EDITORIALS
Management of Asymptomatic Coronary Artery Disease Robert W. Anderson, M.D., and Carl E. Arentzen, M.D.
The value of a coronary bypass operation for the relief of angina pectoris refractory to medical management is well established. Controlled studies have demonstrated that symptomatic patients with left main coronary artery disease have improved survival following successful bypass operations [13]. Recent data suggest that subsets of surgically managed patients with symptomatic multivessel coronary disease have improved survival relative to similar patients medically managed [3, 91. In this issue of The Annals of Thoracic Surgery (p 113), Grondin and colleagues report the results of their attempt to determine in a small and selected group of minimally symptomatic or asymptomatic patients whether the presence of anatomical coronary artery disease is in itself an adequate indication for recommending bypass grafting. They concluded that their patients received little benefit from prophylactic revascularization, and based on these data, even the most enthusiastic surgeon will find little evidence to support surgical therapy in similar patients. The study by Grondin and associates raises several important questions that appear to be central to the management of many patients with coronary artery disease. Can improved diagnostic techniques be utilized to identify patients in whom coronary artery lesions are producing ischemic heart disease, even in the absence of disabling clinical symptoms? Once identified, can the ischemic manifestations of the coronary artery disease be improved by coronary bypass grafting more successfully than by medical management?
From the Department of Surgery, University of Minnesota, Minneapolis, MN. This work was supported by National Institutes of Health Grant HL-22152 from the United States Public Health Service. Address reprint requests to Dr. Anderson, Box 118 Mayo Memorial Building, University of Minnesota, Minneapolis, MN 55455.
Detection of Ischemic Heart Disease in Patients with Coronary Artery Disease Asymptomatic patients with coronary artery disease are brought to medical attention because of a positive exercise stress test, a history of a recent myocardial infarction, or a history of a near lethal arrhythmia. Although it can be argued that patients who have had myocardial infarctions or near lethal arrhythmias are not truly asymptomatic, often persistent evidence of ischemia following infarction or arrhythmia cannot be demonstrated. Nevertheless, when such asymptomatic patients are evaluated with coronary arteriography, many will be found to have "significant" anatomical coronary artery disease. Although there is no doubt that coronary arteriography is a reliable indicator of the anatomical presence of coronary artery disease, it does not identify those patients in whom the disease is physiologically significant. The traditional means of determining whether anatomical coronary artery lesions are producing functionally significant ischemic heart disease is to document a clinical history of angina pectoris. The asymptomatic patient cannot be assessed in this manner, and the physician must rely on other means to determine the presence of ischemic heart disease. The exercise stress test has proved reliable as both a diagnostic and prognostic tool in evaluating the presence of ischemic heart disease in patients with a suggestive clinical history. However, the predictive value of the exercise stress test diminishes if asymptomatic patients without a history of previous cardiac events are examined since the specificity and reliability of the exercise stress test are markedly decreased in this population [l]. Nonetheless, some asymptomatic patients are found to have a positive stress test and there are data that demonstrate that both early positive stress tests (Stage I or 11) and abnormal blood pressure responses to exercise testing are indicative of severe ischemic heart disease and correlate with a decreased life expectancy [6, 71.
