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Dobutamine stress echocardiography is a valuable diagnostic test for predischarge risk assessment in low-risk chest pain patients
SCREENING/PROGNOSIS
Dobutamine stress echocardiography is a valuable diagnostic test for predischarge risk assessment in low-risk chest pain patients Abstracted from: Bholasingh R, Cornel JH, Kamp O et al. Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponinT. J Am Coll Cardiol 2003; 41: 596 ^ 602.
BACKGROUND There are several strategies available for stratifying people with high and low cardiovascular risk presenting with chest pain and a normal or nondiagnostic ECG. Dobutamine stress echocardiography (DSE) is a sensitive and speci¢c means of detecting ischemia in particular at-risk groups, such as in people with known or suspected coronary artery disease or postmyocardial infarction. However, the predischarge prognostic value of DSE for risk-strati¢cation of lowrisk people remains unclear. OBJECTIVE To evaluate the prognostic value of a predischarge DSE in people with low-risk chest pain, as de¢ned by a normal or nondiagnostic ECG and a negative serial cardiac troponinT. SETTING Three hospitals in the Netherlands; time frame not speci¢ed. METHOD Double-blinded multicentre study. PARTICIPANTS Three hundred and seventy-seven people presenting at the emergency room within 6 hours of the onset of chest pain with a normal or nondiagnostic ECG and a negative serial cardiac troponinT (peak value o0.06 ng/mL at 6 and 12 hours after the onset of symptoms). Exclusion criteria were being younger than18 years; incapable of giving informed consent, and having any of the following conditions on admission: unstable coronary artery disease, atrial ¢brillation, conduction disturbances, severe uncontrolled hypertension, severe heart failure, cardiomyopathy, resuscitation, serious noncardiac disease and pregnancy.
doi:10.1016/S1361-2611(03)00067- 8
INTERVENTION People underwent DSE within 24 hours of admission (DSE results were scored as either positive or negative for ischemia, where a positive result was de¢ned as the occurrence of new wall motion abnormality in a minimum of one segment). People were discharged on aspirin and a beta-blocker until the ¢rst outpatient visit 4 weeks later. Follow-up occurred to 6 months. MAIN OUTCOMES The primary outcome was the combination of cardiac death, non-fatal acute myocardial infarction and rehospitalization for unstable angina. The secondary outcome was coronary revascularization. MAIN RESULTS Twenty-six patients (6.9%) had a positive DSE result. A positive DSE had independent prognostic value both for the primary outcome (OR 6.2; 95% CI, 1.6 to 24.3) and for a combined primary and secondary outcome (OR 7.1; 95% CI, 2.5 to 20.2). AUTHORS’ CONCLUSIONS Predischarge DSE has prognostic value in low-risk chest pain patients with a normal or nondiagnostic ECG and a negative serial cardiac troponin T. Sources offunding: Dutch Heart Foundation. Correspondence to: Dr R J de W|nter, Academic Medical Center, Department of Cardiology, Room B2-137, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Email: [email protected] Abstract provided by Bazian Ltd, London
Evidence-based Cardiovascular Medicine (2003) 7, 203^205
203
Commentary 1 Due to the marked difference in outcome between patients with non-cardiac chest pain and those with acute coronary syndromes, investigators have developed decision rules for determining who is low risk and can be safely discharged from the emergency department. In the early 1990s, Goldman et al1 found that patients without hypotension, rales, or known unstable ischemic heart disease (defined as a worsening of previously stable angina, the new onset of post-infarction angina or angina after a coronary-revascularization procedure, or pain that was the same as that associated with a prior myocardial infarction) had a 3-day risk of major cardiac events of only 0.2%. Now that more sensitive troponin assays are available, it is likely that patients with even lower short-term event rates can be identified. In the hope of reducing long-term events, stress tests have been used to