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Asymptomatic myocardial ischemia as a predictor of cardiac events after coronary artery bypass grafting for stable angina pectoris
AsymptomaticMyocardiallschemiaas a Predictor of CardiacEventsAfter CoronaryArtery BypassGrafting for StableAnginaPectoris KENNETH EGSTRUP, MD
Thirty-six patients with chronic stable angina were studied before and after coronary artery bypass grafting (CABG) to assess the prevalence and prognostic implications of asymptomatic myocardiai ischemia obtained by ambulatory monitoring. Ambuiatory monitoring performed during medical therapy before CABG detected 66 episodes of transient ischemia, 54 (62%) being asymptomatic. Ail patients were asymptomatic or with minimal symptoms 3 months after CABG. Additional ambulatory monitoring was performed for 36 hours. There were 39 episodes of silent ischemia detected in the 12 patients of group 1, whereas no episodes of Sl-segment shift occurred in the 24 patients of group 2. Coronary artery bypass grafting reduced the frequency of transient ischemia by 41% (p <0.05) compared with medical therapy, whereas the number of ischemic episodes in group 1 increased from
23 during medical therapy to 39 episodes after CABG (41%, p <0.05). During a follow-up of 9 months, 6 cardiac events occurred: 6 in group 1 comprising sudden death (l), revascuiarfzation (2), and angina (3) and 2 in group 2, including revascuiarization (1) and angina (1) (p = 0.005). KapianMeier analysis demonstrated that asymptomatic myocardiai ischemia was correlated with a significant cumulative probabiiii of cardiac events (p <0.025) and muitiiariate analysis of 11 variables showed that silent ischemia was the most powerful predictor of cardiac events (p
6
by ambulatory monitoring and defined as transient ST-segment shifts, without accompanying angina pectoris after CABG.g,10The fact that silent ischemia has been correlated with reduced myocardial perfusion and compromised left ventricular functionll-l3 indicates a still active ischemic myocardium despite revascularization, a finding of possible importance for morbidity and mortality. This study determined by ambulatory monitoring the presence and extent of silent ischemia 3 months after CABG in asymptomatic or mildly symptomatic patients, as compared with ischemic activity during medical treatment before surgery. An additional goal was to assessif asymptomatic transient myocardial ischemia identifies patients at high risk of cardiac events (sudden death, fatal and nonfatal infarction, angina and new revascularization) during the first year after surgery.
oronary artery bypass grafting (CABG] is a wellestablished method of ameliorating or abolishing anginal pain in patients whose symptoms are severe despite intensive medical treatment.l-4 Symptomatic relief occurs in most patients but angina can persist or recur in others.293The cumulative graft occlusion rate is approximately 20% in the first year5+6and 2 to 4% each year thereafter. 7 However, graft patency only partly correlates with angina reliefs and the mechanisms for symptomatic improvement seem to be based on several factors.g Recent evidence indicates that a remarkably high proportion of patients were asymptomatic for myocardial ischemia, which was detected From the Department of Cardiology, Odense University Hospital, Odense, Denmark. This study was supported by grants from the Danish Heart Foundation. Manuscript received June 17. 1987; revised manuscript received September 23,1987, and accepted September 39. Address for reprints: Kenneth Egstrup, MD, Department of Cardiology, Odense University Hospital, DK-5000 Odense C, Denmark.
