Beneficial Effects of High Intensity Interval Training in a Mouse Model of Hypertrophic Cardiomyopathy

High intensity exercise (HIE) has become a prominent training modality used to ameliorate cardiac disease conditions. The effects of HIE training on Hypertrophic Cardiomyopathy (HCM) have not been previously studied in animal models or in patients, largely due to concerns about triggering sudden arrhythmic events. Employing a transgenic cardiac troponin (cTnT-160E or TG) preclinical murine model that closely recapitulates human HCM, we evaluated the effects of a High Intensity Interval Training (HIIT) protocol on cardiorespiratory capacity (i.e., peak oxygen consumption or pVO2), which is a significant prognostic indicator of disease trajectory. 14 month old TG male mice had lower peak VO2 than non-transgenic (NTG) male mice of the same age at baseline, but there was no difference in pVO2 in female TG compared to nTG mice. HIIT significantly improved pVO2 in both nTG female (18%) , nTG male (18%), TG female (16%) and TG male (12%) mice compared to sedentary controls. There were no changes in structure, function or LV mass as measured by echocardiography or post mortem analyses in any of the groups, and no effect of HIIT on cardiac fibrosis. HIIT led to significant increases in lean muscle mass in both nTG and TG male mice, and nTG female mice but not TG female mice. The results of our study provide foundational evidence that HIE can improve pVO2 in HCM without adverse effects on disease phenotype. Total bulk RNA-Seq profiles of C57BL/6J mice after 6 weeks of HIIT vs sedentary behavior in male and female nTG and TG (cTnT-delta160E ) mice. There were 8 groups total: sedentary nTG female mice, HIIT nTG female mice, sedentary TG female mice, HIIT TG female mice, sedentary nTG male mice, HIIT nTG male mice, sedentary TG male mice, HIIT TG male mice. RNA was extracted from 7-9 samples per group for 64 samples total.