identify those with obstructive coronary disease. These tests use exercise or medication to induce either ischemia that can be detected by ECG (ST-T changes) and echocardiography (wall motion), or perfusion abnormalities that can be detected with single-photon emission computed tomography (SPECT).The American College of Cardiology and the American Heart Association currently recommend one of these tests be performed within 72 hours of discharge following initial evaluation for suspected myocardial ischemia, but do not specify which test should be used.2 The study by Bholasingh et al demonstrates that peri-discharge dobutamine stress echocardiography can identify a group of patients with a very low long-term (6 -month) event rate. Only 1 of 351 (0.3%) died or had a non-fatal myocardial infarction during follow-up. A methodological strength of the study is the double-blind design where the stress test result should not bias the outcome. However, the degree to which blinding can (or should) be maintained for patients with extensive new wall motion abnormalities or ECG changes of ischemia is unclear. Given these results, should dobutamine echocardiography now become the standard evaluation for patients with suspected acute coronary syndromes? Although the dobutamine echocardiography has been shown to be safe and effective, there is no convincing evidence that it is superior in prognostic or diagnostic value to exercise echocardiography. Because the latter also provides information regarding functional capacity, exercise stress should be used when practical. For patients unable to exercise, the alternatives to dobutamine echocardiography include dobutamine, dipyridamole or adenosine SPECT. Although few head to head comparisons have been performed, a recent meta-analysis3 found that dobutamine echo has a similar sensitivity for detecting coronary disease compared with dobutamine SPECT (80%
204
Evidence-based Cardiovascular Medicine (2003) 7, 203^205
and 82%). However the specificity of echocardiography is higher (84% v 75%). Dipyridamole and adenosine SPECT had high sensitivities (89% to 90%) but low specificities (65% to 75%). Studies of nuclear stress tests have shown prognostic value although follow-up is not as long in the current study. An emergency department protocol using the ECG, troponin, physician judgment and exercise or pharmacologic SPECT was able to identify a subgroup with only 0.2% risk of 30 -day acute coronary syndromes.4 Thus, stress SPECT and echocardiography are not clearly different in their prognostic value. Because nuclear and echocardiography stress tests are highly reader dependent, local expertise should be considered when determining the appropriate test. As the authors point out, the cost difference (lower for echocardiography) may be the deciding factor for many centers. Finally, does the test need to be done prior to discharge?There are few studies examining the safety of immediate versus 72hour stress testing. Given that those patients at very low risk for the next 72 hours can be identified, it is reasonable to wait for stress testing if immediate testing is logistically difficult. Paul A Heidenreich MD, MS VA Palo Alto Healthcare System Stanford University, Palo Alto California USA
Literature cited 1. Goldman L, Cook EF, Johnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to emergency departments with acute chest pain. N Engl J Med1996; 334: 1498 ^1504. 2. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA guidelines for the management of patients with AMI and non-STsegment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2000; 36: 970 ^1062. 3. Kim C, KwokYS, Heagerty P, Redberg R. Pharmacologic stress testing for coronary disease diagnosis: A meta-analysis. Am Heart J 2001; 142: 934 ^944. 4. Fesmire FM, Hughes AD, Fody EP, Jackson AP, Fesmire CE, Gilbert MA, Stout PK, Wojcik JF, Wharton DR, Creel JH. The Erlanger chest pain evaluation protocol: a one-year experience with serial 12-lead ECG monitoring, two-hour delta serum marker measurements, and selective nuclear stress testing to identify and exclude acute coronary syndromes. Ann Emerg Med 2002; 40: 584 ^594.
