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ACC/AHA 2002 Guideline Update for Exercise TestingThese guidelines have been reviewed over the course of the past 5 years since their publication in the Journal of the American College of Cardiology, (Full Text—J Am Coll Cardiol 1997;30:260-315; Executive Summary—Circulation 1997;96:345-54). This update is based on the most significant advances in exercise testing that have been published during that time frame. These guidelines are available on the Web sites of both the American College of Cardiology and the American Heart Association. Deleted text is indicated by strikeout, and revised text is underlined. Copies of the full-text guideline incorporating the revisions (not showing strikeout and underlined text) will be available on the ACC and AHA Web sites in the near future. A summary article highlighting the changes to the guideline from 1997 to 2002 will be published in the October 1 issue of Circulation and the October 16 issue of the Journal of the American College of Cardiology and is also available for download on the ACC and AHA Web sites. © 2002 by the American College of Cardiology Foundation and the American Heart Association, Inc. ACC/AHA PRACTICE GUIDELINES—FULL TEXT ACC/AHA 2002 Guideline Update for Exercise Testing A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing) COMMITTEE MEMBERS Raymond J. Gibbons, MD, FACC, FAHA, Chair Gary J. Balady, MD, FACC, FAHA Daniel B. Mark, MD, MPH, FACC, FAHA J. Timothy Bricker, MD, FACC Ben D. McCallister, MD, FACC, FAHA Bernard R. Chaitman, MD, FACC, FAHA Aryan N. Mooss, MBBS, FACC, FAHA Gerald F. Fletcher, MD, FACC, FAHA Michael G. O'Reilly, MD, FACC Victor F. Froelicher, MD, FACC, FAHA William L. Winters, Jr., MD, FACC, FAHA TASK FORCE MEMBERS Raymond J. Gibbons, MD, FACC, FAHA, Chair Elliott M. Antman, MD, FACC, FAHA, Vice Chair Joseph S. Alpert, MD, FACC, FAHA Loren F. Hiratzka, MD, FACC, FAHA David P. Faxon, MD, FACC, FAHA Alice K. Jacobs, MD, FACC, FAHA Valentin Fuster, MD, PhD, FACC, FAHA Richard O. Russell, MD, FACC, FAHA* Gabriel Gregoratos, MD, FACC, FAHA Sidney C. Smith, Jr., MD, FACC, FAHA The ACC/AHA Task Force on Practice Guidelines makes every effort to TABLE OF CONTENTS avoid any actual or potential coflicts of interest that might arise as a result of an outside relationship or personal interest of a member of the writing panel. Preamble....................................................................................2 Specifically, all members of the writing panel are asked to provide disclosure statements of all such relationships that might be perceived as real or potential I. Introduction....................................................................... 2 conflicts of interest. These statements are reviewed by the parent task force, Exercise Testing Procedure............................................... 4 reported orally to all members of the writing panel at the first meeting, and General Overview............................................................4 updated as changes occur. Indications and Safety..................................................... 4 This document was approved by the American College of Cardiology Board Equipment and Protocols................................................ 4 of Trustees in July 2002 and by the American Heart Association Science Exercise End Points........................................................ 6 Advisory and Coordinating Committee in June 2002. Interpretation of the Exercise Test.................................. 6 When citing this document, the American College of Cardiology Foundation Cost and Availability....................................................... 6 and the American Heart Association request the following citation format be Clinical Context.............................................................. 7 used: Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters II. Exercise Testing to Diagnose Obstructive Coronary WL Jr. ACC/AHA 2002 guideline update for exercise testing: a report of the Artery Disease................................................................7 American College of Cardiology/American Heart Association Task Force on Rationale............................................................................8 Practice Guidelines (Committee on Exercise Testing). 2002. American College Pretest Probability..............................................................8 of Cardiology Web site. Available at: www.acc.org/clinical/guidelines/exercise/ Diagnostic Characteristics and Test Performance............. 8 dirIndex.htm. Believability Criteria for Diagnostic Tests...................... 10 This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org) and the American Heart Association Diagnostic Accuracy of the Standard Exercise Test........10 (www.americanheart.org). Copies of this document (the complete guidelines) Confounders of Stress ECG Interpretation......................12 are available for $5 each by calling 800-253-4636 (US only) or writing the Digoxin..........................................................................12 American College of Cardiology Resource Center, 9111 Old Georgetown Left Ventricular Hypertrophy With Repolarization Road, Bethesda, MD 20814-1699 (ask for No. 71-0231). To obtain a reprint of Abnormalities.............................................................. 12 the shorter version (executive summary describing the changes to the guide- Resting ST Depression..................................................12 lines) planned for subsequent publication in the Journal of the American Left Bundle-Branch Block............................................13 College of Cardiology and Circulation, ask for reprint No. 71-0232. To pur- Right Bundle-Branch Block..........................................13 chase additional reprints (specify version and reprint number): up to 999 copies, ST-Segment Interpretation Issues....................................13 call 800-611-6083 (US only) or fax 413-665-2671; 1000 or more copies, call 214-706-1789, fax 214-691-6342, or email [email protected]. III. Risk Assessment and Prognosis in Patients With Symptoms or a Prior History of Coronary Artery *Former Task Force member during this writing effort. Disease......................................................................... 15 Gibbons et al. 2002 American College of Cardiology Foundation - www.acc.org 2 ACC/AHA Practice Guidelines American Heart Association - www.americanheart.org Risk Stratification: General Considerations.................... 15 mates of expected health outcomes when data exist. Patient- Prognosis of Coronary Artery Disease: General specific modifiers, comorbidities, and issues of patient pref- Considerations..............................................................16 erence that might influence the choice of particular tests or Risk Stratification With the Exercise Test.......................17 therapies are considered, as well as frequency of follow-up Use of Exercise Test Results in Patient Treatment..........21 and cost-effectiveness. IV. After Myocardial Infarction............................................. 23 The ACC/AHA Task Force on Practice Guidelines makes Exercise Test Logistics.................................................... 26 every effort to avoid any actual or potential conflicts of Risk Stratification and Prognosis.................................... 27 interest that might arise as a result of an outside relationship Activity Counseling.........................................................30 or personal interest of a member of the writing panel. Cardiac Rehabilitation..................................................... 30 Specifically, all members of the writing panel are asked to Summary.......................................................................... 31 provide disclosure statements of all such relationships that V. Exercise Testing With Ventilatory Gas Analysis.............31 might be perceived as real or potential conflicts of interest. These statements are reviewed by the parent task force, VI. Special Groups: Women, Asymptomatic Individuals, reported orally to all members of the writing panel at the first and Postrevascularization Patients...............................34 meeting, and updated yearly and as changes occur. Women............................................................................. 34 These practice guidelines are intended to assist physicians Diagnosis of Coronary Artery Disease in the Elderly..... 35 in clinical decision making by describing a range of gener- Exercise Testing in Asymptomatic Persons Without ally acceptable approaches for the diagnosis, management, Known CAD.................................................................36 or prevention of specific diseases or conditions. These Valvular Heart Disease.....................................................40 Exercise Testing Before and After Revascularization......42 guidelines attempt to define practices that meet the needs of Investigation of Heart Rhythm Disorders........................ 43 most patients in most circumstances. The ultimate judgment Evaluation of Hypertension............................................. 45 regarding care of a particular patient must be made by the physician and patient in light of all of the circumstances pre- VII. Pediatric Testing: Exercise Testing in Children and sented by that patient. Adolescents..................................................................45 The summary article highlighting changes from the 1997 Appendix 1..............................................................................45 guideline to the 2002 guideline is published in the October 1 issue of Circulation and the October 16 issue of the Journal Appendix 2..............................................................................45 of the American College of Cardiology. The full-text guide- Appendix 3..............................................................................46 line is posted on the ACC and AHA Web sites. Copies of the full-text and summary article are available from both organ- References ..............................................................................46 izations. The 1997 guidelines were officially endorsed by the PREAMBLE American College of Sports Medicine, the American Society It is important that the medical profession play a significant of Echocardiography, and the American Society of Nuclear role in critically evaluating the use of diagnostic procedures Cardiology. and therapies in the management or prevention of disease states. Rigorous and expert analysis of the available data Raymond J. Gibbons, MD, FACC documenting relative benefits and risks of those procedures Chair, ACC/AHA Task Force on Practice Guidelines and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and impact the overall cost of care favorably by focusing resources on the most effective strategies. I. INTRODUCTION The American College of Cardiology (ACC) and the The ACC/AHA Task Force on Practice Guidelines was American Heart Association (AHA) have jointly engaged in formed to make recommendations regarding the appropriate the production of such guidelines in the area of cardiovascu- use of testing in the diagnosis and treatment of patients with lar disease since 1980. This effort is directed by the known or suspected cardiovascular disease. Exercise testing ACC/AHA Task Force on Practice Guidelines, whose charge is widely available and relatively low cost. For the purposes is to develop and revise practice guidelines for important of this document, exercise testing is a cardiovascular stress cardiovascular diseases and procedures. Experts in the sub- test that uses treadmill or bicycle exercise and electrocardio- ject under consideration are selected from both organiza- graphic and blood pressure monitoring. Pharmacological tions to examine subject-specific data and write guidelines. stress and the use of imaging modalities (e.g., radionuclide The process includes additional representatives from other imaging and echocardiography) are beyond the scope of medical practitioner and specialty groups where appropriate. these guidelines. Writing groups are specifically charged to perform a formal The current committee was given the task of reviewing and literature review, weigh the strength of evidence for or revising the guidelines for exercise testing published in against a particular treatment or procedure, and include esti- September 1986. Since that report, many new studies have and and corrected whenever possible. a general tified by gender. including guidelines for periopera- derived from multiple randomized clinical trials that tive cardiovascular evaluation for noncardiac surgery involved large numbers of patients and intermediate (B) if (1)(344). and accuracy of the tech.org Gibbons et al. The cost and accuracy of the technique compared with Class IIa: Weight of evidence/opinion is in more expensive imaging procedures favor of usefulness/efficacy. of exercise testing followed by a discussion of its usefulness in specific clinical situations. The recommendations the American Society of Nuclear Cardiology. as well as by the ACC/AHA Task Force er necessary with specific criteria detailed in the guidelines. The recom. cise testing. The usefulness and cost-effectiveness no data exist. and only selected references are included. and experience of the profession. or C fashion. inated by the AHA. The sensitivity. a family medicine physician. the American College of The committee reviewed and compiled all pertinent pub. Detailed evidence tables were developed whenev.americanheart. Usefulness is considered for 1) A complete list of the hundreds of publications covering diagnosis. 2002 American Heart Association . All of these The ACC/AHA classifications I. II. or prior coronary internist. guidelines for management of patients with acute . The quality. This document made are based primarily on these published data. The effect of positive or negative results on clinical deci. 4) specific clinical populations iden. Specific attention was devot. this is noted in the text. Academy of Family Physicians. were represented. the American Academy of Family Physicians. imaging procedures in selected patient subsets. When few or has been recognized. the following factors are important: general agreement that a given procedure or 1. and cardiologists revascularization. disease (CAD). the usefulness/efficacy of a procedure or nique treatment. lished reports (excluding abstracts) through a computerized Both the academic and private practice sectors. the American sively by an expert in methodologies. (as was done in other bution. as well as search of the English-language literature since 1975 and a both adult and pediatric expertise.www. expertise. The mendations for particular situations are summarized in each committee included representatives of the American section. specificity.org ACC/AHA Practice Guidelines 3 been published regarding the usefulness of exercise testing the data were derived from a limited number of randomized for prediction of outcome in both symptomatic and asymp.acc. summarize indications as follows: In considering the use of exercise testing in individual Class I: Conditions for which there is evidence and/or patients. The potential psychological benefits of patient reassur. This manual search of final articles. These guidelines will be considered current committee has did not ranked the available scientific evi. on Practice Guidelines. Class IIb: Usefulness/efficacy is less well sion making established by evidence/opinion. and 5) pediatric populations. with expertise in the use of stress imaging modalities. nominated by the ACC and three two outside reviewers nom- analyses. B. The usefulness of oxygen consumption ful analyses of nonrandomized studies or observational reg- measurements in association with exercise testing to identi. Sports Medicine. and the American College of Physicians. and the recommenda- of exercise testing has been compared with more expensive tions are based on the expert consensus of the committee. 4. 3) risk assessment of patients early after The committee consisted of acknowledged experts in exer- myocardial infarction. the sion is needed. as well as general cardiologists. treatment is useful and effective. A lower rank (C) was given when expert consensus fy patients who are candidates for cardiac transplantation was the primary basis for the recommendation. 3.www. istries.by outside reviewers nominated by The meta-analyses and evidence tables were reviewed exten. Because will be reviewed 2 years after publication and yearly there- there are essentially no randomized trials assessing health after annually by the task force to determine whether a revi- outcomes for diagnostic testsIn the original guidelines. ACC/AHA documents).American College of Cardiology Foundation . The level of evidence is provided This report overlaps with several previously published for new recommendations appearing in this update. Class III: Conditions for which there is evidence and/or ance general agreement that the procedure/treat- ment is not useful/effective and in some cases The format of these guidelines includes a brief description may be harmful. the American College of Sports inconsistencies in the original publications were identified Medicine. age. unless the task force revises or withdraws them from distri- dence in an A. 5. document was reviewed by three two outside reviewers ed to identification and compilation of appropriate meta. Inaccuracies and College of Physicians. trials that involved small numbers of patients or from care- tomatic patients. al and technical staff performing and interpreting the Class II: Conditions for which there is conflicting evi- study dence and/or a divergence of opinion about 2. The ACC/AHA guidelines for patient treatment that potentially weight of evidence was ranked highest (1) if the data were involve exercise testing. 2) severity of disease/risk assessment/prognosis many decades of exercise testing is beyond the scope of in patients with known or suspected chronic coronary artery these guidelines. other cardiac disease. the American Society of Echocardiography. and III are used to developments are considered in these guidelines. • Acute aortic dissection lines for the use of noninvasive imaging modalities. exercise testing in selected advantages to customizing the protocol to the individual patients can be performed safely by properly trained nurses. Such a description is available patient should be monitored continuously for transient in previous publications from the AHA. patient to allow 6 to 12 minutes of exercise (12). are referred. the reader is referred to the †Relative contraindications can be superseded if the benefits of exercise outweigh the other published guidelines.www. The description of this procedure. These guidelines do apply to both risks. Gibbons et al. the fatigue of the be expected to occur at a rate of up to 1 per 2500 tests (10). Contraindications to Exercise Testing transluminal coronary angioplasty (3)intervention (346).org 4 ACC/AHA Practice Guidelines American Heart Association . Exercise exercise physiologists. Further details are provided in the AHA guidelines for clini- ing in the pediatric age group (9). guidelines for percutaneous Table 1. Absolute guidelines and indications for coronary artery bypass graft • Acute myocardial infarction (within 2 d) surgery (4)(347). Although much of the pub- Physicians/ACC/AHA task force statement on clinical com. ties. to which interested readers cal exercise testing laboratories (8). quadriceps muscles in patients who are not experienced Good clinical judgment should therefore be used in deciding cyclists is a major limitation. smaller. and blood pressure should be moni- in widespread clinical use for many decades.14 ACC/AHA Guidelines for the Management of hensive understanding of the use of these imaging modali. *Appropriate timing of testing depends on level of risk of unstable angina. Absolute and before reaching their maximum oxygen uptake. both less expensive. The general context for the use of • Acute pulmonary embolus or pulmonary infarction exercise testing is outlined in Fig. which is covered in the published guidelines for tract obstruction clinical application of echocardiography (6)(349).www. The electrocardio- Exercise testing is a well-established procedure that has been gram (ECG). guidelines for clinical exer. and guidelines for management of patients • High-risk Uunstable angina not previously stabilized by with chronic stable angina (348). • Hypertrophic cardiomyopathy and other forms of outflow diography. and less noisy than treadmills and myocardial infarction and death have been reported and can produce less motion of the upper body. If exercise capacity is also report- . the committee suggests systolic blood pressure of >200 mm Hg and/or diastolic blood pressure of >110 mm Hg. 2002 American College of Cardiology Foundation . However. rhythm disturbances. and other electro- ment on exercise standards (7). States for exercise testing. ‡In the absence of definitive evidence.7 Exercise Testing Procedure supervision of a physician. myocardial perfusion imaging. As indicated in the American College of variety of published documents. heart rate. These guidelines are not • Acute myocarditis or pericarditis intended to include information previously covered in guide. Modified from Fletcher et al. which are covered in the published guidelines • Electrolyte abnormalities • Severe arterial hypertension‡ for clinical use of cardiac radionuclide imaging (5). lished data are based on the Bruce protocol. physical thera. as defined by these brief references are not intended to provide a compre. Equipment and Protocols Both treadmill and cycle ergometer devices are available for Indications and Safety exercise testing. including the state.acc. physician assistants. or positron emission • Moderate stenotic valvular heart disease tomography. This Relative† report does not include a discussion of radionuclide angiog. Exercise testing should be supervised by an appropriately Commonly used treadmill protocols are summarized in a trained physician. The reader is referred to medical therapy* these other guidelines for a more complete description of the • Uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise role of exercise testing in clinical decision making and a comparison of exercise electrocardiography with noninva- • Symptomatic severe aortic stenosis • Uncontrolled symptomatic heart failure sive imaging modalities. cise testing laboratories (8). It is beyond the tored carefully and recorded during each stage of exercise scope of this document to provide a detailed “how-to” and during ST-segment abnormalities and chest pain. adults and children. there are occasional references to the use of both radionu. Although cycle ergometers are generally Although exercise testing is generally a safe procedure. • Left main coronary stenosis raphy. • Mental or physical impairment leading to inability to exercise adequately ty.org myocardial infarction (2)(345). As a result. there are clear petence in exercise testing (11). because subjects usually stop which patients should undergo exercise testing. cardiographic manifestations of myocardial ischemia. who should be in the immediate General Overview vicinity and available for emergencies.americanheart. and guidelines for exercise test. Patients With Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction (350) (see Table 17). • High-degree atrioventricular block clide and echocardiographic imaging techniques. AHCPR Unstable Angina Guidelines. For such an understanding. relative contraindications to exercise testing are summarized treadmills are much more commonly used in the United in Revised Table 1. capacity should be reported in estimated metabolic equiva- pists. ST-segment changes. This section is intended to provide a brief overview of the exercise testing procedure. 1. or medical technicians working directly under the lents (METs) of exercise. This • Tachyarrhythmias or bradyarrhythmias report also does not include any discussion of stress echocar. For clari. Symptoms warranting yes *Electrocardiogram interpretable unless pre. high-risk if Duke treadmill score yes predicts average annual cardiovascular mortality Is greater than 3% (see Fig 2 resting ECG no for nomogram). myocardial infarction. **For example. or resting ST- segment depression greater than 1 mm. CAD interpretable*? Exercise imaging study indicates coronary artery disease. electrocardiogram. left bundle no branch block. 2002 American Heart Association . left Can patient no Pharmacologic imaging study ventricular hypertrophy. yes treatment. and exercise? ST depression less than 1 mm. MI. Exercise test Is test result high yes Consider coronary risk?** angiography/revascularization no Is diagnosis no Consider imaging and prognosis study/angiography certain? yes Continue/initiate/modify rx as appropriate . electronically paced rhythm.acc.org Gibbons et al. See text for discussion of digoxin use.americanheart.www. and rx.org ACC/AHA Practice Guidelines 5 Patient with stable chest pain or unstable chest pain stabilized by therapy low-risk or intermediate-risk unstable angina or previous MI or post-revascularization CAD Need for Need to diagnosis yes risk/prognostic no guide medical no certain? assessment? management? yes no yes Contra- indications to yes Continue/initiate/modify stress testing? Consider coronary angiogram medical rx Figure 1.American College of Cardiology Foundation . angiography? excitation. ECG. Clinical context for no exercise testing for patients with suspected ischemic heart disease.www. 362. RVUs. There is a Revised Table 3 is a comparison of year 1996 2000 Table 3. 93545. The details of interpretation are ECG indicates electrocardiogram.org Table 2. and coronary angiography. and IVCD. supraventricular tachycar- response to exercise are important findings. 93556 901. Compared with imaging pro- Exercise End Points cedures such as stress echocardiography.americanheart.780* 67*73* 66*72* 533.0 mm) in leads without diagnostic Q-waves (other than V1 or aVR) Relative indications Interpretation of the Exercise Test • Drop in systolic blood pressure of (≥10 mm Hg from baseline Interpretation of the exercise test should include exercise blood pressure despite an increase in workload. or claudica. the nature of the protocol should be specified There are relatively few published studies comparing the clearly. ataxia. Medicare Fees and Volumes of Commonly Used Diagnostic Procedures 2000 Total 1998 Medicare Data (Professional and Technical) Number Percent Charged Percent Procedure 19981996 CPT Code(s) Medicare RVUs Performed by Cardiologists Office-Based Treadmill exercise test 93015 or 93016–93018 3. and those with excessive heart rate • Increasing nervous system symptoms (eg. wheezing. treadmill heart rate. shortness of breath. premature ventricular contractions. The use of rating of perceived exertion scales. or response.7 Cost and Availability ed in minutes. is often helpful in • Technical difficulties in monitoring ECG or systolic blood assessment of patient fatigue.000* Stress echocardiography 93350.956.404 7880 6764 (plus any Doppler charge) 353. PVCs. ICD. Indications for Terminating Exercise Testing wide spectrum of individual subject values around the Absolute indications regression line for maximum heart rate. relative value units. The target heart rate approach has obvious addition- other evidence of ischemia al limitations in patients receiving beta-blockers. intraventricular conduction delay. single-photon emission computed tomography. and electrocardio- • ST or QRS changes such as excessive ST depression (>2 mm of graphic response. The most impor- dia. 66.12 875.4517. particularly if it forces axis shift termination of the test. it should be recognized that other end points exercise testing can be performed at a much lower cost. (summarized in Table 2) are strongly preferred.acc. ton emission computed tomography (SPECT) myocardial jects reach an arbitrary percentage of predicted maximum perfusion imaging. implantable cardioverter-defibrillator discharge. 