Immunomodulation in Heart Failure with Preserved Ejection Fraction: Current State and Future Perspectives

The heart failure (HF) epidemic is growing and approximately half of the HF patients have heart failure with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous syndrome, characterized by a preserved left ventricular ejection fraction (LVEF ≥ 50%) with diastolic dysfunction, and is associated with high morbidity and mortality. Underlying comorbidities of HFpEF, i.e., hypertension, type 2 diabetes mellitus, obesity, and renal failure, lead to a systemic pro-inflammatory state, thereby affecting normal cardiac function. Increased inflammatory biomarkers predict incident HFpEF and are higher in patients with HFpEF as compared with heart failure with reduced ejection fraction (HFrEF). Randomized trials in HFpEF patients using traditional HF medication failed to demonstrate a clear benefit on hard endpoints (mortality and/or HF hospitalization). Therefore, therapies targeting underlying comorbidities and systemic inflammation in early HFpEF may provide better opportunities. Here, we provide an overview of the current state and future perspectives of immunomodulatory therapies for HFpEF.