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The rationale for surgery in preinfarction angina
The rationale for surgery in preinfarction angina Of 123 patients with identical clinical criteria for preinfarction angina, 35 were treated medically and 88 surgically in a nonrandomized manner. There was no statistical difference between these two therapeutic groups in regard to age range, average age, sex distribution, number and distribution of prior myocardial infarction, and duration of chronic and acute anginal symptoms. With medical therapy, 32 sustained a myocardial infarction, and 14 (40 per cent) of these died within I month of hospital admission. Thirteen of 21 survivors or 37 per cent of the original group are asymptomatic on continuing medical therapy an average of 15 months after discharge. The surgical patients were studied by catheterization and angiography and underwent an early operation. Eight (9.4 per cent) demonstrated evidence of postoperative infarction, and 3 (3.4 per cent) died after the operation. Seventy-one (84 per cent) are completely asymptomatic and 6 are less symptomatic an average of 17 months after the operation. Actuarial analysis of the follow-up data reveals that the initial significant difference in survival between the two groups is maintained through the first 36 months. On the basis of this experience, we suggest that surgical intervention is the therapy of choice in patients with preinfarction angina.
Jack M. Matloff, M.D., Hector Sustaita, M.D. (by invitation), Kanu Chatterjee, M.D. (by invitation), Aurelio Chaux, M.D. (by invitation), Harold S. Marcus, M.D. (by invitation), and H. J. C. Swan, M.D., Ph.D. (by invitation), Los Angeles, Calif.
JL-Jynamic alterations in supply and demand of oxygen to the myocardium in patients with obstructive coronary artery disease result in varying degrees of myocardial ischemia. These pathophysiological changes are the basis for the varying clinical manifestations and prognosis seen with coronary atherosclerosis. Although these manifestations broadly describe a continuum, it is possible to identify fairly discrete subsets of patients along this continuum. Given the ability to revascularize ischemic segments of the myocardium by direct aortoFrom the Departments of Thoracic, Cardiac, and Vascular Surgery and Cardiology. Cedars-Sinai Medical Center, Los Angeles, Calif. Read at the Fifty-fourth Annual Meeting of The American Association for Thoracic Surgery, Las Vegas, Nevada, April 22, 23, and 24, 1974. Address for reprints: Jack M. Matloff, M.D., Department of Thoracic, Cardiac, and Vascular Surgery, CedarsSinai Medical Center, 4833 Fountain Ave., Los Angeles, Calif. 90029.
coronary bypass,' the problem becomes one of determining the position of a given patient in the evolution of his disease process at a given time. Thus if surgical therapy is to be undertaken, it can be done at the most optimal time. This philosophy of therapy has as its primary tenet the preservation of myocardial viability.- :i In patients experiencing progressive, acute ischemia, accumulating experience suggests that it is possible to identify a subset of patients in whom the likelihood of progression to infarction is significant.4"7 Unfortunately, other reports do not substantiate the validity of this conclusion.*"1" In part, this discrepancy may result from differences in the criteria used to establish the diagnosis. The present study details our continuing experience with medical and surgical therapy for the entity variously termed intermediate coronary syndrome,11 acute coronary insufn73
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Thoracic and Cardiovascular Surgery
28 -,
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24 20 -
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> 5 YRS.
TIME
Fig. 1. Duration of anginal history in 123 patients with preinfarction angina.
Table I. Clinical data in 123 patients No. of patients Medical therapy
35
Surgical therapy
88
Uncomplicated
58
Complicated
30
Sex 29 6 77 11 52 6 25 5
M F M F M F M F
Age range 35-78 (50.65) 34-73 (54.09) 34-73 (54.06) 41-70 (54.13)
ciency,1- acute coronary failure," unstable angina,11 impending infarction/' impending coronary occlusion,1" or preinfarction angina.1'1 Clinical materials and methods Definition. For the purposes of this study, four clinical criteria were used to establish the diagnosis of preinfarction angina. Each patient fulfilled all criteria. These included the following: (1) severe, prolonged (15 to 30 minutes) episodes of anginal pain, often with a crescendo pattern, either of recent onset or as an exacerbation of a chronic stable anginal state; (2) continuing or repeated episodes of pain while at bedrest in the hospital; (3) documentation of transient ST-segment and/or T-wave changes indicative of ischemia; and (4) no elevation of serum enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and creatine phosphokinase) beyond the 10 per cent range of normal.
Patients with progressive or crescendo patterns of pain were not included unless they also continued to have pain at rest in the hospital. In addition to bedrest, all were treated with sedatives, analgesics, and shortand/or long-acting nitrates. Many were treated with heparin and/or beta blockade with propranolol. Institution of these two latter forms of therapy was variable and at the discretion of the primary physician. No patient was included in this study unless at least two of us agreed on whether the patient met the above criteria. All patients meeting these criteria were followed through their hospital course to discharge. Patient population. From December, 1970, to March, 1974, 123 patients (Table I) were seen who met the above criteria. All were admitted to the COU, ICU, or MIRU* of the Cedars of Lebanon Hospital. This is a consecutive experience but it is also a selective one in that there were a number of primary physicians involved who preselected the patients seen. Furthermore, not all patients admitted to these units with the diagnosis of preinfarction angina were seen by the authors. Therefore, it is not an all-inclusive series from our institution. Two nonrandomized forms of therapy were pursued. Thirty-five patients were continued on their medical regimens. On the basis of clinical criteria, all of these patients were acceptable for surgical therapy, but in each, for a variety of reasons, a decision was made to continue medical therapy. Twelve of these patients were catheterized. The remaining 88 patients underwent cardiac catheterization and angiography, followed by direct revascularization surgery. The age range and average ages were similar (Table I) for the two therapeutic groups. There was no significant difference in the sex distribution. Anginal history. The history of angina has been detailed in terms of the total duration of angina (Fig. 1) and the duration of acute symptomatology (Fig. 2). The latter state was the period of time during which the pain occurred with increased severity at rest *Coronary Observation Unit, Intensive Care Myocardial Infarction Research Unit.
