Association of an Increased Abnormal Mitochondria Ratio in Cardiomyocytes with a Prolonged Oxygen Uptake Time Constant during Cardiopulmonary Exercise Testing of Patients with Non-ischemic Cardiomyopathy

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Objective The cardiac function, blood distribution, and oxygen extraction in the muscles as well as the pulmonary function determine the oxygen uptake (VO₂) kinetics at the onset of exercise. This factor is called the VO₂ time constant, and its prolongation is associated with an unfavorable prognosis for heart failure (HF). The mitochondrial function of skeletal muscle is known to reflect exercise tolerance. Morphological changes and dysfunction in cardiac mitochondria are closely related to HF severity and its prognosis. Although mitochondria play an important role in generating energy in cardiomyocytes, the relationship between cardiac mitochondria and the VO₂ time constant has not been elucidated. Methods We calculated the ratio of abnormal cardiac mitochondria in human myocardial biopsy samples using an electron microscope and measured the VO₂ time constant during cardiopulmonary exercise testing. The VO₂ time constant was normalized by the fat-free mass index (FFMI). Patients Fifteen patients with non-ischemic cardiomyopathy (NICM) were included. Patients were divided into two groups according to their median VO₂ time constant/FFMI value. Results Patients with a low VO₂ time constant/FFMI value had a lower abnormal mitochondria ratio than those with a high VO₂ time constant/FFMI value. A multiple linear regression analysis revealed that the ratio of abnormal cardiac mitochondria was independently associated with a high VO₂ time constant/FFMI. Conclusions An increased abnormal cardiac mitochondria ratio might be associated with a high VO₂ time constant/FFMI value in patients with NICM.