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Updated: Nov 18, 2025

Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Non-alcoholic fatty liver disease and heart failure with preserved ejection fraction: from pathophysiology to
Romain Itier1, Maeva Guillaume2, Jean-Etienne Ricci3
1Department of Cardiology, Institute CARDIOMET, CHU-Toulouse, Toulouse, France.
Abstract:
The prevalence of non-alcoholic fatty liver disease (NAFLD) in heart failure (HF) preserved left ventricular ejection fraction (HFpEF) patients could reach 50%. Therefore, NAFLD is considered an emerging risk factor. In 20% of NAFLD patients, the condition progresses to non-alcoholic steatohepatitis (NASH), the aggressive form of NAFLD characterized by the development of fibrosis in the liver, leading to cirrhosis. The purpose of this review is to provide an overview of the relationships between NAFLD and HFpEF and to discuss its impact in clinical setting. Based on international reports published during the past decade, there is growing evidence that NAFLD is associated with an increased incidence of cardiovascular diseases, including impaired cardiac structure and function, arterial hypertension, endothelial dysfunction, and early carotid atherosclerosis. NAFLD and HFpEF share common risk factors, co-morbidities, and cardiac outcomes, in favour of a pathophysiological continuum. Currently, NAFLD and NASH are principally managed with non-specific therapies targeting insulin resistance like sodium-glucose co-transporter-2 inhibitors and liraglutide, which can effectively treat hepatic and cardiac issues. Studies including HFpEF patients are ongoing. Several specific NAFLD-oriented therapies are currently being developed either alone or as combinations. NAFLD diagnosis is based on a chronic elevation of liver enzymes in a context of metabolic syndrome and insulin resistance, with fibrosis scores being available for clinical practice. In conclusion, identifying HF patients at risk of NAFLD is a critically important issue. As soon as NAFLD is confirmed and its severity determined, patients should be proposed a management focused on symptoms and co-morbidities.
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