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

Abstract

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.

Keywords: Clinical trials; HFpEF; Immunomodulation; Inflammation; LVDD; Preclinical models.

Fig. 1

Pathophysiological mechanisms of heart failure with preserved ejection fraction (HFpEF) as targets for therapy. Comorbidities, such as hypertension, type 2 diabetes mellitus (T2DM), and obesity, lead to chronic systemic inflammation and subsequently HFpEF, associated with myocardial inflammation and damage (red). Immunomodulation targeting either comorbidities or underlying disease mechanisms (green), which is the focus of this review, can decrease myocardial inflammation and damage and are currently under evaluation