Methods Patients: The study included 36 patients with specific characteristics present before and after CABG. 240
February 1, 1988
Before: (1) refractory angina despite optimal medical treatment; (2) documented symptomatic or asymptomatic ischemic episodes during ambulatory monitoring; (3) maximal bicycle exercise test to determine ST-segment change and work capacity; and (41 significant stenosis confirmed by coronary arteriography. After: (1) relief or minimal angina (only use of short-acting nitrates); (2) no ischemic episodes during ambulatory monitoring shortly after CABG (7 to 14 days): and (3) ability to perform a maximal exercise test 3 months after CABG. Patients with bundle branch block, those taking any medication that could influence the evaluation of the ST segment and those with gross left ventricular hypertrophy, severe valvular heart disease and without sinus rhythm were excluded. All patients gave informed consent. Investigation was performed in consecutive patients before CABG during prophylactic medical therapy with metoprolollO0 to 200 mg/day in combination with nifedipine 30 to 60 mg/day and 3 months after CABG. A detailed medical history, maximal exercise testing and ambulatory monitoring during unrestricted daily life were performed. After CABG the patients were treated routinely with aspirin 150 mg once daily, and followed for 12 months after CABG for occurrence of sudden cardiac death, fatal or nonfatal myocardial infarction and recurrence of angina pectoris as indicated by typical and frequent chest pain requiring prophylactic medical treatment or new revascularization. Ambulatory monitoring: Ambulatory monitoring was performed for 36 hours before and 3 months after CABG using a calibrated, amplitude modulated, 2channel tape recorder (Tracker Reynolds). The recorder had been previously evaluated against a frequency modulated system during simultaneous recordingd4 and possessed a frequency response of 0.05 to 100 Hz as per the specifications of the American Heart Association for detection of ST-segment changes.15 Positioning of the bipolar leads corresponded with maximal ST-segment change during exercise testing (including preoperative) or recording CM5 and a modified inferior lead. Great care was taken to avoid leads with pathological Q waves, resting ST-segment depression and effects of postural changes. All tapes were analyzed immediately after recording without knowledge of the patients’ further status during follow-up. The tapes were analyzed visually at 60 times normal speed [Pathfinder II analyzer, Reynolds) and trend curves of ST-segment deviation and heart rate were obtained for the whole monitoring period. Episodes of interest were printed on an electrocardiogram (25 mm/s) for final evaluation, Transient ST-segment depression was defined as >l mm of horizontal or downsloping ST-segment depression, 80 ms after the J point, and ST-segment elevation as 11 mm of ST-segment elevation at the J point. An episode had to last at least 1 minute and at least 2 minutes of normalization of the ST segment were required to define 2 separate episodes. All patients kept a detailed diary and were instructed to activate the event button on the tape recorder when experiencing angina1 chest pain so as to identify possible symptomatic ischemic
THE AMERICAN
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OF CARDIOLOGY
Volume 81
249
TABLE I Cllnlcal Data Characteristic Rs (n) Age Wr) Smoking Previous myocardial infarction Preoperative ejection fraction (56) No. of grafts/patient No. of grafts to LClpatient No. of grafts to K/patient ST-segment change during exercise test* Diuretics Change in exercise capacity before/after surgery (%)
Group 1
Group 2
12 52 f 5 2 6 58% 16 3.5 2.8 0.7 6 5 8 f 23
24 54 f 7 10 16 65f 15 3.1 2.3 0.8 1 6 23 f 37
Clinical characteristics (mean f standard deviation) of 36 patients, 3 months after coronary artery bypass grafting, 12 (group 1) with silent ischemia and 24 (group 2) without silent ischemia during ambulatory monitoring. LC = left coronary artery: RC = right coronary artery. ‘p <0.05.
episodes. The number of symptomatic and asymptomatic ischemic episodes, their duration, maximal STsegment change and heart rate at onset of ischemia were noted for each tape. Exercise testing and coronary arteriography: Maximal bicycle exercise tests were performed in all patients before and 3 months after CABG. A la-lead precordial mapping system was usedI and ST-segment changes were defined in the same way as for ambulatory monitoring. Selective left and right coronary arteriography was performed before CABG in all patients. A lesion was considered significant if the luminal narrowing was 275% in the major coronary arteries. Contrast left ventriculography was performed to assessejection fraction. Statistical analysis: Cox multivariate analysis17was used to examine the predictive value of 11 clinical variables that could be associated with cardiac events during the 9 months of the follow-up period: age; smoking; prior myocardial infarction; use of diuretics 3 months after coronary bypass surgery [without hypertension]: silent ischemia detected by ambulatory monitoring; and ST-segment changes detected by exercise testing at the 3-month follow-up after CABG; left ventricular ejection fraction before surgery; total number of grafts; grafts to the left coronary artery and grafts to the right coronary artery; and, finally, change in maximal exercise capacity before and after CABG. The cumulative probabilities of cardiac events during the g-month follow-up period were examined by KaplanMeier analyses18and differences tested by a log rank test. Data were expressed as mean f standard deviation and the unpaired t test and chi-square test were used to assess differences between means and between groups. Wilcoxon matched-pairs signed rank test was used for within-group comparison.
