EDITORIALS

Isolated Left Anterior Descending Coronary Artery Disease:

Choice of Therapy*

ZAINUL ABEDIN, MD, FRCP(C) SIMON DACK, MD, FACC

New York, New York

Various studies on the natural history of coronary artery disease have demonstrated that the prognosis of the disease is directly related to its severity and to the de- gree of associated left ventricular dysfunction as defined primarily with coronary angiography and ventriculog- raphy.l-g Two and three vessel coronary artery disease and stenosis of the left main coronary artery appear to have a poor prognosis, and the 5 to 10 year outlook is even worse when they are associated with factors such as left ventricular dysfunction, abnormal electrocardi- ogram, hypertension, cardiomegaly and congestive heart failure l-l5

The ‘natural history studies have also shown that patients with single vessel coronary artery disease have a better 5 to 10 year survival rate than patients with double or triple vessel disease.1-2*5-8 However, their prognosis appears to differ according to whether the vessel involved is the left anterior descending, left cir- cumflex or right coronary artery.1*2>5v7-g In view of the surgical implications, we will examine the hypothesis that significant disease isolated to the left anterior de- scending coronary artery is more lethal than any other single vessel coronary disease. This will be examined with three approaches-myocardial infarction studies, angiographic data and data on surgical versus medical treatment.

Myocardial Infarction Studies

Mortality and morbidity are known to be greater after anterior wall infarction (myocardium supplied by the left anterior descending artery or its branches) than after inferior wall infarction (myocardium supplied by the right coronary artery or branches of the circumflex

From the Division of Cardiology, Department of Medicine, The Mount Sinai Hospital and the Mount Sinai School of Medicine of City University of New York, New York. Manuscript received April 11, 1977, accepted May 11, 1977.

Address for reprints: Simon Dack, MD, Division of Cardiology, De- partment of Medicine, Mount Sinai School of Medicine of the City Uni- versity of New York, Fifth Avenue and 100th Street, New York, New York 10029.

artery). For more than 40 years, clinicians have noted that early mortality and incidence of congestive heart failure were almost twice as great in anterior as in in- ferior wall infarction.i6-l8 In a recent international study’s on practolol, 3,038 patients recovering from acute myocardial infarction were studied. In the group receiving placebo, 48 of 768 patients with anterior in- farction and 25 of 476 patients with inferior infarction died, a significant difference. There were 33 sudden deaths in the group with anterior infarction but only 19 in the group with inferior infarction. The most signifi- cant difference appeared within the first month after entry into the trial, when 19 deaths occurred among patients with anterior infarction and only 1 death among those with inferior infarction. Hamby et a1.20 noted that congestive heart failure was twice as common (21 versus 11 percent) in 52 patients with complete oc- clusion of the left anterior descending coronary artery without collateral vessels as in 44 patients with complete occlusion of the right coronary artery without collateral vessels. Cardiomegaly and ventricular conduction blocks are also reported to be more common in patients with anterior myocardial infarction.21,22

Liberthson et a1.23 found that of 42 patients who survived an out of hospital episode of ventricular fi- brillation, were hospitalized and then discharged, 12 died suddenly during the follow-up period. Of these 12 patients, 4 had anterior wall infarction and 4 had an- terior wall ischemia; none had evidence of inferior wall infarction or ischemia. Angel1 and Griffith24 reported angiographic studies in 79 patients who survived sudden arrhythmic death (ventricular fibrillation or ventricular tachycardia). The left anterior descending or the left main coronary artery, or both, was involved in 76 of the 79 patients, and in 14 of the 15 patients with only single vessel disease the obstruction was isolated to the left anterior descending artery. It was concluded that an- teroseptal ischemia or injury secondary to left anterior descending coronary artery disease is an important cause of ventricular fibrillation or tachycardia. Dhur- andar et a1.25 also noted that primary ventricular fi-

‘Editorials published by the Journal reflect the views of the authors and do not necessarily represent the views of the Journal or of the American College of Cardiology.

654 October 1977 The Amerlcen Journal of CARDIOLOGY Volume 40

brillation was approximately twice as frequent in pa- tients with anterior as in those with inferior myocardial infarction. In a more recent study, Moss et al.26 reported that anterior infarction was more common (60 percent) than inferior infarction (24 percent) among 42 patients with myocardial infarction who died within 6 months of hospital discharge (the majority suddenly).