93015 17. in the absence of other evidence of ischemia capacity and clinical.942 Stress SPECT myocardial perfusion imaging 78465. cost-effectiveness of treadmill exercise testing with more expensive imaging procedures. The occurrence of ischemic chest pain horizontal or downsloping ST-segment depression) or marked consistent with angina is important. Abnormalities in exercise capacity. includ. leg cramps. Modified from Fletcher et al. 93543. when accompanied by others. the committee suggests systolic blood pressure of >250 mm Hg and/or a diastolic blood pressure of >115 mm Hg. systolic blood pressure response to exercise.210 Left heart catheterization with left 93510. covered elsewhere in these guidelines. †There are no reliable data regarding this percentage. those with • Moderate to severe angina heart rate impairment. The most commonly used definition for visual inter- tion • Development of bundle-branch block or IVCD that cannot be pretation of a positive exercise test result from an electro- distinguished from ventricular tachycardia cardiographic standpoint is greater than or equal to 1 mm of • Increasing chest pain horizontal or downsloping ST-segment depression or eleva- • Hypertensive response* tion for at least 60 to 80 milliseconds (ms) after the end of *In the absence of definitive evidence. or bradyarrhythmias tant electrocardiographic findings are ST depression and ele- • Fatigue.319 † 3443 (plus isotope charge) 1. Gibbons et al. 2002 American College of Cardiology Foundation . heart block. Rating of perceived exer- • Sustained ventricular tachycardia tion is less helpful in pediatric populations.16 213.www. • Arrhythmias other than sustained ventricular tachycardia.303. after excluding treadmill exercise tests performed with perfusion imaging. stress single-pho- Although exercise testing is commonly terminated when sub.8367. vation.79 889.763 88 <11 ventriculogram and coronary angiography 93555.org 6 ACC/AHA Practice Guidelines American Heart Association . the QRS complex (4) (347). dizziness. and SPECT. hemodynamic. 93015 7.58 728.625 *These numbers are estimates.www. • ST elevation (≥1. such near-syncope) • Signs of poor perfusion (cyanosis or pallor) as the Borg scale (Appendix 1) (13). which may therefore • Drop in systolic blood pressure of >10 mm Hg from baselineblood be beyond the limit of some patients and submaximal for pressure despite an increase in workload. and heart rate ing multifocal PVCs. CPT indicates current procedural terminology. triplets of PVCs. Symptom-limited testing with pressure the Borg scale as an aid is very important when the test is • Subject’s desire to stop used to assess functional capacity. . Special groups who represent exceptions to OBSTRUCTIVE CAD this norm are discussed in detail in sections VI and VII. age. Thus. Pretest Probability of Coronary Artery Disease by Age. procedures. includes a discussion of the implications of acute reperfu- sion therapy for interpretation of exercise testing in this pop- Clinical Context ulation.As shown in Table 3. the depression) with an intermediate pretest probability committee thought that it was important to provide an over. or may be post-myocardial infarction or postrevascularization patients. these more sophisticated procedures. estimated two thirds 72% of the treadmill exercise tests The potential role of treadmill exercise testing in such charged to Medicare in 19941998 were performed as office patients is detailed in section III. Classes II and III below). patients with ages at the extremes of the decades listed may have probabilities slightly outside the high or low range.org ACC/AHA Practice Guidelines 7 Medicare RVUs (relative value units. Patients who are unable to exercise or who have uninter- nical) for treadmill exercise testing and selected imaging pretable ECGs because of pre-excitation. Table 4. ECG. 1). electronically procedures. Class I ical decisions (so-called nodal points) for which exercise Adult patients (including those with complete right testing is used.www. High indicates >90%. description of chest pain. Although this document is not intended to be bundle-branch block or less than 1 mm of resting ST a guideline for the management of stable chest pain. These RVUs provide an estimate of relative paced rhythm. because the sum of the chest pain. but it can be assumed that prevalence of CAD increases with age. and 33%27% of the charges were submitted by Post-myocardial infarction patients represent a common noncardiologists.1 times higher.348-350). which office-based procedure. and set of patients who may need risk or prognostic assessment. there usually is a clin- performed about as often as the most frequent imaging pro. gender. Compared with the treadmill exercise test. and symptoms of in a lower overall cost of patient care. In a few cases. Patients who are candidates for exercise testing may have stable symptoms of chest pain. . which when the initial treadmill exercise test is less accurate than focuses on the use of treadmill exercise testing for diagnosis. or ST depression costs. professional and tech. The clini- coronary angiography 20 21. Even in patients for whom the diagnosis of CAD is certain Treadmill exercise testing is performed frequently (revised on the basis of age.American College of Cardiology Foundation .americanheart.7 times higher. are convenient for the patient because they are often an This subgroup is considered in detail in section IV. and all context for the use of exercise testing to facilitate the use symptoms (specific exceptions are noted under of these guidelines (Fig. <5%. low. 10%–90%.acc. and very low. treadmill exercise tests are history of prior myocardial infarction. left bundle-branch block.www. of CAD (Table 4) on the basis of gender. Gender. and Table 3).4 2. the scope of these guidelines. EXERCISE TESTING TO DIAGNOSE heart disease. given the patient’s history. may be stabilized by medical Class IIa therapy after symptoms of unstable chest pain. Patients with vasospastic angina.7 times higher. The important factors involved in addressing this cost of additional testing and interventions may be higher question are covered in section II of this document. and ered in other ACC/AHA guidelines (5. intermediate. the cost of greater than 1 mm require imaging studies and are beyond stress echocardiography is at least 2. The vast majority of treadmill exercise testing is performed in adults with symptoms of known or suspected ischemic II.org Gibbons et al. 2002 American Heart Association .5 5. They are a sub- widely performed. do not always require a cardiologist. and Symptoms* Age Typical/Definite Atypical/Probable Nonanginal (y) Gender Angina Pectoris Angina Pectoris Chest Pain Asymptomatic 30–39 Men Intermediate Intermediate Low Very low Women Intermediate Very low Very low Very low 40–49 Men High Intermediate Intermediate Low Women Intermediate Low Very low Very low 50–59 Men High Intermediate Intermediate Low Women Intermediate Intermediate Low Very low 60–69 Men High Intermediate Intermediate Low Women High Intermediate Intermediate Low *No data exist for patients <30 or >69 years. treadmill exercise tests are more first presentation of ischemic heart disease. Lower cost of cian should first address whether the diagnosis of CAD is the treadmill exercise test alone does not necessarily result certain. ical need for risk or prognostic assessment to determine the cedure (stress SPECT myocardial perfusion imaging). Sections II through IV reflect the variety of patients and clin. Imaging studies are consid- stress SPECT myocardial imaging 5. <10%. An need for possible coronary angiography or revascularization. and the clinician’s experience with this 3. and gender. gender.www. Patients with the following baseline ECG abnormali. symptoms. Typical or definite 4. The associated with extensive atherosclerosis. plaque will have an abnormal test. tive lesions explain some of the events that occur after a nor- mal exercise test (see section III). and P(CAD). Detailed nomograms are available that incorporate the effects of a history of prior infarction. Although the coronary Cut Point or Discriminant Value angiogram has obvious limitations (16). Smoking and hypercholesterolemia have a minimal tors for atherosclerosis.and T-wave changes. physical examination symptoms. the percentage of those with an abnormal (1) test result who have disease.org 8 ACC/AHA Practice Guidelines American Heart Association . Diabetes has only a modest on exertion.americanheart. The problem with any diagnostic Table 5. those with an abnormal test result but no disease (false-positives). separates the two groups. impact. review of Diamond and Forrester (17). ing (see sections III and IV). or multiple risk fac. Gibbons et al. but most catastrophic events are patients free of disease who will have a normal test. ischemia and risk can be determined by test. Diagnostic testing is ties: most valuable in this intermediate pretest probability cate- gory. 2002 American College of Cardiology Foundation . TN. Atypical or probable angina in a 50-year-old Class III man or a 60-year-old woman is associated with approxi- 1. and hypercholesterolemia (19). and gender. and chest pain characteristics). 2. both 1 and 2. . Typical or definite angina can be • Electronically paced ventricular rhythm defined as 1) substernal chest pain or discomfort that is 2) • Greater than 1 mm of resting ST depression provoked by exertion or emotional stress and 3) relieved by • Complete left bundle-branch block rest and/or nitroglycerin. Patients with electrocardiographic criteria for left angina makes the pretest probability of disease so high that ventricular hypertrophy (LVH) and less than 1 mm of the test result does not dramatically change the probability. those with a normal test result but disease (false-negatives). Results of correla. However. Myocardial ischemia is the most important Diagnostic Characteristics and Test Performance cause of chest pain and is most commonly a consequence of underlying coronary disease. FN. angiographic lesions remain the clinical gold standard. the most predictive clinical finding is a history of chest pain or discomfort. and initial testing. PV1. three characteristics of definite or typical angina (18). Specificity is the percentage of rupture. mately a 50% probability of CAD.acc. impact. Table 4 is a modification of the literature sion and taking digoxin. Meta-analysis of the studies has not disease is to determine a value measured by the test that best demonstrated that the criteria affect the test characteristics.org Class IIb Pretest Probability 1. Patients with less than 1 mm of baseline ST depres. electrocardiographic Rationale Q waves. Patients with a documented myocardial infarction or defined as chest pain or discomfort that lacks one of the prior coronary angiography demonstrating signifi. resting ECG abnormalities. Although other clinical findings. A basic step in the application of any testing procedure for tive studies have been divided concerning the use of 50% or the separation of subjects without disease from patients with 70% luminal occlusion. clinical scores have been developed that could better predict however. electrocardiographic ST. dia- betes. baseline ST depression. Patients with a low pretest probability of CAD by age. Patients with a high pretest probability of CAD by The clinician’s estimation of pretest probability of obstruc- age. FP. and thrombosis. pretest probability. those with a normal test result and no disease (true- negatives). tive CAD is based on the patient’s history (including age. Definitions and Calculation of the Terms Used to Quantify the Diagnostic Accuracy of a Test Sensitivity = [TP/(TP + FN)] × 100 Specificity = [TN/(FP + TN)] × 100 Sensitivity × P(CAD) Predictive value of an abnormal test (PV+) = [Sensitivity × P(CAD)] + [(1 – Specificity)[1 – P(CAD)]] Predictive accuracy = [Sensitivity × P(CAD)] + [Specificity × [1 – P(CAD)]] TP indicates those with an abnormal test result and disease (true-positives). because the test result has the largest potential effect on • Pre-excitation (Wolff-Parkinson-White) syndrome diagnostic outcome. type of problem. such as dyspnea ly affect pretest probability. These nonobstruc- method of calculating these terms is shown in Table 5. may suggest the possibility of CAD. Atypical or probable angina can be 2. the percentage of correct classifications. smoking. predictive accuracy.www. Other cant disease have an established diagnosis of CAD. History and The exercise test may be used if the diagnosis of CAD is electrocardiographic evidence of prior infarction dramatical- uncertain. the test can be performed in these patients for other reasons. pretest probability (351). CAD that has not resulted in Sensitivity and Specificity sufficient luminal occlusion to cause ischemia during stress Sensitivity is the percentage of patients with a disease who (15) can still lead to ischemic events through spasm. americanheart. then the test will have a higher sensitivity for any cut man with typical angina pectoris (high pretest probability). CAD indicates coronary artery disease. In addition. FP.e. Effect of Disease Prevalence on Predictive Value of a Positive Test Number With Number With Prevalence of Test Abnormal Normal Test Predictive Value of CAD (%) Subjects Characteristics Test Result Result a Positive Result 5 500 with CAD 50% sensitive 250 (TP) 250 (FN) 250/(250 + 950) 9500 without CAD 90% specific 950 (FP) 8550 (TN) = 21% 50 5000 with CAD 50% sensitive 2500 (TP) 2500 (FN) 2500/(2500 + 500) 5000 without CAD 90% specific 500 (FP) 4500 (TN) = 83% Calculation of the predictive value of an abnormal test (positive predictive value) using a test with a sensitivity of 50% and a specificity of 90% in two populations of 10.. false-negative. mined by sensitivity and specificity. For 50% prevalence: PV+ = 2500/(2500 + 500) = 83%. Bayes’ theorem states that the probability of a patient having the disease after a test is performed will be Population Effect the product of the disease probability before the test and the Sensitivity and specificity are inversely related. For instance. In a test with characteristics like the exercise ECG. However.. Although the statistical models proposed have proved supe- dictive value is calculated. 1 mm of ST-segment depres- The information most important to a clinician attempting to sion). true-negative. is also required. The same abnormal response would be tion is skewed toward persons with a greater severity of dis. pretest probability) tivity. reducing the test’s sensitivity.e.. If the popula. true-positive. pretest probability). then probability cannot be estimated accurately from the test a substantial number of those with the disease appear to be result and the diagnostic characteristics of the test alone. resting ST depression. the predictive value of 1 mm of ST depression increas- es from 21% when there is a 5% prevalence of disease to 83% when there is a 50% prevalence of disease. giving the test a high specificity.org Gibbons et al. Such a ease have a normal test. the equations were usually demonstrates how disease prevalence affects the calculation. If the value is set high (i. There may be reasons Knowledge of the probability of the patient having the dis- for wanting to adjust a test to have a relatively higher sensi- ease before the test is administered (i. derived in study populations with a higher prevalence of dis- The positive predictive value of an abnormal test result is ease than seen in clinical settings because of workup bias. LVH. and TN. the results of the exercise test were used to decide who have a disease.www. the percentage of persons with an abnormal test result who e. Thus. The clinician the population tested. Note that it is dependent on the rior. and determined by the choice of a cut often makes this calculation intuitively. This explains the greater percentage of false-positive results found when the test is used as a screening procedure in an asymptomatic group (with a low prevalence of CAD) as opposed to when it is used as a diagnostic procedure in patients with symptoms most likely due to CAD (higher prevalence of CAD).American College of Cardiology Foundation . use Table 6. A Mathematical equations or scores developed from multivari- test can have a lower specificity if it is used in persons in able analysis of clinical and exercise test variables provide whom false-positive results are more likely. but sensitivity and specificity are inversely related.acc.e. Table 6 coefficients chosen. one with a CAD prevalence of 5% and the other with a prevalence of 50%. PV+ is the test performance characteristic most apparent to the clinician using the test. the available equations have differed as to variables and prevalence of disease in the population tested. 2002 American Heart Association .org ACC/AHA Practice Guidelines 9 test is that there is a large overlap of measurement values of from the demonstrated specificity or sensitivity of a test. atypical angina has an abnormal exercise test result (low then the population tested must be considered. All tests used it is dependent on disease prevalence (pretest probability of for diagnosis of CAD have considerable overlap in the range disease). intuitively considered a true-positive result in a 60-year-old ease. but a test in the groups with and without disease. TP.www. Once a discriminant value that or she suspects a false result when a 30-year-old woman with determines the specificity and sensitivity of a test is chosen.21).. such as those superior discrimination compared with use of only the ST- with valvular heart disease. 2 mm of ST-segment make a diagnosis is the probability of the patient having or depression) to ensure that nearly all subjects without the dis- not having the disease once the test result is known. variables to apply and how to include them in prediction. Predictive value cannot be estimated directly would undergo cardiac catheterization. Such scores can provide patients taking digoxin. diagnostic interpretation Predictive Value of the exercise test still centers around the ST response. point chosen. four times as many of those with an abnormal test result will be found to have coronary disease when the patient population increases from a 5% prevalence of CAD to a 50% prevalence. affected by probability that the test provided a true result. false-positive. . and segment response to diagnose CAD. the exercise test has a higher sen- sitivity in the elderly and persons with three-vessel disease Scores than in younger persons and those with one-vessel disease. normal. of measurements for the normal population and those with heart disease. Table 5 shows how pre. These calculations demonstrate the important influence that prevalence has on the positive predictive value. probabilities of CAD that are more accurate than ST meas- urements alone (20. for instance. FN. A certain value (discriminant value) is used to Probability Analysis separate these two groups (i.g. For these reasons. For 5% prevalence: PV+ 5 250/(250 + 950) = 21%.000 patients. The predictive value of a positive test is another term that because the clinician remains uncertain about which other defines the diagnostic performance of a test and is deter. when he point or discriminant value. these equa. Several description of the diagnostic accuracy of the exercise test.americanheart.77 0.79 The variability of the reported diagnostic accuracy of the Hung89 1985 171 0. with a range of 23% to 100% and a standard deviation cal cardiologists. Most of the studies failed to fulfill these criteria. In addition.73 ticularly removal of workup bias. from this meta-analysis) that removed patients with a prior myocardial infarction. only the the ST segment in interpreting the exercise test. combined.73 0. The more relevant issue is to evaluate patients who Author Year Patients Sensitivity Specificity are suspected but not known to have the disease of interest Roitman46 1970 100 0.60 Diagnostic Accuracy of the Standard Exercise Test Melin88 1985 135 0.86 predict disease severity but should not be included in studies Currie83 1983 105 0.23). ance of the test. accurately portray the perform- Studies validating diagnostic tests should include consecu. with a range of 17% to (22. results in the 58 studies (which included 11.92 0. Any diagnostic test appears to function well if Table 8.g.55 0. such equations are shown in Appendix 2.48 0.73 Averages with ST 9153 0. Gibbons et al.85 0.69 0.26 Number of Total Number Sens Spec Predictive Grouping Studies of Patients (%) (%) Accuracy (%) Meta-analysis of standard exercise test 147 24.64 0.org 10 ACC/AHA Practice Guidelines American Heart Association .www.80 Huerta87 1985 114 0.79 out disease. Meta-Analyses of Exercise Testing25. par. myocardial infarction. the Meta-analysis of 147 consecutively published reports (Tables Duke treadmill prognostic score has been shown to be better 7 through 13) involving 24. Hlatky84 1984 3094 0. mean specificity was 77%.63 Detry90 1985 284 0.www.82 and to differentiate those who do from those who do not. MI. Machecourt80 1981 112 0. However. Physicians are often urged to “use” more than just 100% and a standard deviation of 17%).48 applied. Workup bias refers to the Others (11)* 1974–1986 861 0.82 myocardial infarction patients may be included in studies to Guiteras81 1982 112 0.62 most certainly have the disease (e. each with <100 subjects. left ventricular hypertrophy.56 0. Weiner91 1985 617 0. 68%.61 Santinga82 1982 113 0.17 the patients enrolled in the study do not represent this diag. specificity.76 Criteria to judge the credibility and applicability of the Ananich92 1986 111 0. These studies demonstrated a mean sensitiv- tive or randomly selected patients for whom the diagnosis is ity of 67% and a mean specificity of 72%.79 0. the predictions have been comparable of 16%. Morales-Ballejo79 1981 100 0.074 patients who underwent both than ST depression alone for diagnosing angiographic coro. Total lenge”).047 68 77 73 Meta-analysis without MI 58 11.70 fact that most reported studies were affected by clinical prac. Spec.69 but not in clinical practice.72 exercise ECG has been studied by meta-analysis (25.61 0.90 0. the test may perform well in the study Weiner77 1979 2045 0. Detrano94 1986 303 0. Problems arise when patients who Marcomichelakis78 1980 100 0. If Erikssen74 1977 113 0.acc.79 0. Post.69 0.70 Dunn76 1979 125 0. 2002 American College of Cardiology Foundation .65 nostic dilemma group.74 tion patients) are included in this diagnostic sample.69 0. thus fulfilling one of the criteria for Believability Criteria for Diagnostic Tests evaluating a diagnostic test. of these equations remains controversial and limited.65 Machecourt86 1985 105 0. post-myocardial infarc.26).82 attempting to distinguish those with disease from those with. Silber75 1979 108 0. O’Hara85 1985 103 0.45 0. depression tice wherein test results were used to determine who should be included.84 0.70 0.691 patients tions provide the only scientific means to do so.71 0. coronary angiography and exercise testing revealed a wide nary disease (352).691 67 72 69 Meta-analysis without workup bias 3 >1000 50 90 69 Meta-analysis with ST depression 22 9153 69 70 69 Meta-analysis without ST depression 3 840 67 84 75 Meta-analysis with digoxin 15 6338 68 74 71 Meta-analysis without digoxin 9 3548 72 69 70 Meta-analysis with LVH 15 8016 68 69 68 Meta-analysis without LVH 10 1977 72 77 74 Sens indicates sensitivity.61 0. In the few studies in doubt (24).92 results of studies evaluating diagnostic tests (27) were Vincent93 1986 122 0. When these computational techniques variability in sensitivity and specificity (mean sensitivity was have been compared with the judgment of experienced clini. However. .68 0..71 0. Studies Including Resting ST Depression obviously normal subjects are compared with those who obviously have the disease in question (a “limited chal.org Table 7.62 0. this analysis provides the best *Eleven other studies. and LVH.69 0. 63 0.82 Nair96 1983 280 0.55 0.86 ST depression Melin88 1985 135 0.65 O’Hara85 1985 103 0. and lower in patients with one-vessel disease. Studies Including Digitalis Total Total Author Year Patients Sensitivity Specificity Author Year Patients Sensitivity Specificity Roitman46 1970 100 0. sensitivity will be higher in patients with three-vessel disease • Sensitivity decreased when equivocal tests were considered normal.68 0.90 0.69 and 90%.69 0.74 LVH with digitalis *Nine other studies.org ACC/AHA Practice Guidelines 11 Table 9.64 0. respectively (28.61 0.69 through through 1986 1986 Averages with 8016 0. digitalis vide a true estimate of how standard electrocardiographic cri. the multivari.70 0. Specificity From Meta-Analysis able scores discussed previously appear to make the tests comparable.66 Averages w/o 840 0.71 0.68 Others* 1971 839 0.353).65 Machecourt86 1985 105 0.17 Nair96 1983 280 0.92 Vincent93 1986 122 0.71 0. *Five other studies.85 O’Hara85 1985 103 0.45 0.45 0.79 0.67 0. teria perform in patients with chest pain typically seen by the internist or family practitioner.73 Detrano94 1986 303 0.68 0.71 0.69 0.70 Silber75 1979 108 0.67 0.62 Weiner77 1979 2045 0.76 Weiner91 1985 617 0.64 0. “better” test lowered the relatively high specificity. The modest sensitivity (about sensitivity of the exercise ECG (publication bias).76 Ananich92 1986 111 0. .79 Hung89 1985 171 0.84 Santinga82 1982 113 0.85 to undergo both procedures. Table 12.65 Marcomichelakis78 1980 100 0.www.64 0. combined.65 Dunn76 1979 125 0.69 0. 2002 American Heart Association . however.70 Dunn76 1979 125 0.68 0.60 Weiner91 1985 617 0. each with <100 subjects. As mentioned previously.American College of Cardiology Foundation . the approximate sensitivity and specificity of 1986 1 mm of horizontal or downward ST depression were 50% Averages w/o 3548 0.83 in which workup bias was avoided by having patients agree Others* 1978 340 0. hypertrophy.66 0.29.www.80 Machecourt86 1985 105 0.69 Machecourt80 1981 112 0. Studies Including Left Ventricular Hypertrophy Table 10.61 0.68 0.79 Hlatky84 1984 3094 0.81 Erikssen74 1977 113 0.61 0. 50%) of the exercise ECG is generally less than the sensitiv- ity of imaging procedures (56. combined.org Gibbons et al. Studies Excluding Digitalis Total Total Author Year Patients Sensitivity Specificity Author Year Patients Sensitivity Specificity Sketch95 1980 107 0.69 Furuse97 1987 135 0. specificity was lowered and sensitivity and independently related to two study characteristics: increased.63 *Four other studies.82 Erikssen74 1977 113 0.93 Hlatky84 1984 3094 0.56 0. thereby fulfilling the other through major criterion.79 0.92 Ananich92 1986 111 0. each with <100 subjects.73 0. Studies Excluding Resting ST Depression Table 11.77 0.83 Morales-Ballejo79 1981 100 0.48 Vincent93 1986 122 0.84 0.62 0.74 Others* 1971–1984 318 0. LVH indicates left ventricular *Ten other studies.48 0.72 0.americanheart.72 Furuse97 1987 135 0.79 0.80 Huerta87 1985 114 0.81 Currie83 1983 105 0.73 0.77 0.acc.349).69 0.64 0.82 Sketch95 1980 107 0. Specificity (percentage of those without coronary disease who had a normal ST response) was found to be significant- Sensitivity From Meta-Analysis ly and independently related to two variables: Sensitivity (percentage of those with coronary disease who • When upsloping ST depression was classified as had an abnormal ST response) was found to be significantly abnormal.82 Machecourt80 1981 112 0.84 0.70 0.77 0.66 0.48 0.59 0. These latter studies pro.78 Guiteras81 1982 112 0.82 Roitman46 1970 100 0.85 0.60 Huerta87 1985 114 0.92 0.69 0.55 0. combined.48 Detrano94 1986 303 0. combined. each with <100 subjects.73 Others* 1974 737 0.17 Silber75 1979 108 0. each with <100 subjects.90 0.69 Averages 6338 0. It is apparent that the true diagnostic value of the exercise ECG lies in its • Comparison with a new.93 Weiner77 1979 2045 0. Detry90 1985 284 0. and it workup bias (354). Of the 58 stud- ies.83 Others* 1971 442 0.66 0. Upsloping ST depression should be considered borderline or Confounders of Stress ECG Interpretation negative. as well as to themselves.82 • Studies that included patients taking digoxin had a Nair96 1983 280 0. with referrals for additional tests only indicated in patients Tables 8 through 13 were developed to resolve the issues of with an abnormal test result. the likelihood of sary to do so before diagnostic testing (32). Hyperventilation is no longer routinely recom- mended before testing. and total Resting ST Depression patient numbers were considered.77 0. studies that excluded patients taking digoxin had Hung89 1985 171 0. specificity.56 0. it is not neces- depression.85 0. This explanation for this association. but an abnormal response.americanheart. analysis makes it important that clinicians use proper . LVH indicates left ventricular specificity. Author Year Patients Sensitivity Specificity • Studies that included patients with resting ST depres- Marcomichelakis78 1980 100 0.77 ficity.72 69%. other studies in apparently healthy persons LVH (see below) have suggested that digoxin use also lowers *Six other studies.74 ificity of 70%.31) and is directly related to age. Digoxin produces an abnormal ST-segment response to exer- the standard exercise test is still thea reasonable first test cise.acc. These studies marker for adverse cardiac events in patients with and with- can be summarized as follows: out known CAD (38-42).79 74%.72 0. Resting ST-segment depression is a marker for a higher prevalence of severe CAD and is associated with a poor Influence of Other Factors on Test Performance prognosis. These meta-analyses provide only indirect evidence regard- ing these potentially important factors.org 12 ACC/AHA Practice Guidelines American Heart Association .69 0. that the study populations were otherwise equal with respect ed with a decreased specificity. tant diagnostic information in such patients and that exercise Therefore. There is a divergence healthy subjects studied (30. Hyperventilation was critical assumption has not been confirmed and may not be once thought to reveal false-positive ST responders by true.63 a mean sensitivity of 72% and a mean specificity of Detry90 1985 284 0. imaging modalities are preferred in this subset of patients. has low specificity. The wide variability in test performance apparent from bringing out ST depression with a stimulus other than this meta-analysis can be explained by differing degrees of ischemia. Furuse97 1987 135 0. there are few patients with resting ST Repolarization Abnormalities depression greater than 1 mm. and therefore further testing is indicated. but it also demonstrates that some of the is no longer recommended as a routine to be per. Digoxin tically useful in these patients. standard exercise testing continues to be diagnos. of opinion regarding two specific patients groups: those who Two weeks are required to alleviate the effect on the repolar- are taking digoxin and have less than 1 mm of ST depression ization patternAlthough patients must be off the medication and those with LVH with less than 1 mm of resting ST for at least 2 weeks for its effect to be gone.62 sion had a mean sensitivity of 69% and a mean spec- Morales-Ballejo79 1981 100 0. It was the consensus of the This ECG abnormality is associated with a decreased speci- committee that exercise testing is unlikely to provide impor- ficity of exercise testing.66 sensitivity of 67% and a mean specificity of 84%. However. but sensitivity is unaffected.79 0. In Left Ventricular Hypertrophy With the published data.77 0. hypertrophy. . because they assume • The use of pre-exercise hyperventilation was associat. resting ST depression. each with <100 subjects.86 Currie83 1983 105 0. Santinga82 1982 113 0. CAD is substantially reduced. If the test result is negative. although there is no to characteristics that might influence test performance. Gibbons et al. Miranda et al.org Table 13.64 0.62 0. the cardiographic evidence of prior myocardial infarction. variability is explained by improper methods for testing and formed before standard testing (26). (43) performed a ret- • Studies that included patients with LVH had a mean rospective study of 223 patients without clinical or electro- sensitivity of 68% and a mean specificity of 69%.www. and only those with more Resting ST-segment depression has been identified as a than 100 patients were considered separately.84 When these results are compared with the average sensitiv- through ity of 67% and specificity of 72%. studies that excluded them had a mean Guiteras81 1982 112 0. 