahajournals. Relationships that exist with no financial benefit are also included for the purpose of transparency. Louisiana State University. SCD.acc. U. *Significant relationship. FDA. Journal of Cardiovascular Electrophysiology. EP. Heart Rhythm Society. FH. JCE. PACES. NHLBI. implantable cardioverter-defibrillator. or ownership of ≥$5. and VVS. †No financial benefit. org/ by guest on November 16. 2017 ACC/AHA/HRS Syncope Guideline Appendix 3.ahajournals. et al. 2017 HCM = hypertrophic cardiomyopathy HF = heart failure ICD = implantable cardioverter-defibrillator ICM = implantable cardiac monitor LCSD = left cardiac sympathetic denervation LQTS = long-QT syndrome LV = left ventricular MRI = magnetic resonance imaging OH = orthostatic hypotension QoL= quality of life RCT = randomized controlled trial POTS = postural tachycardia syndrome SCD = sudden cardiac death SVT = supraventricular tachycardia VA = ventricular arrhythmia VF = ventricular fibrillation VT = ventricular tachycardia VVS = vasovagal syncope © 2017 by the American College of Cardiology Foundation. Inc. and Heart Rhythm Society 81 .. 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Direct medical costs of syncope-related hospitalizations in the United States. Barón-Esquivias G. Boer KR. 95:668-71. Finkler SA. et al.. 733. Martínez A. 18:279- 94. J Cardiovasc Electrophysiol. Faddis MN. American Heart Association. 1982. 2002. Clin Geriatr Med. 734. 2017 ACC/AHA/HRS Syncope Guideline 732. Quality of life within one year following presentation after transient loss of consciousness. and Heart Rhythm Society 109 . The distinction between cost and charges. Does the use of a syncope diagnostic protocol improve the investigation and management of syncope? Heart. 90:52-8. 735. van DN. Europace. Ann Intern Med. Colman N. 96:102-9. Sulke AN. 2017 © 2017 by the American College of Cardiology Foundation. org/ by guest on November 16. Mohamed H. Benjamin C. is located on the World Wide Web at: http://circ.org//subscriptions/ . Goldberger. Benditt. and the Heart Rhythm Society Win-Kuang Shen. 2017 Circulation. Zachary D.org/content/suppl/2017/03/08/CIR. Robert S.0000000000000499. Sun and Clyde W. Forman. Cohen. a service of the Copyright Clearance Center.ahajournals. Online ISSN: 1524-4539 The online version of this article. Circulation is published by the American Heart Association. Andrew D.ahajournals. 7272 Greenville Avenue. Sheldon.lww. not the Editorial Office.ahajournals. Krahn. Reprints: Information about reprints can be found online at: http://www. Raj.DC1 http://circ. Dallas. click Request Permissions in the middle column of the Web page under Services.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ. Mark S. or portions of articles originally published in Circulation can be obtained via RightsLink. Once the online version of the published article for which permission is being requested is located. All rights reserved. Further information about this process is available in the Permissions and Rights Question and Answer document. Yancy Downloaded from http://circ. Satish R.citation Data Supplement (unedited) at: http://circ. 2017. Mitchell I. David G.org/content/suppl/2017/03/08/CIR. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Inc. Link.0000000000000499. published online March 9. Print ISSN: 0009-7322. Grubb.DC2 Permissions: Requests for permissions to reproduce figures.ahajournals. Hamdan.ahajournals. Roopinder Kaur Sandhu.0000000000000499. tables. TX 75231 Copyright © 2017 American Heart Association. Dan Sorajja. Daniel E.org/content/early/2017/03/09/CIR. Brian Olshansky. along with updated information and services. Blair P. Healthcare (Vice Chair) Professor POST 6 Network for Centers of Excellence David G. Biogen Shire Beth Israel Deaconess Medical Johnson & Center. University of Calgary None None None AA Pharma–POST 4 Concordia None Sheldon Department of Medicine— Apotex Corp–POST 5. Pediatric Cardiology—Chief Roy Freeman§ Harvard Medical School— Astellas Pharma None None Dong (DSMB) AstraZeneca None Professor of Neurology. Geriatric Cardiology Section. University of Minnesota Medical Medtronic* None None ZOLL None None Benditt School.. University of Arizona School of None None None Purdue None None Cohen Medicine-Phoenix—Clinical Pharmaceuticals Professor of Child Health.Author Relationships With Industry and Other Entities (Comprehensive)—2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (March 2015) Committee Employment Consultant Speakers Ownership/ Personal Research Institutional. University of Pittsburgh— None None None None None None Forman Professor of Medicine. Phoenix Children’s Hospital. Expert Witness Member Bureau Partnership/ Organizational. University of Washington School None None None None None None © 2017 by the American College of Cardiology Foundation. Center for Autonomic Johnson* and Peripheral Nerve Lundbeck* Disorders—Director Pfizer* Spinifex* Daniel E. . Department of Cardiovascular Diseases Robert S. Cardiovascular St. Mayo Clinic College of Medicine—Chair. University of Pittsburgh Medical Center—Chair. Cardiac Rehabilitation Zachary D. Jude Division—Professor of Medicine Medical* Mitchell I. and Heart Rhythm Society. American Heart Association. (DSMB) Phoenix Children’s Heart Center—Co-Director. Inc. VA Pittsburg Healthcare Systems—Director. or Principal Other Financial Benefit Win-Kuang Mayo Clinic Arizona—Professor None None None None None None Shen (Chair) of Medicine. The University of British Medtronic None None None Boston Scientific* None Krahn Columbia. University of Wisconsin School None None Clinic Notes None None None Hamdan of Medicine. Mercy Hospital North On-X Iowa— Electrophysiologist Satish R. Ingelheim Sankyo Sanofi-aventis Reuters† Cardiovascular Medicine— Daiichi-Sankyo Lundbeck (DSMB) Up to Date Emeritus Professor of Internal Lundbeck (Editor) Medicine. Expert Witness Member Bureau Partnership/ Organizational. None Amarin (DSMB) Thompson None Olshansky College of Medicine. Raj University of Calgary. Department of Medicine. .. Committee Employment Consultant Speakers Ownership/ Personal Research Institutional. Cardiac GE Healthcare None None Apotex Corp American Defendant. Daiichi. Grubb University of Toledo Medical Biotronik None None None None None Center. and Heart Rhythm Society. Sciences—Associate Professor Lundbeck* CIHR* Autonomic postural CANet* Society† tachycardia Medtronic Association of syndrome. Harborview Medical Center Division of Cardiology—Assistant Professor of Medicine Blair P. Inc. Cardiovascular F2 Solutions Medicine—Professor and Chief of Cardiovascular Medicine Andrew D. Division of Cardiology— Director. Cardiac Electrophysiology. American Heart Association. Professor of Medicine Brian University of Iowa Carver Boehringer. Medical None None None None None None © 2017 by the American College of Cardiology Foundation. Medicine and Medtronic Pediatrics—Professor Mohamed H. or Principal Other Financial Benefit Goldberger of Medicine. NIH* Clinical and 2015 Translational Sciences† Dysautonomia International† Roopinder University of Alberta. Link University of Texas None None None None None None Southwestern Medical Center. Division of Medtronic* Cardiology—Professor of Medicine and Head of Division Mark S. acc. or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees. Oregon Health & Science None None None NIH–Syncope Risk None Defendant. Institute† Diversity & Inclusion—Vice Dean This table represents all relationships of committee members with industry and other entities that were reported by authors. The table does not necessarily reflect relationships with industry at the time of publication. Inc.. © 2017 by the American College of Cardiology Foundation. *Significant relationship. Relationships in this table are modest unless otherwise noted. or ownership of ≥$5. Northwestern University None None None None Patient Centered None Yancy Feinberg School of Medicine. at the time this document was under development. †No financial benefit. Sun University—Associate Professor Stratification Study emergency (PI)* medicine NIH (DSMB)† standard of NIH–Identifying care for Hospital Practices to evaluation of Reduce ED Crowding syncope. Relationships that exist with no financial benefit are also included for the purpose of transparency. Outcomes Division of Cardiology— Research Professor of Medicine and Chief. American Heart Association. Please refer http://www. Expert Witness Member Bureau Partnership/ Organizational. .000 of the fair market value of the business entity. A person is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity. Committee Employment Consultant Speakers Ownership/ Personal Research Institutional. including those not deemed to be relevant to this document. and Heart Rhythm Society. None None None None None None Cardiovascular Diseases— Assistant Professor of medicine Benjamin C. or Principal Other Financial Benefit Kaur Sandhu Division of Cardiology— Assistant Professor of Medicine Dan Sorajja Mayo Clinic Arizona. 2014 (PI)† NIH–Effectiveness of Prescription Monitoring Program in Emergency Departments (PI)* NIH–Improving Syncope Risk Stratification in Older Adults (PI)* Clyde W. recusals noted are from the initial round of balloting. CANet. American Heart association. © 2017 by the American College of Cardiology Foundation. and VA. Veteran’s Affairs. Roy Freeman. emergency department. resigned from the writing committee in November 2016. principal investigator. prior to the final balloting process. CIHR. National Institutes of Health. . ED. We thank him for his contributions. and Heart Rhythm Society..§Dr. Heart Rhythm Society. American Heart Association. NIH. the official representative of the American Academy of Neurology. DSMB. PI. HRS. data safety monitoring board. Canadian Institute of Health Research. Cardiac Arrhythmia Network of Canada. Inc. ACC indicates American College of Cardiology. AHA. ......................4) ............3) ........... and Heart Rhythm Society......... Nonrandomized Trials........ and/or Registries of Cardiac Imaging – (Section 3.......2..................................................3............... Nonrandomized Trials...........................5) . Nonrandomized Trials...2............... and/or Registries of Long-QT Syndrome – (Section 4.... and/or Registries of Short-QT Pattern and Syncope – (Section 4.................... 37 Data Supplement 15.......3) ..............2... 16 Data Supplement 6.......3..............4) .....2) .. Nonrandomized Trials.................2..2............. 66 Data Supplement 21...... 68 Data Supplement 22........................................ Nonrandomized Trials.. and/or Registries of Risk Stratification .......................1) ........ and/or Registries Comparing Blood Testing – (Section 3. 19 Data Supplement 8...................................... Observational Studies.......................................... 18 Data Supplement 7...............Data Supplement (Section numbers correspond to the full-text guideline...... Inc..............................................2................ Observational Studies..................4) ........... 8 Data Supplement 4........................... and/or Registries of Neurologic Investigation – (Section 3.............. Nonrandomized Trials.... Observational Studies... RCTs for Disposition After Initial Evaluation – Serious Conditions – (Section 2.. and/or Registries for History and Physical Exam – (Section 2... 72 Data Supplement 23......................................................... Observational Studies........... Observational Studies.). 76 1 © 2017 by the American College of Cardiology Foundation....2........................................................................4) . and/or Registries of Cardiac Monitoring – (Section 3...........1) .....2. Nonrandomized Trials........................................ Nonrandomized Trials......................... Nonrandomized Trials. Observational Studies....................... 25 Data Supplement 11........3.............. 58 Data Supplement 18.... ........3) ........... 8 Data Supplement 3....... RCTs Comparing Cardiac Monitoring – (Section 3......................... and/or Registries of Stress Testing – (Section 3.......3............. Observational Studies............1) ......1) .......2.) Table of Contents Data Supplement 1....... Nonrandomized Trials. 26 Data Supplement 12..........3..............Short-Term Outcomes – (Section 2.............................. Nonrandomized Trials............ and/or Registries of CPVT................................. 35 Data Supplement 14................. Observational Studies............. 21 Data Supplement 9......... and/or Registries of Disposition After Initial Evaluation – (Section 2.... and/or Registries of CPVT-Medical Therapy – (Section 4.. Observational Studies........ and/or Registries of Brugada Syndrome – (4.......... Nonrandomized Trials........................................ Observational Studies.........................2) ...........3.....3) . Nonrandomized Trials.... 46 Data Supplement 16.................................. Observational Studies... and/or Registries of Tilt Table Testing – (Section 3... Nonrandomized Trials........... and/or Registries of Electrophysiology Testing – (Section 3..... and/or Registries of ARVCD – (Section 4............. 5 Data Supplement 2...........3............ 59 Data Supplement 19..... Observational Studies....... Nonrandomized Trials...................................... American Heart Association...LSCD and ICD Therapy – (Section 4........... Nonrandomized Trials.................................. and/or Registries of Blood Testing – (Section 3........ Observational Studies. 22 Data Supplement 10. Observational Studies......5) .................... Nonrandomized Trials......... Observational Studies................................. Nonrandomized Trials...........4) ........................ Observational Studies...................................... 52 Data Supplement 17... Nonrandomized Trials........... Observational Studies..................................3.............. and/or Registries of In-Hospital Telemetry – (Section 3.................6.................... and/or Registries of Electrocardiography – (Section 2.......4). Observational Studies... and/or Registries of Risk Stratification ...... Observational Studies........... Nonrandomized Trials..3......3...........2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope .. 28 Data Supplement 13.......... 14 Data Supplement 5.................................................. Nonrandomized Trials..................... Observational Studies.................... 62 Data Supplement 20.....3) ........... Observational Studies....................................................Long-Term Outcomes – (Section 2....... and/or Registries of Sarcoid Heart Disease – (Section 4...........3)....1) .......3.......................2) ....... ..................................................1) ....................... Observational Studies.................. 94 Data Supplement 30.. American Heart Association...................................................1) ..................................................5) ................................................ 96 Data Supplement 31............................. 78 Data Supplement 25................................... 89 Data Supplement 27....2...................................... and/or Registries of Early Repolarization Pattern – (Section 4.........2) ... RCTs for Neurogenic Orthostatic Hypotension – (Section 6.........1. Nonrandomized Trials.................... Observational Studies........ Nonrandomized Trials................ and/or Registries of Pseudosyncope – (Section 8).............. Observational Studies. Nonrandomized Trials..1................. Observational Studies..... RCTs for Pseduosyncope – (Section 8) ............. Observational Studies..................... Inc......................................2) .. Nonrandomized Trials.......................................2) ................. and/or Registries of Vasovagal Syncope – (Section 5...... Observational Studies.............................. and/or Registries of Pacemakers in Vasovagal Syncope – (Section 5...1) ................................ and/or Registries of Syncope in Athletes – (Section 10......2............... Observational studies....................1....................... RCTs Comparing Carotid Sinus Syndrome – (Section 5.............2..... 131 Data Supplement 41......... 127 Data Supplement 39.................. 114 Data Supplement 36.......................... for Type of Permanent Pacing in Carotid Sinus Hypersensitivity – (Section 5............. Nonrandomized Trials............................................ Observational Studies......1..................2) ........ Nonrandomized Trials... 112 Data Supplement 35..................................Data Supplement 24............ 143 Data Supplement 42.... 81 Data Supplement 26................1)........................................... RCTs Comparing Vasovagal Syncope – (Section 5.........2)............... 99 Data Supplement 32..................... and/or Registries of Geriatrics – (Section 10..................................1) .........................................2) .................... 117 Data Supplement 37............ Observational Studies.........2) ....................................... and Heart Rhythm Society....................................................2) ............................................... 93 Data Supplement 29........ Nonrandomized Trials.......... 100 Data Supplement 34.............1................... Nonrandomized Trials.............. Observational Studies.......................... .................... Nonrandomized Trials....................... and/or Registries of Pediatrics – (Section 10...... RCTs Involving Dehydration and Drugs – (Section 6.............3....1) .......... 147 2 © 2017 by the American College of Cardiology Foundation................................................................................................ 90 Data Supplement 28....... Nonrandomized Trials....... 144 Data Supplement 43.......................... and/or Registries of Neurogenic Orthostatic Hypotension – (Section 6................. Nonrandomized Trials......................................................................... and/or Registries of Neurogenic Orthostatic Hypotension – (Section 6..........................................................................................................3) ...... Nonrandomized Trials................... Observational Studies......... Observational Studies...................... and/or Registries of Dehydration and Drugs – (Section 6..................3) ..................... Observational Studies......... 130 Data Supplement 40.......... and/or Registries of Permanent Pacing in Carotid Sinus Hypersensitivity – (Section 5................................ RCTs Comparing Pacemakers in Vasovagal Syncope – (Section 5.............. 100 Data Supplement 33........ 120 Data Supplement 38.5) .................... RCTs for Type of Permanent Pacing in Carotid Sinus Hypersensitivity – (Section 5...... and/or Registries of Adult Congenital Heart Disease – (Section 10............. vasovagal. ejection fraction. biomarkers. Netherlands. CS. not available. ACS. ventricular arrhythmia. falls. psychogenic pseudoseizures. arrhythmogenic right ventricular cardiomyopathy. odds ratio. LOC. GERD. doctor of medicine. lower body negative pressure. EPS. diabetes mellitus. congestive heart failure. early repolarization syndrome. midodrine. and indexed in MEDLINE (through PubMed). CSR. arrhythmogenic right ventricular dysplasia/cardiomyopathy. France. orthostatic hypotension questionnaire. history. congenital heart disease. MACE. postural. neurally mediated syncope. CAD. CV. that included literature published through October 2015. cardiac output. carotid sinus reaction. OT. BNP. micturition syncope. hazard ratio. EEG. transient loss of consciousness. OH. and other selected databases relevant to this guideline. orthostatic. carotid sinus massage. tilt-test. vasovagal syncope. syncope unit. MCA. BSC. CA. implantable loop recorder. published in English. AV. carotid sarcoidosis. NMS. psychogenic pseudosyncope. heart failure. HUTT. CSH. Key search words included but were not limited to the following: adverse. cTnThs. Italy. Hx. Anatolian Syncope Rule. DVI. laboratory testing. AF. presyncope. LVNC. chronic obstructive pulmonary disease. AV block. ILR. high-sensitivity cardiac troponin T. middle cerebral artery blood velocity. early repolarization. vasodepressor syncope. AMI. H&P. acute myocardial infarction. idiopathic dilated cardiomyopathy. long QT syndrome. fludrocortisone. GTN. loss of consciousness. atrioventricular. LCSD. CAA. bundle branch block. defecation syncope. EMBASE. . Orthostatic Hypotension Symptom Assessment. carotid sinus syndrome. electrophysiologic. florinef. pressure counter maneuvers. brain natriuretic peptide. emergency department. confidence interval. MSA. CHF. Kaplan-Meier. MRI. cardiovascular. PAF. American Heart Association. LBBB. left ventricular non-compaction. AAD. Germany. heart rate. carotid sinus massage. MCOT. GFR. ambulatory monitor. tilt-training. indicates adverse drug events. FINGER. major adverse cardiac event. beta blocker. orthostatic intolerance. MAP. aged. dual chamber pacing. hypertrophic cardiomyopathy. Brugada syndrome. left bundle branch block. 2°. Terms may have been used alone or in combination. left ventricular ejection fraction. and Heart Rhythm Society. PCI. EF. LVH. electroencephalogram. nonsustained ventricular tachycardia. coronary artery disease. electrophysiological. CPR. ED. atrioventricular interval. IVCD. drug. psychogenic syncope. hypertension. Inc. negative predictive value. PCA. CSS. Oral Fluid and Trendelenburg position. atrial fibrillation. echocardiogram. ARVC/D. electrocardiogram. holter monitor. NYHA. HTN. NICM. implantable cardioverter-defibrillator. N/A. cognitive behavioral therapy. hypertrophic cardiomyopathy. COPD. CPVT. carotid artery angioplasty. LQTS. BS. computed tomography.OHDAS. MS. the Cochrane Library. ADE. electrophysiological study. pure autonomic failure. DM. fluoxetine. multiple systems atrophy. myocardial infarction. loop monitor. posterior cerebral artery blood velocity. aortic stenosis. glyceryl trinitrate. early repolarization pattern. intensive care unit. electrocardiogram. acute coronary syndrome. loop recorder. psychogenic non-epileptic seizure. blood pressure. Boston Syncope Criteria. New York Heart Association classification for heart failure. arrhythmogenic right ventricular dysplasia. cardiovascular disease. Calgary Syncope Symptom Score. ER. Osservatorio Epidemiologico sulla Sincope nel Lazio. LVEF. ICD. IDCM. magnetic resonance imaging. not significant. LBNP. Registry. ARVC. HF. cardiovascular disease. history and physical exam. monitor.Methodology and Evidence Review The recommendations listed in this guideline are. HCM. external loop recorder. non-epileptic pseudo seizures. orthostatic hypotension. syncope. AS. short QT Syndrome. carotid sinus hypersensitivity. bradycardia. BP. cardiac arrest. blood pressure. AAI. MD. b-blockers. sensing without pacing. BBB. telemetry. OHQ. chest x-ray. CLS. catecholaminergic polymorphic ventricular tachycardia. antiarrhythmic dug. intravenous fluid. aborted cardiac arrest. electrocardiography. medication. ICD. tilt table test. breath-holding. nonischemic dilated cardiomyopathy. CSM. head-up tilt test. 3 © 2017 by the American College of Cardiology Foundation. EP. OT. NSVT. pacing. intraventricular conduction disturbances. EDOSP. CSSS. salt. atrioventricular block. Carotid Sinus Syndrome. the Agency for Healthcare Research and Quality. implantable loop recorder. NS. hypotension. CI. functional neurologic symptoms. ECG. electrophysiological. implantable cardioverter defibrillator . NPV. ARVD. pediatrics. evaluation of guidelines of syncope study. DS. gastroesophageal reflux disease. OHSA. OESIL. CCU. emergency department observation syncope protocol. closed loop stimulation. ODO. children. CO. left cardiac sympathetic denervation. arrhythmogenic right ventricular dysplasia. aging. OR. LCS. Brugada Syndrome. dual chamber pacing. catecholaminergic polymorphic ventricular tachycardia. left ventricular hypertrophy. carotid sinus hypersensitivity. pacemaker. CHD. PCM. ERP. cardiopulmonary resuscitation. orthostatic tachycardia. appropriate use criteria. whenever possible. rehydration. mobile cardiac outpatient telemetry. LV. OI. EGSYS. exercise stress test. Abbreviations 1° indicates primary. glomerular filtration rate. coronary care unit. left cardiac sympathetic denervation. IV. Other selected references published through May 2016 were incorporated by the writing committee. ICU. evidence based. CBT. diastolic blood pressure. length of stay. mode of pacing. percutaneous coronary intervention. DBP. Orthostatic Hypotension Daily Activity Scale. MI. CXR. KM. LOS. tilt table. AUC. BID. dehydration. BB. two times a day. holter. HR. ACA. diagnosis. stress test. echocardiography. CVD. athletes. ELR. ventricular fibrillation and ventricular tachycardia. long QT Syndrome. Literature included was derived from research involving human subjects.. left cervicothoracic sympathectomy. AVB. DDD. CT. arrhythmogenic right ventricular cardiomyopathy. idiopathic AV block. left ventricle. EST. mean arterial pressure. consciousness. An extensive evidence review was conducted from July through October 2015. secondary. ASR. ventricular arrhythmias. video-assisted thoracic surgery. VT. VFL. quality of life. TIA. TTT. stroke volume. vital signs. SA. ROSE. VVS. sudden cardiac death. SFSR. SBP. TCA. permanent pacemaker. tetralogy of Fallot. PVD. POTS. RR. TLOC. S/P. PNES. VS.physical counter pressure maneuvers. SHD. and Heart Rhythm Society. . sinus node recovery time. SNS. sinoatrial. 4 © 2017 by the American College of Cardiology Foundation. VA. sympathetic nervous system. premature ventricular contractions. ventricular flutter. Ryanodine receptor type 2. SV. physical examination. VVI. SQTS. TOF. systolic blood pressure. SD. syncope of unknown origin. QoL. SUO. SND. relative risk. peripheral vascular disease. pacemaker. PPS. randomized. supraventricular tachycardia. Parkinson disease. sinus node dysfunction. PM. PD. sinus node. double blind. ventricular pacing. SVT. POST. TPR. PMVT. VF. polymorphic ventricular arrhythmias. short QT syndrome. randomized controlled trials. ventricular fibrillation. PES. thermoregulatory sweat test. placebo-controlled trial. SN. vasovagal syncope. Prevention of Syncope trial. sudden death. tilt-table test. SCD. TST. trichloroacetic acid. PE. valvular heart disease. RRR relative risk ratio. VATS. risk stratification of Syncope in the Emergency Department.. postural (orthostatic) tachycardia syndrome. total peripheral resistance. Wolff-Parkinson-White. ventricular tachycardia. RCT. programmed electrical stimulation. PVC. PPM. Inc. transient ischemic attack. and WPW. American Heart Association. spinal cord injury. SNRT. RyR2. psychogenic nonepileptic seizures. psychogenic pseudosyncope. structural heart disease. strategies primary. RDBPCT. San Francisco Syncope Rule. VHD. SCI. transient loss of consciousness. Data Supplement 1. palpitations After syncope: nausea.32 VT. Aim: Establish the clinical features of Inclusion criteria: Pts with Results: VVS differed from other neutrally mediated Considerable overlap between 2004 VVS syncope syncopes in precipitating factors and clinical features. et al. or VT established hx of VT. warmth. different Neurally medicated 14697727 including lower age and prevalence of organic heart syndromes (3) Study type: Prospective Study Exclusion criteria: N/A disease.3. Comment(s) Year Published & 95% CI) Calkins. fatigue Alboni P. higher prevalence and duration of prodrome. Low prevalence of trauma Size: n=461 pts prospectively evaluated. diaphoresis. et al. Male gender distinguishing pts with these 3 7709949 VVS. or AVB Age >54 causes of syncope (1) Study type: Prospective <2 episodes of syncope Exclusion criteria: N/A Size: n=80 pts (16 AVB. Observational Studies. with VVS. Patient Population Primary Endpoint and Results Summary/Conclusion Author. nausea. American Heart Association. specificity: 45%) 97% (2) Study type: Prospective study Exclusion criteria: N/A Size: n=341 pts analyzed Cardiac cause 78 (23%) VVS 199 (58%) Neuro/Psych 4 (1%) Unexplained 60 (18%) Alboni P. OR or RR.. and Heart Rhythm Society. 280 had VVS: Typical VVS n=39 HUTT induced n=142 Complex (CSH+VVS) n=31 5 © 2017 by the American College of Cardiology Foundation. diaphoresis. Study Size (P values. AVB.1) Study Acronym. and/or Registries for History and Physical Exam – (Section 2. Study Type/Design. Aim: Identify +quantitate symptoms Inclusion criteria: 80 pts with Results: Features suggestive of AVB or VT Clinical history is of value in 1995 assoc. Aim: Establish the historical findings Inclusion criteria: Pts with Results: Only heart disease was an independent Absence of heart disease allowed 2001 predictive of the cause of syncope syncope predictor of a cardiac cause of syncope (sensitivity: an exclusion of a cardiac cause in 11401133 95%. Nonrandomized Trials. et al. . 32 Features suggestive of VVS VVS) Before syncope: blurred vision. Inc. Other in 80 pts Size: n=671 pts with a history of TLOC completed a 118 item historical questionnaire FAST Aim: Assess yield and accuracy of an Inclusion criteria: Adults Results: At initial evaluation: Attending physicians can make a Van Dijk.Sheldon.. et al. used a and specificity Questioner of 118 items Exclusion criteria: N/A Size: n=418 pts 235 syncope and positive HUTT n=95 no apparent cause (-HUTT) n=88 pts secondary syncope n=42 pts with CHB n=21 pts with SVT n=6 pts with VT n=5 pts with AS Sheldon. et al. presenting with TLOC to the 119 pts (24%) certain diagnosis diagnosis in 63% of pts with TLOC. PE. . American Heart Association. 2008 and ECG Academic Medical Center 199 pts (40%) had a highly likely diagnosis with a diagnostic accuracy of 88% 17916139 Amsterdam between February Overall diagnostic accuracy was 88% (6) Study type: Prospective analysis then 2000 and May 2002 a 2 y follow-up by an expert committee Exclusion criteria: N/A Size: n=503 pts (with a 2 y follow-up in 99%) 6 © 2017 by the American College of Cardiology Foundation. et al. VT in 90 pts. Aim: Develop criteria that distinguish Inclusion criteria: Pts with Results: The point score based on symptoms 2002 syncope due to VT from VVS in pts syncope and SHD Cause of TLOC known in 539 pts alone correctly classified 94% of pts. initial evaluation using : History. Aim: Establish historical criteria for Inclusion criteria: Pts with Results: The point score correctly classified 90 % of pts The point scoring system can 2006 diagnosis of VVS syncope and no apparent structural with an 89% sensitivity and 91 % specificity distinguish VVS from other causes 16223744 heart disease of syncope with a high sensitivity (4) Study type: Prospective. and Heart Rhythm Society. Primary diagnosing seizures with a 94% (5) Exclusion criteria: N/A Generalized in 52 pts sensitivity and 94% specificity Study type: Prospective analysis Syncope in 437 pts: VVS in 267 pts. 12103268 with SHD Seizures in 102 pts: Complex partial in 50 pts. Inc. signs and symptoms. American Heart Association. Clinical history. 1. that associate with cardiac causes of 2 Pubmed searches using the A total of 10 variables were found associated with effective with moderate accuracy: 2013 syncope following key words: cardiac syncope : >60 y of age 24223233 1.Romme. Diagnosis. 118 item headaches and fatigue after questionnaire and an invasive and syncope lasting >1 min non-invasive diagnostic assessment The point score identified 92% of pts correctly. et al. Absence of nausea Degree of evidence accepted in 9. Low number of spells Lack of prodromal symptoms Pts with ≥1 transient loss of 5. and Heart Rhythm Society. Brief or absent prodrome consciousness 6. Inc. . negative predictive value of >96% PLOS Aim: Develop a model for symptoms Inclusion criteria: Results: A model with 5 variables was as Berecki-Gisolf. Absence of blurred vision Studies reporting ≥2 predictors of cardiac syncope Exclusion criteria: N/A 7 © 2017 by the American College of Cardiology Foundation. diagnosis. Study type: Prospective. Male gender Structural heart disease 2. Aim: Evaluate evidence based criteria Inclusion criteria: Pts with Results: Factors predicting VT were male 2010 to distinguish syncope due to VT from syncope and SHD 21 pts with HUTT+VVS gender and >35 y of age 20586825 VVS in pts with structural heart 78 pts with clinical or EPS Induced VT Factors predicting VVS were (8) disease Exclusion criteria: N/A 35 pts with no cause identified Prolonged sitting or standing. et al. diagnosing VT with Size: n=134 pts 99% sensitivity and 68% specificity.. Structural heart disease Low number of spells Size: n=7 studies syncope 4. Effort syncope vs. Supine syncope A diagnosis of cardiac syncope 7. Age >60 y Male gender (9) Study type: Literature based review vasovagal syncope 2. Absence of diaphoresis each paper 10. Aim: Evaluate the Calgary Syncope Inclusion criteria: Pts with TLOC Results: Sensitivity of Calgary score was 87% but the Sensitivity of the Calgary score 2009 Symptom Score Specificity was 32% similar to original study but the 19687157 Exclusion criteria: N/A specificity less (7) Study type: Prospective trial Size: n=380 pts with TLOC: 237 pts (55%) were diagnosed with VVS using Calgary Score and then compared after 2 y of follow-up Sheldon. et al. 3. pre- syncope preceded by stress. other causes 8. 001. Inclusion criteria: Pts with 1 endpoint: Mortality Only the presence of AF. Ventricular pacing: OR: 21. the ECG was normal for 52% of pts Perez-Rodon J. 95% CI: 1. Study Type/Design. Observational Studies. left ventricular hypertrophy ECG criteria OR: 6. AF OR: 6.3) Study Acronym. Patient Population Primary Endpoint and Results Summary/Conclusion Author.3. Comment(s) Year Published & 95% CI) 8 © 2017 by the American College of Cardiology Foundation. physical and ECG provided information to 1995 observational admitted to hospital due to ofechocardiogram to evaluate pts diagnosis a cause of syncope in 77% of pts (33 of 48 8770716 syncope admitted with syncope pts for whom a cause of syncope was felt to be (10) Size: n=128 pts ultimately determined) Exclusion criteria: Pts with Results: For pts with suspected cardiac disease. Observational Studies.3 p=0.6%) had ECG and ventricular pacing is associated with 1 y all (11) Size: n=524 pts abnormal ECG. Study Type/Design. 33 pts (6.Data Supplement 2. p=0.3%) died cause mortality Exclusion criteria: N/A during f/u. or pts echocardiogram which did not help 52%. prospective. Nonrandomized Trials. . Inc. and Heart Rhythm Society. syncope with known cause.7–8.011.2) Study Acronym. Study type: Retrospective Inclusion criteria: All pts 1 endpoint: frequency of use Hx. Patient Population Primary Endpoint and Results Summary/Conclusion Author. Study Size (P values.5– 26. 64% of pts had 48% and ruled out suspected cause for remaining vertigo. Study type: Multicenter. left ventricular hypertrophy 24993462 12 mo f/u Results: 344 pts (65. intraventricular 2014 observational syncope.8.3. Intraventricular conduction disturbances OR: 3. and echocardiogram.001 Data Supplement 3. 95% CI:4.3. and/or Registries of Electrocardiography – (Section 2. et al.5– 26. seizure..8. 95% CI:1. 90% of pts underwent cardiac echocardiogram confirmed suspected diagnosis for pts with near syncope.8. testing. Nonrandomized Trials. referred to EP testing elucidate cause of syncope. p=0. 95% CI: 1.3. Study Size (P values. and/or Registries of Risk Stratification .Short-Term Outcomes – (Section 2. OR or RR. OR or RR. p=0.011. American Heart Association.3.1–115. readable ECG and conduction disturbances. Comment(s) Year Published & 95% CI) Recchia D. et al.3. MI. .. acute benefit from hospital admission 18206736 anti-arrhythmic therapy. atrial admitted and 34 discharged. acute renal failure.. with no missed adverse rhabdomyolysis. aortic dissection. Study type: Prospective Inclusion criteria: Presyncope. and Heart Rhythm Society. another 2012 observational y of age arrest. head injury Results: Predictors of short-term outcomes (n=41 as cause of loss of consciousness. seizure. consciousness. shock. vertigo. terminal illness.5% in the Quantitative. et al. intracranial bleed. Costantino G. light-headedness. pre. Inc. pts. a 38% reduction in threatening sequelae of syncope (i. modified criteria. substance abuse. cardiac . However. et al. arrhythmia. >18 1 endpoint: Adverse outcomes ( death. coma. MI. may identify low-risk 12727148 ED's Results: Primary outcome occurred in 31 (11. Unclear whether these specific risk scores 2014 meta-analysis from 6 prospective observational severe outflow tract obstruction.681 pts syncope resulting in major trauma consider Exclusion criteria: N/A Results: "OESIL". fractures) Results: 11 pts admitted with 49 adverse outcomes. 9 © 2017 by the American College of Cardiology Foundation. "SFSR. attempts at reproducing n=270 pts. Colivicchi F. 1 y mortality. Study type: Prospective Inclusion criteria: Pts >12 y of age 1 endpoint: 1 y all-cause mortality No "OESIL" risk factors associated with 2003 observational presenting for syncope to one of 6 0%. severe 41 pts with risk factors would have been 22981659 infection/sepsis. These criteria may identify pts who might 2008 observational presenting to one of 4 ED's pacemaker/ICD placement. readmission (15) Size: n=676 pts Exclusion criteria: Dangerous condition identified in ED." "EGSYS" risk scores had similar sensitivity and specificity as clinical judgment. stroke. American Heart Association. ventricular dysrhythmia. Value of risk scores. ICU admission. and male gender. CPR.1%) included abnormal ECG. Study type: Prospective Inclusion criteria: >18 y of age 1 endpoint: 10 d combined death. et al. Validation cohort Exclusion criteria: Seizure. Hx of CV disease. 6. concomitant nonspontaneous return to trauma. If BSC had been followed 41 additional pts admitted and 34 pts discharged. CPR. "OESIL" score predictors include difficult n=328 pts syncope. vertigo pts >65 y of age. admission. CHF. dizziness. et al.e.5%) subgroup that can be discharged (13) Size: Derivation cohort pts in derivation cohort and 28 (8. a 3% increase (12) Size: n=244 ED pts with Exclusion criteria: None dysrhythmia (including SVT and AF with rapid in admission rate. only 68 pts would have hemorrhage. add value to clinical evaluation 24862309 studies pulmonary embolism. pulmonary embolus. validation cohort. Study type: Patient level Inclusion criteria: Patient level data 1 endpoint: 30 d combined death. required admission. using the presyncope ventricular response).Grossman SA. abnormal ECG Costantino G. long bone or cervical spine outcomes on follow-up. hemorrhage. no prodrome. If BSC had been followed strictly. etiology important to (14) Size: n=3. or life. no prodrome. and >17% if EGSYS score ≥3 18519550 ED's Results: "EGSYS" risk score predictors include (18) Size: Derivation n=260 pts. male gender.2% risk of 30 d mortality 22594351 syncope in an integrated health Results: Predictors of short term mortality included (19) Size: n=22. ICU admission. et al. recent visit for syncope. DM. or VHD. Study type: Prospective Inclusion criteria: >18 y of age 1 endpoint: 10 d combined death. sustained ventricular arrhythmia. and dementia Exclusion criteria: None Dipaola F. benefit from hospital admission 22192287 ischemic heart disease. had less than 0. exertional syncope (+3). et al. American Heart Association.. et al. Study type: Prospective Inclusion criteria: Presentation of 1 endpoint: Cardiac cause of syncope Risk of cardiac cause is <3% if EGSYS 2008 observational unexplained syncope to one of 14 score <3. precipitating factors (-1). history of HF. conduction abnormalities requiring pacemaker not rule out dangerous conduction problems 15975670 syncope therapy. heart disease and/ validation n=256 pts Exclusion criteria: None or abnormal ECG (+3). history of HF or ischemic heart disease. . (16) Size: n=11 studies Exclusion criteria: N/A Results: Strongest predictors of an adverse outcome included palpitations preceding syncope. Unclear whether these specific risk scores 2010 observational presenting to one of 2 EDs with pacemaker/ ICD placement. autonomic prodrome (-1) Derose S. 5% event rate at 2. Inc.5 y. readmission (20) Size: n=488 pts Exclusion criteria: None Results: Compared to the "OESIL" and "SFSR" risk scores. refusal to provide consent D'Ascenzo F. et al. Study type: Prospective Inclusion criteria: Normal EPS after 1 endpoint: Combined symptomatic AV block. unstructured clinical judgment had similar sensitivity and higher specificity. exertional syncope. sudden as cause of syncope (17) Size: n=305 pts death Exclusion criteria: None Results: ECG is only independent predictor of long term adverse events Del Rosso A. 10 © 2017 by the American College of Cardiology Foundation. evidence of bleeding Da Costa A. These criteria may identify pts who might 2013 analysis syncope to an ED hospitalization/intervention related to arrhythmia. supine syncope (+2). and Heart Rhythm Society. normal EPS does 2006 observational first onset of syncope or near. acute add value to clinical evaluation 20466221 syncope of unknown cause anti-arrhythmic therapy. Inclusion criteria: Presentation of 1 endpoint: Combined death. CPR. et al. palpitations prior to syncope (+4). seizure. Study type: Retrospective Inclusion criteria: Primary ED 1 endpoint: 30 d mortality Pts without history of HF and <60 y of age 2012 observational diagnosis of syncope or near. Study type: Pooled meta.189 pts system increasing age. VHD. male Exclusion criteria: None gender. or Increasing age and presence of cardiac co- 2010 Retrospective observational diagnosis of syncope or near. OH (+1).. hospitalization. Study type: Prospective Inclusion criteria: >60 y of age with 1 endpoint: Positive tilt test Calgary Syncope Symptom score for VVS 2013 observational suspected VVS and undergoing tilt has lower sensitivity and specificity in elderly 23478089 test Results: CSSS score ≥ -2 has sensitivity of 50% population than previously reported (21) Size: n=180 pts and specificity of 73% Exclusion criteria: None Gabayan G. Exclusion criteria: None ventricular arrhythmia. 4.330 pts system Results: Predictors included >60 y of age. intranial bleed. 5. Hx of outpatient follow-up. et al. Study type: Inclusion criteria: Primary ED 1 endpoint: 7 d death. et al. Hx of CHF. Grossman S. 7. (23) Exclusion criteria: None stroke. Hx of CHF (+1). American Heart Association. PCI. These criteria may identify low risk pts for 2007 observational presenting to an ED with syncope cardiac urgery. 8. change in whom discharge can be considered 17976548 anti-arrhythmic therapy. volume depletion. and Heart Rhythm Society. CPR. >45 y of age. Martin T. persistent abnormal vital signs in ED.". Hx of HF. Study type: Prospective Inclusion criteria: >18 y of age 1 endpoint: 30 d pacemaker/ ICD placement. 6. primary central nervous system event Kayayurt K. procedure related to ischemic heart disease. ischemic heart disease. benefit from hospital admission 22520447 syncope of unknown cause arrhythmic therapy (24) Size: n=231 pts Exclusion criteria: None Results: The "ASR" risk score includes dyspnea (+1). ICU admission. 2. arrhythmia. Inc. Pts validation n=374l without any of these risk factors had <8% risk of the 11 © 2017 by the American College of Cardiology Foundation. blood transfusion. Study type: Prospective Inclusion criteria: >18 y of age 1 endpoint: 7 d rehospitalization. et al. VHD. anti. et al. 3. morbidities is associated with short term 20102895 syncope in an integrated health or arrhythmia serious cardiac outcomes. MI Size: n=362 pts Results: Low risk pts (<3% event rate) had none of the following: 1. sepsis. et al. death. pulmonary embolus. These criteria may identify pts who might 2012 observational presenting to one of 2 ED's with pacemaker/ ICD implantation. "SFSR. ASR at a cut-point of >2 appears to similar test characteristics as the "OESIL. abnormal ECG (+2). worrisome cardiac history. family Hx of sudden death. CPR. precipitating cause for syncope (+1). . suspicion for ACS. and VHD." and "EGSYS" risk scores. (25) Size: Derivation n=252.Exposito V. Study type: Prospective Inclusion criteria: Presentation of 1 endpoint: 1 y mortality or arrhythmia These criteria may identify pts who might 1997 observational syncope to an ED benefit from hospital admission or close 9095005 Results: Predictors include abnormal ECG. signs of conduction disease. pts >58 y of age (+1). death. (22) Size: n=35. arrhythmia. Study type: Prospective Inclusion criteria: Presentation of 1 endpoint: 30 d combined death. the 2004 observational syncope to an ED pulmonary embolism. arrhythmia. and ECG Exclusion criteria: None abnormalities Quinn J. outcome. Prior syncope episodes and lack of prodrome were associated with increased risk of cardiogenic cause. Quinn J. et al. stroke. prior sustained monomorphic VT Numeroso F. or any 62% specificity. significant hemorrhage. subarachnoid "SFSR" risk score has 96% sensitivity and 14747812 hemorrhage. et al. SBP <90 mmHg. significant hemorrhage. 1985382 Results: Risk factors included abnormal signal (26) Size: n=91 pts Exclusion criteria: None averaged ECG. Moazez F. and Heart Rhythm Society. et al. Results: In this derivation study. Inc.. American Heart Association. Study type: Retrospective Inclusion criteria: >18 y of age 1 endpoint: Cardiac cause of syncope These criteria may identify pts who might 2010 observational hospitalized for syncope benefit from hospital admission 20515909 Results: OESIL score <2 had NPV of 98% to (27) Size: n=200 pts Exclusion criteria: None exclude cardiogenic cause. shortness of breath. Hx of CHF. Study type: Prospective Inclusion criteria: Presentation of 1 endpoint: 7 d combined death. MI. stroke. arrhythmia. . the "SFSR" risk score was 98% sensitive and 56% specific. Study type: Prospective Inclusion criteria: Syncope of 1 endpoint: Inducible sustained monomorphic VT These criteria may be used to identify pts 1991 observational unknown origin referred for EPS who might benefit from EPS. subarachnoid have decreased hospitalizations by 7% 16631985 hemorrhage. Use of the "SFSR" in the (29) Size: n=684 visits Exclusion criteria: None condition causing a return ED visit and derivation cohort may have reduced hospitalization for a related event hospitalizations by 10%. Application of the "SFSR" risk score may 2006 observational syncope to an ED pulmonary embolism. 12 © 2017 by the American College of Cardiology Foundation. or any (30) Size: n=791 consecutive Exclusion criteria: None condition causing a return ED visit and visits hospitalization for a related event Results: In this validation cohort. Oh J. "SFSR" risk score predictors include abnormal ECG. Using a cutpoint of 0 risk scores. abnormal LVEF. et al. MI. hematocrit <30%. Study type: Prospective Inclusion criteria: >18 y of age with 1 endpoint: Arrhythmic syncope These criteria may identify pts requiring 1999 observational syncope of unknown origin after initial who might benefit from cardiac monitoring 10030311 evaluation Results: Risk factors included absence of (28) Size: n=275 pts nausea/vomiting prior to syncope. et al. Significant between-study heterogeneity was observed Sarasin F. These criteria may identify pts who might 2010 of syncope/ near-syncope study for definition varied by specific study benefit from hospital admission 20868906 Size: n=18 eligible studies risk score derivation or validation (35) Results: The "OESIL" risk score has a pooled Exclusion criteria: N/A sensitivity of 95% and specificity of 31%. . hypertension (32) Size: n=37. Inc. Study type: Prospective Inclusion criteria: Unexplained 1 endpoint: Arrhythmic syncope Pts without any risk factors had <2% risk of 2003 observational syncope after ED evaluation arrhythmic syncope 14644781 Results: Predictors include abnormal ECG. 13 © 2017 by the American College of Cardiology Foundation. Study type: Meta-analysis Inclusion criteria: External validation 1 endpoint: Combined serious outcomes. n=5. et al. Saccilotto R. The "SFSR" risk score has a pooled sensitivity of 86% and specificity of 49%.5% 1 y 2013 registry an ED with first time diagnosis of mortality rate 23450502 syncope Results: The CHADS2 score (HF [+1]. prior TIA/ stroke [+2] Exclusion criteria: None associated with all-cause mortality. hemorrhage requiring (31) Size: n=550 pts Exclusion criteria: None transfusion. dangerous These criteria may identify pts who might 2010 observational presenting with syncope to an ED arrhythmia. DM [+1]. age ≥75 [+1]. and Heart Rhythm Society.316 studies than originally reported (33) pts Exclusion criteria: N/A Results: The "SFSR" risk score has a pooled sensitivity of 87% and specificity of 52%. et al. chest pain. emergent surgical or endoscopic procedure Results: The "ROSE" risk score predictors include BNP≥300. 269 pts cohort to validate the system Serrano L. Study type: Prospective Inclusion criteria: >16 y of age 1 endpoint: 30 d combined acute MI. et al. "SFSR" risk score appears to be less 2011 study of "SFSR" risk score definition varied by specific study sensitive and specific in external validation 21948723 Size: n=12 studies. ECG with q waves.Reed M. ≥65 y of age develop and cross-validate the risk score. American Heart Association. rectal exam with fecal occult blood.705 pts [+1].. Study type: Retrospective Inclusion criteria: Discharged from 1 endpoint: All-cause mortality CHADS2=0 is associated with 1. pacemaker/ICD placement. The validation cohort demonstrated sensitivity of 87% and specificity of 66%. pulmonary benefit from hospital admission 20170806 embolus. et al. neurologic event. et al. Study type: Meta-analysis Inclusion criteria: ED cohort study 1 endpoint: Combined serious outcomes. bradycardia ≤ 50. oxygen saturation ≤ 94% on room air. hemoglobin ≤ 90 g/l. Ruwald M. Hx of (34) Size: n=175 pts cohort to Exclusion criteria: None CHF. Large variations were noted in methodological quality of studies. et al. Comment(s) Year Published & 95% CI) Numeroso F. complaint of near syncope (-1). CHF. triage SBP >160 mmHg (+1). lack of hypertension. Study type: Retrospective Inclusion criteria: >60 y of age with 1 endpoint: 30 d combined death. benefit from hospital admission 19766355 syncope after ED evaluation aortic dissection. new diagnosis of severe SHD. blue color Exclusion criteria: None at time of event (-4). Patient Population Primary Endpoint and Results Summary/Conclusion Author. et al. GFR (higher value reduces risk) Sun B. SVT. arrhythmia. age at first syncope ≥35 (-3). 14 © 2017 by the American College of Cardiology Foundation. pulmonary embolism. sweating/ warm feeling before episode (+2). abnormal ECG (+1). Score of <1 was associated with 2. et al. Observational Studies. presyncope/ syncope with standing (+1). asystole. and Heart Rhythm Society. episode associated with pain or procedure (+3) Sule S.. (36) Size: n=242 consecutive pts Exclusion criteria: None SFSR risk score.3. OR or RR. cerebral hemorrhage. AS. . cardiomyopathies. MI. and/or Registries of Risk Stratification .871 pts significant anemia requiring blood transfusion Exclusion criteria: None Results: Risk predictors include age >90 (+1).5% event rate Data Supplement 4.3) Study Acronym. trauma. Study type: Prospective Inclusion criteria: Hospitalized for 1 endpoint: Mortality These criteria may identify pts who might 2012 observational syncope benefit from hospital admission 22878409 Results: Predictors included unexplained etiology. Study type: Prospective Inclusion criteria: ED syncope 1 endpoint: Recurrent syncope. abnormal troponin result (+1).Long-Term Outcomes – (Section 2. major N/A 2014 observational procedures. primary arrhythmic diseases) was. history of arrhythmia (+1). stroke/TIA. Inc. American Heart Association. et al. Study Type/Design. These criteria may identify pts who might 2009 observational unexplained syncope or near. Study type: Prospective Inclusion criteria: Prior episode of 1 endpoint: Positive tilt test CSSS ≥-2 has sensitivity of 89% and 2006 observational syncope evaluated in cardiology clinic specificity of 91% for identifying tilt-positive 16223744 or hospital cardiology wards Results: CSSS risk score predictors include: any of syncope (4) Size: n=418 pts bifasciular block. DM (-5). male gender (+1). Nonrandomized Trials. but high risk heart disease (CAD. Study Size (P values. death 24489075 Exclusion criteria: None (38) Size: n=200 consecutive pts Results: Any heart disease not associated with endpoints. intact memory of event (-2). (37) Size: n=2.Sheldon R. CV events. Study type: Observational Inclusion criteria: Syncope 1 endpoint: Recurrent syncope Etiology of initial syncope 63% 2014 NMS.Ungar A. Study type: Prospective Inclusion criteria: ED syncope 1 endpoint: Death Incidence of syncope recurrence not 2010 observational related to mechanism of syncope or 20167743 Exclusion criteria: None Results: Predictors for recurrent syncope were EGSYS score < or ≥3. syncope episodes Koechl B. American Heart Association. while driving Lee S. Study type: Inclusion criteria: Syncope 1 endpoint: Syncope while driving in followup Etiology of syncope while driving 2009 Case control included neutrally mediated (37%) 19720940 Exclusion criteria: None Results: In the syncope while driving group and arrhythmic (12%) (44) Size: n=3877 pts with syncope. Study type: Observational Inclusion criteria: NCS with Positive tilt 1 endpoint: Recurrent syncope Syncope recurred in 22% of those 2010 and > lifetime syncope with <2 episodes in the prior y 20662990 Size: n=208 pts Results: Number of syncope in prior y better compared to 69% in those with >6 (41) Exclusion criteria: None predicted syncope recurrence compared to lifetime episodes. Study type: Observational Inclusion criteria: ED syncope 1 endpoint: Admission for syncope Etiology of syncope found in 69% 2013 retrospective 23332735 Exclusion criteria: None Results: 3% readmitted. and Heart Rhythm Society. 