Commentary 2 Acute chest pain often proves to be of non-cardiac origin. The challenge in people presenting with acute chest pain is urgently to identify whether the pain is due to ischemic heart disease, which is associated with high morbidity and mortality, especially if diagnosis is delayed. Hospital admissions for evaluation of acute chest pain place an enormous economic burden on the public health system. Assessment tools to guide clinical management include clinical presentation, markers of myocardial injury, and exercise electrocardiography. Previous studies have shown that cardiac troponin is a strong predictor for adverse outcome in high-risk patients with acute coronary syndromes. However, negative serial troponin results do not by themselves exclude significant coronary artery disease. Dobutamine stress echocardiography (DSE) is a sensitive, safe and feasible procedure for assessing the presence and extent of coronary artery disease. DSE is particularly useful in patients who are unable to undertake adequate diagnostic exercise testing. This prospective, multicenter, double-blind randomized trial in low-risk patients suggests that major cardiovascular complications can be estimated by pre-discharge DSE. In this study, 377 people presenting with acute chest pain to the emergency room had negative serial troponin and underwent DSE. The study demonstrated the capability of DSE to classify low-risk patients into subgroups with higher and lower risk for subsequent cardiac events.
Importantly, DSE yielded a high negative predictive value of 96%, while the positive predictive value was only a modest 31% in the patient cohort studied. According to Bayes’ theorem, the likelihood of a positive test result is not only determined by the accuracy of the test, but also the probability of the disease in the patient studied. Even a very accurate cardiovascular test with high sensitivity and specificity would, therefore, have little power to detect disease in a population with low disease prevalence. Although multivariate analysis found that pre-discharge DSE had independent prognostic value in low-risk chest pain patients, routine screening will revise the probability of disease only slightly. The evaluation of patients with acute chest pain places an enormous economic burden on the health-care system. Since no analysis on cost-effectiveness was performed, it remains to be seen whether the pre-discharge DSE in low-risk patients is able to save resources. Another important consideration relates to the generalizability of the proposed strategy. As mentioned by the authors, performance and interpretation of DSE requires adequate training and skills.The study was conducted in large medical centers with expertise in non-invasive cardiology and the feasibility of this strategy in smaller hospitals is unknown. Roland R. Brandt MD, FACC Christian W. Hamm MD, PhD, FACC Kerckhoff Heart Center Bad Nauheim Germany
Evidence-based Cardiovascular Medicine (2003) 7, 203^205
205
Dobutamine stress echocardiography is a valuable diagnostic test for predischarge risk assessment in low-risk chest pain patients Abstracted from: Bholasingh R, Cornel JH, Kamp O et al. Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponinT. J Am Coll Cardiol 2003; 41: 596 ^ 602.
BACKGROUND There are several strategies available for stratifying people with high and low cardiovascular risk presenting with chest pain and a normal or nondiagnostic ECG. Dobutamine stress echocardiography (DSE) is a sensitive and speci¢c means of detecting ischemia in particular at-risk groups, such as in people with known or suspected coronary artery disease or postmyocardial infarction. However, the predischarge prognostic value of DSE for risk-strati¢cation of lowrisk people remains unclear. OBJECTIVE To evaluate the prognostic value of a predischarge DSE in people with low-risk chest pain, as de¢ned by a normal or nondiagnostic ECG and a negative serial cardiac troponinT. SETTING Three hospitals in the Netherlands; time frame not speci¢ed. METHOD Double-blinded multicentre study. PARTICIPANTS Three hundred and seventy-seven people presenting at the emergency room within 6 hours of the onset of chest pain with a normal or nondiagnostic ECG and a negative serial cardiac troponinT (peak value o0.06 ng/mL at 6 and 12 hours after the onset of symptoms). Exclusion criteria were being younger than18 years; incapable of giving informed consent, and having any of the following conditions on admission: unstable coronary artery disease, atrial ¢brillation, conduction disturbances, severe uncontrolled hypertension, severe heart failure, cardiomyopathy, resuscitation, serious noncardiac disease and pregnancy.