1983 only LVH and resting ST depression appear to lower speci- Averages w/o 1977 0.93 mean sensitivity of 68% and a mean specificity of Melin88 1985 135 0. LVH.92 0. however. 2002 American College of Cardiology Foundation . this has not been validated. a standard exercise test may still be the first test.61 0. Although specificity is low- ered in the presence of resting ST depression less than 1 mm. Studies Excluding Left Ventricular Hypertrophy studies that excluded them had a mean sensitivity of Total 72% and a mean specificity of 77%. and digoxin use. combined. This abnormal ST depression occurs in 25% to 40% of option because sensitivity is increased.www. only those that provided sensitivity. it appears unnecessary for physicians to accept the risk of stopping beta-blockers before Right-Sided Chest Leads testing when a patient exhibits possible symptoms of In a new approach. because lead II has a high false-positive rate.org ACC/AHA Practice Guidelines 13 Women. 80%). Exaggerated atrial repolarization waves during exercise can cause downsloping ST depression in the absence of Right Bundle-Branch Block ischemia. absence of Exercise-induced ST depression usually occurs with right exercise-induced chest pain. prognostic value because of inadequate heart rate response.www. Atrial repolarization waves are opposite in direction to P mal subjects. and thallium-201 scintigraphy. the precordial Despite the marked effect of beta-blockers on maximal exer.acc. 3. (355).American College of Cardiology Foundation . resting ST depression. in the left chest leads (V5 and V6) or inferior leads (II and aVF). (358) examined 245 ischemia or has hypertension.www.47). (45). (VT) (34. and those taking digoxin or with The decision to remove a patient from beta-blocker therapy valvular or congenital heart disease were excluded.americanheart. V3) and is not associated with ischemia (37). can affect test performance by altering the ers in these patients for diagnosis of any coronary disease hemodynamic response of blood pressure. secutive group of men being evaluated for possible CAD (33). However. ST-segment depression confined to the inferior leads is of lit- tle value for identification of coronary disease (48). “nonspecific” ST-T changes such as T-wave inversions Overview of Confounders: Digoxin. Even up to 1 cm of ST depression can occur in healthy nor. patients with resting ECGs showing left bundle. and LVH as exclusion crite- and the meta-analysis support the conclusion that additional ria in the 58 studies that excluded patients with a myocardial exercise-induced ST-segment depression in patients with infarction. additionally. vasodilators. specificity. Exercise-induced ST depression usually occurs with left bun. The results are summarized in Tables 7 to 13. right ventricular leads.357). Diagnostic end points of two mm of additional exercise. these Electrocardiographic Abnormalities studies included bundle branch blocks. which can lead to accelerated angi- prevalence of severe coronary disease (30%) compared with na or hypertension. . those without resting ST-segment depression (16%). exercise testing in patients who underwent exercise testing with standard 12 patients taking beta-blockers may have reduced diagnostic or leads. leads alone are a reliable marker for CAD. confers diagnostic significance in left bundle-branch block. Other studies have found decreased specificity in patients with resting ST-segment depression (46. Only those that included at least 100 patients and resting ST-segment depression represents a reasonably sensi. and should be done carefully to avoid a potential hemody- segment depression that correlated with nearly twice the namic “rebound” effect. Resting ST and/or flattening. exercise-induced cian. In patients without prior myocardial Beta-Blocker Therapy infarction and with normal resting ECGs. Other Drugs induced ST-segment depression or downsloping depression Various medications. specificity were considered in the average. The presence of right bundle-branch block does not Lead Selection appear to reduce the sensitivity. considering the status of three studies that considered isolated resting ST depression digoxin. the combination of lead V5 with II. for exercise testing should be made on an individual basis cent of these selected male patients had persistent resting ST. had similar associated with exercise-induced ventricular tachycardia results. However. For routine exercise testing. as associated with myocardial ischemia.4.35). Ten per. previous infarction. (44) and Harris et al. tion of nitrates can attenuate the angina and ST depression Smaller studies by Kansal et al. There is no level of ST-segment depression that waves and may extend into the ST segment and T wave. In patients with a normal resting ECG. and markedly downsloping PR bundle-branch block in the anterior chest leads (V1 through segments in the inferior leads (356. and Left Ventricular Hypertrophy ST-segment depression were not considered separately. those with LVH and resting Depression. sensitivity. Michaelides et al. no differences in test performance were found in a con.org Gibbons et al. 2002 American Heart Association . Flecainide has been well as a large study by Fearon et al. Atrial Repolarization dle-branch block and has no association with ischemia (36). The The meta-analysis was reprocessed. tion. when patients were subgrouped according to inferior limb leads adds little additional diagnostic informa- beta-blocker administration initiated by their referring physi. and monitoring of cise heart rate. its ST-Segment Interpretation Issues test characteristics are similar to those of a normal resting ECG. Those studies with less than 100 patients were averaged together as “other” Left Bundle-Branch Block studies. branch block or LVH. or predictive Lead V5 alone consistently outperforms the inferior leads and value of the stress ECG for the diagnosis of ischemia. including antihypertensive agents and of 1 mm or more in recovery were particularly useful mark. 67%. Acute administra- (likelihood ratio. Patients with false-positive exercise tests based on this finding have a high peak exercise heart rate. specificity. However. provided patient numbers as well as both sensitivity and tive indicator of CAD. Accompanying ST depression in such patients can studies in asymptomatic (and therefore very low likelihood) be caused by a second area of ischemia or reciprocal individuals have demonstrated additional prognostic value changes. Exercise-induced ST-segment ele- number of leads for the detection of CAD (363). respectively.org 14 ACC/AHA Practice Guidelines American Heart Association . 88%..www. and 93% and speci. (361) of 1358 individuals undergoing exercise testing (only 152 with catheterization data) and the report by Okin et al. height has not been shown to consistently improve the diag- nostic value of exercise-induced ST depression. been the subject of several reviews since the last publication The committee favored the use of the more commonly used of these guidelines (359. other studies have found The ST/HR slope or index was not found to be more accurate it to be a marker of residual viability in the infarcted area than simple measurement of the ST segment. for the detection as abnormal because of a submaximal effort. infarction. and in to the ST/HR index. ST Elevation (362) considering heart rate reserve (238 controls and 337 patients with coronary disease).acc. i. Several methods of heart rate adjustment have been proposed dictive than upsloping depression.org They found sensitivities of 66%. probably have an increased derived either manually (67) or by computer (68).65). comparable results to perfusion induced changes in R-wave amplitude have no independent scanning when right-sided leads were added. Although some (60-62).g.e. 2002 American College of Cardiology Foundation . A second probability of coronary disease (49. considered consecutive patients with chest pain. III. However. Upsloping ST Depression ST-Heart Rate Adjustment Downsloping ST-segment depression is a stronger predictor of CAD than horizontal depression. considered the Early repolarization is a common resting pattern of ST ele- maximum value of the ST/HR hysteresis over a different vation in normal persons.365). Adjustment would not recommend clinical use of right-sided chest leads of the amount of ST-segment depression by the R-wave until these results are confirmed by others. patients with to increase the diagnostic accuracy of the exercise ECG. the enrollment of relatively left anterior descending artery is involved.. although the test becomes more sensitive. Although not cance (64.www. the between ST depression at peak exercise by the exercise- specificity of exercise testing will be decreased (more false. the Morise study had a small leads II. Limited challenge favors the resents transmural ischemia (caused by spasm or a critical ST/HR index. Nevertheless. these data are not directly appli- cable to the issue of diagnosis in symptomatic patients R-Wave Changes (364. R-wave amplitude typically increases from yet validated. the ST/HR approach in symptomatic patients has at least cise (63). in heart rates and sick patients have low heart rates. is very arrhythmogenic and local- ing to a lower ST/HR index in those without disease and a izes the ischemia. then decreases to a minimum at concerning certain borderline or equivocal ST responses. ST/HR adjustment has positive results). is very rare (0. in the lateral healthy patients in these studies presents a limited challenge leads. If a patient were limited by objective e. divides the difference ing slope is used as a criterion for abnormal findings. and both are more pre. If a slowly ascend. This large. Viik et al. by Viik et al.1% in a clinical laboratory). and an R-wave high prevalence of coronary disease. because healthy patients have relatively high lesion). the higher index in sicker patients. R-wave amplitude would exercise heart rate. but and 220 patients with a low likelihood of the disease referred ST elevation in leads without Q waves occurs in only 1 of for an exercise test. The slowly upsloping ST-segment depression. induced increase in heart rate (69. when maximal slope of the ST segment relative to heart rate is the slope is less than 1 mV/s.360). wall-motion abnormalities (58. However. such as in rendering a judgment beats per minute (bpm). perhaps to a heart rate of 130 approach could prove useful. Likewise. Although the initial reports were promis- increase from rest to such an end point. demonstrating a normal R-wave response but are classified ficities of 88%. the left circumflex and diagonals are involved. the significance of ST elevation is controversial. and 82%. or that 1000 patients seen in a typical exercise laboratory (51-57). ST elevation on a normal ECG (other than in aVR or V1) rep- and both had limited challenge. ST-segment depression associated with a very high signs or subjective symptoms. When it occurs in leads V2 through V4.americanheart. multicenter study followed a protocol to reduce Some studies have suggested that ST elevation is caused by workup bias and was analyzed by independent statisticians.70). neither meta-analysis (25) nor a subsequent study (71) . The major articles that used definition for a positive test: 1 mm of horizontal or this approach for diagnostic testing include Morise’s report downsloping ST depression (zero or negative slope visually). equivalent accuracy to the standard approach. Gibbons et al. the right coronary artery is involved. ST population consisted of 127 patients with coronary disease elevation is relatively common after a Q-wave infarction. with the ST/HR adjustment. The study vation is always considered from the baseline ST level. there are situations in which the ST/HR rest to submaximal exercise. technique. one could take the perspective that Many factors affect the R-wave amplitude response to exer. and the response does not have diagnostic signifi. termed the ST/HR index. and the committee decrease normally occurs at maximal exercise. number of patients who underwent angiography. their predictive power but are associated with CAD because such study was performed in a population with an abnormally patients are often submaximally tested. for example.59). Neither the study by Okin et al. and.50). The only When the resting ECG shows Q waves of an old myocardial study with neither of these limitations was QUEXTA (353). maximal exercise (66). Such patients may be ing. and aVF. 92%. thus lead- contrast to ST depression. Exercise- of CAD by angiography. not take place in isolation but as part of a process that (Level of Evidence: B) includes more readily accessible (and sometimes less expen- 4. that are normal. The • Complete left bundle-branch block or any interven- degree of filtering and preprocessing should always be pre.acc. cate the need for further testing and/or therapy. Intermediate-risk unstable angina patients (see symptom status. 2002 American Heart Association . • Pre-excitation (Wolff-Parkinson-White) syndrome unprocessed ECG data for comparison with any averages the • Electronically paced ventricular rhythm exercise test monitor generates. None of the computerized scores or 17). or performance of a 1. patient’s prognosis. ties in medical practice. and other aspects of revised Table 17) who have initial cardiac markers quality of life are equally important to many patients. AHA standards be the default setting. All averages should be carefully labeled and explained. Patients undergoing initial evaluation with suspected therapeutic trial. 3. This strategy may consist of additional noninvasive testing. and laboratory test data items. Virtually all patient management and. Low-risk unstable angina patients (see revised Table The most important implication of the foregoing for these 17) 8 to 12 hours after presentation who have been guidelines is that risk stratification with the exercise test does free of active ischemic or heart failure symptoms. bundle-branch block or less than 1 mm of resting ST cause it to be modified. Patients with severe comorbidity likely to limit life between averaged ECG complexes. (Level of rate in interpretation of exercise tests. a repeat ECG without significant tions for these discordant findings are detailed elsewhere change. it is more impor. Class III late raw data.72). Using these data.org ACC/AHA Practice Guidelines 15 found convincing evidence of benefit. Averages should be expectancy and/or candidacy for revascularization. greater than 120 ms. Each addi- 2. refer- Class I ral for prompt cardiac catheterization. It is preferable that the periodic monitoring to guide treatment. functional capacity. As described in sections III and IV. previously tional patient-physician encounter provides an opportunity to evaluated. (Level of Evidence: C) measurements have been validated sufficiently to recom- mend their widespread use. and cardiac markers 6 to 12 hours after the (71. To avoid this problem. particularly those that simu. Patients with suspected or known CAD. High-risk unstable angina patients (see revised Table measurement points. Specific exceptions are noted below in assessment. pared with the AHA recommendations (0 to 100 Hz with 2.www. outcomes such as freedom from myocardial infarction.americanheart. Risk or prognostic stratification is one of the pivotal activi- ized measurements are comparable to visual measurements.org Gibbons et al. Whereas prognosis typically refers to probability of sur- Class IIa vival. Evidence: B) Computer Processing Class IIb Although computer processing of the exercise ECG can be 1. (Level of Evidence: B) already known about the patient’s risk status. onset of symptoms that are normal and no other evi- tant to consider exercise capacity rather than exercise heart dence of ischemia during observation. It is preferable that averages • 1 mm or more of resting ST depression always be contiguously preceded by the raw ECG data. tricular conduction defect with a QRS duration sented along with the ECG recordings and should be com. the physi- cian collects a standard data set of history. The additional data that result from these or known CAD.www. Patients with the following resting ECG abnormali- helpful. RISK ASSESSMENT AND PROGNOSIS nation. physical exami- III. the value of exercise testing for risk stratification have been free of active ischemic or heart failure must be considered in light of what is added to that which is symptoms. Intermediate-risk unstable angina patients (see sive) data from the clinical examination and other laboratory revised Table 17) 2 to 3 days after presentation who tests. Most . Simulation of raw data with averaged data should be avoided. or result in a completely revised risk depression. The updated risk assessment in turn may indi- Class IIb. Patients with a stable clinical course who undergo notched power line frequency filters). The potential explana. During the initial encounter. appropriately. the IN PATIENTS WITH SYMPTOMS OR A physician formulates a working diagnosis and risk assess- PRIOR HISTORY OF CAD ment and selects an initial management strategy (98). when combined with scores. including those with complete right management steps may affirm the initial risk assessment. it can result in a false-positive indication of ST ties: depression (73). Obvious breaks should be inserted 1.American College of Cardiology Foundation . they can provide excellent decisions are driven by the clinician’s assessment of the test characteristics (366). now presenting with significant change in update the risk assessment and modify the therapeutic plan clinical status. Thus. the physician should always be provided with ECG recordings of the raw. checkmarked to indicate the PR isoelectric line and the ST 2. At least one study in which these Risk Stratification: General Considerations shortcomings have been addressed has shown that computer. Gibbons et al. 2002 American College of Cardiology Foundation - www.acc.org 16 ACC/AHA Practice Guidelines American Heart Association - www.americanheart.org Table 14. Prognostic Factors for Patients With Coronary Disease and the success of mechanisms used by the cardiovascular Prognostic factors for current risk state system to compensate for that damage are of paramount Left ventricular function/damage importance. Many different clinical and laboratory parame- History of prior MI ters provide information about the extent of left ventricular Pathologic Q waves on the resting ECG dysfunction (Table 14). Ejection fraction is the most com- Congestive heart failure symptoms Cardiomegaly on the chest x-ray monly used measure, but it alone does not completely Ejection fraction describe the prognostic information in left ventricular func- End-systolic volume tion. Another group of prognostic factors describe the Regional LV wall motion abnormalities anatomic extent and severity of atherosclerotic involvement Conduction disturbances on the ECG Mitral regurgitation of the coronary tree. The number of diseased vessels is the Exercise duration/tolerance most common measure of this domain. More details about Severity of CAD the coronary anatomy add important prognostic information Anatomic extent and severity of CAD to this simple measure. A third group of prognostic factors Collateral vessels present provide evidence of a recent coronary plaque rupture, which Transient ischemia on ambulatory monitor Exercise- or stress-induced ST deviation indicates a substantially increased short-term risk for cardiac Coronary plaque event death or nonfatal myocardial infarction. Worsening clinical Progressive or unstable ischemic symptoms symptoms with unstable features is the major clinical mark- Transient ischemia on resting ECG er of a plaque event. The fourth group of prognostic factors Electrical stability Ventricular arrhythmias are related to the presence of electrical instability of the General health myocardium and the propensity for malignant ventricular Age arrhythmia. The final group of prognostic factors describe Noncoronary comorbidity general health and noncoronary comorbidity. Prognostic factors for change in risk state The probability that a given patient will progress to a high- Factors predisposing to disease progression Smoking er- or lower-risk disease state depends primarily on factors Hyperlipidemia related to the aggressiveness of the underlying atherosclerot- Diabetes mellitus ic process (Table 14). Patients with major cardiac risk fac- Hypertension tors, including smoking, hypercholesterolemia, diabetes mel- Other genetic/metabolic factors litus, and hypertension, are most likely to evidence progres- MI indicates myocardial infarction; ECG, electrocardiogram; LV, left ventricular; and sive atherosclerosis with repeated coronary plaque events. CAD, coronary artery disease. Patients with symptomatic coronary disease at a younger age also may have a more aggressive disease process. research on exercise testing, however, has concentrated on A growing body of pathological, angiographic, angioscop- the relation between test parameters and future survival (and, ic, and intravascular ultrasonographic data supports a patho- to a lesser extent, freedom from myocardial infarction). physiological model in which most major cardiac events These outcomes will be primarily considered in this section (sudden death, acute myocardial infarction, and unstable of the guidelines. angina) are initiated by microscopic ruptures of high-risk or vulnerable atherosclerotic plaques. Characteristically, vul- Prognosis of CAD: General Considerations nerable plaques have a cholesterol gruel core and a thin Coronary artery disease is a chronic disorder with a natural fibrous cap. Various nonspecific factors may act as triggers history that spans multiple decades. In each affected individ- and cause a vulnerable plaque to rupture at thinned sites ual, the disease typically cycles in and out of a number of around the shoulders of the cap. This exposes inner plaque clinically defined phases: asymptomatic or presymptomatic, material to the flowing intra-arterial blood and initiates for- stable angina, progressive angina, unstable angina, or acute mation of a platelet-fibrin thrombus over the area of rupture. myocardial infarction. Although the specific approach to risk Clinically, the rupture may seal without detectable sequelae, stratification of the coronary disease patient can vary accord- or the patient may experience worsening angina, acute ing to the phase of the disease in which the patient presents, myocardial infarction, or sudden cardiac death. Several lines some general concepts apply across the coronary disease of evidence have shown that the majority of vulnerable spectrum. plaques appear “angiographically insignificant” before rup- Conceptually, the probability of cardiac death in a patient ture (i.e., less than 75% diameter stenosis). In contrast, most with CAD can be viewed as the sum of the risks at the time “significant” plaques (greater than or equal to 75% stenosis) of evaluation (the current risk state) and the risk that the dis- visualized at angiography are at low risk for plaque rupture. ease will progress over time to a higher or lower risk state. Thus, the ability of stress testing of any type to detect vul- The patient’s current risk state is a function of five major nerable atherosclerotic lesions may be limited by the smaller types of prognostic measures (Table 14). The strongest pre- size and lesser effect on coronary blood flow of these plaques dictor of long-term survival with CAD is function of the left and may explain the occasional acute coronary event that ventricle. In particular, the extent of damage or dysfunction may occur not long after a negative treadmill test. American College of Cardiology Foundation - www.acc.org Gibbons et al. 2002 American Heart Association - www.americanheart.org ACC/AHA Practice Guidelines 17 Table 15. Measurements Available From the Exercise Treadmill Test suggest ischemia should generally undergo exercise testing Electrocardiographic to assess the risk of future cardiac events. As described in the Maximum ST depression ACC/AHA guidelines for percutaneous transluminal coro- Maximum ST elevation nary angioplasty and for coronary artery bypass grafting, ST-depression slope (downsloping, horizontal, upsloping) documentation of exercise- or stress-induced ischemia is Number of leads showing ST changes desirable for most patients who are being evaluated for revas- Duration of ST deviation into recovery ST/HR indexes cularization (3,4)(346,347). Exercise-induced ventricular arrhythmias Choice of initial stress testing modality should be based on Time to onset of ST deviation evaluation of the patient’s resting ECG, the patient’s physical Hemodynamic ability to perform exercise, and local expertise and technolo- Maximum exercise heart rate gy. For risk assessment, the exercise test should be the stan- Maximum exercise systolic blood pressure Maximum exercise double product (HR × BP) dard initial mode of stress testing used in patients with a nor- Total exercise duration mal ECG who are not taking digoxin (99-101). Patients with Exertional hypotension (drop below preexercise value) widespread resting ST depression (greater than or equal to 1 Chronotropic incompetence mm) or patients with, complete left bundle-branch block, an Symptomatic intraventricular conduction defect with a QRS duration Exercise-induced angina Exercise-limiting symptoms greater than 120 ms, ventricular paced rhythm, or pre-excita- Time to onset of angina tion should usually be tested with an imaging modality. Exercise testing may still provide useful prognostic informa- HR indicates heart rate; and BP, blood pressure. tion in patients