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Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain
International Journal of Cardiology 75 (2000) 239–243 www.elsevier.com / locate / ijcard
Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain a, b a Filippo Maria Sarullo MD *, Pietro Di Pasquale MD , Giuseppe Orlando MD , Giuseppe Buffa MD a , Sergio Cicero MD a , Antonino Mario Schillaci MD a , Antonio Castello MD a a
Division of Cardiology, Buccheri La Ferla Fatebenefratelli Hospital, Via S. Puglisi n.15, 90143 Palermo, Italy b Division of Cardiology, ‘‘ Paolo Borsellino’’, G.F. Ingrassia Hospital, Palermo, Italy Received 14 January 2000; received in revised form 30 May 2000; accepted 13 June 2000
Abstract It is common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study evaluates the safety and efficacy of immediate ETT for patients admitted to the hospital with acute chest pain. One hundred and ninety non-consecutive low-risk patients admitted to the hospital from emergency department with acute chest pain underwent ETT using Bruce protocol immediately on admission to the hospital (median time 165130 min). Fifty-seven (30%) patients had positive exercise electrocardiograms, 44 (77.2%) of whom had significant coronary narrowing by angiography. An uncomplicated anterior non-Q-wave AMI was diagnosed in one patient. One hundred and eleven (58.4%) patients had negative and 22 (11.6%) patients had non-diagnostic exercise electrocardiograms. Of these 133 patients, 86 (64.7%) were discharged immediately after ETT, 19 (14.3%) were discharged within 24 h, and 28 (21%) were discharged after 24 h of observation. There were no complications from ETT. During the 1766 months follow-up no patients died, and only eight (7.2%) patients with negative ETT experienced a major cardiac event (one AMI and seven angina). In conclusion, our results suggest that immediate ETT of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission, is effective in further stratifying this group into those who can be safety discharged immediately and those who require hospitalization. 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Exercise treadmill testing; Emergency department; Acute chest pain
1. Introduction Patients admitted to the emergency room with chest pain of suspected cardiac etiology could be identified on the basis of symptoms, coronary risk factors, physical examination, and the electrocar*Corresponding author. Tel.: 139-091-342-336; fax: 139-091-477265. E-mail address: [email protected] (F.M. Sarullo).
diogram (ECG) [1,2]. The coronary event rate in this group is as low as 5% [2]. Nevertheless, remains common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study assesses the use and safety of immediate ETT for selected low-risk patients admitted to the hospital with chest pain of suspected cardiac etiology.
0167-5273 / 00 / $ – see front matter 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00338-7
240
F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
2. Materials and methods
2.1. Patient population All patients aged .30 years who presented to the emergency department (ED) of the Buccheri La Ferla Fatebenefratelli Hospital between July 1995 and December 1996 with a chief complaint of anterior, precordial, or left lateral chest pain unexplained by local trauma or chest X-ray abnormalities were eligible for the study. From this population, 190 low-risk patients were selected, estimating the likelihood of significant coronary artery disease with Pryor normogram [3]. This analysis was based on age, gender, history of diabetes mellitus, systemic hypertension, hypercholesterolemia, tobacco use, typical or atypical angina pectoris, and on electro-cardiogram analysis. The likelihood of significant coronary artery disease was 1365%. Patients with ECGs diagnostic of infarction or ischemia were excluded as were patients with ST-segment and T-wave changes that would preclude accurate interpretation of the exercise ECG. The presence of persistent chest pain did not preclude ETT. Evaluation in the ED included history, physical examination, bilateral arm blood pressure measurements, chest roentgenogram, 12-lead ECG, Doppler echocardiography, cardiac enzyme measurements (creatine kinase-MB, troponin I and myoglobin) in ED and this after 2–4 h admission to the hospital [4].
