Metabolic dysfunction-associated steatotic liver disease and heart failure with preserved ejection fraction: A state-of-the-art review

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has rapidly become the leading cause of chronic liver disease and cirrhosis worldwide, driven by the global surge in metabolic disorders such as obesity, diabetes, hypertension, and dyslipidemia. In parallel, heart failure with preserved ejection fraction (HFpEF) has surpassed heart failure with reduced ejection fraction (HFrEF) as the predominant form of heart failure, particularly in individuals with metabolic comorbidities. Mounting evidence points to a significant overlap in the pathophysiological underpinnings of MASLD and HFpEF, with metabolic dysfunction serving as a common foundation. This review synthesizes current knowledge on the mechanistic links between MASLD and HFpEF, examining metabolic, inflammatory, and fibrotic pathways. We also explore the clinical implications of this association, including diagnostic considerations and therapeutic targets. Shared risk factors and inflammatory pathways have highlighted a strong bidirectional association between MASLD and cardiovascular diseases, particularly HFpEF. Significantly, the degree of hepatic fibrosis in MASLD correlates with HFpEF prognosis and severity, emphasizing the systemic nature of these conditions. Emerging pharmacological and lifestyle-based interventions aimed at managing both conditions underscore the importance of integrated, multidisciplinary care in improving long-term outcomes.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Heart failure with preserved ejection fraction; Diabetes mellitus; Obesity; Hypertension; Dyslipidemia; Obstructive sleep apnea; Inflammation; Metabolic dysfunction

Core Tip: The ever-changing terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) to encompass metabolic dysfunction truly reflects its systemic impact beyond the liver. Cardiovascular diseases remain the leading cause of MASLD-related morbidity and mortality. Amongst the various cardiovascular diseases linked to MASLD, heart failure with preserved ejection fraction (HFpEF) is most closely related to MASLD, sharing a pathophysiologic foundation with MASLD and rooted in common metabolic risk factors. This review explores the intertwined mechanisms linking MASLD and HFpEF, highlighting their clinical convergence and therapeutic relevance.