The aging heart in focus: The advanced understanding of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) accounts for 50 % of heart failure (HF) cases, making it the most common type of HF, and its prevalence continues to increase in the aging society. HFpEF is a systemic syndrome resulting from many risk factors, such as aging, metabolic syndrome, and hypertension, and its clinical features are highly heterogeneous in different populations. HFpEF syndrome involves the dysfunction of multiple organs, including the heart, lung, muscle, and vascular system. The heart shows dysfunction of various cells, including cardiomyocytes, endothelial cells, fibroblasts, adipocytes, and immune cells. The complex etiology and pathobiology limit experimental research on HFpEF in animal models, delaying a comprehensive understanding of the mechanisms and making treatment difficult. Recently, many scientists and cardiologists have attempted to improve the clinical outcomes of HFpEF. Recent advances in clinically related animal models and systemic pathology studies have improved our understanding of HFpEF, and clinical trials involving sodium-glucose cotransporter 2 inhibitors have significantly enhanced our confidence in treating HFpEF. This review provides an updated comprehensive discussion of the etiology and pathobiology, molecular and cellular mechanisms, preclinical animal models, and therapeutic trials in animals and patients to enhance our understanding of HFpEF and improve clinical outcomes.