Unit, and
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Preinfarction angina
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and with electrocardiographic changes. Approximately equal numbers of patients had total durations of a positive anginal history of 1 to 4 weeks, 2 to 12 months, 1 to 5 years, and more than 5 years. In 34 patients there was recent (less than 1 month) onset of angina with rapid progression to the preinfarction state. There was no significant difference (chi square = 1.164; DF* = 3; p = 0.7621) in this temporal distribution between the two therapeutic groups. In contrast to this even distribution between the two therapeutic groups in terms of total anginal history, 83 patients experienced acute anginal histories of 1 to 7 days and an additional 31 had acute symptoms lasting 8 to 21 days. Again, there was no significant difference (chi square = 3.089; DF = 3; p = 0.3781) in the temporal distribution of acute symptoms between the two therapeutic groups. History of prior myocardial infarctions. Fifty-seven patients experienced 66 episodes of remote myocardial infarction (more than 1 month prior to admission) (Table II) by history and electrocardiographic criteria. Approximately twice as many inferior, posterior, and lateral infarcts had occurred as anterior and septal infarcts. There was no significant difference between the therapeutic groups (chi square = 2.7) in terms of the number of patients having prior infarctions, the number of infarctions experienced, and their locations. Surgical considerations. Patients who accepted the recommendation for study and possible surgery underwent right and left heart catheterization, some with pacing and coronary sinus metabolic studies as well, left ventricular angiography, and selective coronary angiography.'7 The clinical diagnosis in each instance was associated with coronary atherosclerosis confirmed by angiography. As a group, the surgical patients experienced multivessel involvement (average 2.8 vessels per patient), with predominate subtotal (80 to 99 per cent) to total occlusive lesions of the left coronary artery and its major branches (179 of the 250 involved vessels). Only 2 patients had pre* Degrees of freedom.
6
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Fig. 2. Duration of acute symptoms in 123 patients with preinfarction angina.
dominate right coronary artery disease. Seventy-seven of the surgical patients experienced hypokinesis, akinesis, or dyskinesis of one or more ventricular segments by analysis of segmental wall motion in the right anterior oblique ventriculogram. Aorto-coronary artery vein bypass grafting was .performed in 87 of the surgical patients; the remaining patient, who had had vein Iigation and stripping in the past, underwent internal mammary artery bypasses to the anterior descending and its first diagonal branch. Surgery was accomplished by use of total cardiopulmonary bypass with total hemodilution at normothermic temperatures. Direct decompression of the left ventricle was carried out via a sump* placed through the left atrium. Intermittent anoxic arrest, by electrical fibrillation and aortic crossclamping for periods of 10 to 12 minutes, was induced during performance of the distal anastomoses. Interrupted 6-0 silk sutures were used. Between distal anastomoses the heart was reperfused, defibrillated, and allowed to beat for 3 to 5 minutes. The distal anastomoses were completed first. All proximal anastomoses were done with either partial or complete bypass, depending on the status of the left ventricle. In patients with unresponsive ventricles after the operation, pharmacologic means of support were used. No mechanical assist devices were utilized. Within 24 to 48 hours after the *Argyle left ventricular vent catheter, Aloe Medical Distributors, Sherwood Medical Industries, Inc., St. Louis, Mo.
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Table II. Prior infarctions* in 123 patients Location No. of patients No. of episodes Ant./septal Medical therapy Surgical therapy
16/35 ( 4 6 % ) 41/88 ( 4 7 % )
16 50
5 (14%) 16 ( 1 8 % )
Inferior 11 ( 3 2 % ) 27 ( 3 1 % )
\ Post./lat. 6
\
Other 1
•Does not include infarctions during month prior to admission.
Table III. Surgical therapy Vessel bypassed LAD First left diag. LCxM RCA Totals
Uncomplicated (58) 55 13 43 20 131 (2.3*)
Complicated (30) 27 4 15 9 55 (1.8*)
Summary 82 17 58 29 186 (2.1*)
Legend: LAD, Left anterior descending coronary artery. LCxM, Left circumflex marginal branch. RCA, Right coronary artery. •Number of bypass grafts per patient.
Table IV. Preoperative complications in 30 patients Myocardial infarction (continued angina) Anterior Posterior/inferior Ventricular tachycardia/fibrillation Hypotension Congestive heart failure Complete heart block Totals
22 12 10 6 5 2 2 37
operation, all patients were given heparin on a 6 hour dosage schedule calculated to maintain a 5 hour clotting time of 15 to 20 minutes. In this series, 16 patients had single, 47 patients double, 24 patients triple, and 1 patient quadruple vessel bypass. One hundred eighty-six of the 250 vessels identified as being diseased were bypassed for an average of 2.1 vessels bypassed per patient (Table III). Over-all, 157 of 179 involved left-sided vessels (88 per cent) were bypassed. Results Early morbidity and deaths. Thirty-two of the patients treated medically sustained a myocardial infarction prior to discharge.
Twenty-one survived this infarction; 7 of these had anterior wall involvement. Eleven died during the hospital course of their acute infarction; 10 of these 11 had anterior or anterior and inferior infarctions. Three of the 21 survivors died shortly after discharge from the hospital, within 1 month of their admissions. Postmortem examinations were not obtained in these 3 patients. Of the 88 patients who had emergent anatomic study and surgery, 30 experienced one or more major cardiovascular complications of their ischemia before the operation (Table IV). In 19 patients complications occurred between the time the diagnosis was established and catheterization undertaken; these precatheterization complications included episodes of ventricular tachycardia and/or fibrillation, complete heart block, congestive heart failure, and progression to anteroseptal or inferior wall infarction. The latter patients were studied and operated upon after they had experienced an acute myocardial infarction, because they continued to have angina with new electrocardiographic evidence of ischemia. A complication developed during catheterization in 3 patients, ventricular fibrillation in 2 and profound hypotension in 1 patient. In 10 patients complications occurred between the catheterization and operation. These included episodes of ventricular tachycardia and/or fibrillation, congestive heart failure, hypotension without infarction, progression to infarction, and cardiogenic shock. In 7 of these patients there was a 24 hour or longer delay between catheterization and the operation; in the remaining 3 there was an 8 to 18 hour delay between catheterization and the operation. Comparative mortality figures are detailed in Table V. Eleven of the deaths in the medical group were a result of a myocardial
Volume 69
Preinfarction angina
Number 1 January, 1975
infarction. As noted, 3 others died outside of the hospital within 1 month of their acute infarctions, presumably of causes related to their ischemic heart disease. In the surgical group, a 74-year-old patient died of occlusion of the superior mesenteric artery 4 weeks after surgery; his death was probably related to hypovolemia. The second patient experienced uncontrollable ventricular tachycardia and cardiogenic shock during the interval between catheterization and the operation and was operated upon in this condition. The third patient had had acute inferior and subendocardial myocardial infarctions prior to catheterization and was studied because he continued to have anginal pain. He is the only patient who died in the operating room. There was a significant difference (chi square = 28.148 and p = < 0.0001) in mortality rates between the therapeutic groups. Follow-up. One hundred nine patients were discharged from the hospital. As noted, 3 of these patients died outside of the hospital, within 1 month of the date of their admission. One hundred six patients were therefore available for follow-up of more than 1 month. For the medically treated patients, follow-up was accomplished by telephone interview with the patient's primary physician; in some instances the patient also was contacted directly. The duration of follow-up was from 1 to 30 months, with an average follow-up of 15 months. Three patients could not be located for follow-up (Table VI). Thirteen patients were considered to be asymptomatic on continuing medical therapy. Some of these patients continued to experience minor anginal discomfort with exercise exceeding well-defined limits. However, they did not consider these episodes to be disruptive in their life patterns. Five patients continued to have significant angina, despite medical therapy and restricted physical activity. Three of these 5 had associated congestive heart failure. Three of the 5 with residual angina, 2 of whom also had congestive heart failure, were subsequently
77
Table V. Mortality rate* in 123 patients No. of patients | No. of deaths Medical therapy Surgical therapy Uncomplicated Complicated
35 88 58 30
14 3 1 2
(40%) ( 3.4%) ( 1.7%) ( 6.6%)
*One month after admission.
