Left ventricular hypertrophy and myocardial fibrosis in heart failure with preserved ejection fraction: mechanisms and treatment

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and is characterized by phenotypical heterogeneity with a high prevalence of multiple, often overlapping cardiometabolic disorders. Comorbidities such as hypertension, obesity, or diabetes are present in many HFpEF patients and are hypothesized to contribute to adverse cardiac remodelling and myocardial fibrosis through a variety of haemodynamic and metabolic impairments, with nearly half of all HFpEF patients exhibiting left ventricular (LV) hypertrophy or concentric remodelling. Myocardial fibrosis and its surrogate changes in LV structure and geometry lead to functional impairments such as increased diastolic stiffness and elevated filling pressures and are associated with reduced exercise tolerance and poor prognosis in patients with HFpEF. Despite recent therapeutic progress, there are currently no evidence-based therapies mechanistically focusing solely on myocardial fibrosis and LV hypertrophy in HFpEF. Recognizing myocardial fibrosis and LV hypertrophy as key features of the heterogeneous HFpEF pathophysiology may contribute to the development of promising targets for future clinical trials. This review elaborates on the pathophysiological role of fibrotic remodelling and LV hypertrophy in HFpEF, outlines contemporary diagnostic standards, and discusses emerging therapeutic strategies, aiming at directly modulating myocardial fibrosis and hypertrophy in HFpEF.