Cardiac Remodeling Following High Intensity Exercise Training In A Preclinical HCM Mouse Model

Abstract

Participation in high intensity exercise for individuals with hypertrophic cardiomyopathy (HCM) remains controversial. Retrospective data has suggested that HCM patients who participate in lifetime vigorous exercise can have favorable cardiac remodeling that resembles that which occurs in healthy athletes. Cardiac hypertrophy is highly variable in HCM patients and may mask physiologic hypertrophy induced by exercise. PURPOSE: Evaluate the effects of high intensity interval training (HIIT) on cardiac hypertrophy in a preclinical transgenic cardiac troponin T delta160E (TG) HCM mouse model. METHODS: C57BL/6J non-transgenic (NTG) (n=6 F, n=5 M) and TG (n=4 F, n=8 M) mice (13-16mos) underwent a translationally parallel cardiac rehabilitation HIIT protocol. One treadmill training bout included 4-4 minute high intensity intervals (~80% preVO2 max speed) interspersed by 5-3 minute recovery intervals (~50% preVO2 max speed) for 31 total minutes. Exercise compliance was measured as percent of total training time completed. Bouts were repeated 3 times/wk for 10wks. Pre and post HIIT murine echocardiography (ECHO) was recorded and analyzed by a blinded technician. Unpaired and paired t-tests were used for data analysis. RESULTS: Training compliance between TG and NTG did not differ (921.90min ± 4.24, 99.13% vs 928.95min ± 1.05, 99.90%; p=0.14). Pre and post HIIT left ventricular (LV) mass was significantly greater in both NTG (Mean difference & SEM: 23.04mg, 6.23; p=0.0042) and TG (Mean difference & SEM: 17.56mg, 6.31; p =0.019) mice. Body weights measured prior to pre and post HIIT ECHOs did not differ in NTG (Mean difference & SEM: 0.473g, 0.8370; p=0.585) or TG (Mean difference & SEM: 1.354g, 0.819; p=0.129) mice. CONCLUSION: In a preclinical HCM mouse model that doesn’t demonstrate pathologic hypertrophy, HIIT training resulted in LV hypertrophy in both NTG and TG mice. Our data provides initial evidence that high intensity exercise training may result in physiologic hypertrophy. Biochemical analyses are underway to elucidate the underlying type of cardiac remodeling.