97 0003-4975/79/080097-03$01.25 @ 1979 by Robert W. Anderson
98 The Annals of Thoracic Surgery Vol 28 NO 2 August 1979
Other important noninvasive techniques are also available that allow more precise identification of patients with ischemic heart disease. Radionuclide perfusion scanning and radionuclide angiocardiography, particularly if performed during both rest and exercise, appear to be valuable in the detection and quantification of myocardial ischemia [lo, 111. Twodimensional echocardiography during rest and stress is currently being developed as a new technique. Cardiac catheterization may not only demonstrate anatomical coronary artery disease but also identify ischemic manifestations by stress ventriculography and studies of lactate metabolism during pacinginduced stress [8, 121. The extension of surgical indications for coronary bypass operations to patients with minimal or no clinical symptoms can be rational only if patients with ischemic manifestations of coronary artery disease can be identified. Failure to differentiate between anatomical coronary artery disease and ischemic heart disease can lead only to results as discouraging as those reported by Grondin and associates. Potential Benefits of Operation in the Asymptomatic Patient If coronary bypass grafting is to be useful in the management of the asymptomatic patient, it must be demonstrated to prevent manifestations of ischemic heart disease other than angina pectoris. Since the natural history of patients with asymptomatic coronary artery disease is unknown at this time, there is no standard against which to compare surgical results in this group of patients. Available data from controlled studies in symptomatic patients are somewhat disquieting: none of them have demonstrated a decrease in the incidence of myocardial infarction or serious arrhythmias in the surgically treated patients [2, 4 , 91. However, these studies may not be entirely relevant since selection criteria were based solely on clinical and anatomical data. That improved longevity in the surgical patients with left main obstruction has been observed and that recent data strongly suggest a similar improvement in patients with multivessel disease provide evidence that those patients who are the most
likely to demonstrate severe ischemia by physiological study are the group most benefited by revascularization. Possible Risks of Prophylactic Coronary Bypass Grafting The risks of prophylactic coronary bypass grafting can be separated into the perioperative and long-term risks. The perioperative risks consist of operative mortality and perioperative myocardial infarction. In tlhe series of asymptomatic patients of Grondin and his colleagues, there was no operative mortality but the incidence of perioperative myocardial infarction was approximately 4%. Thus, prophylactic coronary bypass grafting is not without an early risk to the patient, which must be weighed against the potential benefits. The important long-term risks of coronary bypass grafting consist of graft closure and acceleration of the atherosclerotic process. The patient who undergoes prophylactic coronary bypass grafting and is seen soon after operation with no patent grafts represents a serious problem. The disappointingly large number of patients who had no grafts patent at one year as reported by Grondin and co-workers emphasizes this point. In addition to graft occlusion, there is the reported plhenomenon of acceleration of the atherosclerotic process in the native circulation. Most studies indicate that the progression of disease takes place proximal to the coronary bypass graft [5], and, thus, the distal coronary bed becomes more dependent on the bypass graft and therefore more subject to catastrophic events should the graft become occluded. Conclusion Since the natural history of patients with asymptomatic coronary artery disease is unknown, studies to evaluate medical and surgical therapy must be based on the physiological manifestations of ischemia rather than the anatomical presence of coronary artery disease. Data from controlled studies in patients with stable angina indicate that coronary bypass grafting decreases the sequejlae of ischemic heart disease in those subsets of patients who also have a greater prevalence of profound
99 Editorial: Anderson and Arentzen: Asymptomatic Coronary Artery Disease
