Abnormalities in the Coronary Circulation zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ tha t Occur as a Consequence of Cardiac Hypertrophy MELVIN L. MARCUS, M.D. SAMON KOYANAGI, M.D. DAVID G. HARRISON, M.D. DONALD B. DOTY, M.D. LOREN F. HIRATZKA, M.D. CHARLES L. EASTHAM, B.A. lo wa City, lo wa From the Cardiology Division, Department of Medicine, and Division of Thoracic and Cardio- vascular Surgery, Department of Surgery, The Cardiovascular Center and the University of Iowa and Veterans Administration Hospitals. This study was supported in part by National Institutes of Health (National Heart, Lung, and Blood Institute), Grants HL 14388 and HL 20827, by research funds from the Iowa Heart Association, and by the Vet- erans Administration. Requests for reprints should be addressed to Dr. Melvin L. Marcus, Professor of Medicine, University of Iowa Hospitals, Iowa City, Iowa 52242. Myocardial ischemia is frequently observed in patients with cardiac hypertrophy even when the conduit coronary arteries are normal. Recent studies indicate that impaired coronary reserve in hyper- trophied hearts probably occurs because growth of the coronary bed does not keep pace with increases in cardiac mass. The imbalance between vascular proliferation and muscle growth is probably most severe when cardiac hypertrophy is produced by pressure overload. Experimental studies also suggest that abnormalities intrinsic to pressure-hypertrophied heart muscle (decreased capillary density; decreased coronary reserve; electrophysiologic abnormalities) adversely affect the response of the enlarged heart to sudden cor- onary occlusion. When animals with hypertension and left ventricular hypertrophy are subjected to sudden coronary occlusion, the inci- dence of sudden cardiac death is increased severalfold and infarct size is substantially augmented. These observations suggest that abnormalities in the coronary microcirculation that accompany cardiac hypertrophy play a significant role in the pathogenesis of the complications associated with cardiac hypertrophy. Patients with hypertrophied ventricles often exhibit manifestations of myocardial ischemia such as S-T segment depression and angina with exercise. In addition, in patients with hypertrophied hearts cardiac failure eventually develops. Even though the complications associated with cardiac hypertrophy have been observed for decades, their pathogenesis has been difficult to elucidate. It has often been hy- pothesized that abnormalities in myocardial perfusion may be re- sponsible for the complications associated with cardiac hypertrophy, but convincing data to support this hypothesis have been lacking until recently [ 1,2]. Early studies of resting coronary blood flow in patients with cardiac hypertrophy did not reveal any abnormalities [3,4]. In studies concerning myocardial perfusion in hypertrophied ven- tricles, substantial progress has been made in the past decade pri- marily because practical methods of measuring regional myocardial perfusion in animals became available [5] and several approaches to measuring coronary reserve in human subjects were introduced [6-81. It is now generally acknowledged that certain types of cardiac hypertrophy are associated with major abnormalities in coronary re- serve [1,2]. A conceptual diagram that relates changes in cardiac muscle mass to alterations in coronary microcirculation is shown in Figure 1. The size of the box refers to the size of the heart, and the circles in the box represent the total cross-sectional area of the coronary resistance vessels. The normal relationship between the cardiac mass and the coronary circulation is illustrated by the center box. 62 September 26, 1963 The American Journal of Medicine