PATHOPHYSIOLOGY AND NATURAL HISTORY VENTRICULAR PERFORMANCE Changes in myocardial repolarization in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis: evidence for contraction-xcitation feedback in humans

Alterations in ventricular loading conditions lead to changes in action potential duration and arrhythmias via contraction-excitation feedback; a decrease in load leads to prolongation of repolarization. To determine whether changes in right ventricular load alter ventricular repolarization in man, the corrected QT interval, a measure of overall ventricular repolarization, was measured in 32 patients before and after valvuloplasty for pulmonary stenosis. Right ventricular systolic pressure decreased (82.5 30.7 to 40.5 ± 9.5 mm Hg, p<.001) and the QTc increased concurrently (409.1 + 24.3 to 440.7 28.0 msec, p<.001) after successful valvuloplasty. The increase in QTc was most marked for those patients with a greater than 30 mm Hg decrease in right ventricular pressure (40.0 ± 22.3 vs 16.3 + 21.3 msec, p.006). In a subset of seven patients in whom monophasic action potentials were recorded, monophasic action potential duration, a measure of local repolarization, was prolonged (230.0 ± 24.3 vs 216.9 ± 21.9, p<.001) after successful valvuloplasty, confirming that the QTc prolongation reflected changes in local ventricular repolarization. In addition, during nine acute right ventricular outflew tract occlusions in a subset of six patients, monophasic action potential duration shortened (206.6 ± 17.6 vs 221.7 + 20.9 msec, p<.01) and early afterdepolarizations developed consistent with contraction-excitation feedback. These data suggest that, in humans, changes in mechanical load are associated with changes in ventricular repolarization consistent with contractionexcitation feedback. Circulation 77, No. 1, 70-77, 1988. BALLOON VALVULOPLASTY has evolved as a therapeutic alternative for patients with stenotic pulmonary valves. 1 2 The present study focuses on the electrocardiographic and electrophysiologic changes that develop in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis. The purpose of this study was to demonstrate that changes in ventricular repolarization consistent with contraction-excitation feedback mechanisms occur in man. In patients undergoing balloon dilatation of stenotic valves, three mechanical states are present: (1) before valvuloplasty, at which time pulmonary stenosis assoFrom the Divisions of Cardiology of the Departments of Medicine and Pediatrics, The Johns Hopkins Hospital, Baltimore. Supported in part by a grant from the National Institutes of Health (ROI-HL:34519-02). Address for correspondence: Joseph H. Levine, M. D., 592 Carnegie, Division of Cardiology, The Johns Hopkins Hospital, 600 North Wolfe St., Baltimore, MD 21205. Received June 16, 1987; revision accepted Oct. 1, 1987. Dr. Levine is the recipient of a Clinician Scientist Research Award of The Johns Hopkins Medical Institutions. 70 ciated with increased right ventricular afterload is present, (2) after valvuloplasty of the stenotic valve, associated with decreased afterload and right ventricular pressure generation, and (3) during balloon occlusion of the right ventricular outflow tract and pulmonary valve, at which time maximal afterload and right ventricular pressure generation are noted and tensions approach those seen under isovolumetric conditions. Contraction-excitation feedback theory predicts that the time course of ventricular repolarization will be influenced by the mechanical loading conditions. Studies in isolated preparations and experimental animals have demonstrated that alterations in mechanical load lead to changes in conduction and refractoriness of ventricular myocardium. I2 addition, changes in monophasic action potentials (MAPs) have been recorded in experimental preparations undergoing acute 5-7, 13 15 occlusion of the aorta. Specifically, increases in mechanical stress have led to shortened action potential durations and shortened effective refractory periods CIRCULATION by gest on A ril 8, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-VENTRICULAR PERFORMANCE and afterdepolarizations. Thus, in patients undergoing balloon valvuloplasty, contraction-excitation feedback theory predicts that the time course of ventricular repolarization will be shortest during balloon occlusion of the pulmonary valve, will be longest after successful valvuloplasty, and will be intermediate before valvuloplasty, at which time hemodynamically significant pulmonary stenosis is present. In these patients, the QT interval, a measure of overall ventricular repolarization, was measured to evaluate mechanically induced changes in repolarization. Right ventricular MAPs were measured in a subset of patients to document that changes in QT intervals were due to changes in local ventricular repolarization.