Insights Obtained With Angiography

A second approach is to evaluate the natural history of isolated disease of the left anterior descending, right and circumflex coronary arteries as defined with angi- ography and ventriculography. Webster and Moberg and their colleagues5f7 reported a 6 to 11 year follow-up study of 178 patients with 80 to 100 percent occlusion of a single coronary artery. The yearly attrition rate was 4 percent for patients with disease of the left anterior descending artery and only 2.3 percent for those with disease of the right coronary artery. Among the former group, there was only a minor difference if the lesion was proximal or distal to the major septal perforating branch (36 versus 27 percent). Of 10 patients with 100 percent obstruction of the left anterior descending artery, 4 with faint or no collateral vessels died, whereas 6 with un- compromised collateral vessels survived. Lichtlen and Moccettis reported their experience in 83 patients with single vessel coronary artery disease followed up for 32.5 months. Ten percent of these died during the follow-up period. The 24 patients with disease limited to the left anterior descending artery had a higher mortality rate (20 percent) than the 35 patients with isolated right or left circumflex coronary artery disease (8 percent). Bruschke et al1 reported a 17.3 percent 5 year mortality rate (3 percent a year) among patients with single vessel coronary artery disease. The rate was higher (4 percent a year) in those with a lesion involving the left anterior descending coronary artery. The 5 year cardiac mor- tality rate in patients with single vessel coronary artery disease and associated moderate (less than 50 percent) obstruction in other arteries was 23.4 percent.

Humphries et al.* followed up 32 patients with single vessel disease for 5 to 12 years; 24 had isolated left an- terior descending coronary artery disease, and only 2 of these died during the follow-up period. In this series, the 5 year cardiac mortality rate in patients with single vessel disease was lower than that recorded by

TABLE I

EDITORIALS

others.1J*5*7 This difference may have been related in part to patient selection; 40 of their patients were eliminated from the study because of surgical inter- vention, and some of these may have had single vessel disease. Oberman et al9 reported a 5 year follow-up study of 46 patients with single vessel disease, 2 of whom (4 percent) died during the first 20 months. Discrimi- nant function analysis of important variables revealed that left anterior descending coronary artery disease was an important predictor of mortality. Burggraf and Parker2 reported on a 1 to 10 year follow-up study of 101 patients with significant angiographically documented single vessel coronary artery disease. In 50 percent of the group the disease was confined to the left anterior descending artery; the 5 year survival rate in this group was 87 percent compared with 98 percent for those with isolated right coronary artery disease and 99.4 percent in subjects with a normal coronary arteriogram.

In an attempt to draw more meaningful conclusions, we have combined the results of five of these stud- ies1~2~5,7~8 on survival in single vessel coronary artery disease (Table I). Although the total observed mortality was greater in the group with left anterior descending coronary artery disease, mortality rates did not differ significantly in any individual study among patients with left anterior descending or left circumflex or right coronary artery disease (P >0.40 in all studies). How- ever, when the average difference in the rates of these five studies is examined, the average mortality rate in left anterior descending disease was almost 3 percent a year higher than in left circumflex or right coronary artery disease (t4 = 1.68,O.l <P <0.2). Thus the com- bined data support the observed trend.

Surgical Versus Medical Treatment

Most studies comparing medical and surgical treat- ment have the drawback of not being prospective and randomized. Sheldon et a1.15 reported a 3 to 7 year fol- low-up study of 741 patients with coronary artery dis- ease subjected to a bypass graft operation. Survival in this surgically treated group was then compared with survival in a group previously studied between 1960 and 1965 before the development of graft surgery. The an- nual attrition rate among the surgically treated patients with single vessel disease was 2.4 percent compared with 3.5 percent in those not surgically treated. Among those

Comparison of Mortality Rates in Isolated Lefl Anterior Descending, Left Circumflex or Right Coronary Artery Disease

Authors Duration of

Follow-up (yrs)

Left Anterior Descending Left Circumflex or Right Coronary Artery Coronary Artery

Cases Deaths DeathslYr Cases Deaths Deaths/Yr Difference (no.1 (no.1 (%) (no.1 (no.1 (%I % 2 P

Moberg et al.’ 1.7 36 11 4.4 2.6 0.70 <0.52 Lichtlen and Moccet@ Bruschke et al.’ :

;f 2: :.: :z z :::

5.6 1.03 <0.70

2:3 126 23 3.6 1.9 0.65 CO.48

Burggraf and Parker* z:

6 50 1.9 0.82 <0.59 Webster et aL5 6

t 171.68, :;< 77 1: Z:d 1.7 0.58 CO.44

0.1 0.2

t4 = Student’s t test with four degrees of freedom.

October 1977 The American Journal of CARDIOLOGY Volume 40 666

EDITORIALS

with left anterior descending artery disease, the surgi- cally treated patients survived longer (annual attrition rate 1.7 percent) than those treated without surgery (annual attrition rate 4.8 percent).

