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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ reuptake in cytosolic and nuclear CaTs and impaired Ca²⁺ release kinetics in nuclear CaTs. At 28 weeks, HFpEF cardiomyocytes had depressed CaT amplitudes, decreased sarcoplasmic reticulum (SR) Ca²⁺ content, increased SR Ca²⁺ leak, and elevated diastolic [Ca²⁺ ] following increased pacing rate (5 Hz). In trained HFpEF rats (HIIT or MICT), cardiomyocyte SR Ca²⁺ leak was significantly reduced. While HIIT had no effects on the CaTs (1-5 Hz), MICT accelerated early Ca²⁺ release, reduced the amplitude, and prolonged the CaT without increasing diastolic [Ca²⁺ ] or cytosolic Ca²⁺ load at basal or increased pacing rate (1-5 Hz). MICT lowered pro-arrhythmogenic Ca²⁺ sparks and attenuated Ca²⁺ -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, Ca²⁺ release was impaired under baseline conditions. HIIT and MICT differentially affected Ca²⁺ homeostasis with positive effects of MICT on stroke volume, end-diastolic volume, and cellular arrhythmogenicity.