12% OH. including of which 9. 12% cardiac. (n=381 pts) 72 pts had recurrent syncope. et al. et al.8% had syncope 10 while driving. Inc.5% 2012 22722821 Size: n=242 pts Exclusion criteria: None Results: Increased syncope with age and (42) disability Khera S. et al. et al. unexplained (45) Syncope more common in those with >6 prior episodes and unexplained syncope 15 © 2017 by the American College of Cardiology Foundation. et al. (39) Size: n=380 pts prodromes and palpitations prior to syncope Sule S. 12% 25402339 Size: n=289 pts Exclusion criteria: None Results: 6. Study type: Observational Inclusion criteria: Hospitalized for 1 endpoint: Recurrent syncope Syncope etiology found in 74% 2011 syncope 21259276 Size: n=325 pts Results: Associated with recurrent hospitalized (40) Exclusion criteria: None syncope were DM. CHF and ACS were risk (43) Size: n=352 pts factors Sorajja D.6% with recurrent syncope in 1 y. . Study type: Observational Inclusion criteria: Syncope 1 endpoint: Recurrent syncope Syncope recurrence was 32. et al. et al.. AF and smoking Sumner G. Ruwald MH, et al. Study type: Nationwide Inclusion criteria: Syncope 1 endpoint: Recurrent syncope N/A 2013 administrative registries 24035171 Exclusion criteria: None Results: Predictors of recurrent syncope include: (46) Size: n=5141 pts >85 y of age AS, kidney disease, AV or LBBB, Male, COPD, n=23,454 <85 y of age CHF, AF, Age, orthostatic medications Data Supplement 5. Nonrandomized Trials, Observational Studies, and/or Registries of Disposition After Initial Evaluation – (Section 2.3.4) Study Acronym; Author; Study Type/Design; Patient Population Primary Endpoint and Results Summary/Conclusion Year Published Study Size (include P value; OR or RR; Comment(s) and 95% CI) Sun, et al. Aim: Create standardized reporting Inclusion criteria: Convenience 1 endpoint: 23 serious conditions identified for 2012 guidelines, including serious sample of 24 panelists with clinical or N/A research reporting 22687184 outcomes, for syncope research methodological expertise relevant to (47) syncope research Results: Study type: Modified Delphi consensus process Expert consensus identified final guideline elements from 183 candidate elements Size: n=24 panelists Daccarett, et al. Study type: Inclusion criteria: 1 endpoint: A standardized evaluation algorithm that 2011 Retrospective observational ED visit for syncope identified by ICD Admission rate explicitly identified serious conditions which 21757485 code 780.2 requires admission appears to be safe and (48) Size: n= 254 pts Results: Retrospective application of reduces resource use. Exclusion criteria: Pts with the Utah Faint-Algorithm would have secondary diagnosis of syncope reduced admissions by 52%. Algorithm explicitly defined conditions or high risk criteria for which admission would be indicated. The 7-d serious event rate in pts who should have been discharged per the algorithm (3%) was similar to those who were actually discharged (4%). Framingham Cohort Study Aim: Describe prognosis of Inclusion criteria: Participants in the All-cause mortality Syncope of vasovagal etiology does not Soteriades, et al. syncope in general population original Framingham Heart Study and Over 25 y follow-up period, pts with appear to increase mortality risk 2002 the Framingham Offspring Study presumptive VVS had similar risk- 12239256 Study type: adjusted mortality risk as pts without (49) Prospective cohort Exclusion criteria: N/A syncope 16 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Size: n=7,814 pts Morag, et al. Aim: Assess diagnostic benefit of Inclusion criteria: 1 endpoint: Yield of diagnostic admission appears to 2004 admission for unexplained syncope ED visit for syncope, undergoing Life threatening event or significant be low 15498613 structured evaluation, age ≥ 50 therapeutic intervention (50) Study type: Prospective cohort Exclusion criteria: Intoxicated with Results: Of 30 admitted pts, none drugs or alcohol, had antecedent head experienced the primary endpoint as Size: n=45 pts trauma prompting symptoms, had inpatient or at 30 d follow up witnessed seizure activity with a history of seizures, or if their loss of consciousness promptly responded to medical management (administration of glucose or naloxone) Shiyovich, et al. Aim: Assess diagnostic evaluation, Inclusion criteria: 1 endpoint: A significant proportion of pts have an 2008 costs, and prognosis of pts admitted Hospital admission for evaluation of Diagnostic evaluation, costs, 1 y unrevealing evaluation 18432020 for syncope syncope mortality (51) Study type: Exclusion criteria: pre syncope, Results: 38% had no clear diagnosis Retrospective cohort seizure, malignant arrhythmia at discharge. Size: n=376 pts Schillinger, et al. Aim: Assess evaluation and Inclusion criteria: 1 endpoint: Hospital evaluation had modest 2000 prognosis of pts admitted for Hospital admission for evaluation of No patient has inpatient death or diagnostic yield; population had low short 11098534 syncope syncope recurrent syncope as inpatient. 2% of term mortality risk. (52) pts died within 30 days, all from known Study type: Exclusion criteria: Not admitted after pre-existing disease Retrospective cohort ED evaluation Results: Of 376 pts, 48% had no clear Size: n=127 pts diagnosis at discharge. Long term mortality was higher for pts with cardiac and neurologic etiology. Ungar, et al. Study type: Inclusion criteria: 1 endpoint: Presence of ED observation unit and 2015 Observational ED evaluation for TLOC Disposition hospital based syncope unit is associated 25976905 with lower hospitalization rates compared to (53) Size: n= 362 pts Exclusion criteria: N/A Results: historical experience Disposition included 29% admitted; 20% 17 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. ED observation unit; 20% referred to hospital based syncope unit; 31% discharged. No 1 y death after evaluation in any setting appeared to be related to TLOC Shin, et al. Study type: Quasi experimental, Inclusion criteria: >18 y of age with 1 endpoint: Standardized evaluation, including risk 2013 pre-post w/o control, assess syncope evaluated in ED Admission rate stratification and use of an observation unit, 23918559 implementation of standard reduced admissions , costs, and LOS (54) approach including risk Exclusion criteria: inability to Results: In the 1-y post-period stratification, hospital order set, and consent, prior enrollment in other compared to the 1-y pre- period, there ED observation unit studies, non-syncope syndromes were reductions in admissions (8.3%), costs (30%), and LOS (35%) Size: n= 244 pts Data Supplement 6. RCTs for Disposition After Initial Evaluation – Serious Conditions – (Section 2.3.4) Study Acronym; Author; Aim of Study; Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any); Year Published Study Type; (# patients) / (Absolute Event Rates, Study Limitations; Study Size (N) Study Comparator P values; OR or RR; & Adverse Events (# patients) 95% CI) SEEDS Aim: Assess whether Inclusion criteria: Intervention: Syncope 1 endpoint: Hospital d: 64 in intervention, 140 in Shen, et al. designated syncope unit Syncope of undetermined unit: continuous cardiac Admission rate: 43% in control 2004 in ED improves diagnostic cause after ED monitoring up to 6 h; hourly intervention, 98% in control Presumptive diagnosis: 67% in 15536093 yield and reduces evaluation, AND VS/ orthostatic BP; ECG for intervention, 10% in control (55) admission intermediate risk by semi- abnormal heart sounds or 1 Safety endpoint (if structured criteria ECG; recommended tilt- relevant): Study type: table testing for selected No differences in survival or Summary: 1 site RCT Exclusion criteria: 1. pts; outpatient EP consult, recurrent syncope Structured syncope unit in ED reduced Identified cause of echocardiogram, tilt-table hospital admission and length of stay Size: n=103 pts syncope; 2. Dangerous testing available within 72 h without affecting mortality or recurrent condition requiring after discharge syncope rates. admission; 3. Non- syncope syndrome such Comparator: Standard as light-headedness care (default was admission to hospital) 18 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. EDOSP Aim: Assess whether Inclusion criteria: Pts Intervention: 1 endpoint: Index hospital costs: $629 less in EDOSP Sun, et al. EDOSP reduces resource >50 y of age, AND 12–24 h of cardiac LOS: 29 h in EDOSP, 47 h in vs. control 2014 use without adversely intermediate risk for monitoring; control 24239341 affecting patient oriented serious short-term events echocardiogram for cardiac (56) outcomes by semi-structured murmur; serial troponin 1 Safety endpoint (if Summary: criteria relevant): EDOSP reduced resource use with no Study type: Comparator: Admission to No differences in 30 d serious difference in outcomes, quality-of-life, or 5-site RCT Exclusion criteria: 1. inpatient service outcome rates, quality-of-life patient satisfaction. Dangerous condition scores, patient satisfaction Size: n=124 pts requiring admission; 2. non-syncope syndrome such as seizure Data Supplement 7. Nonrandomized Trials, Observational Studies, and/or Registries Comparing Blood Testing – (Section 3.1) Study Acronym; Aim of Study; Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any); Author; Study Type*; (# patients) / (Absolute Event Rates, Study Limitations; Year Published Study Size (N) Study Comparator P values; OR or RR; & Adverse Events (# patients) 95% CI) Pfister R, et al. Aim: Determine NT-pro-BNP Inclusion criteria: Intervention: None 1 endpoint: NT-pro BNP levels in Post hoc determination of levels 2009 role in the differential diagnosis of Consecutive pts in the different etiology of syncope groups after diagnosis obtained 18237792 pts with syncope. emergency room Comparator: Between No gold standard for most (57) subsequently diagnosed diagnostic categories Study type: Observational Exclusion criteria: groups cohort None Size: n=61 pts Thiruganasambanda Aim: Prognostic value of cardiac Inclusion criteria: Intervention: None 1 endpoint: MACE: death, CPR, Relationship of syncope to MACE moorthy V, et al. biomarkers in the risk Adult syncope pts during MI, structural heart disease, PE, and biomarkers is unclear 2015 stratification of syncope acute management Comparator: None significant hemorrhage, cardiac 26498335 intervention. (58) Study type: Systematic review Exclusion criteria: High sensitivity Troponin and Case reports, children natriuretic peptides showed good Size: N/A sensitivity and specificity for MACE 19 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. GESINUR Aim: Determine outcome Inclusion criteria: Intervention: None 1 endpoint: Summary: Pérez-Rodon, et al. predictors on resting ECG Syncope in the ER with Mortality: 33 total deaths (6.6%), 1 AF, IVCD, LVH and ventricular pacing 2014 1 y follow-up SCD an independent risk factors for 24993462 Study type: Multicenter, mortality (11) prospective, retrospective observational cohort Size: n=524 pts Chiu DT, et al. Aim: Determine the yield of Inclusion criteria: ER Intervention: None 1 endpoint: Yield of 3 diagnostic Summary: Diagnosis in 73 pts (8%). 2014 standard diagnostic tests presentation syncope tests in those pts that had the test Yield: echo 22%, telemetry 3%, 24698512 (no structured indication for why troponin 3%. (59) Study type: Prospective, Exclusion criteria: Comparator: None tests were performed). observational, cohort study of None consecutive ED Safety endpoint (if relevant): None Size: n=570 pts SYSTEMA Aim: Determine role of Inclusion criteria: Intervention: Tilt with CSM 1 endpoint: Levels of C-terminal Summary: Biomarkers divided into Fedorowski, et al. biomarkers in pts with syncope Unexplained syncope and biomarker analysis pro-arginine vasopressin (CT- quartiles, CT-proET-1 and MR- 2013 proAVP), C-terminal endothelin-1 proANP were associated with 23510366 Study type: Observational precursor fragment (CT-proET-1), diagnoses of OH, carotid sinus (60) cohort midregional fragments of pro-atrial hypersensitivity and VVS. natriuretic peptide (MR-proANP) Size: n=270 pts and pro-adrenomedullin (MR- proADM) Reed, et al. Aim: Assess whether plasma Inclusion criteria: Intervention: None 1 endpoint: The proportion of pts Summary: Troponin concentrations 2012 troponin concentration Admitted pts with with a composite serious outcome were above the limit of detection in 22962048 can predict 1 mo and 1 y serious syncope increased across pts stratified into 261 (77%) pts. Peak troponin (61) outcome, or all-cause death quintiles based on peak troponin concentration was associated with concentration at 1 mo (0%, 9%, increasing risk of serious outcome Study type: Prospective 13%, 26%, 70%) and at 1 y (10%, and death, which increases with observational cohort 22%, 26%, 52%, 85%). higher troponin concentrations. Size: n=261 pts Grossman, et al. Aim: Determine role of cardiac Inclusion criteria: Intervention: None 1 endpoint: 3 of 141 pts, or 2.1% Summary: Author conclusion: 2003 enzymes in elderly pts with Consecutive pts 65 y of (95% CI: 0.04%–6.09%), Cardiac enzymes may be of little 14630890 syncope age and older with had positive cardiac enzymes additional value if drawn routinely on (62) syncope in an urban during their hospitalization (CPK, elderly pts with syncope Study type: Retrospective chart teaching hospital ED not TpI study) 20 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. OR or RR. American Heart Association. Primary Endpoint and Results Study Type/Design. renal failure. and Heart Rhythm Society. non-cardiac syncope Study type: Observational none cardiac cause (182 IQR 70–378 cohort pg/ml. study. and “unknown” 14715356 observational Exclusion criteria: AF. Patient Population (P values. Observational Studies. pediatric ED ordered tests in the ED in order of because of automated or non-expert 18082784 syncope. ECG (85%). and identify cardiac syncope. Size: n=113 pts and chest x-ray 37% Data Supplement 8. et al. and/or Registries of Blood Testing – (Section 3.5% Goble MM. et al. weak descriptive (63) tests ordered electrolytes (90%). head CT.7% and a negative predictive value of 91% and 95. NT-pro-BNP at a cut-off of 164 pg/ml identified pts Size: n=61 pts with cardiac syncope with a sensitivity of 90% and 93. Nonrandomized Trials. urinary drug screen. Inc. .8%. Summary/Conclusion Author. R. et al. Aim: determine NT-pro-BNP Inclusion criteria: ED Intervention: None 1 endpoint: Pts with cardiac Summary: NT-pro-BNP assessment 2009 values between cardiac and non. a specificity of 48.001). Study type: Retrospective chart urinalysis. 58%. focusing on diagnostic syncope decreasing frequency were ECG interpretation. or review urinary human chorionic gonadotropin 76%. review Size: n= 319 pts Pfister.1) Study Acronym. complete blood count (80%).. causes could be cardiac (64) who died within 24 h after admission Size: n=118 pts Results: Conclusions: 21 © 2017 by the American College of Cardiology Foundation.8% and 46. p=0. Study Size Comment(s) Year Published & 95% CI) Tanimoto K. Aim: To evaluate ED Inclusion criteria: <18 Intervention: None 1 endpoint: Most commonly Summary: Nearly 100% admitted 2008 management of childhood y of age. syncope syncope had significantly higher was helpful in differentiating cardiac 18237792 cardiac syncope NT-pro-BNP values (514 IQR 286– from (57) Exclusion criteria: 1154 pg/ml) than pts with non. Study type: Inclusion criteria: Pts with syncope 1 endpoint: Limitations: 2003 Retrospective To evaluate the feasibility of measuring BNP to ● Retrospective study. 80. transient loss of (0. small sample. ● Diagnostic accuracy for cTnThs levels AUC: Conclusions: hypoglycemia. (59) Exclusion criteria: inpatient or follow-up that identified etiology of Size: n=570 pts Altered mental status. CI:0. et al. et al.83. no (0. or unknown causes of syncope (p<0. substance. ● Post hoc analysis of a single-center trial— 25447619 syncope not all syncopal pts had troponins.. the sensitivity and specificity identifying cardiac syncope were 82% and 92%.01). troponin: 19/317 (6%) ● Echo the highest yield (low LVEF most common etiology of syncope). no long-term 24698512 observational [suspected AMI]. neurologic. kappa rarely >0. Recchia D. Patient Population Primary Endpoint and Results Summary/Conclusion Author. TLOC due to head Results: low. Comment(s) Year Published & 95% CI) Chiu DT. OR or RR. and/or Registries of Cardiac Imaging – (Section 3.73–0.77. ● At a cut-off value of 40 pg/ml used to determine a cardiac cause of syncope. p<0. Conclusions: presenting to ED with induced LOC. Study Type/Design. seizure. Study type: Inclusion criteria: 1 endpoint: Limitations: 2014 Prospective ≥18 y of age with syncope Finding on diagnostic test (echocardiogram. troponin Single-center study. Study Size (P values. Observational Studies. syncope.6%). ● Echo: 33/150 (22%). American Heart Association. ● Routing testing common. ambulatory monitor) while follow-up.1) Study Acronym. near syncope ● 73 positive tests (12. and Heart Rhythm Society. ● BNP concentrations in the cardiac syncope ● Measurement of BNP concentrations may group (118±42 pg/ml) were significantly higher help confirm cardiac causes of syncope than those with reflex-mediated. Comparable AUC ● cTnThs levels show a limited diagnostic consciousness caused by head injury. Nonrandomized Trials. . although they uncover significant causes of trauma. Study type: Prospective Inclusion criteria: Consecutive pts 1 endpoint: Diagnostic and predictive value of Limitations: 2015 observational presenting to ED with syncope or near cTnThs in pts with syncope.2. but diagnostic yield syncope hypoglycemia.78.83. telemetry: 19/330 (5. coma. of pts with syncope at high risk Data Supplement 9. coma. p<0. (65) Size: n=360 pts Results: Possible bias in selecting pts for whom Exclusion criteria: Persistent altered ● Cardiac syncope present in 22% of pts. telemetry. Study type: Inclusion criteria: 1 endpoint: Limitations: 22 © 2017 by the American College of Cardiology Foundation.001) obtained for and predictive accuracy for the identification phlebotomy or troponin predictive value of cTnThs levels within 30 d. CI:0. ambulatory ECG: 2/56 (3.001).72–0. respectively Christ M. Inc. treating physicians ordered cTnThs mental status or illicit drug-related loss of consciousness. seizure.7%).8%) syncope. et al. or referred for Results: to provide additional useful information. (37%). Sarasin FP. or abnormal ECG. (66) ● EPS not performed. near. ● In pts with positive cardiac history or an abnormal ECG (n=88). suggesting ECG testing ● Echocardiogram normal for 52% pts that syncope alone may not be an indication for ● Echocardiograms of pts with syncope and no clinical echocardiography. positive cardiac history. et al. Inc. echocardiography showed LVEF ≤40%) in 24 (27%) and minor non-relevant findings in remaining 64. ● H&P. the echocardiogram did not appear obvious seizure. evidence of heart disease by H&P. and initial ECG provided sufficient information to permit a diagnosis to be made for 37/48 pts (77%) for whom a cause of syncope was ultimately determined. and electrocardiography ● For pts without suspected cardiac disease after syncope or vertigo. and ECG.. Study type: Inclusion criteria: 1 endpoint: Limitations: 2002 Prospective Adult pts (≥18 y of age) presenting To study the role of echocardiography in the stepwise ● Relatively small sample size of pts with SUO 12231593 observational with chief complaint of syncope evaluation of syncope and/or arrhythmias. stratification—by measuring LVEF. or ECG. a predictor of echocardiography showed no abnormalities that arrhythmias—only in pts with SUO and with a established cause of the syncope. by the initial H&P. American Heart Association. clinically H&P. the echocardiogram confirmed the suspected diagnosis for 48% and ruled out a suspected diagnosis for the remaining 52%. confirmed in 8. over and above that provided Conclusions: Size: n=128 pts Syncope of a known cause.1995 Retrospective Admission for syncope Frequency echocardiography used in evaluation of pts ● Single-center study. ● Among pts for whom cardiac disease was suspected after H&P. electrocardiography were normal (63%) or provided no echocardiography served to confirm or refute the useful additional information for arriving at a diagnosis suspicious in equal proportions. ● Echocardiography is useful for risk ● In pts with unexplained syncope (n=155). or ● For pts with suspected heart disease. ● Echocardiography was normal or non-relevant in all pts with a negative cardiac Hx and a normal ECG (n=67). small sample 8770716 observational admitted because of syncope and to examine the (10) Exclusion criteria: diagnostic information. and Heart Rhythm Society. Size: n=650 pts Exclusion criteria: Results: None specified ● Severe AS suspected in 20/61 pts with systolic Conclusions: murmur was suspected in 20 of these. ● Arrhythmias were diagnosed in 12/24 pts with 23 © 2017 by the American College of Cardiology Foundation. . near syncope) (95%).001). or after hospitalization. Inc. and head CT (63%) were the most frequently ● Many unnecessary tests are obtained to evaluate was documented were excluded. performed in only 38% of episodes.1). American Heart Association. whether the SFSR improved test yield. Probst MA. SFSR. 2001–2010 (p=0. CT ($24. Advanced imaging rates increased from about admissions 21% to 45% and showed a significant upward trend Exclusion criteria: (p<0. . had highest yield in affecting diagnosis (18–26%) or management (25–30%) and determining etiology of the syncopal episode (15–21%). echocardiograms. and Heart Rhythm Society. ●The yields and costs for cardiac tests were better among pts meeting. with syncope ●Postural BP. ● The cost per test affecting diagnosis or management was highest for electroencephalography ($32. None Mendu ML. et al. miscoding syncope diagnoses (67) Size: n=3. potential for residual 25943042 “reasons for visit” included: fainting and associated trends in imaging. passing out. and costs of tests ● Retrospective diagnosis of database of a single- 19636031 study acute care hospital through ED obtained to evaluate older persons with syncope. and electroencephalography all affected higher yield tests would ensure a more informed diagnosis or management in <5% of cases and helped and cost-effective approach to evaluating older pts determine etiology of syncope <2% of the time. Selecting tests based on Hx and ● Cardiac enzymes. telemetry (95%). systolic dysfunction and in 12/64 remaining pts (19%) (p<0. carotid examination and prioritizing less expensive and ultrasounds.500 pts (syncope).01). than not meeting. et al. CTs. includes blacking out. cardiac enzymes Conclusions: consciousness (e. fainting spells.881). hospital admissions. with no Hospital Ambulatory Medical Care 35% and showed no significant downward trend apparent improvements in diagnostic yield for Survey. to center. and cardiac enzymes ($22. with potential for misclassification of (68) (2002–2006). Exclusion criteria: Results: Pts in whom absence of loss of ● ECG (99%).g. obtained tests. and diagnostic frequencies.973). ● No capturing of testing performed in pts not admitted through ED.397) and lowest for postural BP ($17–$20). Conclusions: excludes unconsciousness” from Results: ● Resource utilization associated with ED visits for the ED portion of the National ● Admission rates for syncope pts ranged from 27%– syncope appears to have increased. yield. syncope. confounding.. with an admission or calculate the cost per test yield and determined diagnosis by ICD codes Size: n=2106 pts discharge diagnosis of syncope. Study type: Inclusion criteria: 1 endpoint: Limitations: 2015 Observational cohort ED visits where any of the 3 pts To identify temporal trends in syncope-related ED visits ● Registry study. 24 © 2017 by the American College of Cardiology Foundation. Study type: Inclusion criteria: 1 endpoint: Limitations: 2009 Observational cohort Pts ≥65 y of age admitted to an To determine the frequency. Observational Studies.0002). Pts with a CV cause have a higher ● A CV cause was established in 53 pts and a incidence of sudden death than pts with a non- nonCV cause in 54.2) Study Acronym.8 %) in pts with syncope of unknown origin (p<0. the overall mortality was 14±2. and/or Registries of Stress Testing – (Section 3. et al. and suggested that the exercise. atrial rate and abnormal refractoriness of the His- Purkinje conduction system. Patient Population Primary Endpoint and Results Summary/Conclusion Author. common). Nonrandomized Trials. American Heart Association.005) and 3 ±1.0001). and Heart Rhythm Society. diagnosis should be considered for permanent induced block occurred because of increased cardiac pacing. Conclusions: Tonic-clonic movements.7 % in pts with a nonCV cause (p=0.Data Supplement 10. EPS documented block distal to the AV even in the absence of BBB. ●The incidence of sudden death was 24±6. Study type: Prospective Inclusion criteria: 1 endpoint: Limitations: 1983 cohort Symptoms “comparable with syncope” To determine how often a cause of syncope could ● Descriptive study.2. Comment(s) Year Published & 95% CI) Woelfel.5%. OR or RR. testing. ● At 12 mo. Kapoor WN .. ● The mortality rate (30±6.7%) in pts with a CV cause of syncope was significantly higher than the rate (12±4.02) and the rate (6. (69) Size: n=3 pts treadmill exercise testing Conclusions: Results: ● High grade AV block appearing during Exclusion criteria: ● 3 pts with 1:1 AV conduction at rest developed exercise reflects conduction disease of the His- N/A fixed 2:1 or 3:1 AV block during treadmill exercise Purkinje system rather than of the AV node. 25 © 2017 by the American College of Cardiology Foundation. The cause remained CV or unknown cause (VT and SSS most unknown in 97 pts.6 % in pts with a CV cause.4±2. et al. Study Size (P values. Study Type/Design. Study type: Inclusion criteria: 1 endpoint: Limitations: 1983 Small case series 1:1 AV conduction at rest developed Determine mechanism of high grade block during ● Small case series 6875122 fixed 2:1 or 3:1 AV block during exertion. as compared with 4±2. Pts with this node in all 3 pts. . Inc. post-ictal ● Cause of syncope is frequently not state. aura Results: established. 6866032 be established and to define the prognosis of (70) Size: n=204 pts Exclusion criteria: such pts.8 % in pts with syncope of unknown origin (p=0.4%) in pts with a nonCV cause (p=0. 001. OR or RR. undergoing conventional testing (40% ● Bradyarrhythmias are a frequent vs. ≥16 y of age. (# patients) / (Absolute Event Rates. LVEF <35%. crossover Exclusion criteria: a 2 to 4 wk period of $1. selection bias due to assessment of (72) conventional testing.5.0001). 95% CI: 3. 19%. 16314338 of ILR on pts with single center. injury that warranted CV compared with 6/30 undergoing older population without structural heart investigation. $8.Data Supplement 11. $2. Size: n=60 pts survive for 1y.3) Study Acronym. Aim of Study. p=0. acute syncope presentation. RCTs Comparing Cardiac Monitoring – (Section 3. cause of syncope Krahn AD. Summary: informed consent. Summary: ≥2 SUO in 12 mo. 8%. American Heart Association. SUO or a single episode of ILR with one y of ●14/30 pts monitored diagnosed at ● Single center study.029).4. et al.852±$610/diagnosis. et al. no ● ILR significantly increases diagnostic 26 © 2017 by the American College of Cardiology Foundation. Author. Aim: Inclusion criteria: Recurrent Intervention: 1 endpoint: Limitations: 2003 To compare cost. with possible 12906979 effectiveness of ILR to syncope associated with monitoring (n=30). Comparator: 43% vs. et al.0014). unlikely to monitoring with ELR. disease (excluding pts with a high Study type: “Conventional testing” with p=0.. detected in 14 pts undergoing conventional testing in pts with monitoring compared with 3 pts unexplained syncope. p=0. unlikely to monitoring with an ELR. Study Limitations.005). ● A prolonged monitoring strategy is provide follow-up or give EPS (n=30). result in diagnosis than conventional Conclusions: Size: n=60 pts survive for 1 y. ● A strategy of primary monitoring is more cost-effective than conventional testing in establishing a diagnosis in recurrent SUO. Year Published Study Size (N) Study Comparator P values. Canadian dollars used.731±$285/pts. Conventional (n=98) p<0.2. p=0. 6% HR: 6.527/diagnosis (p<0.0001) and syncope or ventricular arrhythmia). compared with older population without structural heart investigation. injury that warranted CV $5. cross-over Exclusion criteria: a 2 to 4 wk period of ● Prolonged monitoring more likely to syncope or VA). Inc.414 ±$2. pretest probability of neurally mediated RCT. and Heart Rhythm Society.7–11.012). Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any). and provide follow-up or give EPS (n=30). ● Bradycardia (sinus and AVB) more likely to provide a diagnosis than informed consent. unable to followed by tilt table. Aim: Inclusion criteria: Intervention: ILR (n=103) 1 endpoint: Limitations: 2006 To investigate the impact Consecutive pts presenting to ● Time to diagnosis: ● Single center.683±$505/pts (p<0. non-blinded trial. and testing (55% vs. at a pretest probability of neurally mediated RCT. 47%. randomized to prolonged monitoring selection bias due to assessment of (71) in SUO. 20%. & Adverse Events (# patients) 95% CI) Krahn. unable to followed by tilt table. Comparator: conventional testing (52% vs. (73) recurrent SUO. Aim: Inclusion criteria: Recurrent Intervention: 1 endpoint: Limitations: 2001 To compare ILR to SUO or a single episode of ILR with one y of ● Diagnosis achieved in 14/27 pts ● Single center study. LVEF <35%. Farwell. . with possible 11435336 conventional monitoring syncope associated with monitoring (n=30). Study Type. Comparator: 6/30 conventional pts diagnosed (20% disease (excluding pts with a high Study type: “Conventional testing” with vs. 12. basic rate and ECG directed treatments in a RCT.01). Time to second significant subsequent reduction in did not demonstrate a Exclusion criteria: None recurrence longer with ILR. 10. reduction in syncopal stated ● Improved QoL in ILR group (p=0. Conventional (n=37) ● Not designed to test impact of cost 3rd degree AV block. et al. p=NS. OH. Supports early monitoring after first RCT hypersensitivity. poor prognosis recorder) follow-up groups (36. 7 d event between the ILR and conventional Summary: beats VT. VT (1).9. SVT >165 LVEF ≤35%. Aim: Inclusion criteria: Intervention: 1 endpoint: Limitations: 2013 To compare ILR and S/P single syncopal episode ILR (n=41) ● 21/78 developed significant ● Highly-specific subset of pts 23582676 conventional follow-up to with BBB (QRS≥120 ms). p=0.6% vs. SCD (2). American Heart Association. Study type: indication for pacing. 2 endpoint: typical unselected syncopal population. Inc. ILR.67–1. diary.04.8%. in the ILR group. lead ECG. subclavian ● No predictors of AV block identified event. EPS). syncopal events with improved QoL. steal. 33 bifascicular) 27 © 2017 by the American College of Cardiology Foundation. Size: n=201 pts Da Costa A. ● Time to first recurrence: HR: 1. improvement in QoL with ● Overall mortality was 12%. tilt. 34 left BBB. ● <3 y of follow-up arrhythmia (pause >5 s. inability to follow-up. (Outpatient visits every 3 ● Events detectable in 19 pts. p=0. BBB. and Heart Rhythm Society. inducible ● 18 pts received pacemakers.03) events or an for general wellbeing. statistically significant difference found 10 m while awake. p=0. previous study which table unrevealing. arrhythmia: AV block (14). carotid sinus received ICD. and negative Study type: Multicenter VT/SVT. with a heart rate <30 bpm for Exclusion criteria: mo for 36 mo.. EPS. (<1 y). Size: n=78 pts (11 right BBB. 1 isolated syncope. . sick sinus ● Small sample size (unavoidable) (74) estimate prevalence of negative workup (including Comparator: syndrome (4). >10 2nd or 3rd degree AV block.03: ● Long-term follow-up demonstrated a reported 6 mo follow-up (0. ● ILR superior to conventional follow-up bpm).6). in detecting recurrent syncope in pts with HV interval ≥70 m. 18 mo follow-up of workup including Holter. yield for pts with syncope or presyncope None stated as compared with Holter monitors. 17 telemetry monitor within 45 d significantly higher yield than standard centers prior to enrollment. with Class IV HF. presyncope. and Heart Rhythm Society. p<0. ● MCOT superior to ELR for detection of Exclusion criteria: NYHA clinically significant arrhythmias. 24% Holter had ● Non-blinding. Inc. MI within prior 3 shorter time to diagnosis. ELR. candidate for or recent valvular cardiac surgery. et al. pre-enrollment 12867227 utility of ELR to Holter in syncope. and/or Registries of Cardiac Monitoring – (Section 3. evaluation not standardized.0001. Data Supplement 12. ● Utility of loop recorders is limited by rhythm correlation 56% for ELR. Sivakumaran. documented LVEF ≤35%.3). correctly. Study Type/Design. . 15%.001. MCOT provides a Size: n=266 pts. pts <18 y of age. monitoring. Aim: Inclusion criteria: Intervention: 1 endpoint: Limitations: 2003 To compare diagnostic SUO: index symptoms of Initial 48 H Holter (n=51) ●63% ELR vs. Patient compliance not 100%. Observational Studies. Patient Population Primary Endpoint and Results Summary/Conclusion 28 © 2017 by the American College of Cardiology Foundation. Size: n=100 pts ● Probability of obtaining symptom. compared with 75% of ELR pts (although independent strip review). or both. Aim: Inclusion criteria: Intervention: 1 endpoint: Limitations: 2007 To compare the relative A high clinical suspicion of a MCOT (n=134) ● Diagnosis made in 88% of MCOT pts ● Neither patient nor investigator blinded 17318994 value of a MCOT c/w malignant arrhythmia. cause of syncope. (75) determining arrhythmic referred for ambulatory ECG Comparator: p<0. Initial 30 d ELR (n=49) Conclusions: ● Arrhythmia identified as cause of ● ELRs have a much higher diagnostic Study type: RCT Exclusion criteria: syncope in 1 patient with ELR (p=0.008). symptoms of syncope. or severe Loop (n=132) Study type: palpitations occurring less ● MCOT superior in confirming Conclusions: Multicenter RCT frequently than once per 24 H. mo.. presyncope. Rothman SA. condition prohibiting completion of or compliance with protocol. (76) ELR. 22% some pts' inability to operate them for Holter (p<0. unstable angina.00001).3) Study Acronym. diagnosis of clinically significant ● In diagnosis of pts with symptoms of a nondiagnostic 24 H Holter or arrhythmias 41% vs. American Heart Association. et al. frequent PVCs. history of sustained VT/VF.2. Nonrandomized Trials. cardiac arrhythmia. Comparator: (p=0. arrhythmia identified or excluded. respectively. Study type: Inclusion criteria: SUO with 1 endpoint: Long-term findings in pts with unexplained Limitations: 1995 Prospective resting ECG. had a insertion. and 15 pts (94%) had recurrent implanted with negative EPS. absence of significant ILR in pts with isolated syncope and in pts with tilt-positive ● Although documentation of bradyarrhythmia 11551877 observational structural heart disease. Study type: Inclusion criteria: 1 endpoint: Limitations: 2001 Prospective Syncope. 70%. episodes of syncope in the previous ● Syncope recurred in 28 (34%) and 10 pts (34%). EPS performed. Study Size (P values. syncope and negative laboratory investigations. considered diagnostic. were pregnant. unable to recurred in 58 pts (68%) 71±79 days (2. et al. Conclusions: ● Syncope was secondary to sinus arrest in 5. syncope during 13. symptoms are recurrent but too infrequent for ● Successful therapy in all 15 pts. Inc. effective and safe in pts with SUO. ILR ● 16 pts implanted. VT in 1.2 mo after implantation. unable to discriminate Size: n=111 pts negative in 82 (isolated syncope) between an intrinsic cardiogenic abnormality and positive in 29 (tilt-positive). and authors 7671366 observational myocardial imaging. with bradycardia present in 18 were women of childbearing and tachycardia in 3. Study type: Inclusion criteria: 1 endpoint: Limitations: 1999 9918528 Prospective 2 syncopal episodes within the Determine cause of syncope in pts with SUO and recurrent ● Select population and a small proportion of (78) observational previous 12 mo or a single episode undiagnosed syncope with an ILR pts were unable to activate the device after a with a Hx of presyncope as well. without recurrence of conventional monitoring techniques. 2 ys respectively. Size: n=16 pts negative. previously implanted programmable ● Arrhythmia detected in 42% of pts who recorded a rhythm medical device.4±4.6 mo) after ILR ● The strategy of prolonged monitoring is give informed consent.5±4. OR or RR. the likely cause was neurally 29 © 2017 by the American College of Cardiology Foundation. AV block in ● ILR useful for establishing a diagnosis when Exclusion criteria: Pre syncope 2.0±8. or during recurrent symptoms. potential not on a reliable form of ● 5/18 bradycardic pts and 2 additional sinus rhythm pts contraception received a clinical diagnosis of neurally mediated syncope. ● Small number of implants. Comment(s) Year Published & 95% CI) Krahn AD. and Heart Rhythm Society. . ambulatory monitoring. and TTT. Size: n=85 pts Results: Exclusion criteria: ● During a mean of 10. et al. If comment on minimal incidence of morbidity (77) noninvasive investigations were Results: and mortality. tilt-testing was syncope and to evaluate the natural Hx of these pts. ≥3 Results: and a neurogenic mechanism. and a syncope to obtain further information on the mechanism of concurrent with a syncopal episode is (79) normal ECG. ● In most pts. ● Pts who experienced presyncope much less likely to record an arrhythmia during symptoms compared with recurrence of syncope (24% vs.3±2.0 mo of follow-up. Author. symptoms Conclusions: Unlikely to survive 1 y. and ECG correlation was found in 24 (23%) Conclusions: and 8 (28%) pts.. et al. syncope 4. American Heart Association. spontaneous event.0005). Moya A. Krahn AD.4 mo of follow-up. nonarrhythmic in 6. p=0. SVT in 1. ● 32/72 with inclusion criteria had positive EPS. 112 pts with initial TTT were defined as Group B. . selective use of EPS or TTT leads monitoring. Diagnostic yield of a protocol in which EPS. significant non. Inc. Study type: Inclusion criteria: 1 endpoint: Limitations: 2003 Prospective >2 syncopal episodes. TTTs. subsequently had negative TTT. respectively. Exclusion criteria: ● During a follow-up of 3–15 mo. syncope recurred in 22 None specified pts (42%). ● No follow-up of all pts with ILR to confirm 12628723 EPS: Any of presence of structural diagnosis (81) Size: n=184 pts heart disease or family Hx of SCD. asystolic pauses. If these pts (defined as Group A) in 7. and SUO negative conventional workup that includes Results: electrophysiological study. a and 62% of pts. with asystole. or significant Evaluate relative utility of auto-activate ILR based on a ● Small sample.. most ≥prolonged asystolic pause mainly attributable to AV block. Overall. apply only to the minority of those with a Size: n=52 pts negative EPS. and 2 pts had presyncope attributable to AVB sudden-onset paroxysmal AV block. Brignole M . and a on the mechanism of syncope. et al. Results: abnormal ECG. 143/184 pts with positive diagnosis. was one or more prolonged normal sinus rhythm was frequently recorded. which was recorded in 46% was a bradycardic reflex. and Heart Rhythm Society. had negative EPS. ILR immediately before or after syncope. syncopal recurrences have a homogeneous ● The median duration of the arrhythmic event was 47 s. 80/112 had Conclusions: symptomatic arrhythmia on Holter positive TTT. 23/40 with negative EPS had positive TTT. and the most frequent mechanism None specified ● The most frequent finding. In the other cases. An mechanism that is characterized by prolonged additional 3 pts developed nonsyncopal persistent 3rd asystolic pauses. with diagnostic activation can be useful in non-diagnosed cases. et Study type: Inclusion criteria: 184 pts with 1 endpoint: Limitations: al. mainly due to sinus arrest. Study type: Inclusion criteria: 1 endpoint: Limitations: 2001 Prospective All pts with any type of BBB with ILR in pts with BBB and negative EPS to evaluate the ● The results of the present study cannot be 11673344 observational QRS >100 ms. Exclusion criteria: mediated. unclear how generalizable 14516882 observational physical injury with event arrhythmia grading system in terms of the likelihood that scoring system is. Garcia-Civera R. Conclusions: ● The most frequent finding. mainly attributable to degree AVB. ● No pts suffered injury attributable to syncopal relapse. American Heart Association. no documentation of natural history of these pts and obtain additional information generalized to all syncope pts with BBB but (80) 2nd or 3rd degree AV block. Prospective SUO. Exclusion criteria: None Ermis C. et al. recorded in 17 pts. was ● In pts with BBB and negative EPS. ● In SUO. they underwent TTT. 30 © 2017 by the American College of Cardiology Foundation. and ILR ● Authors feel no ATP testing was a limitation 2003 observational are selectively used in SUO. paroxysmal palpitations ILR implanted in 15/17 pts with negative EPS who to positive diagnosis in >70% of cases. Study type: Inclusion criteria: 1 endpoint: Limitations: 2004 Observational.e. ● Auto activation provided 90. and 87. arrhythmias. ● ILR is a valuable and effective tool to ● 3/12 had normal workup. arrhythmia scoring.e. . grades 0 and I). American Heart Association.. Asymptomatic arrhythmias (85) monitor. Inc. results of HUTT and EPS are neither sufficiently sensitive nor specific enough in this pts group. with LVEF ≥35% and SUO Prespecified arrhythmias: ● Population likely to have recurrence and 15309004 observational (negative 24 h ambulatory/inpatient pause >5 seconds.. Holter. 1 PAF medication. ECG. (83) Results: Small sample Size: n=43 pts Exclusion criteria: ● ILR able to record arrhythmic event in 12/43. Krahn.9% of auto-activation ILR systems. 31 © 2017 by the American College of Cardiology Foundation. 10 with None bradycardia.. ≥3 episodes of syncope within Diagnosis of arrhythmia by ILR Not all had full diagnostic workup 14697729 observational 6 mo 18 mo follow-up somewhat limited. and polymorphic Conclusions: VT ICD. Study type: Inclusion criteria: 1 endpoint: Limitations: 2004 Prospective SUO. Study type: Inclusion criteria: 1 endpoint: Limitations: 2004 Prospective ≥30 y. et al. Boersma L. Conclusions: Size: n=2057. et al. considered diagnostic. Solano A. though diagnostic yield and ● During a median follow-up of 13 mo. Exclusion criteria: 52 pts. High-risk syncope: (1) were very ECG diagnosis made by analysis of the ECG tracing ● Limited to high-risk group 15231369 prospective. or (2) were recurrent and obtained during the first syncopal episode that was correctly (84) unpredictable or (3) occurred during recorded by the device. Size: n=60 pts Heart rate <30 beats/min for >10 seconds while awake.(82) they provide a diagnostic basis for syncope. 103 the prosecution of a `high risk' ● Mechanism of SUO is different in pts with ILR activity Results: and without SHD. echocardiogram) had ILR 3rd degree AVB >10 seconds. Others had abnormal HUTT. Size: n=50 pts Exclusion criteria: None Conclusions: Results: ● Study offers strong support for the value of ● Of 529 recordings. grades 0 to III). syncope recorded in safety are similar in both groups. and Heart Rhythm Society. Pts with SHD more frequently had paroxysmal AV Presyncope block and tachyarrhythmias and pts without SHD more frequently had sinus bradycardia/sinus arrest or no arrhythmia.6% (68 of 75 episodes) of all highly likely diagnoses (i. establish an arrhythmic cause for SUO. et al. echo. 2-hospital frequent. The EPS. as well as a all the documented arrhythmia episodes (194/223 episodes basis for encouraging further development of from 30 pts).1% of all arrhythmia diagnoses (196 of 225 episodes) (i. auto activation accounted for 86. then ILR implanted an ILR in pts with and without SHD. Pierre B. narrow complex Conclusions: LVEF <35%. cardiac disease. et al.2 mo. To determine influence of cardiac conduction abnormalities ● Relatively small size with extensive 18325892 observational normal workup including EPS. the ECG was normal. tachycardia >180 beats/min for >30 beats. 5 of these pts went on to have monitoring of pts with syncope. Inc. CSM that turn up on resting ECG and the impact of underlying negative workup. had an ILR documented with SUO. syncope of unknown etiology in pts with or 27/43 pts developed a new syncope associated with an without cardiac conduction abnormalities or arrhythmic event. more pronounced diagnostic arrhythmias of same mechanism during further follow-up. 20 pts had borderline incremental diagnostic usefulness in long-term asymptomatic arrhythmias.. (86) cardiac disease on developments during follow-up. American Heart Association. (87) Size: n=70 pts Exclusion criteria: Results: Conclusions: None ● Syncopal recurrence occurred during 16 mo in 30 pts ● Presence of SHD has little predictive value (91%) with SHD and in 30 pts (81%) without SHD. for the occurrence or type of arrhythmia in pts ● 45% vs. et al. with arrhythmias detected in 14 pts. and Heart Rhythm Society. center. candidates for Results: ● ILR useful diagnostic tool for recurrent primary ICD ● During an average follow-up period of 10. Pezawas T. developed in 9 pts with bradycardia in 7 pts who underwent ● Automatic arrhythmia detection provides pacemaker implantation. ● Syncope no more frequent in subgroup of pts with cardiac conduction abnormalities on resting ECG. respectively. ● Long-term monitoring of pts with neurally mediated syncope unexplained syncope with automatic Results: arrhythmia detection demonstrated that ● Recurrent symptoms developed in 30 pts during the 1 y significant asymptomatic arrhythmias were follow-up period (47%).2±5. including pauses of 6– 17 s duration in 3 pts. . leading Pre-specified significant asymptomatic arrhythmias to a change in patient treatment. limited survival. seen more frequently than anticipated. Study type: Inclusion criteria: 1 endpoint: Limitations: 2008 Prospective SUO (ISSUE classification) with ≥2 Stratify mechanisms and predictors of SUO documented by ● Not necessarily generalizable—referral 17947364 observational episodes. Exclusion criteria: wide complex tachycardia >10 beats. 51%. Study type: Inclusion criteria: 1 endpoint: Limitations: 2008 Prospective SUO: ≥3 episodes of syncope. This argues against an empirical pacing strategy in pts with cardiac conduction abnormalities on resting ECG suffering from recurrent syncope. Size: n=95 pts Exclusion criteria: Conclusions: LVEF ≤30–35%. arrhythmia at time of recurrence which led to specific 32 © 2017 by the American College of Cardiology Foundation. but normal EPS. while the ● The absence of arrhythmic events was frequency of arrhythmic events was similar whether or not frequently reported in all patient subgroups. ● Conversely. 95% CI: 1..” “initial workup. 26. respectively. ● Pts with major depressive disorder are ● The remaining 45% with SHD and 30% without SHD had prone to early recurrence of symptoms and normal sinus rhythm at the time of the recurrence.” or “full 24182906 observational registry least 1 y after implant evaluation” not defined in protocol (89) (PICTURE) Exclusion criteria: No evidence of “unexplained Results: Conclusions: Size: syncope. protocols. no patient with major depressive disorder had asystole compared with 33% without (p<0. et al. Edvardsson N. 33 © 2017 by the American College of Cardiology Foundation. et al. 6. (25% implanted during High number of testing in both protocols initial work-up. the mechanism of syncope in the vast majority of pts. ● 57% of pts with major depressive disorder had sinus rhythm during recurrence compared with 31% of pts without the disorder (p=0. ● Major depressive disorder predictive for early recurrence during ILR follow-up (p=0. Full (14 tests [IQR 10-21]). ● Pts evaluated by an average of 3 different specialists for since the subgroup was small. ● The findings support the recommendation in current guidelines that an ILR should be implanted early rather than late in the evaluation of unexplained syncope. Inc. and 36% after 3. have no evidence of arrhythmia in most cases. HR: 3.35.” no follow-up data. management of their syncope and underwent a median of 13 tests (range 9–20). Conclusions: ● A large number of diagnostic tests were ● The percentages of pts with recurrence of syncope were undertaken in pts with unexplained syncope 19. ILR ● Initial (8 tests [IQR 6-14]) vs. and they have been analyzed Size: n=570 pts Results: and reported together with pts with syncope. Diagnostic yield of ILR high in both n=514 pts with ILR implanted for another reason p<0. American Heart Association. 75% ● Hospitalization and injury before implant less common in may have been mitigated by earlier ILR. Study type: Inclusion criteria: 1 endpoint: Limitations: 2013 Multicenter Recurrent SUO or pre-syncope First recurrence of syncope leading to a diagnosis or for at “Unexplained. (88) observational Exclusion criteria: SUO in everyday clinical practice. of which 128 (75%) were cardiac.0001. .001). treatment.1).1–7. Study type: Inclusion criteria: 1 endpoint: Limitations: 2011 Multicenter Recurrent SUO or pre-syncope To collect information on the use of ILR in the patient care 12% of implanted pts did not have follow-up 21097478 prospective pathway and to investigate its effectiveness in diagnosis of visit data. Pts with pre-syncope only were admitted None specified into the registry.01). events within the study.01. and 12 mo. Linker NJ. and Heart Rhythm Society. In contrast. Of 218 without providing conclusive data. ILR-guided diagnosis was obtained the ILR revealed or contributed to establishing in 170 cases (78%). Study type: Inclusion criteria: Pts underwent 1 endpoint: Limitations: 1984 Retrospective 24 H Holter monitoring Diagnostic yield of Holter for syncope diagnosis ● Large sample (registry). p<0.001. SVT (1 patient).035). Study type: Inclusion criteria: 1 endpoint: Limitations: 1990 Prospective ≥1 episode of SUO Utility of ELR after indeterminate Holter recording ● Referral bias. 34 © 2017 by the American College of Cardiology Foundation. 2371954 observational (92) Exclusion criteria: Results: Conclusions: Size: n=57 pts Prior EPS ● In 14 pts. 95% CI: 14–38%). 79% Palmisano P. shows utility in an arrhythmia was cause of symptoms (diagnostic yield SUO. and the independent predictive factors for detection of periods of asymptomatic bradycardia. . usually VT arrhythmias in pts with syncope ● Presyncope was reported in 241 pts. Inc. 75%. and Heart Rhythm Society.8. Gibson TC. a Hx of conventional ECG monitoring were trauma secondary to syncope (OR: 26.045). a history of trauma ● Clinically significant bradyarrhythmia was detected in 11 secondary to syncope. 36% full at 12 mo Recurrence with ILR diagnosis: 52 vs. American Heart Association. Study type: Inclusion criteria: 1 endpoint: Limitations: 2013 observational.364 that could be diagnostic ● 24 H ambulatory monitoring service rarely total) ● 15 pts had syncope and 7 of the episodes were related to results in identifying relevant symptom-related an arrhythmia. after “full evaluation” pts with “initial work-up”: 53 vs. clear selection bias 23701932 study arrhythmic nature.. p=0. 39%. p<0001. p<0.001. et al. 2 center History of syncope of suspected Identify predictive factors for pacemaker implantation in pts Non-blinded. et al. 75% at 12 mo. p=0. Results: ● An advanced age.9. p=0. small sample. bradyarrhythmias requiring pacemaker performed before ILR implantation (OR: 24. asystole or junctional bradycardia from neurally mediated syncope (3 pts) and normal cardiac rhythms (the remaining 7 pts). with a related arrhythmia in 24 Linzer M.7. high grade AV block (2 pts). loop recording definitively determined whether ● Early study of external LR. negative cardiac receiving an ILR (90) and neurological workup. et al. cardiac dx: 90 vs. as were visits to specialists. and the detection of Exclusion criteria: pts (20%). ● Diagnoses included VT (1 patient). 