Acute Decompensated Heart Failure: Structural and Functional Changes in Mitochondria.

Abstract

Aim: Comparative assessment of structural changes in cardiomyocyte mitochondria of the right atrial appendage and the mitochondrial respiratory function in peripheral blood leukocytes in a cohort of patients after acute decompensated heart failure (ADHF) and with stable chronic heart failure of ischemic etiology with reduced ejection fraction (CHFrEF) or moderately reduced ejection fraction (CHFmrEF) of the left ventricle.

Material and methods: The study analyzed 40 micrographs of right atrial appendage cardiomyocytes obtained from 12 patients with CHFrEF and CHFmrEF. The study protocol was registered on ClinicalTrials.gov: NCT05770349. Electron microscopy was performed with a JEM-1400 transmission electron microscope (Subdiffraction Microscopy Collective Use Center at the Electron Microscopy Department of the Belozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State University). The total area of interfibrillar mitochondria was calculated as a ratio of the total surface area of mitochondria located between the cardiomyocyte contractile fibers to the total area of the interfibrillar space. The respiratory activity of isolated mitochondria was assessed in oxygenated standard incubation media. Patients were divided into two groups based on the occurrence of an ADHF episode within 12 months before inclusion in the study: Group 1 (n=19), patients without ADHF and Group 2 (n=21), patients with an episode of ADHF.

Results: Most of the clinical and anamnestic parameters were comparable between the study groups. Analysis of the mitochondrial respiratory function in peripheral blood leukocytes showed reduced values of the respiratory control level (RCL) in both study groups, 2.14 [2; 2.32] and 2.55 [1.36; 2.84] conv. units. The total area of interfibrillar mitochondria was 41.7 [32; 58]% in the group without ADHF and 33 [21; 46]% in patients with ADHF (p=0.048); significant correlations were found between this parameter and the distance walked in the 6-min walk test (r=0.482; p=0.002) and the peak oxygen consumption during exercise (r=0.395; p=0.012). A ROC analysis was used to determine a threshold value of the total area of interfibrillar mitochondria in patients with ADHF: the cutoff point was 32%.

Conclusion: A decrease in the total area of interfibrillar mitochondria of the right atrial appendage cardiomyocytes of less than 32% as measured by electron microscopy is characteristic of patients with a previous episode of ADHF with reduced and moderately reduced left ventricular ejection fraction. The study results confirm the development and persistence of ultrastructural changes in cardiomyocytes after ADHF.