Results Clinical data: The clinical characteristics of the patients are given in Table I. Twelve patients (group 1) exhibited silent ischemia and 24 (group 2) were without silent ischemia 3 months after CABG.
250
SILENT ISCHEMA AFTER CABG
Ambulatory monitoring: Ambulatory monitoring performed for 36 hours during medical therapy displayed a total of 66 episodes of transient ST-segment depression, with 54 (82%) being asymptomatic. STsegment depressions of 1 to 2 mm were found in 55 ischemic episodes, 2 to 3 mm in 8 and >3 mm in 3. Total duration of ischemia was 855 minutes, with 699 minutes (82%) occurring during transient asymptomatic ischemic episodes (Figure 1). Heart rate at onset of ischemia was 78 f 13 beats/min. Silent ischemia was not detected on the early postoperative Holter tapes and consequently no patient was excluded for that reason. During ambulatory monitoring performed for 36 hours 3 months after CABG, a total of 39 episodesof transient ST-segmentchange were noted, 34 with STsegment depression and 5 with ST-segmentelevation. All episodes of ST-segment elevation were detected in the same patient. The magnitude of ST-segment change was 1 to 2 mm in 36 ischemic episodes and 2 to 3 mm in 3. Total duration of ST-segment change was 602 minutes (569minutes with ST-segmentdepression and 33 minutes with elevation]. Heart rate at onset of ischemia was 92 f 19beats/min. All ischemic episodes were silent and found in 12 patients (group l), whereas no ST-segmentchange was found in 24 patients (group 2).
N-36
90
If the 12 patients with silent ischemia after CABG were to be analyzed separately, they would display 23 episodeswith transient ischemia before CABG, 18 episodeswould be asymptomatic (78%) and total duration of ischemia would reach 302minutes (233minutes during silent ischemia) [Figure 2). Cardiac events: During the g-month follow-up, 8 patients had a cardiac event, 6 in group 1 and 2 in group 2 [Table II]. Of the 6 events in group 1, 1 was sudden death, characterized by 5 episodes of silent ST-segment elevation during the 36-hour ambulatory monitoring period and with a total duration of 33 minutes. Among the others, angina pectoris recurred in 5 patients (2 required new revascularization and 3 received prophylactic medical treatment). In group 2 there were 2 cardiac events,both a recurrence of angina pectoris; of these, 1 patient required new revascularization while the other was treated medically. No patient had a myocardial infarction. Kaplan-Meier analysis demonstrated a significantly higher cumulative incidence of cardiac events in group 1, as compared with group 2 (Figure 3, p KO.0251. In group 1, no significant differences could be detected between those patients experiencing a cardiac event and those who did not. Multivariate Cox analysis of 11 variables indicated that asymptomatic myo-
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FIGURE 1. Frequency and duration ot total and asymptomatlc lsohemia during medical treatment and 3 months after coronary artery bypass graftlng (CABG) In 36 patients. Hatched bars denote silent myocardlal Ischemla.
FIGURE 2. Frequency and duratlon ot total and asymptomatlc lschemla In 12 patients (group 1) wlth silent lschemla after coronary artery bypass graftlng (CABG). /falc/ted bars denote silent myocardlal Ischemla.
