Understanding Exercise-induced Protection in Heart Failure with Reduced Ejection Fraction and Heart Failure with Preserved Ejection Fraction: Molecular Mechanisms and New Therapeutic Opportunities.

Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are subtypes of heart failure with overlapping clinical features but have some distinct functional characteristics and cellular and molecular mechanisms. Exercise training is an accessible, non-pharmacological therapy recommended for the management of HFrEF and is increasingly showing promise for treating HFpEF. This review summarises the underlying pathophysiology of HFrEF and HFpEF and the evidence from clinical and preclinical studies showing that exercise training can improve cardiac function. The authors also summarise the underlying cellular and molecular mechanisms between HFrEF and HFpEF, with respect to cardiac remodelling, fibrosis, mitochondrial adaptations and metabolism, inflammation and inter-organ crosstalk, and provide evidence that exercise training elicits protective adaptations in HFrEF and HFpEF through some different signalling pathways targeted by exercise. Finally, the authors discuss the use of exercise training as a therapeutic intervention for HFrEF and HFpEF through personalised training by phenotype and in combination with emerging pharmacological treatments.