Prognostic importance of exercise-induced ST-segment depression in patients with documented coronary artery disease

Transcription

1 European Heart Journal (1987) 8 (Supplement G), Prognostic importance of exercise-induced ST-segment depression in patients with documented coronary artery disease H. GOHLKE, P. BETZ AND H. ROSKAMM Rehabilitationszentrum fur Hen- und Kreislaufkranke, BadKrozingen, FRG KEY WORDS: ST-segment depression, exercise tolerance, coronary artery disease. Exercise-induced ST-segment depression is a marker of impaired prognosis in patients with suspected or manifest CAD. Whether ST-segment depression remains of prognostic importance, after exercise tolerance and extent of CAD have been considered, is unknown. We analysed the prognostic importance of exercise-induced ST-segment depression (> 0-15 mv') in 1250 medically treated patients with angiographically determined CAD (mean follow-up after angiography 4-5 vears). Based on exercise tolerance (supine bicycle ergometry) patients were divided into two groups: group A patients (n = 677) with lower exercise tolerance ( ^75 W) and group B patients (n = 573) with better exercise tolerance (>75W). Group A patients had a lower 5-year survival rate than group B patients (81-5% versus 94%, P<000001). In group A, patients with ST-segment depression had a lower 5-year survival rate than patients without STsegment depression (76% versus85%, P = 001). In group B, patients with and without ST-segment depression had similar 5-year survival rates (90% versus 96%, P=011). Subgroup analysis of groups A and B according to number of diseased vessels and presence or absence of ST-segment depression revealed that exercise-induced ST-segment depression (>015 mv) was of additional prognostic importance only in patients with triple vessel disease. 5-year survival rates in group A with triple vessel disease were 71% with and80% (P = 0-057) without ST-segment depression. Ingroup B 5- year survival was 80% with and98% without ST-segment depression, (P<0-04). ST-segment depression did not influence prognosis in patients with single and double vessel disease. After consideration of exercise tolerance and extent of CAD, exercise-induced ST-segment depression is of additional prognostic importance only in patients with triple vessel disease. Introduction after the coronary anatomy has been estab- ST-segment depression during exercise is associlished " " l ^ ^(xliye of the / resen ' stud y was ated with an increased risk of coronary death in a < ^ whethe K r exercise-induced ST-segment normal population''^', in an asymptomatic group depression contributes prognostic information and exercise tolerance have of individuals at increased risk for coronary artery f[ ter c ronar y anat0i 7 n li...,. c been taken into consideration. disease 1 ', in patients in the chronic phase of coronary artery disease 14 ' and in patients after myocardial infarction 15^1. The impaired prognosis has been Methods related to the fact that patients with ST-segment,....,.,.... PATIENT SELECTION depression are more likely to have triple vessel lrv^o disease; and patients with 3-vessel disease have a Between 1975 and I97 8 U ' 125 P alients under " poorprognosis.ithasalsobeenshownthatexercise? ent z^^. angiography as well as symptomtolerance is of additional prognostic importance hmited exe K l lesun f} These P atients had more than 50% luminal diameter narrowing of at Address correspondence to: PD Dr. H. Gohlke, Rehab.lilatiomaenleaSt One VeSSel and were treated medically after irum fur Herz- und Kreislaufkranke, D-7812 Bad Krozingen, FRG. angiography X/8708G S The European Society of Cardiology

2 110 H. Gohlke eia\. EXERCISE TESTING All patients underwent exercise testing in the postabsorptive state, after all antianginal drugs had been discontinued for at least 12 hours. Exercise testing was performed with an electrically braked bicycle ergometer in the supine position. Exercise was started at 25 or 50 watts, depending on the previously tested exercise tolerance, and was increased by 25 or 50 watts every 6 minutes until fatigue, severe angina, or more than 0-3 mv STsegment depression occurred, or 80% of the age predicted maximal heart rate was reached. A ninelead ECG was recorded (I, II, III, avr, avl, avf, V2, V4, V6) before and immediately after exercise; during exercise leads V3, V4 and V6 were recorded at the end of each minute at 50mm sec" 1. STsegment depression was measured at msec after the J-point. CORONARY ANGIOGRAPHY Coronary angiography was performed with the Sones technique in the majority of patients. Sublingual nitroglycerin was given, usually before angiography. The reduction of the luminal diameter of the coronary artery was analyzed with the help of an optical gauge in reference to the diameter proximal to the obstruction. Diameter reduction greater than 50% was