2.2. Exercise protocol ETT was performed using continuous 12-lead electrocardiographic monitoring and a maximal or symptom-limited treadmill testing, Bruce protocol (Marquette Max 1, Jupiter, FL, USA). ETT was performed as soon as possible after the emergency room physician’s decision to admit the patient but no later than 5 h after admission. In all cases, ETT was performed after report that two cardiac enzyme measurements were normal. Exercise was terminated for electrocar-diographic changes diagnostic of ischemia (.1 mm horizontal or downsloping ST-segment depression or elevation 80 ms after the J point), significant arrhythmia, systolic blood pressure decrease of .10 mmHg, or significant symptoms. A non-diagnostic test was defined as a negative exercise
ECG with a peak heart rate ,85% of age-predicted maximal heart rate. Experienced staff cardiologists interpreted the exercise tests. The Human Studies Committee of the Buccheri La Ferla Fatebenefratelli Hospital approved this protocol. Each subject gave written informed consent.
2.3. Follow up Outcome data were available for all patients. Follow up was attempted for a minimum of 12 months. Chart review and telephone interviews for consenting patients were used to contact the patients or their relatives. In the follow-up interviews, patients were asked about additional visits to the emergency room because of chest pain, re-admissions to the hospital, and any other cardiac events. Events were defined as acute myocardial infarction (AMI), cardiac death, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG). In every patient was considering only the first event. The follow-up of patients submit to myocardial revascularization was stopped since to perform PTCA or CABG.
2.4. Statistical analysis Results are expressed as the mean6standard deviation (S.D.). Data were analysed by the two-tailed T-test to identify differences between the groups. Nominal data were analysed by the Chi-square test or Fisher’s test. Differences were considered significant at a P-value ,0.05.
3. Results
3.1. Patient characteristics One hundred and ninety patients underwent early ETT between July 1995 and December 1996 (Table 1). There were no significant differences between men and women except for diabetes mellitus, which was more common in women and cigarette smoking which was more common in men.
F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
241
Table 1 Study group demographics
Number of patients Mean age (years) Systemic hypertension b Diabetes mellitus Dyslipidemia c Cigarette smoking Family history of CAD d
Total
Men
Women
P-value a
190 5769 78 (41%) 35 (18.4%) 32 (16.8%) 81 (42.6%) 18 (9.5%)
127 (66.8%) 5668 51 (40%) 14 (11%) 20 (15.7%) 66 (52%) 12 (9.5%)
63 (33.2%) 5867 27 (42.8%) 21 (33.3%) 12 (19%) 15 (23.8%) 6 (9.5%)
0.69 n.s. n.s. 0.005 n.s. 0.022 n.s.
a
Comparisons between men and women. Systolic blood pressure .140 mmHg, diastolic blood pressure .90 mmHg. c Serum cholesterol .200 mg / dl, low-density lipoprotein cholesterol .130 mg / dl. d CAD5coronary artery disease in a first-degree relative ,55 years-of-age. b
3.2. Exercise treadmill testing results Median time from hospital admission to ETT was 165630 min. In 111 (58.4%) patients ETT was negative, in 57 (30%) was positive, and in 22 (11.6%) was non-diagnostic (Table 2). There were no complications in the ETTs. All patients with positive exercise tests underwent in next time (312 days) to cardiac catheterization, that confirm the diagnosis of coronary artery disease in 44 (77.2%) patients. Three patients had 3-vessel disease, 12 had 2-vessel disease, and 29 had 1-vessel disease. A final diagnosis of anterior non-Q-wave AMI was reached in one patient, and seven patients had unstable angina based on history and clinical course. The patient with an anterior non-Q-wave infarction was a 49-year-old man who presented with chest pain that woke him from work and resolved while on route to the emergency room. History was significant for cigarette smoking and dyslipidemia, and his initial ECG was interpreted as having early repolarization. During ETT, he had 2 mm ST-segment elevation in V2–V5 leads with chest pain, which resolved rapidly after
