Heart failure with preserved ejection fraction: A systemic disease linked to multiple comorbidities, targeting new therapeutic options.

Heart failure is a pathology associated with severe morbidity and mortality. In this large field, heart failure with preserved ejection fraction (HFpEF) appears to be an increasing global health problem; it should be considered as a progressive syndrome, characterized by complex mechanisms of systemic and cardiac adaptation that vary over time, particularly with ageing. Multiple biological phenotypes contribute to the heterogeneous clinical syndrome. HFpEF emerges as a model with proinflammatory cardiovascular and non-cardiovascular coexisting comorbidities, leading to systemic inflammation and subsequent fibrosis and to diverse clinical HFpEF phenotypes. All of these aspects are often present in the elderly population, bordering on the emergence of a true geriatric syndrome. The therapeutic approach cannot be uniform, and must involve management of the different comorbidities according to a phenotype treatment strategy, respecting the pharmacological approaches to the biological pathways involved in the proinflammatory comorbidity-related status. Future studies should consider these multiple distinct HFpEF phenotypes in the development of large morbimortality trials adapted to comorbidities or specific risk factors.