considered significant. STATISTICAL ANALYSIS Survival curves were computed according to Cutler and Ederer* 12 ', and comparison of the survival rates between different subgroups was tested by the method of Mantel and Haenszel 1 ' 31. A probability level of 005 was considered significant FOLLOW UP Follow up was obtained by questionnaires. Follow up was 98% complete. The endpoint of follow up was death. In case of bypass surgery the patient was withdrawn from the study at the time of surgery. Results The clinical, angiographic and exercise characteristics of the patients are shown in Table 1. The extent of coronary disease differed in the subgroups with and without exercise-induced ST-segment depression (Table 2). The percentage of patients with triple vessel disease was significantly higher in the group with exercise-induced ST-segment depression (41 1% vs22-6%; P<0000\). The average number of diseased vessels was 2-1 in the group Table I Patient population Number of patients Mean age (years ±SD) Male sex Single vessel disease Double vessel disease Triple vessel disease SO 1 mv ST-segment depression during exercise > 0-15 mv ST-segment depression during exercise Exercise tolerance < 75 W 50-6± (89%) (63%) (37%) (54%) Table 2 Prevalence of /-, 2-, and 3-vessel disease in patients with and without exercise induced ST-segment depression f VD = vessel disease) V-D 1-VD 2-VD 3-VD *P<tOOOOO\. STj >01 mv (300%) (28.9%) (41-1%)* (100%) astj 206 (43 9%) 157 (33-5%) 106 (22-6%)* 469 (100%) with and 1-8 in the group without ST-segment depression. The 5-year survival rate of the cohort based on ST-segment depression (>01 mv) was marginally (89% vs 86%) better for patients without ST-segment depression (P<008; Table 3). If a cut-off point of 015mV ST-segment depression was used for division of the patient cohort, the difference in 5-year surivival between the two subgroups reached statistical significance 90% vs 83%,/><0003). Based on exercise tolerance, the cohort was divided into two approximately equally sized groups. Six hundred seventy seven patients had an exercise tolerance < 75 watts, and 573 patients an exercise tolerance of >75 watts. The extent of coronary disease was again different between the two groups (Table 4). In the group with lower exercise tolerance, the percentage of patients with triple vessel disease was significantly higher compared to the group with better exercise tolerance (45-5vs208%, P< ). The average number of diseased vessels was 2-2 in the patients with lower exercise tolerance versus 1 1 in patients with better exercise tolerance. The survival rate of the group with higher exercise tolerance was better than the survival rate of

3 Prognostic importance of ST-segment depression 111 Table 3 5-year survival rate according to ST-segmenl depression or exercise tolerance (n= 1250) 5-year survival rate (%) _ With vs without ST =s 0-1 mv With vs without ST1 > 0-15 m V Exercise tolerance $ 75 W vs > 75 W 860% vs890% < % vs900% < % vs940% < Table 4 Prevalence of 1-, 2-, and 3-vessel disease in patients with differing exercise tolerance < 75 watts versus > 75 watts VD 1-VD 2-VD 3-VD */>« n (%) Exercise tolerance = 75 watts > 75 watts n (%) 178 (26-3%) 191 (28-2%) 308 (45-5%)' 677 (100%) 262 (45-7%) 192 (33-5%) 119 (20-8%)* 573 (100%) patients with lower exercise tolerance (940vs 81-5%, P<00001). The differences in survival between patients with and without ST-segment depression as well as between patients with better and lower exercise tolerance could be partially explained by the different distribution of the extent of CAD; however, despite a similar distribution of triple vessel disease in patients with ST-segment depression compared to patients with low exercise tolerance, the survival rate was lower in patients with a poor exercise tolerance compared to patients with ST-segment depression. The difference in the 5-year survival rate was 12-5% in the subgroups based on exercise tolerance ( 75 watts) as opposed to only 3% in the subgroups based on 01 mv STsegment depression, and 7% based on the presence or absence of > 0-15 mv ST-segment depression. To analyze the prognostic importance of exercise tolerance and ST-segment depression at a given extent of coronary disease the patient cohorts with single, double, and triple vessel disease respectively were grouped according to exercise tolerance of less than 75 watts or more than 75 watts. Significant differences in survival between groups with better and lower exercise tolerance were seen in patients with single, double, and triple vessel disease respectively (Table 5). If the patients were subgrouped according to the number of diseased vessels and the occurrence of exercise-induced ST-segment depression, differences in survival between patients with and without ST-segment depression reached statistical significance only in patients with triple