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Current medical management versus coronary arterial bypass grafting in patients with stable angina pectoris
Current Medical Management Versus Coronary Arterial Bypass Grafting in Patients With Stable Angina Pectoris
Frederick A. Heupler, Jr., MD, FACC, Cleveland, Ohio
Until very recently, angina pectoris due to coronary atherosclerosis was considered a “medical disease.” However, dramatic innovations in the management of patients with angina pectoris have occurred over the past decade due to the introduction of direct myocardial revascularization surgery. During the 19608, as a result of the pioneering work of F. Mason Sones at the Cleveland Clinic, selective coronary arteriography became widely available for definitive diagnostic evaluation of patients with angina pectoris. This technique permitted the physician to obtain a detailed “road map” of the location and severity of coronary arterial obstructions, without which coronary bypass surgery would have been impossible. In the late 196Os, the introduction of the coronary arterial saphenous vein bypass graft operation by Favaloro permitted surgeons to revascularize these obstructed arteries. Over the past decade, improvement in surgical technique, anesthesia, and pre- and postoperative management of patients with coronary bypass have produced a dramatic decrease in operative mortality and morbidity and an increase in the surgical success rate. As a result, the indications for coronary bypass surgery have expanded. At the same time, the availability of new drugs and a better understanding of the hemodynamic effects of drug therapy have improved the success rate of medical treatment. As with any new operation, controversy has arisen regarding the safety, effectiveness and indications for coronary bypass surgery as well as the relative value of medical versus surgical treatment of patients with angina pectoris. The purpose of this report is to summarize the current status of medical and surgical therapy for patients with angina pectoris. Treatment of Angina Pectoris: General Principles Importance of coronary arteriography: Strictly speaking, the physician does not treat angina pectoris, but rather the disease which causes angina From the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Requests for reprints should be addressed to Frederick A. Heupler, Jr., MD, Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio 44106. Resented at the Sixth Annual Lyman A. Brewer Ill Cardiothoracic Sym posium, Los Angeles, California, December 3 and 4, 1980.
Volume 141, June 1981
pectoris. A variety of conditions, both cardiac and noncardiac, may produce angina-like chest pain. The application of specific antianginal therapy requires identification of the underlying disease which is producing the syndrome. Coronary arteriography and left ventriculography provide the most definitive method for evaluating coronary anatomy, and they also provide important prognostic information. The extent of coronary obstructions and the status of the left ventricle correlate better with prognosis than any other clinical parameter, including symptoms and findings on electrocardiography and stress testing. Therefore selective coronary arteriography is indicated for the evaluation of most patients with angina pectoris. As a result of improved techniques and equipment, the risks of coronary arteriography and left ventriculography have improved dramatically over the past two decades. The risk of mortality in patients undergoing coronary arteriography at the Cleveland Clinic during 1978 and 1979 (more than 11,000 cases) was less than 1 in 2,000, the risk of acute myocardial infarction was less than 1 in 1,000, the risk of stroke was less than 1 in 10,000, of median nerve injury less than 1 in 10,000 and of brachial arterial occlusion 2 in 100. Chronicity of coronary disease: Coronary atherosclerosis is a chronic disease. At present there is no cure, medical or surgical, for patients with angina pectoris due to obstructive coronary arterial disease. However, both medical and surgical therapy can produce major symptomatic improvement. The gratification produced by successful coronary bypass surgery in a young patient with incapaciting angina must be tempered by the realization that the patient is likely to develop progressive atherosclerosis in the future. The atherosclerotic process is then likely to involve the bypass graft as well as the native circulation. Ten to 20 percent of saphenous vein grafts become occluded in 1 year, and the annual attrition rate of saphenous vein grafts thereafter is approximately 2 percent per year. In 1979,4.5 percent of all coronary arterial bypass operations at the Cleveland Clinic were reoperations. In 71 percent of these patients, progressive atherosclerosis in the coronary arteries had occurred since the previous catheterization. 851
Heupler
Complementary relation of medical and surgical therapy: The relation between the medical and surgical therapy of angina is complementary, not competitive. Rare is the cardiologist in the 1930s who would not recommend coronary bypass surgery for a severely symptomatic patient with left main trunk disease. Also, most surgeons would recommend medical therapy consisting of weight and blood pressure control and avoidance of tobacco after coronary bypass surgery. The controversy with regard to medical versus surgical treatment of angina pectoris lies in the selection of subgroups of patients for coronary bypass and the timing of surgery. Medical Treatme~ of Angina Pectoris The medical therapy of angina pectoris due to coronary atherosclerosis may be divided into three approaches: life-style adjustment, treatment of associated diseases and specific medication. An understanding of the mechanism of medical therapy depends on knowledge of the pathoph~iolo~ of angina pectoris. Pathophysiology: Angina pectoris in patients with coronary atherosclerosis is produced by an imbalance between myocardial oxygen demand and supply. A fixed, severe obstruction in one or more coronary arteries limits coronary blood flow (supply), and angina pectoris is usually produced by a transient increase in the myocardial oxygen requirement (demand). Most medical therapy produces a decrease in demand rather than an increase in supply. Therefore, a knowledge of the factors which determine myocardial oxygen demand is necessary to apply medical therapy intelligently. Myocardial oxygen consumption is determined by heart rate, systolic wall tension and myocardial contractility. An increase in cardiac work, and therefore in myocardial oxygen consumption, occurs with an increase in heart rate. Systolic wall tension is determined primarily by the afterload and preload of.the left ventricle. Afterloud refers to the resistance to ejection of blood (impedance) from the left ventricle, which is approximated by the systolic blood pressure. Preload refers to the end-diastolic volume of the left ventricle, which is more difficult to measure than the pulse or blood pressure, but which is reflected by the left ventricular end-diastolic pressure, or the mean pulmonary capillary wedge pressure. Myocardial contractility refers to the vigor of contraction of the myocardium, which is even more difficult to measure clinically, and which is usually not evaluated during therapy of patients with angina pectoris. Complex interactions between these determinants of myocardial oxygen make it difficult to predict the result of manipulations of each factor. For instance, an increase in heart rate, which increases myocardial demand, may be associated with a decrease in left ventricular end-diastolic volume and systolic blood 652