physiological derangements due to isch- 4. Kloster FE, Kremkau EL, Ritzmann LW, et al: Coronary bypass for stable angina: a prospective emia-patients with left main obstruction randomized study. N Engl J Med 300:149, 1979 and multivessel disease. More precise methods 5. Maurer BJ, Oberman A, Holt JH, et al: Changes of patient selection are now available to identify in grafted and nongrafted coronary arteries folpatient populations, both symptomatic and lowing saphenous vein bypass grafting. Circulation 50:293, 1974 asymptomatic, who are more likely to benefit from revascularization because of quantifiable 6 . McNeer JF, Margolis JR, Lee KL, et al: The role of the exercise test in the evaluation of patients for physiological abnormalities resulting from ischemic heart disease. Circulation 57:64, 1978 ischemia. The report of Grondin and associates 7. Morris SN, Phillips JF, Jordan JW, et al: Inciclearly demonstrates the danger of equating dence and significance of decreases in systolic anatomical coronary artery disease with ischblood pressure during graded treadmill exercise testing. Am J Cardiol41:221, 1978 emic heart disease in the absence of clinical 8. Parker JO, Chiong MA, West RO, et al: Sequensymptoms. The potential benefits of myocardial tial alterations in myocardial lactate metabolism, revascularization in such patients can be estabS-T segments and left ventricular function during lished only if a careful selection process is used angina induced by atrial pacing. Circulation to designate those patients with physiological 40:113, 1969 evidence of ischemia, if it can be shown that the 9. Read RC, Murphy ML, Hultgren HN, et al: Survival of men treated for chronic stable angina ischemia can be reversed by revascularization pectoris: a cooperative randomized study. J more successfully than by other therapy, and if Thorac Cardiovasc Surg 75:1, 1978 successful reversal of the ischemic process can 10. Rerych SK, Scholz PM, Newman GE, et al: Cardecrease the long-term sequelae of ischemic diac function at rest and during exercise in norheart disease. mals and in patients with coronary heart disease: evaluation by radionuclide angiocardiography. Ann Surg 187:449, 1978 References 11. Ritchie JL, Trobaugh GB, Hamilton GW, et al: Fortuin NJ, Weiss JL: Exercise stress testing. CirMyocardial imaging with thallium-201 at rest culation 56:699, 1977 and during exercise. Circulation 56:66, 1977 Guinn GA, Mathur VS: Surgical versus medical 12. Sharma B, Goodwin JR, Rapheal MJ, et al: Left treatment for stable angina pectoris: prospective ventricular angiography on exercise: a new randomized study with 1- to 4-year follow-up. method of assessing left ventricular function in Ann Thorac Surg 22:524, 1976 ischemic heart disease. Br Heart J 38:59, 1976 Hammermeister KE, DeRouen TA, Dodge HT: 13. Takaro T, Hultgren HN, Lipton MJ, et al: The VA Evidence from a nonrandomized study that cooperative randomized study of surgery for coronary surgery prolongs survival in patients coronary arterial occlusive disease: 11. Subgroup with two-vessel coronary disease. Circulation with significant left main lesions. Circulation 59:430, 1979 54:Suppl3:107, 1976
Management of Asymptomatic Coronary Artery Disease Robert W. Anderson, M.D., and Carl E. Arentzen, M.D.
The value of a coronary bypass operation for the relief of angina pectoris refractory to medical management is well established. Controlled studies have demonstrated that symptomatic patients with left main coronary artery disease have improved survival following successful bypass operations [13]. Recent data suggest that subsets of surgically managed patients with symptomatic multivessel coronary disease have improved survival relative to similar patients medically managed [3, 91. In this issue of The Annals of Thoracic Surgery (p 113), Grondin and colleagues report the results of their attempt to determine in a small and selected group of minimally symptomatic or asymptomatic patients whether the presence of anatomical coronary artery disease is in itself an adequate indication for recommending bypass grafting. They concluded that their patients received little benefit from prophylactic revascularization, and based on these data, even the most enthusiastic surgeon will find little evidence to support surgical therapy in similar patients. The study by Grondin and associates raises several important questions that appear to be central to the management of many patients with coronary artery disease. Can improved diagnostic techniques be utilized to identify patients in whom coronary artery lesions are producing ischemic heart disease, even in the absence of disabling clinical symptoms? Once identified, can the ischemic manifestations of the coronary artery disease be improved by coronary bypass grafting more successfully than by medical management?
From the Department of Surgery, University of Minnesota, Minneapolis, MN. This work was supported by National Institutes of Health Grant HL-22152 from the United States Public Health Service. Address reprint requests to Dr. Anderson, Box 118 Mayo Memorial Building, University of Minnesota, Minneapolis, MN 55455.
