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 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 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 reuptake in cytosolic and nuclear CaTs and impaired Ca release kinetics in nuclear CaTs. At 28 weeks, HFpEF cardiomyocytes had depressed CaT amplitudes, decreased sarcoplasmic reticulum (SR) Ca content, increased SR Ca leak, and elevated diastolic [Ca ] following increased pacing rate (5 Hz). In trained HFpEF rats (HIIT or MICT), cardiomyocyte SR Ca leak was significantly reduced. While HIIT had no effects on the CaTs (1-5 Hz), MICT accelerated early Ca release, reduced the amplitude, and prolonged the CaT without increasing diastolic [Ca ] or cytosolic Ca load at basal or increased pacing rate (1-5 Hz). MICT lowered pro-arrhythmogenic Ca sparks and attenuated Ca -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 release was impaired under baseline conditions. HIIT and MICT differentially affected Ca homeostasis with positive effects of MICT on stroke volume, end-diastolic volume, and cellular arrhythmogenicity.