Unstable Angina Pectoris w, A. WALLACE. M.D.. J . F. RICHESON.M.D.. P. N. YU,M.D. Cardiology Unit, University of Rochester, School of Medicine and Dentistry, Rochester, New York, USA
Summary: The pathophysiology of unstable angina has beep better elucidated in the past five years and has led
rational therapy. C O K " ~aneries in patients with unstable angina have atherosclerotic plaques which are often complex and are the site of platelet activation and fibrin deposition. Nitrates, one of the oldest therapies, are efficaciousand act not only by dilating coronary vessels but by reducing preload and afterload. Beta blockers have a salutary effect by decreasing myocardial oxygen demand. Calcium channel blockers attenuate smooth muscle contraction and thereby act to decrease coronary artery spasm. Beta blockers and calcium channel blockers aR equally efficacious in unstable angina. The antiplatelet agent, aspirin, has been shown to reduce fatal or nonfatal myocardial infarction and probably overall mortality. The use of heparin acutely for unstable angina has been demonstrated to decrease refractory angina and myocadial infarction, and acutely is probably better than aspirin. For patients with reduced ejection fmctions (0.30-0.49), a prospective randomized trial has shown that cpronary artery bypass graft surgery offers an improved three-year survival compared with medical therapy; however, sucgery does not prevent myocardial infarction. Percutanetransluminal coronary angioplasty may be a reasonable therapeutic alternative for spme patients with single-vessel disease who are refractory to medical theraPY but there are as yet no controlled trials of this questlon. To date a clinical benefit from thrombolytic therapy has not been demonstrated.
Key words: angina, unstable angina, coronary artery disease
toer,,
Address for reprints:
Wayne A . Wallace, M.D. Cardiology Unit University of Rochester %ol of Medicine and Dentistry 601 Elmwood Ave.
679
NY 14642. USA Jqnuary 8. 1990
March 26, 1990
Introduction Unstable angina continues to be a diagnostic and therapeutic challenge. It is a syndrome which bridges chronic stable exercise- or emotion-induced angina pectoris on one side and acute myocardial infarction on the other. Recent evidence suggests that several processes are likely operative in causing the ischemia in unstable angina pectoris and tailoring therapy againvt these will likely improve outcome.
Definition Unstable angina is a syndrome of low threshold myocardial ischemia without myocardial necrosis. This clinical syndrome can express itself in a number of ways: ( I ) more severe, prolonged, or frequent (i.e., crescendo) angina in g patient with previously stable exertion- or emotion-related angina; (2) new onset angina which occurs with minimal exertion; and (3.) angina at rest. Angina occurs independent of extracoronary precipitants such as anemia, thymtoxicosis, or cardiac anhythmias. Angina following acute myocardial infarction and Prinzmeq's variant angina are unique entities which will not be discussed here. Angina following acute myocardial infarction involves several mechanisms, some of which ate probably related to the infarction itself, and therefore patients with w e n t infarction have been excluded from most unstable angina pectoris trials. Prinzmetal's variant angina has coronary artery spasm as its dominant mechanism and therefore has a unique pathophysiology.
Clinical Features The quality of chest pain in unstable angina is similar to that of stable angina and acute myocardial infarction, although it tends to be more intense and prolonged than the former and not as prolonged as the latter. Physical find-
680
Clin. Cardiol. Vol. 13. October 1990
ings of dyskinesis, gallop sounds, or systolic murmur are not distinguishing. The electrocardiogram may show transient ST-segment depressions or elevations and/or T-wave inversions. Continuous electrocardiographic recordings by Holter monitors have demonstrated that patients with unstable angina frequently have ischemic ST-segment abnormalities in the absence of chest pain (“silent ischemia”) in addition to their episodes of overt angina. Q waves are a feature of infarction, not unstable angina. Likewise, cardiac enzymes are not elevated unless myocardial infarction has occurred. By definition, release of cardiac enzymes does not occur in unstable angina, although the interface between a severe episode of unstable angina pectoris and an enzymatically small myocardial infarction is quite hazy. The two may have similar pathophysiology and prognosis. Recent evidence suggests, however, that the conventional enzyme threshold for declaring myocardial necrosis may have been set too high.’
Natural History The natural history of unstable angina can be determined reasonably well from two studies by Mulcahy et al. 23In the first study 101 patients with unstable angina were treated conservatively without routine use of beta blockers, calcium antagonists, nitrates, or coronary artery bypass surgery, although beta blockers and nitrates were used in a few patients. Follow-up was one year. Overall mortality was 12 96 and nonfatal myocardial infarction occurred in 12%. In the later study, which was similar, 100 patients were followed for one year. Overall mortality was 9% and nonfatal myocardial infarction occurred in 14%. A difference was that an additional 11 % had coronary artery bypass graft surgery. Thus it would appear that patients with unstable angina not receiving intensive medical therapy or surgery can be expected to have a 24% incidence of death or myocardial infarction in one year.