pressure, which in turn decreases myocardial oxygen demand. For clinical purposes, the pressure-rate product (systolic blood pressure X heart rate) is used as an approximation of myocardial oxygen consumption. In a patient with stable angina, the pressure-rate product at the onset of angina tends to remain stable unless there is progression of coronary disease [I]. Life-style adjustment: The methods of life-style adjustment in the treatment of angina pectoris are (1) exercise training; (2) diet therapy of obesity and hyperlipidemia; (3) cessation of smoking; and (4) avoidance of emotional stress, postprandial exertion, cold air and caffeine. These methods require more time and effort on the part of both the physician and the patient than other forms of medical therapy. The physician must educate and motivate the patient, since compliance is difficult to obtain with thistype of therapy. Unfortunately, patients often refuse to adjust their life-style since this involves changing longstanding habits. Exercise training improves the ability to perform total body work in relation to cardiac work. This training effect occurs predominantly due to a decrease in the heart rate response to exercise [I]. Thus exercise training permits the patient to perform a larger amount of total body work at a lower pressure-rate product than that which produces angina. For the patient with angina pectoris, an exercise program should be started under supervision, preferably after evaluation by a stress test, The patient should eventually exercise to a heart rate of 70 to 85 percent of the highest level safely achieved on exercise testing. This exercise should be repeated for 20 to 30 minutes at least three to four times a week to obtain a training effect. Weight reduction in obese patients may produce rapid improvement in exercise capacity. Dietary treatment of h~erlipidemia is commonly considered important, but it is not proven that such therapy in a patient with established coronary arterial obstructions retards the progression of disease or produces regression of atherosclerotic plaques. Such therapy does not produce any immediate change in symptoms or exercise tolerance. Cigarette smoking should be stopped completely since it produces immediate and long-term adverse effects in patients with angina pectoris. Patients with angina pectoris should avoid physical exertion in the presence of emotional stress or cold and after intake of caffeine or a large meal. These four factors may further decrease exercise tolerance because they increase pulse rate, blood pressure or both, and therefore increase myocardial oxygen demand. Treatment of associated diseases: Antihypertensive therapy is very important in patients with angina pectoris since systolic blood pressure is a major determinant of myocardial oxygen demand. In patients with angina and severe hypertension, The American Journal 01 Surgery
Bypass
blood pressure control alone may completely eliminate symptoms of angina. In patients with chronic stable angina, a rapid increase in the frequency of angina may be caused by severe anemia, for instance, due to a bleeding peptic ulcer, or by the onset of hyperthyroidism. In the former case, the increased symptoms are produced by decreased myocardial oxygen supply and in the latter by an increased oxygen demand. Specific therapy in each case will dramatically improve symptoms of angina. Medications in the treatment of angina pectoris: Nitrates and beta blockers are the backbone of medical therapy for angina pectoris. These two groups of drugs exert different hemodynamic effects, and they act synergistically to improve angina symptoms (Table I). Both act primarily by decreasing myocardial oxygen demand. Nitrates exert their major antianginal effect by decreasing left ventricular end-diastolic volume (preload reduction) and a minor effect by decreasing systolic blood pressure. These beneficial effects usually overshadow the mild adverse effect of a slight increase in pulse rate, which is also produced by nitrates. Beta blockers exert their major effect by slowing the heart rate, and a minor effect by lowering systolic blood pressure and left ventricular contractility. These beneficial effects usually predominate over the mild adverse effect of an increase in left ventricular end-diastolic volume. With the concomitant use of nitrates and beta blockers, the major bradycardic effect of beta blockers overcomes the adverse tachycardic effect of nitrates, and the nitrates interfere with the tendency of beta blockers to increase left ventricular end-diastolic volume. The dosage and duration of response of some commonly used nitrate preparations are as follows: sublingual nitroglycerin, 0.4 to 0.6 mg every 30 minutes; nitroglycerin ointment, 1 to 2 inches every 6 hours, sublingual isosorbide, 5 to 10 mg every 90 minutes; and oral isosorbide, 20 to 40 mg every 6 hours. Oral isosorbide is effective for prophylaxis of angina if used in adequate doses [2]. Nitroglycerin produces a rapid onset and short duration of effect, and it is useful for the treatment of acute attacks of angina and for prophylaxis immediately before events that tend to produce angina such as emotional upset, cold air and sexual intercourse. The major limiting factor in the use of nitrates is the tendency to produce headaches, especially in patients with a history of migraine. The dosage and duration of response of betablocking agents is as follows: propranolol (Inderalm), 20 to 80 mg 4 times a day, duration 8 hours; nadolol (Corgarda), 80 to 400 mg a day, duration 24 hours; and metoprolol (Lopressofl), 50 to 100 mg 4 times a day, duration 8 hours [3]. Nadolol has the advantage over propranolol of once a day dosage because of its long half-life. However, propranolol is less expensive. Metoprolol has the theoretical advantage of beta-one selectivity, which makes it safer to use in patients Volume 141, June 1981
TABLE I
Grafting
in Angina Pectoris
Physiologic Effects of Antianginal Drugs*
Determinants of Oxygen Consumption Heart rate Systolic wall tension Systolic pressure (“afterload”) Ventricular volume (“preload”) Myocardial contractility
Nitrates
Beta Blockers
t
11
1
1
II
t
f
1
* Arrows pointing upward indicate an adverse effect.