25%.039).512 pts with ● 31/1512 (2%) of pts had “arrhythmia-related symptom” Conclusions: syncope (of 7. implantation in pts receiving an ILR for unexplained syncope. ● Recurrence rate:32 initial vs. and 23% vs. many confounders 6702676 observational Percentages likely low due to sample (91) Exclusion criteria: None Results: Size: n=1. of which 9 cases related to syncopal relapses: periods of asymptomatic bradycardia during None predictive factors: >75 y of age (OR: 29. who Conclusions: Size: n=56 pts underwent ILR. Locati ET. Study Size (P values. history of supraventricular emergency room or hospitalization Results: For syncope.2. true (28.6%) in whom the arrhythmic event occurred simultaneously with the syncopal episode.6% and cumulative diagnostic yield observed may be predictors of diagnostic events were Hx of recurrent an overestimation of the true clinical benefit. Data Supplement 13.6.6.9%) enrolled for a suspected arrhythmic origin of recording (0–15 vs. syncope is unknown.4–9. .001) and early start of recording (p=0. during the 4 wk external ECG monitoring.5%. p=0.1%) for syncope. and predictors of diagnostic events were early start increased the likelihood of diagnostic events (71. principally due to AV block and and presenting HF on admission. remote telemetry in the setting of unexplained generalizable. the 4 wk diagnostic yield was 71.01) and HF on admission (p<0. 17965013 Size: n=122 pts syncope.018). after being discharged from recorder use. documented arrhythmia). and CCU protocols not 2007 unexplained.4) Study Acronym. 95% CI:1. Early (93) multicenter event). especially in those older responsible for the syncope.021) and previous Hx of Diary-reported symptoms/events.7 days). OR or RR. Nonrandomized Trials. 282 pts without a conclusive diagnosis. sustained palpitations (index and/or sustained palpitations of suspected arrhythmic origin work-up of syncope and palpitation. extreme bradycardia. etiology of event unknown (despite None specified p=0.7. Prospective cohort study Presumptive diagnosis of To determine the diagnostic value of cardiac ● Single center study. ● Cardiac remote telemetry was diagnostic in 18 pts (17. Study type: Inclusion criteria: 1 endpoint: Limitations: et al.. >15 days after index event) (OR: 6.2. and 24.001). Patient Population Primary Endpoint and Results Summary/Conclusion Author. and Heart Rhythm Society. Exclusion criteria: supraventricular arrhythmias (OR 3.3–29. Study Type/Design. likely cardiogenic. Comment(s) Year Published & 95% CI) Benezet-Mazuecos.8±2. Study type: Inclusion criteria: Recent (within 1 1 endpoint: To evaluate the role of external 4 wk ECG The 4 wk external ECG monitoring can be 2016 Prospective mo) episode of syncope or monitoring in clinical work-up of unexplained syncope considered as first-line tool in the diagnostic 26519025 observational. Inc. and/or Registries of In-Hospital Telemetry – (Section 3. Observational Studies. and frequent previous events Size: 392 pts. Authors note the For palpitations. American Heart Association. palpitations and 110 95% CI: 1.7%). the 4 wk diagnostic yield was arrhythmia. pts (14. ● ≥86 y of age (p<0. palpitations (p<0. Events requiring useful tool in the management of pts with condition actually or potentially transfer to the coronary care units occurred in 15 unexplained syncope. ●The best cut-off point as a threshold for 35 © 2017 by the American College of Cardiology Foundation. et al.04) were the strongest predictors of events. (94) Results: Conclusions: Exclusion criteria: ● There were no deaths during the time of ● Cardiac remote telemetry appears to be a Syncope and a documented medical monitoring (4. Gibson TC. American Heart Association. Study type: Inclusion criteria: 1 endpoint: Limitations: 1984 Prospective observational Pts admitted to telemetry ● To determine the benefits of telemetry in terms ● Older data. 95% CI: 14-38%). Study type: Inclusion criteria: 1 endpoint: Limitations: 2003 Prospective observational ≥2 SUO within 6 mo. cause. monitoring time was 72 H (sensitivity 73%.364 total) None specified ● 31/1512 (2%) of pts had “arrhythmia-related Conclusions: symptom” that could be diagnostic ● 24 H ambulatory monitoring service rarely ● 15 pts had syncope and 7 of the episodes were results in identifying relevant symptom-related related to an arrhythmia. not limited to syncope 6711429 of arrhythmia diagnosis and therapy administered. ● Significant arrhythmias occurred only in pts with known or suspected CAD or in those with previously documented arrhythmias. et al. with a related arrhythmia in 24 pts Linzer M. negative TTT. 36 © 2017 by the American College of Cardiology Foundation..512 pts with Exclusion criteria: Results: syncope (of 7. Assess diagnostic yield of ELR in pts with ● Low sample size. Schuchert A . Inc. loop recording definitively determined ● Early study of ELR. Study type: Retrospective Inclusion criteria: 1 endpoint: Limitations: 1984 observational Pts underwent 24 H Holter monitoring Diagnostic yield of Holter for syncope diagnosis ● Large sample (registry). . Study type: Inclusion criteria: 1 endpoint: Limitations: 1990 Prospective observational ≥ 1 episode of SUO Utility of ELR after indeterminate Holter recording ● Referral bias. usually VT arrhythmias in pts with syncope ● Presyncope was reported in 241 pts. et al. and Heart Rhythm Society. Lipskis DJ. 2371954 (92) Size: n=57 pts Exclusion criteria: Results: Conclusions: Prior EPS ● In 14 pts. whether an arrhythmia was cause of symptoms (diagnostic yield 25%. asystole or junctional bradycardia from neurally mediated syncope (3 pts) and normal cardiac rhythms (the remaining 7 pts). specificity 86%). many confounders 6702676 ● Percentages likely low due to sample (91) Size: n=1. small sample. (95) Size: n=205 pts Exclusion criteria: Conclusions: None specified Results: ● The diagnostic yield of ECG monitoring in pts ● 14 episodes of significant arrhythmias in 12 pts with syncope may be low in the absence of a who required specific intervention were detected high amount of suspicion about an arrhythmic over 608 patient-days of monitoring. SVT (1 patient). et al. all ELR patient triggered. shows utility in SUO. et al. high grade AVB (2 pts). ● Diagnoses included VT (1 patient). especially 1) EPS in pts with organic heart disease. et al. events during the limited monitoring period in and a negative tilt table test because the cardiac particular. 9214258 (population selected if they addressed remains unexplained after initial clinical assessment. the cause of syncope remains undiagnosed in 50% of pts. or case syncope.. and 5) TTT in pts who have infrequent events or in whom VVS is suspected. testing may be helpful in elucidating cause of syncope. Study Patient Population Primary Endpoint and Results Summary/Conclusion Author. analyze the usefulness of the signal-averaged ECG and of Conclusions: Size: n=100 pts body surface potential mapping in predicting the inducibility of VT. referral diagnostic testing in Conclusions: studies. (include P value. 12930497 no SHD. 3) loop monitoring in pts with frequent events and normal hearts.5) Study Acronym. Study type: Inclusion criteria: 1 endpoint: Limitations: 1991 Prospective Pts with syncope of unclear To compare the results of 24 H monitoring and EPS in the Neurologic and TTT not performed. Hospitalization is indicated for high-risk pts. In such pts. ECG Documented arrhythmia at Results: signal-averaging was useful in predicting VT only in pts 37 © 2017 by the American College of Cardiology Foundation. and electrocardiography. and ECG. EPS had a higher diagnostic yield than Holter Exclusion criteria: monitoring regardless of cardiac pathology. et al. Inc. Nonrandomized Trials. with rare pts with syncopal events. Type/Design. especially those with known heart disease and elderly pts. 2) Holter monitoring or telemetry in pts known to have or suspected of having heart disease. no VVS trigger negative TTT and recurrent syncope. (96) Size: n=24 pts Conclusions: Exclusion criteria: Results: ● Reasons for ELR were infrequent syncopal None specified ● ELR was not useful for arrhythmia detection in events after baseline evaluation. and/or Registries of Electrophysiology Testing – (Section 3. the cause of series) dizziness After a thorough H&P. and additionally to (98) EPS. no overt heart disease. 1950999 cohort etiology who underwent evaluation of pts with recurrent syncope. and Heart Rhythm Society. Lacroix D. Comment(s) Year Published Study Size and 95% CI) Linzer M.2. 4) psychiatric evaluation in pts with frequent events and no injury. and premature termination or rhythm was stored in only 1 of 8 (13%) pts with unsuccessful recording in 21% of pts. methods unclear. (97) studies. . American Heart Association. or Results: After a thorough H&P. Study type: Inclusion criteria: 1 endpoint: Limitations: 1997 Literature review Published papers were To review the literature on diagnostic testing in syncope that Older data. near syncope. Size: N/A Exclusion criteria: N/A information may be derived from the results of carefully selected diagnostic tests. Stepwise syncope remains undiagnosed in 50% of pts. Observational Studies. OR or RR. recurrent syncope Data Supplement 14. especially if pts had organic heart disease. and Heart Rhythm Society. In pts CV collapse.. monitoring -a population frequently encountered in 21 pts had concordance between EP testing and ambulatory clinical EP laboratories. Thirteen deaths occurred. Thus it biases the results monitoring results. Late potentials were recorded in 13 pts with CAD. or with inducible VT (87%). Inc. limited and specific population 3825942 cohort symptomatic pts with BBB symptomatic BBB. 19% undergoing permanent pacing based on EP testing. Results: however. 5 had inducible VT. Conclusions: Severe abnormalities were more frequently detected in our patient population by EP testing than by ambulatory monitoring. (99) undergoing EPS Conclusions: Size: n=112 pts Results: In symptomatic pts with BBB and normal EP test Exclusion criteria: Cumulative 4 y survival rate and recurrent syncope. To determine the role of invasive EP testing in pts with Older data. a study of EP results as compared to Exclusion criteria: Although 29 pts had abnormalities on EP testing. Study type: Inclusion criteria: 1 endpoint: Limitations: 1985 Prospective 24 H ambulatory ECG To assess whether findings on ambulatory monitoring not Not a prospective comparison of ambulatory ECG 4072872 cohort monitoring and then EP obtained during syncope can be used to indicate the results which monitoring and EP testing in all pts with syncope. while Holter monitoring was abnormal in most pts with cardiac disease. in only 6 were the findings suggested by the testing following non diagnostic ambulatory ECG abnormalities recorded during ambulatory monitoring. poorly predicted VT. Abnormal body surface potential mapping was frequently seen (56%). since (100) testing for unexplained are found on EP testing in pts with recurrent syncope. 13 of which ambulatory ECG monitoring in pts who do undergo EP None specified were severe. presentation and those with CAD was found in 46 pts and other heart disease was found in with CAD without BBB. pts whose workup stopped after ambulatory ECG Size: n=59 pts syncope. or requiring 83% in 16 pts with no therapy (normal study results). 63% in 39 pts with antiarrhythmic therapy alone. prognosis is good without treatment. 6% survival is good and rate of symptom recurrence is low. EPS was diagnostic in 44 pts. In 7 other pts with VT. 19% antiarrhythmic therapy is indicated but who nevertheless have a poor prognosis. and EPS guided therapy resulted in a low rate of total cardiac death. but syndrome suggested a diagnosis in only 21 pts. American Heart Association. monitoring were not enrolled in the study. respectively: results. It is. et al. 38 © 2017 by the American College of Cardiology Foundation. but in 15 of the 21 results of both tests were toward the detection of abnormalities by EP tests normal. Study type: Inclusion criteria: 1 endpoint: Limitations: 1987 Prospective Syncope/near syncope. resuscitation 84% in 34 pts with permanent pacing alone. . they were either absent or BBB was found. et al. Body surface potential mapping Wolff-Parkinson-White 19. 33% EP testing identifies pts with inducible VT for whom 84% in 21 pts with both antiarrhythmic therapy. Click RL. especially in CAD (70%). Reiffel JA. permanent pacing was instituted empirically with relief of syncope. (103) cohort etiology who had an ECG.05. origin established according to simple clinical criteria. 95% CI: 1. 11350095 after H&P. In 7 pts.8%) and population that has no ECG abnormality or clinical normal in the remaining 28 pts (82. 95% CI: 1. and Heart Rhythm Society. . OR: 7.Gulamhusein S. exercise stress testing Positive responses to the tilt test were more common in pts who electrophysiology differs in groups of pts with syncope (in selected pts). 3. EPS diagnostic in 4 pts (11. p<0. ECG. a definitive diagnosis was made.2– clinical criteria. intraventricular conduction The lowest rate of positive response was observed in older pts defect or a suspicion of with an abnormal ECG and organic heart disease.7– Exclusion criteria: 9.7. OR 3.6). evaluate because of the high incidence of spontaneous (101) Size: n=34 pts remission in this group. American Heart Association. Over mean follow up of 15 mo. CSM. Inc. an p<0. OR: 1. but this result is difficult to 7137203 PES presyncope. Retrospective Syncope of unknown To assess the diagnostic yield of the head-up tilt test (n=600) and Retrospective study in very specific population of pts 2001 cohort etiology who underwent TTT. p<0. evaluation (12-lead ECG and 24 H ambulatory 39 © 2017 by the American College of Cardiology Foundation. patient. In 4 pts (11. Study type: Inclusion criteria: 1 endpoint: Limitations: 19419396 Prospective Syncope of unknown To assess the utility of noninvasive electrocardiographic Specific population.0005. had suffered their first syncope at an age ≤ 65 y (group I) than in of unknown origin.6%). (102) Size: n=600 pts Holter monitoring. Prospective Unexplained syncope/near To assess the value of clinical EPS using intracardiac recording Empirical permanent pacing in pts with symptoms 1982 cohort syncope who underwent and PES in 34 pts who had unexplained syncope and/or appeared to be beneficial.4%). evidence of cardiac disease. and it was especially low in pts with a normal ECG and without organic heart disease (2.78). Exclusion criteria: Results: None specified. et al. These findings have a bearing on was performed if clinically 2. Study type: Inclusion criteria: 1 endpoint: Limitations: et al. unclear generalizability. The diagnostic yield of EP testing is low in a patient Results were abnormal but not diagnostic in 2 pts (5. et Study type: Inclusion criteria: 1 endpoint: Limitations: al.008.. arrhythmia-related syncope. Sagrista-Sauleda J. 33%. The diagnostic yield from electrophysiology was higher in pts with an abnormal ECG than in those with a normal ECG (22% vs. 16 pts (47%) had no further episodes in the absence of any intervention. established according to simple neurological evaluation. OR: 1. and in pts with a normal ECG and without organic heart selecting the most appropriate test in a particular indicated.1).8%). organic heart disease. 37%.2).8 percent) and led to appropriate Conclusions: therapy that totally relieved symptoms.7%.001. electrophysiology (n=247/600) in pts with syncope of unknown undergoing TTT. Electrophysiology disclosed abnormal findings in group II more often than in group I (23% vs 7%. Gatzoulis KA. p<0. Conclusions: echocardiogram (in selected Results: The diagnostic yield of the TTT and pts). None specified.8. EPS older pts (group II) (47% vs. mostly in pts with disease than in the other subgroups of pts (47% vs. abnormal ambulatory monitor. Gulamshusein S. et al. ambulatory monitor.. ● EPS diagnostic in 4 pts and led to therapy.001). in selected population with SUO. normal neurologic ● During mean 15 mo f/u. abnormal ECG only.9 (p<0. 1 patient with ● The study shows some value in EPS in elucidating quinidine-related VT cause of syncope. Assess diagnostic yield of EPS in SUO. group 3. ORs were 35. Prospective SUO. 7137203 presyncopal episodes. (more inducible VT). normal ECG and ambulatory monitor. any EPS abnormality was low (9.001).1%). an EPS.064) for abnormal findings on EPS. 17. in EPS of pts with None specified Pts were divided into 4 groups: group 1. The likelihood of finding at least one abnormality during EP testing among the 4 groups was highest in group 1 (82. no Results: (101) Size: n=34 pts cause of syncope on exam. Abnormal ECG findings on noninvasive testing are well correlated with potential brady.2%) and lower in groups 2 and 3 (68. Study type: Inclusion criteria: 1 endpoint: Limitations: 1982 Prospective Syncope of unclear etiology Detection of brady and tachyarrhythmias in EPS to elucidate ● Small study and most pts had organic heart disease 7148707 observational cause of SUO. American Heart Association. and 3. and 24 H electrocardiographic recordings) to predict electrophysiology study Conclusions: Size: n=421 pts ambulatory monitoring results in pts with undiagnosed syncope. and Heart Rhythm Society. In group 4. ● EPS less diagnostic than predicted: some pts 1982 observational ≥1 syncopal or ≥2 required pacing despite normal or nondiagnostic EPS. respectively (first 3 groups vs. (104) Exclusion criteria: ● Older data. Conclusions: normal ECG and 48 H ● Diagnostic yield of EPS testing is low in a patient Holter.5 (p=0. et Study type: Inclusion criteria: 1 endpoint: Limitations: al. Size: n=32 pts None specified Results: ● 18/32 pts had definitive EPS diagnosis. all undergoing EPS. et al. CT-head). Inc.1% and 33. the 4th one). 11 pts with inducible VT Conclusions: 5 pts with SND. 1 patient with infra-His AVB. Hess DS . medical therapy changed now. respectively). and group 4. 16 pts had no further episodes in population that has no ECG abnormality or clinical testing (including EEG and absence of any intervention evidence of cardiac disease.7%. . group 2.8 (p<0. normal echo and CXR Exclusion criteria: None specified Akhtar M .or/and Exclusion criteria: Results: tachyarrhythmic causes of syncope. Study type: Inclusion criteria: 1 endpoint: Limitations: 40 © 2017 by the American College of Cardiology Foundation. abnormal ECG and undiagnosed syncope. (107) Exclusion criteria: Results: 41 © 2017 by the American College of Cardiology Foundation. American Heart Association. symptomatic SVT. et al. disturbance in a significant number of cases. sinus hypersensitivity. . not EPS testing. None specified ● 14/16 remained free of symptoms following therapy based on results of EPS during a mean 16 mo f/u. high risk group. the decision to implant PPM was due to evidence of SND. ● In remaining 14/30 pts. 6189057 observational preceding y). et al.8).1983 Prospective SUO (≥ 2 episodes in To assess results of EPS with PES in pts with recurrent syncope All pts received EPS. ● 3/14 pts without clinically significant arrhythmias had structural heart disease. ● HV interval ≥70 ms or greater in 12 pts and effectively treated. EPS and PES did not induce arrhythmia which could account for patient symptomatology. ● Long-term management guided by the results of ESP generally is successful in preventing recurrent syncope. ● Of 15/16 pts with inducible arrhythmias considered clinically significant had structural heart disease. However. SND EPS with PES can uncover type of arrhythmic Exclusion criteria: in 4/30. and Heart Rhythm Society. carotid ptsPPM patient preference.2±6. both had normal EPS clinically significant abnormality. Doherty JU. Study type: Inclusion criteria: 1 endpoint: Limitations: 1984 Prospective SUO undergoing EPS Diagnostic yield of EPS with PES in pts with SUO ● In treated pts who did not have recurrence of 6475778 observational syncope. negative (105) evaluation Results: Conclusions: Size: n=30 pts ● Sustained or nonsustained VT and/or VF induced in 11/30. Intra-His AVB in remaining 1/30.. 11/14 pts experienced a recurrence of symptoms within a 6–25 mo period (mean 16. ● In 2/16 syncope recurred (one arrhythmic and one non- arrhythmic) despite pacemaker therapy for SND detected during EPS. VT. Morady F. Study type: Inclusion criteria: 1 endpoint: Limitations: 1985 Prospective SUO undergoing EPS EPS findings of pts with SUO ● EPS negative group differed in the frequency of 3976512 observational heart disease. it is presumed that syncope did not recur (106) Exclusion criteria: Results: because the cause of syncope was correctly identified Size: n=32 pts 2nd or 3rd degree AV block. or a ● Monomorphic VT induced in 9 pts and polymorphic VT in history consistent with 5AAD Conclusions: classic vasovagal or ● Actuarial incidence of sudden death was 10% at 45 mo of ● Approximately 50% of pts with BBB and unexplained vasodepressor syncope follow-up syncope who undergo EPS are found to have a ● Only 2 pts had recurrent syncope. ● Pathologic infranodal AVB during atrial pacing occurred in 2 ● In some pts. Inc. even hypersensitivity in 15 (9%). ● Total CV mortality 13% in positive EPS response group. Inc. 1987 Study type: Inclusion criteria: 1 endpoint: Limitations: 42 © 2017 by the American College of Cardiology Foundation. In pts therapy. 76%±11% symptom free at follow-up. 4025122 observational (109) Exclusion criteria: Results: Conclusions: Size: n=150 pts None specified ● 162 abnormal EPS findings that could explain SUO in 112 pts ● This study and a review of the literature indicate that ● His-Purkinje disease in 49 pts (30%). 12/60 pts followed had ● Nontrivial number of pts receiving ineffective therapy recurrent syncope. ● VT or SVT inducible in 35%. et al. no control. Teichman SL. and inducible tachycardia common in pts both with and without heart disease. et al. Conclusions: ● 7/13 pts receiving ineffective therapy had recurrence of syncope ● Inducible tachycardias found in approximately 30% or cardiac arrest (p<0. Study type: Inclusion criteria: SUO 1 endpoint: Limitations: 1985 Prospective undergoing EPS To determine the significance of inducible tachycardia in SUO ● Small number lost to follow up 3968306 observational ● Does not factor in that some pts have remission (108) Exclusion criteria: Results: spontaneously Size: n=105 pts None specified ● 65% did not have inducible tachycardia. Size: n=119 pts Known cause of syncope ● Presence of structural heart disease (p=0.025). AVB in 20 (12%). no syncope recurred for heart disease. and Heart Rhythm Society. SND in 19 (12%). ● Adherence to AAD therapy guided by EPS may prevent recurrence. Olshansky B. ● One patient in negative EPS response group and 2 pts in EPS positive group died suddenly. abnormal ECG is present..6 mo (p<0. . when only a single syncopal event has recurrences in 16/34 pts (47%) without and 15/103 pts (15%) with occurred. 15. Study type: Inclusion criteria: 1 endpoint: Limitations: 1985 Prospective SUO undergoing EPS Diagnostic yield and therapeutic efficacy of EPS in pts with SUO ● Observational data. and hypervagotonia in 5 (3%). Krol RB.0033) and previous Conclusions: MI (p=0. when only clearly abnormal findings are considered ● Follow up data in 137 pts (91%) (mean 31 mo) showed diagnostic. and 4% in negative EPS response group.05) were the only clinical or ECG predictors of a positive ● EPS can identify a subgroup of pts at low risk of EPS. or whether or not organic heart disease or an EP findings despite therapy directed by EPS (p<0. therapy inducible supraventricular arrhythmias in 18 (11%). et al. limited sample.05). of pts with SUO. American Heart Association. had high percentage of recurrence. common in pts both with and without ● On resumption of effective therapy. compared to 68%±10% in positive EPS group. ● No clinical variables helped to predict remission in absence of therapy. inducible ventricular EPS useful in elucidating causes of SUO and directing arrhythmias in 36 (22%).0005). with negative EPS results. recurrence and sudden death in the absence of ● Therapy guided by EPS and pts followed for 27±20 mo. carotid sinus ● A significant number of pts benefit from EPS. remote MI (p<0. high grade AV atrial pacing. Size: n=21 pts whose cardiac rhythm had Conclusions: reverted to normal by the Results: ● Negative EPS in a patient with a normal cardiac time of referral ● 3/8 with documented sinus pauses had abnormal EPS including rhythm who has experienced syncope does not a prolonged SNRT in 1 and carotid-sinus hypersensitivity in 2 pts. brady/tachyarrhythmia ● LVEF ≤40% most powerful predictor of a positive EPS known to cause syncope (p<0. American Heart Association. Inc. QT prolongation. ● Probability of a negative study increased as number and duration of syncopal episodes increased. et al. syncope.01).00006). injury related to LOC (p<0.0001) and normal ambulatory ECG monitoring (p<0. Fujimura O.00001). CSH.00003). et al. syncope. inducible VT most common finding postural hypotension.00003). monomorphic VT.00001). ● A negative EPS associated with LVEF >40% (p<0. and Heart Rhythm Society. followed by the presence of BBB (p<0. Study type: Inclusion criteria: ECG 1 endpoint: Limitations: 1989 Prospective evidence of intermittent AV Sensitivity of EPS in detection of transient bradycardia in pts in ● Small study limited to pts with transient ECG 2594030 observational block (n=13) or sinus pauses normal sinus rhythm referred for pacemaker implantation after findings. but ECG documentation of transient bradycardia resulting in syncope. hypotension) SUO can be predicted to have normal or abnormal vasovagal/vasodepressor EPS.3598006 Prospective ≥1 SUO episode To evaluate whether clinical variables enable stratification of pts ● No episodes of syncope with ECG recorded.0001). 1985382 observational predict EPS. normal ECG (p<0. . (26) Exclusion criteria: syncope recurrence Size: n=91 pts BBB. use of type 1 AAD (p<0. and SVT associated with ● On the basis of clinical variables. (71% of positive studies).0003). 43 © 2017 by the American College of Cardiology Foundation. LVEF. CAD (p<0. Moazez F. Study type: Inclusion criteria: 1 endpoint: Limitations: 1991 Prospective SUO undergoing EPS To examine usefulness of clinical and noninvasive variables to ● BBB pts excluded. None specified ● 2/13 with documented AVB had abnormalities suggesting correct diagnosis..00001). majority of pts with block. This may lead to cost-effective use of EPS.01) and male sex (p<0. symptomatic ● 31 pts had positive EPS. unknown data on Conclusions: LVEF or SAECG Results: ● Pts who have inducible sustained monomorphic VT ● Multivariate analysis identified +SAECG. infranodal block during Conclusions: Size: n=104 pts Sustained VT. and history of at EPS can be identified using certain clinical and sustained monomorphic VT as risk factors for induction of noninvasive variables. (110) observational with SUO into low and high probability of having abnormal EPS Exclusion criteria: (SNRT ≥3 seconds. HV interval ≥100 ms. absence of structural heart disease (p<0. HCM. Results: AS. (111) (n=8) causing syncope. and to compare EPS results and therapy with ● No TTT or isoproterenol infusion performed. exclude a transient bradyarrhythmia as a cause of the Exclusion criteria: ● 3/8 pts had abnormalities unrelated to syncope. and the effect of treatment of these abnormalities due to high-risk group. ● Female gender may be an independent predictor of ● 37/40 received pacing or antiarrhythmic therapy c/w 23/94 who favorable outcome. had a negative study and received empiric therapy (p<0. moderate follow-up (113) observational Exclusion criteria: Results: Conclusions: Size: n=134 pts None specified ● Conduction abnormalities and tachyarrhythmia could account ● 19% of pts will have a recurrent event. refractory to treatment.0±8. Conclusions: Size: n=86 pts Exclusion criteria: ● The combination of EPS and HUTT can identify the None specified Results: underlying cause of syncope in as many as 74% of pts ● 34% had abnormal EPS. Denniss AR . ● During a mean follow-up of 22±17 mo. Inc. Study type: Inclusion criteria: 1 endpoint: Limitations: 1992 Prospective SUO undergoing EPS Compare incidence of EPS abnormalities in pts with and without ● Failure to demonstrate mortality reduction may be 1572741 observational heart disease.0001). arrhythmia induced at EPS. with sustained monomorphic VT presenting with SUO. ● The cause of syncope remained unexplained in 26%. et al. SUO having EPS and HUTT and to assess efficacy of various (112) therapies. ● 40% had syncope provoked by HUTT. with 30% of these pts with structural heart disease. et al. induced in 72%. rate of recurrence of syncope similar to pts who had no up. Study type: Inclusion criteria: 1 endpoint: Limitations: 1991 Retrospective SUO undergoing EPS. Size: n=111 pts Exclusion criteria: Conclusions: None specified Results: ● Syncope pts with heart disease more likely to have a 44 © 2017 by the American College of Cardiology Foundation. and To determine the clinical characteristics of subgroups of pts with ● Retrospective evaluation 2029096 observational HUTT if negative. ● During a median follow-up period of 18. and Heart Rhythm Society.005). . for syncope in 40 pts (30%). therapy in reducing the rate of recurrent of scope. ● Small sample. American Heart Association. with 6% of these pts with structural heart disease. et al.5 mo. Muller T. syncope recurred in 9 (10%) pts.. 1991 Study type: Inclusion criteria: 1 endpoint: Limitations: 2044546 Prospective SUO EPS findings of pts with SUO. EP-guided (sustained ● Empiric therapy does not offer any benefit over no monomorphic VT).3 mo of follow. Sra JS. with 76% of these pts with structural heart disease. sustained monomorphic VT at EPS. 22 pts had recurrent syncope and 4 died suddenly ● Men had a higher incidence of recurrent syncope than women (26% vs. P<0. ● Recurrence rates among empiric. their ●17 pts had recurrence of syncope over 19. 6%. and no therapy groups were similar. ● When these pts undergo EP-guided therapy. (114) on recurrence of syncope. . ● Retrospective. Size: n=33 pts “Arrest Group”: NICM with Results: Conclusions: cardiac arrest and ICD ● 50% in Syncope Group vs. p=0.05). and Heart Rhythm Society. lower LVEF (22. ● Predictors of ventricular arrhythmias: BBB (p=0. noninducibility at EPS Sudden cardiac death. (116) underwent ICD (n=14). American Heart Association. longer runs of NSVT (p=0. 42% in Arrest Group received ● The high incidence of appropriate ICD shocks and (n=33) appropriate shocks (p=0.1).08).5±3% vs. Sagristà-Sauleda J. negative EPS.72 in the untreated group (p<0. Study type: Inclusion criteria: 1 endpoint: Limitations: et al. 10235091 observational CAD. Determine outcome of pts with NICM. these pts may warrant treatment with ICDs. et al.09). Observational Group I: first syncope at age To assess diagnostic yield of TTT and EPS in different groups of Retrospective. Mortality during follow-up was only in heart disease group with 5/30 treated dying compared with 3/43 untreated pts (p=NS). compared with a recurrence rate of 18/74 in did not significantly affect mortality. 11350095 Group II: first syncope at (102) Size: n=600 pts age >65 y (n=136 pts) Results: Conclusions: 4 subgroups in both: ● Positive TTT-more common in (group I) than group II (47% vs. and only TTT pts studied. and negative EPS who treated with ICD without stored EGM. Study type: Inclusion criteria: 1 endpoint: Limitations: 1999 Retrospective Syncope or presyncope and Long-term outcome of pts with CAD and non-diagnostic work-up. 17 pts had recurrence. 10%/y. Knight BP. et al. predicts a lower risk of SCD and VT/VF.94 in the treated group and 0. 43±16%).05). p=0.07). with unclear etiology including EPS (115) Conclusions: Size: n=68 pts Exclusion criteria: Results: ● In pts with CAD and syncope. ● Abnormalities detected in 31/73 with heart disease but in only diagnostically useful study than pts with normal hearts. the association of recurrent syncope with ventricular arrhythmias support treatment of pts with nonischemic Exclusion criteria: ● Mean duration from device implant to first appropriate shock in cardiomyopathy. the risk remains up to explained syncope LVEF (p=0. ● All 4 arrhythmias occurred in pts with LVEF ≤25%. untreated group (p<0.. ● At a mean follow-up of 30±18 mo. 72±12 mo (95% CI: 48–96. EPS done 2001 cohort ≤65 y (n=464 pts) pts with SUO established according to simple clinical criteria. 6/38 with no heart disease (p<0. Inc.01). at physician discretion. Link MS.02). noninvasive testing ● Predictors of all-cause mortality: age (p=0. HV ≥90 ms excluded. and SUO ● Small size. Study type: Inclusion criteria: 1 endpoint: Limitations: 1999 Prospective “Syncope Group”: NICM. syncope recurred in 2/37 treated because of detected at EPS reduced recurrence of syncope but abnormal findings. Syncope Group 32±7 mo (95% CI: 18–45) compared to ICD.1). unclear “appropriate” shocks in devices 10362200 observational SUO. ● Probability of remaining free from syncope at 2 y was 0. SUO and a negative EPS with an None specified.05) and reduced ● In pts with a reduced LVEF. The rate of positive responses to the head-up tilt test 45 © 2017 by the American College of Cardiology Foundation. ● Treatment directed at correction of abnormalities ● During follow-up. spontaneous sustained VT. Inc.6 mo.7–9. CI: 1. Patient Population Primary Endpoint and Results Summary/Conclusion Author.3±19.2).p<0. ICD implantation in pts with syncope 89% and 81%. VF arrhythmia or those pts. The overall one and 2 y survival in these pts was 17% of these pts. VF rarely induced with 2 extrastimuli (117) EPS Small sample size Size: n=118 pts Results: Exclusion criteria: ● Sustained monomorphic VT was inducible in 53 (45%) pts. p<0.6. respectively. it was lowest in pts without organic heart (n=44 pts) ECG and without organic heart disease (2. may merit reconsideration. while normal ECG (n=359 pts) older pts with an abnormal ECG and with organic heart B: pts with no organic heart ● EPS disclosed abnormal findings in group II more than in group disease had the lowest rate of positive responses disease (n=122 pts) I (23% vs. OR: 1. in 20 Conclusions: Pts with a documented (17%) pts. OR: 3. and subgroup A (49% was higher in younger pts and in pts with a normal disease and a vs. and/or Registries of Tilt Table Testing – (Section 3.1). et al. 3.) Study Acronym. C: pts with organic heart ECG (subgroups B and D) than in those with a normal ECG (22% in pts with organic heart disease and with an abnormal disease and a normal ECG vs. OR:1. OR or RR. VF was the only inducible arrhythmia. and it was low in pts with a normal ECG (26%). Study Type/Design. and no sustained Induction of VF in pts with CAD and unexplained sustained ventricular ventricular arrhythmia was inducible in the remaining 45 (38%) syncope may be of limited prognostic significance. disease and with a normal ECG (2.7. of undetermined origin in whom only sustained VF is ● No significant difference in survival was observed between pts induced during EP testing. Study Size (include P value. and an abnormal ECG. especially with triple with and without inducible VF. p<0.7%. 95% CI: 1.78).2. (18%)..05. ventricular extrastimuli.008. D: pts with organic heart disease and an abnormal ECG (n=75 pts) Exclusion criteria: None specified Mittal S. 37%.6). 7%. 25.6%).8. ECG and without organic heart disease (49%). Nonrandomized Trials. Observational Studies.0005. Comment(s) Year Published and 95% CI) 46 © 2017 by the American College of Cardiology Foundation. A: pts who no organic heart 33%. Data Supplement 15. .2–2. was the only inducible ventricular arrhythmia at EP resuscitated from sudden ● There were 16 deaths among during a follow-up period of testing (using up to triple ventricular extrastimuli) in cardiac death. American Heart Association. OR: 7. and Heart Rhythm Society. p<0. ● Diagnostic yield from EPS was higher in pts with an abnormal ● The diagnostic yield of EPS was higher in older pts. Study type: Inclusion criteria: 1 endpoint: Limitations: 2001 Prospective CAD and unexplained To determine the incidence and prognostic significance of All pts had CAD (limited generalizability) 11499726 observational syncope who underwent inducible VF in pts with CAD and unexplained syncope.001.6%). Kenny RA. Passman R. or 16% of the whole population reported. Identification of the contribution to syncope In symptomatic pts SBP fell from 150 ± 32 to 56 ± 9 mm Hg (p<0. et Study type: Inclusion criteria: 1 endpoint: Limitations: al. No cardiac pacing may be beneficial.001). (118) Size: n=25 pts Conclusions: (15 test.001) made by changes in heart rate and BP and and heart rate from 62 ± 9 to 38 ± 12 bpm (p<0. tachyarrhythmia (n=3). 11 pts (5%) had apparent tonic-clonic seizure-like activity and 7 pts Conclusions: (3%) had non-tonic-clonic neurologic events. Baseline SBP and heart rate did not differ significantly between pts and controls. (119) None Results: ● Prolonged 60 degrees head-up tilt was performed in 71/93 pts with Conclusions: unexplained syncope. ● The heart rate at the time of test termination was significantly lower in the pts with tonic-clonic seizure-like activity and non-tonic-clonic 47 © 2017 by the American College of Cardiology Foundation. Study type: Inclusion criteria: 1 endpoint: Limitations: 1986 Case-control study Syncope of unclear To investigate the utility of syncope that remained unexplained despite ● Small sample. American Heart Association. percentage (70%) of abnormal findings (limited 2040321 Size: n=322 pts Exclusion criteria: generalizability). although these early similar age without a Hx of syncope (7%). all with EPS 2872472 etiology full clinical and electrophysiological assessment. Study type: Inclusion criteria: Pts 1 endpoint: Limitations: 2003 Retrospective cohort with syncope To assess the prevalence and type of apparent neurologic events ● The retrospective nature of this study may 12963568 associated with tilt table testing. et al. and a random sample of 37 observations do not allow an exact appraisal of pts with AVB (n=16). Inc. 18 pts (8%) had neurologic events during TTT. (19%. et al.04). and this SBP reading at the termination of tilt table testing than all other pts diagnosis should be considered in the evaluation whose TTT results were positive (p=0. of unexplained seizure-like activity. Pacemakers were implanted in 7 pts who have remained symptom free since implant (follow-up 10 ± 3 mo). and reproduced VVS and presenting symptoms in ● TTT is a valuable provocative tool for VVS and 53 (75%). 11% and 0% respectively. In each case therefore permits the selection of pts in whom symptoms during the test reproduced those previously experienced. have resulted in inadequate documentation of all (120) Size: n=694 pts Exclusion criteria: potential seizure-like or atypical neurologic None Results: events at the time of TTT ● 222/694 with positive TTT.01). Fitzpatrick A.01). clinical findings predicted development of syncope during tilt. ● Neurologic events are common during ● The pts with tonic-clonic seizure-like activity had a significantly lower episodes of neurocardiogenic syncope. Retrospective cohort Recurrent syncope To utilize TTT to discover the incidence of malignant VVS in pts with ● All pts underwent EPS. p<0. may reduce the number of syncopal pts that ● Positive tilts were significantly less common in a group of 27 pts of remain undiagnosed. with a large 1991 recurrent syncope.. 10 control) Exclusion criteria: Results: ● Reproduction of symptoms during tilt allows None specified ● In 10 pts and one control VVS developed after 29±19 min (p<0. and Heart Rhythm Society. sick sinus syndrome (n=18) and inducible the sensitivity and specificity of the TTT. . 383 pts with 20046517 without any other cause during HUTT-induced syncope in pts with neurally mediated reflex positive HUTT. single center study 1952474 seizure-like episodes. 67%).157 pts were excluded from the (122) Size: n=226 pts of syncope syncope. ● Upright TTT combined with isoproterenol Results: infusion may be useful to distinguish convulsive Exclusion criteria: ● Syncope associated with tonic-clonic seizure-like activity occurred in syncope from epileptic seizures None 6/15 (40%) during the baseline tilt and in 4/15 during isoproterenol infusion (total positive tests. Study type: Inclusion criteria: 1 endpoint: Limitations: 2010 Retrospective cohort Syncope during HUTT To assess the incidence and characteristics of seizure-like activities ● Retrospective in design. single center. The seizure- ● Comparison of pts with and without seizure-like activities revealed no like activities during HUTT might not be related significant differences in terms of clinical variables and hemodynamic to the severity of the syncopal episodes or parameters during HUTT. American Heart Association. Song PS. no further seizure-like episodes have occurred. ● All pts who had positive test results eventually become tilt table negative after therapy. et al. ● The EEG showed diffuse brain wave slowing (not typical of epileptic seizures) in 5/5 pts during the convulsive episode. et al. diagnosis of convulsive syncope from epileptic seizures in pts with (121) Size: n=15 pts unresponsive to recurrent idiopathic seizure-like episodes. Study type: Inclusion criteria: 1 endpoint: Limitations: 2000 Prospective cohort Diagnosis of epilepsy. 1. neurologic events (p<0. Grubb BP.9%). population (123) Size: n=74 pts despite adequate anticonvulsant drug Results: Conclusions: treatment (n=36 pts) or ● An alternative diagnosis was found in 31 pts (41. highly unique 10898432 with continued attacks pts with apparent treatment-resistant epilepsy. hemodynamic changes during HUTT. neurally mediated reflex syncope. Exclusion criteria: Results: None ● 13/226 pts showed seizure-like activities.1%) of 36 pts taking an anticonvulsant medication. 5/226 (2. with 5/226 having multifocal Conclusions: myoclonic jerky movements. study because they did not lose consciousness during HUTT. and Heart Rhythm Society. Of 1. Study type: Inclusion criteria: 1 endpoint: Limitations: 1991 Prospective cohort Recurrent unexplained To evaluate the usefulness of head-upright TTT in the differential ● Small sample. and 3/226 having upward deviation of during HUTT-induced syncope in pts with eye ball. and asystole was provoked more frequently in these 2 patient populations (p=0.01) than in those with positive test results and no provoked neurologic events. and over a mean follow-up period of 21 ± 2 mo. To investigate the value of CV tests to diagnose convulsive syncope in ● Small sample. identify an alternative diagnosis in many pts with 48 © 2017 by the American College of Cardiology Foundation. Conclusions: antiseizure medication. . noninvasive CV evaluation may uncertainty about the (36. including 13 ● A simple. et al. Inc. Zaidi A..21%) having focal seizure-like ● Seizure-like activities occurred occasionally activity involving one extremity.03). Luzza F. and Heart Rhythm Society. disorder Zaidi A. et al. with pseudosyncope. This may have 49 © 2017 by the American College of Cardiology Foundation. diagnosis of epilepsy. limited number of pts 12846340 some pts affected by unexplained syncope. ● In 3 other pts (0. Study type: Inclusion criteria: 1 endpoint: Limitations: 2003 Retrospective cohort Unexplained syncope To assess the ability of HUTT in recognizing a psychiatric disorder in ● Retrospective design. 2 pts developed psychogenic symptoms during the HUTT. myoclonic jerking in one seizure-like attacks and should be considered in Exclusion criteria: patient) during head-up tilt without significant EEG abnormalities or pts with suspected non-epileptic attack disorder. exclusion criterion for tilt-table testing. 2013 TLOC during tilt-table psychogenic pseudosyncope which concerns episodes of apparent ● A clinical suspicion of PNES was not a formal 23873974 Size: n=800 pts testing without EEG TLOC that mimic syncope. lack of followup. 10512777 episodes and a clinical attack disorder (124) Size: n=21 pts diagnosis of Conclusions: nonepileptic attack Results: ● HUT with suggestion is a safe. . Inc. but (126) changes and without referral selection will have excluded the majority decreases in heart rate Results: of these pts nonetheless. Prospective cohort Episode of apparent To provide a detailed semiology to aid the clinical recognition of ● Referral bias. et al. absence in one patient. provocative EEG test for dissociative shaking in 15 pts. In all 3 cases unconsciousness was prolonged and no pathological finding was present except lack of response. None hemodynamic changes. blackouts. (125) Size: n=986 pts Exclusion criteria: None Results: Conclusions: ● In 266 pts the test induced bradycardia and/or hypotension resulting in ● HUTT may contribute to the recognition of syncope or presyncope. Exclusion criteria: 7 pts had significant ECG pauses during CSM. well tolerated.7%) developed profound hypotension or bradycardia during early in the management of pts with convulsive clinical description of the HUTT. allowing a diagnosis of neurally mediated psychiatric disorder in some pts affected by syncope. Study type: Inclusion criteria: 1 endpoint: Limitations: 1999 Prospective cohort Recurrent seizure-like To assess the value of HUTT as a provocative test for non-epileptic ● Small sample. confirming the diagnosis of VVS. Study type: Inclusion criteria: 1 endpoint: Limitations: et al.3% of the entire population and 1% of the all positive tests) HUTT provoked LOC despite no significant change in heart rate and/or BP. episodes of Suspected psychogenic prolonged bradycardia correlated precisely with seizures according to nonepileptic attack the insertable ECG recorder. unexplained syncope. apparent epilepsy and should be considered on the basis of the ● 19 pts (25. disorder. the seizures (n=38 pts) ● 1 patient had a typical vasovagal reaction during intravenous cannulation. In 2 pts.. ● 17 pts (81%) experienced typical symptoms (non-epileptiform limb sensitive. This phenomenon has been defined as 'pseudosyncope' and related to psychiatric illness Tannemaat MR. select population. American Heart Association. HUTT results were positive in only 2 pts (18%) 50 © 2017 by the American College of Cardiology Foundation. drug not used clinically in most 7798528 blind crossover study positive HUTT. or BP. American Heart Association. Study type: Inclusion criteria: 1 endpoint: Limitations: 1993 Double-blind Recurrent neurally To determine the efficacy of intravenous and oral disopyramide ● Only pts who had a positive response were 8245337 randomized trial mediated syncope and phosphate in preventing neurally mediated syncope induced by a HUTT. complete crossover was achieved in 15 pts. et al. accurately with tilt-table testing and ● A sudden head drop or moving down the tilt table was more common simultaneous EEG monitoring. During the event.05). Morillo CA. The statistical power of the study was (127) only 10%.55. ● In psychogenic pseudosyncope. 95% CI: -14%–40%). et al. . Syncope and a baseline To assess the efficacy of oral etilefrine in preventing a positive response ● Small sample. Study type: Inclusion criteria: 1 endpoint: Limitations: 1995 Randomized double. Exclusion criteria: in psychogenic pseudosyncope than in VVS (p<0. in VVS (p<0. Size: n=30 pts Exclusion criteria: Results: Previous hypertension ● HUTT results were negative in 13 (43%) pts with etilefrine and 15 Conclusions: and 11 (11%) because (50%) with placebo (p=NS). 43 (5. placebo syncope or presyncope HUTT results during this phase were positive in 13 pts (87%) receiving during testing placebo and in 12 pts (80%) receiving disopyramide (p=0. Despite a low statistical HUTT. 10 with etilefrine) but in only 12 during the third (7 with power. (128) 2 or more successive Size: n=22 pts. Inc.4%) resulted in psychogenic affected the prevalence of jerking movements. p<0. to HUTT. The event had to ● Of 800 tilt-table tests. both heart rate and BP increased before and during apparent TLOC (p<0. centers. the high rate of negative response with etilefrine.05) placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in pts with VVS. ● In the oral phase. The rate of positive responses decreased ● Oral etilefrine (10 mg 3x a day) was not of a cardioinhibitory with repeated testing irrespective of the assigned treatment superior to placebo in preventing a positive response to ● A positive response was obtained during the second HUTT in 20 pts response to HUTT.. Moya A. patient or a relative ● The median duration of apparent TLOC was longer in psychogenic Conclusions: (present during the test) pseudosyncope (44 s) than in VVS (20 s. (10 with placebo.0001). movements occurred more frequently in VVS (p<0. provoked by HUTT. 5 with placebo) (p<0.01). and Heart Rhythm Society.0001). but jerking None specified. crossed over to alternative therapy. No significant effect was disopyramide or Failure to produce ● In the intravenous phase. positive HUTT Results: Conclusions: randomly allocated to responses ● HUTT results were positive for syncope in 12 (75%) of 16 pts ● Intravenous disopyramide was ineffective for receive either receiving intravenous placebo and in 12 (60%) of 20 pts receiving the prevention of neurally mediated syncope intravenous Exclusion criteria: disopyramide (p=0. 95% CI: - 19%–32%) and were positive in all pts receiving their initially randomized drug or placebo. observed after oral therapy with disopyramide.0001). be recognized by the pseudosyncope. the ● Psychogenic pseudosyncope is clinically as typical of the eyes were closed in 97% in psychogenic pseudosyncope but in only 7% distinct from VVS and can be diagnosed patient's episodes.50. American Heart Association. mechanistic diagnostic tilt testing CO did not change in pts or in controls. in TPR. ● Blinding – not stated underlie delayed OH intolerance after 3 mins. and (2) documentation Results: Conclusions: Study type: of a delayed decrease ● At the end of the test.54. Syncope during OH or delayed OH ●Referral population.. SV and TPR (in pts ● Laboratory study 19669396 hemodynamic and (1) symptoms and with delayed OH compared to age. Exclusion criteria: controls ●The compensatory increase in HR is Size: n=13 pts and 9 The inability of the ● Administration of elastic compression to the legs counteracts the insufficient to compensate the decline in BP controls patient to collaborate decrease in SBP and TPR. in BP pattern during lower. 25531748 related patterns of SBP angioplasty ● Laboratory study (131) and DBP responses in Results: pts referred for Exclusion criteria: ● 7% had OH within 3 min. 51 © 2017 by the American College of Cardiology Foundation. Aim: Inclusion criteria: 1 endpoint: Limitations: 2009 To investigated the Pts with delayed OH The changes in the SBP. and 40% within 40 min. Heart rate increased decrease in TPR. 43 and 91% were identified within 3 and 30 min. 60° head-up tilt ● Referral population (129) and neurophysiologic performed for 45 min Results: features of delayed OH ● Of 108 pts with OH. dysfunction evident of autonomic testing ● TTT duration should be extended observational. SV and decrease in SBP is associated with progressive control. Gibbons. 95% CI: -42%–24%). ● Delayed OH occurred in 54% of tested Study type: None specified ● Delayed OH was associated with mild sympathetic adrenergic population Retrospective. cardiac output.05). SBP was significant ● In pts with delayed OH. Conclusions: suspected OH to tilt None specified ● 270 OH pts. et al. TPR progressively decreased in pts but not in controls. heart rate. 15% had OH Conclusions: Exclusion criteria: between 3 and 10 min. 35% within 30 min. ● Syncope recurred in 3 (27%) of the 11 pts receiving disopyramide and 3 (30%) of the 10 pts not treated pharmacologically (p>0. Inc. Aim: “Inclusion criteria”: 1 endpoint: Limitations: 2014 (1) To assess time. . in pts compared to controls. while CO and SV show little study in human pts progressively in pts until the end of the test and remained unchanged in change. and Heart Rhythm Society. Aims: “Inclusion criteria”: 1 endpoint: Limitations: 2006 To investigate the OH or delayed during a OH or delayed OH ● Laboratory study 16832073 prevalence. the progressive Prospective. Gurevich T. and 39% had OH after 10 min of HUTT. et al. ●Tilt table testing to 30 minus identifies most but testing respectively no all pts with delayed OH. assigned to placebo and in 3 pts (27%) receiving disopyramide (p=0. 