Rheumatologic Disease as a Substrate for HFpEF: Pathophysiological Mechanisms and Clinical Implications

Systemic inflammation has gained attention in heart failure (HF), particularly HF with preserved ejection fraction (HFpEF); a heterogeneous syndrome representing over half of HF cases and increasingly recognized in individuals with systemic rheumatologic diseases. Although myocardial infarction and HF with reduced EF have traditionally been emphasized in the context of systemic inflammation, recent data suggest that HFpEF is the predominant phenotype, often arising independently of overt coronary artery disease. Despite substantial cardiovascular morbidity and mortality, patients with rheumatologic disease remain underrepresented in HF research, and the mechanisms linking inflammation to HFpEF remain underdescribed in this population. This review examines the intersection of systemic rheumatologic disease and HFpEF, focusing on shared pathophysiology, diagnostic challenges, and therapeutic opportunities. Patients with rheumatologic diseases, including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and systemic sclerosis, exhibit a markedly increased risk of HFpEF. Chronic inflammation, microvascular dysfunction, and myocardial fibrosis emerge as key drivers. These conditions complicate diagnosis because of atypical symptoms and overlapping comorbidities. Although existing HFpEF therapies primarily target hemodynamic and metabolic contributors, they seldom address immune-mediated mechanisms. Anti-inflammatory strategies have shown cardiovascular benefit in selected populations; yet their role in HFpEF among rheumatologic subgroups remains underexplored. Exclusion of patients with rheumatologic disease or immunosuppressive therapy from HFpEF trials further limits generalizability. In conclusion, HFpEF associated with rheumatologic disease represents a distinct, underrecognized inflammatory phenotype. Collaborative cardiology-rheumatology research is needed to refine diagnosis, evaluate immunomodulatory strategies, and design inclusive clinical trials to improve outcomes in this growing population.