Background: Reactive oxygen species (ROS) play some important roles in the development and progression of heart failure. Mitochondria are a major target for ROS damage, as well as a major source of ROS. Therefore, damage of mitochondria by ROS may cause abnormality in the mitochondrial life cycle, thus mitochondrial irregularity would be observed depending on myocardial damage. We hypothesized that mitochondrial irregularity is associated with prognosis of dilated cardiomyopathy (DCM).
Methods: This study included 115 patients with heart failure who had a diagnosis of DCM between 2005 and 2007. All patients underwent cardiac catheterization including hemodynamic measurement and right ventricular endomyocardial biopsy. We measured the size of mitochondria in each electron micrograph: mitochondrial irregularity was expressed by coefficient of variation (Mit-CV: (standard deviation)/(mean minor axis) х100 (%) ).
Results: Average of 99±41 mitochondria of each patients were analyzed. Average Mit-CV level was 40.3±6.8% in this population. In DCM patients, Mit-CV was positively correlated with left ventricular end-diastolic diameter (r=0.23, p=0.011), and negatively correlated with cardiac index (r=-0.20, p=0.036). The optimal cut-off value of Mit-CV was determined to be 41% according to receiver operating characteristic curve to estimate event free rate. Kaplan-Meier analysis demonstrated that all-cause death or LVAS implantation was increased in the high Mit-CV group (log-rank p <0.01). Furthermore, the frequency of cardiac death or LVAS implantation was also increased in high Mit-CV group (p <0.01). Multivariate analysis adjusted for BNP and cardiac index revealed that Mit-CV is an independent factor of adverse events (HR=6.30, p=0.040).
Conclusions: Mitochondrial irregularity was associated with long-term outcome in DCM. Such irregularity might be caused by ROS-induced impaired mitochondrial quality control.