with bronchospasm. However, this selectivity tends to diminish with increasing dosage. The dosage of beta blockers should be increased until the desired effect is achieved or until the resting heart rate is reduced to 50 to 60 beatslmin. These agents should be used with caution or avoided in patients with chronic congestive heart failure, sinus bradycardia, severe valvular heart disease or severe obstructive pulmonary disease. Their use is limited by side effects such as lethargy, depression, impotence and sleep disorders. Calcium flux antagonists, also called “slow channel blockers,” were recently introduced for experimental use in the United States. These drugs include nifedipine, verapamil and diltiazem. They are particularly useful in patients with recurrent angina at rest, which is often produced by coronary arterial spasm. Agents of questionable value in the treatment of patients with angina pectoris include the platelet inhibitors, aspirin, sulfinpyrazone (Anturanea) and dipyridamole (Persantinem). At present, there is conflicting evidence regarding their effectiveness in the treatment of patients with arteriosclerotic heart disease. Effectiveness of medical therapy: Medical therapy ameliorates angina pectoris in approximately 80 to 90 percent of patients with stable angina but in only 60 to 70 percent of those with unstable angina. Due to variations in patient population, patient compliance, drug tolerance and uniformity of medical therapy among physicians, it is impossible to be certain of the incidence of “medical treatment failures” in a large population. For the same reasons, there is no good evidence that nitrate or beta-blocker therapy prolongs survival in patients with coronary atherosclerosis. Surgical Treatment
of Angina Pectoris
Not every patient with angina pectoris is a good candidate for coronary bypass surgery, and not every patient who is operable requires bypass surgery. The likelihood of surgical success varies depending on the preoperative anatomy. Therefore, any discussion of the indications for coronary bypass surgery requires 653
Heupler
Figure 1. Arferiograms of the right coronary artery in the ieft anterior oblique projection. A, angiogrsm of an Meal artery for coronary and BoodTuI101% B, a~~arn of a poor atfety for cotonary bypass, wttb numeroos ~xtmat bypass, w#h a severe proxlmaf ante anddfstal o~truct~~ and tiny branches. C, angiogram of a fair artery for coronary bypass, with distal obstrocthw~~but tarhe branches beyond the obstructions
consideration of operability, operative risk and likelihood of surgical success. Angiographic criteria for coronary bypass surgery: The ideal coronary artery for coronary bypass surgery has a fixed, severe proximal obstruction, large caliber, good runoff, no distal obstruction and functioning myocardium in its distribution There is a large “gray zone” between an ideal artery and an inoperable artery (Figure 1). Graft patency is directly related to artery size, with a patency rate of at least 90 percent for arteries more than 2 mm in diameter and less than 75 percent for arteries less than 1.5 mm in diameter [4]. Also, the patency rates for grafts to the left anterior descending artery are generally higher than those for the right and circumflex arteries. The highest graft patency rates, greater than 95 percent, have been reported with internal mammary artery anastomoses to the left anterior descending artery [5]. The ideal candidate for bypass surgery has wellpreserved left ventricular function. Ideally, coronary bypass grafts should be placed before extensive replacement of myocardium by scar tissue has occurred. Very severe left ventricular dysfunction may markedly increase the risk of surgery, and therefore the evaluation of left ventricular function is important in the candidate for coronary bypass. Angiographic evaluation of left ventricular function alone may occasionally be misleading, since transient myocardial ischemia may artifactually make left ventricular function appear worse. In borderline patients with severe left ventricular dysfunction, clinical evaluation and radionuclide studies are helpful in determining operative risk. Risk of coronary bypass surgery: Operative mortality in coronary bypass surgery is related to the number of arteries grafted and to the degree of left ventricular dysfunction. The operative mortality in 2,414 patients at the Cleveland Clinic in 1979 was 0.6, 1.1 and 1.4 percent for one, two, and three or more bypass grafts, respectively, with an overall mortality 654
of 1.2 percent. These statistics include patients with unstable angina, emergency surgery and repeat surgery. If only patients with stable angina are included, the mortality was even lower, with a total mortality less than 1 percent. The overall risk of myocardial infarction was 1.6 percent. Left ventricular dysfunction independently increases the risk of coronary bypass surgery. This increased risk is detectable only when left ventricular ejection fraction has fallen below 45 percent and is large only when the ejection fraction has fallen below 30 percent [6]. With modern methods of myocardial preservation during surgery, it is now unusual for a patient to be turned down for coronary bypass surgery solely because of left ventricular dysfunction. The assessment of myocardial infarction after coronary bypass surgery is difficult because increases in cardiac enzymes and repolarization abnormalities on the electrocardiogram commonly occur postoperatively in the absence of infarction. New Q waves, which are “hard” evidence of perioperative myocardial infarction, occurred in 1.6 percent of patients undergoing coronary bypass surgery at the Cleveland Clinic in 1979. Benefits of coronary bypass surgery: Coronary bypass surgery produces total relief of angina in more than 60 percent of patients and partial relief in more than 90 percent. Improvement in symptoms is related to the completeness of revascularization. Total relief of angina is expected in more than 90 percent of patients with complete revascularization and 55 percent of those with incomplete revascularization. The impressive s~ptomati~ improvement after coronary bypass surgery may be due to a placebo effect in some patients, since it has been demonstrated that some patients have improvement in symptoms even if all grafts are occluded. However, objective evidence of improved myocardial perfusion after coronary bypass surgery has been demonstra~d by direct measurement of coronary flow at surgery, improved exercise test performance and radionuclide The American Journal of Surgery