February 1,1988
cardial ischemia was the most accurate predictor of cardiac events during a g-month follow-up period (p <0.005) and the presence of silent ischemia indicated a high increase in the relative risk of a cardiac event. Also of predictive value was the change in exercise capacity (p
Discussion Prediction of cardiac events after CABG is difficult to assess and exercise testing as well as quantitative radionuclide studies have limitations in identifying individual patients at risk .8Jg-21Although graft patency has been regarded as the best measure for successful revascularization,21 it does not always provide information on regional myocardial ischemia.g Using ambulatory monitoring, a relation between regional myocardial perfusion defects during ischemic episodes and transient ST-segment shifts has been established,*l so it is possible to examine episodes of transient myocardial ischemia during daily life even in asymptomatic patients. This study has demonstrated that CABG reduces the frequency (4170, p
THE AMERICAN
TABLE II
JOURNAL
OF CARDIOLOGY
Volume 81
251
Cardiac Events Group 1 (n = 12)
Group 2 (n = 24)
p Value
1 2 3 6
0 1 1 2
0.005
Sudden death Angina pectoris with CABG Angina pectoris Total
Cardiac events during g-month follow-up in 12 patients (group 1) with silent ischemia and 24 patients (group 2) without silent ischemia. CABG = coronary artery bypass grafting
quired in 2 and medical treatment in 3. This contrasts with the findings in group 2, where only 2 cardiac events occurred (S%]. Both were angina pectoris, one requiring revascularization and the other medical treatment. The results of the multivariate analysis show that the presence of asymptomatic myocardial ischemia was the most powerful predictor of cardiac events (p
* Probability
I%1
100
No silent
1
2
3
4
ischemia
5 Month
6
7
8
9
FIGURE 3. Kaplan-Meler curves of cumulative probabllltles for cardiac events during a g-month follow-up In 12 patients (group 1) wlth silent lechemla and 24 patients (group 2) without silent lschemla durlng ambulatory monltorlng.
252
SILENT ISCHEMIA
AFTER CABG
raises the question as to whether silent ischemia can persist without development of angina but with an increased risk for other cardiac events such as sudden death or myocardial infarction. These important questions cannot be assessed by this study alone, as the observation period was too short. This study has some other limitations. First, arteriography after CABG was not routinely performed, which precluded any knowledge of graft patency and progression of atherosclerosis in relation to silent ischemia. Even so, a poor correlation has been found between graft patency and occurrence of silent ischemia.g Second, ambulatory monitoring was performed for only 36 hours; more extensive monitoring could have identified silent ischemia in the 2 patients in group 2 with recurring angina pectoris. However, even the relatively short monitoring period used in this study provided important prognostic information.
References 1. Cosgrove DM, Loop FD. Sheldon WC. Results of myocardial revascularization: a 12-year experience. Circulation 1982;65(suppl II):37-43. 2. Braunwald E. Effects of coronary-artery bypass grafting on survival: impiications of the randomized coronary artery study. N Engl J Med 1983;309: 1181-1184.
3. Rahimtoola SH. Coronary bypass surgery for chronic angina-1981. A perspective. Circuiotion 1982;65:225-241. 4. Loop FD, Sheldon WC, Lytle BW, Cosgrove DM, Proudfit WL. The efficacy of coronary artery surgery. Am Heart J 1981;101:86-96. 5. Campeau L. Crochet D, Lesperance J, Bourasse MG, Grondin CM. Postoperative changes in aortocoronary saphenous vein grafts revisited; ongiographic studies at two weeks and at one year in two series of consecutive patients. Circulation 2975;52:369-377. 6. Fitsgibbon GM, Burton JR, Leach AJ. Coronary bypass graft fate: angiographic grading of 1400 consecutive grafts early after operation and of 1132 after one year. Circuiation 1978;57:1070-1074. 7. Seides SF. Borer JS.Kent KM, Rosing DR. McIntosh CL, Epstein SE. Longterm anatomic fate of coronary artery bypass grafts and functional status of patients 5 years after operation. N Engi J Med 1978;298:1213-1217. 8. Bartel AG, Behar VS, Peter RH, Orgain ES, Kong Y. Exercise stress testing
