Endothelin-1 and Cardiac Allograft Vasculopathy (CAV)

Many patients with end-stage heart failure, a condition in which the heart fails to pump enough blood to support the body's other organs, are fortunate enough to receive a heart transplant. However, despite taking medicines aimed at blunting the immune system's response to the donor heart, some of them will develop transplant-related disease in the coronary arteries supplying their hearts. Fifty years after the first human-to-human heart transplant, this disorder-cardiac allograft vasculopathy (CAV)-remains a leading cause of long-term death and has been coined the 'Achilles' Heel' of heart transplantation. Indeed, a better understanding of how CAV occurs and improved therapies to prevent and/or slow its development are desperately needed to meaningfully impact patient outcomes. Endothelin-1 (ET-1) is a key molecular regulator of arterial health, and our prior data suggests that it is associated with accelerated CAV. In this particular study of recent heart transplant recipients, we are asking: Does ET-1 contribute to the coronary artery's capacity to dilate/constrict? To answer this question, during the cardiac catheterization at 1 year post-transplant (standard of care), we will measure blood levels of ET-1 and perform an invasive evaluation of coronary vasomotor function inn a consecutive subset of patients who will have received a 1-week course of the oral endothelin receptor antagonist (macitentan) prior this catheterization, which will allow us to test how much ET-1 contributes to coronary responsiveness. The findings from this study may provide the necessary foundation to study whether endothelin receptor antagonists are able to effectively reduce the rate of accelerated CAV.