Bypass Grafting in Angina Pectoris
studies. Vein graft patency correlates well with both objective evidence of improved myocardial perfusion and relief of angina. Improvement in survival after coronary bypass surgery is considered in detail later in this symposium. Briefly, patients who undergo coronary bypass surgery for left main trunk, double and triple vessel disease have a better 5 and 10 year survival than similar patients treated medically (Table II) [7]. Improved survival is easiest to demonstrate in the high risk subgroups. The failure of the well-publicized VA cooperative study to show an improvement in survival after coronary bypass surgery was due to selection of low risk patients, an unusually high operative mortality and infarction rate, a high graft occlusion rate and incomplete revascularization [8]. A recent collection of reviews which describe improved survival in certain subgroups after coronary bypass surgery includes the results from the University of California at Davis, Emory University, University of Alabama, State University of New York at Buffalo, Texas Heart Institute, Veterans Administration, Hines Medical Center, Baylor, Seattle Veterans Administration Medical Center and the Cleveland Clinic [9]. The improved survival of patients with left main trunk and multiple vessel disease after coronary bypass surgery raises the question of advisability of surgery for asymptomatic patients. Unlike patients with many chronic diseases, patients with coronary atherosclerosis often die suddenly. In many of these patients no cardiac symptoms precede sudden death. Granted that, with improved diagnostic techniques, physicians can often detect coronary artery disease before the onset of symptoms, what further diagnostic and therapeutic procedures should then be undertaken once such a patient is identified? It does not seem logical to wait for the onset of symptoms in all such patients, since the first symptomatic event in more than one third of patients with coronary artery disease is sudden death or fatal myocardial infarction. No studies are available which compare the survival of asymptomatic patients who undergo coronary bypass surgery with those treated medically. However, we feel coronary bypass surgery is indicated in asymptomatic patients who appear at high risk due to extensive coronary disease. Current Indications for Coronary Bypass Surgery Because of the gray zone produced by patients whose coronary arteries and left ventricular function are not ideal for coronary bypass surgery, it is impossible to construct a “laundry list” of indications for surgery. However, the following general guidelines apply to patients with stable angina who are angiographically suitable candidates for coronary bypass surgery: (1) Coronary bypass surgery is superior to medical therapy in producing sustained relief of angina. (2) Operative mortality is less than 1 percent. Volume 141, June 1981
TABLE II
Survival After Coronary Bypass Surgery Survival After 5 Years
(%)
Obstructed Arteries (n)
Medically Treated CABG Candidates
CABG Patients
1 2 3 Left main
66 69 56 56
92 66 65
66
CABG = coronary arterial bypass graft.
(3) Coronary bypass surgery is superior to medical therapy for improving survival in certain high risk subgroups, including patients with left main trunk, double and triple vessel disease, a markedly abnormal stress test, or moderate left ventricular impairment. (4) Coronary bypass surgery should not be delayed until severe, generalized left ventricular dysfunction has occurred because the operative risk is increased and the likelihood of long-term benefit is diminished. Summary The medical treatment of angina pectoris consists of life-style adjustment, treatment of associated diseases, and administration of specific medications, especially nitrates and beta blockers. Coronary bypass surgery relieves or eliminates angina in 90 percent of patients, with operative mortality rates as low as 1 percent. Coronary bypass surgery improves survival in selected patients with left main trunk and multiple vessel disease. References 1. Clausen JP, Trap-Jensen J. Heart rate and arterial blood pressure during exercise in patients with angina pectoris: effects of training and of nitroglycerin. Circulation 1976;53:436-42. 2. Thadani U, Fung HL, Darke AC, Parker JO. Oral isosorbide dinitrate in the treatment of angina pectoris: dose-response relationship and duration of action during acute therapy. Circulation 1960;62:491-502. 3. Frishman W. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 1. Pharmacodynamic and pharmacokinetic properties. Appraisal and reappraisal of cardiac therapy, ed. AC Degraff and J Frieden. Am Heart J 1979;97:66370. 4. Walker JA, Friedberg HD, Flemma RJ, Johnson WD. Determinants of angiographic patency of aortocoronary vein bypass grafts. Circulation 1972;45-6 (Suppl 1):66-90. 5. Loop FD. Spampinato N, Siegel W, Effler DB. Internal mammary artery grafts without optical assistance: clinical and angiographic analysis of 175 consecutive cases. Circulation 1973:47-a (Suppl lll):l62-7. 6. Chaitman BR, Rogers WJ, Davis K. et al. Operative risk factors in patients with left main coronary-artery disease. N Engl J Med 1960;303:953-7. 7. Hurst JW, King SB. Logue B, et al. Value of coronary bypass surgery: controversies in cardiology. Part I. Cardiology t976;42:306-26. 6. Sheldon WC, Loop FD, Proudfit WL. A critique of the VA cooperative study. Cleve Clin Q 1976;45:225-30. 9. Hurst JW, ed. Update II. The heart. New York: McGraw-Hill, 1960; 127-259. 655
Frederick A. Heupler, Jr., MD, FACC, Cleveland, Ohio
