Mitochondrial Structural Abnormalities and Cardiac Reverse Remodeling in Patients With Systolic Dysfunction.

Abstract

Background: Mitochondrial dysfunction in the heart is associated with the development of heart failure (HF). However, the clinical consequences of mitochondrial structural abnormalities in patients with HF remain unexplored.

Methods and results: Ninety-one patients with left ventricular (LV) systolic dysfunction who underwent endomyocardial biopsy (EMB) were enrolled in the study. Myocardial specimens were obtained from the right ventricular septum. Specimens were characterized using electron microscopy to assess mitochondrial size, outer membrane disruption, and cristae disorganization. The primary endpoint was a composite of cardiovascular death and unplanned hospitalization for HF. Patients were classified into LV reverse remodeling (LVRR)-positive (n=52; 57.1%) and LVRR-negative (n=39; 42.9%) groups. Cristae disorganization was observed in 21 (23.1%) patients: 6 (11.5%) in the LVRR-positive group and 15 (38.5%) in the LVRR-negative group (P=0.005). During the 1-year post-EMB observation period, 16 patients (17.6%) met the primary endpoint, with 2 (2.2%) cardiovascular deaths and 14 (15.4%) HF hospitalizations. Cristae disorganization (P=0.002) was significantly associated with the endpoints, independent of age (P=0.115), systolic blood pressure (P=0.004), B-type natriuretic peptide level (P=0.042), and mitral regurgitation (P=0.003).

Conclusions: We classified mitochondrial structural abnormalities and showed that cristae disorganization was associated with LVRR and worse prognosis. These findings may affect the management of patients with HF and systolic dysfunction who undergo EMB.