46% had OH within 3 min of HUTT.and sex-matched controls during a ● Small number of pts (130) mechanisms that signs of orthostatic modified version of the Italian tilt protocol. ● Underlying mechanism possibly early or mild mechanistic sympathetic adrenergic failure Size: n=230 pts Podoleanu. ● Administration of elastic compression to the and to perform tilt legs counteracts decrease in SBP and decrease testing. case. et al. symptoms. (2) To assess the percent of delayed OH and factors associated with it. Study type: Prospective, observational, mechanistic, Size: n=692 pts; 270 with OH or delayed OH Gibbons, et al. Aims: “Inclusion criteria”: 1 endpoint: Limitations: 2015 To define the long-term OH during a 60° head- OH, delayed OH and clinical outcome including mortality ● Laboratory study 26400576 outcome of delayed OH up tilt performed for 45 ● Referral population (132) mins Results: Study type: ● 54% of individuals with delayed OH progressed to OH. Conclusions: Prospective, Exclusion criteria: ● 31% with delayed OH developed an α-synucleinopathy ● Delayed OH frequently progresses to OH longitudinal follow up, None ● 10-y mortality rate in individuals with delayed OH was 29%; with ● Delayed OH frequently progresses to an observational, baseline OH was 64% and in controls was 9%. alpha-synucleinopathy (multiple system atrophy, mechanistic ● 10-y mortality of individuals who progressed to OH was 50%. Parkinson’s disease, dementia with Lewy bodies) Size: n=108 pts with ● Delayed OH has a high associated mortality OH, 75 age- and sex- particularly when it progresses to OH matched controls Data Supplement 16. Nonrandomized Trials, Observational Studies, and/or Registries of Neurologic Investigation – (Section 3.3) Study Acronym; Study Type/Design; Patient Population Primary Endpoint and Results Summary/ Author; Study Size Conclusion Year Published Comment(s) Abubakr A, et al. Study type: Retrospective Inclusion criteria: Syncope pts 1 endpoint: Classification of EEG findings Very few abnormal EEGs, but the larger 2005 chart review selected from a larger population of including variants of normal. population of syncope pts is not reported. 15820355 EEG reports Rare EEG abnormalities. No epileptiform (133) Size: n=1,094 syncope pts Results: 2 (1.5%) abnormal EEGs: one focal features slowing, one diffuse slowing 52 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Al-Nsoor, et al. Study type: Perhaps Inclusion criteria: Syncope in ED 1 endpoint: Abnormality contributing to Very high use of CT scans, and firmness of 2010 prospective cohort seen by a neurologist diagnosis attribution not clear 20672498 (134) Size: n=292 pts Results: 254 CT scans (87%); 10 (3.9% of ordered) helped. Giglio P, et al. Study type: Retrospective Inclusion criteria: Syncope pts in ED 1 endpoint: Proportion with CT scans; Fully 34% had CT, but only 1 (3% of 2005 chart review proportion abnormal related to syncope ordered) had diagnostic utility relevance 16292675 (135) Size: n=128 pts Results: 44 had CT; 1 showed old posterior infarction. Goyal N, et al. Study type: Retrospective Inclusion criteria: Syncope diagnosis 1 endpoint: Any clinically significant finding Inclusion criteria based on CT use, but the 2006 chart review by ED MD larger population of syncope pts is not 17111790 Results: 117 had CT; 0 (0% of ordered) reported. CT had no diagnostic utility (136) Size: n=117 pts with syncope helped. and head CT Johnson PC, et al. Study type: Retrospective Inclusion criteria: Syncope coded in 1 endpoint: Test contributed to alleged CT and MRI performed moderately 2014 chart review billing records, and after non-syncopal diagnosis frequently and of no diagnostic utility. 25365440 diagnoses excluded on chart review Carotid ultrasound less frequently and of no (137) Size: n=167 syncope pts of Results: 131 CT scans (78.4%); 0% helped. diagnostic utility. 1,038 adult Texan in-pts with 18 brain MRI (10.7%); 0% helped. 52 carotid “syncope” screened ultrasounds (31.1%); 0% helped. Kapoor WN, et al. Study type: Prospective Inclusion criteria: Diagnosis of 1 endpoint: Diagnosis of cause of syncope The population was accumulated nearly 40 1983 cohort syncope after inclusion for TLOC y ago. Tests are of minimal diagnostic 6866032 Results: 65 CT scans (32%); 0% helped. 101 utility. (70) Size: n=204 pts in global EEGs (49.5%); 1 (1% of ordered) helped. population Mecarelli O, et al. Study type: prospective Inclusion criteria: recurrent syncope, 1 endpoint: Abnormal EEG The report is restricted to VVS pts, and is 2004 observational controlled positive tilt test, negative brain MRI only one of several. Maybe should delete it, 15639129 cohort Results: 0 (0%) abnormal findings on routine or include them all. (138) EEG but increased slow wave activity during Size: 43 pts with vasovagal hyperventilation syncope; 32 controls Mendu ML, et al. Study type: Retrospective Inclusion criteria: ICD 9 in-hospital 1 endpoint: Chart documentation that the One of the largest, but retrospective, 2009 chart review primary or secondary syncope finding contributed to the diagnosis firmness of attribution not clear. 19636031 diagnosis CT, EEG, carotid ultrasound of minimal (68) Size: n=1,920 pts Results: 1327 CT scans (63%); 35 (2.6% of diagnostic utility. MRI provided some ordered) helped. 154 brain MRI (19%); 23 (15% diagnostic utility 53 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. of ordered) helped. 267 carotid ultrasounds (20%); 3 (1.1% of ordered) helped. 174 EEG (13%); 3 (1.7%) helped Pires LA, et al. Study type: Retrospective Inclusion criteria: ICD 9 syncope in 1 endpoint: Apparently contributed to Weak methodology. 2001 chart review in-patients diagnosis of etiology. All investigations of low diagnostic utility 11493131 (139) Size: n=649 pts Results: 283 CT scans (41%); 5 (1.8% of ordered) helped. 10 brain MRI (1.3%); 3 (30% of ordered) helped. 185 carotid ultrasounds (29%); 0 (0% of ordered) helped. 253 EEG (39%); 6 (2.4%) helped Poliquin-Lasnierl L, et Study type: Retrospective Inclusion criteria: Syncope or falls 1 endpoint: “Yield” of EEGs EEG use an inclusion criterion, so studied al. chart review and EEG ordered population. does not represent the large 2009 Results: 0 (0%) EEGs showed epileptiform syncope population 19960758 Size: n=517 pts activity (140) Scalfani JJ, et al. Study type: Part A Inclusion criteria: ICD primary or 1 endpoint: Causative finding defined as Pooled sequential 2-stage study 2010 retrospective chart review: secondary diagnosis of syncope probably contributing to syncope, OR 20625024 Part B prospective post-CME identifying a high risk subject for arrhythmic (141) cohort death Size: Part A 721; Part B 371 Results: 583 CT scans (53%); 14 (2.4% of pts; pooled 1092 because ordered) helped. 208 brain MRI (19%); 12 CME had no effect on test (5.8% of ordered) helped. 57 carotid ordering ultrasounds (0%); 0 (0% of ordered) helped. Sheldon, et al. Study type: “Inclusion criteria”: 1 endpoint: Limitations: 1982 Prospective observational Syncope or presyncope during head up EEG changes during syncopal episodes ● Laboratory study 9676166 tilt with isoproterenol provocation ● Unblinded (142) Size: n=18 pts Results: ● Small number of pts Exclusion criteria: ● No pts developed EEG abnormalities before None specified the onset of presyncope, Conclusions: ● During presyncope, theta wave slowing ● Presyncope and syncope are associated (8/14) and delta wave slowing (9/14), and with EEG abnormalities background suppression (1/14) were noted ● No single EEG pattern is pathognomonic During syncope, theta wave slowing (9/18) and of presyncope of syncope delta wave slowing (11/18), and background ● The transition from presyncope to suppression (6/18) were noted syncope is marked by abrupt EEG changes. ● Abrupt changes in the EEG rhythm occurred 54 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. within 15 s of the transition to syncope (14/18) Low PA, et al. Aims: Inclusion criteria: “1 endpoint”: Limitations: 2004 To estimate autonomic Known diabetes and willingness to Autonomic symptoms and test results ● Single region and demographic 15562211 symptoms and deficits using a complete general medical and (143) laboratory evaluation of neurological evaluations, and a full Results: autonomic function and a autonomic reflex laboratory evaluation ● OH in 8.4 and 7.4% of type 1 and type 2 Conclusions: validated self-report measure annually diabetes, respectively (using the criterion of 30 ● Autonomic symptoms and deficits are of autonomic symptoms in pts mmHg SBP) common in diabetes, but mild in severity and matched control pts from Exclusion criteria: ● OH in 22.9 and 16.2% of type 1 and type 2 ● The correlation between symptom scores the population None specified diabetes, respectively (using the criterion of 20 and deficits is overall weak in mild diabetic mmHg SBP). neuropathy, emphasizing the need to Study type: ● Autonomic neuropathy, defined using a separately evaluate autonomic symptoms Cross-sectional; population composite testing score, was present in 54% of and objective tests. based, observational type 1 and 73% of type 2 pts Size: n=231 pts with DM (type 1, n=83; type 2, n=148) and n=245 control pts Kim, et al. Aims: Inclusion criteria: “1 endpoint”: Limitations: 2009 To assesses the value of A diagnosis of transthyretin amyloid Autonomic and sensory test results ● Laboratory study 19618439 standard quantitative polyneuropathy ● Referral population (144) autonomic and sensation Results: ● Small number of pts tests in detecting, Exclusion criteria: ● Abnormal postganglionic sympathetic characterizing, and None specified sudomotor dysfunction was found in 74% quantitating the severity of ● The HRdb was abnormal in 25 (69%) Conclusions: transthyretin amyloid ● OH present in 13 pts (36%) ●This study provides a rationale for the use polyneuropathy ● Median SBP fall of 36 mmHg at 1 min (range of quantitative autonomic and sensory 32–80 mm Hg testing as standard, objective, and Study type: quantitative measures for assessing the Retrospective, observational severity of TTR-A-PN Size: n=36 pts Iodice V, et al. Aim: Inclusion criteria: 1 endpoint: Limitations: 2012 To evaluate the autonomic Autopsy confirmed cases of MSA who Autonomic test results, clinical features None 22228725 characterization of MSA in had undergone formal autonomic (145) autopsy confirmed cases testing, including adrenergic, sudomotor Results: Conclusions: and cardiovagal functions and ● OH was present in 21 pts and symptomatic in Severe and progressive generalized Study type: Thermoregulatory Sweat Test 19 pts autonomic failure with severe adrenergic 55 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Retrospective, observational, ● Norepinephrine normal supine and sudomotor failure combined with the autopsy study in human pts Exclusion criteria: (203.6±112.7pg/ml). Orthostatic increment of clinical phenotype is highly predictive of None listed. was reduced (33.5±23.2%) MSA. Size: n=29 pts ● Severe generalized autonomic failure in most pts ● 20/22 had anhidrosis and 18 had thermoregulatory sweat test % anhidrosis >30% Thaisetthawatkul P, et Aim: Inclusion criteria: 1 endpoint: Limitations: al. To assess autonomic function Clinically probable dementia with Lewy Autonomic test results, clinical features Referral bias 2004 in pts with dementia with bodies and MSA pts and clinically Clinical diagnoses 15159482 Lewy bodies definite PD pts Results: Autonomic testing in demented pts (146) ● OH present in 10/20 dementia with Lewy Study type: Exclusion criteria: bodies, 17/20 MSA, and 1/20 PD pts Conclusions: Retrospective, observational Coexistent conditions, such as diabetes, ● Autonomic dysfunction is frequent in study in human pts that account for the symptoms of ● Most common abnormal TST pattern in dementia with Lewy bodies and the severity dysautonomia. dementia with Lewy bodies was distal pattern, is intermediate between that of multiple Size: n=20 DLB pts, 20 age- found in 54% of pts; while in MSA the most system atrophy and Parkinson disease. matched MSA and PD pts common pattern was global pattern, found in 41% of pts Thieben MJ, et al. 2007 Aim: Inclusion criteria: 1 endpoint: Limitations: 17352367 To evaluate the prevalence Baseline sinus rhythm with no evidence Autonomic test results, clinical features ● Referral population. (147) and pathogenetic of arrhythmia or cardiac disease, ● Laboratory study mechanisms of POTS sustained heart rate increment of 30 Results: beats/min or greater in response to 10 ● Mean orthostatic heart rate increment was 44 Conclusions: Study type: mins of head-up tilt, and symptoms of beats/min. ● Findings suggest a neuropathic basis for Observational, retrospective, orthostatic intolerance ● 50% of pts had sudomotor abnormalities at least half the cases of POTS mechanistic Symptoms present for more than 3 mo. (apparent on both the quantitative sudomotor axon reflex test and TST), Size: n=152 pts Exclusion criteria: ● 34.9% had significant adrenergic impairment (1) OH defined as a decline of 30 mm Hg or more in SBP or 20 mm Hg or more in mean BP within 3 mins of standing or HUTT; (2) pregnancy or lactation; (3) presence of another cause of autonomic failure 56 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Gibbons C, et al. 2013 Aim: Inclusion criteria: 1 endpoint: Limitations: 24386408 To define the neuropathology, POTS was defined as an increase in Autonomic test results, clinical features, nerve ● Referral population. (148) clinical phenotype, autonomic heart rate of >30 beats per min upon density from skin biopsy ● Laboratory study physiology and differentiating standing with symptoms of orthostatic features in individuals with intolerance, without any known medical Results: Conclusions: neuropathic and non- condition or medication causing the ● Pts with neuropathic POTS and had ● POTS subtypes may be distinguished neuropathic POTS. tachycardia significantly lower resting and tilted heart rates; using small fiber and autonomic structural reduced parasympathetic function; and lower and functional criteria. Study type: Exclusion criteria: phase 4 Valsalva maneuver overshoot Observational, mechanistic DM, impaired glucose tolerance, vitamin compared with those with non-neuropathic deficiencies, heavily metal toxicity, POTS Size: n=24 pts and 10 thyroid disorders, pheochromocytoma, controls hypoadrenalism, anxiety, cardiac disease, volume depletion, drug abuse and medication side effect Martinez-Fernandez, et Study type: Inclusion criteria: 1 endpoint: Syncope is common in pts undergoing al. Prospective Registry Symptomatic pts with TIA or non- Occurrence of CSR and/or syncope during CAA and can be misdiagnosed as frontal 2008 invalidating stroke, asymptomatic pts. internal CAA seizures, cardio-inhibitory response most 17974603 Size: n=359 pts with 85% stenosis, TCD detected frequent mechanism of syncope. (149) microemboli/ exhausted CVR or silent Results: Limitations: Beat to beat analysis of BP lesions CSR and syncope occurred in 62.7 % and was not performed. 18.6% of pts. EEG changes more prominent in Exclusion criteria: pts. with cardio-inhibitory syncope, N/A Syncope is more frequent in cardio-inhibitory CSR (p<0.001), Risk of syncope during CAA in pts with CSR (OR: 4.2; 95% CI:1.9–9.1) Risk of syncope in pts. with cardio-inhibitory CSR and vasodepressor/mixed CSR (OR: 6.9; 95% CI: 3.2–15.0 and OR: 1.4; 95% CI: 0.6–3.7) respectively. Gibbons, et al. Aims: To define the long-term “Inclusion criteria”: OH during a 60° 1 endpoint: OH, delayed OH and clinical Limitations: 2015 outcome of delayed OH HUTT performed for 45 mins outcome including mortality ● Laboratory study 26400576 ● Referral population (132) Study type: Prospective, Exclusion criteria: None specified Results: longitudinal follow up, ● 54% of individuals with delayed OH Conclusions: observational, mechanistic progressed to OH. ● Delayed OH frequently progresses to OH ● 31% with delayed OH developed an α- ● Delayed OH frequently progresses to an Size: n=108 pts with OH, 75 synucleinopathy alpha-synucleinopathy (multiple system 57 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. OR or RR. Inc. et al.67.013) and shocks for (151) Exclusion criteria: Prior sustained ICD interventions in f/u of 58 mo. et al.001). and Heart Rhythm Society. Study type: Retrospective Inclusion criteria: ARVD/C pts 1 endpoint: Appropriate ICD interventions Syncope was not a predictor of appropriate 2011 receiving ICDs ICD intervention 21939834 Size: n=84 pts Results: Appropriate ICD therapy in 40 (48%) (152) Exclusion criteria: Prior sustained in f/u of 4. with baseline OH was 64% and Lewy bodies) in controls was 9%. 95% CI: 20823389 Size: n=106 pts Results: Of 106 pts 25 (24%) had appropriate 1. Bhonsale A. Syncope independently predicted for an 2010 receiving ICDs appropriate ICD shock (HR: 2.39–5.81) (150) Size: n=132 pts Exclusion criteria: ARVC with only ICD intervention in FU of 39 mo. 95% 14638546 Results: of 132 pts. American Heart Association.7 y. et al..5 for 2003 Retrospective treated with ICD appropriate ICD interventions (p=0. p=0. Study type: Retrospective Inclusion criteria: Diagnosed with 1 endpoint: SCD. IDCM. Study type: Inclusion criteria: ARVC pts 1 endpoint: ICD treated arrhythmia Unexplained syncope had an OR of 7. Comment(s) Year Published & 95% CI) Corrado D.005). Corrado D.94. presyncope and 2013 ARVD/C appropriate ICD intervention palpitation) predicted for ventricular 23671136 Size: n=215 pts arrhythmias (p<0.63. dementia with controls OH was 29%. et al. Of 21 pts with minor criteria. Observational Studies. Nonrandomized Trials. Of 23 pts presenting with syncope VT or VF 10 (25%) had appropriate ICD interventions Bhonsale A.84–1. Study type: Prospective Inclusion criteria: ARVD/C 1 endpoint: Sustained ventricular arrhythmias Syncope was not a predictor of VA.83 to 4. 64 (48%) had appropriate CI: 0. Uhl’s anomaly including 5 with VFL/VF. VT or VF with syncope had a 9%/y incidence of p=0. appropriate ICD intervention. Study Size (P values. 95% CI: 1. syncope 8 (38%) had appropriate ICD therapy myocarditis.and sex-matched ● 10 y mortality rate in individuals with delayed atrophy. age. the primary endpoint was met in 30 (73%). et al. (153) Exclusion criteria: None Results: 86 (40%) had primary endpoint in mean f/u of 7 y.16. . Symptomatic pts (syncope. Link MS. 2014 observational 58 © 2017 by the American College of Cardiology Foundation. OH Data Supplement 17. Study type: Retrospective Inclusion criteria: ARVC pts 1 endpoint: Appropriate ICD interventions. ● Delayed OH has a high associated ● 10 y mortality of individuals who progressed mortality particularly when it progresses to to OH was 50%. Patient Population Primary Endpoint and Results Summary/Conclusion Author.2. Study Type/Design.07.4) Study Acronym. Parkinson’s disease. idiopathic RV VT. sustained arrhythmia. Of 41 pts with syncope. Pts presenting VF/VFL (HR: 3. and/or Registries of ARVCD – (Section 4. Patient Population Primary Endpoint and Results Summary/ Conclusion Author. and Heart Rhythm Society. All pts had either a decrease (n-=4) or complete elimination (n=5) during follow up (19. et al. 16876741 Size: n=8 pts Catheter ablation is only partially (157) Results: All pts had a reduced LVEF except for 1 pts (Mean successful. 2 pts had SCD and an additional 4 recurrent VT. Areas of low-voltage scar were present in the RV in all 8 pts.25011714 Exclusion criteria: Sarcoid cardiac Results: 48 pts with VA. et al. Study type: Retrospective Inclusion criteria: Cardiac 1 endpoint: To define the clinical characteristics of pts with CS Sarcoidosis can be misdiagnosed as 2006 sarcoidosis with recurrent VT and the EP findings during EPS. American Heart Association.6 mo). (158) Results: In 9 out of 21 pts with VT/VF recurrence post-ICD implant. idiopathic VT or ARVD. 34% ± 15%) and had failed previous anti-arrhythmic drug therapy. Of 28 pts with (154) Size: n=137 pts. 5 out of 8 pts eventually required cardiac transplantation.2. Year Study Size Comment(s) Winters SL. The most frequent VT circuit was reentry in the per- tricuspid area. Despite anti-arrhythmic primary therapy in pts with sarcoidosis therapy. Koplan. Steroid ICD therapy is recommended as (156) with ECG abnormalities therapy did not prevent spontaneous VT.. Ablation was only partially helpful. 2009 radiofrequency ablation catheter ablation is effective in 19187909 Size: n=42 pts eliminating or reducing the VT burden. . Inc. 59 © 2017 by the American College of Cardiology Foundation. et al.4 pts and VT received an ICD and all 4 received appropriate therapy. Observational Studies. Jefic. Study type: Retrospective Inclusion criteria: CS 1 endpoint: To determine response to medical therapy and In pts with CS and refractory VT. Study type: Retrospective Inclusion criteria: 1 endpoint: Findings during EPS Poor response to ant-arrhythmic 1991 Documented (n=6) or highly drug therapy 1894867 Size: n=7 pts suspected (n=1) Sarcoidosis Results: Sustained VT was easily inducible in all pts. Study type: Consensus Inclusion criteria: None 1 endpoint: None In ARVC pts with syncope an ICD should be 2015 statement considered 26216213 Exclusion criteria: None Results: None (155) Size: None Data Supplement 18. EPS revealed evidence of scar-related reentry with multiple morphologies. Nonrandomized Trials. drug therapy was ineffective requiring radiofrequency ablation.5) Study Acronym Study Type/Design*. and/or Registries of Sarcoid Heart Disease – (Section 4. et al. 108 with ICDs disease syncope 14 (50%) met primary endpoint Corrado D.8 ± 19. Chapelon-Abric C. and deterioration in 6% of cases. Study type: Retrospective Inclusion criteria: CS and 1 endpoint: Mechanism and outcome of VT associated with While most VT is due to reentry. 2004 Size: n=41 pts Results: Cardiac signs were clinical in 63% of cases and 15525844 electrical in 22%. 87% of pts showed improvement on immunosuppressive therapy and 54% were cured from a clinical and laboratory point of view. women. cardiac transplantation. 7 (39%) of 18 pts with CS or giant cell myocarditis vs. VF. 1 mo followed by tapering by 5mg every 2 to 4 wk until reaching the maintenance dose of 5–10 mg/d. ICD therapy is effective. respectively. Kandolin R. Yodogawa K. et al. The inducibility rate immunosuppressive therapy. . Steroid therapy was reported to result in improvement in 54%. American Heart Association. 1 of the 54 pts in whom AV block remained idiopathic. 2004 sustained monomorphic VT cardiac sarcoidosis inducibility depends on the disease 15119697 Size: n=8 pts state including response to (159) Results: Most VT is due to reentry. immunosuppressive therapy. but 60 © 2017 by the American College of Cardiology Foundation. et al. 89%) were major adverse events. or treated sustained VT (p<0. Study type: Retrospective Inclusion criteria: 1 endpoint: To determine the prevalence of CS and giant cell CS and giant cell myocarditis 2011 study Unexplained AV block myocarditis in young and middle-aged adults undergoing account for >25% of young and 21427276 pacemaker implantation for AV block middle-aged adults presenting with AV (161) Size: n=72 pts block. et al. Study type: Retrospective Inclusion criteria: CS and 1 endpoint: Efficacy of corticosteroid therapy in the treatment Corticosteroid therapy may be 2011 VA of VA effective for VA in the early stage.. Inc. Hiramitsu S. This dose was continued for one-half of the cases. and Heart Rhythm Society. et al. et Study type: Retrospective Inclusion criteria: CS 1 endpoint: Clinical characteristics and response to therapy Most pts with CS respond to al. The majority (16/18. Over an average of 48 mo of follow-up. experienced either cardiac death. depends on the presence or absence of an active phase.001). Study type: Questionnaire Inclusion criteria: CS 1 endpoint: Steroid dose used and pts outcome There is a fairly uniform use of 2005 survey treated with steroid therapy steroid therapy in the management of 16315784 Results: The most common initial steroid dose used was 30 CS with clinical improvement in over (160) Size: n=49 pts mg/day or 60 mg on alternate days. Results: CS and giant cell myocarditis were found in 14 (19%) These pts are at high risk of having and 4 (6%) pts. (162) During an average follow up of 58 m. no change in 40%.Furushima. 69–16. 17. 22812589 Size: n=112 pts prevention of sudden death Results: Over a mean follow up period of 29.1y vs. there were no significant differences in these parameters.0 y.52. VT storms and inappropriate included left or right ventricular therapies occurred in 14. dysfunction. Betensky BP. heart block were associated with appropriate ICD therapy. Schuller JL.2 mo. American Heart Association. 36. p=0.43–17.2 ± 4. 1. Longer ICD follow-up (4.3% of pts. In the advanced LV dysfunction pts.5). et al.2% pts 61 © 2017 by the American College of Cardiology Foundation.86–10. et al.1% of pts Adjusted predictors for ICD therapies (164) received appropriate therapies. and complete observed in 37.8% (15% per y) and 13. . depressed left ventricular EF (35.001). (166) Results: Over a mean follow-up of 4. 22338670 Size: n=45 pts prevention of sudden death predictors of appropriate therapy (165) Longer follow-up. The less advanced LV dysfunction group showed a significantly higher prevalence of gallium-67 uptake compared with the advanced LV dysfunction group (LVEF <35 %.2 % and 11.1).9% ± 15.21496164 Size: n=31 pts is less effective in the late stage. left ventricular Results: Appropriate and inappropriate ICD therapies were systolic dysfunction. p=0. respectively.9%.048) and in the prevalence of NSVT (from 41 to 6%.5% ± 15. (163) Results: Overall.0 y.2 ± 4. Kron J. and complete heart block (47.73.039). in pts with LVEF ≥ 35% (n=17).5 ± 3.. Study type: Retrospective Inclusion criteria: CS and 1 endpoint: ICD therapy in pts with CS Almost one-third of pts with CS and 2012 ICD for primary or secondary ICD receive appropriate therapies. 50. and Heart Rhythm Society.33 95% CI: 1.5% vs. p=0. p=0. there was a significant reduction in the number of PVCs (from 1820 ± 2969 to 742 ± 1425. right ventricular dysfunction (OR: 6.6% of pts respectively. Study type: Retrospective Inclusion criteria: 1 endpoint: To evaluate the efficacy and safety of ICD therapy Almost a third of pts with CS and 2013 Consecutive pts with CS and in pts with CS ICD receive appropriate ICD therapy 23002195 Size: n=235 pts ICD over a mean follow-up of 4. et al. p=0. 32.002). 95% CI: 2. there were no significant differences in the number of PVCs and in the prevalence of NSVT before and after steroid therapy. Study type: Retrospective Inclusion criteria: CS and 1 endpoint: To determine the prevalence and incidence of The annual incidence rate for 2012 ICD for primary or secondary ventricular tachy-arrhythmias in pts with CS and to identify appropriate ICD therapy is 15%. and symptomatic HF (OR: 4. 95% CI: 2.5%. Covariates associated with appropriate ICD therapies included LVEF <55% (OR: 6.5y. n=14).8). However.5 ± 1.1% vs. Inc.048) were associated with appropriate ICD therapy. 1 ± 15.l of the pattern and Hx of SCD and syncope 16836701 cardiac events following criteria: 1) prospective Results: The overall rate was 10% over an average are good predictors of future cardiac (169) cohort studies of the natural history of of 32 mo. p<0.58–7.6%. therapies include a history of syncope. depressed LV function and ventricular Pts who received appropriate ICD therapies were more likely to pacing. Study type: Retrospective Inclusion criteria: Symptomatic and 1 endpoint: Prevalence of fragmented QRS and its Fragmented QRS appears to be a 2008 asymptomatic BS prognostic value marker for spontaneous VF and 18838563 Size: n=115 pts syncope (168) Exclusion criteria: N/A Results: Fragmented QRS was more prevalent in pts with VF (85%) and syncope (50%) when compared to asymptomatic pts (34%). 22.0330). and Heart Rhythm Society.0044).5%. p=0. OR or RR. . ventricular pacing on baseline ECG (16. Study type: Meta-analysis Inclusion criteria: Studies were 1 endpoint: SCD. p=0. 95% CI: 2.13–4.. spontaneous Type I ECG 2006 assessing predictors of included if they m. 36. p≤0. Study Type/Design. 95% CI: data on cardiac events was provided 1.0001) compared with those who did not receive appropriate ICD therapies. Predictors of adverse events included events Size: n=1.8±1.3% received Predictors of appropriate ICD inappropriate shocks.1%. Study type: Retrospective Inclusion criteria: Evidence 1 endpoint: To assess the role of programmed electrical Programmed electrical stimulation 2011 of CS but without symptoms stimulation study in risk assessment in pts with sarcoidosis may help identify pts with CS who are 21193539 Size: n=76 pts at risk of having ventricular (167) Results: 11% of pts were inducible and received an ICD (LVEF arrhythmias.7%.3. et al.0002). 59.8 vs.7 vs. 24. Mehta D. 55. syncope and ICD shock Male sex. p=0. Comment(s) Year Published & 95% CI) Morita H.8 ± 14. et al. 2) Syncope and SCD (RR: 3.2% vs. Patient Population Primary Endpoint and Results Summary/Conclusion Author.1 vs. and a secondary prevention indication (60. Gehi. 2. lower LVEF (38. have a history of syncope (40. Inc. be male (73.2 vs. received an appropriate ICD therapy and 24. Over a median follow-up of 5 y.24.05).47. 3) primary Men compared with women (RR: 3. and/or Registries of Brugada Syndrome – (4.1) Study Acronym.545 pts pts with Brugada-type ECG. compared with 1 death in the negative group (p<0.5%. et al. 48. Observational Studies.93) studies included >10 pts. and 62 © 2017 by the American College of Cardiology Foundation. 6 of 8 pts in the group with inducible VA had ventricular arrhythmia or died.0001).5%.4±4.0001). Data Supplement 19.63). Nonrandomized Trials. Study Size (P values. p<0.5 vs. et al. American Heart Association. ventricular (172) arrest were 14 arrhythmic events. conduction parameters and QTc increased more in women in response to Na channel blocker. whereas the 2012 Size: n=308 pts presence of a spontaneous type I 22192666 Exclusion criteria: Hx of cardiac Results: During a median follow up of 34 mo. ECG (RR: 4. was not different between pts with or without a family Hx of SD of a first-degree relative. Study type: Retrospective Inclusion criteria: Symptomatic and 1 endpoint: Prevalence of fragmented QRS and its Fragmented QRS appears to be a 2008 asymptomatic BS prognostic value marker for spontaneous VF and 18838563 Size: n=115 pts syncope (168) Exclusion criteria: N/A Results: Fragmented QRS was more prevalent in pts with VF (85%) and syncope (50%) when compared to asymptomatic pts (34%).001). Study type: Prospective Inclusion criteria: Pts with BS 1 endpoint: To assess phenotype and prognosis Men with BS present with a greater 2008 follow up study differences between men and women risk clinical profile than women and 19007594 have a worse prognosis. Conversely. American Heart Association. Morita H. 95% CI: 2. 14%) and aborted SCD (6% vs. effective refractory period <200 ms.25–9. PRELUDE Registry. inducible pts. drug-induced type 1 ECG without inducible VT/VF identify high-risk pts.. (170) Size: n=384 pts Exclusion criteria: N/A Results: Men had greater rates of spontaneous Conduction disturbances may be a Type 1 ECG. Study type: Registry Inclusion criteria: Type 1 ECG 1 endpoint: Prevalence of family history of SD and Family Hx of SD is not predictive for 2011 pattern its prognostic value future arrhythmic events even if 21727093 Size: n=280 consecutive considering only SD in first-degree (171) pts Exclusion criteria: N/A Results: SD was present in 69 out of 157 families relatives or SD in first-degree relatives (43%). During follow-up VF or SD-free survival rate at a young age. et al. . syncope (18% vs. et al. between pts with or without a family Hx of multiple SD of a first-degree relative at any age and between pts with or without a family Hx of SD in first-degree relatives’ ≤35 y of age. 9/14 occurred in non. and 4) stated clearly that structural Spontaneous compared with drug-induced Type I heart disease was ruled out. Study type: Registry Inclusion criteria: Spontaneous or 1 endpoint: Arrhythmic events in pts with and VT/VF inducibility is unable to Priori SG.58) Exclusion criteria: If not all inclusion criteria are met Benito B. ST elevation and VF inducibility marker of risk in the female population (p<0.65. et al. Hx of syncope. Inc. 1%). and QRS fragmentation seem useful to Arrhythmia inducibility was not a predictor of identify candidates for primary 63 © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society. there ECG. Sarkozy. et al. 88 with syncope pts died and 18 pts (8%) had appropriate device p=0. and positive Results: During FU (4–160 mo). 4%.9%. The HR for asymptomatic vs. (174) Size: n=47 pts family Hx (n=26) who underwent ICD Results: During a median follow up of 47. All were male (3 documented arrhythmia suggesting a syncope.6% with an annual complication rate of 8. therapy. syncope pts was 0. Syncope and spontaneous Type I ECG (HR: 4. Exclusion criteria: N/A recurrent syncope with no documented arrhythmia. Sacher F.5%). inducibility of VT/VF and 2010 France.43 (CI: 0. Netherlands.7%). 3 + family Hx and 1 had both). Study type: Retrospective Inclusion criteria: Spontaneous or 1 endpoint: Appropriate and inappropriate ICD The authors could not confirm that 2007 single center study drug induced Type 1 ECG pattern shocks. no in asymptomatic pts (12% vs. prevention ICD implants.5%) had appropriate device therapy. Italy. fragmented QRS (HR: 4. 7 pts 4 pts had recurrent syncope with no implant for primary prevention (15%) had appropriate shocks.94) were significant predictors of arrhythmias.20) and VERP<200ms (HR:3. 4 pts had reflex mediated mechanism. Study type: Multicenter Inclusion criteria: BS with ICD 1 endpoint: Appropriate shocks and ICD The annual rate of appropriate ICD 2006 outcome report implant complications including inappropriate shocks therapy is low. None of the pts an arrhythmic event. 1.91). et al. pts with aborted SCD. American Heart Association.24–0. Study type: Retrospective Inclusion criteria: BS pts with ICD 1 endpoint: Efficacy and complications of ICD Appropriate device therapy was 2008 multicenter study (12 Israeli implants: Cardiac arrest (18. et al. Appropriate ICD shocks 17116772 are more frequent in symptomatic than (173) Size: n=220 pts including Exclusion criteria: N/A Results: During a mean follow-up of 38±27 mo. Inc.5 mo.9% in pts with syncope. Exclusion criteria: N/A FINGER Brugada Study type: Registry from Inclusion criteria: Pts with 1 endpoint: SCD Low event rate even in pts with Syndrome Registry 11 tertiary centers in 4 spontaneous or drug-induced Type 1 syncope Probst V. 5/11 pts with CA syncope and/or inducible VF suffered Size: n=59 pts family Hx of SD (0.6%). The annual event rate was 2.74). et al. and the presence of SCN5A mutation were 64 © 2017 by the American College of Cardiology Foundation.7% in Family Hx. European countries: ECG pattern Results: The cardiac event rate per y was 7. et al. and Heart Rhythm Society. Spontaneous Type 1 ECG pattern and NSVT were more frequent among pts with appropriate shocks Rosso R. without prior CA had appropriate device therapy. 7% had syncope recurrence without any documented arrhythmia. 10% received an appropriate shock during a 19. In pts with syncope. Not all syncope in pts with BS is arrhythmic.5–59 mo FU period. therapy limited to CA survivors while none of 18669142 centers) syncope (52.05). . Sarkozy. arrhythmic events. inducible VF in the other pts including those with (175) asymptomatic (23. syncope was an independent predictor 17251258 BrS with syncope (n=26) and/or + of appropriate ICD shocks.. Electrical storm occurred in 4 pts (2.3 mo. at risk for arrhythmic events and could Appropriate ICD shocks occurred in 28 pts (15. familial Size: n=1029 consecutive Hx of SCD.7%) pts had syncope with 53 (50. Appropriate and inappropriate shocks occurred in 10. et al.5%) died. American Heart Association. Multivariate analysis revealed symptoms as a risk factor for predicting cardiac events. 8 pts (4.4%) having a family Hx of SD. Study type: Retrospective Inclusion criteria: BS with age 35 y 1 endpoint: Cardiac events (VF or SCD) The presence of SCD or syncope is 2013 analysis of the Japan of age or younger a risk factor for cardiac events in pts 23702150 Idiopathic Ventricular Results: During a mean follow-up period of with BS (178) Fibrillation registry Exclusion criteria: N/A 43±27mo. be helpful in investigating syncope not and 33 pts (18. et al.7%) had inappropriate shocks. 2 of Size: n=69 pts 17 cases in the Syncope (11.9%). Spontaneous Type 1 pattern was present in 18.1% of cases. Sacher F. cardiac events (VF and/or SCD) developed in 8 cases. aborted SCD and VA inducibility on EP studies were independent predictors of appropriate shock occurrence.8 ± long-term follow-up.8%) and 1 of 40 cases in the asymptomatic group (2. 105 (59. et al. Study type: Prospective Inclusion criteria: 1 endpoint: Cardiac events including syncope VA occurred only in pts with syncope 65 © 2017 by the American College of Cardiology Foundation. not predictive of arrhythmic events. .7%).5% in asymptomatic pts. In multivariate Cox regression analysis.1%. treating potentially 25744005 ECG pattern who underwent ICD lethal arrhythmias in 17% of pts during (177) Size: n=176 pts implantation. 28 p pts (15. related to VAs. whereas sex.5% and 17.9%) experienced device-related complications. spontaneous sustained VAs occurred in 30 by EPS may identify asymptomatic pts Exclusion criteria: N/A pts (17%). (176) (FINGER) mimic BS Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events. inducibility of VT during EPS. Results: During a mean follow-up period of 83. and Heart Rhythm Society. The VF group had a worse prognosis for cardiac events than the Syncope and Asymptomatic group. Inc.3%). Study type: Retrospective Inclusion criteria: Pts with 1 endpoint: Appropriate and inappropriate shocks ICD therapy was an effective 2015 single center spontaneous or drug-induced Type 1 and device complications strategy in BS. with 5 of 12 cases in the VF (41..20100972 Germany Registry Exclusion criteria: Diseases that 0. Risk stratification 57. and the pts presence of an SCN5A mutation were not predictive of arrhythmic events. Conte. Hiraoka.5%). Gaita. short refractory periods. In Group 3. 4 had recurrent syncope. (180) Size: n=15 articles described unique Exclusion criteria: N/A cases of SQTS Results: A total of 61 cases were identified with a mean QTc value of 307 ms (range 248–381 ms). Study Size (P values. Nonrandomized Trials. familial sudden death. and 6 had appropriate ICD therapy. and/or Registries of Short-QT Pattern and Syncope – (Section 4. No sudden death (179) Size: n=203 pts Of 203 pts. 9 pts remained asymptomatic and 7 had recurrent neurocardiogenic syncope. syncope or with syncope of doubtful 17 pts with non-arrhythmic syncope (Group 2) and 17 origin. American Heart Association. et al. whereas 2 points or less makes a diagnosis of SQTS low probability. et al. 66 © 2017 by the American College of Cardiology Foundation. 2012 registry Pts diagnosed with BS between 1999 suspected to be arrhythmic in origin at 22504046 and 2010 Results: a rate of 5. cases of SQTS in English to facilitate the diagnostic evaluation of suspected recognition of this condition and provoke 21310316 cases of SQTS screening of at-risk family members. Data Supplement 20. After mean follow-up of 65 ± 42 mo. & 95% CI) Comment(s) Author.. family and genotype. OR or RR. Year Published Gollob. During EPS (n=4). In Group 2.5% per y. 14 pts in Group 1 remained asymptomatic. (181) with idiopathic short QT interval SD. all pts exhibited a QT and inducible VF. clinical Hx. Inc.3. Study type: Retrospective review of Inclusion criteria: Reported 1 endpoint: The creation of formal diagnostic criteria Diagnostic criteria may lead to a greater 2011 reported cases of SQTS. . 57 (28%) experienced syncope. Short QT syndrome criteria were developed and consisted of 4 components including ECG. with syncope of doubtful origin (Group 3). occurred in pts with nonarrhythmic Exclusion criteria: N/A 23 pts with suspected arrhythmic syncope (Group 1). Study type: Retrospective Inclusion criteria: Short QT 1 endpoint: Comprehensive EP evaluation The short QT syndrome is characterized by 2003 interval with a Hx of syncope. and Heart Rhythm Society. Pts with a score of 3 points are considered to have an intermediate probability of having SQTS. 7 remained asymptomatic and 9 had recurrent syncope. 12925462 Size: n=6 pts belonging to 2 families palpitations or resuscitated Results: At baseline ECG. An overall score of 4 points or greater indicates a high-probability diagnosis of SQTS. Observational Studies. interval ≤280 ms (QTc ≤300 ms). Patient Population Primary Endpoint and Results Summary/Conclusion Acronym.2) Study Study Type/Design. Funada A. Brugada R.1%. . and young adults 14676148 QT syndrome and a high incidence of SCD Results: In 2/3 families. selected middle-aged pts indicate an increased risk for all-cause or CV 2007 17679619 Size: n=10. (182) ventricular arrhythmias and SCD. and Heart Rhythm Society. The prevalence of SQTS (<340ms) was 0. for 36 of the 60 pts with the lowest 1/2 centile of QTc values. Gallagher. normal range does not imply a significant risk (183) reasons ● Information about subsequent survival was available of SD. the prevalence of SQTS was (185) 1.63% in females (2 SD below the Exclusion criteria: Irregular mean). the authors identified 2 caused by mutations in KCNH2. Study type: Retrospective Inclusion criteria: Pts who 1 endpoint: Prevalence of SQTS (<300ms) SQTS is very rare 2008 had an ECG between 18543308 Size: n=10. conduction symptomatic. leading to heterogeneous abbreviation of action potential duration and refractoriness.5 y subsequent to the ECG that demonstrated the short QT interval.9 ±4. et al. disturbances and wide QRS Kobza. different missense mutations resulting in the same Exclusion criteria: N/A amino acid change (N588K) in the S5-P loop region of the cardiac IKr channel HERG (KCNH2). et Study type: Retrospective Inclusion criteria: Randomly 1 endpoint: All cause and CV mortality A short QT interval does not appear to al. Only 3 pts had QTc<300ms. Anttonen O. children.. Inc. American Heart Association. the population of young male adults 67 © 2017 by the American College of Cardiology Foundation.984 pts February 2003 and May 2004 Results: In 10.4% and (<320ms) 0. et al. ventricular arrhythmias or SD in infants.822 randomly selected and followed for mortality (184) and followed up for 29±10 y 29±10 y. Study type: Retrospective Inclusion criteria: Swiss 1 endpoint: Prevalence of LQTS and SQTS Short QT syndrome is a very rare entity in 2009 male citizen 18–19 y of age.984 pts. There were no SD or Exclusion criteria: N/A aborted CA or documented VA during follow up. and reduce the affinity of the channels to IKr blockers. interval and history of SQTS and biophysical mechanism responsible for 2004 Size: 3 families with hereditary short.25% in males and 1. short atrial and ventricular refractory periods were Exclusion criteria: N/A documented in all and increased ventricular vulnerability to fibrillation in 3 of 4 pts. et al. None were rhythms. The mutations dramatically increase IKr.012 pts examination for occupational Results: The shortest QTc encountered was 335 ms.822 pts enrolled in a population study Results: 10. Study type: Retrospective Inclusion criteria: Pts who 1 endpoint: Survival QTc ≤ 330 ms is extremely rare 2006 underwent routine medical QT interval in the lowest 1/2 centile of the 16996877 Size: n=12. Exclusion criteria: N/A ● None of these pts died during the 7. et Study type: Prospective Inclusion criteria: Short QT 1 endpoint: Characterization of the genetic basis for The authors demonstrated a novel genetic al. .free. from the European Short QT registry QTc≤360ms with cardiac Hydroquinidine is effective in preventing 2011 arrest (n=18) or syncope Results: The event rate was 3. 68 © 2017 by the American College of Cardiology Foundation. (n=27) ● Of the 8 pts with syncope.19303371 Size: n=41.767 ECGs Results: The prevalence of SQTS (<320ms) was (186) Exclusion criteria: Artifact. QTc was an independent predictor in LQT1 and LQT2 whereas sex was independent predictor in LQT3. Inc.1/y to present. Study Size (P values.3. et al. 11 had an ICD members of affected pts with 1 receiving appropriate shocks during follow-up.3% per y and was arrhythmic events 21798421 Size: n=53 pts (n=8). Italy (189) Size: n=674 pts Results: Exclusion criteria: N/A The incidence of first cardiac event was 30% (LQT1). 0. 0. & 95% CI) Comment(s) Year Published Ouriel K. During a mean follow up of 1. 46% (LQT2) and 42% (LQT3).3) Study Acronym.1/y(p<0. Exclusion criteria: N/A Data Supplement 21. et al. et Study type: Retrospective review Inclusion criteria: 1 endpoint: Prevalence of arrhythmic events Symptomatic pts are at high risk al. 9/10 developed Horner’s be considered when symptoms are refractory and (188) Size: n=10 pts syndrome. Giustetto C. Study type: Inclusion criteria: LQTS 1 endpoint: Cardiac events LCS is associated with significant clinical benefits in 1995 Retrospective refractory (n=9) or intolerant (n=1) pts with long QT syndrome and the procedure should 8574528 to BB therapy Results: No death. American Heart Association. and Heart Rhythm Society. or when contraindications to β-blockers are Exclusion criteria: N/A decreased from a mean of 7. The frequency of symptoms malignant.3 y. (187) QTc≤340ms and Family ● Of the 12 pts with a previous CA. Study type: Inclusion criteria: 193 1 endpoint: Cumulative probability of cardiac The probability of having a cardiac event depends on 2003 Retrospective consecutively genotyped families event defined as syncope. . Observational Studies. The youngest pts died suddenly 10 mo after surgery. Patient Population Primary Endpoint and Results Summary/Conclusion Author. All but 1 pts remained symptom. 4 received an ICD and only 1 received appropriate shock for VF. Priori SG. 12736279 with LQTS in Pavia. OR or RR. and/or Registries of Long-QT Syndrome – (Section 4. Study Type/Design. Nonrandomized Trials. Asymptomatic limited to pts who were not receiving Hydroquinidine.001).02% and none of the pts had a QTc<300ms pre-excitation and BBB. cardiac arrest or SD the genotype and sex. therapy. indications and Age<20 y. appropriate ICD ICD should not be the first line therapy in pts with a 20170817 syncope as a first symptom were therapy and SCD) single episode of syncope as they have the lowest risk (191) Size: n=1. Zareba W. Jons C et el. 19 12741701 syncope despite BB and 52 for Results: 1 death (1. The lowest risk was in pts with 1 syncopal Exclusion criteria: N/A episode before the start of BB therapy. Results: 91% had symptoms including 44% Absence of these risk factors indicates good Exclusion criteria: N/A with prior CA. and 161 without an ICD and 72 syncope despite BB Exclusion criteria: N/A Schwartz.2 y. QTc >500ms. American Heart Association. Study type: Outcome Inclusion criteria: 1 endpoint: Death during follow up ICD therapy saves lives 2003 data ICD group (n=125): 54 CA. Study type: Inclusion criteria: LQTS pts and 1 endpoint: To evaluate age and sex-related Data derived from a large registry (LQTS International 1998 Retrospective affected family members differences Registry) 9631873 (190) Size: n=479 probands Exclusion criteria: N/A Results: In LQT1. at least 1 shock was received by 28% of pts. and Heart Rhythm Society. No age-sex difference in event rate was detected in LQT2 and LQT3 carriers. Locati EH. prior CA and cardiac events 20837891 Registry follow up despite medical therapy were strong predictors of (193) Size: n=233 pts appropriate ICD therapy.6±3. . Inc.6 fold increase in risk. 125 with an ICD Non-ICD group (n=161): 89 CA follow up. et al. et al. 41% had not been on prior drug prognosis.059 pts drawn from the International LQTS ICD is likely to save lives in pts with syncope despite Registry Results: BB therapy. family members with was higher in males until puberty and higher in LQTS females during adulthood.. Study type: Inclusion criteria: LQTS pts with 1 endpoint: To identify risk factors for fatal Cohort limited to pts with syncope 2010 Retrospective QTc>450 ms presenting with arrhythmias (aborted CA. Predictors of appropriate ICD therapy 69 © 2017 by the American College of Cardiology Foundation. During 4. The same pattern was evident among LQT1 gene carriers. et al. male sex until puberty and female sex and n=1041 affected Among LQTS pts. Pts with syncope after BB or who were not treated with BB therapy had a 3.3%) over 3 y in 73 ICD pts (192) Size: n=286 pts with other reasons and 26 deaths (16%) in non-ICD pts over 8-y LQTS. Study type: Inclusion criteria: LQTS with an 1 endpoint: To determine the characteristics Cohort limited to pts with an ICD 2010 Retrospective ICD in the European LQTS of LQTS pts receiving an ICD. the risk of cardiac events during adulthood increase the risk of cardiac events. non- LQT3 genotype. 9 blocker failures. included age <20 y at implantation. The risk for CA/SD in compliant pts not taking QT-prolonging drugs was dramatically less compared with noncompliant pts on QT- prolonging drugs (OR: 0. Study type: Inclusion criteria: Genetically 1 endpoint: Report outcome Syncope was a predictor of appropriate therapy 2010 Retrospective confirmed LQTS including 51 pts (p=0. None of the 26 pts with CA before BB had CA/SD on BB. QTc >500ms. Vincent GM.3.. are responsible for almost all life-threatening “ beta- QT-prolonging drugs were used by 17 pts. 95% CI: 0. syncope. 70 © 2017 by the American College of Cardiology Foundation. American Heart Association. OR: 12. Horner JM.0. . Predictors included non-LQT1 and QTc predictors of future cardiac events >500ms and first occurrence <7 y of age.03. p=0. Study type: Inclusion criteria: Genotyped 1 endpoint: Cardiac events on BB therapy BB are extremely effective in long-QT syndrome type 2009 Retrospective long-QT1 treated with BB and 1 and should be administered at diagnosis and ideally 19118258 followed for a median of 10 y Results: Cardiac events occurred in 157 pts before the preteen years. TDP and negative family Hx.” of 17 (53%) had CA compared with 17 of 199 nonusers (8. No appropriate ICD therapy within 7 y in pts with none of these factors.5%. (196) Size: n=216 pts (73%) at a median age of 9 y. Study type: Inclusion criteria: Genotyped 1 endpoint: Incidence of cardiac events Response to BB depend on the genotype 2004 Retrospective LQTS pts treated with BB LQT1 pts are better responders when compared to 15367556 Results: Cardiac events occurred in 10%. 22 LQT2. et al. with CA in 26 BB noncompliance and use of QT-prolonging drug Exclusion criteria: N/A (12%). et al. LQT2 and QTc >500ms and first occurrence <7 y of age are LQT3. Inc.3 y.001). no deaths were (194) Size: n=459 pts who received an ICD from 2000 to (24%) of ICD recipients experienced an reported 2010 appropriate shock and none of the no-ICD group died. Predictors of appropriate therapy Exclusion criteria: N/A included secondary prevention indications. and 15 LQT3) Results: During an average FU of 7. et al.003– 0. 12 In 408 pts with no risk factors. 95% CI: 4. prior CA and cardiac events despite therapy. and Heart Rhythm Society. p<0. LQT2 and LQT3. QTc >500ms. Priori SG.1–35. (195) Size: n=335 pts Exclusion criteria: N/A 23% and 32% of pts with LQT1.05) 20816872 (14 LQT1.001).22. and Heart Rhythm Society. in addition to 2009 Retrospective prevention in 11 pts including 8 assisted thoracic surgery traditional LCSD. arrhythmia storms with an implanted defibrillator. BB therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events.001 for all) increase in the risk of subsequent fatal/near- fatal events independently of QTc duration.001). 15% of the symptomatic had breakthrough with the greatest risk among those taking Metoprolol.to 12-fold (p<0. Exclusion criteria: N/A Pts who experienced ≥ 1 episodes of syncope had a 6. LCSD should be considered in pts with recurrent and a post-LCSD QTc <500 ms predicted very syncope despite β-blockade and in pts who experience low risk.648 pts enrolled in registry before the 20 y Results: Multivariate analysis demonstrated episodes and fatal/near-fatal events regardless of QTc age. et al. et Study type: Inclusion criteria: 1 endpoint: To compare the efficacy of Not all BB are the same al. Schwartz P. decreased significantly as in the entire group. Among 74 pts with only syncope cardiac events including sudden cardiac death during Exclusion criteria: N/A before LCSD. Videoscopic denervation surgery. that QTc ≥ 500 ms was a significant predictor duration. of age at BB initiation None of the asymptomatic pts had cardiac events.. Study type: International Inclusion criteria: 1 endpoint: Recurrence of syncope after the Children and adolescents who present after an 2011 Long QT registry QTc ≥ 450 ms and/or documented first event episode of syncope should be considered to be at a 21329841 LQTS-causing mutation and high risk of the development of subsequent syncope (197) Size: n=1. Study type: Inclusion criteria: Secondary 1 endpoint: Outcome with LCSD using video. Liu JF. all types of cardiac events long-term follow-up.16). 