Table VI. Follow-up in 21 survivors of medical therapy No. of survivors
Status Asymptomatic Symptomatic Residual angina Subsequent surgery Congestive failure Late death Lost to follow-up
13 ( 6 2 % ) 5 (24%) 5 3 1 1 3 (14%)
studied in the catheterization laboratory and underwent surgery. Two had left ventricular aneurysmectomies as well as bypass grafts, and all 3 are now asymptomatic. There was one late death in this group, caused by severe uremic pericarditis. The fifth patient with residual angina and congestive heart failure has continued to refuse further study and possible surgery. Of the surgically treated patients (Table VII), 2 were lost to follow-up. We have seen the remaining 83 patients at 6 month intervals. In addition, their primary physicians also have been contacted directly for this review. The duration of follow-up was from 1 to 42 months, with an average follow-up of 17 months. Eight of the survivors of surgery have experienced postoperative infarctions, 7 during the perioperative period and 1 patient 6 weeks after the operation. Two of the seven perioperative infarctions were classified as "unmasking" of a prior inferior wall infarction1* and were not believed to have been surgically induced. All had inferior wall infarctions, and 2 also had anterior wall infarctions. Seventy-one patients have been completely asymptomatic from the time of operation.
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Table VII. Follow-up in 85 survivors of surgical therapy Status
|
Postoperative infarction Asymptomatic Symptomatic Less angina The same degree or more angina Congestive failure Late death Lost to follow-up
Eight have had some degree of postoperative angina; in 6 this has been much less than experienced preoperatively. Four of the 8 have been restudied; in 2 there has been closure of a graft and in 3 significant progression of the atherosclerotic process in vessels that were not originally thought to require bypass. The remaining 2 patients with symptoms have compensated congestive heart failure without angina. Each of these had significant perioperative infarctions, 1 prior to and the other during the operation. There have been two late deaths, both at 1 year. One patient had carcinoma of the pancreas and the other died of a presumed arrhythmia. Discussion Despite an enthusiasm among some that often borders on being evangelical, the indications for aorto-coronary bypass graft surgery continue to be the subject of close study. The most commonly advanced criticism is that for any given indication there is not yet substantial evidence that such surgery prolongs life. This may or may not be valid for the majority of patients who undergo surgery for chronic angina pectoris. However, it is our thesis that in the subgroup experiencing preinfarction angina which is rigidly defined and unresponsive to medical therapy including bedrest, longevity as well as the quality of life is improved in surgically treated patients. In part, such a conclusion generally has been difficult to arrive at because of uncertainty in the literature about the prognosis in this subset .'• "■S1"- -"• 21 The very fact that a di-
Uncomplica,led
;
Compl icatecl 0 24 3
8 47 7 4 2 I
|
Summary 8 ( 9.4%) 71 ( 8 4 % ) 10 ( 1 2 % )
2 1 2 1
0 1
2(2%) 2(2%)
versity of terms has been used for clinical states considered to be similar may be explained by the nonuniformity of diagnostic criteria and hence the underlying disease state reported in various series. In the present study, each patient met our rigidly defined clinical criteria. The fact that there was no statistical difference between our two therapeutic groups in regard to age range and average age, sex distribution, total duration of anginal history, history and distribution of prior myocardial infarctions, and history of acute symptoms supports the contention that we have been able to identify a uniform patient population. This thesis is further supported by the fact that, of the patients studied, there was no incidence of false positives identified by the clinical criteria, in contradistinction to other reports.1" Furthermore, these studies identify an anatomically similar pathological substrate in which there is a predominance of high-grade obstruction and multivessel involvement of the left coronary artery. This observation supports the contention1" that mortality statistics in this syndrome "reflect the prognosis of the basic anatomical substrate rather than anything peculiar to the pain syndrome per se". The high incidence of progression to infarction prior to surgery in both the medically treated and in the surgically treated group, plus the mortality rate in the medically treated group, underscores the malignant nature of this subset. Notwithstanding, the relatively low incidence of complications during catheterization suggests that these patients can be readily studied to precisely
Volume 69
Preinfarction angina
Number 1
79
January, 1975
ARTERIOGRAPHY 100
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define their anatomy. However, the seemingly increased occurrence of complications between the time of catheterization and surgery, when the interval extends beyond 6 hours, has led us to a policy of not proceeding with catheterization until the patient accepts the possibility of surgery beforehand and until an operating team and room are available. With these simple guidelines and expeditiously conducted anesthetic induction and operation, it has been possible to achieve the significantly increased early survival rate reported herein. Actuarial analysis of the follow-up of our patients indicates that this initial difference in mortality rate is maintained through the first 3 years after the operation (Fig. 3). It is all the more dramatic when taken in the context of longevity of patients with chest pain and demonstrated triple vessel disease-'-- -■'' and of patients with clinically diagnosed preinfarction angina in a high-risk subgroup." The 1 year mortality rate of 43 per cent in this latter group, treated medically, approximates the 1 year mortality rate of our medically treated group. In addition to improved survival and longevity, symptomatic improvement in the surgically treated group was significantly better than in the medically treated group. This symptomatic improvement in surgical survivors who have not experienced perioperative infarction has been demonstrated by objective means to be associated with sig-
nificantly improved left ventricular function after successful surgery.-'• -•"■ It is on the basis of these results, i.e., increased longevity and symptomatic improvement in surgically treated patients, that we suggest direct revascularization is the therapy of choice in this subset of patients with preinfarction angina. Two criticisms can be made of the data on which this thesis is founded: (1) Some of the medical patients were not studied by catheterization and angiography to establish by objective criteria that our two therapeutic groups are in fact similar; (2) the selection of therapy was not determined in a prospective and randomized manner. In regard to the first criticism, 12 of the medical patients were studied, and in general their anatomy corresponded very closely to that seen in the surgical patients. There were 3 patients in whom the extent of distal involvement was such that they were not considered to be appropriate surgical candidates; each of these developed an infarction and survived. These were the only patients in the medical group by default from the surgical group. The matter of randomizing the choice of therapy in a prospective study is a much more difficult one to resolve, for both ethical and scientific reasons. Given the setting of the present study and the difference in results from the beginning of the study, we have not felt that the choice of therapy
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should be made for these patients either by default or by assuming that there was insufficient experience to make an appropriate decision. This latter assumption would certainly appear to be valid on the basis of an almost identical recently reported experience derived from a prospective and randomized study.7 It remains to be seen whether these conclusions will be supported by an ongoing cooperative study. REFERENCES 1 Favaloro, R. G.: Saphenous Vein Graft in the Surgical Treatment of Coronary Artery Disease, J.
