Coronary endothelial dysfunction as a predictor of intimal thickening in the long term after heart transplantation

Abstract

Objectives: The mechanisms of cardiac allograft vasculopathy and its predisposing factors are multifactorial and as yet not well established. To determine the influence of endothelial dysfunction on the development of intimal thickening, we prospectively analyzed the vasomotor response to acetylcholine and nitroglycerin, as well as other donor and recipient variables. Findings were correlated with the coronary intimal thickness, which was evaluated by means of intravascular ultrasonography. Methods: Nineteen patients who had undergone heart transplantation 4.89 ± 2.35 years previously and who had angiographically normal coronary arteries were included. Endothelial function was analyzed by quantitative coronary analysis of the vasomotor response of the left anterior descending artery to acetylcholine. An intimal thickness index, reflecting the percentage of intima obstructing the coronary lumen, was calculated. Results: Nine (47%) patients showed endothelial dysfunction, and the remaining 10 (53%) patients had a normal response. Four (44%) of 9 patients with a weight gain of greater than 20% after the operation showed endothelial dysfunction compared with none of the 10 patients with normal responses (P < .04). The severity of the intimal thickness correlated with the years after transplant (r = 0.45, P < .05). Patients with endothelial dysfunction had more intimal thickening than those without (32% ± 17% vs 17% ± 12%, respectively; P < .05). Furthermore, the degree of intimal thickening correlated with the magnitude of the vasomotor response to acetylcholine (r = -0.60, P = .006). No relationship was found between intimal thickness and the vasodilatory response to nitroglycerin. As independent variables for intimal thickness, multivariate analysis detected the magnitude of the response to acetylcholine (P = .0005), years after transplant (P = .01), and ischemic time (P = .03). Conclusions: Cardiac allograft vasculopathy is a multifactorial disease the severity of which increases over time. Endothelial dysfunction is a predictive factor of intimal thickening severity. Predisposing factors that provoke endothelial injury, such as perioperative ischemic time and obesity, may contribute to the development of allograft vasculopathy.