nitrate per os during post-exercise recovery. Serial ECGs, echocardiograms and cardiac enzyme measurements revealed an anterior non-Q-wave AMI. The serum creatine kinase peaked at 16 h after presentation. Cardiac catheterization demonstrated a thrombus in the proximal descending coronary artery. The hospital course was uncomplicated and he underwent successful PTCA before discharge. Of the 111 patients with negative ETTs, 76 (68.4%) were discharged directly after their tests, 13 (11.8%) were discharged in ,24 h, and 22 (19.8%) completed a minimum 24-h observation period in the telemetry unit. No AMI were found. Of the 22 patients with non-diagnostic ETTs, ten (45.5%) were discharged subsequent to a low-risk immediate ETT (no ischemic changes, with 70–84% of age-predicted maximal heart rate), six (27.3%) were discharged in ,24 h, and six (27.3%) completed a minimum 24-h observation period in the telemetry unit with serial ECGs, and four sets of fractionated cardiac enzyme measurements. No AMIs were diagnosed. All patients in next time (865 days) underwent pharmacological stress testing with dipyridamole (Tc-99m-tetrofosmin
Table 2 Exercise test results
Exercise capacity (min) Peak double product METS c Double product b angina Double product ⇓ ST 1 mm a
ETT a positive (n557)
ETT negative or non-diagnostic (n5133)
P
6.0062.24 20.71465132 6.361.8 18.57863314 18.88164371
8.3962.32 27.31864872 9.262.3
,0.0001 ,0.0001 ,0.0001
ETT5exercise treadmill testing. Double product5heart rate3systolic blood pressure. c METS5metabolic equivalent. b
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F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
SPECT myocardial perfusion images) that were normal, and one patient had positive results on myocardial stress scintigraphy followed by coronary arteriography and PTCA for proximal circumflex disease.
3.3. Post hospital follow-up
Table 3 Follow-up results
Death AMI a Unstable Angina CABG b PTCAc
ETT positive (n557)
ETT negative (n5111)
ETT non-diagnostic (n522)
0 1 2 15 29
0 1 (0.9%) 7 (6.3%) 0 0
0 0 1 (4.5%) 0 0
(1.8%) (3.5%) (26.3%) (50.9%)
a
AMI5acute myocardial infarction. CABG5coronary artery by-pass grafting. c PTCA5percutaneous transluminal coronary angioplasty. b
Follow-up data of .12 months (range from 3 to 32, mean 1766) were available in all patients. In this time no evidence of mortality for these patients were detected. All patients with positive ETTs underwent further study (angiography) as previously describer. Fifteen (26.3%) patients were underwent to CABG, 29 (50.9%) to PTCA. One (1.8%) patient with no significant coronary artery disease on angiography sustained a non-fatal inferior AMI at 7 months. Repeat angiography demonstrated a thrombus in the proximal rigth coronary artery. In two (3.5%) patients were diagnosed unstable angina 2 and 5 months after the ETT. The remaining ten (17.5%) patients were stable at follow-up. Of the 22 patients with non-diagnostic tests, five underwent further evaluation and one (4.5%) had a diagnosis of unstable angina after 5 months after ETT, and angiography demonstrated a significant coronary artery disease of the circumflex artery. The remainder patients were stable at follow-up. Of the 111 patients with negative ETTs, eight (7.2%) experienced a cardiac event (one a non-fatal inferior-lateral AMI after 10 months (STsegment elevation with concomitant CK, CK-MB, TnI alterations, and seven had a diagnosis of unstable angina, 4–11 months after ETTs). The diagnoses in these seven patients were verified directly because the patients were hospitalized in our division of cardiology. They showed at entry ST-segment depression at entry ECG and four patients positive TnI determination after 4 h from admission. The other three patients were TnI negative and in the subsequent ETT (3 days after admission) showed ST-segment changes which judged as ischemic. All these patients were referred to perform coronarography that confirmed the ischemic nature of chest pain and ECG changes. The remaining 103 patients were stable at follow-up (Table 3).The sensitivity and specificity of a positive or inconclusive ETT for cardiac events in 1766 months were 84 and 92.5% respectively. Patients
with a negative ETT had a 92.8% probability of not having an event in 1766 months.