2
3
4
5
6
7
8
9
10
11
THORAC.
CARDIOVASC. SURG. 58:
178,
1969. Maroko, P. R., Kjekshus, J. K., Sobel, B. E., et al.: Factors Influencing Infarct Size Following Experimental Coronary Artery Occlusions, Circulation 43: 67, 1971. Forrester, J. S., and Chatterjee, K.: Preservation of Ischemic Myocardium, in Vogel, J. H. K., editor: Advances in Cardiology, Basel, S. Karger. In press. Vahil, R. J.: Preinfarction Syndrome: Management and Follow-up, Am. J. Cardiol. 14: 55, 1964. Chatterjee, K., Swan, H. J. C , Sustaita, H., Matloff, J. M., and Parmley, W. W.: Impending Infarction and Direct Myocardial Revascularization, in Corday, E., and Swan, H. J. C , editors: New Perspectives in Diagnosis and Management of Myocardial Infarction, Baltimore, 1972, Williams & Wilkins Company, p. 362. Gazes, P., Mobley, E. M„ Jr., Faris, H. M.. Jr., Duncan, R. C , and Humphries, G. B.: Preinfarctional (Unstable) Angina—A Prospective Study—Ten Year Follow-Up: Prognostic Significance of Electrocardiographic Changes, Circulation 48: 331, 1973. Bertolasi, C. A., Tronge, J. E., Carreno, C. A., Jalon, J., and Vega, M. R.: Unstable Angina— Prospective and Randomized Study of Its Evolution, With and Without Surgery: Preliminary Report, Am. J. Cardiol. 33: 201, 1974. Murnaghan, D., Hickey, N., and Mulcahy, R.: Immediate and Long Term Experience of Acute Coronary Insufficiency (Abstr.), Br. Heart J. 32: 555, 1970. Hochberg, H. M.: Characteristics and Significance of Prodromes of Coronary Care Unit Patients, Chest 59: 10, 1971. Krauss, K. R., Hutter, A. M., Jr., and DeSanctis, R. W.: Acute Coronary Insufficiency: Course and Follow-Up, Circulation 45, 46: 66, 1972 (Suppl. I ) . Graybiel, A.: The Intermediate Coronary Syn-
drome, U. S. Armed Forces Med. J. 6: 1, 1955. 12 Master, A. M., Jafre, H. L., Field, L. E., and Donoso, E.: Acute Coronary Insufficiency: Its Differential Diagnosis and Treatment, Ann. Intern. Med. 45: 561, 1956. 13 Freedberg, A. S„ Blumgart, H. L., Zoll, P. M., and Schlesinger, M. J.: Coronary Failure: The Clinical Syndrome of Cardiac Pain Intermediate Between Angina Pectoris and Acute Myocardial Infarction, J. A. M. A. 138: 107, 1948. 14 Fowler, N. O.: "Preinfarctional" Angina, Circulation 44: 755, 1971. 15 Sampson, J. J., and Eliaser, M.. Jr.: Diagnosis of Impending Acute Coronary Artery Occlusion, Am. Heart J. 13: 675, 1937. 16 Resnik, W. H.: Preinfarction Angina. I. The Transaminase Test—A Diagnostic Aid. II. An Interpretation, Mod. Con. Cardiovasc. Dis. 31: 751 and 757, 1962. 17 Matloff, J. M„ Marcus, H., Chatterjee, K., Chaux, A., Sustaita, H., and Swan, H. J. C : The Anatomy of Preinfarction Angina. In preparation. 18 Bassan, M. M., Oatfield, R., Hoffman, I., Matloff, J. M., and Swan, H. J. C : New Q Waves After Aortocoronary Bypass: Unmasking of an Old Infarction, N. Engl. J. Med. 290: 349, 1974. 19 Proudfit, W. L., Shirey, E. K., and Sones. F. M., Jr.: Selective Cine Coronary Arteriography: Correlation With Clinical Findings in 1,000 Patients. Circulation 33: 901, 1966. 20 Wood, P.: Acute and Subacute Coronary Insufficiency, Br. Med. J. 1: 1779, 1961. 21 Beamish, R. E., and Stonie, V. M.: Impending Myocardial Infarction: Recognition and Management, Circulation 21: 1107, 1960. 22 Bruschke, A. V. G., Proudfit, W. L., and Sones, F. M., Jr.: Progress Study of 590 Consecutive Nonsurgical Cases of Coronary Disease Followed 5-9 Years. I. Arteriographic Correlations, Circulation 47: 1147. 1973. 23 Webster, J. S., Moberg, C , and Rincon, G.: Natural History of Severe Proximal Coronary Artery Disease as Documented by Coronary Cineangiography, Am. J. Cardiol. 33: 195. 1974. 24 Chatterjee, K., Swan, H. J. C , Parmley, W. W., Sustaita, H., Marcus, H., and Matloff, J. M.: Depression of Left Ventricular Function Due to Acute Myocardial Ischemia and Its Reversal After Coronary Saphenous Vein Bypass, N. Engl. J. Med. 286: 1117. 1972. 25 Chatterjee, K... Swan, H. J. C , Parmley, W. W., Sustaita, H., Marcus, H. S., and Matloff, J. M.: Influence of Direct Myocardial Revascularization on Left Ventricular Asynergy and Function in Patients With Coronary Heart Disease—With and Without Previous Myocardial Infarction, Circulation 47: 276, 1973.
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Preinfarction angina
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January, 1975
Discussion DR.
MATLOFF
(Closing)
I am somewhat surprised that there was not more discussion regarding the validity of the statistical analysis of this type of treatment based on a prospective and randomized study. As all of you know, such a study is being conducted in at least three different ways. I suspect that, within the next year or 2, we will have some beginning data as to the comparability of medical and surgical therapy in this very small, tightly defined subgroup of patients with angina.
I would like to reiterate that our primary tenet in undertaking direct revascularization surgery is clearly to preserve the myocardium; the time during which myocardial function seems to be most depressed and the need for preservation greatest is in the preinfarction state. Once the diagnosis has been established and the patient has been placed into this subset, therapy should be moved along very expeditiously, with catheterization and the operation planned as a single entity. The greatest problems with surgical therapy occur when the decision to operate is delayed for some time after catheterization.