in evaluation of aortocoronary bypass surgery. Circulation 1973;48:141-148. 9. Ribeiro P. Shea M, Deanfield JE,Oakley CM, Sapsford R, JonesT, Walesby R, Selwyn AP. Different mechanisms for the relief of angina after coronary bypass surgery. Physiological versus anatomical assessment. Br Heart J 1984;52:502-509. 10. Quyyumi AA, Wright CA, Mockus LJ. Yacoub M, Fox KM. Effects of myocardial revascularization in patients with effort angina and those with effort and nocturnal angina. Br Heart J 1985;54:557-561. 11. Deanfield JE, Selwyn AP, Chierchia S, Maseri A, Ribeiro P. Krikler S, Morgan M. Myocardial ischemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes. Loncet 1983;2:753758. 12. Chierchia S, Lazzari M, Freedman B. Bunnelli C. Maseri A. Impairment of myocardial perfusion and function during painless myocardial ischemia. JACC 1983;1:924-930. 13. Cohn PF, Brown EJ Jr, Wynne J, Holman BL, Atkins HL. Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocordial ischemia. JACC 1983;1:931-933. 14. Levy RD. Quyyumi AA, Crake T, Fox KM. Practical aspects of ambulatory ST-segment monitoring: comparison of frequency modulated and direct recording systems (obstr]. Br Heart J 1985:53:683. 15. American Heart Association Committee on Electrocardiography. Recommendations for standardization of leads and of specifications for instruments in electrocardiography and vectorcardiography. Circulation 1975;52:11-31. 16. Fox KM, Deanfield JE,Ribeiro P, England D, Wright CA. Projection of STsegment changes to the front of the chest: practical implications for exercise testing and ambulatory monitoring. Br Heart J 1982;48:555-559. 17. Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. New York: John Wiley, 1980. 18.Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481. 19. European Coronary Surgery Study Group. Long-term results of prospective randomized study of coronary bypass surgery in stable angina pectoris. Lancet 1982;2:1173-1180. 20. CASS Principal Investigations and Their Associates. Coronary artery surgery (CA%): a randomized trial of coronary artery bypass surgery. Survivai data. Circulation 1983;68:939-950. 21. Pfisterer M, Emmenegger H, Schmitt HE, Miiller-Brand J, Hasse J,Grade1 E, Laver MB, Burckhardt D, Burkart F. Accuracy of serial myocordial perfusion scintigraphy with thallium 201 for prediction of graft patency. Early and late after coronary artery bypass surgery. Circulation 1982;66:1017-1024. 22. Gottlieb SO, Weisfeldt ML, Ouyang P, Mellits ED, Gerstenblith G. Silent ischemia as o marker for early unfavorable outcomes in patients with unstable angina. N Engl J Med 1986;314:1214-1219. 23. Schwartz JN, Kong Y, Hackel DB. Bartel AG. Comparison of angiographic and postmortem findings in patients with coronary artery disease. Am J Cordioi 1975;36:174-178. 24. Benchimol A, dos Santos A, Desser KB. Relief of angina pectoris in patients with occluded coronary bypass grafts. Am J Med 1976;60:339-343.
Thirty-six patients with chronic stable angina were studied before and after coronary artery bypass grafting (CABG) to assess the prevalence and prognostic implications of asymptomatic myocardiai ischemia obtained by ambulatory monitoring. Ambuiatory monitoring performed during medical therapy before CABG detected 66 episodes of transient ischemia, 54 (62%) being asymptomatic. Ail patients were asymptomatic or with minimal symptoms 3 months after CABG. Additional ambulatory monitoring was performed for 36 hours. There were 39 episodes of silent ischemia detected in the 12 patients of group 1, whereas no episodes of Sl-segment shift occurred in the 24 patients of group 2. Coronary artery bypass grafting reduced the frequency of transient ischemia by 41% (p <0.05) compared with medical therapy, whereas the number of ischemic episodes in group 1 increased from
23 during medical therapy to 39 episodes after CABG (41%, p <0.05). During a follow-up of 9 months, 6 cardiac events occurred: 6 in group 1 comprising sudden death (l), revascuiarfzation (2), and angina (3) and 2 in group 2, including revascuiarization (1) and angina (1) (p = 0.005). KapianMeier analysis demonstrated that asymptomatic myocardiai ischemia was correlated with a significant cumulative probabiiii of cardiac events (p <0.025) and muitiiariate analysis of 11 variables showed that silent ischemia was the most powerful predictor of cardiac events (p
6
by ambulatory monitoring and defined as transient ST-segment shifts, without accompanying angina pectoris after CABG.g,10The fact that silent ischemia has been correlated with reduced myocardial perfusion and compromised left ventricular functionll-l3 indicates a still active ischemic myocardium despite revascularization, a finding of possible importance for morbidity and mortality. This study determined by ambulatory monitoring the presence and extent of silent ischemia 3 months after CABG in asymptomatic or mildly symptomatic patients, as compared with ischemic activity during medical treatment before surgery. An additional goal was to assessif asymptomatic transient myocardial ischemia identifies patients at high risk of cardiac events (sudden death, fatal and nonfatal infarction, angina and new revascularization) during the first year after surgery.