4. Discussion The results of this study confirm that ETT is a safe procedure in low-risk patients with acute chest pain [6–14], and that patients who have negative tests have an excellent 1766 months prognosis. The patients studied were a selected group in whom low risk was defined by no prior history of coronary disease, a normal initial serum creatine kinase, troponin I and myoglobin, and a ECG that was either normal or had only minor non-specific ST-segment and T-wave changes.The exercise test appears useful approach in patients with intermediate risk and in those patients who received observation .12 h without obtaining ECG, humoral marker to relate to myocardial ischemia. To date, trials addressing sensibility, specificity and predictive value are lacking in patients admitted for chest pain in emergency department. Gibler et al. showed in 791 patients admitted for chest pain and with ECG, echocardiogram and CK negative for ischemia that the 98.9% of these patients had ETT negative with predictive value of 44% [15]. Other authors reported similar results [5,13,14]. Polansky et al. showed results similar to those reported in our study, but in this study the follow-up was 6 months only [6].Our approach is based on recent evidence that low-risk patients with a suspected coronary event can be identified clinically by gender, age, symptoms, past history of coronary disease, and ECG. Lee et al. [2] reported an event rate of 5% in patients with normal ECGs on presentation to the emergency department for acute chest
F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
pain. Atypical presentations in patients without a history of coronary disease were associated with very low event rates (,6%). Brush and co-workers [1] demonstrated that a normal initial ECG identified low-risk patients with a life-threatening complication rate of only 0.6%, whereas life-threatening events were 13.8% in patients with abnormal initial ECGs. Based on published algorithms for identifying lowrisk patients [10], we predicted that 5% of our patients would have had a coronary event. Our finding that 7.3% had a coronary event (two patient a non-fatal AMI, and 12 had a diagnosis of unstable angina) confirms the clinical efficacy of these risk stratification approaches. Our results add information about the longer term prognostic implication of ETT results in patients at low-risk for cardiac-related complications. The fact that patients with negative ETT had an extremely low rate of complications at 1766 months and a benign in-hospital course suggest that such patients can often be discharged from the ED or hospital. Our findings emphasize that, even among low-risk patients discharged with a negative non-invasive cardiac examination, subsequent resource utilization is still high. These findings suggest that these patients are still in need of further evaluation and management, even though their risk for coronary disease complications is low. Our data also suggest that among low-risk patients, those with early positive ETTs are truly at risk. In fact only 17.5% of this patients are event-free in the follow-up. Our study has several limitations, most important of which is the relatively small number of patients studied. We do not believe that non-consecutive patients enrolment is a major limitation because the incidence of events was as predicted by prior data [10]. This suggests that the patients studied represent a low-risk group that is typical of those admitted during daily practice. Because not all patients completed a 24-h observation period with four sets of fractionated cardiac enzyme measurements, it is possible that non-Q-wave AMIs were missed. It is also possible that patients with chest pain secondary to coronary vasospasm may have been classified as normal.
243
References [1] Brush JE, Brand DA, Acampora D, Chalmer B, Wachers FJ. Use of the initial electrocardiogram to predict in-hospital complications of acute myocardial infarction. N Engl J Med 1985;312:1137–41. [2] Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest pain in the emergency room. Identification and examination of low-risk patients. Arch Intern Med 1985;145:65–9. [3] Pryor DB, Harrell Jr. FE, Lee KL et al. Estimating the likelihood of significant coronary artery disease. Am J Med 1983;75:771–80. [4] Zimmerman J, Fromm R, Meyer D et al. Diagnostic marker cooperative study for the diagnosis of myocardial infarction. Circulation 1999;99:1671–7. [5] Lewis WR, Amsterdam EA. Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital for suspected acute myocardial infarction. Am J Cardiol 1994;74:987–90. [6] Polanczyk CA, Johnson PA, Hartley LH, Walls RM, Shykevich S, Lee TH. Clinical correlates and prognostic significance of early negative exercise tolerance test in patients with acute chest pain seen in the hospital emergency department. Am J Cardiol 1998;81:288– 92. [7] Zalenski RJ, Shamsa FH. Diagnostic testing of the emergency department patients with chest pain. Curr Opinion Cardiol 1998;13:248–53. [8] Kerns JR, Shaub TF, Fontanarosa PB. Emergency cardiac stress testing in the evaluation of emergency department patients with atipical chest pain. Ann Emerg Med 1993;22:794–8. [9] Tsakonis JS, Shesser R, Rosenthal R, Bittar GD, Smith R, Wasserman AG. Safety of immediate treadmill testing in selected emergency department patients with acute chest pain. Am J Emerg Med 1991;9:557–9. [10] Zalenski RJ, McCarren M, Roberts RR et al. An evaluation of a chest pain diagnostic protocol to excluded acute cardiac ischemia in the emergency department. Arch Intern Med 1997;157:1085–91. [11] Roberts RR, Zalenski RJ, Mensah EK et al. Cost of an emergency department-based accelerated diagnostic protocol versus hospitalization in patients with chest pain: a randomized controlled trial. J Am Med Assoc 1997;278:1670–6. [12] Mikhail MG, Smith FA, Gray M, Britton C, Frederiksen SM. Cost-effective of mandatory stress testing in chest pain center patients. Ann Emerg Med 1997;29:88–98. [13] Lee TH, Juarez G, Cook EF et al. Rouling out myocardial infarction. A prospective multicenter validation of a 12-h strategy for patients at low risk. N Engl J Med 1991;324:1239–46. [14] Lee TH, Rouan GW, Weisberg M et al. Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiol 1987;60:219–24. [15] Gibler WH, Runyon JP, Levy RC et al. A rapid diagnostic and treatment center for patients with chest pain in the emergency department. Ann Emerg Med 1995;25:1–8.
Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain a, b a Filippo Maria Sarullo MD *, Pietro Di Pasquale MD , Giuseppe Orlando MD , Giuseppe Buffa MD a , Sergio Cicero MD a , Antonino Mario Schillaci MD a , Antonio Castello MD a a
Division of Cardiology, Buccheri La Ferla Fatebenefratelli Hospital, Via S. Puglisi n.15, 90143 Palermo, Italy b Division of Cardiology, ‘‘ Paolo Borsellino’’, G.F. Ingrassia Hospital, Palermo, Italy Received 14 January 2000; received in revised form 30 May 2000; accepted 13 June 2000
Abstract It is common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study evaluates the safety and efficacy of immediate ETT for patients admitted to the hospital with acute chest pain. One hundred and ninety non-consecutive low-risk patients admitted to the hospital from emergency department with acute chest pain underwent ETT using Bruce protocol immediately on admission to the hospital (median time 165130 min). Fifty-seven (30%) patients had positive exercise electrocardiograms, 44 (77.2%) of whom had significant coronary narrowing by angiography. An uncomplicated anterior non-Q-wave AMI was diagnosed in one patient. One hundred and eleven (58.4%) patients had negative and 22 (11.6%) patients had non-diagnostic exercise electrocardiograms. Of these 133 patients, 86 (64.7%) were discharged immediately after ETT, 19 (14.3%) were discharged within 24 h, and 28 (21%) were discharged after 24 h of observation. There were no complications from ETT. During the 1766 months follow-up no patients died, and only eight (7.2%) patients with negative ETT experienced a major cardiac event (one AMI and seven angina). In conclusion, our results suggest that immediate ETT of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission, is effective in further stratifying this group into those who can be safety discharged immediately and those who require hospitalization. 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Exercise treadmill testing; Emergency department; Acute chest pain
1. Introduction Patients admitted to the emergency room with chest pain of suspected cardiac etiology could be identified on the basis of symptoms, coronary risk factors, physical examination, and the electrocar*Corresponding author. Tel.: 139-091-342-336; fax: 139-091-477265. E-mail address: [email protected] (F.M. Sarullo).
diogram (ECG) [1,2]. The coronary event rate in this group is as low as 5% [2]. Nevertheless, remains common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study assesses the use and safety of immediate ETT for selected low-risk patients admitted to the hospital with chest pain of suspected cardiac etiology.
