Mitochondrial ultrastructure in cardiac myocytes is associated with the cardiovascular death in patients with heart failure

BACKGROUND Mitochondria are considered a promising target for the treatment of cardiovascular disease. However, there has not been a direct association confirmed between mitochondrial ultrastructure in cardiac myocytes and cardiovascular death (CVD) in patients with heart failure (HF). AIM To evaluate the association between mitochondrial ultrastructure in cardiac myocytes and CVD in patients with HF who underwent coronary artery bypass grafting (CABG). METHODS It was a prospective study of HF patients that used electron microscopy of human cardiac myocytes. A total of 40 patients with HF (left ventricular ejection fraction < 50%) with coronary artery disease who underwent CABG were included (ClinicalTrials.gov: NCT05770349). Right atrial appendage biopsies were obtained during CABG. Ultrastructural analysis of mitochondria was performed using a JEM-1400 transmission electron microscope. The “Total area of interfibrillar mitochondria” and the “Ratio of mitochondrial membrane lengths” were calculated. Patients were followed for 12 months: 6 CVDs were recorded (15%). Statistical analysis was performed using IBM SPSS Statistics version 21; statistical significance was defined as P < 0.05. RESULTS From 3 to 5 Longitudinal sections were examined at 5000 × magnification and at 15000 × magnification for each patient (a total of over 250 micrographs were analyzed). The median of the total area of interfibrillar mitochondria was 41% (34; 63); the median of the ratio of the outer membrane length to the inner mitochondrial membrane length was 30% (22; 36). Univariate analysis demonstrated statistically significant differences between the ratio of mitochondrial membrane lengths in patients with and without CVD [29% (20, 33.5) vs 41% (35, 45), P = 0.001]. Patients with CVDs were also more often hospitalized due to HF before CABG and had a long duration of hospitalization after CABG. CONCLUSION A disruption in the mitochondrial ultrastructure in cardiomyocytes in the right atrial auricle might be associated with the development of CVD in patients with HF who underwent CABG.