with these ECG changes but cannot be used to identify ischemia. The preserved prognostic value of exer- Risk Stratification With the Exercise Test cise ECG testing in patients with nonspecific resting ST-T abnormalities, defined as ST depression of any magnitude, T- The major exercise ECG testing measures that have been wave abnormalities, or both, not due to one of the secondary proposed as prognostic markers are listed in Table 15. causes above, has been demonstrated (367). However, Because the exercise test is a diagnostic tool rather than a because fewer than 20 patients with ST depression greater therapy, its effect on patient outcomes is necessarily indirect. than or equal to 1 mm were included in the study, there are To the extent that the test guides clinicians to select more not enough data to recommend an exercise ECG alone in this appropriate or effective therapies, the exercise test will subgroup. Patients unable to exercise because of physical improve outcomes. However, no randomized trials of exer- limitations that affect exercise capacity (e.g., arthritis, ampu- cise testing versus no exercise testing have been performed. tations, severe peripheral vascular disease, severe chronic The entire evidence base for exercise testing therefore con- obstructive pulmonary disease, or general debility) should sists of observational studies. No direct evidence links dif- undergo pharmacological stress testing in combination with ferent exercise testing strategies with differing outcomes. imaging. As described previously, the risks of exercise testing in In patients with suspected or known symptomatic coronary appropriately selected candidates are extremely low. Thus, disease, exercise testing can be used to estimate prognosis the main arguments for not performing an exercise test in and assist in management decisions. The primary evidence in many clinical situations are that the information provided this area consists of seven nine observational studies of the would not justify the extra costs of obtaining that information prognostic value of the exercise ECG (Table 16). An (i.e., the test would not be cost-effective in that given situa- overview of the available literature has shown some incon- tion) and/or the test might provide misleading information sistency among studies in the exercise variables identified as that could lead to inappropriate or unnecessary additional independent prognostic factors. These differences are at least testing or therapy (both of which may have higher risks than partially attributable to differences in the spectrum of exercise testing). patients referred for testing, the amount of crossover to coro- In reviewing the published evidence in this area, the sub- nary revascularization, and the sample size/statistical power committee focused on studies that examined hard cardiac of the analysis (109). outcome events (death alone or death plus myocardial infarc- One of the strongest and most consistent prognostic mark- tion) and had at least five (and preferably 10) outcome events ers identified in exercise testing is maximum exercise capac- for every candidate variable evaluated. Use of appropriate ity, which is influenced at least in part by the extent of rest- multivariable statistical techniques was also a requirement ing left ventricular dysfunction and the amount of further left for selection. Special emphasis was given to studies that eval- ventricular dysfunction induced by exercise. However, the uated the incremental effects of the exercise test beyond the relation between exercise capacity and left ventricular func- prognostic information available from the clinical evaluation tion is complex, because exercise capacity is also affected by (history, physical examination, and resting 12-lead ECG). age, general physical conditioning, comorbidities, and psy- chological state (especially the presence of depression) Symptomatic Patients With Nonacute CAD (110). Several exercise parameters can be used as markers of Unless cardiac catheterization is indicated, patients with sus- exercise capacity (Table 15), including maximum exercise pected or known CAD and new or changing symptoms that duration, maximum MET level achieved, maximum work- Gibbons et al. 2002 American College of Cardiology Foundation - www.acc.org 18 ACC/AHA Practice Guidelines American Heart Association - www.americanheart.org Table 16. Prognostic Studies of Exercise Testing Years of Length of Study Enrollment N Follow-up (y) Independent Prognostic Factors CASS102 1974–1979 4083 5 1. CHF 2. TM stage 3. Exercise-induced ST depression Duke103 1969–1981 2842 5 1. Exercise-induced ST deviation 2. Exercise-induced angina 3. Exercise duration Long Beach VA104 1984–1990 2546 5 1. CHF/digoxin use 2. METs 3. Max SBP 4. Exercise-induced ST depression Italian CNR105 1976–1979 1083 5.5 1. Q wave 2. Prior MI 3. Effort ischemia 4. Exercise capacity Belgian106 1978–1985 470 5 1. Age 2. Score of maximum HR, ST depression, angina, watts, ST slope German107 1975–1978 1238 4.5 1. Exercise tolerance (watts) 2. Maximum HR Seattle Heart 1971–1974 733 3.3 1. CHF Watch108 2. Maximum double product 3. Max SBP 4. Angina 5. Resting ST depression CASS indicates Coronary Artery Surgery Study; CHF, congestive heart failure; TM, treadmill; VA, Veterans Administration; METs, metabol- ic equivalents; Max, maximum; SBP, systolic blood pressure; CNR, Consiglio Nazionale Ricerche; MI, myocardial infarction; and HR, heart rate. load achieved, maximum heart rate, chronotropic incompe- ing), and duration of ST deviation into the recovery phase of tence, and double product. When the exercise test is being the test. interpreted, it is very important that exercise capacity be Two early influential studies of exercise treadmill testing taken into account; the specific variable used to summarize and prognosis were reported from the Duke Cardiovascular this aspect of test performance is less important. The transla- Disease Databank and the Coronary Artery Surgery Study tion of exercise duration or workload into METs (oxygen (CASS) Registry. Using the Duke database, McNeer and co- uptake expressed in multiples of basal oxygen uptake, 3.5 O2 workers (111) demonstrated that an “early positive” exercise mL/kg per minute) has the advantage of providing a common test result (ST depression greater than or equal to 1 mm in the measure of performance regardless of the type of exercise first 2 stages of the Bruce protocol) identified a high-risk test or protocol used. Although such translations are based on population, whereas patients who could exercise into stage approximations and are not as accurate for individual IV were at low risk regardless of the ST response. Weiner and colleagues (102), using the CASS Registry, analyzed patients as measured maximum oxygen uptake (VO2max), 4083 medically treated patients and identified 12% as high VO2max has not been studied for prognostic purposes in large risk on the basis of greater than or equal to 0.1 mV of exer- series of patients with chest pain. cise-induced ST-segment depression and inability to com- A second group of prognostic exercise testing markers plete stage I of the Bruce protocol. These patients had an relates to exercise-induced ischemia. These markers include average annual mortality rate of 5% per year. Patients who exercise-induced ST-segment depression, exercise-induced could exercise to at least stage III of the Bruce protocol with- ST-segment elevation (in leads without pathological Q waves out ST-segment changes (34%) constituted the low-risk and not in aVR), and exercise-induced angina. In a large group (estimated annual mortality, less than 1%). exercise testing cohort, exercise ST deviation (elevation or Several studies have attempted to incorporate multiple depression) best summarized the prognostic information exercise variables into a prognostic score. Using Cox regres- from this area (103). Other less powerful prognostic ST vari- sion analysis, Mark and colleagues (103) created the Duke ables included the number of leads that showed significant treadmill score with data from 2842 inpatients with known or ST-segment depression, configuration of the exercise- suspected CAD who underwent exercise tests before diag- induced ST depression (downsloping, horizontal, or upslop- nostic angiography. None of the patients had prior revascu- the Duke treadmill score was converted variables). The point at which this line intersects the line for prognosis indicates the 5-year cardiovascular survival rate and average annual cardiovascular mortality for patients with these characteristics. The after the J point.www. 13% of patients) had an average annual car. the Duke than their younger counterparts. although women have a *Note that ST-segment deviation can be measured at 60 to 80 ms lower overall risk for any score value than men (368). the elderly patients (greater than or equal to 65 patients) and an average annual cardiovascular mortality rate years) had more comorbidity and achieved a lower workload of 0. patients had a score greater than or equal to +5 (34% of As expected. was the only treadmill variable associated with all-cause ables (number of diseased vessels and ejection fraction). risk.americanheart.American College of Cardiology Foundation . The high-risk group defined by this score (score less than The value of exercise treadmill testing for prognostic or equal to –11. without prior revascularization or recent myocardial infarction. Exercise time is based on a standard Bruce protocol. A limitation is the small deviation is 0. The resulting the Bruce protocol and corresponding METs. Prognosis is determined in five steps: (1) The observed amount of exercise-induced ST-segment deviation (the largest elevation or depression after resting changes have been subtracted) is marked on the line for ST-segment deviation during exercise.5%. (2) The observed degree of angina during exercise is marked on the line for angina. This nomogram applies to patients with known or suspected coronary artery disease.acc.(115). number of elderly patients represented in studies that evalu- ated this score. Preliminary data suggest that tThe score works equally well with men and women. Workload expressed as METs the standard clinical data plus the major catheterization vari. In multivariable Cox regression analysis. To mortality in both groups (adjusting for clinical prognostic improve ease of use. The score has subse- quently been validated in 613 outpatients at Duke who did Treadmill score = exercise time – 5 × (amount of ST-segment not all proceed to coronary angiography and in exercise-test- deviation in millimeters*) – 4 × exercise angina index (which had a value of 0 if ing populations at several other centers (112-114). (5) The mark for ischemia is connected with that for exercise duration. who undergo exercise testing before coronary angiography. (3) The marks for ST- segment deviation and degree of angina are connected with a straight edge. 1 if exercise mill score was even more useful for outpatients: approxi- angina occurred. which can be treadmill score was calculated: calculated for other treadmill protocols. They also had a significant- treadmill score added significant prognostic information to ly worse unadjusted survival. Patients with <1 mm of exercise-induced ST-segment depression should be count- ed as having 0 mm. (4) The total number of minutes of exercise in treadmill testing according to the Bruce protocol (or the equivalent in multiples of resting oxygen consumption [METs] from an alternative protocol) is marked on the exercise-duration line. Modified from Mark et al. assessment in elderly subjects has been described in the diovascular mortality greater than or equal to 5%. Nomogram of the prognostic relations embodied in the treadmill score.www. If the amount of exercise-induced ST-segment score has also been validated in patients with resting nonspe- deviation is less than 1 mm. whereas both workload and exercise angina were into a nomogram (Fig. 2002 American Heart Association . Low-risk Olmstead County cohort followed by the Mayo Clinic (369). This nomogram uses both time on associated with cardiac events (death plus myocardial infarc- . Angina during exercise refers to typical effort angina or an equivalent exercise-induced symptom that represents the patient's presenting complaint.org ACC/AHA Practice Guidelines 19 Figure 2.org Gibbons et al. 2).112 larization or recent myocardial infarction. and 2 if angina was the mately two thirds had treadmill scores that indicated low reason the patient stopped exercising). the value entered into the score for ST cific ST-T-wave changes (367). The point where this line intersects the ischemia-reading line is noted. The tread- there was no exercise angina. . Gibbons et al. events should have substantially boosted the predictive The importance of this parameter has been confirmed in four power (i. long-term follow-up. results of observational epidemiologic studies. 77% of the Long Beach normal or near-normal exercise myocardial perfusion images Veterans Administration Hospital population were at low risk and normal cardiac size are at low risk for future cardiac (with less than 2% average annual mortality). A positive ST response was not prog. it is difficult to patients. Patients with an intermediate-risk treadmill score and cise blood pressure. and the probability of a follow-up nonfatal myocardial Similar trends have been suggested for a delayed systolic infarction was found (116). no = 0]) + exercise-induced ST formance and interpretation. with proper consider- incompetence. for example. 4 for increase of 0 to 11 mm imaging appears to be of value for further risk stratification Hg.www. the relative value of exercise testing for predicting future car- was associated with an 84% increase in the risk of all-cause diac deaths versus future myocardial infarctions (fatal or mortality over a 2-year follow-up in 1877 men and 1076 nonfatal). 18% were at death and can be managed medically (379). With this score.americanheart. and 6% were The optimal testing strategy remains less well defined in at high risk (average annual mortality.or high-risk categories). validated treadmill test parameters. ery and the Duke treadmill score were independent predic. the Cleveland relate the pathophysiology of coronary events directly to the Clinic investigators reported that abnormal heart rate recov. it is reasonable to use exercise testing for risk stratifi- of other parameters from the exercise test.e. there is no com- Morrow and colleagues (104) have developed a prognostic pelling evidence that an imaging modality adds significant score using 2546 patients from Long Beach Veterans new prognostic information to a standard exercise test. despite the fact that addition of the nonfatal 2428 patients referred for thallium exercise testing (372). no relation between exercise capacity tion from two Veterans Affairs Medical Centers (377). For example. This finding was associated with severe CAD in a occur.org tion) in both groups.. and widespread familiarity in its per- (CHF/digoxin [yes = 1. clinical and exercise testing information. and delayed blood pressure response in the risk nostic in the older patients when tested as a binary variable. This score includes two variables in regard. This presumably occurs because patients with severe study of 493 patients at the Cleveland Clinic who had both and/or extensive coronary disease are much less likely to symptom-limited exercise testing and coronary angiography withstand the challenge to their myocardial circulation (within 90 days) (378). Chronotropic cation in women as readily as in men. the standard treadmill ECG is depression in millimeters + change in systolic blood pressure the most reasonable exercise test to select in men with a nor- score – METs. Pathophysiological considerations based on the women who were referred to the Cleveland Clinic for symp. In this Administration Hospital. Until adequate data are available to resolve this Several studies have highlighted the prognostic importance issue.371). more outcome events should yield better power subsequent studies from the same investigators (373-376) in prognostic models) (103). where systolic blood pressure = 0 for increase mal resting ECG who are able to exercise. Because of its use of digoxin). a distinction should be made between studies that common with the Duke treadmill score (exercise duration or show a statistical advantage of imaging studies over exercise the MET equivalent and millimeters of ST changes) and two ECG alone and studies that demonstrate that the imaging different variables (drop in exercise systolic blood pressure data would change practice (e. women.www. There may.acc. In a study of 9454 consecutive caused by a major plaque event. coronary plaque event model described earlier suggest that tom-limited thallium treadmill testing (370. an abnormal heart rate recovery cardiovascular death plus nonfatal myocardial infarction was was strongly predictive of all-cause mortality at 6 years in almost identical. 1 for increase of 31 to 40 mm Hg. recovery. (114). 2 intermediate-risk treadmill score. in one pattern after exercise testing. lower cost. myocardial perfusion for increase of 21 to 30 mm Hg. by shifting patients from below resting value and history of congestive heart failure or moderate. abnormal heart rate total coronary atherosclerotic burden (obstructive and nonob- . the predictive power of or equal to 12 bpm from peak exercise heart rate to heart rate exercise ST depression for cardiovascular death alone and measured 2 minutes later. and 5 for a reduction below standing systolic pre-exer.org 20 ACC/AHA Practice Guidelines American Heart Association . Defined as a change of less than large cohort of chronic CAD patients. and the Duke Treadmill In patients who are classified as low risk on the basis of Score was not computed in this study. Available data suggest that the blood pressure response after exercise.to low. The acute myocardial infarctions caused by rupture of a relative- Cleveland Clinic investigators have also demonstrated the ly small vulnerable plaque would be difficult to predict accu- prognostic importance of an abnormal heart rate recovery rately with exercise test parameters.g. defined as a value exercise test results give a better guide to the likelihood that greater than 1 for systolic blood pressure at 3 minutes of a patient will die (given that a plaque event occurs) than they recovery divided by systolic blood pressure at 1 minute of do to the likelihood that a nonfatal myocardial infarction will recovery. Further work is needed to define the ber of nonobstructive vulnerable or high-risk plaques and the role of chronotropic incompetence. 15%). stratification of symptomatic patients relative to other well- Quantitative ST-segment deviation with exercise was appar. 85% of the age-predicted maximum exercise heart rate or a One important issue that has received inadequate study is low chronotropic index (heart rate adjusted to MET level). However. defined as either failure to achieve 80% to ation of the importance of the pretest risk state. most of whom were asymptomatic. 2002 American College of Cardiology Foundation . The score is calculated as follows: 5 × simplicity. In patients with an greater than 40 mm Hg. In another exercise cohort with and independently in a comparatively high-risk male popula. 7%). be a correlation between the presence and num- tors of mortality (376). ently not available in this cohort. moderate risk (average annual mortality. It is only through judicious use of ers. many available studies contain both unstable angina and cycle of the patient with chronic coronary disease.acc.g. the post-exercise test prognosis or risk patients with new-onset or progressive angina with symp- points to a particular management strategy that is viewed as toms provoked by walking one block or one flight of stairs. In addi- myocardial infarction) represents an acute phase in the life tion. The natural history of unstable testing in ACS patients with appropriate indications as soon angina ACS involves progression to either death or myocar. exercise testing has no direct ical examination. a monitored hospital bed. One review of this area found 3 studies covering 632 patients with stabilized Patients With Acute Coronary Syndrome unstable angina who had a 0. a presenting feature or may interrupt a quiescent phase of The limited evidence available supports the use of exercise clinically manifested disease. Still others have no evidence of a rup- test result in a patient with evidence of left ventricular dys- tured plaque or atherosclerotic coronary lesions.g. Some have a rup- be referred for additional testing. Patients with a high- ly constructed chest pain management protocol (see section risk exercise test result (e.or moderateintermediate-risk take into account patient preferences and comorbidity. in this scheme can typically be treated on an outpatient basis. exercise or pharmacological stress testing should candidates for revascularization in general should be man- generally be performed unless cardiac catheterization is indi- aged without invasive evaluation. Patients are separated into low-. a predicted average annual cardiac mortality rate less than or Intermediate-risk patients can be tested after 2 to 3 days. as with patients with test result in Fig. These events typically play out to 7 days) exercise test with a test performed at 1 month in over a period of 4 to 6 weeks. the results of exercise testing may be used to titrate ically admitted to an intensive care unit. those with symptoms for a minimum of 48 8 to 12 hours (14). exercise testing in unstable angina ACS relates to this acute The prognostic value of the two tests was similar. patients with a strongly positive on chest pain centers below). who include outcomes.org Gibbons et al. Agency for Health Care Policy and Research (14) The Research on Instability in Coronary Artery Disease recently published guidelines for the diagnosis and treatment (RISC) study group (119) examined the use of predischarge . lier test identified additional patients who would experience The ACC/AHA 2002 Guideline Update for the events during the period before the 1-month exercise test.5% death or myocardial infarc- Acute coronary syndrome (ACS. this population. cise testing in unstable angina (117. (Note that this table is meant to be illustrative rather than the information gained that the test is linked with improved comprehensive or definitive. and cardiac mark- effect on patient outcomes. Thus.www. In most cases. but the ear- and convalescent period. In low-risk patients. Patients with an ECG who are not taking digoxin. The other major man- Exercise or pharmacological stress testing should general- agement step addressed by exercise testing is whether to pro- ly be an integral part of the evaluation of low-risk patients ceed with additional testing. or high-risk groups based on history.g. phys- As a diagnostic technique. especially cardiac catheterization.. patients have been free of active ischemic or heart failure Patients with a low-risk exercise test result (e. as the patient has stabilized clinically. which might ultimately lead to with unstable angina who are evaluated on an outpatient revascularization.org ACC/AHA Practice Guidelines 21 structive).380). Thus. In general. testing should be performed within 72 additional testing. most appropriate. must hours of presentation. In low. Ttesting can be performed when stress testing. Larsson and col- dial infarction on the one hand or return to the chronic stable leagues (118) compared a symptom-limited predischarge (3 phase of CAD on the other. A clinical risk stratification algorithm useful for selecting the initial management strategy is seen in Use of Exercise Test Results in Patient Treatment revised Table 17. and the AHA. 2 or predicted average annual cardiac mor- stable angina. 2002 American Heart Association . patients with unstable angina who have been hospitalized for Patients with severe coexisting diseases that make them poor evaluation. regardless of the results of cated.American College of Cardiology Foundation . (350).americanheart. predicted average A majority of patients with unstable angina have an under- annual cardiac mortality rate of 2% to 3% per year) should lying ruptured plaque and significant CAD. It may be post-myocardial infarction patients. intermediate-risk exercise test result (e.. An intermediate-risk stress any coronary segment. In Management of Patients With Unstable Angina and Non–ST. An important caveat is that decisions about basis. medical therapy up to a desired level. but equal to 1% per year) can be treated medically without need selected patients can be evaluated earlier as part of a careful- for referral to cardiac catheterization. the role and timing of 189 patients with unstable angina or non–Q-wave infarction. Very lLittle function should usually prompt referral for cardiac catheter- evidence exists with which to define the safety of early exer- ization. whereas high-risk patients are typ- However. based on expected outcomes. correlated with of unstable angina. moder- ateintermediate-..www. There is little evidence linking different exercise-defined Most moderateintermediate-risk patients can be cared for in risk groups with alternative classes of medical therapy. these earlier events represented one half of Segment Elevation Myocardial Infarction has been published all events that occurred during the first year. the exercise treadmill test should be the stan- tality rate greater than or equal to 4% per year) should usu- dard mode of stress testing in patients with a normal resting ally be referred for cardiac catheterization. and initial 12-lead ECG. which have been endorsed by the ACC the presence and severity of obstructive coronary disease. unstable angina or acute tion rate within 24 hours of their exercise test (380).) Low-risk patients. in turn. either cardiac catheteriza- tured plaque without angiographically significant lesions in tion or an exercise imaging study. Exercise test results are. Note: Estimation of the short-term risks of death and nonfatal cardiac ischemic events in unstable angina is a complex multivariable problem that cannot be fully specified in a table such as this. prior aspirin use Gibbons et al. Adapted from AHCPR Clinical Practice Guideline No. mitral regurgitation. CCSC indicates Canadian Cardiovascular Society Classification. electrocardiography. From AHCPR Clinical Practice Guideline. 22 Table 17. now Increased frequency. or duration of Pain resolved. BBB.1 mg per ml This table offers general guidance and illustration rather than rigid algorithms. severity.acc.. Estimation of the short-term risks of death and nonfatal myocardial infarction in unstable angina is a complex multivariable problem that cannot be fully specified in a table such as this. 10. ECG. MR. most likely related to Resting angina (>20 min or relieved with Angina provoked at a lower threshold Findings ischemia rest or sublingual nitroglycerin) New or worsening MR murmur Age older than 70 years S3 or new/worsening rales Hypotension. peripheral or cerebrovascular disease. coronary artery bypass graft. inferior. and CCSC.g.. troponin T >0. Number 10. electrocardiogram. coronary artery disease. with moderate or high likelihood of CAD of angina New-onset or progressive Rest angina (<20 min) or relieved CCSC III or IV angina in the ACC/AHA Practice Guidelines with rest or sublingual NTG) past 2 weeks with moderate or high likelihood of CAD. bundle-branch block. mitral regurgitation.org American College of Cardiology Foundation .americanheart.g. May 1994. new or presumed new/sustained Pathologic Q waves unchanged ECG during an episode ventricular tachycardia of chest discomfort Angina with new or worsening MR murmur Angina with dynamic T-wave changes Normal or unchanged ECG Angina with S3 or new/worsening rales New-onset CCSC III or IV angina in the past 2 weeks with moderate or high likelihood of CAD Biochemical Angina with hypotensionElevated (e.www. Canadian Cardiovascular Society class. troponin Pathological Q waves or resting ST Cardiac T or I greater than 0. American Heart Association . Unstable Angina: Diagnosis and Management. MR. Clinical Pulmonary edema. or CABG.1 mg per ml) depression ≥1 mm in multiple-lead Normal Markers groups (anterior.www. bradycardia. CABG. ongoing (>20 min) pain at rest Prolonged (>20 min) resting angina. the table is meant to offer general guidance and illustration rather than rigid algorithms.01 but <0.05 mV T-wave inversions greater than 0. ECG. 2002 Character Prolonged.or intermediate-risk feature but features must be present of the following features must be present: may have any of the following features: History Prior MI. tachycardia Age older than 75 years ECG Angina at rest with dynamic transient ST changes Nocturnal angina New-onset angina with onset 2 weeks to Findings ≥1 mm0. MI.org . lateral) Age >65 y Slightly elevated (e. Short-Term Risk of Death or Nonfatal Myocardial Infarction in Patients With Unstable Angina Feature High Risk Intermediate Risk Low Risk At least one of the following No high-risk feature but must have one any No high.2 mV 2 monthsbefore presentationNormal or BBB. myocardial infarction. Therefore.14 CAD indicates coronary artery disease. CAD. These results are generally representative of the distribution of a coronary lesion of borderline results in the approximately 2100 chest pain patients who severity. 