Serial Assessment of Cardiac Mitochondrial Function in the Early Phase After Heart Transplantation

Mitochondrial dysfunction contributes to cardiac pathology and may influence myocardial recovery after heart transplantation (HTX). However, posttransplant mitochondrial function in human myocardial tissue remains poorly characterized. We hypothesized that myocardial mitochondrial function would recover in the early posttransplant period and that improvements would correlate with cardiac recovery and metabolic status.

In this prospective single-center study, 45 adult HTX recipients underwent serial endomyocardial biopsies from 1 week to 6 mo post-HTX. Mitochondrial function was assessed using high-resolution respirometry, evaluating complex I-mediated respiration, maximal oxidative phosphorylation, respiratory control ratio, and coupling control ratio. Correlations with echocardiographic, hemodynamic, and biochemical variables were evaluated.

Mitochondrial function remained stable throughout follow-up, with no significant changes in complex I respiration, maximal oxidative phosphorylation, respiratory control ratio, or coupling control ratio. Echocardiography showed significant improvement in biventricular function, including a 15% increase in global longitudinal strain ( P  = 0.0003) and a 20% increase in tricuspid annular plane systolic excursion ( P  = 0.0004). At 6 mo, global longitudinal strain correlated with maximal oxidative phosphorylation ( r = -0.552; P  = 0.0005) and respiratory control ratio ( r = -0.479; P  = 0.0031). No associations were found with cardiac output, cardiac index, troponin I, or N-terminal pro-brain natriuretic peptide. Pretransplant glycated hemoglobin correlated inversely with maximal oxidative phosphorylation at 6 mo ( r = -0.351; P  = 0.0026).

Myocardial mitochondrial function remained stable during early posttransplant recovery. Its association with echocardiographic improvement and pretransplant glycemic state suggests a link between left ventricular contractility and mitochondrial function, and a potential influence of metabolism on myocardial energetics.