Jack M. Matloff, M.D., Hector Sustaita, M.D. (by invitation), Kanu Chatterjee, M.D. (by invitation), Aurelio Chaux, M.D. (by invitation), Harold S. Marcus, M.D. (by invitation), and H. J. C. Swan, M.D., Ph.D. (by invitation), Los Angeles, Calif.
JL-Jynamic alterations in supply and demand of oxygen to the myocardium in patients with obstructive coronary artery disease result in varying degrees of myocardial ischemia. These pathophysiological changes are the basis for the varying clinical manifestations and prognosis seen with coronary atherosclerosis. Although these manifestations broadly describe a continuum, it is possible to identify fairly discrete subsets of patients along this continuum. Given the ability to revascularize ischemic segments of the myocardium by direct aortoFrom the Departments of Thoracic, Cardiac, and Vascular Surgery and Cardiology. Cedars-Sinai Medical Center, Los Angeles, Calif. Read at the Fifty-fourth Annual Meeting of The American Association for Thoracic Surgery, Las Vegas, Nevada, April 22, 23, and 24, 1974. Address for reprints: Jack M. Matloff, M.D., Department of Thoracic, Cardiac, and Vascular Surgery, CedarsSinai Medical Center, 4833 Fountain Ave., Los Angeles, Calif. 90029.
coronary bypass,' the problem becomes one of determining the position of a given patient in the evolution of his disease process at a given time. Thus if surgical therapy is to be undertaken, it can be done at the most optimal time. This philosophy of therapy has as its primary tenet the preservation of myocardial viability.- :i In patients experiencing progressive, acute ischemia, accumulating experience suggests that it is possible to identify a subset of patients in whom the likelihood of progression to infarction is significant.4"7 Unfortunately, other reports do not substantiate the validity of this conclusion.*"1" In part, this discrepancy may result from differences in the criteria used to establish the diagnosis. The present study details our continuing experience with medical and surgical therapy for the entity variously termed intermediate coronary syndrome,11 acute coronary insufn73
The Journal of
74
Matloff et al.
Thoracic and Cardiovascular Surgery
28 -,
• A
MEDICAL SURGICAL
24 20 -
(/> K z
16 H
UJ
5
a.
12 8 4 -
<1 MO.
1-12 MOS.
1-5 YRS.
> 5 YRS.
TIME
Fig. 1. Duration of anginal history in 123 patients with preinfarction angina.
Table I. Clinical data in 123 patients No. of patients Medical therapy
35
Surgical therapy
88
Uncomplicated
58
Complicated
30
Sex 29 6 77 11 52 6 25 5
M F M F M F M F
Age range 35-78 (50.65) 34-73 (54.09) 34-73 (54.06) 41-70 (54.13)
ciency,1- acute coronary failure," unstable angina,11 impending infarction/' impending coronary occlusion,1" or preinfarction angina.1'1 Clinical materials and methods Definition. For the purposes of this study, four clinical criteria were used to establish the diagnosis of preinfarction angina. Each patient fulfilled all criteria. These included the following: (1) severe, prolonged (15 to 30 minutes) episodes of anginal pain, often with a crescendo pattern, either of recent onset or as an exacerbation of a chronic stable anginal state; (2) continuing or repeated episodes of pain while at bedrest in the hospital; (3) documentation of transient ST-segment and/or T-wave changes indicative of ischemia; and (4) no elevation of serum enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and creatine phosphokinase) beyond the 10 per cent range of normal.
Patients with progressive or crescendo patterns of pain were not included unless they also continued to have pain at rest in the hospital. In addition to bedrest, all were treated with sedatives, analgesics, and shortand/or long-acting nitrates. Many were treated with heparin and/or beta blockade with propranolol. Institution of these two latter forms of therapy was variable and at the discretion of the primary physician. No patient was included in this study unless at least two of us agreed on whether the patient met the above criteria. All patients meeting these criteria were followed through their hospital course to discharge. Patient population. From December, 1970, to March, 1974, 123 patients (Table I) were seen who met the above criteria. All were admitted to the COU, ICU, or MIRU* of the Cedars of Lebanon Hospital. This is a consecutive experience but it is also a selective one in that there were a number of primary physicians involved who preselected the patients seen. Furthermore, not all patients admitted to these units with the diagnosis of preinfarction angina were seen by the authors. Therefore, it is not an all-inclusive series from our institution. Two nonrandomized forms of therapy were pursued. Thirty-five patients were continued on their medical regimens. On the basis of clinical criteria, all of these patients were acceptable for surgical therapy, but in each, for a variety of reasons, a decision was made to continue medical therapy. Twelve of these patients were catheterized. The remaining 88 patients underwent cardiac catheterization and angiography, followed by direct revascularization surgery. The age range and average ages were similar (Table I) for the two therapeutic groups. There was no significant difference in the sex distribution. Anginal history. The history of angina has been detailed in terms of the total duration of angina (Fig. 1) and the duration of acute symptomatology (Fig. 2). The latter state was the period of time during which the pain occurred with increased severity at rest *Coronary Observation Unit, Intensive Care Myocardial Infarction Research Unit.
Unit, and
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Preinfarction angina
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and with electrocardiographic changes. Approximately equal numbers of patients had total durations of a positive anginal history of 1 to 4 weeks, 2 to 12 months, 1 to 5 years, and more than 5 years. In 34 patients there was recent (less than 1 month) onset of angina with rapid progression to the preinfarction state. There was no significant difference (chi square = 1.164; DF* = 3; p = 0.7621) in this temporal distribution between the two therapeutic groups. In contrast to this even distribution between the two therapeutic groups in terms of total anginal history, 83 patients experienced acute anginal histories of 1 to 7 days and an additional 31 had acute symptoms lasting 8 to 21 days. Again, there was no significant difference (chi square = 3.089; DF = 3; p = 0.3781) in the temporal distribution of acute symptoms between the two therapeutic groups. History of prior myocardial infarctions. Fifty-seven patients experienced 66 episodes of remote myocardial infarction (more than 1 month prior to admission) (Table II) by history and electrocardiographic criteria. Approximately twice as many inferior, posterior, and lateral infarcts had occurred as anterior and septal infarcts. There was no significant difference between the therapeutic groups (chi square = 2.7) in terms of the number of patients having prior infarctions, the number of infarctions experienced, and their locations. Surgical considerations. Patients who accepted the recommendation for study and possible surgery underwent right and left heart catheterization, some with pacing and coronary sinus metabolic studies as well, left ventricular angiography, and selective coronary angiography.'7 The clinical diagnosis in each instance was associated with coronary atherosclerosis confirmed by angiography. As a group, the surgical patients experienced multivessel involvement (average 2.8 vessels per patient), with predominate subtotal (80 to 99 per cent) to total occlusive lesions of the left coronary artery and its major branches (179 of the 250 involved vessels). Only 2 patients had pre* Degrees of freedom.
