Association of Cardiomyocyte Mitochondrial Ultrastructure Features with the Severity of Clinical Manifestations in Heart Failure

Aim    To study the quantitative characteristics of cardiomyocyte mitochondrial ultrastructure using electron microscopy data of patients with chronic heart failure (CHF) and to analyze the association of these characteristics with CHF clinical parameters and severity.
Material and methods    The study analyzed a total of 180 micrographs of right atrial appendage cardiomyocytes from 30 patients with CHF and reduced or mid-range left ventricular ejection fraction (LVEF). Standard laboratory and instrumental tests, including echocardiography, a 6-minute walk test (6MWT), and a cardiorespiratory exercise test, were performed in all patients. Biopsy samples were collected during coronary artery bypass grafting. Electron microscopy was performed with a JEM-1400 transmission electron microscope. The total interfibrillar mitochondrial area (Smtx) was calculated at a magnification of ×5,000. Also, the ratio of the outer membrane length of an individual mitochondrion to the length of its inner membrane at a magnification of ×15,000 was calculated.
Results    The Smtx positively correlated with the exercise tolerance (r=0.593; p=0.033), peak oxygen consumption during exercise (r=0.395; p=0.012), and the distance covered in the 6MWT (r=0.483; p=0.002). A negative correlation was found between Smtx and the concentration of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) (r= -0.472; p=0.017). The ratio of the outer mitochondrial membrane length to the inner membrane length inversely correlated with LVEF (r= -0.593; p=0.033).
Conclusion    The total area of cardiomyocyte interfibrillar mitochondria correlated with exercise tolerance, peak oxygen consumption, and NT-proBNP concentration, while the mitochondrial membrane length ratio correlated with left ventricular ejection fraction. This suggests an association between quantitative parameters of mitochondrial ultrastructure and clinical manifestations of CHF.

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