Enhanced exercise performance and survival associated with evidence of autonomic reinnervation in pediatric heart transplant recipients

Following heart transplantation (HTx), loss of autonomic input to the allograft results in elevated resting heart rate (HR) and decreased chronotropic reserve. As enhanced exercise capacity and HR recovery post exercise are suggestive of reinnervation in pediatric cohorts, we used heart rate variability (HRV) analysis to assess autonomic reinnervation in pediatric HTx recipients. Pediatric patients transplanted between 1996 and 2010 and with serial 24-hour Holter recordings post-HTx were analyzed for HRV using time and frequency domain measures. Of 112 patients, 68 (57%) showed evidence of autonomic reinnervation that was not associated with age at HTx. Evidence of reinnervation was associated with a significant increase in low-frequency power spectrum (p<0.001), suggesting sympathetic reinnervation. Patients with evidence of reinnervation showed higher percent-predicted maxVO₂ on performing an exercise test (+10.2 ± 3.6%, p = 0.006) and improved HR recovery at 3 minutes (-11.4 ± 3.9 bpm, p = 0.004), but no difference in percent-predicted maximal HR. Cox hazards modeling using presumed sinus reinnervation criteria at last Holter recording as a time-dependent covariate was associated with decreased hazard of mortality and/or retransplantation (HR: 0.2, 95% CI 0.04-1.0, p = 0.05). In conclusion, a majority of pediatric HTx recipients demonstrate evidence of reinnervation that is associated with functional outcomes. Studies to assess graft reinnervation as a marker of long-term prognosis are warranted. In this single-center retrospective study, a majority of pediatric heart transplant recipients demonstrate evidence of presumed sinus reinnervation, which is associated with enhanced exercise performance and overall improved patient and graft survival.