Impact of coronary endothelial dysfunction on adverse long-term outcome after heart transplantation

Background. Coronary vasomotor dysfunction is a common finding in cardiac transplant recipients and is an early marker for the development of graft atherosclerosis. The present prospective study tested whether endothelial dysfunction independently predicts cardiovascular-related events and death after heart transplantation (HTx). Methods. Functional and structural coronary changes were evaluated in 185 consecutive patients 25 +/- 33 months after HTx. The following potential risk factors for graft survival were assessed at baseline: hypertension, diabetes, dyslipidemia, donor and recipient characteristics (age, gender, cytomegalovirus-infection, human leukocyte antigen-mismatch), pretransplantation diagnosis, ischemic time, treated rejection episodes, immunosuppressive regimens, and medication. The prespecified prospectively defined endpoints were cardiovascular-related events with progressive heart failure, acute myocardial infarction, coronary revascularization, retransplantation, and death. Patients were followed-up for 60 +/- 17 months. Results. Event-free survival for the entire group was 73% (25 cardiovascular-related events, 25 deaths). Using multivariate analysis, epicardial endothelial dysfunction (relative risk [RR] 1.97; P=0.028), angiographic cardiac allograft vasculopathy (RR 2.11; P=0.023), diabetes (RR 2.32; P=0.022), high serum levels of CyA (RR 3.54; P=0.006) and Tac (RR6.82; P=0.002), uncommon reasons for transplantation (RR4.69; P=0.002), and the absence of statin therapy (RR 0.33; P=0.025) were detected as independent predictors of cardiovascular-related events and death. Conclusion. This is the first study showing that epicardial endothelial dysfunction independently predicts outcome in HTx patients providing functional and prognostic information that complete angiographic risk factor assessment.