doi:10.1016/S1361-2611(03)00067- 8
INTERVENTION People underwent DSE within 24 hours of admission (DSE results were scored as either positive or negative for ischemia, where a positive result was de¢ned as the occurrence of new wall motion abnormality in a minimum of one segment). People were discharged on aspirin and a beta-blocker until the ¢rst outpatient visit 4 weeks later. Follow-up occurred to 6 months. MAIN OUTCOMES The primary outcome was the combination of cardiac death, non-fatal acute myocardial infarction and rehospitalization for unstable angina. The secondary outcome was coronary revascularization. MAIN RESULTS Twenty-six patients (6.9%) had a positive DSE result. A positive DSE had independent prognostic value both for the primary outcome (OR 6.2; 95% CI, 1.6 to 24.3) and for a combined primary and secondary outcome (OR 7.1; 95% CI, 2.5 to 20.2). AUTHORS’ CONCLUSIONS Predischarge DSE has prognostic value in low-risk chest pain patients with a normal or nondiagnostic ECG and a negative serial cardiac troponin T. Sources offunding: Dutch Heart Foundation. Correspondence to: Dr R J de W|nter, Academic Medical Center, Department of Cardiology, Room B2-137, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Email: [email protected] Abstract provided by Bazian Ltd, London
Evidence-based Cardiovascular Medicine (2003) 7, 203^205
203
Commentary 1 Due to the marked difference in outcome between patients with non-cardiac chest pain and those with acute coronary syndromes, investigators have developed decision rules for determining who is low risk and can be safely discharged from the emergency department. In the early 1990s, Goldman et al1 found that patients without hypotension, rales, or known unstable ischemic heart disease (defined as a worsening of previously stable angina, the new onset of post-infarction angina or angina after a coronary-revascularization procedure, or pain that was the same as that associated with a prior myocardial infarction) had a 3-day risk of major cardiac events of only 0.2%. Now that more sensitive troponin assays are available, it is likely that patients with even lower short-term event rates can be identified. In the hope of reducing long-term events, stress tests have been used to identify those with obstructive coronary disease. These tests use exercise or medication to induce either ischemia that can be detected by ECG (ST-T changes) and echocardiography (wall motion), or perfusion abnormalities that can be detected with single-photon emission computed tomography (SPECT).The American College of Cardiology and the American Heart Association currently recommend one of these tests be performed within 72 hours of discharge following initial evaluation for suspected myocardial ischemia, but do not specify which test should be used.2 The study by Bholasingh et al demonstrates that peri-discharge dobutamine stress echocardiography can identify a group of patients with a very low long-term (6 -month) event rate. Only 1 of 351 (0.3%) died or had a non-fatal myocardial infarction during follow-up. A methodological strength of the study is the double-blind design where the stress test result should not bias the outcome. However, the degree to which blinding can (or should) be maintained for patients with extensive new wall motion abnormalities or ECG changes of ischemia is unclear. Given these results, should dobutamine echocardiography now become the standard evaluation for patients with suspected acute coronary syndromes? Although the dobutamine echocardiography has been shown to be safe and effective, there is no convincing evidence that it is superior in prognostic or diagnostic value to exercise echocardiography. Because the latter also provides information regarding functional capacity, exercise stress should be used when practical. For patients unable to exercise, the alternatives to dobutamine echocardiography include dobutamine, dipyridamole or adenosine SPECT. Although few head to head comparisons have been performed, a recent meta-analysis3 found that dobutamine echo has a similar sensitivity for detecting coronary disease compared with dobutamine SPECT (80%
204
Evidence-based Cardiovascular Medicine (2003) 7, 203^205
