Observations on unstable angina pectoris with particular respect to managemen?

P. J. de Feyter, M.D. P. A. Majid, M.B., M.R.C.P. R. Wardeh, M.D. J. P. Roes, M.D. Amsterdam,

The Netherlands

In recent years a great deal of attention has been focused on a small but distinct group of patients with ischemic heart disease who experience prolonged bouts of chest pain at rest accompanied by electrocardiographic changes of myocardial &hernia but without any objective evidence of myocardial necrosis.l:’ Opinion is divided regarding the prognosis and the optimal management in this situation.’ Contrary to previous beliefs,+” it has become apparent that the prognosis of patients within the group as defined above, at least in the acute phase, is relatively benign.ll-‘l There is no definite evidence available about the superiority of medical or surgical treatment.S.l’,lG Consequently a shift in emphasis from acute intervention to a more elective form of surgical therapy has taken place.‘fi.lT In a majority of patients bed rest and beta-adrenoceptor antagonists have been suflicient to relieve symptoms completely and have led to rapid stabilization.“.‘T-?” Beginning in November, 1975, we established a protocol of treatment to study the response prospectively in a group of patients after precise clinical definition. Coronary angiography was performed routinely in all patients. The following report concerns 70 such patients who have now been followed for a mean duration of twenty months (range 4 to 36 months). From The Amsterdam,

Department of The Netherlands.

Cardiology,

Received

for publication

Feb. 13, 1979.

Accepted

for publication

Mar.

F’ree

University

Hospital,

28, 1979.

Reprint requests: Dr. P. J. de Feyter, Academisch Ziekenhuis der Vrije Universiteit, De Boelelaan 1117, lCG7 MB Amsterdam, Postbwtt 7057, The Netherlands.

OCXI2-8703/79/100431

+ 09$00.90/00

1979

The

C. V. Mosby

Co.

Patients

and methods

(Table

I)

Between the period November, 1975, and July, 1978, 70 patients, (58 men and 12 women) with a mean age of 55 years (range 34 to 70), were admitted to our coronary care unit, who met the following clinical criteria: 1. Repeated, typical chest pain at rest lasting for more than 15 minutes, with little relief afforded by nitrates, and needing frequently parenteral opiates for relief from pain. These episodes of pain could be appearing for the first time or could be superimposed on already established angina pectoris. 2. Changing patterns of ST and T wave changes on the electrocardiogram. 3. No enzymatic evidence of myocardial necrosis (creatine phosphokinase, aspartate transaminases, and lactate dehydrogenase repeated at least three times during the first twenty four hours). Coronary arte!iography. Once an infarct was excluded, coronary arteriography and ventriculography was performed within 48 to 72 hours of admission, following Judkin’s technique?’ in all patients. Both major coronary arteries were filmed in multiple projections including craniocaudal projection. Narrowing of the lumen of one or more branches of the coronary arteries of 75 per cent or more was described as critical. If a significant occlusion was present, a second lesion was considered significant if there was a luminal narrowing of 50 per cent or more. The patients were grouped, according to the number of vessels involved-i.e., one-, two-, or three-vessel disease. The left ventricle was opacified in the 30 degree

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I. Clinical details of patients

Table

with unstable Group

Number of patients Mean age (years) Previous angina pectoris Old myocardial infarction Cardiomegaly

I

36 55.4 (36-70) 10 9 3

Il. Hemodynamic

Table

angina pectoris

and angiographic Group

Group

II

5 51.6 (45-61) 2 1 1

I

Group

II

36 36 32 4 12 22 2 -

5 4 1 4 1 2 2 1 -

Angiography: 1 vessel RCA ” LAD ” cx 2 vessel RCA

+ LAD

8 11 1 9

+ CX + CX + LAD

1 4 2

2 1 -

Main ”

RCA LAD RCA

stem: single + RCA + LAD

+ CX + CX

-

right anterior oblique view. The left ventricular end-diastolic pressure was measured through fluid-filled catheters (Cook’s pigtail). A pressure above 14 mm. Hg was considered abnormal. The ejection fraction was calculated by the area-length method.Z’ In cases of aneurysm no ejection fraction was measured. The ejection fraction was classified as normal (above 50 per cent), reduced (25 to 50 per cent), and severely reduced (below 25 per cent). The segmental contraction abnormalities vere assessed visually. The abnormalities of contraction pattern were arbitrarely divided into four groups: Group 1 = normal Group 2 = localized hypo- or akinesia Group 3 = globally reduced contraction pattern Group 4 = aneurysm. Protocol of treatment (Fig. 1). The patients were observed in the coronary care unit. Soon

