Heart failure with preserved ejection fraction as amodel disease for the cardio-pulmonary-renal syndrome : Importance of visceral fat expansion as central pathomechanism

Abstract

Heart failure with preserved ejection fraction (HFpEF) is aheterogeneous syndrome with diverse underlying etiologies and pathophysiological factors. Obesity and type2 diabetes mellitus (T2DM), diseases which frequently coexist, induce acluster of metabolic and nonmetabolic signaling derangements, which promote induction of inflammation, fibrosis and myocyte stiffness, all representing hallmarks of HFpEF. In contrast to other HFpEF risk factors, obesity and T2DM are often associated with the formation of an enlarged visceral adipose tissue (VAT), which is a highly active endocrine organ that can sustainably exacerbate inflammation and fibrotic remodeling of myocardial, renal, and vascular tissues via various paracrine and vasocrine signals. An abnormally large epicardial adipose tissue (EAT) thus not only causes a mechanical constriction of the diastolic filling procedure of the heart but is also associated with an increased release of proinflammatory adipokines that trigger atrial fibrillation and impaired left ventricular contraction parameters. Obese patients with HFpEF therefore belong to aunique HFpEF phenotype with aparticularly poor prognosis that could benefit from an EAT-oriented phenotype-specific intervention. In addition to statins and antidiabetic drugs such as metformin, glucagon-like peptide‑1 (GLP-1) receptor agonists and sodium-glucose transporter2(SGLT-2) inhibitors could also play an important role.