oronary artery bypass grafting (CABG] is a wellestablished method of ameliorating or abolishing anginal pain in patients whose symptoms are severe despite intensive medical treatment.l-4 Symptomatic relief occurs in most patients but angina can persist or recur in others.293The cumulative graft occlusion rate is approximately 20% in the first year5+6and 2 to 4% each year thereafter. 7 However, graft patency only partly correlates with angina reliefs and the mechanisms for symptomatic improvement seem to be based on several factors.g Recent evidence indicates that a remarkably high proportion of patients were asymptomatic for myocardial ischemia, which was detected From the Department of Cardiology, Odense University Hospital, Odense, Denmark. This study was supported by grants from the Danish Heart Foundation. Manuscript received June 17. 1987; revised manuscript received September 23,1987, and accepted September 39. Address for reprints: Kenneth Egstrup, MD, Department of Cardiology, Odense University Hospital, DK-5000 Odense C, Denmark.
Methods Patients: The study included 36 patients with specific characteristics present before and after CABG. 240
February 1, 1988
Before: (1) refractory angina despite optimal medical treatment; (2) documented symptomatic or asymptomatic ischemic episodes during ambulatory monitoring; (3) maximal bicycle exercise test to determine ST-segment change and work capacity; and (41 significant stenosis confirmed by coronary arteriography. After: (1) relief or minimal angina (only use of short-acting nitrates); (2) no ischemic episodes during ambulatory monitoring shortly after CABG (7 to 14 days): and (3) ability to perform a maximal exercise test 3 months after CABG. Patients with bundle branch block, those taking any medication that could influence the evaluation of the ST segment and those with gross left ventricular hypertrophy, severe valvular heart disease and without sinus rhythm were excluded. All patients gave informed consent. Investigation was performed in consecutive patients before CABG during prophylactic medical therapy with metoprolollO0 to 200 mg/day in combination with nifedipine 30 to 60 mg/day and 3 months after CABG. A detailed medical history, maximal exercise testing and ambulatory monitoring during unrestricted daily life were performed. After CABG the patients were treated routinely with aspirin 150 mg once daily, and followed for 12 months after CABG for occurrence of sudden cardiac death, fatal or nonfatal myocardial infarction and recurrence of angina pectoris as indicated by typical and frequent chest pain requiring prophylactic medical treatment or new revascularization. Ambulatory monitoring: Ambulatory monitoring was performed for 36 hours before and 3 months after CABG using a calibrated, amplitude modulated, 2channel tape recorder (Tracker Reynolds). The recorder had been previously evaluated against a frequency modulated system during simultaneous recordingd4 and possessed a frequency response of 0.05 to 100 Hz as per the specifications of the American Heart Association for detection of ST-segment changes.15 Positioning of the bipolar leads corresponded with maximal ST-segment change during exercise testing (including preoperative) or recording CM5 and a modified inferior lead. Great care was taken to avoid leads with pathological Q waves, resting ST-segment depression and effects of postural changes. All tapes were analyzed immediately after recording without knowledge of the patients’ further status during follow-up. The tapes were analyzed visually at 60 times normal speed [Pathfinder II analyzer, Reynolds) and trend curves of ST-segment deviation and heart rate were obtained for the whole monitoring period. Episodes of interest were printed on an electrocardiogram (25 mm/s) for final evaluation, Transient ST-segment depression was defined as >l mm of horizontal or downsloping ST-segment depression, 80 ms after the J point, and ST-segment elevation as 11 mm of ST-segment elevation at the J point. An episode had to last at least 1 minute and at least 2 minutes of normalization of the ST segment were required to define 2 separate episodes. All patients kept a detailed diary and were instructed to activate the event button on the tape recorder when experiencing angina1 chest pain so as to identify possible symptomatic ischemic
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 81
249
TABLE I Cllnlcal Data Characteristic Rs (n) Age Wr) Smoking Previous myocardial infarction Preoperative ejection fraction (56) No. of grafts/patient No. of grafts to LClpatient No. of grafts to K/patient ST-segment change during exercise test* Diuretics Change in exercise capacity before/after surgery (%)
Group 1
Group 2
12 52 f 5 2 6 58% 16 3.5 2.8 0.7 6 5 8 f 23
24 54 f 7 10 16 65f 15 3.1 2.3 0.8 1 6 23 f 37
Clinical characteristics (mean f standard deviation) of 36 patients, 3 months after coronary artery bypass grafting, 12 (group 1) with silent ischemia and 24 (group 2) without silent ischemia during ambulatory monitoring. LC = left coronary artery: RC = right coronary artery. ‘p <0.05.
