Key result
This editorial highlights the growing recognition of HFpEF as a complex systemic inflammatory syndrome and discusses the potential of targeting profibrotic and inflammatory signaling.
This editorial highlights the emerging understanding of HFpEF as a systemic inflammatory and profibrotic syndrome, contextualizing recent therapeutic successes with MRAs, SGLT2 inhibitors, and GLP-1 modulators.
Editorials; heart failure, diastolic Heart failure is a leading cause of morbidity, mortality, and hospitalization worldwide.Despite advances in pharmacologic and percutaneous procedures, mortality from this disease remains staggeringly high, with a 50% 5-year mortality from time of diagnosis.1 Historically, research and development for heart failure therapies have fixated on heart failure with reduced ejection fraction.Yet, heart failure with preserved ejection fraction (HFpEF) accounts for 50% of all heart failure and bears a similar mortality statistic to systolic dysfunction.2 Driven by chronic conditions such as obesity, hypertension, chronic renal disease, and aging, rising disease prevalence has underscored knowledge gaps and generated intense focus on HFpEF pathogenesis and therapeutics.Over the past decade, a growing body of experimental and clinical trial evidence has pointed to HFpEF as a complex systemic inflammatory syndrome.Following numerous failed clinical trials applying heart failure with reduced ejection fraction drugs to HFpEF, the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) demonstrated benefit of the mineralocorticoid receptor antagonist spironolactone in HFpEF, highlighting the potential for inhibiting profibrotic and inflammatory signaling in this disease state.3 More recently, clinical trials of sodiumglucose cotransporter 2 inhibitors or glucagon-like peptide-1 modulators in HFpEF demonstrated dramatic effects on cardiovascular outcomes and systemic inflammation outsized beyond that which weight loss or glycemic control alone could achieve.4,5 Experimental studies utilizing mouse models reproducing the HFpEF phenotype identified the role of inflammatory and cytokine signaling, cardiac fibroblast activation, extracellular matrix deposition, and subsequent posttranslational modification of the sarcomere integrity protein Titin (Ttn) as primary contributors to the disease hallmarks of perivascular fibrosis,
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Glynnis A. Garry (2025) conducted an editorial in Heart failure with preserved ejection fraction (HFpEF). This editorial highlights the growing recognition of HFpEF as a complex systemic inflammatory syndrome and discusses the potential of targeting profibrotic and inflammatory signaling.
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