55 had an indeterminate or high-risk test result. In most of the pub. The goal of a chest 2. evaluation of medical therapy (submaxi- with the use of exercise testing in emergency department mal at about 4 to 76 days). 1010 patients were evalu- ated by clinical examination. increasing experience has been gained prescription. 2002 American Heart Association . AFTER MYOCARDIAL INFARCTION pain but also parameters that reflected cardiac workload. sion and peak exercise workload achieved. infarction (49%). serial measurement of creatine training as part of cardiac rehabilitation in patients kinase-MB levels. in these patients. risk have been screened for high-risk features or other indicators for cardiac events in the next 6 months could be stratified for hospital admission. Use of early exercise test- a predischarge exercise test.2. evaluation of medical therapy. 9 hours of continuous ST mon. 60 met the criteria for hospitalization before ted with unstable angina (51%) or non–Q-wave myocardial stress testing. A variety of physical and was not done (symptom limited.* administrative setups have been used for chest pain centers in 3.org ACC/AHA Practice Guidelines 23 symptom-limited bicycle exercise testing in 740 men admit. These results demonstrate that exercise testing is safe in In 766 unstable angina patients enrolled in the Fragmin low-risk chest pain patients presenting to the emergency During Instability in Coronary Artery Disease (FRISC) study department. Patients with the following ECG abnormalities: extremely low in such chest pain patients. costs) without compromising safety. Late after discharge for prognostic assessment. serial 12-lead ECGs. have undergone exercise testing as part of a chest pain center protocol report (Table 17a) (380). evaluation of medical therapy. In 395 women ing in this setting should only be done as part of a carefully enrolled in FRISC I with stabilized unstable angina who constructed management protocol and only after the patients underwent a symptom-limited stress test at days 5 to 8. • Electronically paced ventricular rhythm There was no significant difference in event rates (death. submaximal (symptom limited. Class I Chest Pain Centers 1. activ- pain center is to provide rapid and efficient risk stratification ity prescription.* chest pain centers (see Table 17a) (380). the 212 patients in the hospital admission group and the 212 patients in the chest pain unit group. . There were no complica- infarction-free survival in multivariable regression analysis tions directly attributable to the performance of a stress test were the number of leads with ischemic ST-segment depres. In addition. Before discharge in patients who have undergone authors estimated a 5% prevalence of CAD in the tested pop. or congestive heart failure) between ticipate in exercise training or cardiac rehabilitation. about 3 to 6 weeks).acc. Periodic monitoring in patients who continue to par- myocardial infarction. cardiac catheterization to identify ischemia in the ulation.1. Important exercise variables included not only ischemic parameters such as ST depression and chest IV. and beyond the scope of these guidelines.americanheart.www. 3. and and management for chest pain patients believed to possibly cardiac rehabilitation if the predischarge exercise test have acute coronary disease. and the risk of adverse events with testing is correspondingly low. testing appears safe in carefully between 1992 and 1994 who had both a troponin T level and selected intermediate-risk patients. 12-lead ECG. Of the total chest pain *Exceptions are noted under Classes IIb and III. from 1% to 19%. After discharge for activity counseling and/or exercise itoring. exercise testing has been reserved for the inves. activity Over the last decade. and resting echocardiograms. Class IIa In the study by Gibler et al. the combination of a positive ing in emergency department chest pain centers improves the troponin T and exercise-induced ST depression stratified efficiency of management of these patients (and may lower patients into groups with a risk of death or myocardial infarc. exercise test- tion that ranged from 1% to 20% (381). and the 1. • Complete left bundle-branch block Farkouh and colleagues from the Mayo Clinic examined • Pre-excitation syndrome the use of exercise testing in 424 intermediate-risk unstable • LVH angina patients (as defined by the ACC/AHA Committee to • Digoxin therapy Develop Guidelines for the Management of Patients With • Greater than 1 mm of resting ST-segment depression Unstable Angina) as part of a randomized trial of admission to a chest pain unit versus standard hospital admission (383). (382). Before discharge for prognostic assessment. There were no adverse events from the testing. Early after discharge for prognostic assessment. Patients who have undergone coronary revascularization.* tigation of patients who are low-risk on the basis of history and physical examination. However. The prevalence of CAD is 2.org Gibbons et al. without high-risk markers on the basis of this evaluation (78%) underwent a symptom-limited Bruce exercise ECG Class IIb test. The major independent predictors of 1-year and 97 had a negative stress test. and serum markers. activi- medical centers across the country. unit group. review of these details is ty prescription.American College of Cardiology Foundation .www. about 14 to 21 days). cardiac rehabilitation if the early exercise test was lished series. 4%. pts admitted Specificity = 50%‡.1 months Modified Bruce (SLM) 0 0 Exercise testing was safe Kerns (1993) (424) 32 6 months Bruce (APMHR) 0 0 Exercise testing was safe. Negative Predictive Value = 98. 24 Table 17a. reduced cost vs. reduced cost vs. * Death or myocardial infarction. no difference in clinical outcomes¶. reduced cost vs. of Follow-up Adverse % Disease Clinical Investigator. SLM = symptom-limited maximum end point. for reference Negative Predictive Value diagnosis = 98%‡ Polanczyk (1998) (427) 276§ 6 months Modified Bruce 0 25 Sensitivity = 73%.acc. Summary of Studies Using Exercise ECG Testing in Chest Pain Centers No. ‡ With respect to reference diagnosis from admission of all patients. ¶ Comparison of those admitted to hospital vs.org American College of Cardiology Foundation . Specificity 74%. † With respect to diagnosis if admitted. Positive Predictive Value = 44%†.americanheart. admitted control APMHR = age-predicted maximum heart rate end point. American Heart Association .org . chest pain center.5 Sensitivity = 90%. 2002 Tsakonis (1991) (423) 28 6. admission ACC/AHA Practice Guidelines Gibler (1995) (382) 1010 30 days Bruce (SLM) 0 5 Sensitivity = 29%. Specificity = 99.7%† Gomez (1996) (425) 50 None Cornell (SLM) 0 6 No difference in clinical 50 controls outcome. admitted control Zalenski (1998) (426) 317 None – Modified Bruce 0 9. Negative Predictive Value = 98% Farkouh (1998) (383) 424 6 months Not specified 0 Intermediate risk patients were studied.www. and 30-day follow-up on all patients. § Included 70 patients (25%) with a history of CHD.102:1463-7 (380). Reprinted with permission from Stein et al. Circulation 2000.www. y Reference Subjects Period ExECG Events* Prevalence Outcome Gibbons et al. acc. If the patient is on digoxin or if the baseline electrocardiogram precludes accurate interpretation of ST-segment changes (eg. cardiac arrhythmia. greater use of revascular- already been selected for. If the exercise test studies are negative. Another strategy (strategy III) is to perform a submaximal exercise test at 4 to 7 days after myocardial infarction or just before hospital dis- charge. 3 are large. and 8% had coronary Although some of the evidence is presented in more detail artery bypass surgery. 2002 American Heart Association . Medications at the time of hospital here and a few references are added. At any time to evaluate patients with acute myocar.americanheart. 20% underwent coronary angioplasty.org Gibbons et al. Lavie . 2. a second symptom- limited exercise test could be repeated at 3 to 6 weeks for patients undergoing vigorous activity during leisure time activities. Because therapies and dial infarction who have uncompensated congestive treatment strategies for myocardial infarction have changed heart failure.org ACC/AHA Practice Guidelines 25 Figure 3. (Level of Evidence: C) myocardial infarction are quite heterogeneous. For patients initially deemed to be at low risk at the time of discharge after myocardial infarction. of Patients With Acute Myocardial Infarction (2)(345). and aspirin in 86%. patients after myocardial infarction. Severe comorbidity likely to limit life expectancy Exercise testing is useful in evaluation and treatment of and/or candidacy for revascularization. role of exercise testing must be viewed in the context of the (Level of Evidence: C) patients who present for testing. One is a symptom-limited exercise test at 14 to 21 days (strategy II). they should undergo invasive evaluation to determine if they are candidates for coronary revascularization procedures (strategy I). A small area contiguous to the infarct zone may not necessarily require catheterization. The Canadian Assessment of Myocardial Infarction (CAMI) study (121) The above recommendations. particularly over the past decade. and increased use of beta-adrenergic catheterization. and Fig. Although a stress test may be useful blocking agents and angiotensin converting enzyme before or after catheterization to evaluate or identify inhibitors continue to change the clinical presentation of the ischemia in the distribution of a coronary lesion of postinfarction patient (120-125). The results of exercise testing should be stratified to determine the need for additional invasive or exercise perfusion studies. Before discharge to evaluate patients who have spread use of thrombolytic agents. angiotensin con- believe that there was sufficient new evidence to justify a verting enzyme inhibitors in 24%. wide- 3. hence. The exercise test results could be stratified using the guidelines in strategy I. Not all patients will have borderline severity.www. at work. 1. baseline left bundle branch block or left ventricular hypertrophy). 45% received thrombolytic agents. survivors of mended. stress imaging tests are recom. or have undergone. If patients are at high risk for ischemic events. or exercise training as part of cardiac rehabilitation. based on clinical criteria. Shorter hospital stays. The extent of reversible ischemia on the exercise imaging study should be considered before proceeding to cardiac catheterization.American College of Cardiology Foundation . cardiac ization strategies.www. the committee did not discharge included beta-blockers in 61%. then an initial exercise imag- ing study could be performed. reported that among 3178 consecutive patients with acute ly based on the ACC/AHA Guidelines for the Management myocardial infarction.2345 Class III major revision of the previously published recommenda- tions. or noncardiac dramatically. the current conditions that severely limit their ability to exercise. Strategies for exercise test evaluation soon after myocardial infarction. the text. two strategies for performing exercise testing can be used. Modified from ACC/AHA guide- lines. received each of these various therapies. or greater than or equal to a 10-mm this background. or digoxin therapy. noting that a greater proportion of patients who days after infarction (126. 1. The timing of the predischarge exercise ly time is reported as a mean value or a range so that it is test continues to shorten. With ventricular arrhythmias. more data are needed to establish undergo exercise testing because of either clinical instability the safety and utility of this very early protocol. or vascular impairment of the lower extrem.org 26 ACC/AHA Practice Guidelines American Heart Association .385). In the largest series to date. Some studies have evaluated symptom-limited protocols at Exercise testing after myocardial infarction yields informa.129-132). Timing of pre. Exercise testing after myocardial infarction appears to be pre-excitation syndrome.137.www. (126) and those who have not (127-129) reported that patients who are unable to perform an exercise test have a greater than or equal to 2 mm of ST-segment depression. It must also be realized occurrence of exercise-related deaths. However. myocardial infarction. uncon. The majority of the Timing and Protocol safety data are based on exercise testing performed more Exercise tests can be characterized according to the time than 7 days after myocardial infarction. to use other diagnostic or treatment options. however. because the accuracy of arrest is 0.acc. The ramp treadmill or cycle ergometer the ACC/AHA Guidelines for Clinical Use of Cardiac protocols offer the advantage of steady gradual increases in Radionuclide Imaging (5).131. established Postdischarge tests have been performed early trolled heart failure. early symptom-limited tests have the potential to be 3) assessment of adequacy of medical therapy and the need more useful in activity prescription before discharge. the additive prognostic value from information obtained from the performance of symptom-limited proto- Exercise Test Logistics cols within days rather than weeks after myocardial infarc- Exclusions From Testing tion has not yet been established. Guidelines for the Clinical work rate and better estimation of functional capacity (136) Application of Echocardiography (6)(349). The most commonly used treadmill proto- cological imaging studies (nuclear and echocardiography) is cols are the modified Bruce. angina. or at 6 months after infarc- ical. because their use is presented in detail in standard Bruce (131). an exercise or pharmacological myocardial infarction and successfully resuscitated cardiac imaging study should be considered. nonfatal depression or elevation. the role of exercise testing after myocardial Hg drop in systolic blood pressure from the resting blood infarction will be presented. and complex arrhythmias. or a peak patient cohort did not undergo exercise testing within 28 MET level of 5 (131). or those safe. Symptom-limited tests are designed to days of myocardial infarction. although the overall fatal event rate is quite low (130. including domestic and ly twice as often as submaximal tests and represents a better occupational work evaluation and exercise training as part of estimate of peak functional capacity (130. demonstrate that such testing yields ischemic responses near- scription after hospital discharge. Gibbons et al. and Thus.09%. fatigue. much higher adverse event rate than those who are able. is the exercise ECG in detecting provokeable ischemia is 1. These studies ment of prognosis. The exercise protocols can be either submaximal ities. the modified Naughton. pressure) (135).www. In patients with an abnormal resting ECG because of left bundle-branch block.9 times that of submaximal tests. mined end point. unstable angina.g.org et al. In 2 separate observa- undergo exercise testing after myocardial infarction tend to tional studies. 2) functional capacity for activity pre. and the not discussed here.03%. has not been or disabling comorbidities. (14 to 21 days). exercise tests have been performed as early as have inferior infarcts and Q-wave infarcts.e. 4 to 7 days after myocardial infarction and have included tion in the following areas: 1) risk stratification and assess. orthopedic. as does the hospital stay for patients impossible to determine how many patients were studied at 4 with an uncomplicated myocardial infarction. . The number of after myocardial infarction when the test is performed and patients reported at 4 to 7 days is more limited.135. comprehensive cardiac risk reduction and rehabilitation. and typical- the protocol used. tion (134).americanheart. uncontrolled arrhythmias. This report and several other continue until the patient demonstrates signs or symptoms studies in patients who have received thrombolytic therapy that necessitate termination of exercise (i. or 70% of the predicted maximum heart rate. including VT. Infarction (2)(345). often defined as a peak heart rate of 120 2) investigators (123) reported that nearly 40% of the 10. is 0.4%. are older.. the Gruppo Italiano per lo or symptom limited. The incidence of fatal cardiac events. and Guidelines but have not been widely studied in patients early after for the Management of Patients With Acute Myocardial myocardial infarction.. Submaximal protocols have a predeter- Studio della Sopravvivenza nell’Infarto Miocardico (GISSI. days. e.135). at 6 weeks (133). and within 3 days after myocardial infarction (124. and neurolog. The absolute and relative contraindications to exercise test- Safety ing are presented in revised Table 1. discharge exercise tests in the literature ranges from 5 to 26 ments. 2002 American College of Cardiology Foundation . (122) documented increased use of these newer treat. patients treated with thrombolytic agents.219- bpm. LVH.384) without have a greater functional capacity. The use of exercise or pharma. that a large percentage of postinfarction patients will not or sustained VT. including fatal who demonstrate major (greater than 1 mm) ST-segment myocardial infarction and cardiac rupture. Symptom-limited protocols have an event rate that is reduced. The prognosis among survivors of myocardial infarction continues to improve. This observation appears to hold true for tests per- received thrombolytic therapy.americanheart.4% and was distinctly lower in the era demonstrated that exercise-induced ischemic ST-segment 45% of patients who received thrombolytic therapy (3. a worse prognosis (129.www.www. However. dial infarction than in those without ischemia (144-146). spective of the test results. Such patients death or nonfatal myocardial infarction.7 compared with those without such far different from less-selected historical populations or con. Data from GISSI-2 trial (123) demonstrated that symptomatic but not the GISSI-2 study (386) demonstrated that elderly patients silent ischemic ST depression greater than or equal to 1 mm (aged 70 years or more) treated with thrombolytic therapy. are 1) less likely to have severe three-vessel CAD.129.386) demonstrate that those patients unable to per. dictor of cardiac mortality (139-141). of such patients remains low (1.6% at 1 year.151). Inability to Exercise Blood Pressure Data from GUSTO (138) and other large thrombolytic trials Failure to increase systolic blood pressure by 10 to 30 mm (123. A comparison of selected studies is shown in Tables 18 and 19. level (148.129. and 3) frequently undergo coronary within 6 weeks of myocardial infarction demonstrated the angiography in lieu of exercise testing. or ST depression among patients with con- The improvement in 1-year mortality in patients who have trolled heart failure (127) to be independent predictors of received thrombolytic therapy is multifactorial.132.7%) by historical standards.org Gibbons et al. myocardial infarction (123.143). Angiographic studies have demonstrated more multivessel sive procedures) at 4 days after myocardial infarction. more recent plasty (3% mortality) or coronary artery bypass surgery studies are limited in that coronary revascularization inter- (3.132. the positive predictive value of exercise- current patient populations not treated with thrombolytic induced ST depression for cardiac death or myocardial therapy. stroke. attain a systolic blood pressure greater than 110 mm Hg pre- ment by exercise testing. infarction at 1 year was found to be only 8% in patients treat- fore not surprising and substantially reduces the predictive ed with thrombolytic agents versus 18% in those not treated accuracy of early exercise testing. and intravenous beta-blockers (48%) who patients treated with thrombolytic therapy was an independ- were able to perform an exercise test within the first month ent predictor of cardiac mortality. the odds ratio for cardiac death among those with exercise- patient population that presently undergoes predischarge induced ischemic ST-segment depression (greater than or exercise testing in clinical trials of thrombolytic therapy is equal to 1 mm) to be 1.134. Earlier studies in patients not dicted poor outcome in patients with Q-wave infarcts (129) receiving thrombolytic agents demonstrated a similarly high but not among those with non–Q-wave infarcts (127). or inva. Although their subsequent mortality rates are MET level or exercise duration achieved on exercise testing lower than in patients treated in the prethrombolytic era is an important predictor of adverse cardiac events after because of therapeutic advances and revascularization. their myocardial infarction (123. whereas uncomplicated stable patients have a low car.149). with thrombolytic agents (150). Their low cardiac event rate after discharge is there.135. ST depression at a low exercise than that in younger patients (1.021 patients who predictive value of exercise-induced ischemia for cardiac received thrombolytic therapy had no complications (no death or reinfarction. One-year postdischarge mortality in the Some but not all studies performed in the prethrombolytic CAMI study (121) was 8.7% mortality).142. formed on the treadmill and the cycle ergometer.129).acc. Data from the Global Utilization of ventions are often performed in persons who demonstrate an Streptokinase and TPA for Occluded Arteries (GUSTO) trial ischemic response (126.148). heart failure. on exercise testing at 28 days after myocardial infarction in aspirin (90%).153).148. However.134.134.126. The CAD in those with exercise-induced ischemia after myocar- mortality rate was 1% at 1 month and 3. 2) have a A meta-analysis (Table 18) that evaluated exercise testing smaller infarct size.org ACC/AHA Practice Guidelines 27 Risk Stratification and Prognosis event rate in those patients unable to exercise (127.125.3% but still higher greater than 2 mm (147). particularly in patients who have Exercise-Induced Ischemia received thrombolytic therapy and revascularization during hospitalization. recurrent ischemia. thus reducing the (138) demonstrated that 57% of the 41. absolute event rates are higher than in patients who have 149.152. Consequently.7% depression after myocardial infarction was an important pre- mortality) and in the 28% who underwent coronary angio. ischemia. The 6-month mortality rate in Other studies have shown only ST-segment depression these patients was remarkably low at 2.147. The Recurrent ischemia occurred in 7% of this group. The . Although the available evi.American College of Cardiology Foundation . 2002 American Heart Association . Hg during exercise testing has been shown to be an inde- form an exercise test have the highest adverse cardiac event pendent predictor of adverse outcome in patients after rate. Inability to diac event rate even before they undergo further risk assess.1%). exercise testing presumably can still assist achieve 5 METs during treadmill exercise is associated with in the risk stratification of such patients. There is limited evidence of the ability of exercise testing to risk stratify patients who have not received reperfusion in Exercise Capacity the current era. Failure to dence is limited. but the absolute mortality after myocardial infarction had a favorable prognosis irre.143. reinfarction. 28 Table 18. myocardial infarction. • Exercise ST depression (or 1.7) 1980–1995) • Impaired systolic blood pressure (or 4.613 Meta-analysis 10. ETT indicates exercise treadmill testing.70 y Patients excluded from exercise testing (1987) of 24studies or cycle had the highest mortality.acc.067 Treadmill 1–6 wk 1y The odds ratio for cardiac death was significantly (1996) (2 studies of or cycle higher for patients with: exercise-ETT. American Heart Association .0) The rate of cardiac death or MI in persons with exercise-induced ST depression is lower in those receiving thrombolytic therapy compared with those without thrombolysis (8% vs 18%).www. Exercise-induced ST-segment depression is predictive of increased risk only in patients with inferiorposterior MI.25–5.0 wk 0.6 –9. Submaximal or predischarge testing has greater predictive power than postdischarge or maximal testing.americanheart.org American College of Cardiology Foundation . Shaw150 15.0) • Limited exercise capacity (or 4. 2002 Number Number of Patients of Patients Author Who Treated With Timing Length of (Year) Underwent ETT Thrombolysis Type of Test After MI Follow-up Outcome ACC/AHA Practice Guidelines Froelicher141 5331 Meta-analysis 0 Treadmill 1. (1973–1986) Abnormal systolic blood pressure response and poor exercise capacity were predictive of poor prognosis. Meta-Analyses of Exercise Electrocardiographic Testing After Myocardial Infarction Gibbons et al.www. and MI.org . 3% underwent revascularization before discharge Stevenson148 256 256 Symptom-limited 7–21 d 10 mo • Predictors of recurrent ischemia: (1993) (6–12 mo) — ST segment ↓ ≥1 mm — Exercise tolerance <7 METs Arnold153 981 490 Symptom-limited Predischarge 1y • 260 of 981 subjects were randomly (1993) assigned to receive immediate PTCA • 3. metabolic equivalents. SBP. MI.13) • 9.4 wk 1y • ST depression >1 mm predicted future (1993) angina but not reinfarction or death Piccalò169 157 157 Symptom-limited 15 d 6 mo • 30% of patients with positive exercise test (1992) underwent coronary revascularization • 90% of patients without angina or ST ↓ ≥1 mm had no cardiac events in follow-up *Selected studies were derived from a MEDLINE search of reports from 1980 to 1995 of all studies that presented a separate analysis to evaluate predischarge exercise-electrocardiographic testing and included patients (some or all) who have received thrombolytic therapy. 0.4% mortality with exercise ST ↓ vs.1% mortality in those unable to exercise GISSI-2 study • 1. TIMI-2.3% in those who underwent ETT • 2.6 relative risk of mortality in those unable to exercise • Exercise test predictors of mortality: — SBP rise <30 mm Hg from rest Mickley157 123 35 Symptom-limited 1.www. Modified from ACC/AHA guidelines. percutaneous transluminal coronary angiography. Selected Studies* of Exercise Testing After Myocardial Infarction in the Thrombolytic Era Number Number of Patients of Patients Author Who Treated With Timing Length of (Year) Underwent ETT Thrombolysis Type of Test After MI Follow-up Outcome Villella123 (1995) 6296 6296 Symptom-limited 28 d 6 mo • 7. ETT indicates exercise electrocardiographic testing.org Chaitman126 (1993) 2502 2502 Submaximal 2 wk 1y • 1261 who underwent ETT were randomly American College of Cardiology Foundation .7% mortality in those with a positive test result • 0.9% mortality in those with negative test results • Predictors of mortality: — Angina + ≥1 mm ST? — ST ↓ ≥1 mm at <100 W or <6 min exercise — <6 min exercise or peak work rate <100 W — SBP rise <28 mm Hg from rest American Heart Association . systolic blood pressure. METs.www.org TIMI-2 Study assigned to conservative strategy • 9. myocardial infarction.6% without (P = 0 . Studies in which exercise imaging variables were entered into multivariate analysis were excluded.2 ACC/AHA Practice Guidelines Gibbons et al. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico 2 Trial. 