View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector lACC Vol. 6, No.2 275 August 1985:275-84 Silent Myocardial Ischemia: Qemodynamic Changes During Dynamic Exercise in Patients With Proven Coronary Artery Disease Despite Absence of Angina Pectoris HEINZ O. HIRZEL, MD, RUTH LEUTWYLER, HANS P. KRAYENBUEHL, MD Zurich, Switzerland The hemodynamic changes during exercise occurring in fraction decreased (from 59 ± 7 to 50 ± 15 and from 36 patients with proven coronary artery disease (10 with• 60 ± 4 to 52 ± 9% in the study and control groups out and 26 with previous myocardial infarction) who without prior infarction and from 54 ± 9 to 47 ± 10 tolerated the stress test without angina were analyzed and 55 ± 9 to 50 ± 4% in the respective groups with aud compared with changes observed in a control group prior infarction). Whereas the changes from rest to ex• of 36 carefully matched patients whose exercise was lim• ercise were highly significant within each group, no sig• ited by angina. All patients were exercised to the same nificant differences were noted between the correspond• extent, reaching a similar rate-pressure product at the ing groups. Regional de novo hypokinesia appeared in end of the stress test (19,508 ± 4,828 [SD] versus 19,247 all patients without prior infarction and in 25 and 22 ± 4,1l7 beats/min x mm ~g [NS] in the study and patients, respectively, of the groups with prior infarction. control groups without prior infarction, and 19,665 ± Thus, under similar physical stress conditions, com• 3,950 versus 17,701 ± 4,600 beats/min x mm Hg [NS] parable hemodynamic changes indicative of ischemia are in the respective groups with infarction). In all groups observed in patients with significant coronary artery le• left ventricular end-diastolic pressure increased from rest sions with or without previous myocardial infarction ir• to exercise (from 18 ± 4 to 36 ± II and from 13 ± 5 respective of the occurrence of angina. Therefore, an• to 29 ± 9 mm Hg, respectively, in the study and control gina pectoris cannot be considered a prerequisite for groups without prior infarction and from 17 ± 7 to 32 hemodynamically significant ischemia during exertion. ± 13 and from 19 ± 7 to 36 ± 9 mm Hg in the respective (J Am Coil Cardiol 1985;6:275-84) groups with prior infarction). Left ventricular ejection Angina pectoris is considered a sensitive marker of ischemic scure and little is known about the hemodynamic changes events. Indirect evidence, however, suggests that ischemia associated with such attacks. may also occur silently, without accompanying chest pain. Whereas global and regional changes of left ventricular Such evidence has been derived from exercise induced ST function in the anginal state induced by various stress tests segment changes (1-6), clear-cut perfusion defects at stress are well studied (15-25), only a few reports (25-27) have scintigraphy (7,8) or typical ischemic electrocardiographic dealt with alterations of function during dynamic exercise alterations during continuous ambulatory Holter monitoring tolerated without angina despite significant coronary artery (8-14) in asymptomatic patients with arteriographically proven lesions. Thus, we examined the hemodynamic changes dur• coronary artery lesions and patients who later developed ing exercise occurring in 36 of 258 consecutive patients symptomatic coronary heart disease. Yet, the underlying with proven coronary artery disease who tolerated the stress pathophysiologic mechanisms of silent ischemia remain ob- test without symptoms. Methods From the Department of Medicine. Medical Policlinic. Division of StuJly patients (Groups I and II). Of 258 consecutive Cardiology. University Hospital. Zurich. Switzerland. This work was sup• ported in part by a grant of the EM DO-Foundation, Zurich. Switzerland. patients with arteriographically severe coronary artery le• Manuscript received December 5. 1984; revised manuscript received March sions who were evaluated by dynamic exercise during the 12. 1985. accepted March 29. 1985. invasive examination, 36 were angina-free on admission and Address for reprints: Heinz O. Hirzel, MD. Department of Medicine. Medical Policlinic. Division of Cardiology. University Hospital. CH-8091 had no anginal symptoms during a bicycle stress test con• Zurich. Switzerland. ducted in the upright position on the day before cardiac © 1985 by the American College of Cardiology 0735-1097/85/$3.30 276 HIRZEL ET AL. JACC Vol. 6, No.2 HEMODYNAMIC CHANGES IN SILENT ISCHEMIA August 1985:275-84 catheterization and at catheterization. All 36 patients had weeks before the present admission. Thus, at hospital entry, experienced one or more episodes of chest pain 4 to 8 months none of the patients was receiving appropriate antianginal before admission and 26 patients had a history of myocardial therapy. infarction that dated back more than 6 months. The indi• Control patients (Groups III and IV). The 36 patients cation for catheterization was posed at the time when symp• without exercise-induced angina were matched with 36 pa• toms occurred or in the early recovery period after myo• tients who were limited by angina at stress. These control cardial infarction and was determined on the basis of objective patients were similar to the patients without stress-induced findings such as a positive exercise stress test or exercise• angina in age, number of diseased vessels, extent of ath• induced reversible perfusion defects in the thallium-20l erosclerosis, left ventricular end-diastolic pressure at rest, scintigram, or both. All patients were male, ranging in age ejection fraction and absence of site of prior myocardial from 26 to 63 years (Table 1). Group I consisted of 10 infarction. The diagnosis of a previous myocardial infarction patients without prior myocardial infarction and Group II was based on the history of an appropriate event associated of 26 patients with prior myocardial infarction. with electrocardiographic or enzymatic changes, or both, Before hospital entry, 5 of the 10 patients without prior and circumscribed left ventricular asynergy in the angiogram infarction in Group I were treated intermittently with beta• at rest. Despite continued medical therapy, all control pa• receptor blocking agents, and long-acting nitrates, 3 patients tients continued to have effort-induced angina. To obtain with beta-blocking agents, long-acting nitrates and calcium the most precise information regarding the clinical relevance channel antagonists, 1 with beta-blocking agents and cal• and severity of the disease, all medication with the excep• cium antagonists and 1 with beta-blocking agents only. The tion of short-acting nitrates was discontinued in all patients 26 patients in Group II had received beta-blocking agents on admission. No withdrawal effects necessitated restoration and long-acting nitrates prophylactically for 3 months fol• of full antianginal therapy in any patient. lowing hospital discharge after infarction. Because symp• Clinical evaluation. All patients were examined clini• toms did not reappear when discontinuing medication the cally and by routine laboratory tests including a 12 lead majority of these patients had stopped medication several standard electrocardiogram at rest and a continuous muIti- Table 1. Characteristics of the Four Patient Groups With Proven Coronary Artery Disease Patients Without MI Patients With MI Group I Group III Group II Group IV (without AP) (with AP) (without AP) (with AP) Patients (no.) 10 10 26 26 Age (yr) Mean 52 ± 7 50 ± 6 48 ± 9 49 ± 8 Range 38 to 63 39 to 63 26 to 61 33 to 60 Levine vascularization index -1.7 ± 0.9 -1.7 ± 0.8 -1.8 ± 0.9 -1.9 ± 0.8 Number of diseased vessels I vessel 2 2 8 6 2 vessels 6 6 5 7 3 vessels 2 2 13 13 Critically stenosed vessels (>70% narrowing) LAD 5 6 21 24 LCx 8 7 II 11 RCA 6 6 17 17 Site of infarction Anterior II II Posterior 15 15 Upright bicycle stress test 131 ± 21 98 ± 39* 129 ± 37 97 ± 32t work load attained (walls) ST segm~nt depression 3 6 12 13 (>0.1 mY) ST segment elevation o o (>0.1 mV) Angina pectoris o o 26t Values are expressed as mean values ± I SO. *p < 0.05 versus Group I; tp < 0.01 versus Group II; tp < 0.001 versus Groups I and II, respectively (unpaired t tests). AP = exercise-induced angina pectoris; LAD = left anterior descending coronary artery; LCx = left circumflex coronary artery; MI = myocardial infarction; RCA = right coronary artery. JACC Vol. 6, No.2 HIRZEL ET AL. 277 August 1985:275-84 HEMODYNAMIC CHANGES IN SILENT ISCHEMIA stage bicycle exercise test in the upright posture with re• Coronary angiography. The angiographic severity of cording of precordial leads V2 , V4 , and Vo. Exercise testing coronary artery disease was assessed by the numerical score was performed according to a modified Bruce protocol (28). proposed by Levine et al. (32). Thus, fixed values were The target work load was determined from a nomogram that assigned to each obstructive lesion located in any of the adjusted for age, sex and height (29). Exercise was started three coronary vessels and their major side branches. Le• at about one third of the target work load; the work load sions with less than 70% reduction in luminal diameter were was then increased stepwise every 3 minutes until chest considered hemodynamically insignificant and were as• pain, dyspnea, fatigue or muscle weakness forced interrup• signed the value O. A 70 to 90% stenosis was assigned the tion of exertion. value - 0.5, and a more than 90% stenosis or occlusion Cardiac catheterization and angiography. Premed• of the vessel was given the value - 1.0. By summing the ication consisted of chlordiazepoxide (Librium), 10 mg, values calculated for each individual coronary artery system given perorally I hour before the study. After left heart the vascularization index was established.