Mitochondrial Function is Impaired in Heart Transplant Patients with Cardiac Allograft Vasculopathy

Abstract

Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival of heart transplanted (HTx) patients. CAV affects approximately 50 % of HTx patients 10 years after transplant. We evaluated whether cardiac allograft vasculopathy is associated with mitochondrial dysfunction. A total of 36 HTx patients (18 patients with CAV and 18 patients without CAV) ≥ 12 months after HTx were enrolled. Endomyocardial biopsies were analyzed using high-resolution respirometry for glucose-coupled mitochondrial respiration. Echocardiography and coronary angiography were used to grade CAV according to ISHLT nomenclature. Maximally coupled respiration of mitochondrial complex I and II was significantly reduced in patients with CAV compared with patients without CAV (97.2 pmol O2/(s*mg) [65.5; 133.6] vs. 59.1 pmol O2/(s*mg) [53.9; 83.0], p = 0.009) (Fig. 1). Patients with positive donor specific antibodies (MFI > 3000) had a lower maximally coupled respiration compared with patients without (56.5 pmol O2/(s*mg) [53.3; 69.0] vs. 90.6 pmol O2/(s*mg) [59.8; 113.9], p = 0.009). Mitochondrial respiratory function measured as oxidative phosphorylation coupling efficiency was positively associated with both left ventricular function (global longitudinal strain, r2=0.239, p = 0.0045) and right ventricular function (tricuspid annular plane systolic excursion, r2=0.133, p=0.03). Mitochondrial respiration is impaired in patients with CAV compared with patients without CAV. Decreased mitochondrial respiratory function is associated with impaired myocardial contractile function.