and 82%). However the specificity of echocardiography is higher (84% v 75%). Dipyridamole and adenosine SPECT had high sensitivities (89% to 90%) but low specificities (65% to 75%). Studies of nuclear stress tests have shown prognostic value although follow-up is not as long in the current study. An emergency department protocol using the ECG, troponin, physician judgment and exercise or pharmacologic SPECT was able to identify a subgroup with only 0.2% risk of 30 -day acute coronary syndromes.4 Thus, stress SPECT and echocardiography are not clearly different in their prognostic value. Because nuclear and echocardiography stress tests are highly reader dependent, local expertise should be considered when determining the appropriate test. As the authors point out, the cost difference (lower for echocardiography) may be the deciding factor for many centers. Finally, does the test need to be done prior to discharge?There are few studies examining the safety of immediate versus 72hour stress testing. Given that those patients at very low risk for the next 72 hours can be identified, it is reasonable to wait for stress testing if immediate testing is logistically difficult. Paul A Heidenreich MD, MS VA Palo Alto Healthcare System Stanford University, Palo Alto California USA
Literature cited 1. Goldman L, Cook EF, Johnson PA, Brand DA, Rouan GW, Lee TH. Prediction of the need for intensive care in patients who come to emergency departments with acute chest pain. N Engl J Med1996; 334: 1498 ^1504. 2. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA guidelines for the management of patients with AMI and non-STsegment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2000; 36: 970 ^1062. 3. Kim C, KwokYS, Heagerty P, Redberg R. Pharmacologic stress testing for coronary disease diagnosis: A meta-analysis. Am Heart J 2001; 142: 934 ^944. 4. Fesmire FM, Hughes AD, Fody EP, Jackson AP, Fesmire CE, Gilbert MA, Stout PK, Wojcik JF, Wharton DR, Creel JH. The Erlanger chest pain evaluation protocol: a one-year experience with serial 12-lead ECG monitoring, two-hour delta serum marker measurements, and selective nuclear stress testing to identify and exclude acute coronary syndromes. Ann Emerg Med 2002; 40: 584 ^594.
Commentary 2 Acute chest pain often proves to be of non-cardiac origin. The challenge in people presenting with acute chest pain is urgently to identify whether the pain is due to ischemic heart disease, which is associated with high morbidity and mortality, especially if diagnosis is delayed. Hospital admissions for evaluation of acute chest pain place an enormous economic burden on the public health system. Assessment tools to guide clinical management include clinical presentation, markers of myocardial injury, and exercise electrocardiography. Previous studies have shown that cardiac troponin is a strong predictor for adverse outcome in high-risk patients with acute coronary syndromes. However, negative serial troponin results do not by themselves exclude significant coronary artery disease. Dobutamine stress echocardiography (DSE) is a sensitive, safe and feasible procedure for assessing the presence and extent of coronary artery disease. DSE is particularly useful in patients who are unable to undertake adequate diagnostic exercise testing. This prospective, multicenter, double-blind randomized trial in low-risk patients suggests that major cardiovascular complications can be estimated by pre-discharge DSE. In this study, 377 people presenting with acute chest pain to the emergency room had negative serial troponin and underwent DSE. The study demonstrated the capability of DSE to classify low-risk patients into subgroups with higher and lower risk for subsequent cardiac events.
Importantly, DSE yielded a high negative predictive value of 96%, while the positive predictive value was only a modest 31% in the patient cohort studied. According to Bayes’ theorem, the likelihood of a positive test result is not only determined by the accuracy of the test, but also the probability of the disease in the patient studied. Even a very accurate cardiovascular test with high sensitivity and specificity would, therefore, have little power to detect disease in a population with low disease prevalence. Although multivariate analysis found that pre-discharge DSE had independent prognostic value in low-risk chest pain patients, routine screening will revise the probability of disease only slightly. The evaluation of patients with acute chest pain places an enormous economic burden on the health-care system. Since no analysis on cost-effectiveness was performed, it remains to be seen whether the pre-discharge DSE in low-risk patients is able to save resources. Another important consideration relates to the generalizability of the proposed strategy. As mentioned by the authors, performance and interpretation of DSE requires adequate training and skills.The study was conducted in large medical centers with expertise in non-invasive cardiology and the feasibility of this strategy in smaller hospitals is unknown. Roland R. Brandt MD, FACC Christian W. Hamm MD, PhD, FACC Kerckhoff Heart Center Bad Nauheim Germany
Evidence-based Cardiovascular Medicine (2003) 7, 203^205
205