Until very recently, angina pectoris due to coronary atherosclerosis was considered a “medical disease.” However, dramatic innovations in the management of patients with angina pectoris have occurred over the past decade due to the introduction of direct myocardial revascularization surgery. During the 19608, as a result of the pioneering work of F. Mason Sones at the Cleveland Clinic, selective coronary arteriography became widely available for definitive diagnostic evaluation of patients with angina pectoris. This technique permitted the physician to obtain a detailed “road map” of the location and severity of coronary arterial obstructions, without which coronary bypass surgery would have been impossible. In the late 196Os, the introduction of the coronary arterial saphenous vein bypass graft operation by Favaloro permitted surgeons to revascularize these obstructed arteries. Over the past decade, improvement in surgical technique, anesthesia, and pre- and postoperative management of patients with coronary bypass have produced a dramatic decrease in operative mortality and morbidity and an increase in the surgical success rate. As a result, the indications for coronary bypass surgery have expanded. At the same time, the availability of new drugs and a better understanding of the hemodynamic effects of drug therapy have improved the success rate of medical treatment. As with any new operation, controversy has arisen regarding the safety, effectiveness and indications for coronary bypass surgery as well as the relative value of medical versus surgical treatment of patients with angina pectoris. The purpose of this report is to summarize the current status of medical and surgical therapy for patients with angina pectoris. Treatment of Angina Pectoris: General Principles Importance of coronary arteriography: Strictly speaking, the physician does not treat angina pectoris, but rather the disease which causes angina From the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Requests for reprints should be addressed to Frederick A. Heupler, Jr., MD, Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio 44106. Resented at the Sixth Annual Lyman A. Brewer Ill Cardiothoracic Sym posium, Los Angeles, California, December 3 and 4, 1980.
Volume 141, June 1981
pectoris. A variety of conditions, both cardiac and noncardiac, may produce angina-like chest pain. The application of specific antianginal therapy requires identification of the underlying disease which is producing the syndrome. Coronary arteriography and left ventriculography provide the most definitive method for evaluating coronary anatomy, and they also provide important prognostic information. The extent of coronary obstructions and the status of the left ventricle correlate better with prognosis than any other clinical parameter, including symptoms and findings on electrocardiography and stress testing. Therefore selective coronary arteriography is indicated for the evaluation of most patients with angina pectoris. As a result of improved techniques and equipment, the risks of coronary arteriography and left ventriculography have improved dramatically over the past two decades. The risk of mortality in patients undergoing coronary arteriography at the Cleveland Clinic during 1978 and 1979 (more than 11,000 cases) was less than 1 in 2,000, the risk of acute myocardial infarction was less than 1 in 1,000, the risk of stroke was less than 1 in 10,000, of median nerve injury less than 1 in 10,000 and of brachial arterial occlusion 2 in 100. Chronicity of coronary disease: Coronary atherosclerosis is a chronic disease. At present there is no cure, medical or surgical, for patients with angina pectoris due to obstructive coronary arterial disease. However, both medical and surgical therapy can produce major symptomatic improvement. The gratification produced by successful coronary bypass surgery in a young patient with incapaciting angina must be tempered by the realization that the patient is likely to develop progressive atherosclerosis in the future. The atherosclerotic process is then likely to involve the bypass graft as well as the native circulation. Ten to 20 percent of saphenous vein grafts become occluded in 1 year, and the annual attrition rate of saphenous vein grafts thereafter is approximately 2 percent per year. In 1979,4.5 percent of all coronary arterial bypass operations at the Cleveland Clinic were reoperations. In 71 percent of these patients, progressive atherosclerosis in the coronary arteries had occurred since the previous catheterization. 851
Heupler
Complementary relation of medical and surgical therapy: The relation between the medical and surgical therapy of angina is complementary, not competitive. Rare is the cardiologist in the 1930s who would not recommend coronary bypass surgery for a severely symptomatic patient with left main trunk disease. Also, most surgeons would recommend medical therapy consisting of weight and blood pressure control and avoidance of tobacco after coronary bypass surgery. The controversy with regard to medical versus surgical treatment of angina pectoris lies in the selection of subgroups of patients for coronary bypass and the timing of surgery. Medical Treatme~ of Angina Pectoris The medical therapy of angina pectoris due to coronary atherosclerosis may be divided into three approaches: life-style adjustment, treatment of associated diseases and specific medication. An understanding of the mechanism of medical therapy depends on knowledge of the pathoph~iolo~ of angina pectoris. Pathophysiology: Angina pectoris in patients with coronary atherosclerosis is produced by an imbalance between myocardial oxygen demand and supply. A fixed, severe obstruction in one or more coronary arteries limits coronary blood flow (supply), and angina pectoris is usually produced by a transient increase in the myocardial oxygen requirement (demand). Most medical therapy produces a decrease in demand rather than an increase in supply. Therefore, a knowledge of the factors which determine myocardial oxygen demand is necessary to apply medical therapy intelligently. Myocardial oxygen consumption is determined by heart rate, systolic wall tension and myocardial contractility. An increase in cardiac work, and therefore in myocardial oxygen consumption, occurs with an increase in heart rate. Systolic wall tension is determined primarily by the afterload and preload of.the left ventricle. Afterloud refers to the resistance to ejection of blood (impedance) from the left ventricle, which is approximated by the systolic blood pressure. Preload refers to the end-diastolic volume of the left ventricle, which is more difficult to measure than the pulse or blood pressure, but which is reflected by the left ventricular end-diastolic pressure, or the mean pulmonary capillary wedge pressure. Myocardial contractility refers to the vigor of contraction of the myocardium, which is even more difficult to measure clinically, and which is usually not evaluated during therapy of patients with angina pectoris. Complex interactions between these determinants of myocardial oxygen make it difficult to predict the result of manipulations of each factor. For instance, an increase in heart rate, which increases myocardial demand, may be associated with a decrease in left ventricular end-diastolic volume and systolic blood 652