432

III

13 57.5 (47-67) 3 5 1

findings in patients

Number of patients LVEDP 14 mm. Hg LVEDP 14 mm. Hg Ejection fraction >50 P, ,r 25-50 ,, ,, :. ‘.V.V ;.y..:.:

~ II

I I

~FlSYMPTOMflTlC

II

~SYMPTOMFITIC~ELECTIVE

III=RCUTE

IV

III

!v

SURGERY

SURGERY

=INOPERRBLE

Fig. 4. Bar graph presenting follow-up percentages in the four groups of patients. Patients were followed for a mean of 22 months with a range of 4 to 36 months.

it was higher than 20 mm. Hg. The ejection fraction was severely reduced in four patients and normal in one patient. Ventriculography demonstrated generalized hypokinesia in seven patients, in four a localized hypo- or akinesia, and in two patients an anterolateral aneurysm. CORONARY ARTERIOGRAPHY. Arteriograms revealed three-vessel disease is seven patients, twovessel involvement in two patients, three-vessel disease and severe left main coronary artery lesion in one patient, and one-vessel disease (LAD) in one patient. FOLLOW-UP. During the acute phase none of the patients went on to myocardial infarction. During the follow-up period three patients have died suddenly. Of the eight surviving patients, five continue to have moderately severe angina1 symptoms, and two patients have associated left ventricular failure adequately controlled with treatment. One patient sustained a non-fatal myocardial infarction. Group V. This group comprised five patients (7 per cent) who on coronary arteriography were found to have “normal” coronary arteries and left

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ventricular function. In two of these patients coronary artery spasm was demonstrated during pain on arteriography. In two patients signs consistent with cardiomyopathy were observed. In one patient no immediate explanation of signs and symptoms was apparent; however, a routine cholecystography in this patient revealed multiple stones in the gall bladder. After cholecystectomy the patient has become symptom-free and manifests a disappearance of electrocardiographic changes. Discussion

Unstable angina pectoris is the presently preferred term to describe all the patients who occupy a twilight zone between classical acute myocardial infarction and exercise-induced angina pectoris.1. 23.24 For over 40 years this clinical syndrome has been reported regularly under a variety of names: impending acute coronary artery occlusionZA intermediate coronary syndrome,Z1i acute coronary insufficiency,Zj status anginosus,~S impending myocardial infarction,X!l and pre-infarction angina~-each one implying varying degrees of urgency and foreboding in terms of treatment and prognosis, respectively. In the studies reported before 1970, a high acute infarction rate (21 to 80 per cent) and mortality rate (up to 60 per cent)S-l” were observed, but important differences in the clinical presentation of the series of patients described, lack of precise diagnostic criteria, and an ever-changing pattern of medical management makes it difficult to draw any useful conclusion about the natural history of the clinical syndrome as a whole. Besides, the last decade has seen several interventions in the natural history of ischemic heart disease which preclude reference to the previous observations. Thus widespread dissemination of knowledge through the media about the gravity of chest pain with consequent rapid hospitalization and intensive monitoring in the coronary care units has led to early recognition of patients at high risk. The early institution of optimal medical therapy in the shape of nitrates, beta-adrenoceptor antagonists, and antiarrhythmic agents has contributed significantly to a reduction in early morbidity and ~~~~~~~~y~.l.l~.2~l As a direct consequence, a number of studies which appeared during the 1970’s registered a sharp drop in the acute myocardial infarction rate as low as 5 to 10 per cent, and a low mortality

