Acute Myocardial Infarction with Angiographically Demonstrated Normal Coronary Arteries in the Presence of Hypertrophic Cardiomyopathy

man M. A comparative study of atropine sulfate and isoproterenol hydrochloride in chronic bronchitis. Am Rev Respir Dis 1975; 112:371-6.

5 Tashkin DD, Katz RM, Kerschnar H, Rachelefsk7 CS, Siegel SC. Comparison of aerosolized atropine, isoproterenol, atropine plus isoproterenol, disodium cromoglycate and placebo in the prevention of exercise-induced asthma. Ann Allergy 1977; 39:311-8. 6 Chick TN, Jenne JW. Comparative bronchodiJator response to atropine and terbutaline in asthma and chronic bronchitis. Chest 1977; 72:719-23. 7 Larsen GL, Barron RJ, Cotton EK, Brooks JG. A comparative study of inhaled atropine sulfate and isoproterenol hydrochloride in cystic fibrosis. Am Rev Respir Dis 1979; 119:399-407. 8 Cavenaugh MJ, Cooper DM. Inhaled atropine sulfate dose response characteristics. Am Rev Respir Dis 1976; 114:517-

524.

Acute Myocardial lnfardion with Angiographically Demonstrated Normal Coronary Arteries in the Presence of Hypertrophic Cardiomyopathy* Philip E.

Newtr~~~n,

M.D.t

°From the Division of Cardiology, Denver General Hospital, and the Department of Medicine, University of Colorado Health Science Center, Denver. tActing Director, Division of Cardiology. Reprint requests: Dr. Newtr~~~n, Di1Jision of Cardiology,

Denver General Hospital, Denver 80204

A 51-yi!III'-Oid blaek womu wiih lmowa, ecboem'dlo-

graphically-docameoted hypertrophic cmllomyopatby was admitted ~ _die hospital with m acate myoeudW Infarction diaposed by both electrocardlograhic md sernm eozyme cb8nces. Sis weelm following dllduqe, the patient nnderwent left-sided heart adheterization, left ventriculography, and coronary arterlCJ118Phy, and she was fonnd to bave entirely normal coronary uteriel. There are possible pathogenetic JIMldwan""" of myocardial infarction in the presence of normal coronary arteries in patients with hypertrophic cardiomyopathy, and it is also pGIIIIihly significant that nayocardiallnfardion .. seen in patients with hypertropic cardiomyopathy.

well known that patients with hypertrophic I t cardiomyopathy frequently present clinical maniis

festations suggestive of myocardial ischemia, and the association between hypertrophic cardiomyopathy and atheromatous coronary artery disease has been reported. 1 • 3 Kossowsky et al' reported the first case of acute transmural myocardial infarction in a patient with echocardiographically and hemodynamically documented hypertrophic cardiomyopathy, and Maron and colleagues3 recently reported a pathologic study of seven patients with hypertrophic cardiomyopathy who at necropsy were found to have transmural myocardial infarctions in the absence of signiJicant atheromatous coronary artery disease. The following is the first reported case of a patient with echocardiographically-documented hypertrophic cardiomyopathy who sustained a myocardial infarction diagnosed by both electrocardiographic and enzyme changes and who had angio-

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F'IcuBE 1. Upper left. Pre-morbid ECG from 1977, essentially uormal. Lower left, Admission ECG taken on AprilS, 1979, revealing evidence of hi-atrial enlargement and marked ST depression and T inversion in leads 1, aVL, ant:J;V8 • Upper right, ECG taken on April 6, 1979, revealing significant resolution of anterolateral ST-T wave changes. Chest recorded at o:oe half standard. Lower right, ECG taken on April13, 1979, revealing an accelerated junctional vs idioventricular rhythm, anterolateral T wave inversion, and diminutive R voltage in the anteroseptalleads. Chest leads one half standard.

CHEST, 78: 6, DECEMBER, 1980

ACm MYOCARDIAL INFARcnOI 83

graphically demonstrated normal coronary arteries.