episodes. The number of symptomatic and asymptomatic ischemic episodes, their duration, maximal STsegment change and heart rate at onset of ischemia were noted for each tape. Exercise testing and coronary arteriography: Maximal bicycle exercise tests were performed in all patients before and 3 months after CABG. A la-lead precordial mapping system was usedI and ST-segment changes were defined in the same way as for ambulatory monitoring. Selective left and right coronary arteriography was performed before CABG in all patients. A lesion was considered significant if the luminal narrowing was 275% in the major coronary arteries. Contrast left ventriculography was performed to assessejection fraction. Statistical analysis: Cox multivariate analysis17was used to examine the predictive value of 11 clinical variables that could be associated with cardiac events during the 9 months of the follow-up period: age; smoking; prior myocardial infarction; use of diuretics 3 months after coronary bypass surgery [without hypertension]: silent ischemia detected by ambulatory monitoring; and ST-segment changes detected by exercise testing at the 3-month follow-up after CABG; left ventricular ejection fraction before surgery; total number of grafts; grafts to the left coronary artery and grafts to the right coronary artery; and, finally, change in maximal exercise capacity before and after CABG. The cumulative probabilities of cardiac events during the g-month follow-up period were examined by KaplanMeier analyses18and differences tested by a log rank test. Data were expressed as mean f standard deviation and the unpaired t test and chi-square test were used to assess differences between means and between groups. Wilcoxon matched-pairs signed rank test was used for within-group comparison.
Results Clinical data: The clinical characteristics of the patients are given in Table I. Twelve patients (group 1) exhibited silent ischemia and 24 (group 2) were without silent ischemia 3 months after CABG.
250
SILENT ISCHEMA AFTER CABG
Ambulatory monitoring: Ambulatory monitoring performed for 36 hours during medical therapy displayed a total of 66 episodes of transient ST-segment depression, with 54 (82%) being asymptomatic. STsegment depressions of 1 to 2 mm were found in 55 ischemic episodes, 2 to 3 mm in 8 and >3 mm in 3. Total duration of ischemia was 855 minutes, with 699 minutes (82%) occurring during transient asymptomatic ischemic episodes (Figure 1). Heart rate at onset of ischemia was 78 f 13 beats/min. Silent ischemia was not detected on the early postoperative Holter tapes and consequently no patient was excluded for that reason. During ambulatory monitoring performed for 36 hours 3 months after CABG, a total of 39 episodesof transient ST-segmentchange were noted, 34 with STsegment depression and 5 with ST-segmentelevation. All episodes of ST-segment elevation were detected in the same patient. The magnitude of ST-segment change was 1 to 2 mm in 36 ischemic episodes and 2 to 3 mm in 3. Total duration of ST-segment change was 602 minutes (569minutes with ST-segmentdepression and 33 minutes with elevation]. Heart rate at onset of ischemia was 92 f 19beats/min. All ischemic episodes were silent and found in 12 patients (group l), whereas no ST-segmentchange was found in 24 patients (group 2).