46% remained high-risk LQTS pts when compared with pre-LCSD (199) Size: n=147 pts treated with BB remaining symptomatic. Collura. Retrospective LQT1 and LQT2 pts on BB therapy Propranolol. The mean yearly number of events. LCSD is not entirely effective in preventing (P<0. Chockalingam P. Metoprolol and LQT1/LQT2 Nadolol 23083782 Size: n=382 (101 Nadolol) (198) symptomatic) pts with Results: QTc shortening was significantly LQT1/LQT2 Exclusion criteria: Less than 1 y greater with Propranolol. American Heart Association. et al. offers a safe and effective treatment 19467503 with LQTS and primary prevention option for the personalized medicine required for pts 71 © 2017 by the American College of Cardiology Foundation. of a first syncope episode (HR: 2. symptomatic cardiac events per patient dropped by 91% However. Study type: Inclusion criteria: LQTS pts who 1 endpoint: Long-term efficacy of LCSD LCSD is associated with a significant reduction in the 2004 Retrospective underwent LCSD (99% incidence of aborted cardiac arrest and syncope in 15051644 symptomatic with 75% of those Results: Post-LCSD. Metoprolol and Nadolol in pts with Propranolol appears to be better than Metoprolol and 2012 (Proprnolol. et al. . Inc. there has been a marked reduction in cardiac events. are at high risk for subsequent cardiac events.(200) Size: n=20 pts including in 9 pts. Flecainide mono-therapy is an option 2016 Retrospective mutations in the RyR2 gene who refused therapy in pts with CPVT in pts with CPVT who are intolerant to 26416620 (n=1) or were intolerant to BB therapy (n=7) BB therapy.530 pts or nadolol). (202) Size: n=8 pts Results: Flecainide mono-therapy was better Exclusion criteria: N/A than. Inc. Observational Studies. GJ.5 mo (range 4–40 mo). metoprolol. or CA occurred in pts on flecainide mono-therapy during the follow-up period of 37.1 mo (range1. Patient Population Primary Endpoint and Results Summary/Conclusion Author. Study type: Inclusion criteria: Pts with LQTS 1 endpoint: Compare efficacy of different BB BB efficacy differed by genotype. Among pts who had a prior cardiac event while taking BB.40 (95%CI: group.004). 12 with LQTS. metoprolol. and Exclusion criteria: Prescribed BB but in LQT2. OR or RR.16 to 0. . The average length of available genotype negative LQTS Exclusion criteria: N/A follow-up was 16.5 mo).4) Study Acronym.6 ± 9. syncope. 0. Comment(s) Year Published & 95% CI) Padfield. American Heart Association. cardiac events was similar among the 4 BB Pts experiencing cardiac events during BB therapy (atenolol. and/or Registries of CPVT-Medical Therapy – (Section 4. Results: There were no perioperative with LQTS/CPVT. efficacy for recurrent events differed by drug (p=0. nadolol provided the only propranolol is the least effective drug in this high-risk after the age of 40 or have an ICD significant risk reduction (HR: 0. (201) Size: n=1. propranolol and nadolol). and Heart Rhythm Society. and 2 CPVT Among the 18 pts who underwent VATS-LCSD. Nonrandomized Trials. Results: In LQT1.. Nadolol was the 2014 Retrospective who were prescribed common BB only BB associated with a significant risk reduction in 25257637 (atenolol. BB mono- therapy in reducing exercise-induced arrhythmia.4–75. the average time from operation to dismissal was 2. Study Type/Design. Among those receiving LCSD as secondary prevention.98). 2 JLNS. 4 complications. the majority being next-day dismissals.3. or at least as effective as. Data Supplement 22. the risk reduction for first pts with LQT2.6 d (range 1–15 d). Study Size (P values. Study type: Inclusion criteria: CPVT secondary to 1 endpoint: Safety of flecainide as mono. propranolol. et al. No episodes of arrhythmic pre-syncope. et al. and propranolol was the least effective compared with the other BB. Abu-Zeitone A. 72 © 2017 by the American College of Cardiology Foundation. Study type: Inclusion criteria: Syncope due to 1 endpoint: Syncope recurrence and exercise First report of adrenergic-dependent 1995 Observational documented or suspected VA. 3 arrhythmias syncopal events and 2 sudden deaths occurred. sudden death occurred in 24% of the pts. and a family pharmacological therapies. PMVT (n=12) characterization heterogeneous disease manifesting 12093772 and catecholaminergic idiopathic VF (n=4) beyond pediatric age with a spectrum (204) Size: n=30 probands and Results: Genotype-phenotype analysis showed of polymorphic arrhythmias. Over a follow-up of ≈2 y. et al. 75% by catecholamine infusion. 18 of 39 pts treated with β-blockers had cardiac arrhythmias. et al. et al. All 39 clinically affected pts were treated with BB. Priori.Leenhardt. 50% of pts with the ICD received an appropriate shock to terminate ventricular tachyarrhythmias. Inc. . BB completely controlled CPVT in only 31% of cases. Calcium antagonists partially suppressed CPVT in 73 © 2017 by the American College of Cardiology Foundation. There was 100% inducibility of CPVT by Exclusion criteria: N/A exercise. and Heart Rhythm Society. Study type: Inclusion criteria: 1) Exercise or 1 endpoint: Questionnaire responses and ECG Pts with CPVT have a poor 2003 Questionnaires were catecholamine induced VA (>3 beats) with at characteristics prognosis. syncope in RyR2-CPVT (RR:4.8 (4. and none by programmed stimulation. antiadrenergic drugs provided only incomplete protection from recurrence of sustained VT and VF. however.9) y. polymorphic tachyarrhythmias disappeared. Sumitomo. induced VA ventricular tachy-arrhythmia in pts with 7867192 normal QT interval and no structural (203) Size: n=21 pts Exclusion criteria: N/A Results: On BB therapy. During a follow up of 6. Size: n=29 centers and 3) no evidence of long QT or Brugada. the pts’ symptoms and heart disease. but in 30% younger age than do pts with non-genotyped of pts an implantable defibrillator may CPVT and that male sex is a risk factor for be required. BB help suppress exercise induced During a mean follow-up period of 7 y. cardiac arrest (7%).2). Study type: Inclusion criteria: Exercise or emotion 1 endpoint: Clinical and genetic CPVT is a clinically and genetically 2002 Retrospective induced bidirectional VT (n=14). An ICD was recommended and implanted in12/18. American Heart Association. probably due to treatment interruption. Hx (14%).. BB do not always control 12482795 sent to major Japanese least 2 morphologies 2) absence of known symptoms thus the need for other (205) pediatric centers secondary causes including electrolyte Results: The initial CPVT manifestations were pharmacological and non- abnormalities and structural heart disease syncope (79%). 118 family members Exclusion criteria: N/A that pts with RyR2 CPVT have events at a BB reduce arrhythmias. 21) were independent predictors.80–16. 19398665 identification of a mutation in the RYR2 or CA. Inclusion criteria: CPVT pts 1 endpoint: Arrhythmic.33– 0. and Heart Rhythm Society. (208) cardiac Calsequestrin Results: Exercise tests comparing flecainide in 74 © 2017 by the American College of Cardiology Foundation. respectively. Study type: Multicenter Inclusion criteria: Exercise induced 1 endpoint: Incidence of cardiac events BB reduce the cardiac event rate in 2009 observational study polymorphic ventricular arrhythmias or (exertional or stress induced syncope.2% (95% CI: 16.89) were independent predictors.68) and younger age at diagnosis (HR: 0.6% (95% CI: 8.6–57.and 8 y arrhythmic event rates were 18. Estimated 4. non-fatal and fatal The variability in outcome with BB 2012 analysis including 11 events therapy is due to multiple factors 21893508 studies using BB and Exclusion criteria: N/A including the dose.3–28. et al.6– 4. Results: During a mean follow-up of 7. Absence of BB (HR: 5.9) and 37. Hayashi.4–23.17–26.9 y.3% (95% CI: 7. including 2 mutation carriers with normal exercise tests. respectively. including flecainide and Verapamil. 95% CI: 0. Exclusion criteria: >55 y of age cardiac events occurred in 27 pts (27%).7). 95% CI: 1. aborted both CPVT pts and affected families. The estimated 8 y event rate for fatal or near fatal events (ACA. autosomal dominant cases. respectively.54. van der Werf. Absence of BB HR: 5.7–11.2–9. et al. Study type: Meta. . American Heart Association.15) and Hx of aborted CA (HR: 13. SCD) was 13%. et al. The estimated 8 y event rate was 32% in the total population and 27% and 58% in the pts with and without BB. Fatal events occurred in 3.7% (95% CI: 3.54 per decade.4% (95% CI: 3.8) at 4 y and 6. appropriate ICD shocks or SCD) however. 95% CI: 2.48–68. compliance and (207) review of other therapies Results: Median FU was 20 mo 8 y. Study type: Chart Inclusion criteria: 1 endpoint: Reduction of VA during exercise Flecainide reduced exercise-induced 2011 review from 8 tertiary 1) Exercise induced PMVT or bidirectional VT testing VA in pts with CPVT not controlled by 21616285 referral centers 2) Mutation in the gene encoding RyR2 or conventional drug therapy.and 8 y near-fatal arrhythmic event rates were 7. Size: n=403 pts The estimated overall 4..01.3). 95% CI: 1.7) and 15. 88% of pts concomitant use of other drugs were given BB.48. Inc.6) at 8 y follow-up van der Werf.2% (95% CI: 1. they are not completely (206) Size: n=101 pts CASQ2 gene protective. Physiology study with no long-term 127 ± 27 min−1.. that verapamil can suppress 15720454 human pts premature ventricular complexes and (209) Exclusion criteria: N/A Results: Premature ventricular complexes non-sustained ventricular salvoes in Size: n=6 pts appeared later and at higher heart rate during CPVT caused by RyR2 mutations. Results: Presentation was CA in 33% and associated with adverse outcomes induced polymorphic or bidirectional VT of ≥ 4 syncope in 56%. et al. breakthrough 21315846 physical activity or acute emotion in arrhythmias occur and may be (211) Size: n=27 pts conjunction with exercise or adrenaline. et al.05). Study type: Inclusion criteria: Hx of sudden cardiac 1 endpoint: Long-term outcome and relation Despite BB therapy and selective 2011 Retrospective arrest or symptoms occurring in the context of between age and clinical presentation ICD implantation. verapamil compared to baseline (119 ± 21 vs. et al. Magnesium did not follow up inhibit the arrhythmias. American Heart Association.001). Size: n=33 pts addition to conventional therapy with Exclusion criteria: N/A conventional therapy alone were available for 29 pts. Short-term study Size: n=5 pts blockers. 3) 1 pts with recurrent spontaneous VT leading to multiple shocks from her ICD despite maximal blocker therapy remained free of arrhythmias for 7 mo since the addition of verapamil therapy. No pts experienced worsening of exercise- induced VA. 2) The number of Exclusion criteria: N/A ventricular ectopic beats during the whole exercise test went down from 78 ± 59 beats to 6 ± 8 beats. Sy R. Study type: Inclusion criteria: CPVT pts with a Hx of 1 endpoint: Exercise induced arrhythmias and The combination of calcium channel 2007 Retrospective 2 center syncope or CA and exercise induced clinical outcome blockers with BB might be better than 17765612 study ventricular ectopy despite maximally tolerated BB alone. Study type: Prospective Inclusion criteria: Pts with clinical diagnosis 1 endpoint: Effect of verapamil and First study to demonstrate in vivo 2005 physiology study in of CPVT and carrying a RyR2 mutation magnesium on exercise induced VA. 22 pts (76%) had either partial (n=8) or complete (n=14) suppression of exercise-induced VA with flecainide (p<0. beats. Inc. Swan. p<0. and 11% were asymptomatic. and Heart Rhythm Society. (210) BB therapy Results: 1) 3 pts had non-sustained VT on _. 75 © 2017 by the American College of Cardiology Foundation. . and none of them had VT on combination therapy. Rosso. Polymorphic or bidirectional VT was provoked First-degree relatives of affected individuals with exercise in 63% and adrenaline in 82%. The median daily flecainide dose in responders was 150 mg (range 100 to 300 mg). and Heart Rhythm Society. quarter of pts on flecainide. cardiac arrest dosing were often reported. treatment failure. Study Type/Design. were diagnosed with CPVT if polymorphic or During follow-up of 6.4) Study Acronym. Study type: Inclusion criteria: 170 probands and 56 1 endpoint: Treatment outcome BB were almost universally initiated. 4 pts received ICD VT was observed during exercise or therapy for VT. 2015 Retrospective cohort relatives however. (80%) and less likely to have RyR2 (Ryanodine receptor type 2) mutations (33%). OR or RR. et al. LCSD in 8%. and 25% experienced at least 1 the indication was variable. Study type: Retrospective Inclusion criteria: 10 y of age boy with 1 endpoint: Safety of simultaneous ICD Simultaneous ICD insertion and 2011 Case report CPVT insertion and thoracoscopic sympathectomy thoracoscopic sympathectomy is feasible and 21478052 safe in pts with CPVT (213) Size: n=1 patient Exclusion criteria: N/A Results: The procedure was safe suggesting that it is a better approach than sequential procedures 76 © 2017 by the American College of Cardiology Foundation.7 y. on Holter monitoring. and fatal Exclusion criteria: N/A events were not observed during follow-up (4. Comment(s) Year Published & 95% CI) Moray A.. et al. n=10) were often female causing mutation in the family.1± 3.6 y). or therapy for SVT. and 5 pts had inappropriate adrenaline challenge. treatment failure event. and/or Registries of CPVT. ICDs were placed in 121 ICDs were common despite (54%) and were associated with electrical storm numerous device-related in 22 (18%). Study Size (P values. Pts presenting with late-onset if genetic testing was positive for the disease. 6 deaths (3%) occurred during a cumulative follow-up of 788 pts-y.2±5. BB were prescribed in 205 of 211 pts (97%) on LCDS was not uncommon although medication. . Inc. Size: n=226 pts (p<0.LSCD and ICD Therapy – (Section 4. Roston TM.001). Observational Studies.3. American Heart Association. 25713214 study Results: Symptomatic presentation was reported noncompliance and sub-therapeutic (212) Exclusion criteria: N/A in 176 (78%).008) Treatment failure was rare in the occurred more often in probands. Patient Population Primary Endpoint and Results Summary/Conclusion Author. and treatment failure (p=0. Syncope (p<0. CPVT (>21 y of age.001). Nonrandomized Trials. 2 pts died bidirectional despite having an ICD. Flecainide was used in 24% and complications. Data Supplement 23. 29 (66%) reported left sided underwent LCSD including dryness. Whenever 26019152 pts from 11 centers Results: LCSD was performed in 9 syncope occurs despite optimal medical (216) worldwide Exclusion criteria: N/A asymptomatic and 54 symptomatic pts therapy. respectively. De Ferrari. and Heart Rhythm Society. Study type: Retrospective Inclusion criteria: 1 endpoint: Cardiac events First study to provide evidence that left 2008 single center experience CPVT with symptoms despite BB cardiac sympathetic denervation may be an 18463378 therapy 3/3) and mexiletine (1/3) Results: LCSD resulted in marked reduction effective alternative treatment.6 ± 3.5 y.. assisted thoracoscopic LCSD and effects of LCSD and pts satisfaction. 7. 5 (11%) permanent ptosis (4 77 © 2017 by the American College of Cardiology Foundation. 1 endpoint: Physical and psychological Despite significant morbidity resulting from 2015 Retrospective Survey. 4 died suddenly.001) after LCSD. Implantation of an ICD should be considered in Syncope was the main complaint in 11. and 10. especially for pts (215) Size: n=3 pts in cardiac arrhythmias and improvement in whose symptoms are not adequately controlled Exclusion criteria: N/A QOL.5 y. by means of BB therapy. those resistant to drug therapy. ICD was implanted in 4 pts. treatment and CPVT must be considered in the differential 2009 outcome diagnosis of syncope in children without heart 19102802 Size: n=16 children pts disease but with a normal QT interval.8 ± 2. Medical (214) Exclusion criteria: N/A Results: The mean age of pts at the onset of treatment with propranolol and verapamil may symptoms and at the time of diagnosis was decrease the incidence of arrhythmia. The 1 and 2 y cumulative event-free survival rates were 87% and 81%. Study type: Inclusion criteria: Asymptomatic and 1 endpoint: Cardiac events LCSD is an effective antifibrillatory 2015 Retrospective including symptomatic pts intervention for pts with CPVT. 17 (39%) differential hand temperatures. The percentage of pts with major cardiac events despite optimal medical therapy (n=38) was reduced from 100% to 32% (p <0. pts with LQTS and CVPT have high 26224781 based completion of a telephone survey levels of post-operative satisfaction. LCSD. 26 (59%) a Harlequin-type 40 with LQTS and 7 with (unilateral) facial flush. Study type: Retrospective Inclusion criteria: Diagnosis of CPVT 1 endpoint: Clinical features.Celiker A. therapy. 24 (55%) contralateral CPVT hyperhidrosis. et al. Waddell-Smith. giving a rate of mortality of 25%. Inc. Study type: Inclusion criteria: Underwent video. Of the 16 pts. Treatment included propranolol plus verapamil if VT was still inducible. et al. et al. et al. (217) Results: Side effects were reported by 42 of Size: n=47 pts who Exclusion criteria: N/A 44 (95%). Wilde AA. American Heart Association. . LCSD could be considered the next including 38 pts (25 syncope) with step rather than an ICD and could complement Size: n=63 pts breakthrough events despite optimal medical ICDs in pts with recurrent shocks. Marai. Exclusion criteria: N/A arrhythmia and 43 (68%) were ineffective. 20 rhythm treated. 8 pts refused ICD with 6 eventually dying. Comment(s) Year Published & 95% CI) Mahida S. No death occurred in the ICD group. Study type: Inclusion criteria: ER syndrome 1 endpoint: Inducibility of VA Programmed stimulation 2015 Retrospective with a history of aborted sudden protocols do not enhance risk 78 © 2017 by the American College of Cardiology Foundation. Observational Studies. Patient Population Primary Endpoint and Results Summary/Conclusion Author. Nonrandomized Trials. 5 received an ICD with 4/5 experiencing a VT storm not responsive to ICD shocks but with spontaneous termination. Roses-Noguer. . et al. and Heart Rhythm Society. Shocks delivered to initiating (219) Size: n=13 pts (32%) were effective in terminating sustained triggered arrhythmias nearly always fail. 83% effective. No pts died. nearly always failed (1 of 40.001). Data Supplement 24. 22481011 Exclusion criteria: N/A Results: 27 pts were followed for 1-15 y These pts may have recurrent ventricular (218) Size: n=27 pts (median 9). 3% effective). to ventricular fibrillation. 38 pts (86%) were happy with procedure. while shocks delivered to VF were usually successful (19 of 23. 40 (91%) pts were happy with their scar. and/or Registries of Early Repolarization Pattern – (Section 4. American Heart Association.. p<0. Study type: Inclusion criteria: CPVT 1 endpoint: Death ICD should be recommended in pts refractory 2012 Retrospective to BB therapy. whereas those for subsequent VF are usually Shocks delivered to triggered arrhythmias effective. Inc. 20 were symptomatic at baseline tachycardia storms treated but not terminated and 13 remained symptomatic after treatment by recurrent ICD shocks. Study Size (P values. Study type: Inclusion criteria: CPVT with an ICD 1 endpoint: Effectiveness of ICD shocks The effectiveness of ICD shock therapy in 2014 Retrospective implant for cardiac arrest (7 pts) and CPVT depends on the mechanism of the 24120999 syncope (6 pts) Results: Among appropriate shocks.3. 33 (75%) felt safer and 40 (91%) recommend the procedure. 5 (11%) have thermoregulation difficulties. Study Type/Design. et al. (9%) transient ptosis). 4 (9%) a sensation of left arm paraesthesia and 3 (7%) lost their sympathetic flight/fright response. OR or RR. without degeneration with high dose BB. et al.5) Study Acronym. p<0. Haissaguerre M. 5%. 95% CI: 1.1. whereas 21 of 63 (33%) pts disease and >60 y of age. Study type: Inclusion criteria: Resuscitated 1 endpoint: Prevalence of ER Among pts with a Hx of 2008 Retrospective from cardiac arrest due to idiopathic idiopathic VF. The frequency of J- 79 © 2017 by the American College of Cardiology Foundation. third extra stimuli that induced nonclinical VT/VF were often shorter than the coupling significantly shorter than the corresponding coupling intervals intervals required to induce Exclusion criteria: N/A that induced the clinical VTs. Morady F.54.9 y. the shortest the specificity of EP studies when coupling interval required to induce a clinical VT was 180 ms. et al. who were non-inducible experienced recurrent VF (p=0. Size: n=81 pts Exclusion criteria: Structural heart EPS experienced VF recurrences. Study type: Inclusion criteria: 52 pts with a Hx 1 endpoint: Characteristics of coupling intervals that induce The results of this study 1986 Retrospective of documented.008). p<0. Nunn LM. sex.25593056 multicenter study death due to ventricular fibrillation Results: VF was inducible in only 18 of 81 (22%) pts. VT/VF induced by 3 extrastimuli required a coupling interval of less than 180 ms to induce. et al.2–3.93). clinical VT raising concerns about Regardless of the basic drive cycle length. During stratification in pts with ER (220) follow-up of 7. . et al. Rosso. Inc. defibrillator monitoring matched for age. showed a higher incidence of recurrent ventricular fibrillation in race and level of case pts with a repolarization abnormality than in those without physical activity such an abnormality (HR: 2. 13%..001).001). sustained clinical and non-clinical VT and VF demonstrate that the coupling 3717024 monomorphic VT and inducible VT intervals required to induce non- (221) Size: n=109 pts and 57 pts with non-clinical inducible Results: The mean coupling intervals of the first. repolarization. American Heart Association. second and clinical forms of VT or VF are polymorphic VT or VF. aggressive stimulation protocols Depending on the drive cycle length. and 412 control pts Exclusion criteria: Age >60 y of age During a mean follow-up of 61 ± 50 mo. and Heart Rhythm Society. J-point elevation in the inferolateral leads was controls. control pts Results: J-point elevation was more common among pts with idiopathic VF than among healthy (224) Size: n=45 pts with idiopathic VF than among matched control pts (42% vs. control pts. et al. This indicates that ER is present in 23% of relatives and 11% of control pts (OR: 2. there is an 18463377 VF Results: ER was more frequent in case pts with idiopathic increased prevalence of early (223) Size: n=206 case pts ventricular fibrillation than in control pts (31% vs.90. an important potentially 95% CI: 1. p=0.66–3. 6 of 18 (33%) pts with inducible VF during syndrome. 29 to 70% of nonclinical are used.5. Study type: Case Inclusion criteria: Idiopathic VF 1 endpoint: Prevalence of J point and ST elevation J-point elevation is found more 2008 control study compared with age and sex matched frequently among pts with 18926326.0±4. inheritable pro-arrhythmic trait or marker of pro-arrhythmia in sudden arrhythmic death syndrome. Study type: Inclusion criteria: Families of 1 endpoint: The prevalence of J-point elevation among the J-point elevation is more 2011 Retrospective sudden arrhythmic death syndrome relatives of sudden arrhythmic death syndrome probands prevalent in the relatives of 21737021 probands sudden arrhythmic death (222) Size: n=363 pts Results: A total of 363 first-degree relatives from 144 families syndrome probands than in Exclusion criteria: N/A were evaluated. 11). death from arrhythmia and leads of a standard ECG is 19917913 death from any causes associated with an increased risk (226) Size: n=10. inferior leads and 262 (2.28.92.001) and V5 (44% vs. early repolarization in 2 or more leads was with increased risk of life- (227) Size: n=60 pts (CAD + more common in cases than control pts (32% vs. p=0.7% among pts with idiopathic VF.013).01). J-point elevation of at least 0. 95% CI: 1. 3%. 95% CI: 1. Study type: Case Inclusion criteria: CAD + ICD 1 endpoint: Prevalence of ER ER and. p=0.001) and from arrhythmia (adjusted RR: 2. p= 0. Exclusion criteria: N/A of death from cardiac causes in aged pts Results: ER was present in 630 pts (5. American Heart Association. 8%. ICD + no arrhythmic events) Tikkanen. 5%. in particular.009). et al. 95% CI: 1.001).85–4.2 mV in inferior leads (n=26. p=0. 8%. threatening VA in pts with CAD. idiopathic VF and 121 Exclusion criteria: The presence of p=0. p=0. p=0. arrhythmic events) and acute MI during follow up. CAD or the presence of an V4 (44% vs.03). and a trend was noted in leads V4 n=60 control pts (CAD + BS and pts with QRS ≥120 ms through V6 (12% vs.006) and for J-point elevation in leads I to aVL athletes is higher than among (13% vs. (LQTS. P=0. p=0.4%) in lateral leads. 7. BS or ARVD) Tikkanen. et al. 0.45–5.03). Patel. suspected (23% vs. with a arrhythmia susceptibility syndrome similar trend in lead V6 (33% vs.. ICD + sustained Exclusion criteria: Pts who had an Early repolarization was noted more commonly in inferior leads even after adjustment for LVEF. Study type: Inclusion criteria: Pts participating 1 endpoint: Mortality over a 30±11 y follow up period ST-segment morphology 80 © 2017 by the American College of Cardiology Foundation. J-point elevation in V(4) to V(6) occurred healthy adults but lower than with equal frequency among pts and matched control pts (6. 1%.86).98.04–1. 8%. QRS notching was malignant variants of ER than in (225) Size: n=39 cases of Exclusion criteria: Structural heart significantly more prevalent among cases when present in leads benign cases.005). Study type: Inclusion criteria: Idiopathic VF and 1 endpoint: Prevalence of ER and QRS notching Left precordial terminal QRS 2009 Retrospective ICD implant notching is more prevalent in 19892058 Results: ER was present in 9/39 (23%) pts.006). p=0.3%. p<0.864 middle. 8%. notching 2010 Control design implant + sustained arrhythmic in the inferior leads is associated 20657030 events Results: Overall.8%): 384 (3. .5%) in middle-aged pts. J-point elevation of more than 0.3%) had a markedly elevated risk of death from cardiac causes (adjusted RR: 2. Merchant FM. 5%. Study type: Inclusion criteria: Community 1 endpoint: Prevalence and prognostic significance of ER An ER pattern in the inferior 2009 Retrospective based general population including death from cardiac cause. p=0. p=0. This was true for J-point elevation in the inferior leads point elevation among young young athletes an etiology for the cardiac arrest (27% vs. et al.92.1 mV in inferior leads was associated with an increased risk of death from cardiac causes (adjusted RR: 1. with elevations in both leads in 16 pts (0. The presence of ST-segment elevation or QRS slurring did not add diagnostic value to the presence of J-point elevation. Inc. SQTS.1%). idiopathic VF disease. et al. WPW.59. vs.89. and Heart Rhythm Society. 21–5.05–3.2011 Retrospective in the Finnish Social Insurance variants associated with ER 21632493 Institution’s Coronary Heart Disease Results: Pts with ER≥ 0. in pts with ascending ST variant.43.55). p=0.213 detected (p=0. . Inc.to 4-fold increased risk of 20668657 case-cohort design Exclusion criteria: N/A cardiac mortality in individuals (229) Results: Prevalence of ERP was 13. (# patients) 95% CI) Adverse Events Lu CC.89.94). any).65 (95% CI: 1.1 mV and horizontal/descending ST separates pts with and without an (228) Size: n=10.83. p<0. the relative RR for athletes. HUTT HUTT): 13 of 15 (87%) ingesting pure orthostatic stress.56–6. were Age-stratified analyses showed HRs for cardiac mortality of analyzed 1. Sinner. and Heart Rhythm Society.001) for men between 35-54 y of age. perhaps by (230) in young healthy volunteers any medications water were able to complete the full tilt vasodilatation in splanchnic Comparator: Ingestion of pure without presyncope.30). et al. water 5 mins before 70 degree ingesting glucose water could osmolality which may enhance 81 © 2017 by the American College of Cardiology Foundation.58–6. 95% CI: 0. ERP was associated between 35 and 54 y. and 1972.96 (95% CI: 1. the Exclusion criteria: Pts with missing arrhythmic death increased to HR: 3. but 7 of 15 (47%) circulation or raising plasma Study type: Analytical.005).1. Data Supplement 25. increased risk. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3. p=0.61. the HR of segments after the J-point.1%. seems to be a benign arrhythmic death was not increased (RR: 0. 95% CI: 1.05–1.27 (95% CI: 1.945 pts with cardiac and all-cause mortality. RCTs Comparing Vasovagal Syncope – (Section 5. Study Type. individuals. et al.957 pts Study who had undergone clinical variant (n=412) had an increased HR of arrhythmic death (RR: increased risk of arrhythmic death baseline examinations between 1966 1. p=0. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if Author. dominant ST pattern in healthy data However.14 (95% CI: 1.15 (95% CI: 1. American Heart Association. a clear ERP-age interaction was associated with a particularly population of 6. in middle-aged pts.28. Study type: Population Inclusion criteria: 25-74 y of age 1 endpoint: Prevalence of ERP and its association with ERP was associated with about 2010 based study applying a cardiac and all-cause mortality a 2.1) Study Acronym. An inferior Size: n=1.2 mV) in inferior Rapidly ascending ST leads and horizontal/descending ST-segment variant.90–9. most pronounced in those of localization of ERP was representing a source younger age and male sex. Aim of Study.015) for men between 35–54 y of age.52– variant of ER 1. (# patients) / (Absolute Event Rates. OR or RR. & Study Limitations.001) for both sexes and to 4. Year Published Study Size (N) Study Comparator P values.68. When modeled for higher amplitude ER (>0.035) for both sexes and 2.. Aim: Assess whether Inclusion: Healthy male Intervention: Ingestion of 10% 1 endpoint: Orthostatic tolerance Glucose water attenuates 2008 glucose water ingestion will glucose water before 70 degree (time to presyncope during 70 degree reflex role of PVR during 18772858 reduce orthostatic tolerance Exclusion: Hx of syncope. Open label: to orthostatic stress (time to 24 H urinary sodium excretion) Size: n=20 pts. There Size: n=15 pts was no difference in symptom scores (p=0. SV. American Heart Association. all pts increase in orthostatic Randomized placebo then 60 degree HUTT with with increased plasma and blood tolerance. and these pts showed improved symptoms of orthostatic tolerance Brignole M. With HUTT.6 min). BP. pure water group (43 +/. 1 endpoint: Syncope or presyncopal 63% in the active arm 2002 arm-tensing would increase episode of syncope. Intervention: Slow sodium 10 presyncope) did not benefit from additional Study type: Analytical. nonsparkling mineral water significantly different with 500 mLwater Increase in peripheral prospective crossover then 60 degree HUTT for 20 drinking. “mineral dietary supplement”) Safety endpoint: N/A prospective cohort then 60 degree HUTT with Size: n=11 pts LBNP up to -40 mmHg Open label: 7 of 11 taking salt had increased plasma and blood volumes. -60 mmHg 45+/-2% to -38+/-3%. Aim: To assess water Inclusion: Healthy volunteers Intervention: 500 mL 1 endpoint: Drinking 500 mL water Water drinking 500 mL 2002 drinking on orthostatic nonsparkling mineral water at prolonged time to presyncope in 11 increases orthostatic tolerance.. .0 +/. Sodium chloride 10 mmol showed significant increases in plasma >90 mL) had significant (232) Study type: Analytical. Randomized controlled HUTT complete the full tilt. prospective terminated sooner in glucose water cohort. et al. p=0.9 min) vs.02).001).6. 5% vs. prospective LBNP up to -40 mmHg volumes showed improved tolerance high salt intake at baseline (by cohort. contraceptives Comparator: 50 mL and cardiac output were not increasing plasma volume. ≥1 tensing recurrence with maneuver became asymptomatic vs.008. 11% 12475469 BP during impending syncopal episodes preceded in control (p<0.5.26) between 2 groups. mmol 12x daily (pts told it was a salt loading observational.01 Safety endpoint: N/A El-Sayed. vs. mediated with factors beyond Study type: Analytical. Supine heart rate. Size: n=13 pts each at -20. Inc. then -40. and Heart Rhythm Society. performed on different days maneuver prevented syncope 82 © 2017 by the American College of Cardiology Foundation. Aim: Whether handgrip or Inclusion criteria: ≥1 Intervention: Hand-grip or arm. syncope Comparator: Placebo 1 Safety endpoint: N/A developed syncope (p=0. 3 of 10 taking placebo (increasing plasma volume by 8673750 with orthostatic intolerance. randomized controlled. open label. tone may have role.05). Aim: To evaluated salt Inclusion: Recurrent syncope RDBPCT: 1 endpoint: RDBPCT: 8 of 10 pts Pts with salt supplementation 1996 supplementation in syncope without etiology Intervention: taking salt. reproduced during 2 tilt tests F/U 9+3m 99% performing Study type: Randomized. p<0. Test was barorefex control of SNS.01). group (40. crossover. 12451007 tolerance in healthy pts Exclusion: Regular room temperature pts from 31 +/-3 min to 36+/-3 min with the effect apparently (231) medication except oral (P<0. 500 mL water resistance and vasoconstrictor min followed by LBNP for 10 min drinking blunted decrease in SV from . et al. 47% (233) syncope and avoid LOC by prodromal. et al. Safety endpoint: N/A Schroeder. Pts with signs of controlled. Exclusion: None Comparator: Placebo 12x daily and blood volumes (p<0. 005). Standing against wall 1– syncope recurrence group and 53% in control 17461874 self-training 2 times a day until prodrome of (p=0. performed tilt-training. arm tensing 1 Safety endpoint: N/A syncope burden lower in PCM (234) Study type: Randomized (≥1 syncope and ≥3 group (p<0. Aim: Effectiveness of Inclusion criteria: Recurrent Intervention: Conventional+tilt. presyncope 45%. et al. ≥18 y. (p=0. 16. other causes for Summary: standard+PCM n=106 syncope. placebo. et al. median yearly 17045903 syncope episodes in 2 y or hand grip. PCM effective. therapy Size: n=223 pts Exclusion criteria: Heart standard n=117. and Heart Rhythm Society. OH. Aim: Assess effectiveness Inclusion criteria: Recurrent Intervention: Conventional 1 endpoint: Syncope recurrence 32% PCM vs.82) during comprehensive evaluation. et al.5% controls (p=0. syncope or pre- (236) Exclusion criteria: Other for up to 30 min 1 Safety endpoint: N/A syncope occurred in 42. . Study type: Randomized causes of syncope after 41. controlled. 2 consecutive (30min standing against wall 6 syncope recurrence 28%. Comparator: No tilt-training n=16. single-blind. life-expectancy <1. F/U 1 y.. Aim: Effectiveness of Inclusion criteria: VVS by Intervention: Daily sessions x 4 1 endpoint: Tilt response at 1 min.9% vs. 56% positive HUT in training 2007 repeated home orthostatic positive HUTT wk.85). safe in VVS unable to follow-up with prodrome. recurrence 56% control and 83 © 2017 by the American College of Cardiology Foundation. syncope recurrence al. disease. (multicenter) Exclusion criteria: Other Comparator: No tilt-training causes of syncope Summary: Size: n=68 pts. in preventing tilt-induced syncope. 51% control 2006 of PCM in daily life syncope and prodome (≥3 therapy+ PCM (leg-crossing. 1 endpoint: Syncope recurrence Follow up 12+2 m. tilt-training Tilt-training not effective in n=35. 17% 2004 syncope positive nitrate-potentiated days a 1 wk x 3 wk). American Heart Association. syncope (>2 events in 6m) training (Standing against wall 1. of the 5 15121070 head-up tilt test 1 Safety endpoint: N/A compliant 3 neg tilt table.9 m of F/U.004). syncope 2008 repeated orthostatic self. tilt-training structural heart disease. control n=17 Summary: Tilt-training ineffective in reducing positive HUT response. On YK. none (235) Study type: Randomized had recurrence. et Aim: Efficacy of tilt training Inclusion criteria: Recurrent Intervention: Tilt-training 1 endpoint: Positive tilt test. Duygu. controls n=33 reducing tilt-testing positivity because of poor compliance. RRR: 39% in (multicenter) presyncope in 1 y Comparator: Conventional PCM group. Foglia-Manzillo. Inc. cross-over tilt Summary: efficacy study Exclusion criteria: N/A Isometric arm contraction helps to abort impending syncope Size: n=19 pts BP increased Van Dijk. Size: n=33 pts. <18 y of age. side effects and QoL recurrence did not differ 21752826 responding to non. florinef 0. pharmacotherapy for rx VVS double-blind crossover (3 m Summary: then 1 wk washout) Addition of midodrine to non- pharmacological therapy not Size: n=23 pts effective Kaufman H. Inc. prodrome in or presyncope. no prior 55% active arm (p<0. Summary: Tilt-training did not reduce syncope recurrence Salim. (74 vs. then every other frequency of recurrence similar Study type: Randomized Exclusion criteria: Other day x2 m then 2x a wk) in all types of VVS. p=0. Aim: Effectiveness of Inclusion criteria: >3 Intervention: Midodrine 1 endpoint: Recurrence of syncope Syncope and presyncope 2011 midodrine in pts not syncope in 2 y. rate of causes of syncope after episodes higher in Size: n=82 pts. control n=14 Romme JJ. and Heart Rhythm Society. Aim: Effectiveness of salt Inclusion criteria: >1 Intervention: florinef 0.1).04). 65% (239) pharmacological treatment 1 Safety endpoint: N/A . Comparator: Placebo 1 Safety endpoint: N/A heart rate (240) double-blind cross-over Exclusion criteria: N/A Response to HUT: NMS 67% on placebo and 17% on Size: n=12 (5 mg or placebo midodrine (p<0. 78%. Study type: randomized. +HUT significant change in BP or 12205647 Study type: Randomized. p-0. Aim: Efficacy of midodrine Inclusion criteria: ≥2 Intervention: Midodrine 1 endpoint: Recurrence of syncope Midodrine produced no 2002 syncope in 1 y. already using differ. 1:1 comprehensive evaluation Comparator: Conventional vasodepressor type. (237) to 30 min x 1m.02) day 1 and opposite on day 3) 84 © 2017 by the American College of Cardiology Foundation. et al. .1mg/day and salt 1g/d n=18. and salt 1g/d recurrence recurrence 36% in controls and 15708690 prevention of VVS in children +HUTT. 2005 and fludocrotisone in syncope or presyncope . et al. 80% episodes. Size: n=32 pts.22).18439174 training and + HUTT 2X a d until prodrome of for up 1 Safety endpoint: N/A 37% tilt-training (p=0. American Heart Association..90) (STAND-trial) Exclusion criteria: LOC not Side effects and QoL did not due to VVS. et al. (238) therapy for syncope Comparator: Placebo 1 Safety endpoint: N/A Study type: Randomized Summary: (pediatric) Exclusion criteria: No Symptoms were more frequent structural heart disease in the placebo group. +HUTT Comparator: Placebo between treatment (48 vs.1mg/day 1 endpoint: Syncope or pre-syncope Follow up 176+117d . conventional n=30 causes of syncope. conventional n=13 85 © 2017 by the American College of Cardiology Foundation. et al.0001). 6 midodrine Study type: Randomized Exclusion criteria: Did not (p=0.01) (double-blind placebo meet inclusions controlled cross over) Summary: Midodrine associated with reduced Size: n=16 pts symptom frequency. and Heart Rhythm Society. Intervention: midodrine x 1 mo 1 endpoint: Symptom frequency and Midodrine 7.3 symptom free 1998 symptom frequency and syncope or syncope. midodrine Exclusion criteria: 1) other Comparator: Conventional Summary: Midodrine provides n=31. Aim: Benefit of midodrine on Inclusion criteria: >2 pre. Inc. required) q 6 daytime 1 Safety endpoint: N/A asymptomatic (p<0.. . and 1 h after HUTT Perez-Lugones. American Heart Association. syncope per mo and (2) a pot id titrated up to 15 tid if 4% in conventional remained 2001 Study type: Randomized positive HUTT. et Aim: Efficacy of midodrine Inclusion criteria: ≥1 Intervention: Midodrine (5 mg 1 endpoint: Syncope recurrence F/u 6m. 80% 2006 midodrine in prevention of syncope/y midodrine (1. symptom HUTT and improved QoL.5 mg 1 Safety endpoint: N/A (p=0. reproducible syncope Comparator: Placebo QoL improved with midodrine. (242) during HUTT with GTN on HUTT 1 Safety endpoint: N/A 14 placebo group tilt-induced syncope vs. 3) SBP150 mmHg or dBP 95 mmHg Ward. Qingyou.25 mg bid if +HUTT controls vs. 81% midodrine and al. 22% midodrine 17137891 VVS in children after 1wk then increased 2. et al. (pediatric) Comparator: Conventional Size: n=26 pts. 2)CVD a significant benefit compared and /or systemic disease. midodrine+ conventional n=13.001) 11513446 (241) Size: n=61 pts. Aim: Effectiveness of Inclusion criteria: ≥3 Intervention: conventional + 1 endpoint: Syncope recurrence Follow up 10+8 m. 9505918 hemodynamic response meds. no HTN hemodynamic response HUTT days than placebo (p<0. or to conventional therapy.023) (243) Exclusion criteria: Other bid then another med added if Study type: Randomized causes of syncope after still +HUTT after 1 wk) Summary: Midrodrine effective (open-label) comprehensive evaluation in treating VVS in children. 2 +HUTT n=2. Inclusion criteria: ≥2 Intervention: Metoprolol 1 endpoint: Syncope recurrence 36% in control and 36% Sheldon. Intervention: Drugs: atenolol 1 endpoint: Syncope recurrence Follow up 10±7m. placebo n=24 placebo. stocking ± drug n=3 placebo Exclusion criteria: Other Size: n=30 pts. n=7. 1 endpoint: Syncope and pre.. drug addiction with atenolol compared to n=26. POST Aim: Effectiveness of b. nadolol and syncope 3m.45 for time to first recurrence (244) (double-blind and placebo. syncope recurrence syncope and pre-syncope 12142117 placebo in recurrent VVS over reduced by all drugs. n=108. blockers in prevention VVS syncope over lifetime or ≥1 metoprolol (p=0.4. metoprolol contraindication to b-blocker. et al. chi-square mo cross-over COPD. PVD =60. p<0. +HUTT Comparator: Placebo 1 Safety endpoint (: N/A 16505178 Study type: Randomized Summary: (247) (multicenter) Exclusion criteria: Oother Syncope recurrence did not cause of syncope. differ between metoprolol or Size: n=208 pts. Follow up 3m periods 2002 propranolol. neoplastic or syncope similar in pts treated Size: n=50 pts. American Heart Association. placebo 3 mo cross. Inc. et al. Aim: Efficacy of medical Inclusion criteria: Frequent. 1:1 causes of syncope after Comparator: Placebo Summary: Outcomes similar in comprehensive evaluation either medically treated or placebo groups. Aim: Efficacy of atenolol Inclusion criteria: ≥2 Intervention: Atenolol 50 mg/d 1 endpoint: Time to syncope ITT. Flevari.0001 for presyncopal attacks Size: n=33 Summary: B-blockers and placebo equally effective in decreasing syncope and pre- syncope Brignole. [ANOVA]: (245) Exclusion criteria: 1 Safety endpoint: N/A chi-square =67. placebo n=100 prior trial b-blocker ≥25 mg bid 86 © 2017 by the American College of Cardiology Foundation. p<0. KM p value 11216978 Study type: Randomized Comparator: Placebo 0. HTN. 1 Safety endpoint: N/A controlled) AV disease.99) 2006 syncope 6 mo. atenolol psych. et al. PPM. DM. autonomic Summary: Recurrence of dysfunction.dihyroergotamine syncope recurrence after 20m 1632399 syncope. . cafedrine 1 Safety endpoint: N/A 70% treatment and 67% (246) Study type: Randomized n=1. Aim: Efficacy of Inclusion criteria: ≥2 Intervention: Propranolol. Comparator: See above syncopal attacks. et al. +HUTT nadolol.0001 for Study type: Randomized 3 Autonomic failure.Madrid.domperidone n=2. syncope recurrence 2001 syncope 1 y recurrence similar both groups. Exclusion criteria: PAD.1. and Heart Rhythm Society. placebo groups. absence of 1992 treatment in preventing VVS unexplained syncope or pre. 02). Aim: Effectiveness of Inclusion criteria: Recurrent Intervention: Paroxetine 20 mg 1 endpoint: Syncope recurrence 17. 1 endpoint: Syncope or pre-syncope 41% controls. comprehensive evaluation (EPS).1:1 causes of syncope after therapy. cardiac disease. 22% fluoxetine.01) before and after (multicenter) cause of syncope.0001) 10193720 to other drugs therapy.Theodorakis. Di Girolamo. 1 Safety endpoint: N/A (250) +HUTT Comparator: Placebo Summary: Paroxetine Study type: Randomized improves recurrence in pts Exclusion criteria: Other intolerant to conventional Size: n=68.05. et al. or calcium antagonists. propranolol n=24. and Heart Rhythm Society. propranolol. et al. Intervention: Fluoxetine 20 mg 1 endpoint: Syncope Decreases arterial 2002 CV reflexes +CSM or LBNP (lower body daily baroreceptor sensitivity but 12234955 negative pressure) 1 Safety endpoint: N/A does not prevent presyncope (249) Study type: Randomized Comparator: Placebo LBNP (double-blind) Exclusion criteria: Psychiatric. Aim: Effect of fluoxetine on Inclusion criteria: Healthy. American Heart Association. . contraindications to study Size: n=96 pts. placebo medications Summary: n=22. control n=10. Fluoxetine equivalent to fluoxetine n=30 propranolol and placebo. treatment. depression or panic disorder Gaggioli. 52. long-acting results randomized study nitrates. Aim: To determine the effect Inclusion criteria: 1) ≥1 Intervention: Vasodepressor 1 endpoint: Vasovagal reaction Results: TTT positive in 85% 1997 of vasodilator therapy on episodes of syncope therapy continued during upright tilt testing 2 wk after who continued vasodepressor 9352988 upright tilt testing for occurring during chronic (>6 randomization therapy and 52% who (251) syncope m) vasodilator treatment with Comparator: Vasodepressor discontinued (p=0. log 16627439 fluoxetine in VVS last 1m prior.6% paroxetine vs.9% 1999 paroxetine in VVS resistant syncope. type of angiotensin-converting therapy discontinued 1 safety: N/A medication did not influence Study type: Case-control enzyme inhibitors. failed conventional daily placebo (p<0. neurological or Summary: Prevention of Size: n=19. well-being (248) 1 Safety endpoint: N/A improved in the fluoxetine Study type: Randomized Exclusion criteria: Other Comparator: See above group (p<0. prior SSRI or presyncope does not occur in fluoxetine n=9 MOI LBNP. Inc. Aim: Effectiveness of Inclusion criteria: ≥5 Intervention: Placebo. effective for reducing pre- syncope.. propranolol. syncope lifetime or ≥2 in 1 y. no drugs rank p>0. 51% 2006 placebo. et al. or an association Summary: Chronic vasodilator 87 © 2017 by the American College of Cardiology Foundation. improves well-being. fluoxetine recurrence metoprolol. Takata TS. et al. or ~10 mm Hg in DBP. all therapy enhances susceptibility given within the to VVS during TTT. 2) positive response to upright TTT performed during the same treatment which had been administered at the time of the occurrence of the spontaneous syncopal spell(s). which was defined as a decline 220 mm Hg in SBP. 88 © 2017 by the American College of Cardiology Foundation. namely. Size: n=45 of these or with diuretics. recommended dosage range. Exclusion criteria: Identifiable causes of syncope 1) OH. etc. at an angle of ~60” 2) presence of important clinical conditions contraindicating the interruption of vasodilator therapy. (3) recent (within the previous 6 mo) MI or stroke or other diseases. . (5) concomitant therapy with BB or any other vasoactive drugs. American Heart Association. within 3 min of standing or using a tilt table in the head-up position. and 3) negative work- up for other causes of syncope. (4) very severe general diseases. Inc. and Heart Rhythm Society. and (6) intermittent or discontinuous vasodilator administration. overt HF. severe hypertension.. 3% control vs. et al. 19 compliant for 1 y syncope after comprehensive evaluation no syncope recurrence reported Kinay. positive nitrate-potentiated 15557724 In-hospital training: 3 head-up tilt test Results: F/U 356 +45 d. BP to postural maneuvers. et al. in pts standing Size: n=7 pts BP did increase after water. before and after BP during postural maneuvers. of control group and 95. Study Type/Design*. Study type: Inclusion criteria: Recurrent VVS 1 endpoint: Syncope recurrence Short-term tilt-training is effective. carbohydrate ingestion 15316842 syncope pts and control pts ≥episode in prior 6 m. et al. Inc. BP after crouch increased largely after meal but smaller after water. Krediet. positive tilt table after tilt test and use of counter-maneuvers alleviate prodromal symptoms and can 12270863 lower body tensing 30s prevent in some recurrent syncope.. 82% free of syncope. 0% in training group (p<0. et al. Patient Population Primary Endpoint and Results Summary/Conclusion Author. Nonrandomized Trials. positive nitrate-potentiated symptoms in those unresponsive or (254) up to 40 min head-up tilt test Results: HUTT response evaluated at 1m: 26. Comment(s) Year Published & 95% CI) Pitt. crouching carbohydrate or water Exclusion criteria: Evidence of cardiac Before meal or water no difference btw groups in or neurological etiology on work-up BP or in response to maneuvers.2±5. 2002 Study type: Observational Inclusion criteria: Recurrent VVS 1 endpoint: Syncope recurrence Syncope recurrence may improve 12418741 (long term f/u).0001) Reybrouck. 89 © 2017 by the American College of Cardiology Foundation.1% intolerant of medications.3 m) 56. American Heart Association. syncope recurrence n=24 and refusal (n=23) syncope after comprehensive evaluation (18. OR or RR.8% of training group Size: n=47 pts. 10 with presyncope benefited. Study type: Observational Inclusion criteria: syncope or 1 endpoint: BP response In pts with posturally related syncope 2004 Determine whether presyncope related to upright posture. 1999 Study type: Controlled Inclusion criteria: Refractory VVS 1 endpoint: Syncope recurrence Tilt training significantly improves 10534467 Study. Study Size (P values. et al.8 m). Study type: Observational Inclusion criteria: Recurrent VVS 1 endpoint: Syncope or presyncope recurrence Counter-maneuvers can help to 2002 Effects of leg crossing and syncope.81% free of recurrent (256) consecutive session w/o syncope. 29/38 abandoned tilt training. standing against wall syncope. 2004 Observational syncope. In follow up (10m) 13 pts Size: n=21 pts used counter-maneuver in daily life and 2 fainted.Data Supplement 26. Di Girolamo. +HUTT: drop in Results: Carbohydrate : 85% meal or 500 ml of and water result in opposite effects on (252) show different responses of SBP <80 mmHg with symptoms tap water alternated 1-2 wk. Observational Studies. consent Exclusion criteria: Other causes of became tilt-neg (p<0.0001).1. and Heart Rhythm Society. and/or Registries of Vasovagal Syncope – (Section 5. (253) Exclusion criteria: Other causes of Results: 5/20 (25%) vasovagal reaction averted BP increased syncope after comprehensive evaluation by maneuver prior to tilt. 6/7 recurrent Size: n=38 Exclusion criteria: Other causes of syncope discontinued training. . (255) against will pharmacological provocation Results: Follow up (43±7. 1-2m syncope and positive tilt without symptoms. unlike in control.1) Study Acronym. 52 received b.0001).1%. Year Study Size (N) Study Comparator Event Rates. CVA Sheldon. Study type: Post-hoc Inclusion criteria: Obs: ≥2 VVS 1 endpoint: Syncope recurrence B-blocker prevents syncope recurrence 2012 POST. Intervention: PPM with 1 endpoint: Adjusted RRR 90. Inclusion criteria: ≥2 VVS syncope or 1 1 endpoint: Syncope recurrence B-blocker may not have significant 1996 randomized syncope and ≥4 presyncope. Study type: Observational Inclusion criteria: Recurrent VVS 1 endpoint: Syncope recurrence Midodrine effective and safe in pts with 2001 syncope >1 y. 14/18 resolution (257) Exclusion criteria: BP >160/90. RCTs Comparing Pacemakers in Vasovagal Syncope – (Section 5. effect on presyncope 9935002 pharmacological therapy in NS (p=0. et al. American Heart Association. .36). retrospective syncope or 1 syncope and ≥4 in middle-aged pts (>42 y of age). 22972872 observational presyncope or 1 syncope with trauma. 101 control syncope after comprehensive evaluation syncope similar in both groups Sheldon.8% (CI: 71.52 (CI: 0.31) for <42 Size: n=160.9 (15. and Heart Rhythm Society. and HR: 0.01) for ≥42. Exclusion criteria: Other causes of pt control.. et al. Study type: Non. Inc. BB=52 in Inclusion POST y. et al. failed >2 meds VVS refractory to standard drug therapy.27–1. of symptoms. Summary and 95% CI) Connolly. actuarial probability of remaining blocker. <42 or >42 y of age Exclusion criteria: Other cause of syncope. prior trial b-blocker >25 mg bid Data Supplement 27. (# patients) / (include Absolute Study Limitations. p<0. OR or RR. obs. Author Study Type*. ( # patients) value. et al.00–2. PPM. 28/101 after a positive HUT.56) (260) recurrent VVS Exclusion criteria: Other causes of Comparator: Placebo Mean age no PPM 40 and PPM 46 y of syncope after comprehensive evaluation age. Aim: Effectiveness of PPM Inclusion criteria: ≥6 lifetime syncope. syncope. contraindication to b- blocker. (258) Size n=153. POST n=108. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any). home: 2 session Exclusion criteria: Other causes of standing against wall 15 syncope after comprehensive evaluation min 2m.1. +Iso HUTT effects in preventing syncope recurrence 8806338 Results: Event occurred 17/52 b-blockers. P Adverse Events. no activity Size: n=32 Samniah.0%– 1999 compared with +HUTT rate drop Syncope recurrence 97. Results: A pooled analysis of both studies yielded (259) +HUTT an estimate of the HR: 1. 4 partial response symptomatic IHD.58 (CI: 1. 11423066 Size: n=20 Results: Follow up 21. 90 © 2017 by the American College of Cardiology Foundation.2) Study Acronym Aim of Study. age.0006. 