2002 29 . Thrombolysis in Myocardial Infarction II Trial.3% mortality in those unable to exercise vs 2. GISSI-2.americanheart.acc. and PTCA.Table 19. counseling patients and their families about domestic. In the treatment of acute ischemia and arrhythmia and for their 15% of persons in the labor force whose work involves heavy effect in reducing early and late mortality after infarction manual labor (162). dress.161). ational. Simulated work tests can be performed in patients adrenergic blockade attenuates the ischemic response. recre- month mortality after myocardial infarction (relative risk.2 like scrubbing floors or lifting or moving to 4. or 4 METs Do light work around the house throwing a baseball or football? like dusting or washing dishes? Greater than Participate in strenuous sports like swimming. myocardial infarction show consistent trends toward survival . two with low functional capacity. tempera- (122). Energy demands for lifting heavy objects. bowling. or use the toilet? Walk on level ground at 4 mph or 6. the exercise test data should not be used (2)(345). and environmental and psychological stresses are not angina and ischemic ST changes and lengthen the time to assessed by routine exercise tests and must be taken into con- ischemia on exercise testing (128. or exercise-induced ischemia and in those who are otherwise long-term follow-up studies demonstrated that these agents apprehensive about returning to a physically demanding do not interfere with poor functional capacity as a marker of occupation (163-165. football.org 30 ACC/AHA Practice Guidelines American Heart Association . as well as control. Randomized trials of cardiac rehabilitation after ling heart rate and blood pressure response during exercise.org Table 19a. They are used in the occupational activities require fewer than 5 METs.159-161). Functional capaci- the overall mortality rate in this study population was low ty in METs derived from the exercise test can be used to (387). (166). 2002 American College of Cardiology Foundation .americanheart. sideration.8 km per h? heavy furniture? Participate in moderate recreational activities like golf.71) in patients treated with thrombolytic therapy.700× Exercise testing after myocardial infarction is useful for during exercise testing was an independent predictor of 6. GISSI-2 investigators reported that a peak heart rate (in Activity Counseling bpm)–blood pressure (in mm Hg) product less than 21. Because patients will be taking these medications for an indefinite period after infarction. dancing. Most domestic chores and non–Q-wave infarctions (130.144.www. estimate tolerance for specific activities. The use of The follow-up symptom-limited testing performed 3 to 6 weeks after myocardial infarction can assist in further activ- beta-adrenergic blocking agents after myocardial infarction ity prescription and issues concerning return to work. One study activities require fewer than 5 METs. or skiing? MET indicates metabolic equivalent. 10 METs singles tennis.154-157). ty at which activities are performed will directly influence induced ischemia was similar in patients with Q-wave and the amount of energy required.389). Estimated Energy Requirements for Various Activities* 1 MET Can you take care of yourself? 4 METs Climb a flight of stairs or walk up a hill? Eat. and occupational activities that can be safely per- 1. *Adapted from the AHA Exercise Standards (7) and Duke Activity Status Index (428). adverse prognosis (128. a submaximal found that exercise-induced ST-segment depression in test at the time of hospital discharge can be useful in coun- patients with non–Q-wave myocardial infarction was associ. sion in patients with Q-wave infarction (158). Published charts that provide an estimate of energy requirements for various Other Variables activities are available (see Table 19a) (7.acc. Patients taking beta-blockers after myocardial infarction should continue to do so at the Cardiac Rehabilitation time of exercise testing. Cardiac rehabilitation combines prescriptive exercise train- ing with coronary risk factor modification in patients with cise test response while patients are taking beta-blockers heart disease. the exer. the number of patients taking these agents at as the sole criterion for recommendations regarding return to the time of the postinfarction exercise test continues to grow work. Most has increased over the past decade.135. although formed after discharge from the hospital. Although beta. Beta-adrenergic blockers reduce the occurrence of ture. doubles tennis. Gibbons et al. left ventricular dysfunction. hence.www. seling regarding the first several weeks after myocardial ated with greater risk of cardiac death than that of ST depres. infarction.388) but should be used only as a guide. It is considered standard care that should be provides information about the adequacy of medical therapy integrated into the treatment plan of patients with CAD in preventing ischemia and arrhythmias. basketball. Thus.4 km per h? Walk indoors around the house? Run a short distance? Walk a block or two on level Do heavy work around the house ground at 2 to 3 mph or 3. with the understanding that the intensi- Several studies demonstrated that the occurrence of exercise. 148. farction patient include ischemic ST-segment depression higher levels of physical fitness according to an exercise tol. Maximal VO2 is defined as the point at . or controlled heart failure) Class I (7. Meta-analyses of these trials have calculat. symptom-limited exercise testing before program initi- ation is needed for all patients in whom cardiac rehabilitation V. although there are no available studies to assess its monary limitations as a cause of exercise-induced dys- value. and uncertain. evaluate improvement in functional capacity. VO2 at maximal exercise is be performed. Strategies for exercise test evaluation after myocardial grams (162. thrombolytic agents. Their low cardiac event rate peutic interventions in which improvement of exercise substantially reduces the predictive accuracy of early exer. recent coronary angio- plasty.americanheart. Class IIa Summary Evaluation of exercise capacity when indicated for Contemporary treatment of the patient with acute myocardial medical reasons in patients in whom subjective the infarction includes one or more of the following: medical estimates of exercise capacity from exercise test time therapy. exchange primarily include oxygen uptake (VO2). ed a significant 20% to 25% reduction in cardiovascular Exercise test predictors of adverse outcome in the postin- death in patients enrolled in such programs (167).164168. For these rea.org ACC/AHA Practice Guidelines 31 benefit among patients enrolled in cardiac rehabilitation pro. and in evaluation prescription and assess the patient’s response to and progress of training program outcome (7. EXERCISE TESTING WITH VENTILATORY is recommended (ie. increase from resting level). dioxide output (VCO2). tolic blood pressure less than 110 mm Hg or less than 30 mm efits among those who are most unfit (166). 2. at about 14 to 21 days. 3 (3). sidered for heart transplantation. or work rate assessment of maximal exercise is are These interventions have led to marked improvement in the unreliable. Assistance in the differentiation of cardiac versus pul- after. cise testing. pnea or impaired exercise capacity when the cause is scription. The patient popula. Evaluation of the patient’s response to specific thera- selected historical populations. GAS ANALYSIS recent coronary artery bypass surgery. Patients who have Ventilatory gas exchange analysis during exercise testing is not undergone coronary revascularization and are unable to a useful adjunctive tool in assessment of patients with car- undergo exercise testing have the worst prognosis. Exercise testing in cardiac rehabilitation is essential in Exercise testing is useful in activity counseling after dis- development of the exercise prescription to establish a safe charge from the hospital. carbon Submaximal testing can be performed at about 4 to 76 days.129.www.390). 1.151). Such testing may be useful to rewrite the exercise pre.166).166). and coronary revascularization. Alternatively. chronic stable angina. Their mortality rates are higher than for those who either have Class III received thrombolytic therapy or have undergone coronary Routine use to evaluate exercise capacity. infarction are outlined in Fig. It is used to develop and modify the exercise required during exercise training sessions. provide feedback to the patient (166). particularly those who have been treated with reperfusion. a symptom-limited exercise test can ventilatory/anaerobic threshold.American College of Cardiology Foundation . sons. Thus. revascularization. with the greatest ben.134. 2002 American Heart Association . Evaluation of exercise capacity and response to thera- Exercise testing in the stable cardiac patient who continues py in patients with heart failure who are being con- an exercise training program is often performed after the ini. and about 3 to 6 weeks later. greater than or equal to 1 mm. prognosis of the postinfarction patient.acc. Exercise testing is also an impor- and effective training intensity.www. in the exercise training program.143. symptom-limited tests can be considered the best index of aerobic capacity and cardiores- conducted early after discharge.149. diovascular and pulmonary disease.org Gibbons et al. Measures of gas Exercise testing after myocardial infarction is safe. or in the presence of (123. those with recent myocardial infarction. reperfusion therapy according to risk in the current era. tial 8 to 12 weeks of exercise training and periodically there. piratory function. Moreover. there is limited evidence of the ability 2. Class IIb tion eligible for predischarge exercise testing in clinical trials of thrombolytic therapy is therefore far different from less 1. However. exercise testing presumably can still assist in risk stratification of such patients. in risk stratification of tant tool in exercise training as part of comprehensive cardiac patients to determine the level of supervision and monitoring rehabilitation. functional capacity less than 5 improves exercise capacity among cardiac patients by 11% METs. minute ventilation. and inadequate blood pressure response (peak sys- to 66% after 3 to 6 months of training. Determination of the intensity for exercise training as of exercise testing to stratify patients who have not received part of comprehensive cardiac rehabilitation. particularly if accompanied by erance test are associated with reduced subsequent mortality symptoms.132. tolerance is an important goal or end point. Exercise training controlled heart failure. at a low level of exercise. www. part on the predominant fuel used for cellular metabolism. all limit the reliability of threshold is a defined end point that can be established by VO2 estimates. However. es anaerobic glycolysis for energy generation. The measurement of gas exchange variables has been sim- plified in recent years with the development of rapid gas analyzers for oxygen and carbon dioxide and computerized on-line analysis systems.7 to 0. However. which demonstrates the wide scatter of meas. Shortly beyond ured VO2 per given treadmill time on a progressive treadmill the anaerobic threshold. Although the anaerobic impaired by heart or lung disease. The VAT cannot be measured in some patients.85 at rest and is dependent in From Froelicher et al174 with permission. direct measures of VO2 are reliable several different methods.org 32 ACC/AHA Practice Guidelines American Heart Association . This is a highly reproducible plateau in measured VO2 is reached. 2002 American College of Cardiology Foundation . and the application of a single not meet the oxygen requirements. generally ranges from 0. in patients with heart failure. Table 20. . This hypothesis is supported by the fact that measured lactate lev- els increase at the point at which minute ventilation begins its curvilinear relation to work rate. physiological and methodological inaccuracies. Gibbons et al. Relation between measured versus predicted oxygen uptake Hard 60–84 for the Bruce protocol and progressive ramp protocol in patients with Very hard ≥85 heart failure. The respiratory exchange ratio Figure 4. yielding lac- lations (171). this may not be the case. Peak VO2 is the highest VO2 attained during Another index of relative work effort is the ventilatory/ graded exercise testing. CO2 production exceeds VO2. the oxygen supplied to exercising muscles does ing treadmill exercise (170). other valuable measures can be obtained. Thus. This is illus. The respiratory exchange ratio repre- sents the amount of carbon dioxide produced divided by the amount of oxygen consumed.www. work rate.americanheart.0 often indi- increase in work rate (a plateau is reached) during graded cates that the subject is giving a near-maximal level of effort. the onset of blood lactate accumulation. those with very poor exercise capacity (391). At exercise is often difficult to determine precisely. Classification of Exercise Intensity Based on Oxygen Uptake177 Intensity % VO2max Very light <25 Light 25–44 Moderate 45–59 Figure 5. In addition to peak or maximal VO2. In most patients. and which no further increase in measured VO2 occurs despite an thus a respiratory exchange ratio greater than 1. particularly trated in Fig. Exercise protocols with large increments in work anaerobic threshold is based on the hypothesis that at a given rate per stage (136) (Fig. which range from the extremely fit to those tate as a metabolic byproduct (173). From Froelicher et al174 with permission. 4. fatigue usually ensues. the VAT is highly reproducible. Gas exchange data can provide important information to evaluate functional capacity and distinguish cardiovascular from pulmonary limitations dur- ing exercise. the actual cause of the observed abrupt rise in minute ventilation remains controversial. the use of handrail support dur. endurance time is greatly dimin- aerobic capacity with published formulas based on exercise ished. VO2max indicates maximal oxygen uptake. exercise testing. Most clinical studies point during exercise at which ventilation abruptly increases report peak VO2 rather than maximal VO2 because the latter despite linear increases in work rate and VO2. how- time or work rate without direct measurement is limited by ever. The term protocol. This imbalance increas- regression formula to a wide variety of heterogeneous popu. At high levels of exercise. but the term does not imply that a anaerobic threshold (VAT). 5).org and reproducible and provide the most accurate assessment of functional capacity (172). Unity is achieved when predicted oxygen uptake is equal Maximal 100 to measured oxygen uptake. Relation of treadmill time (independent of specific protocol) to measured oxygen uptake using a progressive treadmill protocol. whether mus- cle hypoxia is a main stimulus for increased lactate produc- tion is not yet clear. the true anaerobic threshold at the muscle cell level. CHF indicates congestive heart failure. Minute ven- tilation and its relation to carbon dioxide production and oxygen consumption yield useful parameters of cardiac and pulmonary function.acc. and the VAT are separate but related events that occur during exercise. Estimation of peak intensities beyond the VAT. Classification of Exercise Capacity in Patients With Heart Failure. Rating of perceived exertion is also helpful in this setting. The VAT is determined by several easily recognized meas- urements that can be obtained during respiratory gas analy- sis. 2002 American Heart Association . . From Froelicher et al174 with permission. ventilatory anaerobic threshold.174).www. These include 1) a departure of linearity of minute venti- lation (VE) and VCO2 with increasing work rates and an abrupt increase in the respiratory exchange ratio and fraction of O2 in expired air (FEO2). 2) an increase in VE/VO2 without an increase in VE/VCO2. VO2 indicates oxygen uptake. Normal values for maximal oxygen uptake among healthy adults at different ages are available (7) and may serve as a useful reference in the evaluation of exercise capacity. Normal values for VAT in children are provided elsewhere (9). and an increase in VEO2 without a decrease in the fraction of CO2 in expired air. This may be most useful when the heart rate response to exercise is not a reliable indicator of exercise intensity (e.g. patients with fixed-rate pacemakers). Guidelines for Peak Exercise Oxygen Uptake as a Criterion for Cardiac Transplantation184 Category for Peak VO2 Transplant (mL/kg/min) Figure 6. as shown in Table 20 (177). fraction of expired air that is oxygen. Data derived from exercise testing with ventilatory gas analysis have proved to be reliable and important measures in the evaluation of patients with heart failure (178-181.org Gibbons et al.American College of Cardiology Foundation . or total fitness in children. Further details on the methodology and inter- pretation of data obtained during ventilatory gas analysis are available (8. and assist in differentiating cardiac from pulmonary limitations in exercise capacity (176). oxygen Probable indication <14 Inadequate indication >15 uptake. VE indicates Accepted indication <10 minute ventilation. VO2.americanheart. The VAT has been proposed as a more sensitive index of fitness than maximal VO2. VCO2. Determination of exercise training intensity to maintain or improve health and fitness among persons with or without heart disease can be derived from direct measurements of peak oxygen consumption. objectively track the progression of disease that may limit exercise capacity. heart rate. 3) the lowest VE/VO2 value measured during exercise. objectively evaluate the response to interventions that may affect exercise capac- ity. and 4) a curvilinear increase in VE and VCO2 with a linear increase in VO2 (Fig. carbon dioxide production. Based on Peak Oxygen Uptake and Ventilatory Anaerobic Threshold182 Peak VO2 VAT Class Impairment (mL/kg/min) (mL/kg/min) A None to mild >20 >14 B Mild to moderate 16–20 11–14 C Moderate to severe 10–16 8–11 D Severe <10 <8 VO2 indicates oxygen uptake.www.acc.175). 6) (173.org ACC/AHA Practice Guidelines 33 Table 21.. and FeO2. and VAT. grade the severity of functional impairment.174.392- Table 22. Measurements used to determine the gas exchange anaerobic threshold (Atge) using a progressive treadmill protocol. Measurement of expiratory gases during exercise testing can provide the best estimate of functional capacity. and the nature of symptoms come in patients with heart failure (394. in women. n = 33 51%. The exercise capacity of patients with heart failure VI. weighted mean sensitivity of 0. SPECIAL GROUPS: WOMEN. n = 28 59%. is most commonly in the low. n = 43 Williams198 (1994) 70 60 >50% dia 19 57 67%. and na. with Gas exchange measurement systems are costly and require ST-segment abnormalities more commonly reported in third- meticulous maintenance and calibration for optimal use grade girls than boys (188). Personnel who administer tests and interpret results of ST-segment interpretation for the diagnosis of coronary must be trained and proficient in this technique.to intermediate-probabil- tion of the rate of VO2 decline during exercise recovery (VO2 ity range.189-192. n = 35 Hung195 (1984) 92 51 >70% dia 16 51 75%. n = 24 78%. n = 42 66%. n = 194 86%. . changes. Rationale Stratification of ambulatory heart failure patients by this technique has improved ability to identify those with the Cardiovascular disease is one of the principal causes of death poorest prognosis. women less than 60 years old best prognostic information in heart failure patients. †Derivation set. CAD indicates coronary artery disease. Compared with men. n = 70 Linhart190 (1974) 98 46 >50% dia na 34 71%.184) (Table 22). ‡Validation set. n = 159 *Studies of >50 women. Moreover. n = 30 68%. n = 81 74%. exercise appears to be gender related from an early age. who were (399) than in those with normal oxygen kinetics. n = 169 64%.acc. Table 23. Abnormal ventilatory and tor of 11 (185). Women sarily reflect the daily activities of heart failure patients. The probability of coronary disease in chronotropic responses to exercise are also predictors of out. and a lower cardiac index women with anginal symptoms in CASS (187). n = 71 60%. n = 46 Barolsky192 (1979) 92 50 >50% dia 16 41 60%. diameter stenosis. (84. the disease according to gender are summarized in Table 23 test requires additional cost and time. AND classes.org 394).www. younger than 65 years of age. exceeding mortality due to breast cancer by a fac- plantation (183. n = 62 Weiner193 (1979) 580 na >70% dia 16 48 76%.61 (95% confidence interval. n = 27 74%.org 34 ACC/AHA Practice Guidelines American Heart Association . 2002 American College of Cardiology Foundation . Studies examining the accuracy (170). n = 74 Sketch191 (1975) 56 50 >75% dia na 27 50%. dia. n = 419 Melin88 (1985) 93 51 >50% dia 20 30 58%. lower peak VO2 (396-398). Most inves. based on their peak VO2 and VAT can be divided into four ASYMPTOMATIC INDIVIDUALS. women. based on age. n = 37 Marwick199 (1995) 118 60 >50% dia 17 58 77%. n = 69 Robert196 (1991) 135 53 >50% dia 29 37 68%. From a Bayesian stand- Evaluation of submaximal and recovery ventilatory respons. n = 64 Hlatky84 (1984) 613 na >75% dia na na 57%. ease in women may be difficult to make: almost half the ance. peak exercise capacity does not neces. n = 10 78%. n = 151 Morise200 (1995)‡ 288 57 >50% dia 26 36 55%. This classification sys.www. especially in premenopausal women. The technique of ventilatory gas measurement has a num. reported a eration (8). not available. Moreover. gender. had normal coronary arteri- tigators conclude that measurement of peak VO2 yields the ograms. as shown in Table 21 (182). Kwok et al.194-199). the lower prevalence of CAD presents a particularly es may be particularly useful when exercise to near-maximal difficult situation for noninvasive testing. as well as patient coop.88. evalua. Finally. n = 56 48%. n = 48 56%. POSTREVASCULARIZATION PATIENTS tem is limited in that age and gender are not taken into account. Gibbons et al.186. point. n = 106 74%.395). (17). n = 79 Chae197 (1993) 114 na >50% dia na 54 66%. n = 70 Morise200 (1995)† 264 56 >50% dia 27 33 46%. the levels (respiratory exchange ratio greater than 1) is not results of functional testing (exercise capacity. Accuracy of ECG Analysis in Women. who should be considered for heart trans. and imaging tests) may be influenced by gender. Prolonged recovery as it is in men (186). had less extensive coronary disease. Although kinetics) may provide additional information regarding the typical angina is as meaningful in women older than 60 years functional state in heart failure patients. The ST response to ber of potential limitations that hinder its broad applicability. the clinical diagnosis of coronary dis- time of VO2 has been correlated with poorer exercise toler. Also. ST-segment achieved (394-399). Sensitivity and Specificity of Exercise Electrocardiography in Women* Positive Sensitivity: Specificity: Mean Exercise Test Women Women n Age Definition of Multivessel Result (% of (n = Patients (n = Patients Author (year) (Women) (y) CAD CAD (%) Women) With CAD) Without CAD) Guiteras189 (1972) 112 49 >70% dia 12 38 79%. n = 24 80%. n = 411 Ilsley194 (1982) 62 51 >50% dia 27 44 67%.americanheart. Significant gender differences were reported in The accuracy of the exercise ECG for diagnosis of coro- unbiased estimates of sensitivity and specificity. The ST/heart rate relation has been as the initial test for CAD in women. One possible presence of cardiac symptoms (e. and differences in performance and although the exercise score concept is attractive. not all centers have reported these favorable findings (198). which might include the greater prevalence of before the patient proceeds to angiography (88). tion and multivessel disease). patients likely to exercise submaxi- careful analysis of the incremental diagnostic value of tread. women (28).org ACC/AHA Practice Guidelines 35 0. continuous analysis of the ST segment may recover groups: 65 to 75 years. 3.9%.www. respectively (368). body habitus. subdivision of this group (205) is the “young old” (65 to 75 pnea). hemodynamic and women. Avoidance of identifying ST depression in the inferior Diagnosis of CAD in the Elderly leads and identification of test positivity based on persistent Rationale changes (204) enhance the predictive value of a positive test but may compromise the predictive value of a negative test. coronary physiology. mum aerobic capacity (201.americanheart.5%.www. including exercise capacity. imaging approaches may be an efficient initial alternative to The standard approach to exercise testing involves catego. respectively.68) and specificity of 0. and high. Concern about false-positive ST-segment Studies that have documented lower specificity in women responses may be addressed by careful assessment of have cited both lower disease prevalence and non-Bayesian posttest probability and selective use of stress imaging tests factors (192). and 46%. with 1. and prevalence of CAD ed. The exercise test provides a wealth capacity declines 8% to 10% per decade in sedentary men of other material. and workload were strongly associated with all-cause mor- risk Duke treadmill score predicted CAD greater than or tality in cardiac events in both sexes (401). CAD is highly not apparent in ST analysis alone. there are cur- be enhanced by attention to features other than the absolute rently insufficient data to justify routine stress imaging tests level of ST depression. The accuracy of exercise testing in women may nosis of CAD in women remains to be defined. The diagnostic contribu. and 89. There are few published data on exercise testing in able. although Table 23 demonstrates that this finding has not been These problems reflect differences in exercise physiology. and are years) and the “old old” (older than 75). Physicians must be cognizant of the influence of submaximal clude the use of treadmill exercise testing in women (28).70 (95% confidence interval. differences hand. equal to 75% in 19.54–0.7%. In a series of 976 symptomatic women spective population-based cohort study of 1452 men and 741 referred for exercise testing and coronary angiography.g.org Gibbons et al.75) in a meta-analysis of 19 ECG studies in women. Maximal aerobic Non-ECG End Points. A exercise on sensitivity. Patients older than 65 years are usually defined as “elderly. stress testing. and high-risk scores compared 12.368). the difficulties posed by clinical evaluation of proba- in microvascular function (leading perhaps to coronary bility of CAD in women have led to speculation that stress spasm). focuses on patients older than 75 years.2% of subjects. The diagnosis of CAD in women presents dif- monly viewed as less specific in women than in men. Although the optimal rization of the ST-segment response as “positive” or “nega.American College of Cardiology Foundation . tion of these findings has been calculated in multivariate 0. that are used in interpretation of the test result. the ST-segment response was found to be less accurate in between men and women. resulting in development of equations that give the each of which included at least 50 subjects (400). women. ischemic ECG changes. 34. Alexander et al. moderate-. The accuracy of exercise testing was in results in women may be caused by the use of different cri. With the . On the other mitral valve prolapse and syndrome X in women. models. compared the Duke treadmill score in 976 women and 2249 respectively (368). 5. which reflects a lower prevalence of severe but exertional angina in women was less often correlated CAD and the inability of many women to exercise to maxi. with coronary disease presence (352. than in men (84).” Finally. The exercise ECG is com. mally should undergo be considered for pharmacological mill testing found similar values in men and women (200). selection (including prevalence of prior myocardial infarc. prevalent in symptomatic patients in both groups. nary disease in women may have important limitations. with an approximate 50% reduction in exercise (heart rate and blood pressure) response to exercise.4%. the exercise ECG in women (199). significantly increased by the use of a multivariate model teria for defining coronary disease. This analysis has been combined with non-ECG end subjects 85 years or older. 75 to 85 years. 2002 American Heart Association . and than or equal to 75% or left main coronary disease was 3.1%. The frequency of 3-vessel disease greater men.2%.6% for low-. and 16.acc. exercise-induced angina.202). chest discomfort or dys. However.. including criteria for ST-segment positivity and ical application in women has remained limited. shown to be of value (203) but awaits widespread applica- tion. uniform. moderate-. Conclusion. these were modest (less than 10%) and did not appear to pre. Women Exercise-induced ST depression is less sensitive in women had a similar frequency of angina on the treadmill as men. 2-year mortality rates for women were 1%. its clin- of the test. because the ST-segment response is a continuous The elderly population is often classified in the following age variable.8%.64–0. Alexander et al. Even after patients with referral bias were exclud.6% in men. and 85 years or older the information lost from its analysis as a dichotomous vari. reported that a low-. However. and the capacity between ages 30 and 80 years (403). 