Effects of different exercise modalities on cardiac dysfunction in heart failure with preserved ejection fraction

AIMS: Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent disease. Physical exercise has been shown to alter disease progression in HFpEF. We examined cardiomyocyte Ca(2+) homeostasis and left ventricular function in a metabolic HFpEF model in sedentary and trained rats following 8 weeks of moderate‐intensity continuous training (MICT) or high‐intensity interval training (HIIT). METHODS AND RESULTS: Left ventricular in vivo function (echocardiography) and cardiomyocyte Ca(2+) transients (CaTs) (Fluo‐4, confocal) were compared in ZSF‐1 obese (metabolic syndrome, HFpEF) and ZSF‐1 lean (control) 21‐ and 28‐week‐old rats. At 21 weeks, cardiomyocytes from HFpEF rats showed prolonged Ca(2+) reuptake in cytosolic and nuclear CaTs and impaired Ca(2+) release kinetics in nuclear CaTs. At 28 weeks, HFpEF cardiomyocytes had depressed CaT amplitudes, decreased sarcoplasmic reticulum (SR) Ca(2+) content, increased SR Ca(2+) leak, and elevated diastolic [Ca(2+)] following increased pacing rate (5 Hz). In trained HFpEF rats (HIIT or MICT), cardiomyocyte SR Ca(2+) leak was significantly reduced. While HIIT had no effects on the CaTs (1–5 Hz), MICT accelerated early Ca(2+) release, reduced the amplitude, and prolonged the CaT without increasing diastolic [Ca(2+)] or cytosolic Ca(2+) load at basal or increased pacing rate (1–5 Hz). MICT lowered pro‐arrhythmogenic Ca(2+) sparks and attenuated Ca(2+)‐wave propagation in cardiomyocytes. MICT was associated with increased stroke volume in HFpEF. CONCLUSIONS: In this metabolic rat model of HFpEF at an advanced stage, Ca(2+) release was impaired under baseline conditions. HIIT and MICT differentially affected Ca(2+) homeostasis with positive effects of MICT on stroke volume, end‐diastolic volume, and cellular arrhythmogenicity.