CASE REPoRT This 51-year-old black woman with echocardiograpbically documented hypertrophic cardiomyopathy (January 1977) being treated with propranolol 40 mg daily, was admitted to the Denver General Hospital in April 1979, having awakened early in the morning with marked dyspnea, cough, and a substernal "pressure" sensation which radiated down the left arm. She reported having experienced some exertional dyspnea, as well as intermittent orthopnea over the recent few months, and having on occasion experienced similar chest discomfort, but never as severe nor as frightening as that of the morning of admission. It is of note that in July 1977, she had undergone 24-hour Holter monitor evaluation which had revealed two episodes of junctional vs idioventricular tachycardia. Physical examination was remarkable in revealing bilateral inspiratory rales posteriorly as well as end-expiratory wheezing; a laterally displaced bi6d apical impulse; both atrial and ventricular gallops; a grade 3/6 systolic ejection murmur heard best at the lower left sternal border which increased in intensity with Valsalva maneuver; and a brisk carotid upstroke without a bi6d contour. Chest x-ray 6lm revealed mild cardiomegaly with left ventricular prominence, increased pulmonary vascularity, and small bilateral pleural effusions. Admission ECG (Fig 1, lower left) revealed evidence of hi-atrial enlargement and marked ST depression and T inversion in leads 1, aVL, and V3 - V6 which were not present on the previous ( 1977) ECG (Fig 1, upper left). On the day following admission, April 6, the anterolateral ST-T wave changes had signi6cantly resolved ( Fig 1, upper right), yet on this day, the serum creatinine phosphokinase (CPK) level rose from 84 units/L on the day of admission to 566 units/L with a positive MB band. Between the second and seventh days of hospitalization, the electrocardiographic STT wave changes waxed and waned, while the serum CPK level progressively fell to 59 units/L. On the eighth day, April 12, the serum CPK abruptly rose to 758 units/L, but it was reported as "MM band positive only," while the serum glutamic oxaloacetic transaminase ( SGOT) rose from 14 to 102 mg/100 ml and the serum lactic dehydrogenase (LDH) from 236 to 295 mg/100 ml, concomitantly. On the following day, the ECG revealed a new accelerated junctional vs idioventricular rhytlun, anterolateral T wave inversion, left anterior fascicular block, and the R voltage in the anteroseptal leads had become diminutive ( Fig 1, lower right). Following the day of her admission, the patient experienced no further chest pain despite her Huotuating electrocardiographic and enzyme changes. Her initial pulmonary congestive symptoms and findings responded nicely to discontinuation of beta-blockade and gentle diuresis. On the tenth hospital day, she insisted upon leaving the hospital against medical advice, but she agreed to continue to be observed in the cardiology outpatient clinic. Her outpatient convalescence was uneventful. Four days following discharge, she underwent echocardiography which clearly documented the presence of asymmetric septal hypertrophy and the absence of systolic anterior motion of the mitral valve (Fig 2). In May 1979, the patient returned for elective left-sided heart catheterization, left ventriculography, and coronary arteriography. Resting simultaneous left ventricular and left femoral arterial pressure tracings revealed the absence of a resting pressure gradient and also noted the bi6d contour of the ventricular tracing and the brisk upstroke without bi6d

894 PHIUP L NEWMAN

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FIGURE 2. Upper, ECG revealing unremarkable mitral valve motion without systolic anterior motion ("SAM"). Lower, ECG revealing marked asymmetric septal hypertrophy ("ASH").

contour of the arterial tracing. Left ventricular to central aortic pressure pull-back recording con6rmed the absence of a resting gradient between the left ventricle and the central aorta. While a postventricular ectopic complex did not show either a provoked gradient or a reduction in pulse pressure, inhalation of amyl nitrate did provoke a mild gradient of 18 mm Hg. In view of the recency of the myocardial infarction, isoproterenol administration was not attempted. Coronary arteriography was entirely normal (Fig 3, upper and lower left). Biplane cine left ventriculography revealed excellent global wall motion with classic "cavity obliteration" and no akinetic regions were appreciated. Mild mitral regurgitation was evident (Fig 3, upper and lower right). DISCUSSION

