Heart Failure With Preserved Ejection Fraction With CKD: A Narrative Review of a Multispecialty Disorder

Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome with varying phenotypic expression. The phenotype chronic kidney disease (CKD) associated HFpEF is increasing in prevalence globally and is associated with increased morbidity and mortality compared to other HFpEF variants. These 2 conditions share common risk factors, including obesity, diabetes, and metabolic syndrome, as well as similar pathophysiology, including systemic inflammation, oxidative stress, elevated neurohormones, mineralocorticoid-receptor activation, and venous congestion. Given the coexistence of CKD and HFpEF, the diagnosis of HFpEF can be difficult. Moreover, treatment options for HFpEF have remained limited despite the success seen in its counterpart, heart failure with reduced ejection fraction. HFpEF encompasses complex multisystem pathophysiological perturbations beyond neurohormones, it is unlikely that a single agent can have significant benefit in this population. Recent data on sodium–glucose cotransporter 2 (SGLT2) inhibitors in HFpEF and CKD, and on glucagon-like peptide-1 (GLP-1) agonists and mineralocorticoid-receptor antagonists in metabolic syndrome, which target multiple pathways simultaneously, have led to promising therapeutics for HFpEF and CKD. In this perspective, our goal is to increase awareness of HFpEF as a multisystem disorder that shares the same disease processes seen in CKD and to emphasize that its management in individuals with CKD warrants a collective and multidisciplinary approach.