Inflammation in heart failure: pathophysiology and therapeutic strategies

Abstract

A role for inflammation in the development and progression of heart failure (HF) has been proposed for decades. Multiple studies have demonstrated the potential involvement of several groups of cytokines and chemokines in acute and chronic HF, though targeting these pathways in early therapeutic trials have produced mixed results. These studies served to highlight the complexity and nuances of how pro-inflammatory pathways contribute to the pathogenesis of HF. More recent investigations have highlighted how inflammation may play distinct roles based on HF syndrome phenotypes, findings that may guide the development of novel therapies. In this review, we propose a contemporary update on the role of inflammation mediated by the innate and adaptive immune systems with HF, highlighting differences that exist across the ejection fraction spectrum. This will specifically be looked at through the lens of established and novel biomarkers of inflammation. Subsequently, we review how improvements in inflammatory pathways may mediate clinical benefits of existing guideline-directed medical therapies for HF, as well as future therapies in the pipeline targeting HF and inflammation.

Keywords: Cardiomyopathy; Cytokines; Heart failure; Immune system; Inflammation.

Fig. 1

Established and Novel Biomarkers of Inflammation in Heart Failure. Ang angiotensin, BNP brain natriuretic peptide, CKD chronic kidney disease, CRP C-reactive protein, ESR erythrocyte sedimentation rate, GAL-3 galectin-3, HF heart failure, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, HHF heart failure hospitalization, IL interleukin, IL-1 RA interleukin-1 receptor antagonist, LVEDV left ventricular end-diastolic volume, MACE major adverse cardiac events, NLR neutrophil-to-leukocyte ratio, NP natriuretic peptide, sST2 soluble suppression of tumorigenesis-2, STEMI ST-elevation myocardial infarction, CMP cardiomyopathy

Fig. 2

Therapies in Heart Failure and Inflammation. ACEI: angiotensin-converting enzyme inhibitor. ACS acute coronary syndrome, ARB angiotensin receptor blocker, ARNI angiotensin receptor neprilysin inhibitor, CRP C-reactive protein, CV cardiovascular, GAL-3 galectin-3, HF heart failure, HHF heart failure hospitalization, IFN interferon, IL interleukin, LVEF left ventricular ejection fraction, RAS renin–angiotensin system, SGLT2i sodium glucose transporter 2 inhibitor, sST2 soluble suppression of tumorigenesis-2, TNF tumor necrosis factor