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rate during the acute phase of unstable angina pectoris.“-14 These studies also emphasized the heterogeneity of the patient population, which led Conti and colleagues” to try to distinguish several subgroups so as to allow the study of natural history in real perspective and at the same time permit proper comparison of treatment. The cohorts which became easily recognizable were : 1. Patients with angina pectoris of recent onset 2. Changing pattern in patients with stable angina pectoris 3. Angina at rest. Of course there could be a considerable overlap between the three groups; thus Group 3 patients may or may not have had angina1 symptoms previously. The adverse prognostic significance of persistent pain, history of previous myocardial infarction, and angina pectoris was also stressed.ll, IX Perhaps the greatest impact has been made by the safe use of coronary arteriography. Precise anatomical characterization of the coronary arterial tree not only establishes the severity of the obstructive coronary artery disease, but also identities patients who have either no demonstrable coronary atherosclerosis or those with critical left main coronary artery stenosis. Left ventricular angiography and the related hemodynamic parameters give essential information about left ventricular function. Both the severity of obstructive coronary artery disease and left ventricular dysfunction have a significant influence on the prognosis and management of unstable angina pectoris.Z” In the majority of the series where angiography was done routinely, the presence of extensive coronary atherosclerosis in patients with unstable angina was confirmed.l-‘. ‘;. x ,il-~:%The distribution of arterial abnormalities was similar to that found in patients with stable angina pectoris. Of particular interest was the fact that 5 to 10 per cent of the patients were invariably found to have normal or minimally diseased arteries in all studies I. 17.!I-:!‘! In the late 1960’s the advent revascularization added an extra the management of ischemic heart rally one of the earliest targets for py were patients who presented

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angina pectoris. This was on the assumption that the clinical syndrome of unstable angina pectoris was a harbinger of acute myocardial infarction and possibly of sudden death. At least on theoretical grounds, the surgical intervention was advocated to bring about reduction in the morbidity and mortality rates. Enthusiasm for acute operative treatment was also generated by the favorable outcome in a small number of patients reported.‘i’m,!‘l However, several comparatively large-scale studies, albeit uncontrolled, showed that surgical therapy, at least during the acute phase, ‘: was not without appreciable risk. Evidence gathered from the recently reported series’. ” provided the platform to launch our own study. It soon became apparent that despite the favorable response to medical therapy described in these series, all the patients were operated eventually. The natural history of medically treated patients was available only where the patients had either refused operation or were inoperable.‘. ‘$’ In the only series where an attempt was made to treat all patients medically, 70 per cent of the patients were operated because of unacceptable angina peetori&” The results of the latter study might give the impression that the majority of patients with unstable angina pectoris are more likely to have persistent angina1 symptoms despite optimal medical therapy. Yet the entire series of these patients had a previous history of angina pectoris and 50 per cent had sustained myocardial infarction in the past-the risk factors which have been shown to adversely affect the course and prognosis of the clinical syndrome of unstable angina pectoris.“’ In our own study we decided to follow-up prospectively a series of carefully selected patients with rest angina, where intensive medical therapy formed the primary basis in the management. Surgical intervention would be considered only if the medical had failed in relieving symptoms and in cases of left main coronary artery stenoses. The importance of coronary angiography in this respect cannot be overemphasized. We were fully cognizant of the potential risks’, Z1.3Z involved, but on the basis of available evidence we realized that coronary arteriography performed early in the course of the syndrome was mandatory to the future management. In our series the investigation was done without any fatal incident. It provided us with the framework on which to base our policy of future management. Thus

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patients with substantial left main coronary artery disease were operated acutely. This group of patients has been shown to respond unfavorably to medical treatment and may have an improved prognosis if operated early?+ Seven per cent of the patients were found to have normal coronary arteries, which finding has regularly been reported in all other series also. All the other patients, operable and inoperable, were offered intensive medical treatment initially. We believe that coronary angiography in expert hands is safe, and does not carry any extra risks. The risks, such as they are, may have to be taken in those very patients where precipitate action is warranted, either because of persistent symptoms or the presence of life-threatening obstructive lesions.12. 14,‘42.ZIH..,!I Symptoms. The symptoms conform to the experience of others; 82 per cent of the patients in our series became rapidly symptom-free on medical treatment, and only 18 per cent were operated within the first week of admission, either because of persistent symptoms or because of left main coronary artery lesions. Another 7 per cent were electively operated within six months of admission because of the recurrence of symptoms under optimal medical treatment. During a maximal follow-up period of three years (range 4 to 36 months) 27 patients remain asymptomatic on medical treatment. Eight patients in Group I continue to have symptoms, although they are controlled adequately with treatment. Analysis of the arteriographic abnormalities in the latter group of patients demonstrated either isolated left anterior descending artery stenosis or multiple vessel disease. None of the patients with isolated right coronary artery disease have persistent symptoms. The majority of patients treated surgically are symptom free. Only three patients out of 18 continue to have mild symptoms which can be explained entirely by the graft patency. Myocardial infarction. Among the medically treated group, 6 per cent of the patients sustained a new myocardial infarction within the first year of admission. Among the surgically treated group, two patients developed perioperative infarction and one patient sustained a new infarction within three months of operation (4 per cent). Recatheterisation in the latter revealed closure of all the grafts. The number of patients in both groups are too small to allow any statistical comparison.

