ABSTRACT
Heart failure with preserved ejection fraction (HFPEF) is considered one of the greatest mysteries in cardiovascular research. Currently, many authors agree that HFPEF is a metabolic disease, with distinct phenotypes according to the comorbidities associated, which hinders the search for a specific and effective therapy for this syndrome. Thus, this review describes the main impact of each comorbidity in HFPEF phenotype along with the main findings of experimental studies using animal models of HFPEF with distinct comorbidities associated. Increased cardiomyocyte passive stiffness and fibrosis of extracellular matrix have been experimentally described, however the mechanisms inducing these alterations are still under debate. The answer could be endothelial dysfunction and reactive fibrosis, but further studies are still required.