2004 syncope recurrence in last y.004. OR 2001 compared with syncope 2 y. 50%. 8(50%) on vs. PPM significantly early) reduces syncope recurrence. 6% PPM 10899092 syncope recurrence and 39%. major non Size: n=100 pts. recurrent syncope. et al. p=0. (multicenter) recent MI.0004) (261) Exclusion criteria: Other causes of Comparator: placebo Mean age no PPM 56 and PPM 64 y of Study type: Randomized syncope after comprehensive evaluation.3%) PPM vs. chronic disease Summary: In those with cardio-inhibitory Size: n=42. 1 Intervention: DDD with 1 endpoint: Follow up med 715d.3. Aim: Effectiveness of PPM Inclusion criteria: >35 y of age. Study type: Randomized Summary: Size: n=54. KM 1. Inc. 12734133 (263) Study type: Randomized Exclusion criteria: Other causes of Comparator: ODO Summary: Pacing did not reduce risk of (multicenter. American Heart Association.3 Intervention: DDD with 1 endpoint: Cumulative risk at 6m 40% (25%–52%) 2003 syncope recurrence in 3 y. et al. Aim: Effectiveness of DDI Inclusion criteria: :≥3 syncope 2 y. ≥3 Intervention: PPM with 1 endpoint: 2 (4.5 y 0%. +HUTT rate drop Syncope recurrence ODO and 31% (-33%–63%) DDD. et al. (multicenter) Size: n=93. +HUTT with syncope and rate drop Syncope recurrence 0.14.133 (0.. 2000 pacemaker with rate drop on cardio inhibitory response (HUTT) hysteresis Syncope recurrence p<0. valvular. no response. 11435337 pharmacological therapy in bradycardia (262) recurrent VVS Comparator: atenolol Summary: DDD with rate drop more Exclusion criteria: Other causes of effective than atenolol for prevention of Study type: Randomized syncope after comprehensive evaluation syncope. 12 (25. double-blind. p=0. 14 (61%) non-PPM. PPM n=19. ECG abnormalities ODO n=52 Raviele A. + Intervention: DDI + 1 endpoint: 1 (5%) PPM vs. double-blind) syncope after comprehensive evaluation. myocardial. coronary. +HUTT(asystole or mixed) rate drop Syncope recurrence 5(38%) off (p=NS).028–0. HF (NYHA III-IV). syncope after comprehensive evaluation Summary: Active pacing was not 91 © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society. Aim: If pacing reduces Inclusion criteria: ≥6 lifetime syncope.1:1 (terminated In severely symptomatic. DDD n=48. 75% no PPM (p=0. Aim: if pacing reduces Inclusion criteria: ≥6 lifetime syncope. CVD. DDI pacing with hysteresis PPM=23 reduces likelihood of syncope. (264) Study type: Randomized Exclusion criteria: Other causes of Comparator: OOO (multicenter. PPM n=46. . Ammirati.632). no difference in the 15451153 mixed and asystole subgroups.6%. no PPM n=47 terminated early Connolly. et al. Sutton R.5%) drug. electrocardiographic) Pacemaker on Syncope recurrence recurrence PPM 0 (0%). No PPM 6 (60%) 11228858 abnormal adenosine 5. carotid sinus 30 bpm Dual chamber PPM reduces syncope by Study type: Randomized hypersensitivity. double-blind. Inc.25 (0.56) 22086879 positive adenosine 5. BS. 27/41 (66%) HR: 0. syncope 1999 in symptom recurrence with cardioinhibitory (i.12–0.heart passive n=41 transplant list. nonsyncopal loss of consciousness. placebo-controlled) significant associated with reduction in syncope recurrence compared to inactive Size: n=29 pts. >3 Intervention: DDD with 1 endpoint: 2 y estimated recurrence 57% (40%- 2012 pacing in NMS and asystole syncope in 2 y. degree AV block). Size: n=77. et al. Aim: Effectiveness of pacing Inclusion criteria: VVS and abnormal Intervention: 1 endpoint: Follow up mean 52m. + PPM and ICD . response during ATP test. (265) Comparator: ODO absolute RR 32% and relative RR 57% Study type: Randomized Exclusion criteria: >1 cardiac with DDD (multicenter. (266) triphosphate Comparator: No Pacemaker 1 (10%) Exclusion criteria: Syncope due to Pacemaker off Study type: Randomized neurological.multicenter) atrial or VT documented sinus or AV node conduction disorders (including first- Size: n=80. All-cause mortality: Pacemaker 3 (30%). Aim: effectiveness of cardiac Inclusion criteria: :>40 y of age. ILR with >3s asystole or rate drop Syncope recurrence 74%) ODO and 25% (13%-45%) DDD. on n=16.e. Dual chamber Pacemaker on n=10. abnormalities that suggested cardiac placebo-controlled) syncopesinus bradycardia <50 bpm or Summary: DDD effective in reducing sinoatrial block. CSS Flammang. (single blind . sustained or episodic 75%. Mobitz I second-degree recurrence of syncope in >40 y of age with AV block. administration (267) triphosphate Comparator: back-up Summary: Exclusion criteria: >1+EPS. Aim: effectiveness of pacing Inclusion criteria: syncope of unknown Intervention: DDD 70 1 endpoint: Follow up mean 16m. and Heart Rhythm Society. BBB.. active n=39. asthma or 92 © 2017 by the American College of Cardiology Foundation. 22565936 >6s asystole w/o syncope p=0. American Heart Association. prolonged QT interval. et al. off pacing. 8/39 (21%) active 2012 in unexplained syncope and origin. rapid paroxysmal SVT or severe asystolic component. preexcited QRS complexes. . off n=13 VT. AV or SA block >10s under ATP bpm Syncope recurrence vs. et al.039. Pacemaker off n=10 Flammang. on n=16. metabolic or arrhythmic Summary: (open label) etiology PPM in pts with abnormal ATP have fewer syncope recurrences Size: n=20. pregnancy. ARVC). n=13 Brignole. Patient Population Primary Endpoint and Results Summary/Conclusion (if applicable) Study Size (include P value. Year and 95% CI) Deharo. multicenter) Size: n=26 pts. crossover) VASIS) Summary: Size: n= 50 pts Exclusion criteria: other causes of Effectiveness of DDD-CLS in preventing syncope after comprehensive evaluation VVS with cardioinhibition Data Supplement 28. refractoriness to conventional drug Comparator: DDD CLS phases Pts with presyncope at 18 mo: therapy and/or tilt-training.2) Study Acronym Study Type/Design*. Inclusion criteria: >40 y of age. primary endpoint. programmed to DDD- CLS Study type: Randomized (single blind. . and Heart Rhythm Society. Comment(s) Author. systemic infection. Pacemaker Study type: Randomized cardioinhibition . and/or Registries of Pacemakers in Vasovagal Syncope – (Section 5. et al. sinus Intervention: DDD CLS 1 endpoint: Pts with syncope recurrence at 18 mo: 2013 chamber CLS in the rhythm. et al. Summary: intracardiac impedance during Randomization Effectiveness of DDD-CLS in preventing systolic phase of cardia cycle Exclusion criteria: previous MI. Aim: The effect of dual. recurrent unpredictable syncope. between DDD (9/26) VVS with cardioinhibition on beat-to-beat basis. during 1 y follow-up.8%) (single blind. Study type: Observational Inclusion criteria: Sudden onset 1 endpoint: Pathophysiology of Low adenosine plasmatic levels 2013 syncope without prodrome and normal sudden-onset syncope defines distinct form syncope from 93 © 2017 by the American College of Cardiology Foundation. severe chronic bronchitis. Inc. +HUTT with off Pacemaker CLS ON 4 (8%). Aim: To determine whether Inclusion criteria: >5 syncopal episodes Intervention: DDD 1 endpoint: 2 VVS Follow up mean 44 m. severe chronic disease (17/26) and DDI only activates AV sequential during 1st y pacing when detecting increased contractility during 24 pts recruited in 2nd y early phase of VVS. et al. OR or RR.. 7/9 DDI had met 2004 dual-chamber rate adaptive and/or >2 in the last y before enrolment. Pacemaker 23723446 prevention of syncope no medications that could affect circulatory in the CLS on and off CLS OFF 8 (16%) (269) recurrence in refractory VVS control. American Heart Association.asystole >3 s ( 2B CLS OFF 18 (27. Observational Studies. CHF. on Syncope recurrence Pacemaker CLS ON 1 (2%). control n=17 Russo. 41 pts programmed to 15519257 CLS prevents recurrence of refractoriness to conventional drug therapy Comparator: DDI (40 DDD-CLS none had VVS (268) VVS and tilt-training+HUTT with cardio bpm) CLS – tracks variation of inhibition (+2A or 2B VASIS). or DM Occhetta. Nonrandomized Trials. active n=9.1. 23810895 Size: n=15 pts with syncope without heart and ECG; VVS VVS. (270) prodrome and normal heart and ECG Results: Study group- lower median compared to n=31 VVS Exclusion criteria: Other causes of adenosine plasmatic level; <0.36 umol/l syncope after comprehensive evaluation 73% sensitivity; 93% specificity Brignole, et al. Study type: Observational Inclusion criteria: Syncope; normal 1 endpoint: Clinical characteristics Efficacy of PPM in idiopathic AVB. 2011 ECG, no structural heart disease, unexplained syncope with paroxysmal 21570228 Size: n=18 pts paroxysmal 3AVB associated with AVB (271) syncope Results: Follow up mean 4+4 y; AVB Exclusion criteria: Other causes of without P-P cycle or PR interval syncope after comprehensive evaluation prolongation; 17 pts had dual-chamber PPM no syncope recurrence. Lelonek M, et al. Study type: Observational Inclusion criteria: Tilt-induced cardio 1 endpoint: Syncope recurrence Pacemaker or pharmacological 2007 depressive syncope with asystole >3 s treatment effective (272) Size: n=34 pts (2B VASIS) Results: Syncope recurrence at 18 mo: Pacemaker n=22 (DDI +hysteresis) Pacemaker 5 (23%); No pacemaker 3 No pacemaker n=12 (pharmacological: Exclusion criteria: Other causes of (25%); p>0.05 midodrine or b-blocker) syncope after comprehensive cardiac -all educated on behavior measures and neurological evaluation No injury in either group Data Supplement 29. RCTs Comparing Carotid Sinus Syndrome – (Section 5.1.3) Study Acronym Aim of Study; Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any); Author Study Type*; (include # patients) / (include Absolute Event Study Limitations; Year Study Size (N) Study Comparator Rates, P value; OR or Adverse Events; (include # patients) RR; and 95% CI) Summary Brignole, et al. Aim: Efficacy of permanent Inclusion criteria: Recurrent Intervention: Pacing 1 endpoint: Symptom Syncope recurrence in 57% of the non- 1992 pacing. syncope or presyncope causing recurrence pacing group and 9% of the pacing group 1561975 trauma or future trauma or Comparator: No pacing (p=0.0002); the actuarial rate of absence of (273) Study type: RCT decreased QoL; cardioinhibitory 1 Safety endpoint: N/A syncopal recurrence after 1,2,3 and 4 y was or mixed symptoms reproducible 64%, 54%, 36%, and 38%, respectively, for Size: n=60 pts; no CSM; no other cause (extensive the nonpacing group, and 100%, 97%, 93%, pacing=28; pacing 32 w/u monitoring, neuro, EPS) and 64%, respectively, for the pacing group (VVI=18, DDD=14) (p=0.0001). Exclusion criteria: SN dysfunction, prolonged HV AV Summary: Permanent pacing effective in block on EPS CSS 94 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Claesson, et al. Aim: Effect of symptoms in Inclusion criteria: ≥1 episodes Intervention: Pacing 1 endpoint: Syncope Rate of syncope in the non-paced group 2007 cardioinhibitory CCS with of syncope or presyncope; (pre-syncope) recurrence was 40% compared with 10% in the paced 17823136 and without pacing induced cardioinhibitory CSS Comparator: No pacing group (p=0.008). (274) 1 Safety endpoint: N/A 10 pts (33%) with recurrent syncope in the Study type: RCT Exclusion criteria: N/A NP group later crossed-over to receive a pacemaker implant, and 8 of these 10 pts Size: n=60 pts; no pacing= were asymptomatic at the 12-mo follow-up 30 Pre-syncope occurred in 2 pts (7%) in the pacing=30 NP group and in 8 (27%) in the P group. Summary: Permanent pacing effective to prevent syncope recurrence in CSS Parry, et al. 2008 Aim: Effect of falls in CCS Inclusion criteria: ≥ 55 y of Intervention: 1 endpoint: Number of ● 25 pts completed study 19124530 with pacing on and off age; ≥3 episodes of unexplained DDD/RDR falls ● Pacing did not affect the number of falls (275) falls but no syncope in prior 6 ● 3 pts cross-over to DDR mode Study type: RCT(double- mo; induced cardioinhibitory (>3 Comparator: ● Hx of presentation with falls in ODO mode blind, cross-over, placebo- s induced 5 s) or mixed (<50 mm ● ODO – unclear bradyarrhythmias controlled) Hg with atropine) ● 6 mo then cross-over ● Pacing did not affect the number of falls Size: n=34 Exclusion criteria: Other cause with extensive cardiac, neurological w/u; any Hx of syncope; severe cognitive impairment Kenny, et al. Aim: Whether cardiac Inclusion criteria: ≥ 50 y of Intervention: Dual-chamber 1 endpoint: syncope Pts with syncope recurrence at 12 mo: 2001 pacing reduces falls in older age; Cognitively normal pts pacemaker programmed ON recurrence Pacemaker 10 (11%); No pacemaker 19 11691528 adults with cardioinhibitory (MMSE> 23/30 points) who were (22%); p=0.063 (276) carotid sinus adults ; ED visit for a non- Comparator: No pacing 2 endpoint: fall Syncope recurrent events at 12 mo: hypersensitivity accidental fall. recurrence Pacemaker 22 events; No pacemaker 47 events; OR 0.53 (CI: 95%: 0.23–1.2) Study type: RCT; open- Exclusion criteria: Cognitive 1 Safety endpoint: N/A Pts with no syncope recurrence at 12 mo: label impairment; accidental fall such Pacemaker 77 (89%); No pacemaker 69 as a slip or trip, or not (78%) Size: n=175 attributable to a medical cause 2 outcomes: Pacemaker=87 such as epilepsy, stroke, alcohol Fall events at 12 mo: pacemaker 216 No pacemaker=88 excess, OH, other arrhythmias events; No pacemaker 699 events Pts with fracture due to fall at 12 mo: pacemaker 3 (3.4%); No pacemaker 4 95 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. (4.5%) Pts with soft tissue injury due to fall at 12 mo: pacemaker 26 (29.9%); no pacemaker 32 (36.4%) All-cause mortality at 12 mo: pacemaker 5 (5.7%); No pacemaker 3 (3.4%) Summary: Pacing associated with less falls and injury; no reduction in syncope events Ryan, et al. Aim: Cardiac pacing for Inclusion criteria: ≥ 65 y; Intervention: Pacing 1 endpoint: Number of Pts reporting syncope after pacemaker 2010 recurrent falls in pts with symptoms consistent with CSH falls after implant. implant RR: 0.47 (95% CI: 0.26–0.86); The 19933747 cardioinhibitory CSH would with a minimum of 2 unexplained Comparator: No pacing number of syncopal events was also (277) reduce fall recurrence. falls and/or one syncope in prior 2 endpoint: Time to fall significantly less after implant, 0.52 (95% CI: 1 y; 3 s of asystole in response event, presyncope, quality 0.29–0.95). to CSM; a MMS >19. of life and cognitive function Syncope recurrent events at 24 mo: Study type: RCT, open Pacemaker 0.42 mean events; No label Exclusion criteria: Neoplasm, 1 Safety endpoint: N/A pacemaker 0.66 mean events; RR: 0.87 renal or hepatic failure; and at (95% CI: 0.3–2.48) Size: n=141; ITT n=129; time of randomization significant Pacing on n=68 HF. 2 endpoints: No pacemaker (ILR) n= 61 Pts with falls at 24 mo: Pacemaker 44 (67%); No pacemaker 33 (53%); RR 1.25 (95% CI: 0.93–1.67) Syncope-related falls at 24 mo: pacemaker 4.33 events; No pacemaker 6.52 events; RR: 0.79 (95% CI: 0.41–1.5) Summary: No difference in falls, syncope and other secondary endpoints between 2 groups. Data Supplement 30. Nonrandomized Trials, Observational Studies, and/or Registries of Permanent Pacing in Carotid Sinus Hypersensitivity – (Section 5.2.2) Study Acronym Study Type/Design*; Patient Population Primary Endpoint and Results Summary/Conclusion (if applicable) Study Size (include P value; OR or RR; Comment(s) Author, Year and 95% CI) Sugrue, et al. Study type: Retrospective, Inclusion criteria: ≥1 episodes of 1 endpoint: Symptom recurrence PPM effective in CSS 1986 observational study of untreated syncope or presyncope; predominately cardioinhibitory 96 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. 3941204 compared to pacing or cardioinhibitory, vasodepressor or Results: Incidence of recurrence 27% no treatment, (278) anticholinergic drugs mixed; no other cause 22% drug group, 9% pacing group; those with cardioinhibitory CSS had no recurrence of syncope with Size: n=56 Exclusion criteria: N/A DVI pacing (9/9) and 8 of 10 were asymptomatic with untreated=13 VVI pacing anticholinergic=20 pacing=23 Blanc, et al. Study type: Retrospective, Inclusion criteria: Cardio inhibitory 1 endpoint: Symptom recurrence after pacemaker PPM effective in CSS 1984 observational implant 6424619 Exclusion criteria: N/A (279) Size: n=54 pts; no pacing=33 Results: 50% of pts had recurrence of syncope with no pacing=21 pacing vs. 0% in pacing group Morley, et al. Study type: Prospective, Inclusion criteria: Cardioinhibitory 1 endpoint: Symptom persistence, vasodepressor PPM effective in CSS; AV 1982 observational with pacemaker response, pacemaker effect sequential pacing preferred 7073901 (280) Size: n=70 pts; pacing mode Exclusion criteria: N/A Results: Persistence of symptoms with a final pacing (VVI, DVI, DDD, AAI) mode VVI 11%; 8% DVI and 8% DDD, AV sequential pacing eliminated hypotensive effects of VVI pacing Gaggioli, et al. Study type: Retrospective, Inclusion criteria: Cardioinhibitory 1 endpoint: Symptom recurrence after pacemaker PPM effective in CSS; 1995 observational or mixed; no other cause implant recurrence does occur in mixed 7572635 type (281) Size: n=169 pts; VVI n=59 Exclusion criteria: N/A Results: Syncope recurrence was 7% at 1 y, 16% at 3 DDD n=110 y, and 20% at 5 y; 21% syncope recurrence in pts with vasodepressor response. Maggi, et al. Study type: case-control (age- Inclusion criteria: Cardio inhibitory 1 endpoint: Syncope recurrence Cardio inhibitory CSS predicts 2007 sex matched 2:1) CSM and spontaneous syncope by associated with asystole during 17507364 ILR Results: Asystole 89% CSS and 50% controls; 14 of spontaneous syncope benefit from (282) Size: n=18 pts Control group: negative CSM, tilt CSS with asystole DCH PPM; f/u 35 ±22m syncope pacing and ATP burden decreased 1.68 (1.66–1.70) episodes to 0.04 (0.038–0.042) with PPM (98% RR) Exclusion criteria: Structural cardiac disease, conduction, symptomatic OH, non-syncopal cause of LOC Lopes, et al. Study type: Retrospective Inclusion criteria: Cardio inhibitory 1 endpoint: Symptom recurrence after pacemaker Permanent pacing effective in 2011 observational or mixed in whom pacemaker implant CSS; recurrence does occur in 21169606 implanted mixed type (283) Size: n=138 pts Results: Syncope recurrence 10.9%; 5.8% minor 97 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. Exclusion criteria: N/A symptoms/presyncope; mixed CSS predicted recurrence (HR: 2.84; 1.20–6.71; p=0.017) Brignole, et al. Study type: Systematic review Inclusion criteria: Cardioinhibitory 1 endpoint: Syncope recurrence; Benefit of cardiac pacing with 2011 or mixed up to 5 y follow-up significant reduction in recurrence; 21570228 Size: 12 studies; n=601 pts with lead to reduced morbidity (271) pacing and 305 untreated Exclusion criteria: Case reports Results: 0–20%in pacing group and 20-60% in Recurrence 20% of paced pts at untreated group; 3 studies with control groups RR 0.24 5y (0.12–0.48) Menozzi, et al. Study type: Prospective Inclusion criteria: Recurrent or 1 endpoint: Occurrence of asystolic episodes Asystolic response to vasovagal 1993 observational severe episodes of syncope and Results: Follow up 15 + 7 mo; asystolic episodes maneuvers predicts occurrence of 8237805 presyncope causing major trauma or occurred in 74% of pts; actuarial estimate of occurrence spontaneous asystolic episodes. (284) Size: n=23 pts risk of death; asystolic response >3 of asystolic episodes of >3 and >6 s were 82% and 53% Spontaneous episodes are s with CSM or eyeball compression after 2 y. 12 episodes >3–6 s (0.7%) and 20 episodes of asymptomatic and incidence is low. with and without positive head-up tilt >6s (43%) test; VVI pacemakers ability to track asystolic episodes. Exclusion criteria: No other identifiable cause Striyger, et al. Study type: Prospective Inclusion criteria: Repeated 1 endpoint: Efficacy of VVI pacing in preventing VVI pacing for isolated form of 1986 observational syncope of unknown cause; CSM recurrence cardioinihibitory syncope results in 2429277 asystole of >4 sec; cardioinhibitory complete resolution of symptoms. (285) Size: n=20 pts based on EPS Results: Mean 20 mo; no pts had reoccurrence of syncope Exclusion criteria: N/A Walter, et al. Study type: Prospective Inclusion criteria: Syncope of 1 endpoint: N/A PPM in cardio inhibitory syncope 1978 observational unknown cause or pre-syncope; is associated with less 356576 CSM ventricular asystole of >3 sec Results: 17 pts had cardio inhibitory, 2 vasodepressor reoccurrences. (286) Size: n=21 pts and 2 mixed. 11 pts PPM of these 9 had no further Exclusion criteria: N/A symptoms or rare pre-syncopal events; 2 of the pts with PPM had mixed response on CSM and had pre-syncope or syncope related to drop in BP. Crilley, et al. Study type: Prospective Inclusion criteria: recurrent falls, 1 endpoint: Outcomes of DCH PPM on elderly with DCH PPM is effective for 1997 observational pre-syncope or syncope and CSM falls, pre-syncope and syncope associated with hypersensitive cardioinhibitory 9338027 >3 s ventricular asystole cardioinhibitory syncope syncope. (287) Size: n=42 pts Results: All pts had DDI pacemaker implant; 84% no Exclusion criteria: N/A longer had further syncope mean follow up 10 mo and 98 © 2017 by the American College of Cardiology Foundation, American Heart Association, Inc., and Heart Rhythm Society. 2) Study Acronym Author Aim of Study. (# patients) and Summary 95% CI) Brignole. Year Study Type*. DDR 1 endpoint: Syncope and Frequency of V pacing in VVI mode 2012 of pacing modes Cardioinhibitory/ mixed with sudden brady response pre-syncope recurrence. .001). (single blind. Aim: Evaluate Inclusion criteria: Mixed Intervention: DVI/DDD 1 endpoint: Symptom DVI vs. ventriculoatrial conduction and OH are present. and Heart Rhythm Society. Aim: Investigate impact Inclusion criteria: Intervention: DDDR.001) and recurrence and QoL Exclusion criteria: presyncope (258–17. QoL overall Size: n=21 pts did not differ 99 © 2017 by the American College of Cardiology Foundation. OR or RR. American Heart Association. PPM 6 m) Summary: No clear superiority of one pacing mode over another. et al.. pre-syncope in 48% 2463565 synchronism for mixed Comparator: VVI OH. Study Size (N) Study Comparator Rates. When Size: n=23 pts pacemaker effect. Inc. (# patients) / (include Absolute Event Study Limitations.2. P value. cause for LOC. therefore DVI/DDD stimulation is indicated McLeod. vs. VA conduction. Adverse Events. 74% (p=0. VVI. RCTs for Type of Permanent Pacing in Carotid Sinus Hypersensitivity – (Section 5. cross- over) Summary: DVI/DDD pacing effective in 61% compared to VVI. symptoms and VVI 9SF-36) (p=0.04) (289) sudden brady response reproducible CSM For any pacing mode syncope and VVI) on syncope Comparator: 1 Safety endpoint : N/A recurrence (29–2. 13% (p= 0. DDR with CSS. p<0. syncope occurred in 0% 1988 importance of atrial CSS recurrence. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any). symptoms unchanged in 22% Data Supplement 31. another increase bodily pain and vitality (double-blind.04). structural measures in the DDDR mode sequential cross over – heart disease. remaining Isolated cardioinhibitory or 1 Safety endpoint : N/A 36% did not express any preference Study type: RCT vasodepressor (p=0.001) reduced Isolated vasodepressor Pacing modality found to marginally Study type: RCT response to CSM. VVI failure is possible. pacemaker effect vs.25). DVI was the (288) CSS Exclusion criteria: modepreferred by 64% of pts. QoL marginally less than any DDDR modes 22548372 (DDDR. et al. p<0. DVI/DDD compared with other modes (291) pacemaker inserted Results: Failure to control syncope for various Size: n=202 pts modes: AAI 50%. & Adverse Events (# patients) 95% CI) Anley C. (p=0. MS . at the termination of. et al.031) n=208 Exclusion criteria: Other cause of syncope or unknown not consistent with VVS (clinical & HUTT) Data Supplement 33. oral fluid and 1 endpoint: Time to discharge: no With no difference in time to 2011 treatment protocol for athletes at 2 Ironman Trendelenburg position significant difference between IV (52. VVI 18% and DVI/DDD 9% Exclusion criteria: N/A Bae MH. and Heart Rhythm Society. . p=0. et al. OR or RR. VVI hemodynamic compromise resulting 6702680 of symptoms or dizziness. VVI syncope 98%. for Type of Permanent Pacing in Carotid Sinus Hypersensitivity – (Section 5. but significantly less 20584756 exercise-associated Triathlon competitions and min) and OT group (58+/-23 min). Study Size (P values. RCTs for Neurogenic Orthostatic Hypotension – (Section 6. Aim: To assess which Inclusion: All collapsed Intervention: OT. p=0. (# patients) / (Absolute Event Rates. intravenous fluid Secondary: heart rate and BP changes: NS compared to IV group. 37 mm origin Hg. frequency of drinking Size: n= 680 consecutive after urination alcohol higher in MS (<0.2.1) Study Acronym. 27%.001) and a higher rate of symptom persistence (91% vs.. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any).18 discharge. or immediately male more likely MS (p=0.2) Study Acronym. VVS factor/underlying disease (p=0. the 100 © 2017 by the American College of Cardiology Foundation. Study Type/Design*. MS n=38.036). Study type: Case series Inclusion criteria: syncope or pre. Study Limitations. MS in 2011 Retrospective. Study Type. Inclusion criteria: Cardioinhibitory 1 endpoint: Changes in BP after CSM in pts paced VVI results in significant 1984 observational DVI vs. DDD vs. DVI (59 vs. 1 endpoint: Syncope recurrence The most effective pacing mode is 1989 AAI vs.004) and first syncope (p=0. p=0. Year Published Study Size (N) Study Comparator P values. during or immediately after defecation statistics to compare btw groups) middle-age men and drinking alcohol 22188510 observational study and during abdominal cramping or precipitator (292) comparing defecation.001) as was CV risk DS n=38. Aim of Study. Inc. Observational studies. during. Patient Population Primary Endpoint and Results Summary/Conclusion Author. et al.47 fluid given in OT group (293) postural hypotension one ultra-distance footrace Comparator: IV.Data Supplement 32. OR or RR. et al. Comment(s) Year Published & 95% CI) Madigan. urge to defecate. Author. Study type: Prospective. VVI with partial or complete reproduction in DVI mode vs.002). American Heart Association.008) Exclusion criteria: N/A Sutton.syncope Results: DS occurred in older age of diagnosis micturition and VVS occurring at the beginning of. near or in increased symptoms (290) Size: n=11 pts syncope compatible with cardiac Results: Drop in BP in VVI vs. younger VVS. Study type: Inclusion criteria: DS occurring 1 endpoint: Clinical characteristics ( using standard DS occurred in older women. positive CSM.5 +/. for 60 mins after ingestion significantly increased at 30 min (p=0. All medications that Comparator: 16 ox (473 mL) of to 129±9 mmHg 30 min after ingestion double the effect of salt water. Test was terminated osmolality which may enhance Study type: Analytical. pure water group (43±5.001.018) increase in SBP. Exclusion: None the gastropressor response randomized controlled. The osmolality after water ingestion of salt water may have reduced Study type: Analytical. Comparator: Pure water 5 min (87%) ingesting pure water were able to orthostatic stress. pressor response could impair BP regulation distilled water then noninvasive (p<0. heart rate and BP were measured ingestion (p=0. sooner in glucose water group (40. Inc.001). p<0. Randomized controlled vs. American Heart Association.139) Schroeder C.005).6 min). and was significantly less than IV resulting in venous pooling Randomized controlled. and Heart Rhythm Society. only water ingestion compared with water in were withdrawn for 5 half. Size: n=15 pts Raj SR.149 ml. perhaps by (230) tolerance in young any medications before 70 degree HUTT complete the full tilt without presyncope. but 7 vasodilatation in splanchnic healthy volunteers of 15 (47%) ingesting glucose water could circulation or raising plasma complete the full tilt. et al. water: increased SBP at 30 min post 16785332 water would increase symptoms and were 18 y SBP increased from 92±8 mmHg at baseline ingestion. associated postural hypotension Exclusion: Abnormal Total volume of fluid in OT group was 204 is peripheral vasodilatation Study type: Analytical.022). Supine with the effect apparently 101 © 2017 by the American College of Cardiology Foundation. group 1045+/-185 ml.. and 110±12 mmHg 60 min after By 60 m.001). et Aim: To assess water Inclusion: Healthy Intervention: 500 mL 1 endpoint: Drinking 500 mL water Water drinking 500 mL al. drinking on orthostatic volunteers nonsparkling mineral water at prolonged time to presyncope in 11 pts from increases orthostatic tolerance. probable cause of exercise discharge. crossover. prospective cohort Size: n=28 pts Lu CC. 1 endpoint: Hemodynamic response to salt which likely is not just due to prospective crossover water: blood volume. et al. 2002 tolerance in healthy pts room temperature 31 ±3 min to 36 ±3 min (p<0. Aim: Assess whether Inclusion: Healthy male Intervention: 10% glucose water 1 endpoint: Orthostatic tolerance (time to Glucose water attenuates 2008 glucose water ingestion presyncope during 70 degree HUTT): 13 of 15 reflex role of PVR during 18772858 will reduce orthostatic Exclusion: Hx of syncope. p=0. Plasma norepi continued to show significant OH lives before testing. SBP increased from 94 ±9 mmHg as Size: n=9 pts baseline to 112 ±9 mmHg 30 min after ingestion (p=0. Aim: To assess if Inclusion: OH pts with at Intervention: Distilled water 1 endpoint: Hemodynamic response to Water and salt water both 2006 ingestion of salt with least 6 mo Hx of orthostatic mixed with 2 g of NaCl added. serum sodium +/.9 min) barorefex control of SNS. and 104 ±9 mmHg (p=0.008. prospective There was no difference in symptom scores cohort (p=0. .0±6.26) between 2 groups. with water having (294) magnitude of acute of age. results in earlier in 2006 and 2007 changes were seen. OH 5 mg. -2mmHg for placebo (p<0. n=22 improvement was significant with 10 mg for controlled.05) during HUTT standing. but phenylephrine infusion. renal or hepatic impairment.4 middle cerebral artery velocity intolerance concomitant decrease in mmHg.01) and to decreased cerebral blood flow sectional cohort symptoms of OI with SBP decreased by 5–10 mmHg) at end of HUTT (14+/-5 bpm (p<0. p<0.5%). symptoms) due to (p<0. Aim: Effect of Inclusion: At 18 centers Intervention: Midodrine 2. (n=18. alpha-agonist 1998 loading and alpha. prospective Parkinson disease. With HUTT. p<0. cross. Size: n=13 pts at -20.001). plasma norepi level >600 Comparator 1: Phentolamine blockade). SV. syncope. . the increased upright heart rate (-20+/-3.01). p<0. 500 mL water drinking Increase in peripheral resistance prospective crossover. (placebo at rate similar to volume loading.2 blunted decrease in mean (296) idiopathic orthostatic standing without a 10 bpm or SBP increased by 5-10 bpm. randomized controlled.. mean Size: n=9 pts significantly relieved by cerebral blood flow velocity decreased by lying down Comparator 2: Normal saline 33+/-6% at HUTT. et al. With placebo. Symptom blind placebo Shy Drager. then -40. and cardiac output were mediated with factors beyond (231) Study type: Analytical. 3 mmHg for placebo HTN (8%) 7687093 OH (15 mmHg fall from supine (p<0. least 6 mo Hx of typical rate increased by 5–10 bpm or heart rate at 5 min (20+/-3.7 bpm. then drinking. hemodynamics with alpha- Study type: Analytical. BP. and Heart Rhythm Society. p<0. pheochromocytoma. or 10 mg 3x daily. supine 1993 midodrine in neurogenic between 1989 to 1990.5 mg. Randomized double.5 and 5 mg doses. HUTT. Midodrine increased standing DBP Midodrine significantly improves (295) to standing position plus Comparator: Placebo for 4 wk by 15 mmHg vs. which were or compared with placebo. 3 mmHg for placebo standing SBP and symptoms of Study type: Analytical. Excessive Randomized placebo pg/mL with standing. DM) (p<0. -60 mmHg Jankovic JJ. and energy level cohort. or severe cardiac abnormalities Jordan J.001). vs. Improvement with energy level occurred with midodrine 2. Inc. but effect diminished at end of (despite worsening systemic SBP/DBP >20/10 mmHg).001). contraceptives nonsparkling mineral water. (>30 bpm increase in heart (infusion rate increased until placebo.001).001) as did phenylephrine (-18+/-3. Supine SBP increased 13 mmHg OH. volume loading significantly blunted infusion.01 have role. bpm. for 4 wk SBP by 22 mmHg vs. autonomic failure. medication except oral Comparator: 50 mL not significantly different with 500 mLwater increasing plasma volume. and phentolamine infusion all Exclusion: Systemic illness pheylephrine or phentolamine attenuated the decrease in mean middle 102 © 2017 by the American College of Cardiology Foundation. and alpha-blockade all 9774366 adrenergic agonism in rate within 5 min of either heart rate decreased by 5. Size: n=97 pts Exclusion: Pre-existing supine hypertension (>180/110 mmHg). et al. at (infusion rate increased until heart Phentolamine significantly increased upright sympathetic activity contributes controlled.12451007 Exclusion: Regular heart rate. Aim: To assess volume Inclusion: Idiopathic OI Intervention: Phenylephrine 1 endpoint: At 5 m HUTT compared to Volume loading. American Heart Association. 60 degree HUTT for 20 min blunted decrease in SV from -45+/-2% to -38 and vasoconstrictor tone may followed by LBNP for 10 m each ±3%. 1 endpoint: Midodrine increased standing Scalp tingling (13. n=27 blurred vision. prospective contraindications to pressor Comparator 3: Ibuprofen 600 elicited similar pressor responses. Aim: Assess midodrine Inclusion: 18 y of age or Intervention: Midodrine 10 mg 1 endpoint: Primary: improvement in Piloerection 13%. amyloidosis) Comparator 3: All pts were volume loaded with 2000 mL normal saline over 3 H. and in midodrine. In 4 pts. p<0. increasing severity of autonomic (298) Study type: Analytical. 9091692 neurogenic OH (due to a mmHg. Comparator 2: indomethacin indomethacin (standing +28+/-2 mmHg. paresthesia 9%. CHF) mg. cohort.5 mg. Comparator 6: Midodrine 5 mg Kaufmann H.05). and effect to phenylopropanolamine Study type: causes of autonomic failure mg.35+/-0.001. Exclusion: None midodrine. symptomatic 3x daily standing SBP: mean increased SBP of 21. the Not every pts received each 1998 medication effect in to multiple system atrophy Phenylpropanolamine 12. cerebral artery velocity with upright posture autonomic nervous system (p<0.5 mg pressor response was significant for drug so direct comparison was 9727818 severe OH from or PAF (25 mg in pts not responsive to phenylpropanolamine (12. American Heart Association.05 for each). effect of midodrine OH multiple system atrophy. Pts with 2452997 for 7 days. Inc. (DM.4 (standing SBP 36+/-13 mmHg. yohimbine described as having similar Exclusion: Secondary Comparator 1: yohimbine 5. et Aim: To assess the Inclusion: Several OH with Intervention: Midodrine titrated 1 endpoint: Midodrine increased standing Midodrine improves BP and al.then 75 degree HUT for 30 m Jordan J. et al. p<0. randomized adrenergic pathways.5 mg). with somewhat less effect seen Randomized placebo (DM. Midodrine was (297) autonomic failure 12. improves symptoms of OI. Aim: To assess various Inclusion: severe OH due Seated BP effect of Intervention: 1 endpoint: Compared to placebo.33 mg) and independent of wearing Midodrine 10 mg 3 x daily double-blind placebo central or peripheral). that could affect the infusion). et al. 50 mg. and may worsen OH blind placebo controlled Low dose fludrocortisone these pts the decrease paralleled decrease in due to extracellular fluid loss crossover.8 (scalp) 10%. Size: n=7 pts Low PA. cohort change. or from 2.. prospective mmHg SBP postural lightheadedess improved over entire study. amyloidosis). . and Heart Rhythm Society. but without specific controlled. standing SBP not possible. or plasma Size: n=35 pts Comparator 5: Methylphenidate catecholamine levels 5 mg. pruritus 1997 in neurogenic OH older. association between drug response and Comparator 4: Caffeine 250 mg.05) and symptoms of OH in selected pts 1988 in autonomic failure idiopathic OH. Comparator: Placebo increase standing BP or symptoms.05). 15 compression garments. fludrocortisone. No hemodynamic numbers. Midodrine effect was supine HTN 4% (299) Study type: Multicenter structural lesion of Comparator: Placebo independent of fludrocortisone (mean dose analytical. p<0. and the combination did not function may not respond to Randomized double.1 mg daily continued body weight. symptoms. p<0.5 mg/kg (25-40 mg/d) these pts reported improved orthostatic with autonomic failure. prospective 0. postmenopausal and reached significance at second wk of 103 © 2017 by the American College of Cardiology Foundation. +37+/-12 mmHg.05). cohort. 0. dose of 0. autonomic function testing.5 mg 4x daily to total daily BP significantly in 3 of 7 pts (p<0. Phenylpropanolamine and midodrine in figure 4. Symptoms of increases standing BP and controlled. agents (CAD. preexisting sustained Parkinsonism. Exclusion: Pregnant or n=37 pts. p=0. neuropathy. whether atomoxetine autonomic failure (PAF. beyond 1 h after medication or DBP ≥10 mmHg within 3 Comparator 2: Placebo. single. prospective Exclusion: autonomic improve OH related symptoms (p=0. p=0. No study of time of SCI bodied Exclusion: Smokers. PAF.5 randomized. midodrine improved orthostatic tolerance in control SCI by 59% (p=0. DBP. women or on contraception medication. Atomoxetine improved DBP al. Stage and time at which carotid. and symptoms greater than 2014 would be superior to multiple systems atrophy. and heart rate extent than midodrine (means difference =7. upright DBp and heart rate. not midodrine 104 © 2017 by the American College of Cardiology Foundation. flow response to tilt is similar in SCI and AB. or upstream (300) SCI compared to able.02. adrenoreceptor alpha- agonist or antagonists. Supine BP was not 25185131 midodrine in improving Parkinson disease) with OH mg DBP. p=0. American Heart Association.02) but crossover failure secondary to DM. BP was measured (301) upright BP and OH defined as SBP ≥20 mmHg Questionnaire and Q1 symptom scores. Atomoxetine controlled.003) as calculated by orthostatic tolerance index calculated by the Size: n=20 pts formula orthostatic tolerance index = final tilt degree x time the last stage was tolerated. . Ramirez CE. 45. et al.1mmHg. until assessment by tilt. diabetic lactating women. history of CV disease separate days Study type: Analytical.03) and upright DBP (means blind placebo difference =4. Comparator 1: Midodrine 5–10 Secondary: Post-treatment seated SBP and midodrine. n=37 pts. n=40 pts. Atomoxetine improved upright SBP to a great administration Study type: Analytical. et Aim: To assess Inclusion: Pts with severe Intervention: Atomoxetine 18 mg Primary: Post-treatment upright SBP at 1 min. Steady state and dynamic cerebral blood randomized controlled. or vasoactive drugs. vertebral. participant withdrew or was withdrawn from tilt arteries. or significant systemic illness Phillips AA. Then tilt table testing on 2 were recorded. Global symptom relief Size: n=171 pts at 25 centers score improved significantly. min of standing or 60 with SBP. concomitant administration of sympathomimetic agents. degree HUTT assessed Q5 mins for 60 m mmHg. and Heart Rhythm Society. and OH assessed.. prospective case. n=19 supine HTN of 180/110 pts) mmHg. and 60 degrees) and PCA. without measurement of 24436297 cerebral blood flow in bodied individuals (n=10) Comparator: Baseline symptoms.05). (multiple system atrophy. Inc. Aim: Assess effect of Inclusion: SCI (n=10) and Intervention: Midodrine 10 mg 1 endpoint: Tilt table (Progressively tilted Only assessment of MCA and 2014 midodrine on OH and age and sex matched able from supine to 30. BP: significant association between change in symptom score at 1 h to change in standing Exclusion: Pregnant. placebo. Comparator 1: Pyridostigmine midodrine 5 mg significantly increase standing symptoms without significantly OH autoimmune autonomic 60 mg + midodrine 2. renal disease.5 mg DBP compared to pyridostigmine + midodrine affecting supine HTN. double.. n=14. amyloidosis. n=9. symptoms of OH. Comparator 2: Pyridostigmine almost significantly compared to randomized. p<0. placebo neurogenic OH. prospective defined as SBP drop 30 Comparator 3: Placebo Secondary: Influence on SBP and supine BP: crossover. postmenopausal if a Comparator: Placebo Midodrine 20 mg increased standing SBP Midodrine at doses of 10 mg controlled.85). diabetic 2. and Heart Rhythm Society.36) or DBP 20 mmHg within 3 min of (p=0. and cerebrovascular accidents. neuropathy. and multiple Midodrine 10 mg increased standing SBP mg. system atrophy n=7). n=6).001 lactating. concomitant therapy with anticholinergic. significant CAD. et al. double. Intervention 2: Midodrine 10 mg time point. Supine SBP >200 mmHg 9674789 neurogenic OH SBP drop with standing.5 mg (p=0. 56+/-17 mmHg (p=0. occurred in 17% of pts on 10 (303) PAF.002) and Study type: Analytical. Aim: To assess dose Inclusion: >18 y of age. Aim: To assess Inclusion: Adults >18 y of Intervention: Pyridostigmine 60 Primary: Standing DBP at 1 h post drug: Pyridostigmine alone and in 2006 pyridostigmine alone or age with neurogenic OH mg pyridostigmine increased it from 49+/-14 to combination with midodrine with 16476804 in combination with (multiple system atrophy. OH controlled. increase of 34 mmHg.05. relation of symptoms to change in Size: n=58 pts standing.02). American Heart Association. n=15. in SBP (p=0. BP. Intervention 1: Midodrine 2. evidence of failure of other organ systems or of systemic illness that could affect autonomic function. blind. . prospective woman or taking significantly at 1 to 4 h post ingestion with a and 20 mg improves SBP with 105 © 2017 by the American College of Cardiology Foundation. and in 41% of pts taking 20 Study type: Analytical. Inc. hypothyroidism. or Size: n=65 pts paraneoplastic syndrome Singer W. PAF. p<0. CHF. or unspecified 60 mg + midodrine 5 mg pyridostigmine alone (p=0. severe anemia.03) and placebo (p=0. et al. and Intervention 3: Midodrine 20 mg significant 1 h post ingestion with a mean mg. Pyridostigmine with resultant improvement in (302) midodrine in neurogenic n=17. mmHg or mean BP drop no significant change. randomized. n=11. vasoactive agents Wright RA.5 mg did not Excessive HTN with 20 mg 1998 effect of midodrine in neurogenic OH (15 mmHg significantly increase standing SBP at any dose. autonomic neuropathy.51) blind. significant arrhythmia. adrenergic antagonists.5 mg 1 endpoint: Midodrine 2. norepi reuptake inhibitors. PAF. occurred with 10 mg and 20 mg doses. fatigue (5.9 mg 3x daily.001). use of vasoconstrictive agents within 2 d. symptomatic OH (n=6. 106 © 2017 by the American College of Cardiology Foundation. dizziness (304) of neurogenic OH system atrophy. or favor use of droxidopa in significant cardiac symptomatic neurogenic OH. tilted SBP (p<0.01) with degree tilt orthostatic challenge. American Heart Association. or gastrointestinal illness. Secondary endpoints 180/110 mmHg. parallel-groups mmHg within 3 mins placebo for 14 days of persistence of symptomatic phase 3 study standing Secondary: Change in OHSA items 2–6: improvement during withdrawal vision disturbance.8 in droxidopa group vs. or clinically significant abnormalities on exam. current use of TCA. renal.6% 2015 whether droxidopa is symptomatic OH assoc with TID and adjusted upward. prospective or DBP decrease ≥ 10 adjustment then withdraw to droxidopa but not statistically Unanticipated carryover effect cohort. weakness.9 +/-3.01) and tilted DBP (p<0. group. and head/neck discomfort). arrhythmia.5%).509). cardiac. mmHg. current use of anti HTN meds. crossover. p<0. et al. 1 endpoint: DL-DOPS increased supine The norepi precursor DL- 1999 DOPS in neurogenic failure pts with severe. most commonly 25350981 beneficial in treatment Parkinson disease. Biaggioni I. fatigue. significant systemic. mean and 4-item OHDAS: reported ≥1AE. contraception mean increase of 43 mmHg. SBP (p<0. Intervention: Droxidopa 100 mg Self Rated OH Questionnaire [6-item OHSA During open label 58. with Comparator: After upward 2.05). or non-diabetic Primary: OHSA item 1 increased by 1.180.. Secondary: Favored controlled. and Heart Rhythm Society. URI (4%). symptoms. 1.3%). concomitant administration of sympathomimetics or vasoactive drugs. autonomic neuropathy. Inc. During dopamine beta-OHase randomized to continue droxidopa double blind treatment. trouble phase even in the placebo Size: n=101 pts Exclusion: Severe HTN ≥ concentrating. supine dose. Freeman R. With increasing lactating. Inclusion: Autonomic Intervention: 3-4-DL. +/.05. AF. DOPS) 1000 mg DBP (p<0. there is also increased hypertension 180/110 frequency of supine HTN. Multinational. (2%). supine DOPS decreases BP fall with 60 10599797 OH. Aim: To assess DL.2 in and dizziness (4%) Randomized placebo SBP decrease ≥ 20 mmHg adjustment of droxidopa placebo (p=0. then dizziness/lightheadedness (8.6 Primary: pts change on OHSA item 1: headache (11%).3+/. Aim: To evaluate Inclusion: 18 y of age. multiple dose at randomization was 389. falls Study type: deficiency. threodihydroxyphenylserine (DL. et al. standing in dose-dependent Significant improvement in symptoms fashion with improvement in Size: n=25 pts Exclusion: Pregnancy. . headache (4%). Analytical. prospective cohort. with dose based on dose ranging mmHg) and standing (60 +/-4 to 100+/-6 12885750 severe neurogenic OH n=8 with PAF study mmHg. blind. Aim: To assess Inclusion: 51 pts with Intervention: Droxidopa Primary: Change in OH questionnaire 17 droxidopa recipients (71%) 2014 droxidopa effect in Parkinson disease enrolled dosage optimization for ≤ 2 wk composite score from baseline to wk 8 with AE. but the Randomized double.06) peripheral vascular disease. cause OH. administration of carbidopa blind placebo controlled mmHg while sitting). hyponatremia in 1 pts 2003 orthostatic tolerance in multiple system atrophy. Inclusion: Severe Intervention: L-threo-3. peak SBP occurring 300 m after medication Study type: Analytical. American Heart Association. Exclusion: Sustained. Size: n=51 pts 98% of falls occurred in 22 pts (43%). 24326693 neurogenic OH in in clinicaltrials. n=4. 94% of pts were able to orthostatic tolerance in severe Study type: Analytical. Secondary: OH questionnaire item 1 in 2 (8%) for neurogenic OH in mean study-drug dosage was 433 (dizziness. Mean OH qiestionnaire composite score OHQ. L-DOPS showed increase in plasma NE (which inhibits conversion of L- 107 © 2017 by the American College of Cardiology Foundation. neurogenic OH. dizziness (306) Parksonson disease. 1.gov followed by 8 wk of maintenance headache in 3 (13%). and tilt after DL-DOPS ingestion (p<0001). DOPS effect on BP and symptomatic OH (n=11 with dihydroxyphenylserine (L-DOPS) mean BP in supine (101+/-4 to 141 +/-5 placebo. Inc. Plasma norepi increased in supine Randomized double. (insignificant) rate of falls with controlled. symptoms and quality of life of orthostatic Size: n=10 pts cerebrovascular disease. affecting autonomic placebo. was too small to analyze benefit of droxidopa. controlled crossover. prospective Exclusion: N/A Droxidopa group with 1. Kaufmann H. then stand compared to 84% with placebo. 1 endpoint: L-DOPS significantly increased Supine HTN 45% vs.(305) multiple system atrophy. 23% in al. significant CAD. Trend toward improvement in function. droxidopa therapy (100-600 mg 3x daily). et Aim: To assess L.. randomized analysis. pregnancy or child-bearing potential not on birth control.21 (p=0. falls/wk in placebo (p=0. nausea in 3 (13%). . p<0. systemic illness forearm vascular resistance with DL-DOPS vs.001) L-DOPS improves BP and (307) At 3 m of standing. Comparator: Placebo. lightheadedness) and pts reported There was no benefit of Study type: Multicenter Parkinson disease interim mg falls droxidopa as measured by analytical. or malignant cardiac arrhythmias. NCT01176240. et al. medication impairing vasomotor function except fludrocortisone Hauser RA.9 droxidopa.4.2 vs.98). and Heart Rhythm Society. but this subgroup cohort phase 3 trial. or intolerance seen with DL-DOPS (p<0. There was a lower double-blind placebo Comparator: Placebo change at wk 8 was -2.001. placebo Exclusion: Alternative then 60 degree tilt table There was no significant effect on heart rate. -.0 falls/wk vs.16). severe HTN (>180/110 active standing p<0. PAF) Comparator: Placebo ingestion. dizziness al.9%) 24944260 OH system atrophy. 3.6%). multiple binder in place.2 vs. cohort adrenergic failure as compression that pts believed preference or ease of use. 4 protocol vs. . p=0. inability to tolerate 108 © 2017 by the American College of Cardiology Foundation. neuropathy Intervention: 7 d double blind randomization to end of study No continuous BP monitoring Randomized placebo trial of droxidopa Secondary: changes in symptom and controlled. blunt drop in BP.5%).003). 23 other failures. 0. Secondary: Pts assessment of preferences which apply pressure over larger prospective crossover of moderately severe Comparator 4: With abdominal and ease of use. prospective Exclusion: 95 titration symptom-impact composite scores. nausea (4.9%). plus a ≥ 10 mmHg increase from palpitations (1. in responders by 7 unit.03) Exclusion: pregnancy. prospective clinically significant CAD. multiple daily) followed.03) but other levels of compression did not have neuropathy. American Heart Association. or day washout and then baseline in standing SBP (308) non-diabetic autonomic Primary: OHQ improvement from Only 1 w duration of therapy. motor impairment affecting hand coordination. and cohort. With 10 OH defined as SBP ≥ 30 mmHg compression: -50 mmHg (interquartile mmHg or DBP ≥ 15 mmHg range -33 to -70 mmHg. and Heart Rhythm Society. 46 H. increasing effect unlike Study type: Analytical.93 units. Parkinson disease pts Size: n=19 pts disease. or cardiac DOPS. PAF. dementia. Inc. Aim: Assess effect of Inclusion: Moderately Moving from supine to standing Primary: Postural changes in SBP. level that remained significantly elevated for at DOPS to norepi peripherally) cohort cerebrovascular disease. measure by Valsalva. whether droxidopa neurogenic OH due to optimization (100 to 600 mg 3x defined as improvement on OHQ item 1 ≥ 1 (6. system atrophy. Mean standing SBP violations. diabetic Comparator 2: With abdominal 50 mmH (p=0. failure.9 mmHg. 2014 improves neurogenic Parkinson disease. arrhythmias Kaufmann H. et al. Additional (309) SBP with OH. Comparator 1: Without abdominal compression (10 mmHg) prior to compression of 10 mmHg may 25448247 on postural changes in diagnosis of Parkinson abdominal compression. crossover. rising blunted drop in BP from -57 mmHg to .001) Size: n=162 pts 6 randomized in error Figueroa JJ. parallel-group failures (50 had treatment Comparator: Placebo individual OHQ items trial of droxidopa failure. severe systemic illness. laboratory evidence tolerable abdominal compression. There was no difference in areas. et Aim: To determine Inclusion: Symptomatic Open-label droxidopa dose 1 endpoint: Responders to droxidopa Headache (9. may limit L-DOPS effect in peripheral vascular Cardidopa abolished pressor response to L. lactation. 6 withdrew OHQ composite score improvement (1. increase of 11. Mild Abdominal binders at minimal 2015 abdominal compression severe neurogenic OH. disease. consent.. autonomic Comparator 3: With maximal specialized shock garments Randomized controlled. compression did not have additional benefit. p=0. p <0.83 responders. would be tolerable for prolonged Size: n=13 pts induced hypotension period Standing without binder: -57 mmHg (interquartile -40 to -76 mmHg). Study type: Analytical. 12 AEs. p=0. and ankle placebo 27.and beta-adrenergic agonists for 5 half-lives prior to study. and 17010806 in elderly persons standing in initial 3 m. but (20 – 30 mmHg) for 10 m +/-25 mmHg with tilt for 10 m then to 106 +/.4%).2.9%). of graded calf volunteers mmHg. n=10 (2 mmHg. Symptom testing burden vis SSS-OI questionnaire decreased Size: n=21 pts from 35. p=0. prospective progressive decrease in BP degree modified Italian HUTT mmHg (p=0. due to spaceflight) pts given plasma volume loss between control (17. et Aim: To assess lower Inclusion: Pts with Intervention: Leg compression 1 endpoint: Sham placebo leg bandage Leg compression stocking is al. then measured effect on 60 SBP was 129 +/-19 mmHg. and then 127 +/- cohort pattern during diagnostic tilt 21 mmHg. suit inflatable in 25.18 mmHg to 112 with postural change. Change in SBP of control pts Pts not exposed to all Size: n=35 pts Comparator: Russian Kentavr – (-16 mmHg) was greater than antigravity suits deconditioning effect of non-inflatable elastic shorts and group (8 mmHg. bandage effect on OH (asymptomatic after m and then of the abdomen too SBP decreased from 125 +/.1%). calf placebo 29.1.0 m. and Heart Rhythm Society. et al.6 +/. Podoleanu C.9 +/.005) and Kentavr group microgravity.4 m. reduce symptoms over 1 mo (311) cannot tolerate afterward 25 mmHg after 20 m. and -60 mmHg for 10 min significantly different between compression difference in time to presyncope 2011 compression stockings each) on 3 occasions with stocking 26 +/. 