Detection of Ischemic Heart Disease in Patients with Coronary Artery Disease Asymptomatic patients with coronary artery disease are brought to medical attention because of a positive exercise stress test, a history of a recent myocardial infarction, or a history of a near lethal arrhythmia. Although it can be argued that patients who have had myocardial infarctions or near lethal arrhythmias are not truly asymptomatic, often persistent evidence of ischemia following infarction or arrhythmia cannot be demonstrated. Nevertheless, when such asymptomatic patients are evaluated with coronary arteriography, many will be found to have "significant" anatomical coronary artery disease. Although there is no doubt that coronary arteriography is a reliable indicator of the anatomical presence of coronary artery disease, it does not identify those patients in whom the disease is physiologically significant. The traditional means of determining whether anatomical coronary artery lesions are producing functionally significant ischemic heart disease is to document a clinical history of angina pectoris. The asymptomatic patient cannot be assessed in this manner, and the physician must rely on other means to determine the presence of ischemic heart disease. The exercise stress test has proved reliable as both a diagnostic and prognostic tool in evaluating the presence of ischemic heart disease in patients with a suggestive clinical history. However, the predictive value of the exercise stress test diminishes if asymptomatic patients without a history of previous cardiac events are examined since the specificity and reliability of the exercise stress test are markedly decreased in this population [l]. Nonetheless, some asymptomatic patients are found to have a positive stress test and there are data that demonstrate that both early positive stress tests (Stage I or 11) and abnormal blood pressure responses to exercise testing are indicative of severe ischemic heart disease and correlate with a decreased life expectancy [6, 71.
97 0003-4975/79/080097-03$01.25 @ 1979 by Robert W. Anderson
98 The Annals of Thoracic Surgery Vol 28 NO 2 August 1979
Other important noninvasive techniques are also available that allow more precise identification of patients with ischemic heart disease. Radionuclide perfusion scanning and radionuclide angiocardiography, particularly if performed during both rest and exercise, appear to be valuable in the detection and quantification of myocardial ischemia [lo, 111. Twodimensional echocardiography during rest and stress is currently being developed as a new technique. Cardiac catheterization may not only demonstrate anatomical coronary artery disease but also identify ischemic manifestations by stress ventriculography and studies of lactate metabolism during pacinginduced stress [8, 121. The extension of surgical indications for coronary bypass operations to patients with minimal or no clinical symptoms can be rational only if patients with ischemic manifestations of coronary artery disease can be identified. Failure to differentiate between anatomical coronary artery disease and ischemic heart disease can lead only to results as discouraging as those reported by Grondin and associates. Potential Benefits of Operation in the Asymptomatic Patient If coronary bypass grafting is to be useful in the management of the asymptomatic patient, it must be demonstrated to prevent manifestations of ischemic heart disease other than angina pectoris. Since the natural history of patients with asymptomatic coronary artery disease is unknown at this time, there is no standard against which to compare surgical results in this group of patients. Available data from controlled studies in symptomatic patients are somewhat disquieting: none of them have demonstrated a decrease in the incidence of myocardial infarction or serious arrhythmias in the surgically treated patients [2, 4 , 91. However, these studies may not be entirely relevant since selection criteria were based solely on clinical and anatomical data. That improved longevity in the surgical patients with left main obstruction has been observed and that recent data strongly suggest a similar improvement in patients with multivessel disease provide evidence that those patients who are the most
