Sex Differences in Early Myocardial Repolarization

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DESCRIPTION (provided by applicant): Sex differences in the QT interval have been known since the early 1900s. In contrast, sex differences in the ST segment consisting of a higher ST height and elevated J point have only recently been studied in detail. There are sex differences in clinical arrhythmias that may be associated with the sex ECG differences. Ventricular tachycardia is inducible in 35-40 percent of men but only 20 percent of women with coronary artery disease and LV dysfunction. Women are only half as likely as men to develop VF as a cause of cardiac arrest are. The fact that there are important sex differences in susceptibility to certain arrhythmias suggests the existence of fundamental electrophysiologic distinctions between males and females that remain to be elucidated. The overall hypothesis of the present study is that sex differences in early myocardial repolarization are rate dependent, are due to effects of sex hormones and alter the propensity to clinical arrhythmias. The following specific hypotheses will be tested. 1) A major determinant of ST height is the level of sex hormones. We will also seek to determine whether the ST elevation seen most often in athletic males sometimes called "early repolarization" is a distant clinical syndrome. 2) Sexrelated differences in myocardial repolarization are dependent on both heart rate and autonomic tone. This aim will be accomplished by examining the heart rate dependence of ST height before and after autonomic manipulations in both men and women. 3) Androgens but not estrogens or progesterone modulate early repolarization. This aim will be accomplished by studying subjects who will undergo sex hormone therapy. 4) ST elevation that has previously been characterized as benign based on incomplete data alters the propensity to arrhythmias under appropriate pathologic conditions. In this aim, the relationship between ST elevation on the resting ECG and ventricular tachycardia and ventricular fibrillation will be examined. Studies will be performed in patients with acute and healed myocardial infarction and in patients with non-ischemic dilated cardiomyopathy. It is hoped that the results of this study will improve the understanding of myocardial physiology and improve risk stratification and therapy for arrhythmias by uncovering important sex related differences.