32–54 y of age. Kentavr suits were able to 19456003 garments to prevent and passing a modified Air furosemide 0. due to increasing Comparator: Sham compression.2 to 22. Kentavr vs.02. With active bandage: randomized controlled hypotensive symptoms. control. resolve orthostatic intolerance (310) hypovolemia-related OI Force Class III physical. limb compression symptoms signs of OI bandages at 40 -60 mmHg for 10 and placebo abdominal bandage: able to decrease the SBP drop 2006. low-salt diet for 36 H during HUT. withholding of anticholinergic-/alpha.03.8 between compression stockings 22194814 on orthostatic tolerance Exclusion: CV or different types of stocking: m. consumed antigravity suit (16. et Aim: To assess effect Inclusion: Healthy HUTT and LBNP (-20 mmHg. control. Smaller to placebo. then 127 +/-17 cross-over. or Kentavr (18. -40 1 endpoint: Time to presyncope was not There was no significant al. to collaborate and to perform tilt testing Protheroe CL.035). control pts Intervention: NASA antigravity complete HUT.03) at 10 m tilt. Inc.9 mmHg Kentavr (10 pts) were able to complete HUTT: compressive force. although the and n=16 hypovolemic Only 9 of 16 (56%) control pts were able to Kentavr provided same benefit Study type: Analytical. p=0.01) after 1 mo of leg Exclusion: Inability of pts compression stocking therapy. inability to withhold midodrine night before evaluation Platts SH. prospective cohort Exclusion: none increments. follow-up Study type: Analytical. .5 (p=0. n=9 antigravity suit vs. 109 © 2017 by the American College of Cardiology Foundation. Aim: To assess ability Inclusion: n=19 healthy (To mimic plasma volume loss 1 endpoint: No significant difference in Both the antigravity suit and 2009 of 2 compression volunteers. (p=0. All antigravity suits (9 pts) and at approximately ½ of the randomized controlled..2. p=0. just acutely gaiters.5 mg/kg. No difference in diastolic reduced plasma volume then did 15 m 80 degree HUTT BP.02) at 20 min. American Heart Association. mean cerebral blood flow impedance and muscle tensing 17679677 to reduce OH in n=4. and not pts blind placebo-controlled length socks not designed to with OI. improve with compression stockings more Testing was performed in randomized double. TPR decreased by 30+/-15% (p<0. et al. et al. No alcohol. n=1) and symptomatic OH. Aim: Assess leg Inclusion: Healthy pts Orthostatic tolerance challenged 1 endpoint: All pts sustained greater Leg crossing increased 2006 crossing to increase at same time orthostatic challenge with leg crossing (34 +/-2 orthostatic tolerance in healthy 16714361 orthostatic tolerance. tobacco. and Heart Rhythm Society. DBP >20 mmHg within 15 s Comparator: Standing alone On standing with isometric handgrip. in MAP and cardiac output in Study type: Analytical. Parkinson disease.01). Aim: To evaluate Inclusion: Pts with Intervention: Inspiratory 1 endpoint: IO increased MAP by 8 mmHg (. heart rate increased by 62+/-18% standing can blunt the decrease (313) initial OH (defined as while maintaining isometric (p<0. Muscle tensing increased MAP by 9 mmHg (1 flow velocity. prospective provide compression (calf cohort placebo).05). p<0.001). had similar effects in increasing (315) autonomic failure atrophy.. and increase was lower (+13 bpm) with leg Randomized placebo caffeine use. Exclusion: No medications min). No Randomized controlled. Aim: Effect on isometric Inclusion: Young pts Intervention: Isometric 1 endpoint: With standing alone compared Maximum force isometric 2010 handgrip on initial OH in median age: 17 y of age contraction of nondominant arm to baseline.05). than during control (26 +/-2 min) or with pts (314) except oral contraceptive. noted. compression stocking. crossing (+18 bpm. Heart rate Study type: Analytical.01). Inc. than others. obstruction through narrowing of 1 to 13 mmHg). mCBFV by 9% (-7 to 18%).01). Comparator 1: NS to 10 mmHg). nonrebreathing valve (IO) MAP and mean cerebral blood n=1. symptom improvement was randomized controlled.01). Comparator 1: Without leg crossing during HUTT compared to control controlled crossover. MAP decreased by 42+/-10% handgrip before and during 20350727 young persons range 15-22 y of age with for 1 m then standing for 5 m (p<0. Intervention: With leg crossing placebo (23+/-3 min. anti-Hu neuropathy. cardiac Exclusion: Systemic output decreased by 2+/-14% (p<0. Muscle tensing and inspiratory 2007 respiratory impedance autonomic failure (PAF. and TPR was unchanged at younger pts with initial OH. n=3. n=1. and disease. . American Heart Association. et al.65). Comparator 1: Ankle-length Size: n=15 pts socks (ankle-placebo) Clarke DA.05) cross-sectional cohort Comparator 2: Placebo table Size: n=9 pts Thijs RD. >40 mmHg or a decrease in 17+/-21% (p=0. chronic OI Krediet CT. crossover. cardiac output decreased by 33+/. p<0.(312) neurological disease Intervention: Calf-length graded calf circumference may predict individuals who Study type: Analytical.01)%. vasovagal fainting. Size: n=14 pts increased by 33+/-17% (p<0. healthy volunteers. prospective crossover Healthy pts as control Comparator 2: Muscle tensing of Pursed lips during inspiration increased MAP 110 © 2017 by the American College of Cardiology Foundation. transient decrease in SBP handgrip 17% (p<0. but no difference in Study type: Analytical. Less than maximal of standing) with symptoms decreased by 31+/-9% (p<0. multiple system inspiratory tube of 2 way velocity (mCBFV) by 8% (2 to 23%). heart rate force handgrip not performed. formal evaluation of symptoms prospective cohort. amyloidosis. MAP performed. Comparator 1: Standard calf. prospective defined as SBP drop 30 Comparator 3: Placebo Secondary: Influence on SBP and supine BP: crossover. lactating.36) or DBP 20 mmHg within 3 m of (p=0.03) and placebo (p=0. squatting (+38 mmHg. et al. (n=10) legs without leg crossing by 1 mmHg (-7 to 8 mmHg).0 mmHg. Singer W. n=11. Other Study type: Analytical. et al. to perform it adequately.002) and Study type: Analytical. countermaneuvers increase BP randomized controlled. p=0. Pyridostigmine with resultant improvement in (302) midodrine in neurogenic n=17. autonomic neuropathy.001). mmHg or mean BP drop no significant change. Exclusion: Cardiac Comparator 3: Breathing through disease or used pursed lips during inspiration No significant difference in symptom scores antihypertensive was noted between maneuvers medications Comparator 4: Inspiratory sniffing Tutaj M.5 mg. pyridostigmine increased it from 49+/-14 to combination with midodrine with 16476804 in combination with (multiple system atrophy. PAF. Aim: To assess Inclusion: Adults >18 y of Intervention: Pyridostigmine 60 Primary: Standing DBP at 1 h post drug: Pyridostigmine alone and in 2006 pyridostigmine alone or age with neurogenic OH mg. squatting (+49 mmHg. BP but only 7 of 17 pts with (316) and active standing Comparator 1: Squatting. p=0. Comparator 1: pyridostigmine midodrine 5 mg significantly increase standing symptoms without significantly OH autoimmune autonomic 60 mg + midodrine 2. p=0. p=0. p=0. American Heart Association.02). with leg prospective crossover midodrine for 18 h. n=9.6 mmHg. (+2. leg crossing (+8. p<0.01). neuropathy. OH controlled. 56+/-17 mmHg (p=0. BP. n=15.30).02) but no change during abdominal compression. p=0.. or unspecified 60 mg + midodrine 5 mg. diabetic 2. relation of symptoms to change in Size: n=58 pts standing. DBP compared to pyridostigmine + midodrine affecting supine HTN. pyridostigmine alone (p=0.5 mg (p=0. in SBP (p=0. . abdominal compression (+27 mmHg). BP: significant association between change in symptom score at 1 h to change in standing Exclusion: Pregnant.51) blind. and Heart Rhythm Society. placebo neurogenic OH. countermaneuvers.001. for 18 h prior to procedures p=0. n=6).0005). Inc. midodrine) held mmHg. to lesser degree. 16 of 17 pts able to countermaneuver in increasing 16096819 familial dysautonomia gene mutation perform at least 2 countermanuevers.004). mCBFV by 2% (- Size: n=20 pts 11 to 9%).002). Aim: Assess effect of Inclusion: Familial Physical countermaneuvers 1 endpoint: 7 of 17 pts able to perform all 4 Squatting was most effective 2006 countermaneuveres in dysatuonomia with IKBKAP Intervention: Leg crossing. comply with discontinuation Comparator 2: Bending forward p=0. double.85). evidence of failure of other organ systems or of systemic illness that 111 © 2017 by the American College of Cardiology Foundation. SBP increase during bending forward (+23 familial dysautonomia were able Exclusion: Pts unable to mmHg.3 mmHg. Comparator 2: pyridostigmine almost significantly compared to randomized.0005). leg crossing (+11. crossing likely least effective Medication affecting CV system DBP increase during bending forward (+12 Size: n=17 pts (fludrocortisone. of fludrocortisone or with abdominal compression. renal disease. lives before testing with BP increase also seen in (318) Healthy controls. MSA. in autonomic failure and healthy 10073520 case control. and cerebrovascular accidents. et al.4 mmHg (p<0. Inc. healthy controls. OH.001). . Healthy controls also noted an increase in SBP of 11+/- 2. could affect autonomic function. Protocol 1: Inclusion criteria: 18 consecutive 1 endpoint: Rapid water ingestion of 480 2002 Study type: Analytical.001). Study Type/Design. BP increased 33+/-5/16+/-3 mmHg in BP was 30 to 35 mins after Exclusion criteria: Secondary (p<0. 10662747 case control. There was no difference between drinking cold vs. Jordan J. No significant change sympathetic activation Size: n=30 pts in plasma volume was seen in healthy controls and 5 pts with Exclusion criteria: None autonomic failure. and Heart Rhythm Society. n=10. et al. Results: In both autonomic failure and healthy controls. and increased 37+/-7/14+/-3 mmHg in PAF ingestion. Observational Studies. prospective autonomic failure with “disabling” Vasoactive medications and fludrocortisone discontinued ≥5 half.001) in MSA. multiple system atrophy. Inclusion criteria: Severe OH 1 endpoint: 480 mL tap water Water ingestion increased BP 1999 observational. The peak elevation Size: n=66 pts Results: With water drinking. n=11 ingestion raised SBP by 11 mmHg (p<0. n=19. CHF. possibly through (317) n=9). This effect is largely causes of autonomic failure (DM. (p<0. water controls.001). hypothyroidism. healthy pts. adrenergic antagonists. Inclusion criteria: primary 1 endpoint: 480 mL tap water Water ingestion has a pressor 2000 observational. prospective due to autonomic failure (PAF. Enhanced pressor effect present with yohimbine plus water. pts with primary autonomic failure Protocol 1: mL at room temperature 112 © 2017 by the American College of Cardiology Foundation. Study type: Analytical.. Shannon JR. vasoactive agents Data Supplement 34. Nonrandomized Trials. concomitant therapy with anticholinergic. and/or Registries of Neurogenic Orthostatic Hypotension – (Section 6. warm sympathetically driven. n=28. Drinking 480 mL had a greater pressor response than 240 mL water. response in autonomic failure. OR or RR. Comment(s) Year Published & 95% CI) Jordan J. significant arrhythmia. n=19.1) Study Acronym. American Heart Association. significant CAD. PAF. et al. Norepi levels increased in controls with water ingestion. Healthy controls undergoing ganglionic blockade did not have pressor effect with water. Patient Population Primary Endpoint and Results Summary/Conclusion Author. Study Size (P values. severe anemia. amyloidosis) water. Study type: Analytical. Study type: Inclusion: PAF with sympathetic 1 endpoint: 480 mL distilled room temperature water. and 7 pts (Stand 2) in standing BP appeared related Size: n=14 pts with PAF which is postganglionic to increase in baseline BP after water ingestion. Study type: Analytical. prospective Protocol 2: cohort Intervention: eat a meal then 480 mL tapwater at room temperature Size: n=27 pts Comparator: no tapwater then active standing Results: Protocol 1: Seated BP increased from 117/67 mmHg before water drinking to 150/78 mmHg with water drinking (P<0. 113 © 2017 by the American College of Cardiology Foundation. mins) Water ingestion raised SBP and DBP and lowered heart rate at 3 min of Stand 2 compared to before water. BP increased from 83/53 mmHg before water drinking to 114/66 mmHg with water drinking (p<0. randomized and parasympathetic dysfunction cycle ergometer followed by active standing 18469030 controlled crossover. with severe OH.01). all mins) compared to MSA (13 p<0. Inclusion criteria: chronic 1 endpoint: 480 mL of distilled water at room temperature within 5 Water ingestion increased 2004 observational.. et al.01. Exclusion criteria: None observational. p<0. With water ingestion. After 1 min of standing. and pts with autonomic failure as Size: n=27 pts n=9 pts with idiopathic orthostatic Comparator: no tapwater well as post-prandial intolerance with 6 mo of symptoms. Inc. but at 5 min.01).01. Increase (320) which is preganglionic. et al. prospective (multiple system atrophy n=9. and with eating BP reached an average nadir of 95/57 mmHg. . Maximal tolerated standing time increased from 5+/-3 min before water drinking to 11+/-10 min after drinking (p=0. and Heart Rhythm Society. and average nadir of 116/65 mmHg Young TM.06). Humm AM. Protocol 2: Baseline BP was 138/77 mmHg. hypotension Protocol 2: then active standing Study type: Analytical. then supine N/A 2008 Analytical. only SBP and DBP had significance. Pressor effect Results: Water ingestion raised SBP and DBP and lowered heart occurred sooner in PAF (within 5 Exclusion criteria: None rate at 3 min and 5 min of Stand 1 compared to before water. BP increased to average peak 174/86 mmHg. American Heart Association. and Intervention: 480 mL tapwater at room temperature in <5 min improves orthostatic tolerance in (319) cohort PAF n=9) with disabling OH.01.11904109 observational. all p<0. prospective autonomic failure (7 pts with min then remained seated for 15 mins before standing for 5 min standing BP and reduced 15548493 cohort multiple system atrophy [MSA] (Stand 1) then seated for 15 min then standing for 5 min again symptoms due to OH. .6 mg TID No placebo control. Study Size (N) Study Comparator P values. n=1). standing with greater blind. with exercise.1) Study Aim of Study. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any). Size: n=8 pts With water ingestion.5 to 10 mg 3x daily. ephredine Size: n=8 pts persistent supine hypertension 80 mmHg (p<0. prospective cohort Size: n=9 pts Fouad-Tarazi Aim: To assess efficacy Inclusion: autonomic Intervention: Midodrine Results: Mean midodrine dose 8. 7503082 unable to tolerate other Midodrine and ephedrine both increased supine Midodrine was able to (323) Study type: Analytical. et al. and placebo Exclusion: recent history of mmHg and standing SBP placebo (p<0. open which was continued label. scalp tingling (n=1) 1995 ephedrine. OR or RR.(321) prospective cohort Results: Without water ingestion.9+/-10 mmHg). placebo) did not increase maintenance of SBP with controlled crossover.1 mmHg) but BP remained higher after water intake although not quite significant (p=0. midodrine effect in dysautonomia. Inc. Nonrandomized Trials. Data Supplement 35. & 95% CI) Adverse Events Year Published (# patients) Axelrod FB. or resistant daily) to where supine SBP Ephedrine (vs. and Heart Rhythm Society. placebo retention. whereas with water ingestion. treatments because of physical Comparator: ephedrine BP vs. Only midodrine produced a >180/100 mmHg unrelated to significant reduction in postural symptoms as 114 © 2017 by the American College of Cardiology Foundation.1+/-24. Exclusion: None Comparator: No midodrine dizziness.01 for both) not significantly improve tolerance to Randomized double. Without water ingestion. standing BP but did heart rate (p<0. n=7. fluid (titrated from 6 to 24 mg 3x significantly different from each other. daily) Mean ephedrine dose 22. OH 3x daily titrated up All 9 pts had dizziness at baseline. DBP fall (25.09). placebo (p<0. (# patients) / (Absolute Event Rates. disability. standing compared to ephedrine prospective cohort and supine DBP <100 Midodrine increased standing SBP and DBP vs. gastric irritation.0+/-9.001). Study Limitations..05). 5 pts were on fludrocortisone observational. Author. 3 of 8 pts completed 5 min standing protocol. SBP fall was still present (49. and with noted symptomatic improvement 1995 treating OH in familial midodrine 7 had improvement or resolution of in this small open label study 8690848 dysautonomia. Observational Studies. Mean increase in standing BP was (322) not significant. of midodrine with insufficiency (idiopathic OH. Acronym. but most pts al.001) and vs. Study type: Analytical. FM. 7 of 8 pts completed protocol.4 mg 3x Midodrine: supine HTN (n=1).9 mmHg). American Heart Association. Study Type.5 Results: Average dose: 3. multiple system atrophy.8+/-18. and/or Registries of Neurogenic Orthostatic Hypotension – (Section 6. et Aim: To assess Inclusion: Familial Intervention: Midodrine 2. (titrated from 2. with exercise there was SBP fall Exclusion: None (42.4 mmHg). DBP fall (26.3 mg 3x daily. hypokalemia between 140-180 mmHg. symptomatic CAD. pheochromocytoma. drug therapy.2 y of age (range 62-89 y Graduated elastic compression 1999 compression hosiery in reproducible.4%.7 mmHg. Parkinson’s disease. symptomatic OH elastic compression hose of age). mental dizziness. serum creatinine significantly from baseline with L-DOPS.01 vs. upset (9. 2001 in management of autonomic failure and symptoms from 100 mg BID to 300 mg standing (22+/-28 mmHg. p<0. SBP 30 mmHg or mean BP to 40 mmHg as 1) bilateral followed by Abdomen 102.1%). Aim: Whether Inclusion: Pts with neurogenic Intervention/ Comparator: Results: Order of efficacy in reducing Compression of abdomen and 1997 compression of OH (multiple system atrophy. and Heart Rhythm Society. G suit with 5 separate orthostatic symptoms from best to worst: All (13 legs. AF. shown by increased ability to stand (5. et al. p=0.1%). Exclusion: idiopathic In 25 pts (78%).0 prospective cohort. 6) baseline tilt (80 noncompression.1%) Multicenter. American Heart Association. neurogenic OH Maximal improvement in orthostatic BP OH defined as decrement in Compartments were inflated occurred with All (115. vs.1+/-17. The other compartments compression low Abdomen. improves BP. Size: n=33 pts >130 micromol/L. combination of 1) and 2). 2) bilateral thighs. orthostatic symptoms and symptomatic Exclusion: None calf bladders). concomitant MAO inhibitors Denq JC. observational. degrees for 5 min) without compression Improvement correlated to increase in TPR. No supine disorder. prospective current use of any BP definition. syncope) and OH BID to baseline SBP. Aim: Effect of Inclusion: elderly pts with Intervention: Graduated Results: Mean: 77. p<0. but no HTN was seen. Inc.0001) compared (12.9+/-7. related symptoms in pts with cohort antiparkinsonian drugs.0124) compared to baseline DBP. Compression hosiery resolved hose improves orthostatic 10406369 elderly persons with OH (>20 mmHg) symptoms of orthostatic dizziness in 7 of 10 tolerance and symptoms 115 © 2017 by the American College of Cardiology Foundation.3+/-4. there was a decrease in OH. 3) p<0.2 headache (9. standing SBP 80 mmHg dementia. et Aim: Effect of L-DOPS Inclusion: 18–75 y of age with Intervention: L-threo-DOPS Results: L-DOPs blunted SBP decrease with Increase lactate dehydrogenase al.1%). narcotic correlation was found between change in abuse. urinary tract infection 11710796 neurogenic OH (dizziness. .005)) Study type: Analytical.2+/-8. > moderate alcohol postural SBP decrease and change in clinical consumption (>1 L of beer or symptom scores. and blurred vision improved autonomic failure.4 mmHg. 14. OH was no longer observed by L-DOPS reduces OH and label. child-bearing potential. and even abdominal 9430805 different capacitance PAF. p=0. 5) All sites results were not significantly different from Size: n=14 pts combined. observational. significant liver correlated in increased percentage with disease. Mathias CJ. 64%) > calves compression alone improves (324) beds can improve abdominal. 93%) > abdomen (9 of 14.01) vs. 2 thigh. 20 mmHg calves. analytical. (325) (drop in SBP ≥20 mmHg) decrease with 2-min standing (8.1%). and 2 + thighs = calves alone > thighs. equivalent daily). Symptoms of light-headedness.6+/-7. and stomach Study type: mmHg. or autonomic neuropathy) compartments (lower of 14. et al. drug hypersensitivity Henry R. 4) mmHg).4% acute or chronic renal failure..0+/-6. prior use or In 14 ps (44%). akinesia (9. L-DOPs blunted DBP (12. noncompression (89. placebo) which thyrotoxicosis. open. 005).005. 2006 with inflatable study enrolling between 7/2004 standing test. Supine SBP elevation was antihypotensive medications (327) hemodialysis pts with Intervention 2: Some pts not seen with the abdominal band (149 vs. chronic hypotension (defined as pre-dialysis SBP of <100 mmHg) Ten Harkel AD. Leg improved BP. admission to n=3 hospital. bleeding medications (L-threo-3. mm Hg) vs. Exclusion: None without compression hose baseline to 0. with squatting (329) Exclusion: None Intervention 1: leg-crossing crossing improved SBP to 95/60 mmHg with having larger effect. p<0. et Aim: To assess Inclusion: Hemodialysis pts and Intervention: Inflatable Results: Delta SBP was significantly less after Inflatable abdominal band was al. observational. Aim: Effect of leg Inclusion: normotensive pts Intervention: leg crossing Results: Leg crossing resulted in increase in Leg crossing increases BP and et al. abdominal compression OH for at least 6 mo before abdominal band then active hemodialysis with the abdominal band (-19. Exclusion: None output. symptoms such as leg edema DOPS].8 mmHg at acutely. 153 OH Exclusion: severe anemia received antihypotensive mm Hg). hypervolemic dihydroxyphenylserine [L- observational. MAP 58 mmHg). Size: n=25 pts apparent infection.01. poor compliance. Inc. n=7. treatment for Intervention 3: midodrine. muscle pumping and (n=6). American Heart Association. (BP 139/75 mg supine decreasing to orthostatic intolerance and 1348300 autonomic failure 75/50 mmHg upright. 7 pts had orthostatic dizziness within 10 min of improved symptoms of 1992 orthostatic tolerance in with OH.4 mmHg+/-8. maneuvers can improve dysfunction (hypoadrenergic) upright until presyncopal. 2. and then standing upright MAP 72 mmHg.2 mmHg with required. With recurrence of 116 © 2017 by the American College of Cardiology Foundation.(326) Comparator: baseline pts. hypoadrenergic OH (OH. Study type: Analytical. crossing normal pts vs. healthy pts.01 respectively) Size: n=10 pts Yamamoto N. and Heart Rhythm Society. open compression hose (p=0. . n=5. observational.2 in pts already receiving 17003821 abdominal band in to 8/2004. pts respectively. 5 of Both leg crossing and squatting al. cross- sectional cohort Size: n=13 pts Van Lieshout. prospective cohort and pleural effusion. Mean fall was label. and p=0. et Aim: Whether physical Inclusion: autonomic Comparator: Standing Results: In autonomic dysfunction group. Delta HR after hemodialysis was (Hematocrit <25%). Pts with PAF (328) and non-PAF noted increase in BP and cardiac Study type: Analytical. Long term studies are Study type: Analytical. Mean fall in SBP was 20. p<0.4 able to reduce post dialysis OH. prospective then 90 degree HUTT significantly blunted with compression at HUTT cohort mins 1. without the abdominal band (-36. mm Hg.3+/-3. and 3 (p<0.002). n=6 followed by standing. tendency. BP (13+/-2 mmHg vs.. 9+/-7 mmHg). 7874844 pressure n=4. 38+/-15%) in and hypoadrenergic OH.4. significantly greater with the band Study type: Analytical. and cardiac output in both normal 1994 tensing on orthostatic n=7) of which PAF comprised Comparator: no leg cardiac output (49+/-13% vs. & 95% CI) Adverse Events (# patients) Anley C. prospective to cooperate (CHF. Singer W. CAD.01) before study Data Supplement 36. adrenergic antagonists. BP was 74/47 mmHg with MAP 56 prospective cohort. (p=0. SV.0 vs. severe anemia. any). Squatting increased BP to 131/81 Intervention 2: followed by mmHg (MAP 100 mmHg). Then 70 degree HUTT for 5 significant difference in SBP. significant arrhythmia. significant sensitivity (BRS): significantly higher after cohort. observational open. until presyncopal presyncope. (# patients) / (Absolute Event Rates. pyridostigmine (p<0. upright until presyncopal In healthy.03) and upright therapy with anticholinergic. that could affect study results. Study Limitations. autonomic function or pts ability mins cardiac index. or Heart rate blunting and increased plasma medications that could interfere catecholamine levels were associated with with autonomic function unless significant amelioration of orthostatic symptoms discontinued for 5 half-lives (p=0. vasoactive agents. Acetylcholinesterase inhibition 2006 acetylcholinesterase old with orthostatic intolerance 60 mg heart rate was significantly lower in both supine may enhance sympathetic 17016160 inhibition in orthostatic (73.. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if Author. et al. Symptoms improved Size: n=13 pts squatting and then standing with both maneuvers. 78. Year Published Study Size (N) Study Comparator P values. p<0.005) positions. et al.2) Study Acronym. oral fluid and 1 endpoint: Time to discharge from the With no difference in time to 117 © 2017 by the American College of Cardiology Foundation. failure of other organ pyridostigmine systems or of systemic illness Secondary: Other CV parameters: no Study type: Analytical. Aim: To assess which Inclusion: All Intervention: OT. there was much milder increase with leg-crossing (+4/0 mmHg) and with squatting (+12/4 mmHg). 123. pyridostigmine for supine (p=0. American Heart Association. RCTs Involving Dehydration and Drugs – (Section 6.005).6 ganglionic transmission and (330) intolerance during Exclusion: Pregnancy or Comparator: No vs.7 bpm. Study Type. . OR or RR. Influence on plasma catecholamines: plasma Size: n=18 pts hypothyroidism. observational. renal disease.9 bpm) and upright position (110. Inc. Aim: To assess Inclusion: at least 18 y of age Intervention: Pyridostigmine Primary: Heart rate: 1 h after pyridostigmine.001) improves orthostatic intolerance HUTT lactating. and Heart Rhythm Society. Influence on baroreflex label. MAP. Aim of Study. DBP. mmHg. and norepi significantly higher 1 h after cerebrovascular accidents). discretion. 10 mL every 5 mins if ≥4 y of stay: department stay. over 30 min period. rate of 1. p=0.2 access for reasons other than hydration Relapse after being discharged: Results: 0% in both ORT and IV groups Keneflick RW. IV: 65+/-44 dehydration.8 min vs. the results in earlier ultra-distance footrace IV (52.8+/-32 min vs.. n=18 care compared to intravenous randomized.1% vs. Exclusion: Abnormal Secondary endpoint: Heart rate and BP vasodilatation resulting in randomized. prospective Secondary endpoints: rehydration for pediatric pts cohort Exclusion: Chronic Comparator: IV therapy (initial bolus Staff time require for pts care: presenting with moderate illness. and was significantly less than IV group 1045+/-185 ml.47 associated postural hypotension is peripheral Study type: Analytical. but significantly less 20584756 exercise-associated two Ironman Triathlon fluid given in OT group (293) postural hypotension competitions and one Comparator: IV Results: No significant difference between compared to IV group. Size: n=28 pts Total volume of fluid in OT group was 204 +/- 149 ml. quickly than oral rehydration. Atherly-John YC.7 +/. subsequent exercise in Sensation of thirst was 118 © 2017 by the American College of Cardiology Foundation. and intake was advanced to twice Results: Oral replacement therapy: 224. p<0. This was followed by IV Parent satisfaction: no accompanying solution of 5% dextrose in 0. time required for pts care. .03 protracted vomiting. rehydration therapy with with moderate therapy: 5 mL every 5 min if <4 y of Duration of pediatric emergency department shortens emergency 2002 IV therapy for moderate dehydration (having at age. p=0. IV: 37. reduces staff 12444837 dehydration in children least 4 standard age.5%. p<0. and (331) published criteria) at the initial volume if there was no 77.001.7% vs. et Aim: To determine Inclusion: Healthy Each subject performed 3 trials: 1 endpoint: To determine effects of rapid Although IV hydration al. Inc. on CV.5 +/. p=0.45% or Results: ORT: 77. oral rehydration immediately restored plasma volume more 2006 IV vs oral rehydration men pts walked or ran for 75 min at 50% after dehydration.5 times daily maintenance.01 guardian. IV 358 +/-160 min. Size: n=34 pts dehydration or shock.18 min) and OT group (58+/-23 probable cause of exercise discharge in 2006 and 2007 min). single center vomiting during the first H. and Heart Rhythm Society. and second bolus min. Aim: To compare oral Inclusion: Children Intervention: Oral replacement 1 endpoint: Oral rehydration therapy et al. American Heart Association. was given per treating physician absent bowel sounds.2011 treatment protocol for collapsed athletes at Trendelenburg position medical tent (in min) discharge. effects of rapid (<30 min) non heat acclimated 1) Dehydration phase. 17146319 immediately after VO2 max with airflow directed to and perceptual responses during subsequent there was no significant effect (332) dehydration during Exclusion: N/A enhance evaporative sweat loss exercise on exercise duration. (<30 min) IV vs. no contact 0. IV: 25%. thermoregulatory. Hospital admission rate: and those requiring IV n=16 Results: ORT: 11.33% saline depending on age at a telephone number. severe of 20 mL/kg of isotonic sodium chloride Results: ORT: 35. prospective serum sodium changes: venous pooling cohort Results: No significant changes were seen. p=0.01 improves satisfaction with pts Study type: Analytical. Then: Sensation of thirst was significantly lower in 3) heat-tolerance test: oral rehydration than IV fluid (p<0.45% However. oral Intervention 3: No fluid rehydration. Merson SJ.6+/- Size: n=8 pts Intervention 2: Oral rehydration 28. et al. receive amount of fluid lost during volume restoration (p<0.5 times of fluid with increasing sodium (333) after exercise Exclusion: N/A body mass loss of: Results: concentration Intervention 1: Net fluid balance at end of trial: Study type: Analytical. Na content 2 mmol/L (108 mosmol/kg) Sodium content 2 mmol/L: -689 mL randomized. the heat 2) Rehydration phase Rehydration Results: improved with oral rehydration. Intervention 3: 40 mmol/L Pts retained more of test drink as the did not affect repeat exercise randomized.6+/-8.05) randomized. and Heart Rhythm Society. American Heart Association. et al. Aim: To investigate Inclusion: Healthy Exercise via cycle ergometer with 1 endpoint: Sodium chloride concentration Increased sodium content of 2008 differing sodium chloride men without Hx of CV measured VO2 max then drinking effect on rehydration after exercise and the test drink improved 18463891 concentrations affect or renal disease 150% of fluid lost as sweat: subsequent exercise capacity hydration compared to lower (334) rehydration Intervention 1: NaCl 0 mmol sodium and no sodium test Exclusion: N/A Intervention 2: NaCL 30 mmol/L Results: drinks. Inc.45% saline) heat tolerance testing with IV vs. there was no significant saline) improvement in exercise duration (IV: 72.2 min) during the (0. . oral: 70. Aim: To study the effect Inclusion: Healthy Pts were dehydrated by intermittent 1 endpoint: Effect of sodium content of Rehydration and retained 1995 of sodium content of males cycle exercise in warm and humid drinks on rehydration after exercise volume is greater with ingestion 8549573 drinks on rehydration environment then ingested 1. prospective Intervention 4: 50 mmol/L sodium concentration of the drink increased performance. prospective Intervention 2: Sodium content 26 mmol/L: -359 mL cohort Na content 26 mmol/L (158 Sodium content 52 mmol/L: 2 mL mosmol/kg) Sodium content 100 mmol/L: 98 mL Size: n=6 pts Intervention 3: Na content 52 mmol/L (206 Plasma volume was higher with sodium mosmol/kg) contents of 52 and 100 mmol/L compared to Intervention 4: 2 mmol/L Na content 100 mmol/L (300 Cumulative urine output was higher on mosmol/kg) sodium content 2 mmol/L than with 52 mmol or 100 mmol/L.05) immediately after 30 min rehydration period.9 min. pts performed a 75 min heat tolerance test in 37°C chamber Maughan RJ. Higher sodium drinks Study type: Analytical. prospective dehydration: cohort Intervention 1: IV rehydration (0. 119 © 2017 by the American College of Cardiology Foundation.. treatments were randomly assigned to IV rehydration resulted in more rapid plasma Study type: Analytical. prospective with LBNP up to -40 mmHg taking placebo showed significant increases 24 h urinary sodium excretion) cohort. (335) by astronauts to restore plasma Intervention 1: water 120 © 2017 by the American College of Cardiology Foundation. Study Size (P values. Greater net negative fluid balance was seen 4 h after finishing drinking with lower sodium concentration test drink.01).2) Study Acronym. Patient Population Primary Endpoint and Results Summary/Conclusion Author.Sayed H. Pts with signs of Randomized placebo 60 degree HUTT RDBPCT: 8 of 10 pts taking salt.. Comment(s) Year Published & 95% CI) Greenlead JE. and/or Registries of Dehydration and Drugs – (Section 6. There was no effect of the sodium content of the drink on time to exhaustion on repeat exercise (p>0.8) El. Observational Studies. and these pts showed improved symptoms of orthostatic tolerance Data Supplement 37. nonsmokers. no drug plasma osmolality (298-305 mOsm/kg) then drank 1 of 6 fluid more important than total osmotic 9737753 formulations for consumption use formulations (12 mL/kg: 898-927 mL): content for inducing hypervolemia. American Heart Association. Inc. in plasma and blood volumes (p<0. Exclusion: N/A Comparator: Placebo 12x daily then Results: tolerance. OR or RR. Aim: To evaluate various Inclusion: Healthy young Pts dehydrated for 24 h with moderate dehydration confirmed by Sodium content appears to be 1998 carbohydrate electrolyte fluid men. prospective cohort then 60 degree HUTT with LBNP up to Open label: 7 of 11 taking salt had increased Size: n=11 pts -40 mmHg plasma and blood volumes. et al. et al. and Heart Rhythm Society. . 3 of 10 high salt intake at baseline (by controlled. cohort (as measured by corresponding decreasing Then exercised again to 95% of VO2 urine output). Significantly more fluid was Size: n= 8 pts peak or exhaustion retained on 40 and 50 mmol/L NaCl compared to 0 mmol/L (p<0. Aim: To evaluated salt Inclusion: Recurrent RDBPCT: 1 endpoint: Effect of salt administration on Pts with salt supplementation 1996 supplementation in syncope without Intervention: plasma volume and orthostatic tolerance in (increasing plasma volume by 8673750 syncope with OI etiology sodium chloride 10 mmol pts with posturally related syncope >90 mL) had significant (232) increase in orthostatic Study type: Analytical. Study Type/Design. all did not benefit from additional Size: n=20 pts Open label: pts with increased plasma and blood salt loading Intervention: slow sodium 10 mmol volumes showed improved tolerance to Study type: Analytical.05). Nonrandomized Trials. open dietary supplement”) label. 12x daily (pts told it was a “mineral orthostatic stress (time to presyncope) observational. vs. Intervention 4: 19. Shirreffs SM. cohort Both drinks also contained small amounts of potassium and Size: n=12 pts glucose (90 mmol/L). 157 Na resulted in 7. .05. water was the least effective with an initial loss (17%) of plasma volume within the first 9 min of exercise. drinking 157 Na (the largest Na content). drinking formulations with higher sodium had greater increases in plasma volume. induced the greatest hypervolemia: 7. Aim: To study the interaction Inclusion: Healthy men Each subject exercised to induce sweat loss of 2% of body mass Drinking a large volume beverage 1996 between volume and then drank beverages with different sodium concentration and may be inadequate to rehydrate if 8897383 composition of fluids ingested Exclusion: N/A volumes: the sodium concentration is (336) for rehydration effectiveness Sodium concentration: insufficient.6 mEq/L Na Intervention 3: 157 mEq/L Na Study type: Analytical.. prospective Intervention 2: high sodium (61 mmol/L) volume is not consumed. p<0. However.6 mEq/L Na + glucose observational. water ingestion did not increase plasma volume. and Heart Rhythm Society.6%. At rest. et al. high sodium intake beverages were no more effective than low sodium beverages for plasma volume stabilization. Volume: Intervention A: 50% of body mass loss Intervention B: 100% of body mass loss Intervention C: 150% of body mass loss Intervention D: 200% of body mass loss 121 © 2017 by the American College of Cardiology Foundation. Or be inadequate if a large enough observational. American Heart Association. Inc. prospective Intervention 5: Performance® ~20 mEq Na cohort Intervention 6: Power Surge® ~20 mEq Na Size: n=7 pts 1 endpoint: Plasma volume and total body water Results: At rest. With exercise. Lower sodium content beverages but with higher total osmolality did not hydrate as well. and drinking a high- Intervention 1: low sodium (23 mmol/L) sodium concentration beverage may Study type: Analytical. volume Exclusion: N/A Intervention 2: 19.6% increase in plasma volume. G3: 35 min. Jeukendrup AE. 6% glucose. C=867 mL. . n=10 pts) fluid delivery. or 9% 122 © 2017 by the American College of Cardiology Foundation. and Heart Rhythm Society. C=602 mL. B=260 mL. G6:43 min. Aim: To study the effects of Inclusion: Healthy males Each subject undertook 4 trials each >7 days apart Increasing the glucose content 2009 increasing carbohydrate and above 3% did not further increase 19232115 sodium content on fluid delivery Exclusion: N/A Carbohydrate group (CHO. et al. Intervention 2: G3: 3% glucose + 20 mmol/L sodium although there was a trend for observational. American Heart Association. Study type: Analytical. Total urine output with high sodium beverage: A=144 mL.. 1361 mL. Repeat tests were separated 1 wk apart 1 endpoint: Rehydration effectiveness as measured by urine volume output and whole body net fluid balance Results: Total urine output with low sodium beverage: A=135 mL. D. G9:51 min) Plasma deuterium enrichment was significantly greater with 3% glucose (p<0. D=1001 mL Pts rehydrating with low sodium beverage were in a more negative state of fluid balance with Intervention A (-909 mL) than Intervention C (-128 mL) or D (-135 mL) Pts rehydrating with high sodium beverage were in a more negative state of fluid balance with Intervention A (-958 mL) than Intervention D (+427 mL). Inc. Sodium content did (337) Intervention 1: G0: water + 20 mmol/L sodium not significantly affect fluid delivery. Size: n=20 pts Sodium group (Na. B= 493 mL. Intervention 4: G9: 9% glucose + 20 mmol/L sodium with higher sodium content. n=10 pts) Intervention 1: Na0: 6% glucose Intervention 2: Na20: 6% glucose + 20 mmol/L sodium Intervention 3: Na40: 6% glucose + 40 mmol/L sodium Intervention 4: Na60: 6% glucose + 60 mmol/L sodium 1 endpoint: Fluid delivery surrogately measured by plasma deuterium enrichment Results: Glucose group: trend for time to plateau with increasing carbohydrate concentration (GO:34 min.001) than no carbohydrate. prospective case Intervention 3: G6: 6% glucose + 20 mmol/L sodium reaching plateau time more quickly control. gender.0–1. Na60:16 min) Plasma deuterium enrichment did not differ between groups (p=0. Postural fall in SBP defined as Postural fall in SBP was not related to HTN. Very Elderly Trial).092). cross-sectional 219 mmHg) and diastolic and in DBP was 1. (339) Study type: Descriptive cross 5/1985 and 9/1985 of Results: Hypnotics and antidepressants sectional survey individuals age 65 y of Women were more likely to report falls than men (p<0. at least Results: (338) 80 y of age with sustained Mean sitting BP was 182/100 mmHg. age. 96 (7. dementia. There was no significant difference in antihypertensives Exclusion: Mental (p=NS) or diuretics (p=NS). but sleeping aid use was (340) Postural fall in SBP was related to alcohol intake >20 mL/day. . associated causes survey (Activity and Ageing elderly arthritis. et al. higher anxiety level. systolic (average SBP 160.121) Beckett NS. Study type: Analytical. Results: fall. from sitting to standing 123 © 2017 by the American College of Cardiology Foundation. glucose. Na40:18 min. Aim: To assess OH prevalence Inclusion: Pts in HYVET 1 endpoint: Orthostatic fall in BP in hypertensive pts Prevalence of OH in elderly pts 1999 and associated factors in trial (Hypertension in the with hypertension was 12% 10618673 elderly hypertensive pts. Exclusion: N/A sleeping tablet use.3) observational.3–8. BB (p=0. Average fall in SBP on standing was 8 mmHg (95% CI: 7.3 mmHg (95% CI: 1.6). Study type: Descriptive. Hypnotics (p<0. Aim: To assess falls and their Inclusion: Community 1 endpoint: Prevalence of and factors associated with falls in the Decreasing handgrip strength. et al.05) and incompetence.001).001). Inc. diabetes.05). associated.. cross. American Heart Association. Older (tricyclic antidepressants) were the age who reported 1 fall in respondents were more likely to report falls (p<0. and lower body mass sectional survey index. and foot difficulties were 3266440 survey conducted between strongest predictors of falls.7%) had a study hypertension (average DBP drop of 20 mmHg systolic and 66 (5.01) were more associated falls acute organic brain syndrome Burke V. Na20:19 min. Aim: To assess relation of drug Inclusion: Independent 1 endpoint: Factors associated with postural fall in SBP There was no relation of anti- 1992 treatment to postural fall in BP elderly volunteers (pts >60 hypertensive medication to postural 1484937 in elderly. Increasing medication classes associated with Size: n=356 pts preceding y number of prescribed drugs correlated increased prevalence of falls falls. 20 mmHg decrease when changing Size: n=843 pts or cardiac medications [verapamil (p=0. antidepressants (p<0.241 pts Exclusion: Pts on BP lowering treatment for reasons other than HTN Blake AJ.4%) had a drop of 10 90-109 mmHg) mmHg diastolic Size: n=1. Sodium group: trend for decrease in time to plateau with increasing sodium content (Na0: 23 min. and Heart Rhythm Society. (p<0. 1988. y of age) in Perth. et al.728). Australia. Aim: Assess prevalence of OH Inclusion: Pts 65 y of 1 endpoint: Prevalence of OH Withdrawal of anti-HTN therapy 1994 in elderly HTN pts whether anti. benzodiazepine 26%. BB 12%. Inc. remain standing for 10 min the CV medication did affect BP observational. p<0. then Post-prandial responses in BP and 1996 hypotension and relation to residents. For pts stopping anti-HTN medication. 3. and 7971628 fall in SBP) implicated in 80% of cases.05) and had higher pre- was 175 mmHg and/or withdrawal SBP (164+/-21 vs. criteria for anti-hypertensive cohort having angina or known Results: withdrawal major illness. Following treatment Pts with OH on treatment (vs. calcium antagonist 8%. et al. Aim: To assess post-prandial Inclusion: Nursing home Comparator: Standing test.199)]. sinus rhythm. the number of OH fell from OH defined as mean SBP fall 20 Size: n=47 pts Parkinson disease. American Heart Association. p=0. be heart rate are similar. age. 6. affect post-meal findings. poor mobility 44%. Study type: Analytical. Size: n=50 pts Medication usage in OH pts: Diuretic 56%. 7870633 HTN therapy was continued or on pharmacological Intervention: Anti-HTN medication withdrawal. . unsteadiness 38%. confusion 22%. Those with OH on anti-HTN (342) not. 147 +/-17 mmHg. Aim: Presentation of OH in Inclusion: Elderly pts with 1 endpoint: Factors associated with orthostatic fall in SBP 20 Medication was primarily 1994 elderly OH (defined as 20 mmHg mmHg responsible for OH in 66%. BP measured at 1.356). et al. 74 y of age. anti- parkinsonian therapy 22%. prospective 1 endpoint: BP and heart rate before and after postural change. 12 mo. prospective within preceding 6 mo. (341) Study type: Descriptive Results: retrospective chart review Exclusion: N/A Presenting features of OH: Falls 64%. 5 (38% at baseline. hydralazine 10%. diabetes. 9. However. and Heart Rhythm Society. Fotherby MD. or on 11 (23%) on anti-HTN treatment to 4 (11%. diuretics (p=0.02) whose DBP >100 mmHg on 2 occasions were withdrawn from the study and deemed unsuitable for anti-HTN withdrawal Jansen RW. after standing suggesting this 124 © 2017 by the American College of Cardiology Foundation. treatment >1. and 4 (31%) at 12 affect BP mo. nitrates 6%..05) off treatment. Craig GM. those with OH on treatment) were withdrawal. mmHg on standing from supine medication other than anti. et al. and 12 mo of anti-HTN therapy withdrawal treatment tended to be older and had higher prewithdrawal SBP Study type: Analytical. or vasodilators (p=0. and CV 8636581 chronic use of CV medications able to stand from supine Intervention: repeat standing test after eating meal. BP <175/100 mmHg can decrease OH occurrence. The pts continuing anti-HTN medication showed no significant hypertensives known to change in prevalence of OH. p=0. anti-depressant 24%. medication administration did not (343) position within 30 s and Same protocol repeated in 3 to 14 days. Exclusion: MI or stroke Comparator: Continuing on anti-HTN had BP measure at 6 and 13 of the 47 pts did not meet observational. phenothiazine 18%. pts whose SBP older (79 y of age vs. 001).001) McLachlan CY. of age) in pts screened for medication with OH or falls.05. and Heart Rhythm Society. American Heart Association. Administration of CV medications did not affect significantly subsequent BP response after meals but did affect SBP after standing. but 26135806 CV. p<0. multicenter. Kamaruzzaman S. COPD. or cancer. and MAP all declined 45 min after the meal as SBP decline of 20 mmHg within (p<0. 95% CI:1. 40%.. et Aim: Association of OH and Inclusion: British Women’s 1 endpoint: Prevalence of OH OH was associated with al. 23% for medication observational. mean DBP. Size: n=285 pts Exclusion: N/A There was no difference in proportions of pts receiving drugs or drug potentially associated with falls and/or OH. OH was associated with all-cause mortality (OR: 1.775 pts of OH (OR: 1. p<0. Postprandial hypotension occurred in 10 pts in first test and 1 additional pts in second test. . observational cross-sectional 60-80 y of age.001) at 45 min and by OH defined as SBP decline 12+/-4 mmHg (p<0. Inclusion: All admissions 1 endpoint: Prevalence of ADE ADE comprises a significant 2014 nature. Polypharmacy disease. p=0.30–3. without OH were more likely to have falls (62% vs.10. (79% vs.99. 90 min study period Mean SBP declined 16+/-4 mmHg (p<0. Among BP lowering medication. No association of OH to coronary heart associated with OH. insulin.001 for each). Aim: To assess frequency. 0) had increased odds Size: n=3.001).001) and syncope (29% vs. p<0. 95% CI: 1. p<0.47.003).001). and death. only BB had cohort higher odds of OH (OR: 1. and 84+/-4 y of age which could affect response to Study type: Prospective mmHg in DBP within 3 min without OH. in of itself was not associated with Study type: Retrospective. diabetes.6–29. et al. OH (defined as SBP Results: Use of BB and use of 3 or more 19897539 Study 20 mmHg and/or diastolic Higher prevalence of OH in women with HTN than without HTN antihypertensive medications were (345) Cross-sectional analysis BP 10 mmHg). or diuretic effect OH (defined as reduction of Results: many pts in this study had frailty (344) ≥20 mmHg in SBP or ≥10 Mean age was 85+/-5 y of age in pts with OH. and causality of ADE at single center in New amount of admissions at this single 24750276 resulting in acute admissions Zealand between 10/1/2011 Results: center. Prevalence of OH was 41% (30% for SBP. postprandial hypotension Size: n=22 pts dependent DM Results: Post-prandial hypotension defined Mean SBP.26. Pts with OH vs.14. et al.4) among women OH. p<0. 2010 Women’s Heart and Health cohort. with the syncope being the 125 © 2017 by the American College of Cardiology Foundation. 64%.09–1. MAP similarly declined in each test after standing means (p<0. medication use in British Heart and Healthy Study increasing age.01) during second test with no difference during first and/or third min after between the 2 tests. cohort Exclusion: Presence of BP and heart rate before and after meals response may be distinct from pacemaker. of standing DBP). 4%. Inc.07–1. Women on multiple antihypertensive drugs ( 3 vs.01). 95% CI: 1. Jodaitis L. HTN. Exclusion: N/A Prevalence of OH was 28% (95% CI: 26. Aim: Association of OH with Inclusion: Older (pts ≥75 y 1 endpoint: Prevalence of OH There was no association of any 2015 use of drugs with psychotropic. antianginal. p=0.05) with were.1. admitted to 4 to 7 days (“wk 1”) after stroke onset therapy is not associated with OH. (165 +/-24/87+/-14 mmHg to 155 +/-24/83+/-14 mmHg. 1-min standing BP.6%) were related to ADE. diltiazem. Panayiotou B. antiarrhythmics. and standing within 3 d of stroke onset (“day 1”). mild or moderate sitting.36. and diuretics (16%). 12/24/2011 to 4/4/2012. hemoglobin <10 g/dL. male gender. related admissions cohort Exclusion: N/A Most common adverse effects were postural hypotension and/or vasovagal syncope (29%) Size: n=96 pts Most common implicated medications were vasodilators (23%).5. and Heart Rhythm Society. 126 © 2017 by the American College of Cardiology Foundation. OH occurred in 5 Exclusion: Hemorrhagic treated and 8 untreated pts.. observational be on antihypertensive Between d 1 and wk 1. life and heart rate was not associated with OH. expectancy >3 mo. chronotropic medications [amiodarone. onset. urea >10 mmol/L. antibiotic requirement. serious illness. p=0. 65 (19. prospective ADE. American Heart Association. et al. HTN stroke score. know postural hypotension. et al. medication (“treated group”. Only cardiac dysfunsion was stroke. 96 (28. supine BP fell significantly in treated group cohort. were caused by ADE. Vasodilators Study type: Analytical. On day 1. p=0. but no significant difference in Size: n=80 pts group”. . Inc. lower body mass index. Aim: To assess for clinical Inclusion: Nursing home 1 endpoint: supine BP.003 for n=40) or not (“untreated SBP and p=0. p=0.(346) to 11/11/2011 and Of 336 admissions.48 MI in previous 3 mo. After multivariate analysis. and ACE- Size: n=911 pts inhibitors were not associated with OH. 3-min standing BP. n=40) untreated group.2%) were contributed to by an and diuretics comprise 39% of ADE- observational. comorbidity associated with OH on multivariate analysis (OR: 3. (348) hospital 24 h of stroke Presence of cardiac dysfunction was Study type: Analytical. 95% CI: 1. psychotropic medications (18%). BB. Aim: To assess Inclusion: Pts 65 y of 1 endpoint: BP and heart rate measurements while supine. able to lower body mass index and (347) stand at least 1 min Results: Parkinson disease medications Study type: Analytical. living at home. but 9109468 change.3%) most frequent effect. and 31 (9. In pts with mild to moderate 2002 antihypertensive medications in age.05) independent of age. At wk 1. severe HF (NYHA III or IV). Anti-HTN medication was not associated with OH. AF.0– affecting BP regulation (DM 13. lightheadedness cohort with standing. p=0. prospective observational Exclusion: N/A OH were: elevated supine BP before breakfast. Parkinson disease medications.03 for diastolic BP. OH was observed within 5 min in 11 treated and 5 untreated pts. digoxin] (11%) Ooi WL. and again ischemic stroke. antihypertensive 11824858 acute stroke for OH ischemic stroke. Antihypertensive medication use 1997 correlates for orthostatic BP residents ≥ 60 y of age. and anti-HTN or Parkinson disease). could Results: associated with OH prospective. significantly associated (p<0. Diuretic. treatment.09. et al. 2. Study Size (P values. Predisposing factors for postural hypotension: elevated supine BP orther antihypertensives) was observational. associated with postural cohort institution Chronic CV diseases. The (349) relation to medications readings. Patient Population Primary Endpoint and Results Summary/Conclusion Author.. No (350) Finland in 347 pts. (MEDVAMC) between with a significant relationship x2=15. Aim: To describe prevalence of Inclusion: Pts ≥75 y of 1 endpoint: Prevalence of OH. Prevalence OH in pts on 1. but there 7726701 in elderly (pts >65 y of age) in Turku. 10 y mortality Only supine HTN was associated 1995 factors to postural hypotension y follow-up survey of elderly with postural hypotension. prospective Exclusion: Living in an (p<0. and measurements. Observational Studies. no assessment of terazosin (54%) for cardiac medications. 