PATHOPHYSIOLOGY AND NATURAL HISTORY LEFT VENTRICULAR PERFORMANCE Altered left ventricular diastolic properties during pacing-induced angina in patients with aortic stenosis

An increase in left ventricular diastolic pressure has been repeatedly observed during angina in patients with coronary artery stenoses and regional demand ischemia, but the role of relaxation abnormalities versus left ventricular segmental dyssynchrony is controversial. In contrast, patients with angina due to aortic stenosis are likely to have diffuse rather than segmental ischemia and thus may provide an alternative model for examining the diastolic physiology of angina in man. Accordingly, we examined the hemodynamic manifestations of angina in eight patients with aortic stenosis without significant coronary artery disease. Angina was induced by pacing tachycardia, and hemodynamic and echocardiographic variables were measured in the control period and during angina in the beats immediately after cessation of pacing. Heart rate (control vs angina, 69 + 12 vs 70 + 11 beats/min, p = NS) and left ventricular peak systolic pressure (207 39 vs 222 22 mm Hg, p = NS) were similar in the control and postpacing angina periods. Left ventricular end-diastolic pressure, on the other hand, was significantly higher during postpacing angina (15 ± 7 vs 28 8 mm Hg, p < .01). The time constant of left ventricular pressure decline during isovolumetric relaxation (TL), calculated as the slope of a linear fit of the natural log of pressure vs time, increased from 44 + 5 to 51 + 7 msec (p < .05); the time constant TD, derived from the slope of a linear fit of dP/dt vs pressure, also increased slightly, although the change was not statistically significant (69 + 5 vs 75 + 5 msec, p = .06). High-quality two-dimensional targeted M mode echocardiograms in the control and postpacing periods were available in four patients; left ventricular end-diastolic and end-systolic dimensions and percent fractional shortening were unchanged. The left ventricular diastolic pressure-volume relationship and pressure-wall thickness relationship were shifted upward during angina in these patients. We conclude that angina in patients with aortic stenosis is accompanied by a substantial and reversible increase in left ventricular end-diastolic pressure; this increase appears to be due in part to an impairment of diastolic distensibility of the left ventricle and left ventricular relaxation. These findings, which are similar to those observed during pacing-induced angina in patients with coronary stenoses, suggest that the increase in left ventricular end-diastolic pressure that occurs during angina is a manifestation of demand ischemia per se, and does not depend on the presence of dyssynergistic contraction of ischemic and nonischemic regions. Circulation 74, No. 4, 675-683, 1986. ANGINA is a common symptom in patients with aortic stenosis, and is frequently the presenting complaint.' In patients with coronary artery disease, angina provoked by exercise or pacing tachycardia is often acFrom the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth Israel Hospital, and the Department of Medicine (Cardiovascular Divisions) of Beth Israel Hospital and the Brigham and Women's Hospital and Harvard Medical School, Boston. Address for correspondence: Beverly H. Lorell, M.D., Cardiovascular Division, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215. Received Dec. 20, 1985; revision accepted June 26, 1986. Dr. Lorell was supported in part by grant HL31371-OlA1 from the National Heart, Lung, and Blood Institute. Dr. Bourdillon was supported by a British-American Research Fellowship of the British Heart Foundation, and the American Heart Association. *Current address: Cardiac Unit, Massachusetts General Hospital, Boston, MA 02114. **Current address: Cardiology Division, University of Michigan Hospital, Ann Arbor, MI 48109. Vol. 74, No. 4, October 1986 companied by a rise in the left ventricular end-diastolic pressure, associated with a decrease in diastolic distensibility.2` The mechanisms that are responsible for this transient impairment in left ventricular diastolic function during demand ischemia are unclear. Abnormalities of the isovolumetric relaxation period have been repeatedly observed during demand ischemia in patients with coronary stenoses3 6 8. 9 and in experimental animal preparations of coronary stenoses.' ` These observations suggest that the increase in left ventricular diastolic pressure during angina may be related to impaired inactivation of the myosin-actin interaction in ischemic myocardium.2' 13 On the other hand, regional dyssynchrony of ischemic and nonischemic segments is an alternate mechanism that has been proposed. 1-16 675 by gest on A ril 3, 2017 http://ciajournals.org/ D ow nladed from