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Mortality. In the medically treated group, four patients died (6 per cent) but three of these patients had severe left ventricular dysfunction and were therefore considered inoperable. In the surgically treated group, there was no operative mortality rate (0 per cent), but one patient died suddenly two months after operation. Medical vs surgical treatment. Although no comparison of the two treatments is implied in our study, there are several points which are worthy of comment. In the first instance the majority of patients during the acute phase became quickly symptom-free on medical treatment, in common with the experience of others. Secondly, the declining trend in the morbidity rates in patients on medical treatment is confirmed in the present study.“-” Finally, surgical treatment in properly selected cases can be undertaken with acceptable risk and a good clinical result. Considerable support for these findings has been provided by the publication of the National Cooperation Study Group on unstable angina pectoris,9t’ in which have been obtained in a large series of randomized patients treated medically and surgically. Finally, the results of this study allow us to make the following conclusions; 1. Coronary angiography played an important role in the diagnosis, prognosis, and management in this group of patients. 2. Prognosis was relatively benign in patients with mild to moderately severe coronary sclerosis. 3. The majority of the patients responded rapidly to medical therapy and an appreciable number have stayed symptom-free. 4. Surgery, acute or selective, was required in about 25 per cent of the patients. Summary

Seventy patients with a diagnosis of unstable angina pectoris were admitted. They met the following criteria: (1) repeated typical chest pain at rest lasting for more than 15 minutes, (2) changing patterns of ST and T wave changes on the electrocardiogram, and (3) no evidence of myocardial necrosis. In all patients coronary arteriography was performed within 48 to 72 hours after admission without any untoward effects. All patients received intensive medical treatment: bed rest,

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propranolol, and nitrates when necessary. Response to this treatment determined the future management. Those patients who remained symptomatic during the acute phase and those with left main coronary artery stenosis were operated within two or three weeks after the trial with medical therapy. Those who became symptom free were followed up at three-monthly intervals. Surgical treatment was offered if there was a recurrence or progression of angina pectoris. Those who were inoperable and those with no detectable abnormalities on the angiogram were also followed up regularly. With intensive medical therapy, 82 per cent of the patients became symptom free; only 18 per cent were operated either because of persistent symptoms or because of left main coronary artery lesions. During follow-up, however, another 7 per cent were operated electively because of the recurrence of symptoms, despite adequte medical treatment. Among the medically treated group 6 per cent sustained a new myocardial infarction, while among the surgically treated group two patients developed a perioperative infarction and one patient sustained a new infarction during followup (4 per cent). Four patients in the medically treated group (6 per cent) died, but three of these patients were considered inoperable. In the surgically treated group there was no perioperative mortality; one patient died suddenly two months after surgery. It is concluded that the majority of patients with unstable angina become rapidly symptom free on medical therapy following the trend observed during the last decade. Coronary angiography performed early is essential for dictating future management. Surgery, if required, can be undertaken safely on an elective basis. REFERENCES Conti, C. R., Brawley, R. K., Griffith, L. S. C., Pitt, B., Humphries, J., Gott, V. L., and Ross, R. S.: Unstable angina pectoris: morbidity and mortality in 57 consecutive patients evaluated angiographically, Am. J. Cardiol. 32:745, 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, Am. ,J. Cardiol. 33:201, 1974. Fischl, S. L., Herman, M. V., and Gorlin, R.: The intermediate coronary syndrome, N. Engl. J. Med. 288:1193, 1973. Ernst, J. M. P. G., Herpen, van, G., Nieuwenhuyzen, van, C. L. C., Vermuelen, F. E. E., Huysmans, H. A., and

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