pressure, which in turn decreases myocardial oxygen demand. For clinical purposes, the pressure-rate product (systolic blood pressure X heart rate) is used as an approximation of myocardial oxygen consumption. In a patient with stable angina, the pressure-rate product at the onset of angina tends to remain stable unless there is progression of coronary disease [I]. Life-style adjustment: The methods of life-style adjustment in the treatment of angina pectoris are (1) exercise training; (2) diet therapy of obesity and hyperlipidemia; (3) cessation of smoking; and (4) avoidance of emotional stress, postprandial exertion, cold air and caffeine. These methods require more time and effort on the part of both the physician and the patient than other forms of medical therapy. The physician must educate and motivate the patient, since compliance is difficult to obtain with thistype of therapy. Unfortunately, patients often refuse to adjust their life-style since this involves changing longstanding habits. Exercise training improves the ability to perform total body work in relation to cardiac work. This training effect occurs predominantly due to a decrease in the heart rate response to exercise [I]. Thus exercise training permits the patient to perform a larger amount of total body work at a lower pressure-rate product than that which produces angina. For the patient with angina pectoris, an exercise program should be started under supervision, preferably after evaluation by a stress test, The patient should eventually exercise to a heart rate of 70 to 85 percent of the highest level safely achieved on exercise testing. This exercise should be repeated for 20 to 30 minutes at least three to four times a week to obtain a training effect. Weight reduction in obese patients may produce rapid improvement in exercise capacity. Dietary treatment of h~erlipidemia is commonly considered important, but it is not proven that such therapy in a patient with established coronary arterial obstructions retards the progression of disease or produces regression of atherosclerotic plaques. Such therapy does not produce any immediate change in symptoms or exercise tolerance. Cigarette smoking should be stopped completely since it produces immediate and long-term adverse effects in patients with angina pectoris. Patients with angina pectoris should avoid physical exertion in the presence of emotional stress or cold and after intake of caffeine or a large meal. These four factors may further decrease exercise tolerance because they increase pulse rate, blood pressure or both, and therefore increase myocardial oxygen demand. Treatment of associated diseases: Antihypertensive therapy is very important in patients with angina pectoris since systolic blood pressure is a major determinant of myocardial oxygen demand. In patients with angina and severe hypertension, The American Journal 01 Surgery
Bypass
blood pressure control alone may completely eliminate symptoms of angina. In patients with chronic stable angina, a rapid increase in the frequency of angina may be caused by severe anemia, for instance, due to a bleeding peptic ulcer, or by the onset of hyperthyroidism. In the former case, the increased symptoms are produced by decreased myocardial oxygen supply and in the latter by an increased oxygen demand. Specific therapy in each case will dramatically improve symptoms of angina. Medications in the treatment of angina pectoris: Nitrates and beta blockers are the backbone of medical therapy for angina pectoris. These two groups of drugs exert different hemodynamic effects, and they act synergistically to improve angina symptoms (Table I). Both act primarily by decreasing myocardial oxygen demand. Nitrates exert their major antianginal effect by decreasing left ventricular end-diastolic volume (preload reduction) and a minor effect by decreasing systolic blood pressure. These beneficial effects usually overshadow the mild adverse effect of a slight increase in pulse rate, which is also produced by nitrates. Beta blockers exert their major effect by slowing the heart rate, and a minor effect by lowering systolic blood pressure and left ventricular contractility. These beneficial effects usually predominate over the mild adverse effect of an increase in left ventricular end-diastolic volume. With the concomitant use of nitrates and beta blockers, the major bradycardic effect of beta blockers overcomes the adverse tachycardic effect of nitrates, and the nitrates interfere with the tendency of beta blockers to increase left ventricular end-diastolic volume. The dosage and duration of response of some commonly used nitrate preparations are as follows: sublingual nitroglycerin, 0.4 to 0.6 mg every 30 minutes; nitroglycerin ointment, 1 to 2 inches every 6 hours, sublingual isosorbide, 5 to 10 mg every 90 minutes; and oral isosorbide, 20 to 40 mg every 6 hours. Oral isosorbide is effective for prophylaxis of angina if used in adequate doses [2]. Nitroglycerin produces a rapid onset and short duration of effect, and it is useful for the treatment of acute attacks of angina and for prophylaxis immediately before events that tend to produce angina such as emotional upset, cold air and sexual intercourse. The major limiting factor in the use of nitrates is the tendency to produce headaches, especially in patients with a history of migraine. The dosage and duration of response of betablocking agents is as follows: propranolol (Inderalm), 20 to 80 mg 4 times a day, duration 8 hours; nadolol (Corgarda), 80 to 400 mg a day, duration 24 hours; and metoprolol (Lopressofl), 50 to 100 mg 4 times a day, duration 8 hours [3]. Nadolol has the advantage over propranolol of once a day dosage because of its long half-life. However, propranolol is less expensive. Metoprolol has the theoretical advantage of beta-one selectivity, which makes it safer to use in patients Volume 141, June 1981
TABLE I
Grafting
in Angina Pectoris
Physiologic Effects of Antianginal Drugs*
Determinants of Oxygen Consumption Heart rate Systolic wall tension Systolic pressure (“afterload”) Ventricular volume (“preload”) Myocardial contractility
Nitrates
Beta Blockers
t
11
1
1
II
t
f
1
* Arrows pointing upward indicate an adverse effect.
