Coronary Allograft Vasculopathy is Associated with Decreased CD34+ Cell Count in Heart Transplant Recipients

Abstract

Purpose The underlying mechanisms of coronary allograft vasculopathy (CAV) after heart transplantation remain incompletely understood. Since CD34+ cells represent one of the key determinants of coronary vascular homeostasis we investigated the potential association between CAV and CD34+ cell count in heart transplant recipients. Methods In a single-center prospective pilot study we included 18 adult heart transplant recipients without history of congenital heart disease, multi-organ transplantation or oncologic therapy. All patients underwent coronary CT angiography and CAV was defined in accordance with the ISHT criteria. At the time of CT angiography we collected blood samples and measured CD34+ cell count using Beckman-Coulter Navios EX flow cytometry according to ISAGE protocol. Results CAV was present in 6 patients (33%; Group A) and absent in 12 patients (67%; Group B). The two groups did not differ in age (58±8 years in Group A vs. 53±14 years in Group B,P=0.46), gender (male: 100% vs. 83% in Group B,P=0.31), underlying disease etiology (ischemic: 67% vs. 33%,P=0.20), presence of hypertension (83% vs. 75%,P=0.70), diabetes (50% vs. 33%,P=0.52) or renal insufficiency (17% vs. 33%,P=0.48). Furthermore, donor age (45±9 years in Group A vs. 38±10 years in Group B,P=0.22), allograft ischemic time (205±68 min vs. 193±63 min,P=0.72), tacrolimus trough levels (6.9±1.3 μg/L vs. 6.8±1.2 μg/L,P=0.76), and NT-proBNP levels (478±288 pg/mL vs. 473±373 pg/mL,P=0.97) were comparable. Though total leukocyte count was similar (7.5±3.4 × 109/L in Group A vs. 6.8±2.1 × 109/L in Group B,P=0.60), we found significantly lower CD34+ cell count in Group A compared to Group B (1.37±0.36 × 106/L vs. 2.15±0.81 × 106/L,P=0.04). When stratifying patients according to CD34+ cell count, patients with cell count below the median displayed increased incidence of CAV compared to patients with cell count above the median (55% vs. 11%,P=0.04). Overall, patients with CAV ISHLT score>1 had lower CD34+ count when compared patients with ISHLT grade 1 CAV (0.91±0.06 × 106/L vs. 1.32±0.14 × 106/L,P=0.03). Conclusion Lower CD34+ cell count appears to be associated with CAV in heart transplant recipients. Further clinical trials are warranted to better define the underlying mechanisms and investigate the potential of CD34+ cells in the prevention and treatment of CAV in this patient cohort.