The association between chest pain and hypertrophic cardiomyopathy and between coronary artery disease and hypertrophic cardiomyopathy has been discussed and reported repeatedly. 1 • 8 Kossowsky et al4 were the 6rst to report the occurrence of a transmural anteroseptal

CHEST, 78: 6, DECEMBER, 1980

FIGURE 3. Upper left, Normal left coronary artery. shallow RAO projection. Lowef' left,

Normal right coronary artery, LAO projection. Upper right and lower right, Biplane

cine left ventriculogram revealing excellent

global wall motion, classic "cavity obliteration," and mild mitral regurgitation. Upper right is RAO projection, end-diastole; lower right is RAO projection, end-systole.

myocardial infarction in a patient with previously known echocardiographically and hemodynamically documented IHSS, in whom subsequent coronary arteriography revealed an anterior descending artery which was occluded just proximal to its 6rst septal perforator. It was of interest that following this infarction, both echo and hemodynamic evidence of IHSS disappeared. In a very eloquent and well-illustrated necropsy study, Maron et al 5 became the first to report pathologic evidence of an association between hypertrophic cardiomyopathy and transmural myocardial infarction in patients without significant coronary artery disease. In reviewing the necropsy records of 48 patients with echocardiographic, hemodynamic, angiographic, and necropsy evidence of hypertrophic cardiomyopathy who had not undergone surgical treatment, they found that seven ( 15 percent) had, by gross inspection of the heart, transmural myocardial scarring of the left ventricle, and that none of these seven patients had significant atherosclerotic coronary artery disease. This case report presents the 6rst documentation of an acute myocardial infarction, supported by both electrocardiographic and serum enzyme evidence, in a patient with echocardiographically proven hypertrophic cardiomyopathy, with subsequent angiographic demonstration of entirely normal coronary arteries. We have long speculated as to the possible mechanisms of chest pain, myocardial ischemia, and myocar-

CHEST, 78: 6, DECEMBER, 1980

dial infarction in patients with normal coronary arteries. Three pathogenetic mechanisms of acute myocardial infarction in patients with normal coronary arteries are commonly proposed as follows: coronary artery embolism with subsequent clot lysis, retraction, or recanalization,8·9 coronary artery spasm,t0 • 12 and disease of the "small vessels" or "intra-mural" coronary arteries ( IMAs). The 6rst two of these proposed mechanisms have not been shown to have specific relevance to hypertrophic cardiomyopathy, but two reports which describe abnormalities of the intramural coronary arteries in patients with hypertrophic cardiomyopathy make the third proposed mechanism a most attractive one. In a necropsy study of 32 patients with hypertrophic cardiomyopathy, 20 of whom had resting left ventricular outflow gradients (group 1) and 12 of whom had no significant left ventricular outflow gradients at rest or with provocation (group 2), McReynolds and Roberts 18 found that 16 of the 20 in group 1 and 8 of the 12 in group 2 had abnormalities in the intramural coronary arteries consisting of mild degrees of cellular intimal proliferation in 22 patients (in none was the luminal narrowing greater than 50 percent), and severe medial hypertrophy in two patients. These changes were seen ill the septum and left ventricular free wall in 22 patients, and in the right ventricle in only 1 patient. 13 In the recent report by Maron et al,6 it is noted that six of the seven patients with hypertrophic cardiomyopathy,