with bronchospasm. However, this selectivity tends to diminish with increasing dosage. The dosage of beta blockers should be increased until the desired effect is achieved or until the resting heart rate is reduced to 50 to 60 beatslmin. These agents should be used with caution or avoided in patients with chronic congestive heart failure, sinus bradycardia, severe valvular heart disease or severe obstructive pulmonary disease. Their use is limited by side effects such as lethargy, depression, impotence and sleep disorders. Calcium flux antagonists, also called “slow channel blockers,” were recently introduced for experimental use in the United States. These drugs include nifedipine, verapamil and diltiazem. They are particularly useful in patients with recurrent angina at rest, which is often produced by coronary arterial spasm. Agents of questionable value in the treatment of patients with angina pectoris include the platelet inhibitors, aspirin, sulfinpyrazone (Anturanea) and dipyridamole (Persantinem). At present, there is conflicting evidence regarding their effectiveness in the treatment of patients with arteriosclerotic heart disease. Effectiveness of medical therapy: Medical therapy ameliorates angina pectoris in approximately 80 to 90 percent of patients with stable angina but in only 60 to 70 percent of those with unstable angina. Due to variations in patient population, patient compliance, drug tolerance and uniformity of medical therapy among physicians, it is impossible to be certain of the incidence of “medical treatment failures” in a large population. For the same reasons, there is no good evidence that nitrate or beta-blocker therapy prolongs survival in patients with coronary atherosclerosis. Surgical Treatment
of Angina Pectoris
Not every patient with angina pectoris is a good candidate for coronary bypass surgery, and not every patient who is operable requires bypass surgery. The likelihood of surgical success varies depending on the preoperative anatomy. Therefore, any discussion of the indications for coronary bypass surgery requires 653
Heupler
Figure 1. Arferiograms of the right coronary artery in the ieft anterior oblique projection. A, angiogrsm of an Meal artery for coronary and BoodTuI101% B, a~~arn of a poor atfety for cotonary bypass, wttb numeroos ~xtmat bypass, w#h a severe proxlmaf ante anddfstal o~truct~~ and tiny branches. C, angiogram of a fair artery for coronary bypass, with distal obstrocthw~~but tarhe branches beyond the obstructions
consideration of operability, operative risk and likelihood of surgical success. Angiographic criteria for coronary bypass surgery: The ideal coronary artery for coronary bypass surgery has a fixed, severe proximal obstruction, large caliber, good runoff, no distal obstruction and functioning myocardium in its distribution There is a large “gray zone” between an ideal artery and an inoperable artery (Figure 1). Graft patency is directly related to artery size, with a patency rate of at least 90 percent for arteries more than 2 mm in diameter and less than 75 percent for arteries less than 1.5 mm in diameter [4]. Also, the patency rates for grafts to the left anterior descending artery are generally higher than those for the right and circumflex arteries. The highest graft patency rates, greater than 95 percent, have been reported with internal mammary artery anastomoses to the left anterior descending artery [5]. The ideal candidate for bypass surgery has wellpreserved left ventricular function. Ideally, coronary bypass grafts should be placed before extensive replacement of myocardium by scar tissue has occurred. Very severe left ventricular dysfunction may markedly increase the risk of surgery, and therefore the evaluation of left ventricular function is important in the candidate for coronary bypass. Angiographic evaluation of left ventricular function alone may occasionally be misleading, since transient myocardial ischemia may artifactually make left ventricular function appear worse. In borderline patients with severe left ventricular dysfunction, clinical evaluation and radionuclide studies are helpful in determining operative risk. Risk of coronary bypass surgery: Operative mortality in coronary bypass surgery is related to the number of arteries grafted and to the degree of left ventricular dysfunction. The operative mortality in 2,414 patients at the Cleveland Clinic in 1979 was 0.6, 1.1 and 1.4 percent for one, two, and three or more bypass grafts, respectively, with an overall mortality 654
of 1.2 percent. These statistics include patients with unstable angina, emergency surgery and repeat surgery. If only patients with stable angina are included, the mortality was even lower, with a total mortality less than 1 percent. The overall risk of myocardial infarction was 1.6 percent. Left ventricular dysfunction independently increases the risk of coronary bypass surgery. This increased risk is detectable only when left ventricular ejection fraction has fallen below 45 percent and is large only when the ejection fraction has fallen below 30 percent [6]. With modern methods of myocardial preservation during surgery, it is now unusual for a patient to be turned down for coronary bypass surgery solely because of left ventricular dysfunction. The assessment of myocardial infarction after coronary bypass surgery is difficult because increases in cardiac enzymes and repolarization abnormalities on the electrocardiogram commonly occur postoperatively in the absence of infarction. New Q waves, which are “hard” evidence of perioperative myocardial infarction, occurred in 1.6 percent of patients undergoing coronary bypass surgery at the Cleveland Clinic in 1979. Benefits of coronary bypass surgery: Coronary bypass surgery produces total relief of angina in more than 60 percent of patients and partial relief in more than 90 percent. Improvement in symptoms is related to the completeness of revascularization. Total relief of angina is expected in more than 90 percent of patients with complete revascularization and 55 percent of those with incomplete revascularization. The impressive s~ptomati~ improvement after coronary bypass surgery may be due to a placebo effect in some patients, since it has been demonstrated that some patients have improvement in symptoms even if all grafts are occluded. However, objective evidence of improved myocardial perfusion after coronary bypass surgery has been demonstra~d by direct measurement of coronary flow at surgery, improved exercise test performance and radionuclide The American Journal of Surgery