likely to demonstrate severe ischemia by physiological study are the group most benefited by revascularization. Possible Risks of Prophylactic Coronary Bypass Grafting The risks of prophylactic coronary bypass grafting can be separated into the perioperative and long-term risks. The perioperative risks consist of operative mortality and perioperative myocardial infarction. In tlhe series of asymptomatic patients of Grondin and his colleagues, there was no operative mortality but the incidence of perioperative myocardial infarction was approximately 4%. Thus, prophylactic coronary bypass grafting is not without an early risk to the patient, which must be weighed against the potential benefits. The important long-term risks of coronary bypass grafting consist of graft closure and acceleration of the atherosclerotic process. The patient who undergoes prophylactic coronary bypass grafting and is seen soon after operation with no patent grafts represents a serious problem. The disappointingly large number of patients who had no grafts patent at one year as reported by Grondin and co-workers emphasizes this point. In addition to graft occlusion, there is the reported plhenomenon of acceleration of the atherosclerotic process in the native circulation. Most studies indicate that the progression of disease takes place proximal to the coronary bypass graft [5], and, thus, the distal coronary bed becomes more dependent on the bypass graft and therefore more subject to catastrophic events should the graft become occluded. Conclusion Since the natural history of patients with asymptomatic coronary artery disease is unknown, studies to evaluate medical and surgical therapy must be based on the physiological manifestations of ischemia rather than the anatomical presence of coronary artery disease. Data from controlled studies in patients with stable angina indicate that coronary bypass grafting decreases the sequejlae of ischemic heart disease in those subsets of patients who also have a greater prevalence of profound
99 Editorial: Anderson and Arentzen: Asymptomatic Coronary Artery Disease
physiological derangements due to isch- 4. Kloster FE, Kremkau EL, Ritzmann LW, et al: Coronary bypass for stable angina: a prospective emia-patients with left main obstruction randomized study. N Engl J Med 300:149, 1979 and multivessel disease. More precise methods 5. Maurer BJ, Oberman A, Holt JH, et al: Changes of patient selection are now available to identify in grafted and nongrafted coronary arteries folpatient populations, both symptomatic and lowing saphenous vein bypass grafting. Circulation 50:293, 1974 asymptomatic, who are more likely to benefit from revascularization because of quantifiable 6 . McNeer JF, Margolis JR, Lee KL, et al: The role of the exercise test in the evaluation of patients for physiological abnormalities resulting from ischemic heart disease. Circulation 57:64, 1978 ischemia. The report of Grondin and associates 7. Morris SN, Phillips JF, Jordan JW, et al: Inciclearly demonstrates the danger of equating dence and significance of decreases in systolic anatomical coronary artery disease with ischblood pressure during graded treadmill exercise testing. Am J Cardiol41:221, 1978 emic heart disease in the absence of clinical 8. Parker JO, Chiong MA, West RO, et al: Sequensymptoms. The potential benefits of myocardial tial alterations in myocardial lactate metabolism, revascularization in such patients can be estabS-T segments and left ventricular function during lished only if a careful selection process is used angina induced by atrial pacing. Circulation to designate those patients with physiological 40:113, 1969 evidence of ischemia, if it can be shown that the 9. Read RC, Murphy ML, Hultgren HN, et al: Survival of men treated for chronic stable angina ischemia can be reversed by revascularization pectoris: a cooperative randomized study. J more successfully than by other therapy, and if Thorac Cardiovasc Surg 75:1, 1978 successful reversal of the ischemic process can 10. Rerych SK, Scholz PM, Newman GE, et al: Cardecrease the long-term sequelae of ischemic diac function at rest and during exercise in norheart disease. mals and in patients with coronary heart disease: evaluation by radionuclide angiocardiography. Ann Surg 187:449, 1978 References 11. Ritchie JL, Trobaugh GB, Hamilton GW, et al: Fortuin NJ, Weiss JL: Exercise stress testing. CirMyocardial imaging with thallium-201 at rest culation 56:699, 1977 and during exercise. Circulation 56:66, 1977 Guinn GA, Mathur VS: Surgical versus medical 12. Sharma B, Goodwin JR, Rapheal MJ, et al: Left treatment for stable angina pectoris: prospective ventricular angiography on exercise: a new randomized study with 1- to 4-year follow-up. method of assessing left ventricular function in Ann Thorac Surg 22:524, 1976 ischemic heart disease. Br Heart J 38:59, 1976 Hammermeister KE, DeRouen TA, Dodge HT: 13. Takaro T, Hultgren HN, Lipton MJ, et al: The VA Evidence from a nonrandomized study that cooperative randomized study of surgery for coronary surgery prolongs survival in patients coronary arterial occlusive disease: 11. Subgroup with two-vessel coronary disease. Circulation with significant left main lesions. Circulation 59:430, 1979 54:Suppl3:107, 1976