2. this section primarily points into multivariate models (see below). Therefore. differences in population compared with ST-segment evaluation alone (196). ficulties that are not experienced in the investigation of men. and possibly hormonal differences. Variations likelihood of disease. (402). In a retro- type of exercise. strategy for circumventing false-positive test results for diag- tive” results. as shown in other age groups. and the prevalence and risk of coronary disease increase with positive predictive value of these features may be enhanced advancing age. peripheral vascular disease and chron- conduction delays. but nonetheless. Unfortunately. Functional capacity is often compromised Class IIa because of muscle weakness and deconditioning. Gibbons et al. 2. but are not necessarily an For example. and in 1989. both CAD and severe CAD. Chronotropic incompetence (failure to achieve 85% of extensive coronary disease in older patients (404). Elderly years and women older than 50 55 years: patients are much more likely to hold on to the handrails tightly.. including prior myocardial infarction and intraventricular • Who are at high risk for CAD due to other dis- eases (e. *Multiple risk factors are defined (212) as hypercholesterolemia These false-positive results may also reflect the coexistence (greater than 240 mg per dl). hypertension (systolic blood pressure of LVH caused by valvular disease and hypertension.5% in women over 75 years of age. Evaluation of asymptomatic men older than 40 45 mill exercise protocol in elderly patients (209). Interpretation of exercise testing in the elderly differs • Who are involved in occupations in which impair- ment might impact public safety or slightly from that in the young. monly occult. Because of the greater prevalence of Routine screening of asymptomatic men or women.* gradual protocols should be favored in selection of a tread. patients older than 70.Although angiographic tables show an adverse feature unless associated with evidence of ischemia increased gradient of risk for coronary disease and more (209). more attention must be given to 1. 2002 American College of Cardiology Foundation .org aging of the population.g. An alter- tion for coronary intervention may be less. and exercise capacity (406). cardiac death in a first-degree relative younger than 60 years. The performance of exercise testing poses several problems None. This disease is com. (Level of Evidence: C) coordination. and scores for assessing prognosis The presence of ST depression in asymptomatic elderly have not included the very elderly patients. score consistent with at least a moderate risk of serious cardiac events ical therapy may itself carry risks in this group. the National by consideration of other exercise parameters and a stepwise Health Interview Survey (206) reported that the prevalence of diagnosed CAD was 1. attention should be paid tial proportion of patients. the former now constitute a substan.www. in the elderly. Nonetheless. been published with respect to the use of exercise testing for Arrhythmias occur more frequently with increasing age. but it is certainly not contraindicated in this group (405). In some patients with problems of gait and 39). it is not surprising that the exer- cise ECG in this group has a slightly higher sensitivity (84%) and lower specificity (70%) than in younger patients (210). and there- fore the decision whether to send the patient for an exercise Evaluation of asymptomatic persons with diabetes or pharmacological stress test is more important than in mellitus who plan to start vigorous exercise (see page younger patients. within 5 years (213). thus. erly patients (407). . there are age-predicted maximum heart rate) is more common in eld- few data from patients older than 75 years. diabetes.acc. Resting ECG abnormalities. but in older patients. the application of standard ST-segment response criteria to elderly subjects is not associated with significantly different accuracy from Class III younger people (84). the results of native approach might be to select patients with a Framingham risk exercise testing in the elderly remain important because med. the section on screening. may compromise the availability of diag- ic renal failure) nostic data from the ECG. Presumably tThe patients is not associated with high event rates (211). this section focuses on to chronotropic and inotropic responses to exercise. exercise- patients older than 75 years. Although the risk of coronary Hg). More guide to risk-reduction therapy. if treadmill exercise is used. In addition to ST-segment criteria. On Bayesian grounds. Class IIb bicycle exercise is often limited by unfamiliarity. Evaluation of persons with multiple risk factors as a the mechanical hazards of exercise in elderly patients. diagnostic and prognostic assessment of CAD in this group. with silent ischemia estimated to be present in 15% of 80-year-olds (207). used for the iden. reducing the validity of treadmill time for estimating • Who plan to start vigorous exercise (especially if sedentary) or METs. as well greater than 140 mm Hg or diastolic blood pressure greater than 90 mm as conduction disturbances. and both it and a hypotensive response to tification of pretest disease probability do not consider exercise are ominous features. Certainly. especially at higher workloads.www. . a bicycle exercise test may be more attractive than a treadmill exercise test (208).8% in men over the age of 75 and approach combined with stress imaging tests. discussed in 1. the high Exercise Testing in Asymptomatic Persons prevalence and greater severity of coronary stenoses in this Without Known CAD group increase the sensitivity of testing and make it harder to Class I rule out significant disease.americanheart. fFew data have induced arrhythmias. and family history of heart attack or sudden angiography may be greater in the elderly and the justifica. smoking.org 36 ACC/AHA Practice Guidelines American Heart Association . undergo angiography. tACIP was a pilot study. even with the current position that simple risk reduction should be if ST changes are associated with risk factors. Nonetheless. the posttest probability of coronary dis. the relative risk of a subsequent event is increased in method to detect occult coronary disease. several studies have rec- rence of subsequent myocardial infarction. Both CASS and ACIP were stud.225-227. observational approach ST-SEGMENT RESPONSE. mild coronary disease. other exercise parameters. pre- enhanced by consideration of not only the ST-segment sumably asymptomatic military personnel and civilians response but also other exercise variables (223).www. Unfortunately.1 mV of ST-segment . In asymptomatic patients been addressed in only the Seattle Heart Watch (212). First. These numbers are obviously influenced by workup bias.acc. Because of with a negative exercise test) does not preclude the occur. make it more likely that chest pain symptoms are interpreted ies of patients with angiographically documented coronary as anginal. range of 4:1 or 5:1. and probably never will be. and Blood Institute follow-up study has sug. exercise testing has been shown to be pre- ease is dependent on the accuracy of the test and the pretest dictive of hard events (225.5 million hospital- usually compromise the predictive value of a negative test. expensive. and for this reason.226. In addition. early diagnosis of CAD in the hope that treatment may avoid complications and reduce the cost of acute treatment. attention has turned to the blood pressure response to exercise (224). carry important cost implications. because these persons could not and the results of stress imaging tests. because intervention can be postponed until had angina or were asymptomatic at other times). the predictive value of a positive test may be changes of atherosclerosis to be prominent in young. the use of exercise testing to screen for minority of patients with a positive test result experience CAD poses problems from standpoints of both positive and cardiac events. at a cost of more than Nonetheless. Lung.www. and Asymptomatic Cardiac Ischemia Pilot (ACIP) study of Lipid Research Clinics (226) studies. In CASS. asymptomatic subjects after infarction coronary disease but to predict outcome. coronary its onset without harming the patient. the use of revascularization was associated with a better long-term out. CAD is responsible for more attempts to enhance the predictive value of a positive test than half a million deaths each year and 1. Traditionally. although the ischemia may stratify patients for the intensity of risk factor absolute risk of a cardiac event in an asymptomatic popula- modification (219). the role of false-positive test results. Studies of the natural history of CAD have shown early Nonetheless. Diagnosis of patients with a positive exercise test result.org Gibbons et al.230. additional risk stratification is possible by tak- $100 billion per year in the United States (185). Conversely. and potentially hazardous interven- sons. the identification of function. in the era of managed care. variate analysis. other gested that acute cardiac events in predominantly low-risk studies using a composite end point including angina have patients are unpredictable (218). or supplemented use of greater than 0. the showed a trend toward improved survival after coronary prediction of myocardial infarction and death is considered bypass surgery when three-vessel disease and impaired left the most important end point of screening. exercise test result is more predictive of later development of al impairment may motivate patients to be more compliant angina than of occurrence of a major event. most patients with subsequent cardiovascular events occur because of plaque rupture involving minor death have a negative test result. Even taking all with risk factor modification (113).org ACC/AHA Practice Guidelines 37 Rationale which has ranged between 25% (221) and 72% (222). risk factors. A positive attempted in all patients (220). the like- disease. come than medical therapysuggest that revascularization because the presence of a previous positive exercise test may may prolong life (216. ommended consideration of other data complementary to the presence of greater than 1 mm of ST-segment depression. the absence of flow-limiting stenoses (associated detecting subsequent cardiovascular death is low. data from the CASS and In the Multiple Risk Factor Intervention Trial (MRFIT) (225). Angina is a less impor- patients with silent myocardial ischemia during testing (who tant end point. angina as an end point has a methodological weakness.americanheart. In extrapolated to the use of exercise testing as a screening general. with relative risks in the probability of disease. More recent studies have replaced involves analysis of the predictive value of a positive test. izations for myocardial infarction.232). because the sensitivity for stenoses.232. may be identified. with severe coronary disease. although dying of other causes (214). An alternative. The findings cannot be been included in Table 24 (212. In light of ing into account the severity of ST-segment depression and these human and economic costs. which is prognostically benign. unnecessary. 2002 American Heart Association . The purpose of screening is to either prolong life or Prognostic Evaluation improve its quality because of early detection of disease Despite these observations. because many coronary Furthermore.American College of Cardiology Foundation . the real issue is not to identify (215). Although this may seem inconsistent tion remains in only the 1% to 2% range per year (225). Diagnostic Considerations When other factors have been taken into account in a multi- As discussed earlier.217). tions. but those with a positive test result may suf- negative predictive value. the accuracy of exer. a On the other hand. because they may undergo for the diagnosis of coronary disease in asymptomatic per.233). However. end points (including subsequent angina) into account. because these tests are used fer from being labeled at risk. and a National lihood of re-presentation with progressive symptoms may Heart. These include other aspects of the ST- cise testing in asymptomatic persons has never been defined segment response. although this has ventricular function were present. 1. 1986)225 6008 0 1972 Various Submaximal ST depression 12.2. 1991)232 index.6 4.5 pain = 3.2 MI n/a 13. short duration.5 AP+MI+SCD 5. MHR < 90% (34) composite 10.6 ST depression = 1. exercise criteria. and HR. sudden cardiac death.7 Bruce229 (1983) 4158 13 1971 Bruce Maximal Chest pain. Exercise duration = depression. R wave = Allen230 (1980) 888 35 1973 Ellestad Maximal ST depression. combined = 3. ST/HR 14.5 1. Prediction of Cardiac Events by Exercise Testing in Studies of >500 Asymptomatic Individuals Prevalence of ST Women Exercise Depression Events per Relative Risk for Follow-up Author or Study (year) n (%) First ECG Protocol End Point Criteria (%) Events 1000 Patient/Y Events (y) Froelicher227 (1974) 1390 0 1965 Various Maximal ST depression 10. response.1. 1. 6.4 for ST duration. myocardial infarction. angina pectoris. SCD. 3.6 W.8 AP+MI+SCD 10.2 ST/HR = 2.4 M. MHR .4 (univariate. Screening for coronary artery disease. 38 Table 24. CHD.0.1 3. MI.4. 3. AP. RPP <80% MHR = 2. 14. 6.2 CHD death 2.5 M. 29 for 2 of 4 exercise 5. MI) AP 3.7 W Giagnoni226 (1983) 514 27 1971 Various Submaximal ST depression 26. all positive = 4.8 2.9 W.3 D ST depression = 2. ed. ST 11.8W.1 AP+MI+SCD 3. exercise exercise duration = duration 5. MI 5. rate–pres- sure product.4 Strong positive = 5.292 . Detrano R.1 recovery loop = 2.6 4.7 CHD death 2.>10%. AP 18.6 (multivariate) 6. In: Marwick T.7 M.6 M.4 (univariate AP) AP+MI+SC 5.9 Balke 12.6 M. Cardiac Stress Testing and Imaging.7 Bruce 1.3 6. recovery loop *Bruce protocol: The four exercise criteria were chest pain with exercise.6 AP (23)+ MI MI = 3. ST 14.8 W. 90% depression predicted McHenry228 (1984) 916 0 1968 Modified Maximal ST depression 2.3 Bruce212 (1980) 2365 0 Before 1975 Bruce Maximal Chest pain.9 W. ischemic ST depression.1.1.7 W 8. RPP.6 depression. RPP = 2.1 AP+MI+SCD 5. ST = 2.2 MRFIT 7 (Rautaharju.4 M. chest duration. 6. ECG indicates electrocardiogram.7 M. 1.3 Framingham 3168 52 1971 Bruce Maximal ST depression. MHR. R-wave 11.2.1 predicted 1. heart rate. heart rate impairment .* 3.3 W.8 (Okin. New York: Churchill Livingstone. 1986)231 3178 0 1972 Modified Maximal ST response 5.6 LRC (Gordon. Modified from Sada M. exercise (11)+ SCD AP = 7. coronary heart disease. maximal heart rate.6 AP+MI+SCD 4.3 W.4 M. predicted.3 14. 1996. in asymptomatic persons from the Framingham study (213).408). and the ST/HR tor–modification group when the exercise test was positive slope. used a com. The impor.acc. BEFORE FITNESS PROGRAM. 2002 American Heart Association . exercise for fewer with previous cardiac transplantation (239) or chronic renal than 6 minutes. risk factors should be strictly defined: hypercholes- than 6 minutes of the Bruce protocol has been associated terolemia as total cholesterol greater than 240 mg/dL. ent: age older than 35 years. matic persons has not been routinely recommended Attempts to extend screening to persons with lower degrees (235. smoking. in a first-degree relative less than 60 years old. hyper- with a relative risk of 6. even though this group accounted Unfortunately. increment of cardiac risk.org Gibbons et al. and ischemia at fewer than 5 minutes of exercise diastolic blood pressure greater than 90 mm Hg. and history of heart attack or sudden cardiac death 5. in part because of the prevalence of for a small fraction (less than 10%) of the study population. In this study. exceedingly rare (17).www.org ACC/AHA Practice Guidelines 39 depression with the ST integral (225. cardiac events were reduced in the risk fac. presence of microvascular disease (proliferative retinopathy Who to Screen? POPULATION SCREENING. General screening or nephropathy.e. those that attempt to identify young cular disease. or ST-segment depression). Although the physical risks of exercise An alternative approach would be to study patients with a testing are negligible (7). of risk are not recommended because screening is unlikely to SCREENING IN PATIENTS WITH CAD RISK FACTORS. and the addition of 10 years’ duration. patients with a positive after cardiac transplantation (241). a positive test result was best illustrated in the Seattle Heart Some patient subgroups are known to be at particularly high Watch Study (212). ful prognostic information from exercise testing. that ST-segment analysis alone was not predictive of out. the use of exercise testing in healthy asympto. improve patient outcome. the more workload is associated with a relatively high risk of subse. there was a 30-fold lished coronary disease that requires intervention. This can in the most recent national guidelines for cholesterol man- be done by applying the test only to patients with risk factors agement (ATP III).diabetes. presence of this disease. Such data have been derived these reasons. For also the severity of risk factors. risk of coronary disease and are often asymptomatic in the ing were not predictive of outcome in the group as a whole. including exercise test- not with abnormal standard exercise test criteria as judged by ing. Interestingly. tance of accounting for the clinical situation of patients with SCREENING IN OTHER PATIENT GROUPS AT HIGH RISK OF CAD. Detailed recommendations diac risk was associated with an abnormal ST/HR index but regarding cardiovascular screening. dia- relation between the performance of maximal or submaximal betes. significant concentration of car.236. the results of exercise test.jsp). On the basis of prognostic considerations. stress exercise test result significantly benefited by risk factor mod.226). there appears to be no factors (hypercholesterolemia. thereby accounting for not only the presence but adverse consequences in relation to work and insurance. These patients are more likely to have estab- heart rate.226).6 in women tension as systolic blood pressure greater than 140 mm Hg or (212. Exercise testing is patients with early disease) have the limitation that severe recommended if an individual meeting the criteria is about to CAD (requiring intervention) in asymptomatic patients is embark on moderate.410).. The Bayesian issues posed by testing tance of more intensive risk factor management of persons patients with a low probability of CAD may be reduced with diabetes has been increasingly recognized.www. peripheral vas- programs (for example. smoking. although the intervention and standard noninvasive tests have proved particularly group showed only a trend to more favorable outcome com. For these pur- quent events. however. before an exercise training program is begun are provid- computer interpretation (237).American College of Cardiology Foundation . as reflected somewhat by screening a slightly higher-risk group. any additional atherosclerotic risk factor for CAD. or autonomic neuropathy.6 in women (230). functional testing is often nondiagnostic. the likelihood of cardiovas- be of value for screening patients with a family history of cular disease is increased if at least 1 of the following is pres- coronary disease. The impor- RISK FACTORS. attainment of less than 90% of predicted failure (240). trol (see http://www. hypertension (JNC VI) and diabetes con- for CAD (see next section). The latter was predictive of outcome despite the fact according to the ST/HR index (409). the predictive value of the exercise data alone (234). Similarly. coexisting LVH. the development of evidence of ischemia at low the number of risk factors (i.americanheart. The greater However. Compared with patients in the ed elsewhere (388. Exercise testing has been shown to asymptomatic diabetic persons. likely the patient will profit from screening. In these groups. imaging tests may be of more value for risk stratification. asymptomatic come in the Framingham study (232). insensitive for detection of coronary artery vasculopathy pared with the usual care group. type 2 diabetes of greater than posite end point rather than hard events. hypertension. in the MRFIT study. ST-segment depression that occurs after fewer poses.7 in men and 3.org/main/info/link. The study by Blumenthal et al. asymptomatic patients with and without a history of cardiac . male patients older than 40 45 years with one or more risk EXERCISE CAPACITY.411). In MRFIT. In addition to patients with diabetes but in patients with 1 or more risk factors and 2 abnormal and peripheral vascular disease (238). false-positive test results may certain level of cardiovascular risk expressed as a continuous engender inappropriate anxiety and may have serious variable. type 1 diabetes of greater than 15 years’ thallium imaging to the exercise test substantially increased duration.to high-intensity exercise (408. A distinction must be made between usual-care group. these include persons features on exercise testing (chest pain. has been associated with a relative risk of 14. In STRESS IMAGING TESTS. including microalbuminuria). pretest probability). ification (237).7 in men and diabetes. or family history of premature CAD) may obtain use- testing and the predictive value of the ST-segment response. www. adverse psychological implications. heart rate and blood pressure response to exercise cardiac causes. and this association is much greater in sedentary than Class I in active persons (244).org 40 ACC/AHA Practice Guidelines American Heart Association . the risk of sudden death dur. In chronic aortic regurgitation. Gibbons et al. and there are no data to justify or criticize test- ing. minimally symptomatic patients with left ventricular dysfunction. Many Some asymptomatic patients presenting for The response to a positive exercise test should be modulat- advice about becoming fit are doing so because of the devel. prognostic assessment although in some cases. evaluation of symp- undergo periodic exercise testing for assessment of exercise toms and functional capacity before participation in capacity and prognostic evaluation of possible coronary dis. and law enforcement officers) often 1.americanheart. ed by the remainder of the exercise data. Cardiac arrest is more likely to occur during exercise than Valvular Heart Disease at rest. There are insufficient data to justify this approach. assessment of func- lesterolemic men. In valvular disease or with the following baseline ECG view of these limitations.4 years (246). include unnecessary and expensive additional testing.www. In the Lipid Research Clinics study of 3617 hypercho. 2. Thus. a minority of the committee abnormalities: favored a Class III recommendation for the use of exercise testing as a screening technique for CAD in patients with • Pre-excitation multiple risk factors or asymptomatic men older than 40 • Electronically paced ventricular rhythm years or women older than 50 years who plan to start vigor. The consequences of such findings (412). Comprehensive discussion is found although disease may be identified. ease. SPECIAL GROUPS. lar heart disease. • Greater than 1 mm ST depression ous exercise.acc.3% over 1 year and 4% over 7. firefighters. asymptomatic patients without known cardiac disease. when a sedentary person starts None. Implications for Clinical Practice The use of exercise testing for identification of CAD in Class IIb asymptomatic persons is a controversial topic for which the committee had difficulty defining guidelines concordant with Evaluation of exercise capacity in patients with valvu- widespread current practice.000 hours) is higher response to the test might therefore vary from risk factor than that of the general population (242). exercise testing is variables to further investigation with an imaging protocol recommended as a means of stratifying risk (243). • Complete left bundle-branch block .* dle-aged or older (i. there is presumably a period of increased risk.e. including exercise opment of symptoms that they either deny or ascribe to non. the predictive value of a positive exercise tional capacity and symptomatic responses in patients test result for subsequent activity-related events was only with a history of equivocal symptoms. For this reason. evaluations are done for statutory before aortic valve replacement in asymptomatic or reasons.. these Diagnosis of CAD in patients with moderate to severe issues must be discussed and informed consent obtained. patients with diabetes and those undergoing antihypertensive and treatment of CAD in patients with a markedly positive therapy may benefit from exercise testing before training as test result and multiple risk factors. Similarly. Before an exercise test is performed on an asymptomatic patient. In chronic aortic regurgitation. In those with a his- modification for a positive result in the absence of other risk tory of cardiac disease (including CAD). capacity. 2002 American College of Cardiology Foundation . many more patients have in the ACC/AHA valvular heart disease guidelines false-positive test results.org disease. The (which has been estimated at 1 per 784. a means of adjusting their exercise prescription. and in recovery. exercise testing of asympto. Persons whose occupations may affect Class IIa public safety (airline pilots. truck or bus drivers. the absolute risk of a major cardiac event during activity is still Class I small (245). The existing data indicate that lar heart disease. Class IIb matic men older than 45 years and women older than 55 Evaluation of exercise capacity of patients with valvu- years can be considered it has been recommended that mid. and misuse of data to Class III influence employment and insurance decisions. 0. older than 40 to 50 years) men should Class III undergo a screening exercise test if an exercise program Diagnosis of CAD in patients with valvular heart dis- more vigorous than walking is to be pursued.blood pressure response to exercise. in ease. railroad engineers. athletic activities. Although small. and ing supervised exercise in patients with cardiac disease nonexercise considerations such as risk factor status. However. an exercise program. In chronic aortic regurgitation. lier surgery (257). mean gradients of 18 to 64 mm Hg) have ejection fraction is a poor guide to ventricular function in shown that with the appropriate precautions. in patients with mitral valve prolapse. exercise area. excessive exercise-induced pulmonary hyperten- implications for medical. evidence of functional capacity used to counsel patients ume overload provoked by assumption of a supine position.5 cm2. and exercise should be terminated for inappropri. 