0167-5273 / 00 / $ – see front matter 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 00 )00338-7
240
F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
2. Materials and methods
2.1. Patient population All patients aged .30 years who presented to the emergency department (ED) of the Buccheri La Ferla Fatebenefratelli Hospital between July 1995 and December 1996 with a chief complaint of anterior, precordial, or left lateral chest pain unexplained by local trauma or chest X-ray abnormalities were eligible for the study. From this population, 190 low-risk patients were selected, estimating the likelihood of significant coronary artery disease with Pryor normogram [3]. This analysis was based on age, gender, history of diabetes mellitus, systemic hypertension, hypercholesterolemia, tobacco use, typical or atypical angina pectoris, and on electro-cardiogram analysis. The likelihood of significant coronary artery disease was 1365%. Patients with ECGs diagnostic of infarction or ischemia were excluded as were patients with ST-segment and T-wave changes that would preclude accurate interpretation of the exercise ECG. The presence of persistent chest pain did not preclude ETT. Evaluation in the ED included history, physical examination, bilateral arm blood pressure measurements, chest roentgenogram, 12-lead ECG, Doppler echocardiography, cardiac enzyme measurements (creatine kinase-MB, troponin I and myoglobin) in ED and this after 2–4 h admission to the hospital [4].
2.2. Exercise protocol ETT was performed using continuous 12-lead electrocardiographic monitoring and a maximal or symptom-limited treadmill testing, Bruce protocol (Marquette Max 1, Jupiter, FL, USA). ETT was performed as soon as possible after the emergency room physician’s decision to admit the patient but no later than 5 h after admission. In all cases, ETT was performed after report that two cardiac enzyme measurements were normal. Exercise was terminated for electrocar-diographic changes diagnostic of ischemia (.1 mm horizontal or downsloping ST-segment depression or elevation 80 ms after the J point), significant arrhythmia, systolic blood pressure decrease of .10 mmHg, or significant symptoms. A non-diagnostic test was defined as a negative exercise
ECG with a peak heart rate ,85% of age-predicted maximal heart rate. Experienced staff cardiologists interpreted the exercise tests. The Human Studies Committee of the Buccheri La Ferla Fatebenefratelli Hospital approved this protocol. Each subject gave written informed consent.
2.3. Follow up Outcome data were available for all patients. Follow up was attempted for a minimum of 12 months. Chart review and telephone interviews for consenting patients were used to contact the patients or their relatives. In the follow-up interviews, patients were asked about additional visits to the emergency room because of chest pain, re-admissions to the hospital, and any other cardiac events. Events were defined as acute myocardial infarction (AMI), cardiac death, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG). In every patient was considering only the first event. The follow-up of patients submit to myocardial revascularization was stopped since to perform PTCA or CABG.
2.4. Statistical analysis Results are expressed as the mean6standard deviation (S.D.). Data were analysed by the two-tailed T-test to identify differences between the groups. Nominal data were analysed by the Chi-square test or Fisher’s test. Differences were considered significant at a P-value ,0.05.
3. Results
3.1. Patient characteristics One hundred and ninety patients underwent early ETT between July 1995 and December 1996 (Table 1). There were no significant differences between men and women except for diabetes mellitus, which was more common in women and cigarette smoking which was more common in men.
F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
241
Table 1 Study group demographics
Number of patients Mean age (years) Systemic hypertension b Diabetes mellitus Dyslipidemia c Cigarette smoking Family history of CAD d
Total
Men
Women
P-value a
190 5769 78 (41%) 35 (18.4%) 32 (16.8%) 81 (42.6%) 18 (9.5%)
127 (66.8%) 5668 51 (40%) 14 (11%) 20 (15.7%) 66 (52%) 12 (9.5%)
63 (33.2%) 5867 27 (42.8%) 21 (33.3%) 12 (19%) 15 (23.8%) 6 (9.5%)
0.69 n.s. n.s. 0.005 n.s. 0.022 n.s.
