Coronary Endothelial and Microvascular Function Testing

Abstract

Mayo Clinic Cardiac Catheterization Laboratory’s role in understanding the pathophysiology, establishing the diagnosis, predicting the prognosis, and advancing treatment of coronary endothelial dysfunction has been, and in fact remains, crucial. Following Robert F. Furchgott’s 1986 historic announcement on the major role of endothelium-derived nitric oxide (NO) in regulation of vascular tone, Mayo Clinic researchers demonstrated that the functional and structural integrity of the vascular endothelium is not only important to maintain balance between circulating endothelium-derived vasodilator and vasoconstrictor molecules but also confers protection against arterial atherosclerosis and thrombosis. Acetylcholine catheter-based evaluation protocol of coronary epicardial and microvascular endothelial function was initiated in 1994 as part of an NIH grant and approved for clinical practice in 1997. In 1994, the Mayo Endothelial Database – world’s current largest invasive database of coronary endothelial and microvascular function assessment – enrolled its first patient. In a series of subsequent cutting-edge high-impact studies between 1997 and 2000, our lab demonstrated the association between coronary endothelial and microvascular dysfunction, myocardial ischemia, and increased risk of severe adverse cardiovascular events. Since 2001, we have investigated new therapeutic options for coronary endothelial dysfunction that either constitute current mainstay clinical therapy for this challenging disease entity, such statins and L-arginine, or cornerstone early studies of potentially promising investigational therapies such as endothelin-1 antagonists and most recently autologous intracoronary CD34+ cell therapy. In 2018, we were among the first to introduce and advance the concept of endothelial dysfunction as a systemic disease with not only cardiac but also numerous extracardiac clinical manifestations.