Clinical determinants of ventricular sympathetic reinnervation after orthotopic heart transplantation

Abstract

Background - It has been demonstrated that ventricular sympathetic reinnervation after cardiac transplantation improves exercise performance. The extent of reinnervation increases with time but is variable. Little is known about other influencing factors. Methods and Results - Seventy-seven nonrejecting transplant recipients were cross-sectionally studied by PET with the catecholamine analogue C-11 hydroxyephedrine at 4.8±3.5 years after transplantation. Results were compared with history-derived parameters related to recipient's clinical course before, during, and after surgery; donor characteristics; and immunogenetics. Partial reinnervation was observed in 52 patients (extent, 21±16% of left ventricle). Complete denervation was found in 25 patients at various times after transplantation. Reinnervation extent correlated with time after surgery (r=0.387; P<0.001) but also inversely with donor age (r=-0.309, P=0.006) and recipient age (r=-0.243, P=0.032). Maximal hydroxyephedrine retention correlated inversely with frequency of rejection episodes (r=-0.267, P=0.019), was reduced when aortic complications occurred perioperatively (9 patients), and correlated inversely with aortic cross-clamp time (r=-0.331, P=0.006). Other parameters were not associated with reinnervation. Patients were surveyed for clinical complications over >12 months after PET (until 7.3±4.2 years after transplantation), but significant effects of reinnervation on outcome were not observed. Conclusions - The present data suggest that sympathetic reinnervation after cardiac transplantation is not simply a function of time. Reinnervation is more likely with young age, fast and uncomplicated surgery, and low rejection frequency. Despite few effects on prognosis in otherwise healthy recipients, improved understanding of clinical determinants may contribute to enhance allograft reinnervation and thereby augment exercise capacity in the future.