vessel disease (Table 5). Thus exercise tolerance appears to be of greater prognostic importance than ST-segment depression at any extent of coronary disease. To evaluate the independent prognostic importance of exercise induced ST-segment depression and to eliminate the prognostic influence of the extent of CAD and of exercise tolerance, the Table 5 Prognostic importance of exercise tolerance or exercise-induced ST-segment depression in patients with documented coronary anerv disease 5-year survival rate in patients with exercise tolerance of ^ 75 watts > 75 watts (n) % (n) % P 5-year survival rate in patients with ST-segment depression of >0 15mV <015mV (n) % (n) % P 1-vessel disease 2-vcssel disease 3-vessel disease (178) (191) (308) 90% 82-1% 75-7% (122) (192) (119) 95-4% 94-7% 88-2% (122) (131) (210) 91-7% 87-9% 73-6% (318) (252) (217) 93-7% 88-8% 84-6% (677) 81-5% (573) 94% (463) 83% (787) 90% 0003

4 112 H.GohlkeelaL Table 6 Five-year survival rate in relationship to exercise tolerance and ST-segment depression during exercise ^0 (n) 5-year survival in patients with exercise tolerance of < 75 W and ST-segment depression of >0 15mV % (n) % l5mv P $0 (») 5-year survival in patients with exercise tolerance of > 75 W and ST-segment depression of >015mV % (n) % l5mv P 1-vessel disease 2-vessel disease 3-vesscl disease (132) (126) (162) 90% (46) 89 8% 84% (65) 78-3% 80% (146) 71% (186) (126) (55) 96-6% (76) 92-7% 93-6% (66) 96-8% 98% (64) 79 6% (420) 84-5% (257) 76-3% 001 (367) 95 8% (206) 90 2% 011 patients were grouped into six subgroups according to exercise tolerance of less or more than 75 watts and according to the extent of coronary disease (Table 6). If exercise tolerance and extent of coronary disease are taken into consideration, ST-segment depression is of additional prognostic importance only in patients with triple vessel disease. Thus the extent of coronary disease and exercise tolerance contain most of the information in predicting survival up to 5 years after angiography and exercise testing (Table 6). Exercise-induced ST-segment depression adds prognostic information only in patients with triple vessel disease. Discussion Exercise-induced ST-segment depression in patients with suspected and manifest coronary disease has long been known to be a marker of impaired prognosis' 1 ''. Our analysis shows that the impaired prognosis in patients with angiographically defined coronary disease and exerciseinduced ST-segment depression is mainly due to three mechanisms: (1) Patients with ST-segment depression are more likely to have multivessel disease with the associated reduced life expectancy. (2) Patients with ST-segment depression are more likely to have a low exercise tolerance than patients without ST-segment depression. Low exercise tolerance in patients with established coronary disease is of great prognostic importance at any extent of coronary disease' 10 " 1. (3) Exercise-induced ST-segment depression is of additional prognostic importance in patients with triple vessel disease after exercise tolerance has been taken into consideration. Thus, ST-segment depression is of less prognostic importance than exercise tolerance in patients with single and double vessel disease. In patients with triple vessel disease the prognostic importance of ST-segment depression is comparable to that of exercise tolerance; patients with triple vessel disease and an exercise tolerance of > 75 watts with ST-segment depression of «;OI5mV had a 5-year survival rate of 98% whereas patients with similar exercise tolerance but with ST-segment depression of > 0-15 mv had a 5- year survival rate of only 80% (f<004). Patients with low exercise tolerance (<75W) and ST-segment depression ^015mV had a 5- year survival rate of 80% compared to 71 % of those with exercise induced ST-segment depression of >015mV (/> = 0-057). In these patients, STsegment depression identified patients at increased risk after extent of coronary disease and exercise tolerance have been considered. In contrast, in patients with single and double vessel disease, exercise-induced ST-segment depression is of little, if any, prognostic importance beyond the extent of coronary disease and exercise tolerance. Limitations of the study This study is a retrospective analysis of consecutive patients with significant coronary disease and without other significant cardiac disease in whom medical management was preferred for a variety of reasons. It is not clear whether these results can be extended to patients who are surgical candidates. However, similar relationships were seen between preoperative excerise performance and postoperative survival' 1415 ' in patients undergoing bypass surgery, suggesting that the results of exercise testing are of prognostic importance in several subsets of patients with CAD including those undergoing bypass surgery.