Kouchoukos et a1.14 reported the results of surgical versus medical treatment of isolated left anterior de- scending coronary artery disease. Twenty-nine surgi- cally treated patients were followed up for 31 months. There were no operative or early postoperative deaths. The late cardiac mortality rate was 6.9 percent (yearly attrition rate 2.7 percent). The early postoperative myocardial infarction rate was 10 percent and the graft patency rate was 68 percent. Twenty-four patients were treated medically and followed up for 45 months. There were no cardiac deaths and only one patient had myo- cardial infarction. The authors concluded that surgical treatment is more effective than medical treatment in relieving angina and improving exercise performance; however, it did not enhance the already favorable prognosis of the medically treated group. This is an important study that attempted to answer the question of selection of therapy for patients with isolated left anterior descending coronary artery disease. However, the patients in the medical and surgical groups were not identical as in relation to site, severity and extent of disease in the left anterior descending coronary artery. Thus, the following points need further elaboration: (1) More patients in the surgical than in the medical group had additional narrowing of 50 percent or less of either the left circumflex or right coronary artery. It has been showniJ that mortality in patients with single vessel disease is greater when there is associated (but less than 50 percent) obstruction in other vessels. (2) Total oc- clusion of the left anterior descending coronary artery was more than twice as common in the medically treated as in the surgically treated patients. Although Kou- choukos et al. did not consider this difference impor- tant, patients with a completed lesion are not at risk of sudden occulsion of this vessel with its devastating complications. (3) More patients in the medical than in the surgical group had lesions distal to the first diagonal branch of the left anterior descending coronary artery. Hence, it is possible that the amount of myocardium in jeopardy beyond the distal lesion is relatively small and thus, if infarction occurs, there will be less morbidity and mortality.28-30 This finding may explain the seemingly more favorable prognosis in the medically treated patients in this series. (4) In the surgically treated group subsequent (late postoperative) cardiac events such as myocardial infarction or death were not necessarily related to anterior myocardial infarction or to occlusion of the bypass graft to the left anterior de- scending artery. If those patients who subsequently had right coronary artery or circumflex artery disease or died of posterior infarction are excluded, then even in this series the surgically treated patients with isolated dis- ease of the left anterior descending coronary artery have shown no early or late (31 months) cardiac mortality. (5) As Mathur2s pointed out, the exercise tolerance time in the study of Kouchoukos was 50 percent longer in the medically treated than in the surgically treated patients.

In addition, only half of the patients in the medical group had angina as a limiting factor during exercise testing. Thus, there may have been better myocardial perfusion through collateral vessels or for other reasons in the medical group.

Problems and Possible Solutions

A major problem is the lack of uniformity in assessing the significance of a given coronary arterial lesion. Different studies have used different criteria for se- lecting patients. Some1 have included patients with 50 percent or more narrowing of coronary arterial luminal diameter. Others15,i6 have accepted only patients with 70 percent or more narrowing and still others5 have excluded patients with less than 80 percent narrowing. These differences make it difficult to compare and evaluate the results of published studies.

A second major problem is that patients with single vessel coronary artery disease at the time of entry into the study may later have double or triple vessel in- volvement. Thus, their prognosis and outcome may change. An urgent problem, therefore, is finding ways to identify the progression of disease during follow-up study short of repeat coronary angiography.

Lastly, it is important to identify various subgroups of patients with an isolated significant lesion of the left anterior descending coronary artery according to clinical status, site and severity of the lesion and presence or absence of hypokinesia or akinesia.

An asymptomatic patient with complete (100 per- cent) obstruction of the left anterior descending artery with excellent collateral vessels or with an akinetic scar in the distribution of this artery may not derive as much benefit from bypass surgery as a symptomatic patient with a significant isolated proximal left anterior de- scending lesion without collateral circulation and with normally contracting myocardium in the distribution of this artery. Such subgrouping of patients will be useful in planning prospective studies in an attempt to evaluate the benefits and risks of medical and surgical therapy. It is also essential that these groups not be mixed with one another. A prospective and randomized study, in which large numbers of patients with an iso- lated significant left anterior descending coronary ar- terial lesion would be treated medically or surgically and followed up for 5 to 10 years might provide a decisive and meaningful answer.

In conclusion, on the basis of the foregoing discus- sion, the following points emerge: (1) There are various subgroups among patients with isolated significant left anterior descending coronary artery disease depending on the site and severity of the lesion and amount of myocardium in jeopardy. The natural history of these subgroups varies. (2) Not all patients with an isolated left anterior descending lesion, irrespective of severity, site of lesion and left ventricular wall motion charac- teristics, will benefit from bypass surgery. (3) Because the purpose of performing bypass surgery is to prevent myocardial infarction, alleviate angina and prolong life, the aim should be to achieve low rates of surgical mor- tality and perioperative infarction and a high rate of

656 October 1977 The American Journal of CARDIOLOGY Volume 40

EDITORIALS

patency of the bypass graft. For a single left anterior benefit a subgroup of symptomatic patients with an descending artery bypass, a competent surgical team isolated proximal lesion of the left anterior descending should be able to achieve an operative mortality rate of coronary artery, without collateral vessels and with less than 1 percent, a perioperative myocardial infarc- normally contracting myocardium in its distribution. tion rate of less than 4 percent and a patency rate of the We believe that this can be achieved with available bypass graft of more than 90 percent. Provided that surgical skill and techniques, particularly when an in- such low morbidity and mortality rates can be achieved, ternal mammary artery graft can be used, and recent it is logical to anticipate that surgical therapy will reports31-s3 have shown encouraging results.

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