Markers of Endothelial Function in Heart Transplant Recipients and Associations with Cardiac Allograft Vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival in heart transplant recipients (HTR) accounting for almost 30% of deaths after 5 years. Early non-invasive detection remains a major challenge due the insensitivity and invasiveness of current diagnostic tests. Small vessel disease and endothelial dysfunction are key players in the pathophysiology of CAV. We hypothesize that in HTR there is an impairment of endothelial cellular repair and changes in arterial elasticity, especially in small arteries, resulting in a reduction of small artery elasticity (SAE), an increase in the number of circulating endothelial cells (CEC), and increased CEC activation. In addition, these changes are significant in HTR who develop CAV. Methods: Ninety-seven HTR and 22 normal controls were included in this study. SAE was measured from the radial artery. CEC (CD146+ cells) were enumerated and assessed for activation based on VCAM expression. Continuous variables were analyzed using t-test and dichotomous variables using Chi-square. Logistic regression using stepwise selection was performed to evaluate determinants of CEC, CEC activation, and SAE. Results: The median age was 61years(range, 18-76). The mean duration of transplant was 5.4 ± 5.3 year. 77 % were male and 57% had CAV. HT was associated with significantly lower SAE (p<0.0001) and increased CEC activation (p=0.0004) when compared to healthy controls. We also found that CAV was significantly associated with SAE and CEC (p = 0.04 and 0.01, respectively). On stepwise regression, hypertension treatment and duration of transplant were associated with CAV. Conclusion: Heart transplant is characterized by endothelial activation and dysfunction as evidenced by a reduction in SAE and increased CEC activation. Prospective studies to evaluate these markers as predictors of risk are needed for further evaluation.