5 Prognostic importance of ST-segment depression 113 References [1] McDonald L. Very early recognition of coronary heart disease. In: Yu P, Goodwin J (eds) Progress in Cardiology', vol. 8. Philadelphia: Lea & Febiger, 1979: [2] Bruce RA, Hossaclc KF, DeRouen TA, Hofer V. Enchanced risk assessment for primary coronary heart disease events by maximal exercise testing: 10 years' experience of Seattle heart watch. J Am Coll Cardiol 1983; [3] Multiple Risk Factor Intervention Trial Research Group Exercise ECG and coronary heart disease mortality in the multiple risk factor intervention trial. Am J Cardiol 1985; [4] Cole JP, Ellestad M. Significance of chest pain during treadmill exercise, correlation with coronary events. Am J Cardiol 1978; 41: [5] Paine TO, Dye LE, Roitman DI, Sheffield LT, Rackley CE. Russel RO, Rogers WJ. Relation of graded exercise test findings after myocardial infarction to extent of coronary artery disease and left ventricular dysfunction Am J Cardiol 1978; 42: [6] Samek L, Roskamm H, Rentrop P, Kaiser P, Sturzenhofecker P, Schober B, Gomandt L, Velden R. Belastungsprufungen und Koronaraugiogramm im chronischen Infarktstadium. Z Kardiol 1975; [7] Starling MR, Crawford MH, Kennedy GT, O'Rourke RA. Exercise testing early after myocardial infarction: predictive value for subsequent unstable angina and death Am J Cardiol 1980; 46: [8] Tubau JF, Chaitman BR, Bourassa MG, Waters DD. Detection of multivessel coronary disease after myocardial infarction using exercise stress testing and multiple ECG lead systems. Circulation 1980; 61: [9] Weiner DA. McCabe C, Klein MD, Ryan TJ. STsegment changes post-infarction: predictive value for multivessel coronary disease and left ventricular aneurysm. Circulation 1978; 58: [10] Gohlke H, Samek L, Betz P, Roskamm H. Exercise testing provides additional prognostic information in angiographically defined subgroups of patients with coronary heart disease. Circulation 1983; 68: [11] Weiner DA, McCabe CH, Ryan TJ. Prognostic assessment of patients with coronary artery disease by exercise testing. Am Heart J 1983; 105: [12] Cutler S, Ederer F. Maximum utilization of the life table method in analyzing survival. J Chron Dis 1958; 8: 699. [13] Mantel N, Haenszcl W. Statistical aspects of the analysis of data from retrospective studies of disease. J Nat Cancer Inst 1959; 22: [14] Gohlke H, Gohlke-Barwolf C, Samek L, Roskamm H. Erleichtert die Belastungsuntersuchung die Indikationsstellung zur Bypassoperation bei Patienten mit ZweigefaBerkrankung? Z Kardiol 1983; 72: 265 (Abstract). [15] Weiner DA, Ryan TJ, McCabe CH, Chaitman BR, Sheffield LT, Ferguson JC, Fisher LD, Tristani F. The value of preoperative exercise testing in predicting long-term survival in patients undergoing aortocoronary bypass surgery. Circulation 1984; 70 (Suppl I):