a
Comparisons between men and women. Systolic blood pressure .140 mmHg, diastolic blood pressure .90 mmHg. c Serum cholesterol .200 mg / dl, low-density lipoprotein cholesterol .130 mg / dl. d CAD5coronary artery disease in a first-degree relative ,55 years-of-age. b
3.2. Exercise treadmill testing results Median time from hospital admission to ETT was 165630 min. In 111 (58.4%) patients ETT was negative, in 57 (30%) was positive, and in 22 (11.6%) was non-diagnostic (Table 2). There were no complications in the ETTs. All patients with positive exercise tests underwent in next time (312 days) to cardiac catheterization, that confirm the diagnosis of coronary artery disease in 44 (77.2%) patients. Three patients had 3-vessel disease, 12 had 2-vessel disease, and 29 had 1-vessel disease. A final diagnosis of anterior non-Q-wave AMI was reached in one patient, and seven patients had unstable angina based on history and clinical course. The patient with an anterior non-Q-wave infarction was a 49-year-old man who presented with chest pain that woke him from work and resolved while on route to the emergency room. History was significant for cigarette smoking and dyslipidemia, and his initial ECG was interpreted as having early repolarization. During ETT, he had 2 mm ST-segment elevation in V2–V5 leads with chest pain, which resolved rapidly after
nitrate per os during post-exercise recovery. Serial ECGs, echocardiograms and cardiac enzyme measurements revealed an anterior non-Q-wave AMI. The serum creatine kinase peaked at 16 h after presentation. Cardiac catheterization demonstrated a thrombus in the proximal descending coronary artery. The hospital course was uncomplicated and he underwent successful PTCA before discharge. Of the 111 patients with negative ETTs, 76 (68.4%) were discharged directly after their tests, 13 (11.8%) were discharged in ,24 h, and 22 (19.8%) completed a minimum 24-h observation period in the telemetry unit. No AMI were found. Of the 22 patients with non-diagnostic ETTs, ten (45.5%) were discharged subsequent to a low-risk immediate ETT (no ischemic changes, with 70–84% of age-predicted maximal heart rate), six (27.3%) were discharged in ,24 h, and six (27.3%) completed a minimum 24-h observation period in the telemetry unit with serial ECGs, and four sets of fractionated cardiac enzyme measurements. No AMIs were diagnosed. All patients in next time (865 days) underwent pharmacological stress testing with dipyridamole (Tc-99m-tetrofosmin
Table 2 Exercise test results
Exercise capacity (min) Peak double product METS c Double product b angina Double product ⇓ ST 1 mm a
ETT a positive (n557)
ETT negative or non-diagnostic (n5133)
P
6.0062.24 20.71465132 6.361.8 18.57863314 18.88164371
8.3962.32 27.31864872 9.262.3
,0.0001 ,0.0001 ,0.0001
ETT5exercise treadmill testing. Double product5heart rate3systolic blood pressure. c METS5metabolic equivalent. b
242
F.M. Sarullo et al. / International Journal of Cardiology 75 (2000) 239 – 243
SPECT myocardial perfusion images) that were normal, and one patient had positive results on myocardial stress scintigraphy followed by coronary arteriography and PTCA for proximal circumflex disease.
3.3. Post hospital follow-up
Table 3 Follow-up results
Death AMI a Unstable Angina CABG b PTCAc
ETT positive (n557)
ETT negative (n5111)
ETT non-diagnostic (n522)
0 1 2 15 29
0 1 (0.9%) 7 (6.3%) 0 0
0 0 1 (4.5%) 0 0
(1.8%) (3.5%) (26.3%) (50.9%)
a
AMI5acute myocardial infarction. CABG5coronary artery by-pass grafting. c PTCA5percutaneous transluminal coronary angioplasty. b
Follow-up data of .12 months (range from 3 to 32, mean 1766) were available in all patients. In this time no evidence of mortality for these patients were detected. All patients with positive ETTs underwent further study (angiography) as previously describer. Fifteen (26.3%) patients were underwent to CABG, 29 (50.9%) to PTCA. One (1.8%) patient with no significant coronary artery disease on angiography sustained a non-fatal inferior AMI at 7 months. Repeat angiography demonstrated a thrombus in the proximal rigth coronary artery. In two (3.5%) patients were diagnosed unstable angina 2 and 5 months after the ETT. The remaining ten (17.5%) patients were stable at follow-up. Of the 22 patients with non-diagnostic tests, five underwent further evaluation and one (4.5%) had a diagnosis of unstable angina after 5 months after ETT, and angiography demonstrated a significant coronary artery disease of the circumflex artery. The remainder patients were stable at follow-up. Of the 111 patients with negative ETTs, eight (7.2%) experienced a cardiac event (one a non-fatal inferior-lateral AMI after 10 months (STsegment elevation with concomitant CK, CK-MB, TnI alterations, and seven had a diagnosis of unstable angina, 4–11 months after ETTs). The diagnoses in these seven patients were verified directly because the patients were hospitalized in our division of cardiology. They showed at entry ST-segment depression at entry ECG and four patients positive TnI determination after 4 h from admission. The other three patients were TnI negative and in the subsequent ETT (3 days after admission) showed ST-segment changes which judged as ischemic. All these patients were referred to perform coronarography that confirmed the ischemic nature of chest pain and ECG changes. The remaining 103 patients were stable at follow-up (Table 3).The sensitivity and specificity of a positive or inconclusive ETT for cardiac events in 1766 months were 84 and 92.5% respectively. Patients
with a negative ETT had a 92.8% probability of not having an event in 1766 months.
