ABSTRACT
Heart failure with preserved ejection fraction (HFpEF) is an important condition that has increased in prevalence considerably over the past decades. Comorbidities that contribute to its development include obesity, hypertension, chronic kidney disease, and diabetes. Alongside these multiple risk factors, there exist multiple pathophysiologic mechanisms that likely contribute to observed phenotypic differences in HFpEF. As a result, universal therapies remain limited for this heterogeneous condition, warranting a need to better understand the onset and progression of HFpEF phenotypes. In this chapter, we explore the various pathophysiologic mechanisms that contribute to HFpEF disease states, including delayed myocardial relaxation, ventricular stiffening, and endothelial dysfunction, ventricular-arterial coupling, inflammatory mechanisms, adiposity-ventricular and cardiopulmonary interactions, and skeletal muscle metabolism and myocardial energetics. Distinguishing these mechanisms may offer insights in identifying therapeutic targets toward improving morbidity and mortality in HFpEF.