6
n
A
48 -
% MEDICAL A SURGICAL
40-
zlii
32 -
<
2416 -
• A
•
•
8 1-7 DAYS
A
8-14 DAYS
15-20 DAYS
A
•
>1 MO.
TIME
Fig. 2. Duration of acute symptoms in 123 patients with preinfarction angina.
dominate right coronary artery disease. Seventy-seven of the surgical patients experienced hypokinesis, akinesis, or dyskinesis of one or more ventricular segments by analysis of segmental wall motion in the right anterior oblique ventriculogram. Aorto-coronary artery vein bypass grafting was .performed in 87 of the surgical patients; the remaining patient, who had had vein Iigation and stripping in the past, underwent internal mammary artery bypasses to the anterior descending and its first diagonal branch. Surgery was accomplished by use of total cardiopulmonary bypass with total hemodilution at normothermic temperatures. Direct decompression of the left ventricle was carried out via a sump* placed through the left atrium. Intermittent anoxic arrest, by electrical fibrillation and aortic crossclamping for periods of 10 to 12 minutes, was induced during performance of the distal anastomoses. Interrupted 6-0 silk sutures were used. Between distal anastomoses the heart was reperfused, defibrillated, and allowed to beat for 3 to 5 minutes. The distal anastomoses were completed first. All proximal anastomoses were done with either partial or complete bypass, depending on the status of the left ventricle. In patients with unresponsive ventricles after the operation, pharmacologic means of support were used. No mechanical assist devices were utilized. Within 24 to 48 hours after the *Argyle left ventricular vent catheter, Aloe Medical Distributors, Sherwood Medical Industries, Inc., St. Louis, Mo.
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Table II. Prior infarctions* in 123 patients Location No. of patients No. of episodes Ant./septal Medical therapy Surgical therapy
16/35 ( 4 6 % ) 41/88 ( 4 7 % )
16 50
5 (14%) 16 ( 1 8 % )
Inferior 11 ( 3 2 % ) 27 ( 3 1 % )
\ Post./lat. 6
\
Other 1
•Does not include infarctions during month prior to admission.
Table III. Surgical therapy Vessel bypassed LAD First left diag. LCxM RCA Totals
Uncomplicated (58) 55 13 43 20 131 (2.3*)
Complicated (30) 27 4 15 9 55 (1.8*)
Summary 82 17 58 29 186 (2.1*)
Legend: LAD, Left anterior descending coronary artery. LCxM, Left circumflex marginal branch. RCA, Right coronary artery. •Number of bypass grafts per patient.
Table IV. Preoperative complications in 30 patients Myocardial infarction (continued angina) Anterior Posterior/inferior Ventricular tachycardia/fibrillation Hypotension Congestive heart failure Complete heart block Totals
22 12 10 6 5 2 2 37
operation, all patients were given heparin on a 6 hour dosage schedule calculated to maintain a 5 hour clotting time of 15 to 20 minutes. In this series, 16 patients had single, 47 patients double, 24 patients triple, and 1 patient quadruple vessel bypass. One hundred eighty-six of the 250 vessels identified as being diseased were bypassed for an average of 2.1 vessels bypassed per patient (Table III). Over-all, 157 of 179 involved left-sided vessels (88 per cent) were bypassed. Results Early morbidity and deaths. Thirty-two of the patients treated medically sustained a myocardial infarction prior to discharge.
Twenty-one survived this infarction; 7 of these had anterior wall involvement. Eleven died during the hospital course of their acute infarction; 10 of these 11 had anterior or anterior and inferior infarctions. Three of the 21 survivors died shortly after discharge from the hospital, within 1 month of their admissions. Postmortem examinations were not obtained in these 3 patients. Of the 88 patients who had emergent anatomic study and surgery, 30 experienced one or more major cardiovascular complications of their ischemia before the operation (Table IV). In 19 patients complications occurred between the time the diagnosis was established and catheterization undertaken; these precatheterization complications included episodes of ventricular tachycardia and/or fibrillation, complete heart block, congestive heart failure, and progression to anteroseptal or inferior wall infarction. The latter patients were studied and operated upon after they had experienced an acute myocardial infarction, because they continued to have angina with new electrocardiographic evidence of ischemia. A complication developed during catheterization in 3 patients, ventricular fibrillation in 2 and profound hypotension in 1 patient. In 10 patients complications occurred between the catheterization and operation. These included episodes of ventricular tachycardia and/or fibrillation, congestive heart failure, hypotension without infarction, progression to infarction, and cardiogenic shock. In 7 of these patients there was a 24 hour or longer delay between catheterization and the operation; in the remaining 3 there was an 8 to 18 hour delay between catheterization and the operation. Comparative mortality figures are detailed in Table V. Eleven of the deaths in the medical group were a result of a myocardial
Volume 69
Preinfarction angina
Number 1 January, 1975
infarction. As noted, 3 others died outside of the hospital within 1 month of their acute infarctions, presumably of causes related to their ischemic heart disease. In the surgical group, a 74-year-old patient died of occlusion of the superior mesenteric artery 4 weeks after surgery; his death was probably related to hypovolemia. The second patient experienced uncontrollable ventricular tachycardia and cardiogenic shock during the interval between catheterization and the operation and was operated upon in this condition. The third patient had had acute inferior and subendocardial myocardial infarctions prior to catheterization and was studied because he continued to have anginal pain. He is the only patient who died in the operating room. There was a significant difference (chi square = 28.148 and p = < 0.0001) in mortality rates between the therapeutic groups. Follow-up. One hundred nine patients were discharged from the hospital. As noted, 3 of these patients died outside of the hospital, within 1 month of the date of their admission. One hundred six patients were therefore available for follow-up of more than 1 month. For the medically treated patients, follow-up was accomplished by telephone interview with the patient's primary physician; in some instances the patient also was contacted directly. The duration of follow-up was from 1 to 30 months, with an average follow-up of 15 months. Three patients could not be located for follow-up (Table VI). Thirteen patients were considered to be asymptomatic on continuing medical therapy. Some of these patients continued to experience minor anginal discomfort with exercise exceeding well-defined limits. However, they did not consider these episodes to be disruptive in their life patterns. Five patients continued to have significant angina, despite medical therapy and restricted physical activity. Three of these 5 had associated congestive heart failure. Three of the 5 with residual angina, 2 of whom also had congestive heart failure, were subsequently
77
Table V. Mortality rate* in 123 patients No. of patients | No. of deaths Medical therapy Surgical therapy Uncomplicated Complicated
35 88 58 30
14 3 1 2
(40%) ( 3.4%) ( 1.7%) ( 6.6%)
*One month after admission.
