Effects of thyroid hormone on the cardiac function: the relative importance of heart rate, loading conditions, and myocardial contractility in the regulation of cardiac performance in humanhyperthyroidism.

The cardiovascular manifestations of thyroid hormone excess, including tachycardia, a widened pulse pressure, a brisk carotid and peripheral arterial pulsation, a hyperkinetic cardiac apex, and loud first heart sound have long been recognized and are a cornerstone for clinical diagnosis (1, 2, 3, 4, 5, 6, 7, 8, 9). A number of studies in the past decades have provided critical insights into the mechanisms that are responsible for the hyperdynamic cardiocirculatory state in overt hyperthyroid patients, suggesting that it probably results from the combined effects of thyroid hormone on certain molecular pathways on the heart and vasculature, at both the genomic and nongenomic level (10). Despite these advances, it is not yet clear whether, in spontaneous human hyperthyroidism, the high cardiac output state (11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) is sustained prevalently by changes in peripheral hemodynamics (vascular hypothesis), or by changes in myocardial contractility (myocardial hypothesis) (19, 21). This issue has major clinical and pathophysiological implications. In fact, although peripheral and myocardial mechanisms are not mutually exclusive, the major contribution of one of the two mechanisms may have important consequences with regard to the “economy” of the cardiovascular system, given the notion that increased cardiac performance due to inotropic stimulation is less efficient than that due to modulation of the loading status. Accordingly, here we review research on the effects of spontaneous human hyperthyroidism on heart rate, preload, afterload, and myocardial contractility in an attempt to establish how these factors interact with each other and to what extent they contribute to increasing cardiac performance at rest.