Coronary Endothelial Dysfunction After Heart Transplantation Predicts Allograft Vasculopathy and Cardiac Death

Abstract

Background-Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. Methods and Results-Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (Ͼ50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-g bolus), acetylcholine (54 g over 2 minutes), and nitroglycerin (200 g) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1Ϯ2.9% versus dilation of 1.7Ϯ2.2%, Pϭ0.01) and microvascular (flow increase of 75Ϯ20% versus 149Ϯ16%, Pϭ0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point.Responses to adenosine and nitroglycerin did not differ significantly. Conclusions-Endothelial

Human endothelial dysfunction: EDCFs

“…Interestingly, an inverse relationship has been described between the presence of intramural plaques as detected by intravascular ultrasound and vasodilation to intracoronary acetylcholine in patients without angiographic evidence of coronary atherosclerosis [57]. These data are supported also by longitudinal studies, showing a significant augmented risk of developing arteriolosclerosis and plaques in heart-transplanted patients with coronary endothelial dysfunction [21].…”

Probucol Protects against Hypochlorite-induced Endothelial Dysfunction

“…Impaired endothelial function predicts the occurrence of vascular events (42,43), and ⅐ NO bioavailability is attenuated by irreversible chemical modification and/or decreased catalytic activity of endothelial nitric-oxide synthase. Oxidative reactions are increasingly implied in these processes.…”

Intravascular Ultrasound Correlates with Coronary Flow Reserve and Predicts the Survival in Angiographically Normal Cardiac Transplant Recipients

“…It has been reported that the coronary endothelium was the early target of vasculopathy [26, 27]; rapid progression in intimal thickness within the first year after transplantation was a powerful predictor of mortality, graft loss or angiographically evident CAV [9, 10]. Although information on the progression of intimal thickness was not available in the current study [28], our results suggest that maximum area stenosis, but not measurements of dipyridamole 201 Tl SPECT or CFR, is an independent predictor of allograft failure in a population with normal coronary angiogram, emphasizing the prognostic significance of epicardial coronary lesions.…”