Table VI. Follow-up in 21 survivors of medical therapy No. of survivors
Status Asymptomatic Symptomatic Residual angina Subsequent surgery Congestive failure Late death Lost to follow-up
13 ( 6 2 % ) 5 (24%) 5 3 1 1 3 (14%)
studied in the catheterization laboratory and underwent surgery. Two had left ventricular aneurysmectomies as well as bypass grafts, and all 3 are now asymptomatic. There was one late death in this group, caused by severe uremic pericarditis. The fifth patient with residual angina and congestive heart failure has continued to refuse further study and possible surgery. Of the surgically treated patients (Table VII), 2 were lost to follow-up. We have seen the remaining 83 patients at 6 month intervals. In addition, their primary physicians also have been contacted directly for this review. The duration of follow-up was from 1 to 42 months, with an average follow-up of 17 months. Eight of the survivors of surgery have experienced postoperative infarctions, 7 during the perioperative period and 1 patient 6 weeks after the operation. Two of the seven perioperative infarctions were classified as "unmasking" of a prior inferior wall infarction1* and were not believed to have been surgically induced. All had inferior wall infarctions, and 2 also had anterior wall infarctions. Seventy-one patients have been completely asymptomatic from the time of operation.
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Table VII. Follow-up in 85 survivors of surgical therapy Status
|
Postoperative infarction Asymptomatic Symptomatic Less angina The same degree or more angina Congestive failure Late death Lost to follow-up
Eight have had some degree of postoperative angina; in 6 this has been much less than experienced preoperatively. Four of the 8 have been restudied; in 2 there has been closure of a graft and in 3 significant progression of the atherosclerotic process in vessels that were not originally thought to require bypass. The remaining 2 patients with symptoms have compensated congestive heart failure without angina. Each of these had significant perioperative infarctions, 1 prior to and the other during the operation. There have been two late deaths, both at 1 year. One patient had carcinoma of the pancreas and the other died of a presumed arrhythmia. Discussion Despite an enthusiasm among some that often borders on being evangelical, the indications for aorto-coronary bypass graft surgery continue to be the subject of close study. The most commonly advanced criticism is that for any given indication there is not yet substantial evidence that such surgery prolongs life. This may or may not be valid for the majority of patients who undergo surgery for chronic angina pectoris. However, it is our thesis that in the subgroup experiencing preinfarction angina which is rigidly defined and unresponsive to medical therapy including bedrest, longevity as well as the quality of life is improved in surgically treated patients. In part, such a conclusion generally has been difficult to arrive at because of uncertainty in the literature about the prognosis in this subset .'• "■S1"- -"• 21 The very fact that a di-
Uncomplica,led
;
Compl icatecl 0 24 3
8 47 7 4 2 I
|
Summary 8 ( 9.4%) 71 ( 8 4 % ) 10 ( 1 2 % )
2 1 2 1
0 1
2(2%) 2(2%)
versity of terms has been used for clinical states considered to be similar may be explained by the nonuniformity of diagnostic criteria and hence the underlying disease state reported in various series. In the present study, each patient met our rigidly defined clinical criteria. The fact that there was no statistical difference between our two therapeutic groups in regard to age range and average age, sex distribution, total duration of anginal history, history and distribution of prior myocardial infarctions, and history of acute symptoms supports the contention that we have been able to identify a uniform patient population. This thesis is further supported by the fact that, of the patients studied, there was no incidence of false positives identified by the clinical criteria, in contradistinction to other reports.1" Furthermore, these studies identify an anatomically similar pathological substrate in which there is a predominance of high-grade obstruction and multivessel involvement of the left coronary artery. This observation supports the contention1" that mortality statistics in this syndrome "reflect the prognosis of the basic anatomical substrate rather than anything peculiar to the pain syndrome per se". The high incidence of progression to infarction prior to surgery in both the medically treated and in the surgically treated group, plus the mortality rate in the medically treated group, underscores the malignant nature of this subset. Notwithstanding, the relatively low incidence of complications during catheterization suggests that these patients can be readily studied to precisely
Volume 69
Preinfarction angina
Number 1
79
January, 1975
ARTERIOGRAPHY 100
^""*
PREINFARCTION
^[VESSEL
100
> w 9= 60 3
N^LOW RISK
80 -\
80 \ 3
VESSEL
60
-
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PREINFARCTION ANGINA
l0
ir~v_ \
^
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° [w
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60
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0
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YEARS F i g . 3. Prognosis in c o r o n a r y artery disease
define their anatomy. However, the seemingly increased occurrence of complications between the time of catheterization and surgery, when the interval extends beyond 6 hours, has led us to a policy of not proceeding with catheterization until the patient accepts the possibility of surgery beforehand and until an operating team and room are available. With these simple guidelines and expeditiously conducted anesthetic induction and operation, it has been possible to achieve the significantly increased early survival rate reported herein. Actuarial analysis of the follow-up of our patients indicates that this initial difference in mortality rate is maintained through the first 3 years after the operation (Fig. 3). It is all the more dramatic when taken in the context of longevity of patients with chest pain and demonstrated triple vessel disease-'-- -■'' and of patients with clinically diagnosed preinfarction angina in a high-risk subgroup." The 1 year mortality rate of 43 per cent in this latter group, treated medically, approximates the 1 year mortality rate of our medically treated group. In addition to improved survival and longevity, symptomatic improvement in the surgically treated group was significantly better than in the medically treated group. This symptomatic improvement in surgical survivors who have not experienced perioperative infarction has been demonstrated by objective means to be associated with sig-
nificantly improved left ventricular function after successful surgery.-'• -•"■ It is on the basis of these results, i.e., increased longevity and symptomatic improvement in surgically treated patients, that we suggest direct revascularization is the therapy of choice in this subset of patients with preinfarction angina. Two criticisms can be made of the data on which this thesis is founded: (1) Some of the medical patients were not studied by catheterization and angiography to establish by objective criteria that our two therapeutic groups are in fact similar; (2) the selection of therapy was not determined in a prospective and randomized manner. In regard to the first criticism, 12 of the medical patients were studied, and in general their anatomy corresponded very closely to that seen in the surgical patients. There were 3 patients in whom the extent of distal involvement was such that they were not considered to be appropriate surgical candidates; each of these developed an infarction and survived. These were the only patients in the medical group by default from the surgical group. The matter of randomizing the choice of therapy in a prospective study is a much more difficult one to resolve, for both ethical and scientific reasons. Given the setting of the present study and the difference in results from the beginning of the study, we have not felt that the choice of therapy
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should be made for these patients either by default or by assuming that there was insufficient experience to make an appropriate decision. This latter assumption would certainly appear to be valid on the basis of an almost identical recently reported experience derived from a prospective and randomized study.7 It remains to be seen whether these conclusions will be supported by an ongoing cooperative study. REFERENCES 1 Favaloro, R. G.: Saphenous Vein Graft in the Surgical Treatment of Coronary Artery Disease, J.