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895

pathologic evidence of transmural myocardial infarction, and essentially uninvolved extramural coronary arteries had markedly abnormal intramural coronary arteries featuring thickened walls due to intimal proliferation, medial hypertrophy, or both, and narrowed lumens. These abnormal intramural coronary arteries were seen most in the septum in areas of scarring. This case report emphasizes that 6ndings resembling those of acute myocardial infarction can appear in patients with hypertrophic cardiomyopathy and normal coronary arteries. The maximal height of the enzyme rise and the lack of left ventricular segmental dysfunction on cineangiography suggest that the area of myocardial necrosis was probably not large. Conceivably, the infarctional episode described in this report might represent a single small step in a direction that may ultimately lead to the extensive scarring demonstrated by Maron et al5 in 15 percent of patients dying with hypertrophic cardiomyopathy. The clinical significance of a single such episode is uncertain. The association between hypertrophic cardiomyopathy and acute myocardial infarction draws attention to the question of the mechanism of sudden death which has been reported in patients with the former. 14- 15 Maron et al, 5 reporting clinical and pathologic findings in a group of 26 patients in whom sudden death was the initial manifestation of hypertrophic cardiomyopathy, found that the only characteristics common to all were moderate to severe septal thickening, and a distinctly abnormal ECG. Of 12 who were previously catheterized, six did and six did not have significant resting left ventricular outflow gradients. Undoubtedly there are multiple pathogenetic mechanisms operative in sudden death in patients with hypertrophic cardiomyopathy; acute myocardial infarction suggests itself as one such mechanism, perhaps by induction of a terminal arrhythmia. In this regard, it is of note that in the two above cited articles by Maron et ai, 14,15 in each of the two groups of patients reported, there was one patient with a large transmural ventricular septal infarct with widely patent extramural coronary arteries. Though the clinical significance and prognosis of acute myocardial infarction in patients with hypertrophic cardiomyopathy is as yet uncertain, its occurrence has been documented, and it is suggested that such episodes receive more thorough evaluation and follow-up than they are currently accorded.

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PHIUP E. NEWMAN

REFERENCES 1 Lardani H, Serrano JA, Villamil RJ: Hemodynamics and coronary arteriography in idiopathic hypertrophic subaortic stenosis. Am J Cardiol 1978; 41:476-481 2 Walston A, Behar VS: Spectrum of coronary artery disease in idiopathic hypertrophic subaortic stenosis. Am J Cardiol1976; 38:12-16 3 Gulotta SJ, Hamby RI, Aronson AL, et al: Coexistent idiopathic hypertrophic subaortic stenosis and coronary arterial disease. Circulation 1972; 46:890-896 4 Kossowsky WA, Mohr B, Dardashti I, et al: Acute myocardial infarction in idiopathic hypertrophic subaortic stenosis. Chest 1973; 65:529-532 5 Maron BJ, Epstein SE, Roberts WC: Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J Cardiol1979; 43:1086-1102 6 Arnett EN, Roberts WC; Acute myocardial infarction and angiographically normal coronary arteries. Circulation 1979;43:1~1102

7 Rosenblatt A, Seher A: The nature and clinical features of myocardial infarction with normal coronary arteriogram. Circulation 1977; 55:578-580 8 Roberts WC: Coronary embolism: a review of causes, consequences, and diagnostic considerations. Cardiovasc Med 1978; 3:699-706 9 O'Reilly RJ, Spellberg RD: Rapid resolution of coronary arterial emboli: myocardial infarction and subsequent normal coronary arteriograms. Ann Intern Med 1974; 81:348...:350 10 Maseri A, L'Abbate A, Baroldi G, et al: Coronary vasospasm as a possible cause of myocardial infarction: a conclusion derived from the study of "preinfarction" angina. N Engl J Med 1978; 299:1271-1277 11 Johnson AD, Detwiler JH: Coronary spasm, variant angina and recurrent myocardial infarctions. Circulation 1977; 55:947-950 12 Cheng TO, Bashour T, Singh BK, et al: Myocardial infarction in the absence of coronary arteriosclerosis: result of coronary spasm (A). Am J Cardiol1972; 30:680682

13 McReynolds RA, Roberts WC: The intramural coronary arteries in hypertrophic cardiomyopathy, abstracted. Am J Cardiol1975; 35:154 14 Maron BJ, Roberts WC, Edwards JE, et al: Sudden death in patients with hypertrophic cardiomyopathy: characterization of patients without previous functional limitations. Am J Cardiol1978; 41:803-810 15 Maron BJ, Lipson LC, Roberts WC, et al: "Malignant" hypertrophic cardiomyopathy: identification of a subgroup of families with unusually frequent premature deaths. Am J Cardiol1978; 41:1133-1140

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