N-36
90
If the 12 patients with silent ischemia after CABG were to be analyzed separately, they would display 23 episodeswith transient ischemia before CABG, 18 episodeswould be asymptomatic (78%) and total duration of ischemia would reach 302minutes (233minutes during silent ischemia) [Figure 2). Cardiac events: During the g-month follow-up, 8 patients had a cardiac event, 6 in group 1 and 2 in group 2 [Table II]. Of the 6 events in group 1, 1 was sudden death, characterized by 5 episodes of silent ST-segment elevation during the 36-hour ambulatory monitoring period and with a total duration of 33 minutes. Among the others, angina pectoris recurred in 5 patients (2 required new revascularization and 3 received prophylactic medical treatment). In group 2 there were 2 cardiac events,both a recurrence of angina pectoris; of these, 1 patient required new revascularization while the other was treated medically. No patient had a myocardial infarction. Kaplan-Meier analysis demonstrated a significantly higher cumulative incidence of cardiac events in group 1, as compared with group 2 (Figure 3, p KO.0251. In group 1, no significant differences could be detected between those patients experiencing a cardiac event and those who did not. Multivariate Cox analysis of 11 variables indicated that asymptomatic myo-
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FIGURE 1. Frequency and duration ot total and asymptomatlc lsohemia during medical treatment and 3 months after coronary artery bypass graftlng (CABG) In 36 patients. Hatched bars denote silent myocardlal Ischemla.
FIGURE 2. Frequency and duratlon ot total and asymptomatlc lschemla In 12 patients (group 1) wlth silent lschemla after coronary artery bypass graftlng (CABG). /falc/ted bars denote silent myocardlal Ischemla.
February 1,1988
cardial ischemia was the most accurate predictor of cardiac events during a g-month follow-up period (p <0.005) and the presence of silent ischemia indicated a high increase in the relative risk of a cardiac event. Also of predictive value was the change in exercise capacity (p
Discussion Prediction of cardiac events after CABG is difficult to assess and exercise testing as well as quantitative radionuclide studies have limitations in identifying individual patients at risk .8Jg-21Although graft patency has been regarded as the best measure for successful revascularization,21 it does not always provide information on regional myocardial ischemia.g Using ambulatory monitoring, a relation between regional myocardial perfusion defects during ischemic episodes and transient ST-segment shifts has been established,*l so it is possible to examine episodes of transient myocardial ischemia during daily life even in asymptomatic patients. This study has demonstrated that CABG reduces the frequency (4170, p
THE AMERICAN
TABLE II
JOURNAL
OF CARDIOLOGY
Volume 81
251
Cardiac Events Group 1 (n = 12)
Group 2 (n = 24)
p Value
1 2 3 6
0 1 1 2
0.005
Sudden death Angina pectoris with CABG Angina pectoris Total
Cardiac events during g-month follow-up in 12 patients (group 1) with silent ischemia and 24 patients (group 2) without silent ischemia. CABG = coronary artery bypass grafting
quired in 2 and medical treatment in 3. This contrasts with the findings in group 2, where only 2 cardiac events occurred (S%]. Both were angina pectoris, one requiring revascularization and the other medical treatment. The results of the multivariate analysis show that the presence of asymptomatic myocardial ischemia was the most powerful predictor of cardiac events (p
* Probability
I%1
100
No silent
1
2
3
4
ischemia
5 Month
6
7
8
9
FIGURE 3. Kaplan-Meler curves of cumulative probabllltles for cardiac events during a g-month follow-up In 12 patients (group 1) wlth silent lechemla and 24 patients (group 2) without silent lschemla durlng ambulatory monltorlng.
252
SILENT ISCHEMIA
AFTER CABG
raises the question as to whether silent ischemia can persist without development of angina but with an increased risk for other cardiac events such as sudden death or myocardial infarction. These important questions cannot be assessed by this study alone, as the observation period was too short. This study has some other limitations. First, arteriography after CABG was not routinely performed, which precluded any knowledge of graft patency and progression of atherosclerosis in relation to silent ischemia. Even so, a poor correlation has been found between graft patency and occurrence of silent ischemia.g Second, ambulatory monitoring was performed for only 36 hours; more extensive monitoring could have identified silent ischemia in the 2 patients in group 2 with recurring angina pectoris. However, even the relatively short monitoring period used in this study provided important prognostic information.
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