Pathophysiology Ambrose et al. qualitatively examined the coronary artery lesions in patients with stable angina and unstable angina by coronary arteriography.* Lesions >50% (diameter) were categorized as (1) concentric (symmetric narrowing). (2) eccentric type I (asymmetric narrowing with smooth borders and a broad neck), (3) eccentric type I1 (asymmetric with a narrow neck or irregular borders or both), and (4) multiple irregular coronary narrowings in series (Fig. 1). Overall eccentric type I1 lesions in diseased vessels were seen in 54% of patients with unstable angina and in 7% of patients with stable angina (p
Summary: The pathophysiology of unstable angina has beep better elucidated in the past five years and has led
rational therapy. C O K " ~aneries in patients with unstable angina have atherosclerotic plaques which are often complex and are the site of platelet activation and fibrin deposition. Nitrates, one of the oldest therapies, are efficaciousand act not only by dilating coronary vessels but by reducing preload and afterload. Beta blockers have a salutary effect by decreasing myocardial oxygen demand. Calcium channel blockers attenuate smooth muscle contraction and thereby act to decrease coronary artery spasm. Beta blockers and calcium channel blockers aR equally efficacious in unstable angina. The antiplatelet agent, aspirin, has been shown to reduce fatal or nonfatal myocardial infarction and probably overall mortality. The use of heparin acutely for unstable angina has been demonstrated to decrease refractory angina and myocadial infarction, and acutely is probably better than aspirin. For patients with reduced ejection fmctions (0.30-0.49), a prospective randomized trial has shown that cpronary artery bypass graft surgery offers an improved three-year survival compared with medical therapy; however, sucgery does not prevent myocardial infarction. Percutanetransluminal coronary angioplasty may be a reasonable therapeutic alternative for spme patients with single-vessel disease who are refractory to medical theraPY but there are as yet no controlled trials of this questlon. To date a clinical benefit from thrombolytic therapy has not been demonstrated.
Key words: angina, unstable angina, coronary artery disease
toer,,
Address for reprints:
Wayne A . Wallace, M.D. Cardiology Unit University of Rochester %ol of Medicine and Dentistry 601 Elmwood Ave.
679
NY 14642. USA Jqnuary 8. 1990
March 26, 1990
Introduction Unstable angina continues to be a diagnostic and therapeutic challenge. It is a syndrome which bridges chronic stable exercise- or emotion-induced angina pectoris on one side and acute myocardial infarction on the other. Recent evidence suggests that several processes are likely operative in causing the ischemia in unstable angina pectoris and tailoring therapy againvt these will likely improve outcome.
Definition Unstable angina is a syndrome of low threshold myocardial ischemia without myocardial necrosis. This clinical syndrome can express itself in a number of ways: ( I ) more severe, prolonged, or frequent (i.e., crescendo) angina in g patient with previously stable exertion- or emotion-related angina; (2) new onset angina which occurs with minimal exertion; and (3.) angina at rest. Angina occurs independent of extracoronary precipitants such as anemia, thymtoxicosis, or cardiac anhythmias. Angina following acute myocardial infarction and Prinzmeq's variant angina are unique entities which will not be discussed here. Angina following acute myocardial infarction involves several mechanisms, some of which ate probably related to the infarction itself, and therefore patients with w e n t infarction have been excluded from most unstable angina pectoris trials. Prinzmetal's variant angina has coronary artery spasm as its dominant mechanism and therefore has a unique pathophysiology.
Clinical Features The quality of chest pain in unstable angina is similar to that of stable angina and acute myocardial infarction, although it tends to be more intense and prolonged than the former and not as prolonged as the latter. Physical find-
680
Clin. Cardiol. Vol. 13. October 1990
ings of dyskinesis, gallop sounds, or systolic murmur are not distinguishing. The electrocardiogram may show transient ST-segment depressions or elevations and/or T-wave inversions. Continuous electrocardiographic recordings by Holter monitors have demonstrated that patients with unstable angina frequently have ischemic ST-segment abnormalities in the absence of chest pain (“silent ischemia”) in addition to their episodes of overt angina. Q waves are a feature of infarction, not unstable angina. Likewise, cardiac enzymes are not elevated unless myocardial infarction has occurred. By definition, release of cardiac enzymes does not occur in unstable angina, although the interface between a severe episode of unstable angina pectoris and an enzymatically small myocardial infarction is quite hazy. The two may have similar pathophysiology and prognosis. Recent evidence suggests, however, that the conventional enzyme threshold for declaring myocardial necrosis may have been set too high.’
Natural History The natural history of unstable angina can be determined reasonably well from two studies by Mulcahy et al. 23In the first study 101 patients with unstable angina were treated conservatively without routine use of beta blockers, calcium antagonists, nitrates, or coronary artery bypass surgery, although beta blockers and nitrates were used in a few patients. Follow-up was one year. Overall mortality was 12 96 and nonfatal myocardial infarction occurred in 12%. In the later study, which was similar, 100 patients were followed for one year. Overall mortality was 9% and nonfatal myocardial infarction occurred in 14%. A difference was that an additional 11 % had coronary artery bypass graft surgery. Thus it would appear that patients with unstable angina not receiving intensive medical therapy or surgery can be expected to have a 24% incidence of death or myocardial infarction in one year.
Pathophysiology Ambrose et al. qualitatively examined the coronary artery lesions in patients with stable angina and unstable angina by coronary arteriography.* Lesions >50% (diameter) were categorized as (1) concentric (symmetric narrowing). (2) eccentric type I (asymmetric narrowing with smooth borders and a broad neck), (3) eccentric type I1 (asymmetric with a narrow neck or irregular borders or both), and (4) multiple irregular coronary narrowings in series (Fig. 1). Overall eccentric type I1 lesions in diseased vessels were seen in 54% of patients with unstable angina and in 7% of patients with stable angina (p