60%.Poon IO. medication (nitrates.18. Nonrandomized Trials. who attended 189 (55%) pts had OH. Data Supplement 38. Aim: To evaluate predisposing Inclusion: Baseline and 10 1 endpoint: Prevalence of postural hypotension. Other medications OH defined as SBP reduction ≥20 sitting and standing BP. Comment(s) Year Published & 95% CI) 127 © 2017 by the American College of Cardiology Foundation. Potentially causative medications of OH were those reported with >1% incidence of OH Raiha I.symptoms Parkinson disease. diuretics. as there are 6/2002 and 6/2003 many pts on these medications Size: n=342 pts Associated with highest prevalence of OH was without orthostatic symptoms or BP Exclusion: Pts unable to hydrochlorothiazide (65%). Study type: Analytical. Results: was not effect on mortality. p=0. and quetiapine (56%) mins of standing +/. American Heart Association. the 15811171 OH in elderly veterans and sitting and standing BP Results: prevalence of OH increased. BB. Prevalence of OH in pts who had no highest association among cardiac geriatric clinic in electronic causative medication was 35%. furosemide (56%).001). medication. and/or Registries of Pseudosyncope – (Section 8) Study Acronym. or ≥ medications included HCTZ and Study type: Retrospective medical record database 3 causative medications was 58%. stand. associated with OH included paroxetine (86%). mmHg or DBP ≥10 mmHg within 3 autonomic dysfunction. and hypotension. abnormal ECG were not associated with postural hypotension Postural hypotension was defined Size: n=347 pts as ≥ 20 mmHg after 3 mins of standing. . body mass index. medication prevalence With increasing number of 2005 symptomatic and asymptomatic age. Study Type/Design. Prevalence of postural hypotension was 28%.002) is not accounted for. with documented causative medications. trazodone (58%). and Heart Rhythm Society. lisinopril. et al. Inc. olanzapine (57%). OR or RR. and 65% respectively. lisinopril (60%). The effect of work-up bias chart review. American Heart Association. Iglesias. medically unexplained symptoms. pts with vasovagal syncope McKenzie PS. 69 Exclusion criteria: N/A test. et al.Moya. often many times a d Size: N/A 2. and Heart Rhythm Society. . et al. No apparent trigger for attack 5. Eyes closed 3. Study type: Retrospective Inclusion criteria: 1 endpoint: New onset of medically unexplained Many PPS/PNES pts exhibit other 2010 observational study of PNES pts Diagnosed PPS/ PNES symptoms (MUS) in pts diagnosed with PPS/PNES. Study type: Single center Inclusion criteria: 1 endpoint: Frequency of PPS/PNES in a TLOC A stepwise evaluation of apparent 2009 prospective syncope evaluation Presentation of TLOC or population TLOC cases in an ambulatory clinic may 19250095 apparent TLOC yield a diagnosis in 2/3. 60% are young woman with multiple pre- syncope and syncope 128 © 2017 by the American College of Cardiology Foundation. Prolonged episodes. PPS/PNES. Study type: Tilt-test induction of Inclusion criteria: 1 endpoint: Pseudosyncope Provides a quantitative assessment of 2013 PPS/PNES examined retrospectively Diagnosis of PPS/PNES by clinical features distinguishing 23873974 to assess clinical features Tilt-test and video EEG Results PPS/PNES can be diagnosed and PPS/PNES from vasovagal syncope (126) differentiated from vasovagal syncope by use of a tilt- Size: n=43 pts with PPS/PNES vs. More than 50% (353) Size: n=131 PPS/PNES cases out of Results: of cases are either vasovagal syncope or 939 pts undergoing TLOC evaluation Exclusion criteria: N/A 14% of all pts were considered PPS/PNES. Frequent attacks. Approx. Prone to being ‘suggestible’ which favors triggering attacks in clinic/laboratory Tannamaat. et al. Study type: Practice guideline Inclusion criteria: N/A 1 endpoint: N/A Summarizes the key clinically useful 2009 consensus (European Society of markers to aid recognition of PPS/PNES 19713422 Cardiology) Exclusion criteria: N/A Results: (351) 1. often many mins in duration 4. 25% of PNES pts develop new medically diagnosis of PPS/PNES and only Size: n=187 pts unexplained symptoms after initial diagnosis infrequently became manifest for the first time later during the approx.. but in 21421771 diagnosed by inpatient or outpatient most cases the medically unexplained (352) EEG or video-EEG Exclusion criteria: N/A Results: symptoms were present prior to Approx. et al. Inc. 1 y follow- up. 25% were utilization. anxiety. .. diminish adverse life-style impact of this (355) Size: n=44 previously diagnosed reporting symptom Results: condition. et al. 18061753 psychotherapy in pts with functional symptoms but NOT just (357) neurologic impairment PPS/PNES Results: Questionnaires throughout approx. during follow-up and 10/44 had >50% reduction of event frequency. 63 completed Exclusion criteria: N/A revealed that multiple patient-centered psychiatric treatment and 34 completed final instruments improved by at least 1 SD in 50% of pts questionnaires 129 © 2017 by the American College of Cardiology Foundation. 2014 Quantitative assessment in PNES Retrospective study of pts PPS/PNES in an epilepsy monitoring unit physical/sexual abuse) as well as co- 25262500 alone or PNES with epilepsy admitted to an epilepsy morbidities (e. et al. Inc. epilepsy 281. 7 of 44 became symptom free. 6 mo follow-up Size: n=91 enrollees.Elliot JO.5/mo over 6 mo.g. Health care utilization declined significantly (p=0. cases questionnaires or otherwise Median self-reported symptom frequency dropped from reported symptom frequency 10 to 7.039) Reuber M. Study type: Observational Inclusion criteria: 1 endpoint: Predictors of video-EEG confirmed Psychosocial issues (e. Study type: Uncontrolled Inclusion criteria: 1 endpoint: Therapeutic impact of individualized Individualized psychotherapy may be 2007 observational assessment of tailored Functional neurological psychotherapy using validated questionnaires beneficial but one-size does not fit all. Study type: Prospective Inclusion criteria: 1 endpoint: PPS/PNES event frequency Psychodynamic interpersonal therapy 2010 observational of psychodynamic Diagnosed PPS/PNES may be associated with reduction of 20561022 psychotherapy (no controls) Results: symptom frequency and healthcare (356) Exclusion criteria: With follow-up of 12–61 mo (mean 50 mo). et al. et al. No Controls 1 Psychological predictor Exclusion criteria: N/A 2 Social predictors Mayor. PNES + period 5 Biologic predictors of PNES alone PPS/PNES pts. Mayor. baseline levels of life-style impairment Exclusion criteria: N/A did not improve. American Heart Association.. (354) monitoring unit over a 6 y Results: GERD) are important features of Study size: PNES alone 84. Size: n=66 pts of whom 47 were N/A symptom free and 40% achieved event reduction followed full study duration >50%. Nevertheless.g. and Heart Rhythm Society. prior head injury. Study type: Prospective Inclusion criteria: Prior 1 endpoint: Symptom recurrence after being told the Apart from identifying the diagnosis of 2012 observational diagnosis of PPS/PNES in nature of the diagnosis PPS/PNES. further efforts are needed to 23168089 which pts completed self.. and 51% had reduced number of attacks. Data Supplement 39. Study Limitations.086) Safety endpoint (if relevant): N/A 130 © 2017 by the American College of Cardiology Foundation. the CBT group tended to have a better 3-mo event freedom (OR: 3. Author. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any). Inc.. (358) Size: Exclusion criteria: N/A Results: Sertraline was associated with 48% However. RCTs for Pseduosyncope – (Section 8) Study Acronym. Year Published Study Size (N) Study Comparator P values. & Adverse Events (# patients) 95% CI) Goldstein LH. et al. p<0. However.LaFrance Jr WC. 20548043 Size: n=36 pts therapy (360) randomized to standard Exclusion criteria: N/A Result therapy vs. OR or RR. resulted in no significant difference Santos. et al. n=26 completed study symptom reduction vs. 8% with placebo. . and Heart Rhythm Society. (# patients) / (Absolute Event Rates.125. Study type: Inclusion criteria: 1 endpoint: Symptom recurrence frequency during Individual psychoanalytic therapy 2014 Observational effects of PNES diagnosed by video. Study type: Prospective double-blind Inclusion criteria: 1 endpoint: Symptom frequency sertraline vs. Sertraline initially appeared to be more 2010 RCT of sertraline in PPS/PNES Diagnosed PPS/PNES placebo effective than placebo with reduction of 20739647 symptom frequency from baseline. Study Type. 30% had cessation of symptoms. et al. Aim of Study. no controls EEG study (359) Results: Size: n=37 pts Exclusion criteria: N/A During 1 y follow-up. differences the effect was deemed intention-to-treat not reported and baseline differences nonsignificant. Study type: RCT Inclusion criteria: Diagnosis Intervention: CBT in 1 endpoint: Symptom CBT tended to improve short-term outcomes 2010 of PPS/PNES addition to standard recurrence frequency but larger controlled studies are needed. follow-up proved beneficial in this uncontrolled 25650860 psychoanalytic therapy. CBT Comparator: With short-term application of psychotherapy Standard therapy alone CBT. American Heart Association. after adjustment for baseline 38 enrollees. Aim: Aimed to measure the Inclusion criteria: <18 y of Intervention: 1 endpoint: Initial HUTT can help with the diagnosis.. No An extensive neurological work-up should be <18 y of age with syncope. et al. neuro condition (i. EPS Comparator: None CPVT (n=6) Study type: Single center. Clinical Evaluation 28 Non cardiac Diagnosis mid-exertional syncopal event may not 26277987 among children with mid. (# patients) / (Include Absolute Event Study Limitations.e. vertigo seizure) syncope. . Exclusion criteria: Pts with not yield a definitive 1) n=382 HUTT identified HUTT can help make the diagnosis of VVS. Aim: Aimed to evaluate the Inclusion criteria: ≤18 y of Intervention: 1 endpoint: Reported symptoms before and after a 2015 incidence of cardiac disorders age with mid-exertional None. or shock used if unexplained syncope. POTS in 87. An 2009 diagnostic value of a protocol age with syncope as defined 1st Step: H&P. Psych evaluation. Author. HUTT was only VVS in 203. and/or Registries of Pediatrics – (Section 10. (20 event (additional testing is mo period) unnecessary unless challenged by H&P). final diagnosis in 89 pts reserved for pts whose H&P is concerning for were excluded. Aim of Study. Nonrandomized Trials. Study Type*. and Heart Rhythm Society. Year Published Study Size (N) Study Comparator Rates. LVNC (n=1) 2012) No difference in symptoms Size: n=60 pts between cardiac and noncardiac pts preceding syncope or following syncopal event. Size: n=474 consecutive pts Comparator: None 2) n=10 had a neurological presenting with syncope. Holter. prospective consecutive pts symptoms compatible with diagnosis. exertional syncope (1999. SVT (n=5) Summary: retrospective evaluation of Exclusion criteria: Pts with VT (n=2) Mid-exertional syncope in children carries a children who presented for known structural heart defects VF (n=2) high-risk of being diagnosed with a cardiac cardiac evaluation with or known arrhythmia disorders HCM (n=2) condition. and at least one of the LQT (n=10) condition and a cardiac condition. seizures. (TILT YIELD): 76% a neuro condition. syncope an EKG and ECHO Only 32 Cardiac Diagnosis distinguish between a benign noncardiac (362) exertional syncope. American Heart Association. and ECG diagnostic work-up (H&P & extensive neurological work-up is not 19183119 on the management of as TLOC and postural tone 2nd Step: Echo. following: TTT.4%). (# patients) and 95% CI) Summary Zhang Q.Data Supplement 40. 2nd Step diagnosis in 59 (12. P value. Observational Studies. OR or RR. vertigo. Inc. Patient Population Study Intervention Endpoint Results Relevant 2 Endpoint (if any). Adverse Events. Summary: Study type: Multi center. ECG) gave a definitive indicated unless the H&P is suspicious for a (361) children and adolescents with caused by cerebral hypo. CT. Miyake.1) Study Acronym. 131 © 2017 by the American College of Cardiology Foundation. et al. EST. perfusion diagnostic maneuvers were 2nd Step diagnostic work-up only performed if 1st step did required in 326 (87%). and head of syncope had an odds ratio of 17 in Study type: Single center Exclusion criteria: Pts with CT).Zhang. Exclusion criteria: N/A HUTT can help make the diagnosis of neurocardiogenic syncope. Exclusion criteria: N/A controls specificity 83% retrospective study of syncopal pts and prospective Summary: HUTT has a high specificity in 132 © 2017 by the American College of Cardiology Foundation. syncope prospective consecutive pts Comparator: None Summary: <18 y of age with syncope. All pts complete Unexplained 15 (5%) Study type: Multicenter China 118 item questionnaire Summary: prospective consecutive Multivariate analysis showed the history of series of pts in the Pediatric Exclusion criteria: Pts with Comparator: None exercise-triggered syncope or ECG Syncope Unit known CHD or known abnormalities were independent predictors of arrhythmia disorders cardiac syncope. Size: n=275 pts <18 y of age Qingyou. prospective study of pts with known structural heart defects unexplained syncope. EKG. Aim: Measure the diagnostic Inclusion criteria: <18 y of Intervention: 1 endpoint: Syncope on tilt 25/44 (58%) of symptomatic pts ha a 1993 value of a HUTT in pts with age with strong clinical HUTT following Hx and test positive tilt 7681189 syncope compared to healthy suspicion of neurocardiogenic clinical examination 3/18 (17%) normal volunteers had a (366) controls w/o syncope syncope positive tilt Comparator: Healthy Sensitivity of a positive tilt 57% and Study type: Single center. Aim: Aimed to measure the Inclusion criteria: <18 y of Intervention: 1 endpoint: Recurrent 16/18 (90%) with clinical suspicion of 2004 diagnostic value of a HUTT age with strong clinical HUTT following Hx and syncope vasodepressor syncope had a positive tilt 15269465 suspicion of neurocardiogenic clinical examination test (365) Study type: Single center. Aim: Value of Hx taking in Inclusion criteria: ≤18 y of Intervention: 1 endpoint: Results 2013 identifying children with age with suspected syncope Clinical history. and a negative tilt response group (II) Udani. Summary: Negative tilt groups Clinical history of a prodrome prior to Size: n=47 pts divided into a syncope in conjunction with a positive HUTT positive response group (I) supports diagnosis of vasovagal syncope. et al. or known arrhythmia disorders Comparator: Positive tilt vs. BP measurements Autonomic mediated 214 (78%) (363) Syncope Unit of 5 hospitals in and ECG. Inc. American Heart Association. physical Clinical diagnosis made Cardiac 31 (11%) 22417947 cardiac syncope admitted to the Pediatric exam. Prodrome (364) exam. and Heart Rhythm Society. Size: n=18 pts Fouad. predicting positive TTT results. et al. et al. Aim: To determine usefulness Inclusion criteria: ≤18 y of Intervention: 1 endpoint: Results 2004 in children with unexplained age with unexplained All syncopal pts (all Clinical diagnosis made HUTT positive results more common in 12– 14727100 syncope. Echo. et al. unexplained) had a normal 16 y of age than younger children. syncope. .. In these pts. Exclusion criteria: Healthy controls Summary: HUTT offers a simple. undergoing ILR after interrogation to explain with reflex-mediated syncope. Size: n=44 syncope pts (16±3 y vs. while in 3 of 21 (15%) other study of pts with unexplained definitive diagnosis. Inc. Exclusion criteria: None Summary: ILR may be beneficial in children Size: 42 pts (25 males) with a with syncope of unknown etiology to rule-out median age of 11. 14 of 21 (67%) were diagnosed 19694968 unexplained syncope. et al. 18 healthy controls (16±2 y) Lerman-Sagie. et Aim: Measure the diagnostic Inclusion criteria: <18 y of Intervention: 1 endpoint: Syncope on tilt 6/15 (43%) of symptomatic pts ha a al. Aim: Measure the usefulness Inclusion criteria: Pts with Intervention: 1 endpoint: Identification of Among the 21 pts who presented with 2009 of ILR in children with unexplained syncope ILR implantation a substrate on ILR syncope. n=10 healthy controls (11–18 y of age) Al Dhahri. rare.4–19. and 2 of 21 (9%) with Study type: Retrospective testing failed to provide a arrhythmias. Size: n=15 syncope pts (10– 18 y of age vs. with seizures.0 y of age) underwent of infection and need for device removal is ILR implantation. value of a HUTT in pts with age with strong clinical HUTT following Hx and test positive tilt 1991 syncope compared to healthy suspicion of neurocardiogenic clinical examination 0/10 (0%) normal volunteers had a positive 2019920 controls w/o syncope syncope. high-yielding diagnostic tool for the evaluation of syncope in children. the ILR device was implanted at a median age of 12. prospective study controls without syncope. The risk (1. identified cause of syncope. . causes were found. 133 © 2017 by the American College of Cardiology Foundation. American Heart Association.7–17.5 y of age arrhythmias as a cause of syncope.5 y of age).4 y of age (2. tilt (367) Comparator: Healthy Study type: Single center. but we were able to rule syncope after initial evaluation out arrhythmias as a possible etiology.. 2 of 21 (9%) (368) conventional diagnostic Comparator: None causal syncope. noninvasive. study of healthy controls diagnosing vasodepressor syncope. and Heart Rhythm Society. There were 14 pts (33%) with normal ECGs and echocardiograms. exception 1 pts having TOF. 12949317 conventional testing failed to interrogation to explain Junctional bradycardia (1) (370) Study type: Retrospective produce a diagnosis. All pts had a interrogation to explain PMVT (3) (371) Study type: Retrospective normal ECG and event Comparator: None causal syncope. pts with unexplained syncope. American Heart Association.4± 4. SVT (2) multi-center center TdP (1) Exclusion criteria: None Asystole (1) Size: n=21 pts (12. Rossano.3 y of No complications of ILR age) underwent ILR. Aim: Measure the usefulness Inclusion criteria: Pediatric Intervention: 1 endpoint: Identification of 14 pts (61%) underwent ILR for recurrent 2007 of ILR in children pts undergoing ILR ILR implantation a substrate on ILR syncope or presyncope. SVT (n=1) single center Type II AV block (n=1) 1 pts would infection and 1 pts relocated for Size: n=23 pts (11. (50%) were identified as having pre- 2015 of ILR in children pts with unexplained syncope ILR implantation a substrate on ILR syncope: 25348219 undergoing ILR. Aim: Measure the usefulness Inclusion criteria: Pediatric Intervention: 1 endpoint: Identification of 6 pts. et al. majority of pts with syncope or presyncope with zero complication rates.Babikar. 4 were structurally normal heart with identified as having a malignant arrhythmia. NST (1) Size: n=12 pts (9. CPVT (1) single-center center recorder and 10/12 had a Asystole (1) normal EST. mo 134 © 2017 by the American College of Cardiology Foundation. 6 (40%) were identified as 2003 of ILR in children pts undergoing ILR where ILR implantation a substrate on ILR having an arrhythmia to explain syncope.. Comparator: None causal syncope. and Heart Rhythm Society. . et al. ILR should strongly be considered in pts with Average monitoring period: 20 unexplained exertional syncope.4± 4.3 y of discomfort age) underwent ILR. majority of pts with syncope or pre-syncope syncope underwent ILR. No complications of ILR 16 underwent ILR for Summary: ILR facilitated diagnosis in unexplained syncope. Summary: ILR is useful in establishing Of the 12 pts 6 had exertional symptom rhythm correlation in the majority of syncope.3± 5. 11 pts Summary: ILR facilitated diagnosis in with syncope and 3 with pre. All had a Exclusion criteria: None Of the 6 pts with exertional syncope. Of these. Aim: Measure the usefulness Inclusion criteria: Pediatric Intervention: 1 endpoint: Identification of Of the 16 pts. Inc. ILR uncovered: 17764457 interrogation to explain Polymorphic VT (n=1) (369) Study type: Retrospective Exclusion criteria: None Comparator: None causal syncope. Ergul. et al. with a relatively low complication rate.3 y of VT (1) age) underwent ILR. sensitive.9 y of neurocardiogenic syncope in pediatric pts. case-control identifiable cause of syncope age-matched controls 2) Sensitivity 75% following ECG.5) with Hx & physical exam 4) 40% of positive tilt responders had a family unexplained syncope and 10 Hx healthy controls Summary: The head-up tilt test is a noninvasive. Inc.. Aim: Understand the Inclusion criteria: Syncope Intervention: None 1 endpoint: Comparison Of the 76 pts with diagnosis of syncope. .3±2. EEG. ECHO. Aim: Assess sensitivity and Inclusion criteria: Syncope Intervention: 1 endpoint: Tilt results 1) During TTT. et al. 2000273 (374) Study type: Prospective Exclusion criteria: No Comparator: None Summary: The head-up tilt test is a single center identifiable cause of syncope noninvasive. et al. specific diagnostic tool for evaluating children with unexplained syncope. et al. tool for evaluating children with unexplained Size: n=35 pts (8-19) with H&P syncope. single center. 3) Specificity 90% Size: n=20 pts (12.5%) (372) Exclusion criteria: None Study type: Retrospective Summary: Family Hx of vasovagal single center. sensitive.8±2. symptoms were elicited in 26 1991 specificity of TTT diagnosis HUTT (75%) of the pts with unexplained syncope. EEG. American Heart Association. age) with syncope and n=29 control non syncopal pts (11. Thilenius.001). specific diagnostic following ECG. case-control symptoms should be meticulously sought and is of value in the diagnosis of Size: n=76 pts (11.Vlahos. and Heart Rhythm Society. symptoms were elicited in 15 1996 specificity of TTT diagnosis HUTT 25 mins (75%) of the pts with unexplained syncope 8833492 but in only one (10%) of the control group (373) Study type: Prospective Exclusion criteria: No Comparator: 10 healthy (p<0. ECHO. unexplained syncope 135 © 2017 by the American College of Cardiology Foundation. 68 2008 relationship of family Hx in diagnosis family Hx of syncope had a positive family history of syncope 17899242 diagnosing syncope Comparator: None between 2 groups (89%) compared to 1/29 (3. Aim: Assess sensitivity and Inclusion criteria: Syncope Intervention: 1 endpoint: Tilt results 1) During TTT.9 y of age) Alehan.0±2. no prior (238) therapy for syncope Comparator: Placebo 1 Safety endpoint (if Summary: Symptoms were more frequent in Study type: Randomized relevant): (pediatric) Exclusion criteria: No the placebo group. A prodrome was a emergency department. 21629199 children presenting with vital sign measurements and Cardiogenic syncope accounted for 1. et al. recurrence 36% in 2005 and fludocrotisone in syncope or presyncope.0 y of age) 136 © 2017 by the American College of Cardiology Foundation. Aim: Analyze the spectrum Inclusion criteria: Intervention: All pts 1 endpoint: Vasovagal syncope was diagnosed in 32% 2011 of underlying diseases in Presentation with syncope underwent H&P.6 y of age) Clinical Hx with particular attention to the events is the most critical piece of information required. Aim: Analyzed the etiology of Inclusion criteria: Intervention: 1 endpoint: Of the 226 pts presenting with syncope. Study type: Prospective significant (p<. 2004 consecutive cases of syncope Primary complaint of syncope None Clinical diagnosis neurocardiogenic accounted for 80% of the 15289772 presenting to a pediatric (witnessed and unwitnessed) diagnosis. and Heart Rhythm Society. Limitation: ECG were not obtained in 58% of the pts and as such the utility of an ECG cannot be measured in this study.Salim. 05) factor in diagnosing cohort study Exclusion criteria: None neurocardiogenic syncope (present in 88% of cases). Exclusion criteria: None an ECG. however a prodrome was also Size: n=252 presentations of observed in 52% of those with a neurologic syncope in 226 pts (mean age disorder. <18 y of age. Safety endpoint: None the cases. POTS was diagnosed in 32% of pts. Aim: Effectiveness of salt Inclusion criteria: >1 Intervention: Florinef 1 endpoint: Syncope or Follow up 176+117d . 15708690 prevention of VVS in children +HUTT. Inc. et al. . Neurologic disorders were (375) emergency room. control n=14 Massin MM.5% of the Study type: Multicenter Comparator: None cases of syncope were undiagnosed.1mg/day and salt 1g/d pre-syncope recurrence controls and 55% active arm (p<0. structural heart disease Size: n=32. et al. 10.. retrospective chart review Size: n=888 children (median age 12. orthostatic Clinical diagnosis of pts. upon presentation to the Comparator: None Safety endpoint: None identified in 9%.5% of (376) syncope.8 ± 3. florinef 0. American Heart Association.0 ± 3.1mg/day and salt 1g/d n=18.04). Approximately 31. 0. Chen L. There was no difference between the 2 23992679 distinguishes VVS from presenting to the outpatient Comparator: Vasovagal comparison between 2 groups with respect to chest pain or (378) cardiac syncope. This is in contradistinction to (377) presenting with syncope who Safety endpoint: None pts presenting to the ED with syncope are more likely to have LQT Exclusion criteria: >40 y of Comparator: LQT pts syndrome. outpatient. 137 © 2017 by the American College of Cardiology Foundation. characteristics that (newborn to 18 y of age) Syncope at follow-up and 1. Study type: Retrospective (identified from the ICD dizziness. and detailed family Hx. of a Dutch Fainting Assessment Trial Summary: A family Hx or syncope and Size: n=32 LQTS pts. Aim: To identify Inclusion criteria: All pts Intervention: None 1 endpoint: Results: 2013. faculty with diagnosis of Symptoms vs. Compared to 17 Summary: Any one of the following 4 parts pediatric pts over the same of a cardiac screen: (1) abnormal cardiac era that were diagnosed with physical exam ± (2) abnormal findings on cardiac syncope. cardiac syncope. Cardiac groups of etiology palpitations. Aim: To determine whether Inclusion criteria: Intervention: Clinical 1 endpoint: Results: 72% of pts with LQTS had a family 2009 Hx taking can be used as a All LQT pts confirmed assessment with detailed Hx Clinical comparison Hx of syncope and 66% had a family Hx of 19482852 tool in identifying pts genotype positive. ECG ± (3) concerning family Hx ± (4) exertional syncope has 100% specificity and 60% specificity. n=113 sudden cardiac death are important pts in ED with syncope. Tretter JT. sudden death. syncope) Syncope Symptoms 2.Colman N. visual and hearing changes were review of pts presenting a Exclusion criteria: None database and the cardiac Safety endpoint: None significantly less common in the cardiac vasovagal syncope vs. The control department the LQTS cohort compared to the ED cohort was evaluated as part cohort.001). Preceding symptoms of lightheadedness. Inc. 3. compared to a consecutive without LQT where the family Hx of syncope heterogeneous group of was 9% and sudden death 10% (p<0. American Heart Association. Study type: Retrospective patients with syncope Syncope while supine and syncope with study comparing 2 presenting to the emergency exercise were significantly more common in populations. ECG established the diagnosis 47% of time compared to 0% in vasovagal cohort. 84%). and questions that should be asked when n=69 known vasovagal evaluating a young group of pts with syncope pts. et al. Size: n=89 pts 4–18 y of age 4. . syncope. et al. 11/17 (65%) with cardiac syncope had presenting to cardiology episodes of syncope surrounding exertion. stress lab database) group (41% vs.. age. and Heart Rhythm Society. HUTT results.5 to 18 y of previously known cardiac Safety endpoint: None age) disease (cardiomyopathies. mean age: 14 ± 6 y of age) Numan M.8 s) were managed with education. review of consecutive gene not genetically confirmed. neurocardiogenic syncope. and symptoms before the Syncope diagnosis amongst presentation of syncope. Aim: To report experience Inclusion criteria: Intervention: No uniform 1 endpoint: Clinical 25 pts with cardiac asystole (mean pause 2015. Aim: Understand the clinical Inclusion criteria: Intervention: None 1 endpoint: Use of H&P. unknown by H&P. symptoms in pts with Syncope diagnosis and ECG in identifying pts syncope. and exercise BB. All pts symptom awareness. (2) (379) Exclusion criteria: Pts with abnormal ECG. Comparator: None Safety endpoint: None A variety of treatments were used including echocardiogram. Aim: Understand the utility of Inclusion criteria: Intervention: 1 endpoint: Results: During the baseline HUTT 6 pts 1992 HUTT testing in the evaluation A minimum of 3 episodes of Baseline HUTT (30 mins) Clinical outcomes following (20%) had a positive HUTT and 15 1382276 of recurrent syncope of syncope in the preceding 6 with or without isoproterenol.Ritter S. a (1) personal Hx of exercise 10799622. or CHD) MacCormick JM. Size: n=480 pts (1. 13. additional pts (50%) during an isoproterenol (381) unknown etiology in children mo with the cause of syncope infusion (total 70%) had a positive HUTT. arrhythmias. ECG. . American Heart Association. and 4) normal echo. induced syncope.. Florinef. No further syncope occurred. syncope. Results: Of the 21 pts with cardiac related 2000. Grubb BP. females. and transdermal scopolamine. Study type: Retrospective syncope and LQT that was same authors. et al. 25087055 during HUTT absence of ventricular activity of cardiac asystole. et Aim: Understand the signs Inclusion criteria: Intervention: None 1 endpoint: Clinical Results: 20 pts with syncope (median age al.9 y of age) with 17 describing symptoms 2011 cardiac syncope and before consecutive gene positive Comparator: Comparison prior to syncope (lightheadedness and 21616715 the patient was diagnosed probands. Study type: Prospective stress test. The presence of symptoms before and after fainting may not Size: n=35 pts (8-19) with completely distinguish between benign unexplained syncope neurocardiogenic and cardiac syncope. et al. (2) positive family Hx. and Heart Rhythm Society. with pts with cardiac asystole Cardiac asystole (defined as treatment strategy follow-up recurrent syncope 9.2± 5. Summary: Young pts with cardiac syncope positive probands and frequently have symptoms similar to symptoms before syncope. literature based control not in weakness post –syncope were noted in 64% Exclusion criteria: Pts with the same time period or by of cases. Similarly drowsiness and (380) with a channelopathy. and adolescents. alpha agonists and all 138 © 2017 by the American College of Cardiology Foundation. and one of the (382) of >3 s) received education of Safety endpoint: None following Florinef. was done on a historical and Safety endpoint: None dizziness in 47%). BB. et al. Inc. Comparator: None with cardiac syncope. This study study was not designed to look at one particular Exclusion criteria: None treatment arm over another but asses the Size: 30 pts (15 males and 15 utility of the HUTT itself. and Heart Rhythm Society. et al. syncopal events. Brugada. Size: n=1. fluids but one responded to medical management. Average age of 1st syncope (12. 21329841 and adolescents with LQT pathogenic QT mutation. Study type: Retrospective symptom awareness. and do not necessarily need a pacemaker pacemaker therapy. number of previous syncopal episodes were (383) Exclusion criteria: Excluded Comparator: Compare Safety endpoint: None predictive of recurrent syncope. Positive Study type: Retrospective CHD. LQT. Inc. LQT1 male pts had the highest rate of first (197) syndrome. Aim: Define predictors of Inclusion criteria: 8–18 y of Intervention: VVS pts follow 1 endpoint: Recurrent syncope predictors: age at initial 2012. Summary: Size: 150 pts (8–18 y of age) Number of prior syncopal episodes and between 2007–2011. as a defined endpoint. or Recurrent syncope group HUTT did not predict recurrence of VVS. Syncope recurrence syncope. Comparator: Different LQT syncope and LQT2 females had the highest genotypes and BB utilization Safety endpoint: Aborted Study type: Retrospective Exclusion criteria: QTc with recurrent syncope. Aim: Identify risk factors for Inclusion criteria: Intervention: 1 endpoint: Results: A QTc ≥ 500 ms was a significant 2011 recurrent syncope in children QTc ≥450 msec.8±4.. immediately. significantly (>70%) reduced subsequent Registry.1 y) Liu JF. rate of first and subsequent syncopal events. syncope group (n=110). or a known Registry follow-up Occurrence of recurrent predictor of a first syncopal event (HR: 2. cardiac arrest and LQT review of data from the ≤450 ms without pathogenic related sudden cardiac death BB treatment for LQT1 & LQT 2 pts International Long QT mutation. Size: Retrospective analysis of 537 pts (age 6-22 y of age) Comparator: None Summary: Children and young adults (<25 y and follow-up of 25 pts with of age) with cardiac asystole at time of HUTT cardiac asystole. Yilmaz S. Exclusion criteria: None and salt and additional Only 1 patient required a pacemaker for treatment. positive family Hx of syncope. syncope.16). Result HUTT does not and Group II HUTT negative predict recurrence. American Heart Association.7 family Hx of syncope predict clinical Group I HUTT positive (N=97) y recurrence of VVS. (n=53 pts) and follow to see if clinical VVS reoccurs. and 22459868 syncope. et al. Follow-up 19 This study did not compare can be managed with pharmacologic agents ± 10 mo medical management vs. failing numerous pharmacologic strategies. study. Average Follow up: 3.648 pts <20 y of age with LQT (genotype or genotype and phenotype) 139 © 2017 by the American College of Cardiology Foundation. observational study medications that affect the (n=40) and Non-recurrent heart rate. after HUTT.3±3. no placebo group. and syncopal episodes. recurrence of vasovagal age with clinical VVS. . reduced the recurrence rate of syncope in Group II (n=79) conventional children 7–17 y of age.Younoszai AK. adrenergic agonist prevents Recurrent syncope and a HUTT discharged on Clinical symptoms Follow up: 11. and awareness) Oral Rehydration Salts significantly oral rehydration salts) vs. randomized. cannot Study type: Retrospective.7–27. positive with isoproterenol. episodes of syncope in prior therapy + midodrine (Group Syncope recurrence (AIM 1) Group I (Midodrine): Effective rate of 17137891 12 mo and “positive” tilt with I) or sole conventional and repeat HUTT (AIM 2) repeat HUTT evaluation 75%. (386) BID Safety endpoint: Tolerance Study type: Single center. Safety endpoint: (39%) and No change in syncope (5%).. Exclusion criteria: Tilt encouragement to drink Safety endpoint: Tolerance No control and not randomized. (64 oz/daily) and syncopal events. 1998 therapy in children with Clinical diagnosis of VDS and positive TTT pts were 90% had resolution of Treatment of neurally-mediated syncope 9491043 vasodepressor syncope on positive TTT prescribed oral fluid therapy syncope with oral rehydration reduced the number of (384) clinical recurrence. tilt training. (Children 7. Aim: Whether oral Inclusion criteria: Intervention: Conventional 1 endpoint: Results: 1998 rehydration salts is effective in At least 2 episodes of therapy +/. Study type: Single center. Recurrence 140 © 2017 by the American College of Cardiology Foundation. (education – symptom Summary: education. Inclusion criteria: Intervention: Following 1 endpoint: Results: 1993. 17) 6 mo Decrease in syncope (47%) and No change controlled. children without significant side effects. 6 mo-f/u in syncope (14%). Pseudoephedrine alleviates syncope in medication. Size: 58 pts (8. Aim: Whether alpha. account for placebo effect.6 mo. KCl. clinical diagnosis of VVS. et Aim: Assessment of oral fluid Inclusion criteria: Intervention: Following a 1 endpoint: Results: al. non comparison study caffeine. Strieper MJ. more fluid and avoid of fluid bolus. preventing VVS in children. therapy. Size: n=16 pts (mean 13 y of age) Qingyou Z.6 y) Comparator: None Chu W. therapy without midodrine Safety endpoint: rate of clinical syncope: 22%. Recurrence (243) Study type: Single center. 15/16 (94%) pts reported 8101533 syncope positive HUTT pseudoephedrine 60 mg PO control of clinical symptoms. Exclusion criteria: Other Comparator: Placebo plus p<0.oral rehydration Clinical symptoms Group I (oral rehydration salts): No 25577227 treatment of children with VVS syncope in prior 6 mo. and head imaging. et al. et al. conventional therapy conventional therapy (health EEG. Group II (Conventional): Effective rate of between 2003-2004. randomized control trial (Group II). diagnosis of VVS. salts (oral rehydration salts: recurrence (56%). .05 Size: Group I (n=87) disease ruled-out by ECG. and Heart Rhythm Society. Not Exclusion criteria: At least 3 repeat HUTT evaluation 20%. et al. dissolved in 500 ml H2O) for Group II (Placebo): No recurrence (39%). Aim: Efficacy of midodrine in Inclusion criteria: At least 3 Intervention: Conventional 1 endpoint: Results: 2006. Decrease in syncope (385) Positive HUTT with clinical glucose. placebo. Inc. NaCl. Exclusion criteria: of alpha-adrenergic Summary: prospective study Free of any other cardiac Comparator: None medication. American Heart Association. responders. a major limitation of this paper is No placebo group the absence of a placebo group. Size: n=28 pts. no control. tilt. period Of the 11 nonresponders 10 were treated BB 141 © 2017 by the American College of Cardiology Foundation. Age 12. and mo groups. ECP.05) 12 mo AND “positive” tilt with no additional Size: Group I (n=13) clinical diagnosis of VVS. response. Aim: Outcomes of children Inclusion criteria: Age <20 y Intervention: Of 100 pts 1 endpoint: Response to Results: Of the 100 orthostatic positive 1994. conjunction with conventional episodes of syncope in prior therapy + metoprolol (Group syncope in 2 wk after recurrence 6/14 (43%) 18376348 treatment in reducing VVS in 12 mo along with a positive I) or sole conventional beginning therapy. et al. et al. Summary: Oral treatment of neurally randomized echocardiogram. headaches) (388) TTT (BL or Isuprel). Zhang Q. Summary: prospective randomized. Not blinded. in children. and Heart Rhythm Society. rate of clinical syncope 80% (p<0. No difference was suicide ideation. Florinef in treatment of episodes of syncope in positive TTT randomized to 48/58 (82%) cured or Atenolol had an adverse event. mediated syncope with Florinef or Atenolol is Comparator: Atenolol (N=29 Safety endpoint: No safe and efficacious.3±3 y of age with 22±10 mo. American Heart Association. Aim: Efficacy of BB in Inclusion criteria: At least 3 Intervention: Conventional 1 endpoint: Recurrence of Results: Group I (Metoprolol): Syncope 2008. tilt placebo. Aim: Comparison of Atenolol Inclusion criteria: ≥2 Intervention: Following a 1 endpoint: Secondary Comment: 11/29 (38%) o 1995 vs.1 mg) followed 6 observed between the 2 Study type: Prospective had a normal H&P. In a prospective randomized study (2001-2003) causes of CV or systemic conventional therapy. with neurocardiogenic of age with ≥3 episode of positive orthostatic medical management. no placebo. Size: n=58 pts Exclusion criteria: None pts) vs. episodes of syncope in prior Comparator: Midodrine vs. and salt) vs.. Group II No significant adverse side effects of (n=13) conventional therapy midodrine. Of these 65% complete resolution Structurally normal heart. (depression. Group I (n=14 pts) Metoprolol and Group II (n=14 pts) control Scott WA. blinded. with fludrocortisone and improved over a 12 mo and 17% some improvement Study type: Single center normal ECG (normal QT) NaCl. . Balaji S. Inc. 84 were treated Syncope present. Group II (Conventional): Syncope (387) children. therapy. absent. training. not considered a failure of Study type: Single center. only. 84 treated with fludrocortisone 7906701 syncope. All pts Florinef (0. syncope in preceding 12 mo. pharmacotherapy 6 mo Summary: midodrine & conventional follow-up. no Midodrine is effective in reducing clinical therapy (health education. and NaCl. Safety endpoint: None Metoprolol was not effective in reducing VVS causes of syncope. et al. 6 mo follow-up plus repeat HUTT. Exclusion criteria: Other Comparator: Metoprolol vs. therapy without metoprolol Presyncope symptoms were recurrence 4/14 (29%) (Group II). 7639169 neurally mediated syncope preceding 6 mo and a positive Atenolol (25 or 50 mg) or improved. recurrence of syncope. Florinef (N=29 pts) However. positive autonomic maneuver Exclusion criteria: Comparator: Orthostatic Safety endpoint: No vs.. Aim: To determine whether Inclusion criteria: Intervention: 1 endpoint: Results: Children paced either VVI or DDD 1999 reflex bradycardic seizures Children >2y of age. mean 4 y). Inc. negative autonomic Other disease ruled-out by (autonomic abnormal) Summary: response. (12. clinical Pacing strategy DDD. and head response compared to Benefit to combination salt and imaging.(389) study comparing pts with and 4 responded. VVI. Duration of This study did not compare documented asystole (10-40 medical management vs. Summary: s) pacemaker therapy. of age. . Study type: Randomized 1/wk different pacing protocol. Parent and patient events compared to a “sensing only” mode. American Heart Association. et al. EEG. ECG.8 y when paced. 4 Safety endpoint: None 6 pts no further syncope when paced reflex anoxic seizures at least mo randomization to a DDD/VVI compared to sensing only.8 y of age) compared 100 Cannot exclude placebo effect positive orthostatic response to 62 negative orthostatic response McLeod KA. and Heart Rhythm Society. No control group of pts without a pacemaker. blinded to PM strategy. or ODO. Exclusion criteria: None Comparator: None 2 pts continued to have episodes of syncope Size: n=12 pts (median 2. Clinical recurrent syncope significant reduction in number of syncopal 10573501 can be prevented by cardiac Hx reflex anoxic seizures. (390) pacing documented asystole >4 s. Cannot exclude placebo effect from pacemaker alone (though pts <3 y of age) **Recommend hysteresis and rate drop features be applied 142 © 2017 by the American College of Cardiology Foundation. 3 pts no further syncope regardless paced or double blind study not paced. orthostatic negative Fludrocortisone in pts with orthostatic Size: n=162 pts with syncope response intolerance. First blinded study demonstrating efficacy of pacing in severe neurally mediated syncope secondary to pallid breath holding spells. Study type: Retrospective review Size: n=10 pts (median PM implant at 14. and Heart Rhythm Society. Nonrandomized Trials. Study type: Inclusion criteria: 1 endpoint: Composite of sustained VT or SCD Programmed ventricular stimulation is of 2004 Retrospective Cohort Programmed ventricular diagnostic and prognostic value in risk stratifying 15051640 Multicenter (6) stimulation between 1985 Results: Age at EPS ≥18 y. BB respectively (p=0. the etiology of ventricular tachyarrhythmias. 11533339 pallid-breatholding spells with requiring PM implantation. et al. 19808416 Results: Annual rates of appropriate shocks were Supraventricular arrhythmias may be implicated in (393) Size: n=37 pts Exclusion criteria: N/A 0. cardiothoracic Size: n=252 pts ratio ≥0. prior pts with repaired TOF. Aim: Determine resolution of Inclusion criteria: Intervention: 1 endpoint: 10 pts (mean asystolic pauses 11.Kelly AM. 2 only had minor color changes without loss (391) permanent pacemaker (PM) Comparator: None Safety endpoint: None of consciousness. Study Type/Design. 5 pts 2001 significant bradycardia related Pallid breath-holding spells Pacemaker Implantation Clinical Outcome had complete resolution of syncope (spells). palpitations. Inc.0% in primary and secondary prevention. Modified Lown ≥2. American Heart Association. (392) and 2002 palliative surgery.0366) seem protective. Patient Population Primary Endpoint and Results Summary/Conclusion Author. AV canal Khairy P. .6 Exclusion criteria: Unrepaired TOF. and 3 continued to have implantation Exclusion criteria: None minor brief spells..9 s). and/or Registries of Adult Congenital Heart Disease – (Section 10. pulmonary atresia. Study Size (P values.5% and 6.2) Study Acronym. Study type: Multicenter Inclusion criteria: TGA 1 endpoint: Risk factors for shocks High rates of appropriate shocks are noted in 2004 cohort study atrial baffle with ICD secondary but not primary prevention. and inducible VT does not seem to predict future events. Observational Studies. et al. OR or RR. et al. Comment(s) Year Published & 95% CI) Khairy P.5 mo) Data Supplement 41. 143 © 2017 by the American College of Cardiology Foundation. observational were included. Aim: To assess for CCS Inclusion criteria: 1 endpoint: Combination of Summary 2011 mediated falls in older adults Unexplained Falls TT/CSM provided diagnosis in Diagnosis using TT/CSM in 62% pts. OH was the most commonly observed abnormality (test positivity 21382922 pts referred to a tertiary referral of 60. relevant): N/A median age (IQR) was 77 (68–82) y of age. 2010 character of VVS in OA syncope clinic. diagnostic sensitivity was 22067373 (comparing those ≥80 y of age 62% of pts.. Of 194 pts with carotid sinus hypersensitivity.7 y 1 Safety endpoint (if Exclusion criteria: those with relevant): N/A Study type: Proxpective an identifiable medical cause for Observational the fall or a Hx of loss of 144 © 2017 by the American College of Cardiology Foundation. . 61–79 y pf age) Exclusion criteria: Pts with more likely to be positive in pts clear cardiac or neurological ≥80 y of age (68% vs. They had a median (IQR) y age of 23 (17–29). et al.3%).002 pts were 57 pts with isolated postural orthostatic tachycardia Exclusion criteria: N/A syndrome.3) Study Acronym. Duncan GW. Study type: Prospective etiology of their syncope were p=. 75% were female. and Heart Rhythm Society. Study Size (P values. Neurocardiogenic syncope demonstrated a bimodal (395) Study type: syncope unit over a decade 1 Safety endpoint (if age distribution. Older pts were less likely to give a typical Hx. American Heart Association. Nonrandomized Trials. Aim: To assess type of Inclusion criteria: All 1 endpoint: Type of Syncope Summary: 2011 syncope wth age consecutive in relation to age. Of the total pts. There Size: n=3. and was significantly relatively higher in those ≥80 yrs.001) Observational treated as appropriate and excluded from this analysis. and/or Registries of Geriatrics – (Section 10. 20444805 those <60 to those ≥60 younger pts. Observational Studies. Inc. et al. OR or RR. Comment(s) Year Published & 95% CI) Paling D.8±5. Study Type/Design. Comparisons of Diagnosis The clinical presentation differed significantly between older vs. et al.Data Supplement 42. Aim: To clarify prevalence and Inclusion: Pts presenting to 1 endpoint: Summary: Older pts even more likely than young to have VVS. Aim: To explore the Inclusion criteria: 1 endpoint: 5/21 of those with Summary: 2012 relationship between falls and Study of consecutive admissions nonaccidental falls had NMS Syncope underestimated in older adults as many have NMS with 22284256 NMS for falls aged ≥65 y associated amnesia often confounding assessment (397) Age 76. (396) Study type: Prospective. Those with vasovagal syncope (n=80) had a median (IQR) y of age of 30 (19–44). 1 Safety endpoint (if observational Exclusion criteria: <18 y of relevant): N/A age Size: n=1. the Retrospective. (394) vs. Patient Population Primary Endpoint and Results Summary/Conclusion Author. 50%.060 pts Anpalaham M. . et al. Safety endpoint (if relevant): Size: n=101 pts with N/A unexplained falls Cooke J. . or (4) presence of carotid bruit GIS Aim: Older adults (≥65 Inclusion criteria: 65 and older 1 endpoint: Summary: Ungar A. et al. (2) presented with a readily or subsequently diagnosed medical cause. Inclusion: Unexplained fallers 1 endpoint: diagnosis of CSS Summary: 1997 mediated syncope in pts with age ≥50 y with cardiac inhibition 65/279 had cardioinhibitory carotid hypersensitivity. (5) lived outside a 15 mile radius of the RVI.1%. observational presented with a single simple accidental fall (simple slip or Size: n=279 pts trip). Aim: to assess for CSS. (6) were immobile. and Heart Rhythm Society. suspected in 57. or (7) were registered blind. . (3) were cognitively impaired (4) unable to speak English or illiterate. American Heart Association. consciousness Size: n=200 pts Richardson DA. raising 9080518 falls question of pacing.9% 2006 79±7). referred to ER) (mean age with transient LOC Diagnosis Definite diagnosis in 40. (3) history of ventricular dysrhythmia. (398) Study type: Exclusion criteria: (1) Prospective. Inc. et al. Exclusions to CSM were: (1) MI within 3 mo. (2) stroke within 3 mo. 160 ≥75 17038070 Exclusion criteria: Presyncope 1 Safety endpoint (if (399) Study type: Observational or cognitive impairment relevant): N/A Size: n=231 pts 145 © 2017 by the American College of Cardiology Foundation. 7±6. Utility of TT 9823747 falls. 2 y f/u syncope/falls or dizziness Increased recurrence and mortality with age Size: n=242 pts Exclusion criteria: Recurrence corresponded to age and disability Exclusion criteria were symptoms limited to pre- syncope. 2011 outcomes in older adults (age algorithm 21908471 ≥60. and Heart Rhythm Society. Aim: Diagnostic sensitivity of Inclusion criteria: 1 endpoint: Summary: 1998 algorithm in pts 61–91 y of age Pts with unexplained syncope.5% and syncope 32. mean 78. still with successful w/ 2015 (83±6 yo) with falls or syncope. guideline algorithm on assessed using GIS diagnostic Recurrent syncope and mortality Total mortality 17. et al.5%. in pts with dementia dementia Pts with dementia and high comorbidity. Diagnostic sensitivity and High aggregate sensitivity of clinical thought process. 1 Safety endpoint (if workup 25820493 Study type: (52% falls. . 45% syncope and relevant): N/A (53) Observational 3% overlap). (401) Study type: Observational referred for assessment 1 Safety endpoint (if Size: n=54 pts Exclusion criteria: N/A relevant): Aging Clin Exp Res Aim: To assess w/u of protocol Inclusion criteria: Pts ≥65 with 1 endpoint: Diagnosis Summary: Ungar. American Heart Association. severe cognitive impairment . active (<5 y) malignancies and disability in more than 4 activities of daily living O’Mahony..8) 1 Safety endpoint (if Higher death in pts with cardiac syncope (400) Pts referred to clinic for relevant): N/A Study type: Controlled. 60% did not remember episode Size: n=296 pts Exclusion criteria: Absence of informed consent 146 © 2017 by the American College of Cardiology Foundation.GIS Aim: To study 2 y f/u of Inclusion criteria: Pts 1 endpoint: Summary: Ungar A. Inc. et al. or dizziness were specificity esp in context of syncopal amnesia. et al. 866 athletes congenital coronary artery anomalies (17%) Exclusion criteria: N/A Maron BJ.79 deaths/100.9 Exclusion criteria: N/A deaths/100. Inc. but low 19221222 arrest.001) and top (OR: 25.036) and after (p=0.. American Heart Association. Patient Population Primary Endpoint and Results Summary/Conclusion Author. and/or Registries of Syncope in Athletes – (Section 10. Observational Studies. For pts in top quartile. 0. Nonrandomized Trials. et al. Incidence of SCD in athletes decreased by 89%.3. p<0. James CA. OR or RR. Study Type/Design. HF. Study type: Longitudinal Inclusion criteria: Athletic and 1 endpoint: Incidence of CV death and cause specific Incidence of SCD declined after 2006 cohort non athletic population 12–35 y of CV death in screened athletes and unscreened non implementation of pre participation 17018804 age in Veneto. Study type: Multicenter Inclusion criteria: ICDs 1 endpoint: ICD intervention terminating VT or VF ICD interventions effective in pts with 2007 registry implanted between 1986 and HCM 17652294 2003 Results: ICD intervention terminated VT or VF in 103 pts (403) Size: n= 506 pts (20%) Exclusion criteria: N/A Corrado. & 95% CI) Comment(s) Year Published Maron BJ. p= mutations.000 person-years) and 265 sudden deaths in unscreened non athletes (0. 1974–2004 per 100. et al. The incidence of SCD in unscreened nonathletic pts did not change significantly.5) Study Acronym. Study type: Longitudinal Inclusion criteria: Pts with 1 endpoint: VT/VF. et al. a reduction in exercise decreased VT/VF risk (p=0.7.04) 147 © 2017 by the American College of Cardiology Foundation.001) quartiles were increasingly likely to meet Task Force Criteria for ARVC/D. Italy between athletes screening program for young athletes (404) Size: Population based.013) third (OR: 16.6 y of age) Results: Most common CV cause were HCM (36%) and nonetheless (<100 per y) (402) Size: n=1. Survival from first VT/VF event was lowest among those in top quatile before (p=0.64 p= 0. . and ARVC/D Endurance and frequent exercise 2013 cohort desmosomal mutations increased the risk of VT/VF.000 person- years). pts in ARVC/D in pts with desmosomal (405) Size: n=87 pts Exclusion criteria: N/A the second (OR: 6. 19 y of age (+/.000 person years Results: 55 SCD in screened athletes (1. HF and 23871885 Results: Compared to those who did not exercise. Study type: National Inclusion criteria: Athletes who 1 endpoint: SCD or cardiac arrest SCD in young US athletes was higher 2015 registry died suddenly or survived cardiac than previously estimated. and Heart Rhythm Society. Study Size (P values. et al.Data Supplement 43.005) exercise. J Emerg Med. 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