Longitudinal Changes in Heart Rate Recovery After Maximal Exercise in Pediatric Heart Transplant Recipients: Evidence of Autonomic Re-innervation?

Abstract

Cardiac autonomic innervation modulates heart rate (HR) response during and HR recovery after exercise in normal subjects. Heart transplantation results in surgical interruption of autonomic innervation. We assessed whether HR response during exercise and HR recovery after exercise in pediatric heart transplant recipients are consistent with autonomic denervation of the heart after transplant and whether they evolve over years in a manner consistent with autonomic re-innervation. We compared HR response during and HR recovery after a maximum treadmill exercise test in 35 children (median age 13.4 years) after a median follow-up of 1 year after heart transplant with two control groups: post-operative Fontan patients (n = 31) and normal children (n = 35). We then analyzed 153 treadmill exercise tests performed serially in 45 heart transplant recipients (median 3 tests/patient) for longitudinal changes in peak HR and HR recovery after exercise. Transplant recipients had higher body mass index, higher resting HR and significantly attenuated 1- and 3-minute HR recovery after cessation of exercise compared with both control groups (p < 0.001). In transplant recipients with serial exercise tests, peak HR increased an average of 2.0 beats/min per year after transplant (p < 0.001), percent predicted peak HR increased by 1.3% per year (p < 0.001), 1-minute HR recovery increased by 1.0 beats/min per year (p < 0.001), and 3-minute HR recovery by 2.6 beats/min per year (p < 0.001). HR response to exercise and HR recovery after exercise in pediatric heart transplant recipients are consistent with autonomic denervation after transplant and suggestive of late autonomic re-innervation of these hearts.