2002 American Heart Association . which may have of exercise. ate blood pressure augmentation. the course of treatment is usually clear. left ven- matic patients. useful in evaluating aortic valve gradients in low-output flow Mitral Regurgitation. aortic valve replacement is probably not jus. principally patients with mitral regurgitation. sion. evaluation of LV function during exercise with issues. Hypotension during exercise in asymp- found in the ACC/AHA Guidelines for the Management of tomatic patients with aortic stenosis is sufficient reason to consider aortic valve replacement. In truly asympto. the development of for surgery in mitral stenosis is symptom status. Management of Patients With Valvular Heart Disease (412) Mitral Stenosis. which implies a fixed stroke volume. Exercise testing with increasing exercise. who should proceed to surgery. The decision to pro- stenosis. or pulmonary exercise ECG for diagnosis of CAD in these situations is lim. particularly Exercise testing is an accepted means of evaluating pedi. and it may be difficult to plan treatment on clin- gery are largely based on resting ejection fraction. in counseling tion are generally well compensated. However. many eld. tricular systolic dysfunction. excessive heart rate responses to a relatively low level imaging modalities. and syncope (258).acc.americanheart. The test provides objective od on the treadmill is advisable to avoid left ventricular vol. The hemodynamic response to cise testing is not commonly required.412). However. in whom more aggressive therapy medical therapy (256). or premature beats. and Uses of Exercise Testing in Patients With Valvular Heart either failure to augment systolic blood pressure with exer- Disease as detailed in the ACC/AHA Guidelines on cise or decreasing pressure with increasing workload. The use of the ischemia secondary to low cardiac output. If the blood may help clarify objectively the functional capacity of the pressure response to exercise is abnormal. Patients with severe atric patients with aortic stenosis (248-250). and social decision mak. reduction of cardiac output with exercise (evidenced by ing.5 to 1. asymptomatic because of inactivity or when a discrepancy The primary value of exercise testing in valvular heart dis. Exercise testing is also Patients With Valvular Heart Disease (412). The left ventricular response to exercise may be asymptomatic patients who are hemodynamically compro- used to monitor the response of asymptomatic patients to mised by aortic stenosis. patient who is a poor historian.American College of Cardiology Foundation . promised by false-positive ST-segment changes. exercise testing can value in documenting occult dysfunction and provoking ear- be safely performed in patients with aortic stenosis (413. In these circumstances. and left ventricular size (255). and because Aortic Stenosis. the test should be mitral regurgitation in patients with mitral valve prolapse but directly supervised by a physician familiar with the patient’s without regurgitation at rest has been associated with the condition. and along with Doppler imaging. Because the major indication exercise testing is not required.org Gibbons et al.org ACC/AHA Practice Guidelines 41 Rationale capacity. unless symptoms are exercise may be of value in selecting a subpopulation of ambiguous. Because volume overload is less ECG changes. subsequent development of progressive mitral regurgitation. exercise capacity is maintained until unquestionable in patients with severe symptomatic aortic late in the course of aortic regurgitation. exists between the patient’s symptom status and the valve ease is to objectively assess atypical symptoms. and output by increasing heart rate. the reduction of diastolic duration with exercise favors for- sidered a contraindication to exercise testing. slowing of the heart rate congestive heart failure.www. Apart from exercise mitral regurgitation in a patient with symptoms out of pro- . Because resting 0. exercise test- Doppler echocardiography has increased the number of ing is of the most value when a patient is thought to be asymptomatic patients with defined valvular abnormalities. and extent of disability. and exer- ical grounds in these patients. Severe aortic stenosis is classically con. tified on prognostic grounds (247. This is particularly of importance in the elderly. Because ejection fraction is a reliable index of left ventricu- erly patients in this situation are asymptomatic because they lar function in aortic regurgitation. other important responses include a rapid augmen- tation of heart rate. hypertension) are indicators in favor of earlier surgery. who are exercise-induced hypotension). and this is ward cardiac output. Mild and moderate mitral regurgita- states. The documentation of exercise-induced 415)(251-253). and chest pain (caused by often asymptomatic because they are inactive. Additional recommendations are might be considered. although exercise test- asymptomatic subjects with moderate to severe aortic valve ing in these situations for assessment of CAD is often com- gradients who are considering athletic programs. ceed to valve surgery is based on symptom status.www. demanding on the heart than pressure overload. a cool-down peri. before they embark on a physical activity program. decisions regarding sur- are inactive. Patients with severe mitral stenosis have a In symptomatic patients with documented valvular stenosis fixed stroke volume and are only able to augment cardiac or regurgitation. Functional limitation is commonly found in asymptomatic Concomitant Doppler imaging may demonstrate severe patients with aortic stenosis (254). combinations of exercise involving careful observation of the patient with frequent testing and assessment of left ventricular function may be of blood pressure checks during exercise. ited by false-positive responses caused by LVH and baseline Aortic Regurgitation. When exercise testing is performed to clarify these capacity. Three studies in mitral regurgitation may demonstrate reduction of exercise adults with moderate to severe aortic stenosis (valve areas of capacity and exercise-induced hypotension. surgical. Because of these con- however. or disease progres. 5 to 10 years artery bypass grafting without specific indications. Frequently.americanheart. periodic monitoring of asymptomatic few years after the revascularization procedure (416). use of the exercise ECG is inappropriate in situa. namic response.www. Silent restenosis is a common clinical manifes- after revascularization. stress imaging tests are more favored in this group. The conversion of a markedly positive test result done before neous coronary intervention (PCI). more reliance must be placed on symptom status. It is recognized that there are two phases after revasculariza. In patients des- . Localization of ischemia for determining the site of gone successful coronary bypass grafting is not predictive of intervention. have documented ischemic or viable myocardium. This ization or valvular interventions. subsequent events when the test is performed within the first 2. taneous transluminal coronary angioplastypercuta.org portion to mild mitral regurgitation observed on the resting guiding an appropriate cardiac rehabilitation program and echocardiogram.347). The exercise ECG has a number of limitations after coro- Exercise Testing Before Revascularization nary bypass surgery.g. This may reflect lower sensitivity of the exercise ECG for Class III ischemia and may be less true with stress imaging tests. together with the need to document the site of ECG. ischemia.acc. recoil. Exercise testing may be helpful in having ischemia on exercise testing (265). which is often atypical after surgery. of left ventricular function. Incomplete Class IIa revascularization or graft occlusion may be identified with the exercise ECG (260). hemodialysis. left ventricular ejection fraction sion. a particular frequency of testing. Demonstration of ischemia before revascularization. and neointimal proliferation. the goal of exercise testing is to development of restenosis. especial. In the early phase. with 25% of asymptomatic patients documented as (as outlined in section III).www. chest pain . Gibbons et al. or Rationale immunosuppressive therapy). in the presence of typical ischemia symptoms. and second or late phase. i. although there are insufficient data to justify recommending Moreover.. clinical end point reflects a complex underlying pathophysi- ology that involves various combinations of residual coro- Exercise Testing After Revascularization nary stenosis. hemody- ly if they are asymptomatic (3.org 42 ACC/AHA Practice Guidelines American Heart Association .259. espe.4. Exercise testing in an asymptomatic patient who has under- 1. Resting ECG abnormalities are fre- Patients who undergo myocardial revascularization should quent. surgery to a negative postoperative test result does correlate 2. graft occlusion. diabetes mellitus. but not exercise variables was predictive of outcome (264). the goal of exercise testing is to assist many persons experience silent ischemia (false-negative in evaluation and treatment of patients 6 months or more symptoms). 1. particularly in the setting of one-vessel disease. Exercise Testing After PTCAPCI while in patients undergoing either myocardial revascular- Restenosis remains the single major limitation of PCI. and exercise capacity.. in a fol- matic patients for restenosis. this requires a more sensitive test than the exercise siderations. In the cardiac pain after angioplasty (false-positive symptoms). Unfortunately. exercise testing may be used to dis- 2. In asymptomatic patients. Detection of restenosis in selected. In symptomatic patients. high-risk asympto. many patients complain of non- determine the immediate result of revascularization. ment of silent graft disease. decisions are based on not only the presence but the site and extent of ischemia. symptom status is an unreliable index to tion. although not all results have been After discharge for activity counseling and/or exercise favorable (261). with successful revascularization (263). 2002 American College of Cardiology Foundation . especially with venous conduits. and because management who have undergone coronary revascularization. incom. Because of concerns about the accuracy of training as part of cardiac rehabilitation in patients the exercise ECG in this group.e. Evaluation of patients with recurrent symptoms that tinguish between cardiac and noncardiac causes of recurrent suggest ischemia after revascularization.346. However. and if an imaging test is not incorporated in the study. return-to-work decisions (see section IV). The patients after percutaneous transluminal coronary test provides more useful information when the likelihood of angioplasty (PTCA) intervention (PCI) or coronary coronary disease progression is enhanced (e. the exercise ECG is less desirable than Class IIb stress imaging tests (262). there is concern about develop- matic patients within the first 12 months after percu. high-risk asympto. Exercise Testing Before and After Revascularization Exercise Testing After Coronary Artery Bypass Class I Graft Surgery 1. Documentation of baseline exercise capacity may be worth. with chronic established CAD tation. Routine. tions in which the culprit vessel must be defined. cially if the revascularized vessel supplies the posterior wall. Periodic monitoring of selected. after coronary bypass grafting. low-up study of events after exercise testing and evaluation plete coronary revascularization. worsens prognosis (276. bundle-branch block. hazardous occupations. MI. multivessel CAD. Examples middle-aged patients without other evidence of CAD. lar block or type I second-degree Wenckebach.acc. with sen. Whichever policy is followed. Table 25 summarizes the variability in predictive value of the 2. Some authorities have advocated routine 2. is to use a selective evaluation in patients considered to be at particularly high risk.American College of Cardiology Foundation . before and after PCI. The insensitivity of the exercise ECG portion of restenosis. 3 to 6 months) after PTCAPCI. previous sudden death. particular testing regimen after PCI. tined to develop restenosis.org Gibbons et al. PV. the use of an testing in this context.americanheart. which reflects in part patients considering increased physical activity or the different populations studied. The rationale of this approach is that atrial fibrillation).www. The presence of ischemia in these tests is predictive of In conclusion. several centers have reported success in probably reflects the high prevalence of one-vessel disease in performing exercise testing early (1 to 3 days) after PTCA this population.279). and CAD.278) or exercise echocar- Because residual plaque is responsible for a significant pro. (Level of cise ECG is an insensitive predictor of restenosis. Identification of appropriate settings in patients with tested later (for example. Evidence: C) . diography (6. participation in competitive sports. significantly less than the onset of restenosis by several months (417). Class I If the aim of exercise testing is to identify restenosis rather than predict its probability of occurrence. in addition to the benefit of early exercise testing dures performed and widespread variation in use of exercise for the prediction of subsequent restenosis. Evaluation of patients with known or suspected exer- functionally significant) one-vessel stenoses to lead to sig. compared with imaging techniques and its inability to local- ate predictor. Predictive Value of Exercise Electrocardiographic Testing for Identification of Restenosis After Percutaneous Transluminal Coronary Angioplasty Post-PTCA Restenosis PV+ PV– Author (year) n Clinical (m) (%) (%) (%) Definition of Restenosis Kadel268 (1989) 398 Consecutive Up to 6 33 66 75 >70% luminal diameter stenosis Honan269 (1989) 144 Post MI 6 40 57 64 >75% luminal diameter stenosis Schroeder270 (1989) 111 Asymptomatic 6 12 53 63 >70% luminal diameter stenosis Laarman271 (1990) 141 Asymptomatic 1 to 6 12 15 87 >50% luminal diameter stenosis el-Tamimi272 (1990) 31 Consecutive 6 45 100 94 Loss of >50% initial gain of lumen diameter Bengtson265 (1990) 200 Asymptomatic (n = 127) 6 44 46 63 >75% luminal diameter stenosis 200 Symptomatic (n = 66) 6 59 76 47 >75% luminal diameter stenosis Roth273 (1994) 78 1-vessel CAD 6 28 37 77 >50% luminal diameter stenosis Desmet274 (1995) 191 Asymptomatic 6 33 52 70 >50% luminal diameter stenosis PTCA indicates percutaneous transluminal coronary angioplasty. stent placement generally delays sitivities ranging from 40% to 55%. the lower sensitivity of the exercise ECG restenosis (266). Investigation of Heart Rhythm Disorders and exercise when unstable plaque exists may (at least theo- retically) risk provoke vessel occlusion. the exer. which the committee Class IIb favors. myocardial infarction. there are insufficient data to justify a exercise test within 1 to 3 days of angioplasty PCI may facil. predictive value. although the safety of this approach has not been established. rate-adaptive pacemakers. (Level of teria for restenosis. Evaluation of medical. nificant ischemia. Whereas ST-segment changes are a univari. surgical. Investigation of isolated ventricular ectopic beats in of controlling silent ischemia needs to be proved. those obtainable with SPECT (5. Despite the large numbers of proce- Moreover.www. PCI. ize disease limits its usefulness in patient management both sis proved to be ischemia on myocardial perfusion imaging. left mal left anterior descending disease. of patients who are likely to be at high risk include those with 2. patients may be 1. or diabetes mellitus. participation in competitive sports.277). proxi. Evaluation of congenital complete heart block in exercise test for restenosis (268-275). whether painful or silent. or ablative therapy in testing because restenosis is frequent and commonly induces patients with exercise-induced arrhythmias (including silent ischemia. The alternative approach. Investigation of prolonged first-degree atrioventricu- decreased left ventricular function. itate earlier return to work and daily living activities (267). False-negative results may be Class IIa caused by the failure of moderate (angiographically but not 1. coronary artery disease. 2002 American Heart Association . the frequency. ischemia. and suboptimal isolated ectopic beats in young patients considering PTCA PCI results. and the cri. because the prognostic benefit 1. cise-induced arrhythmias. the independent predictor at multivariate analy. right bundle-branch block.org ACC/AHA Practice Guidelines 43 Table 25. False-positive study results may be the Evidence: C) result of incomplete revascularization and angiographically unrecognized plaque fissures. supraventricular arrhythmias during exercise often display Cardiac Pacemakers. Prolonged tachycardia able. In patients taking dromes.www.3% incidence of arrhyth. sustained exercise-induced VT is associated imum) (287). an exercise response. however. Moreover. Using maximal exercise testing in patients at risk of ventricular various definitions. both in terms of patients (285). Exertional syncope due to titration of additional drugs for this purpose may be facilitat- tachycardias may reflect the presence of ischemia. However. be particularly useful in showing the benefits serve as an adjunct in the evaluation and treatment of these of sensor-triggered rate-adaptive pacing. Although it is sufficiently reproducible to may. The previous edition of the marked tachycardia because of their heightened adrenergic ACC/AHA guidelines for exercise testing (291) suggested state. and increased circulating catecholamines. mias that require cardioversion. the most common definition being failure rate for those with complex ectopy exceeds that for those to achieve 85% of age-predicted maximum heart rate (i. incompetence in patients with sinus node dysfunction. VT may be reproducibly induced during exer. with simple ectopy (281). atrioven. In adrenergic-dependent rhythm disturbances demonstrate an abnormal chronotropic response late during (including monomorphic VT and polymorphic VT related to exercise (53% being slow).293). absolute heart rate attained and the rate of increase of heart Supraventricular Arrhythmias. response early during exercise (74% being fast). the ventricular response Evaluation of Patients With Known or Suspected is governed by the atrioventricular node. Gibbons et al. 95% demonstrate an abnormal chronotropic a normal heart. has been used to unmask proarrhythmic responses. that exercise testing was inappropriate in most patients with exercise testing may be used to help evaluate the risk of a permanent pacemaker. the use of ic reserve used by stage II of the Bruce protocol (290). because the adrenergic state speeds conduction in the atrioventricular node and therefore reduces the area of Routine Iinvestigation of isolated ectopic beats in myocardium that is stimulated prematurely from the acces- young patients. In patients with atrial fibrillation. even in this population. tuning these devices (292. The use of exercise testing ed reproducibility. atrial fibrillation. and a normal test result does not negate the pos- with malignant ventricular arrhythmias is related to its limit. the development of adaptive rate than in the atrioventricular node.. the majority of patients long-QT syndromes). diagnostic standpoint. this response to exercise may be difficult to recog. according to the cause of the tachycardia. Moreover. The use of a heart rate response less than 100 with a high risk of sudden death (282). Syncope due to sinus node dysfunction. exercise testing response (which is seen in well-trained subjects with pre- may be of prognostic value in these patients: 12-month mor. In some syn. the mortality variously defined. intravenous drugs. tion with resting bradycardia and in patients who fail to make induced ectopy than in those with ectopy at rest only (280). such as right ventricular outflow tract tachycardia in medication. followed by delayed acceleration in very early exercise and The usefulness of exercise testing in patients with VT is vari. Use of exercise testing is therefore a useful pre. Effective rate control at rest does not nec- tricular block. both of which may be influenced fy those with CAD.acc. testing of this marker for sinus node dysfunction as being subopti- can be performed with low mortality and few lasting morbid mal. Patients developing rate. In patients with Wolff-Parkinson-White syndrome. and 84% cise testing.org Class III nize. Nonetheless.org 44 ACC/AHA Practice Guidelines American Heart Association . effective refractory period. some authors have reported chronotropic arrhythmia is associated with a 2. Abrupt loss of pre-excitation during exercise infers a testing with imaging may be problematic for the diagnosis of longer antegrade refractory period in the accessory pathway coronary disease. other ed by exercise testing.www. Exercise testing may distinguish infrequent. other testing is also required. In a series of 21 patients with . dominant parasympathetic tone) from sinus node dysfunc- tality is 3 times greater in persons exhibiting exercise. and the heart rate is Exercise-Induced Arrhythmias therefore dependent on the rate of repolarization and the Use of exercise testing in patients with syncope may identi. and the Ventricular Arrhythmias. A more complicated definition shown to be prognostically Although serious arrhythmias are uncommon in unselected significant (289) is the ratio between heart rate and metabol- populations undergoing exercise testing (283). and tachycardias may also be identified. often persists into the recovery period. sory pathway. 2002 American College of Cardiology Foundation . this remains true from a developing rapid ventricular response during atrial arrhyth. or resus. an exaggerated heart rate response. whereas others have identified the sensitivity and specificity citation (284). more than two standard deviations below age-predicted max- mic therapy. Indeed. essarily signify adequate rate control during exercise. although this is not usually the cause of by antiarrhythmic drugs used for rate control in patients with syncope. the exercise response being an important constituent in fine- However. The heart rate response to exercise in structural abnormalities that induce an abnormal cardiac atrial fibrillation comprises an initial reduction of heart rate response to stress. and exercise testing bpm with maximal exercise (288) is specific but insensitive. and even the combination of exercise mias. Thus. sibility of sinus node dysfunction. resting bradycardia with a normal exercise heart rate lude to electrophysiological study. The main limitation of exercise testing in patients this respect. In patients undergoing antiarrhyth. exercise testing has limited reproducibility in events. Chronotropic incompetence has been and in patients with exercise-induced ectopy. particularly if the patient is sedentary and the arrhythmia is Sinus Node Dysfunction.e. response to exercise (286). It is unlikely that a rapid pacing with various physiological sensors has led to study of ventricular response will occur at heart rates above this rate. ambulatory ECG monitoring may fail with atrial fibrillation demonstrate an abnormal chronotropic to supply the circumstances necessary for induction of VT.americanheart. Med Sci Sports Exerc. If the device has been implanted for APPENDIX 1: BORG SCALE FOR RATING ventricular fibrillation or fast VT. (343) studied a total of 915 consecutive abnormal blood pressure response destined to develop hyper. because they are both unpleasant and OBSTRUCTIVE CAD potentially hazardous (296). a formal exercise test may not be necessary. sinus rate crossover (295). . Table 26). Identification of such patients may allow preventive coronary artery bypass surgery who were referred to the measures that would delay or prevent the onset of this dis. CAD. however. and the required data The pediatric section published as part of the original 1997 could be obtained during a 6-minute walk (294). Before testing.acc.420). very hard Maximum Double product 2/13 15 20 Maximal systolic BP 1/12 8 *From Borg GA. Indeed. 1982.org ACC/AHA Practice Guidelines 45 single-lead VDD systems. The patients were greater than 214 mm Hg. left) and the newer 10-point category scale informative if the test is being performed to assess the risk of with ratio properties (right). the programmed detection interval of the device should be known. Reproduced with permission. Care should be taken to avoid FOR THE DIAGNOSIS OF unnecessary shocks. Morise generated the following logistic regression poor blood pressure control (421). electrocardiogram. 2002 American Heart Association . exercise laboratory at West Virginia University Medical ease. In asymptomatic normotensive subjects. this approach is tion (6 to 20. Additionally. In all of these situations. percentage of synchronized atrioventricular events and in evaluating the evolution of P-wave amplitude during exercise VII. The following examples of multivariable equations that can estimate the presence of angiographic CAD were chosen Evaluation of Hypertension because they have been validated in large populations. at a later date and is omitted from this document (including rillators (ICDs) may provoke arrhythmias or ICD discharge. patients without a history of prior myocardial infarction or tension. Exercise testing has been used to identify patients with Morise et al. TESTING IN CHILDREN AND ferent pacing modes with respect to their influence on exer. the prevalence of disease in this population was (419. exercise testing was helpful in hypertension may cause exercise-induced ST depression in evaluating the quality of atrial sensing best expressed by the the absence of atherosclerosis (422). a number of studies have compared dif. Exercise tolerance is decreased in patients with 41%.www. ACC/AHA Guidelines on Exercise Testing will be updated Exercise testing in patients with implantable cardiac defib. PEDIATRIC TESTING: EXERCISE (418). and the test can be terminated as the heart rate approaches 10 bpm below Table A1 shows the original scale for rating perceived exer- the detection interval of the device. BP indicates blood pressure. coronary artery disease.americanheart. ADOLESCENTS cise capacity. very light 0.14:377–381. very strong Maximal heart rate 16/28 57 (almost maximum) Exercise capacity 11/24 46 18 Exercise-induced angina 11/26 42 19 Very. All patients had coronary angiogra- during exercise. and ECG. the ICD may be reprogrammed to a faster rate for the test or temporarily deactivated (usually by APPENDIX 2: MULTIVARIABLE ANALYSIS superimposition of a magnet). or elevated systolic or diastolic classified as having disease if there was at least a 50% lumen blood pressure at 3 minutes into recovery is associated with diameter narrowing in 1 or more vessels.www.American College of Cardiology Foundation . very weak (just Gender 20/20 100 noticeable) Chest pain symptoms 17/18 94 8 1 Very weak Age 19/27 70 9 Very light 2 Weak (light) Elevated cholesterol 8/13 62 10 3 Moderate Diabetes mellitus 6/14 43 11 Fairly light 4 Somewhat strong Smoking history 4/12 33 12 5 Strong (heavy) Abnormal resting ECG 4/17 24 13 Somewhat hard 6 Hypertension 1/8 13 14 7 Very strong Family history of CAD 0/7 0 15 Hard 8 ST-segment slope 14/22 64 16 9 ST-segment depression 17/28 61 17 Very hard 10 Very. Center between June 1981 and December 1994 for evalua- ed exercise systolic and diastolic blood pressure response tion of coronary disease. When this criterion significant increased long-term risk of hypertension was used. In patients with slower pro- grammed detection rates. exaggerated peak systolic blood pressure phy within 3 months of the exercise test. and severe systemic equation: Table A2 Table A1* Predictor 15-Grade Scale 10-Grade Scale Variables Significant (%) 6 0 Nothing 7 Very.5 Very.org Gibbons et al. an exaggerat. this rate will normally PERCEIVED EXERTION exceed that attainable during sinus tachycardia. Smoking was coded as 2 for current smoking.acc. Deleted during update. Wechsler AS.22(7):2033-2054. MPH. Negative ST diac surgery: a report of the American College of was coded as 1 if ST depression was less than 1 mm depres. coded as 0 for women. Ryan TJ. Thompson. Parker JO. Bonow RO. 2. and coef. Cheitlin MD. Resting 1.61 + (0.11 × Cardiovascular Procedures (Committee on Percutaneous symptoms) – (0. A report of the ficients are listed below: American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic 1. Gwen C. O’Rourke RA. and no pain) and coded with values of 4. Science and Medicine 2.02 × maximal heart rate) American Heart Association Sidney C. Anderson JL. Cardiology/American Heart Association Task Force on Practice sion horizontal or downsloping or ST depression was less Guidelines (Committee on Perioperative Cardiovascular than 1.17(3):543-89.33 × number of risk factors) Paula M. Sheldon WC. 2002 American College of Cardiology Foundation . Weaver WD. MLS. BD. Twiss RD. J Am Coll Cardiol. Ryan TJ. Taubert. (0. and y are variable values as follows: STAFF –0. Exercise angina was coded as 1 Cardiology/American Heart Association Task Force on for presence and –1 for absence. Riegel BJ.05 × METs) – (0. Project/Publication Manager (0. and the preva- the American College of Cardiology/American Heart Association lence of disease according to this criterion was 64%. Senior Research Analyst – (0. Spencer WH III. ST-T–wave abnormalities.02 × ST slope) – (0. Librarian sion) + (1.28 × smoking) – (1.02 × maximal Transluminal Coronary Angioplasty). Detrano in the preparation of Tables 7 through 12.64 × symptoms) + (0. Detrano et al.65 × diabetes) + American College of Cardiology (0. and 1. McCallister Gender was coded as 1 for female and –1 for male. Gibbons RJ. Table A2 shows the results of 24 studies that used multivari.40 × resting ECG)]) + (0.americanheart. Fleisher LA. Guidelines for clini- able techniques to predict disease presence (30 equations cal use of cardiac radionuclide imaging: report of the American . Braniff BA. and obesity (body mass index greater than or equal to 27 kg/m2). MD. (23) included 3549 patients from eight insti. ECG was coded as 0 if normal and 1 if there were QRS or Spittell JA Jr. Pigman. PhD. Deleted during update. contributed significant and independent information to dis.12 + (4. King SB III. Califf RM. Chaitman BR. Califf RM. 1996. et al. Kathryn A. nonanginal pain. Cohen LS. Ritchie JL. Ritchie JL. Kouchoukos NT.46 × body surface area) + Dawn R. 3.33 × gender) + (0.025 × age) – (0.50 × estrogen) + (0. respectively. and –1 for estrogen positive (premenopausal or taking estrogen).6 × gender) – (0.5 × [–3.5 mm upsloping.36 × exercise-induced angina) + 1993. Hiratzka LF. Smith SC Jr. Harrell FE Jr. Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Coronary Artery Bypass Graft APPENDIX 3 Surgery).27:910-948. Kereiakes DJ. cise testing and angiography between 1978 and 1989. Phoubandith. 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