4. Discussion The results of this study confirm that ETT is a safe procedure in low-risk patients with acute chest pain [6–14], and that patients who have negative tests have an excellent 1766 months prognosis. The patients studied were a selected group in whom low risk was defined by no prior history of coronary disease, a normal initial serum creatine kinase, troponin I and myoglobin, and a ECG that was either normal or had only minor non-specific ST-segment and T-wave changes.The exercise test appears useful approach in patients with intermediate risk and in those patients who received observation .12 h without obtaining ECG, humoral marker to relate to myocardial ischemia. To date, trials addressing sensibility, specificity and predictive value are lacking in patients admitted for chest pain in emergency department. Gibler et al. showed in 791 patients admitted for chest pain and with ECG, echocardiogram and CK negative for ischemia that the 98.9% of these patients had ETT negative with predictive value of 44% [15]. Other authors reported similar results [5,13,14]. Polansky et al. showed results similar to those reported in our study, but in this study the follow-up was 6 months only [6].Our approach is based on recent evidence that low-risk patients with a suspected coronary event can be identified clinically by gender, age, symptoms, past history of coronary disease, and ECG. Lee et al. [2] reported an event rate of 5% in patients with normal ECGs on presentation to the emergency department for acute chest
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pain. Atypical presentations in patients without a history of coronary disease were associated with very low event rates (,6%). Brush and co-workers [1] demonstrated that a normal initial ECG identified low-risk patients with a life-threatening complication rate of only 0.6%, whereas life-threatening events were 13.8% in patients with abnormal initial ECGs. Based on published algorithms for identifying lowrisk patients [10], we predicted that 5% of our patients would have had a coronary event. Our finding that 7.3% had a coronary event (two patient a non-fatal AMI, and 12 had a diagnosis of unstable angina) confirms the clinical efficacy of these risk stratification approaches. Our results add information about the longer term prognostic implication of ETT results in patients at low-risk for cardiac-related complications. The fact that patients with negative ETT had an extremely low rate of complications at 1766 months and a benign in-hospital course suggest that such patients can often be discharged from the ED or hospital. Our findings emphasize that, even among low-risk patients discharged with a negative non-invasive cardiac examination, subsequent resource utilization is still high. These findings suggest that these patients are still in need of further evaluation and management, even though their risk for coronary disease complications is low. Our data also suggest that among low-risk patients, those with early positive ETTs are truly at risk. In fact only 17.5% of this patients are event-free in the follow-up. Our study has several limitations, most important of which is the relatively small number of patients studied. We do not believe that non-consecutive patients enrolment is a major limitation because the incidence of events was as predicted by prior data [10]. This suggests that the patients studied represent a low-risk group that is typical of those admitted during daily practice. Because not all patients completed a 24-h observation period with four sets of fractionated cardiac enzyme measurements, it is possible that non-Q-wave AMIs were missed. It is also possible that patients with chest pain secondary to coronary vasospasm may have been classified as normal.
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