Bypass Grafting in Angina Pectoris
studies. Vein graft patency correlates well with both objective evidence of improved myocardial perfusion and relief of angina. Improvement in survival after coronary bypass surgery is considered in detail later in this symposium. Briefly, patients who undergo coronary bypass surgery for left main trunk, double and triple vessel disease have a better 5 and 10 year survival than similar patients treated medically (Table II) [7]. Improved survival is easiest to demonstrate in the high risk subgroups. The failure of the well-publicized VA cooperative study to show an improvement in survival after coronary bypass surgery was due to selection of low risk patients, an unusually high operative mortality and infarction rate, a high graft occlusion rate and incomplete revascularization [8]. A recent collection of reviews which describe improved survival in certain subgroups after coronary bypass surgery includes the results from the University of California at Davis, Emory University, University of Alabama, State University of New York at Buffalo, Texas Heart Institute, Veterans Administration, Hines Medical Center, Baylor, Seattle Veterans Administration Medical Center and the Cleveland Clinic [9]. The improved survival of patients with left main trunk and multiple vessel disease after coronary bypass surgery raises the question of advisability of surgery for asymptomatic patients. Unlike patients with many chronic diseases, patients with coronary atherosclerosis often die suddenly. In many of these patients no cardiac symptoms precede sudden death. Granted that, with improved diagnostic techniques, physicians can often detect coronary artery disease before the onset of symptoms, what further diagnostic and therapeutic procedures should then be undertaken once such a patient is identified? It does not seem logical to wait for the onset of symptoms in all such patients, since the first symptomatic event in more than one third of patients with coronary artery disease is sudden death or fatal myocardial infarction. No studies are available which compare the survival of asymptomatic patients who undergo coronary bypass surgery with those treated medically. However, we feel coronary bypass surgery is indicated in asymptomatic patients who appear at high risk due to extensive coronary disease. Current Indications for Coronary Bypass Surgery Because of the gray zone produced by patients whose coronary arteries and left ventricular function are not ideal for coronary bypass surgery, it is impossible to construct a “laundry list” of indications for surgery. However, the following general guidelines apply to patients with stable angina who are angiographically suitable candidates for coronary bypass surgery: (1) Coronary bypass surgery is superior to medical therapy in producing sustained relief of angina. (2) Operative mortality is less than 1 percent. Volume 141, June 1981
TABLE II
Survival After Coronary Bypass Surgery Survival After 5 Years
(%)
Obstructed Arteries (n)
Medically Treated CABG Candidates
CABG Patients
1 2 3 Left main
66 69 56 56
92 66 65
66
CABG = coronary arterial bypass graft.
(3) Coronary bypass surgery is superior to medical therapy for improving survival in certain high risk subgroups, including patients with left main trunk, double and triple vessel disease, a markedly abnormal stress test, or moderate left ventricular impairment. (4) Coronary bypass surgery should not be delayed until severe, generalized left ventricular dysfunction has occurred because the operative risk is increased and the likelihood of long-term benefit is diminished. Summary The medical treatment of angina pectoris consists of life-style adjustment, treatment of associated diseases, and administration of specific medications, especially nitrates and beta blockers. Coronary bypass surgery relieves or eliminates angina in 90 percent of patients, with operative mortality rates as low as 1 percent. Coronary bypass surgery improves survival in selected patients with left main trunk and multiple vessel disease. References 1. Clausen JP, Trap-Jensen J. Heart rate and arterial blood pressure during exercise in patients with angina pectoris: effects of training and of nitroglycerin. Circulation 1976;53:436-42. 2. Thadani U, Fung HL, Darke AC, Parker JO. Oral isosorbide dinitrate in the treatment of angina pectoris: dose-response relationship and duration of action during acute therapy. Circulation 1960;62:491-502. 3. Frishman W. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 1. Pharmacodynamic and pharmacokinetic properties. Appraisal and reappraisal of cardiac therapy, ed. AC Degraff and J Frieden. Am Heart J 1979;97:66370. 4. Walker JA, Friedberg HD, Flemma RJ, Johnson WD. Determinants of angiographic patency of aortocoronary vein bypass grafts. Circulation 1972;45-6 (Suppl 1):66-90. 5. Loop FD. Spampinato N, Siegel W, Effler DB. Internal mammary artery grafts without optical assistance: clinical and angiographic analysis of 175 consecutive cases. Circulation 1973:47-a (Suppl lll):l62-7. 6. Chaitman BR, Rogers WJ, Davis K. et al. Operative risk factors in patients with left main coronary-artery disease. N Engl J Med 1960;303:953-7. 7. Hurst JW, King SB. Logue B, et al. Value of coronary bypass surgery: controversies in cardiology. Part I. Cardiology t976;42:306-26. 6. Sheldon WC, Loop FD, Proudfit WL. A critique of the VA cooperative study. Cleve Clin Q 1976;45:225-30. 9. Hurst JW, ed. Update II. The heart. New York: McGraw-Hill, 1960; 127-259. 655