2
3
4
5
6
7
8
9
10
11
THORAC.
CARDIOVASC. SURG. 58:
178,
1969. Maroko, P. R., Kjekshus, J. K., Sobel, B. E., et al.: Factors Influencing Infarct Size Following Experimental Coronary Artery Occlusions, Circulation 43: 67, 1971. Forrester, J. S., and Chatterjee, K.: Preservation of Ischemic Myocardium, in Vogel, J. H. K., editor: Advances in Cardiology, Basel, S. Karger. In press. Vahil, R. J.: Preinfarction Syndrome: Management and Follow-up, Am. J. Cardiol. 14: 55, 1964. Chatterjee, K., Swan, H. J. C , Sustaita, H., Matloff, J. M., and Parmley, W. W.: Impending Infarction and Direct Myocardial Revascularization, in Corday, E., and Swan, H. J. C , editors: New Perspectives in Diagnosis and Management of Myocardial Infarction, Baltimore, 1972, Williams & Wilkins Company, p. 362. Gazes, P., Mobley, E. M„ Jr., Faris, H. M.. Jr., Duncan, R. C , and Humphries, G. B.: Preinfarctional (Unstable) Angina—A Prospective Study—Ten Year Follow-Up: Prognostic Significance of Electrocardiographic Changes, Circulation 48: 331, 1973. Bertolasi, C. A., Tronge, J. E., Carreno, C. A., Jalon, J., and Vega, M. R.: Unstable Angina— Prospective and Randomized Study of Its Evolution, With and Without Surgery: Preliminary Report, Am. J. Cardiol. 33: 201, 1974. Murnaghan, D., Hickey, N., and Mulcahy, R.: Immediate and Long Term Experience of Acute Coronary Insufficiency (Abstr.), Br. Heart J. 32: 555, 1970. Hochberg, H. M.: Characteristics and Significance of Prodromes of Coronary Care Unit Patients, Chest 59: 10, 1971. Krauss, K. R., Hutter, A. M., Jr., and DeSanctis, R. W.: Acute Coronary Insufficiency: Course and Follow-Up, Circulation 45, 46: 66, 1972 (Suppl. I ) . Graybiel, A.: The Intermediate Coronary Syn-
drome, U. S. Armed Forces Med. J. 6: 1, 1955. 12 Master, A. M., Jafre, H. L., Field, L. E., and Donoso, E.: Acute Coronary Insufficiency: Its Differential Diagnosis and Treatment, Ann. Intern. Med. 45: 561, 1956. 13 Freedberg, A. S„ Blumgart, H. L., Zoll, P. M., and Schlesinger, M. J.: Coronary Failure: The Clinical Syndrome of Cardiac Pain Intermediate Between Angina Pectoris and Acute Myocardial Infarction, J. A. M. A. 138: 107, 1948. 14 Fowler, N. O.: "Preinfarctional" Angina, Circulation 44: 755, 1971. 15 Sampson, J. J., and Eliaser, M.. Jr.: Diagnosis of Impending Acute Coronary Artery Occlusion, Am. Heart J. 13: 675, 1937. 16 Resnik, W. H.: Preinfarction Angina. I. The Transaminase Test—A Diagnostic Aid. II. An Interpretation, Mod. Con. Cardiovasc. Dis. 31: 751 and 757, 1962. 17 Matloff, J. M„ Marcus, H., Chatterjee, K., Chaux, A., Sustaita, H., and Swan, H. J. C : The Anatomy of Preinfarction Angina. In preparation. 18 Bassan, M. M., Oatfield, R., Hoffman, I., Matloff, J. M., and Swan, H. J. C : New Q Waves After Aortocoronary Bypass: Unmasking of an Old Infarction, N. Engl. J. Med. 290: 349, 1974. 19 Proudfit, W. L., Shirey, E. K., and Sones. F. M., Jr.: Selective Cine Coronary Arteriography: Correlation With Clinical Findings in 1,000 Patients. Circulation 33: 901, 1966. 20 Wood, P.: Acute and Subacute Coronary Insufficiency, Br. Med. J. 1: 1779, 1961. 21 Beamish, R. E., and Stonie, V. M.: Impending Myocardial Infarction: Recognition and Management, Circulation 21: 1107, 1960. 22 Bruschke, A. V. G., Proudfit, W. L., and Sones, F. M., Jr.: Progress Study of 590 Consecutive Nonsurgical Cases of Coronary Disease Followed 5-9 Years. I. Arteriographic Correlations, Circulation 47: 1147. 1973. 23 Webster, J. S., Moberg, C , and Rincon, G.: Natural History of Severe Proximal Coronary Artery Disease as Documented by Coronary Cineangiography, Am. J. Cardiol. 33: 195. 1974. 24 Chatterjee, K., Swan, H. J. C , Parmley, W. W., Sustaita, H., Marcus, H., and Matloff, J. M.: Depression of Left Ventricular Function Due to Acute Myocardial Ischemia and Its Reversal After Coronary Saphenous Vein Bypass, N. Engl. J. Med. 286: 1117. 1972. 25 Chatterjee, K... Swan, H. J. C , Parmley, W. W., Sustaita, H., Marcus, H. S., and Matloff, J. M.: Influence of Direct Myocardial Revascularization on Left Ventricular Asynergy and Function in Patients With Coronary Heart Disease—With and Without Previous Myocardial Infarction, Circulation 47: 276, 1973.
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Discussion DR.
MATLOFF
(Closing)
I am somewhat surprised that there was not more discussion regarding the validity of the statistical analysis of this type of treatment based on a prospective and randomized study. As all of you know, such a study is being conducted in at least three different ways. I suspect that, within the next year or 2, we will have some beginning data as to the comparability of medical and surgical therapy in this very small, tightly defined subgroup of patients with angina.
I would like to reiterate that our primary tenet in undertaking direct revascularization surgery is clearly to preserve the myocardium; the time during which myocardial function seems to be most depressed and the need for preservation greatest is in the preinfarction state. Once the diagnosis has been established and the patient has been placed into this subset, therapy should be moved along very expeditiously, with catheterization and the operation planned as a single entity. The greatest problems with surgical therapy occur when the decision to operate is delayed for some time after catheterization.