HFpEF Beyond the Heart: Exploring the Heart–Liver–Pancreas Axis

Feb 19, 2026ESC heart failure

Heart Failure with Preserved Pumping Strength and Its Links to Liver and Pancreas Function

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Abstract

Heart failure with preserved ejection fraction (HFpEF) is linked to inflammatory processes, congestion, and metabolic dysbiosis rather than structural heart abnormalities.

Heart failure with preserved ejection fraction (HFpEF) is associated with liver congestion and fibrosis, which contribute to inflammation and metabolic dysregulation.
The connection between the heart, liver, and pancreas suggests that pancreatic ischemia and exocrine insufficiency may worsen malnutrition and heart failure.
Acute pancreatitis can lead to heart failure and arrhythmia due to systemic inflammatory response syndrome mediated by cytokines.
Understanding the hepato-pancreato-cardiac axis may inform integrated treatment approaches for HFpEF, focusing on anti-inflammatory and metabolic interventions.
Future studies may include multi-organ imaging and therapeutic trials to target this interconnected inflammatory circuit and assess outcomes in HFpEF.

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It has become increasingly recognized that heart failure with a preserved ejection fraction (HFpEF) results from an inflammatory process, congestion, and metabolic dysbiosis rather than an intrinsic structural heart abnormality. Recent studies have highlighted the close link between the heart, the liver, and the pancreas, which are organically connected via the same inflammatory processes and pathways. Liver congestion and fibrosis are responsible for the inflammatory process and the lack of metabolic adaptation, whereas pancreatic ischemia and insufficiency of the exocrine glands aggravate malnutrition and cachexia, worsening the heart condition. Acute pancreatitis may cause heart failure and arrhythmia through injury and systemic inflammatory response syndrome (SIRS), an inflammatory process mediated by the cytokines released during the injury process. Recognition of this hepato-pancreato-cardiac axis offers a paradigm shift toward integrated management of HFpEF, emphasizing anti-inflammatory, metabolic, and hemodynamic interventions. Future research integrating multi-organ imaging, inflammatory biomarkers, and therapeutic trials such as GLP-1 receptor agonists, SGLT2 inhibitors, and cytokine blockers will be critical to disrupt this tri-organ inflammatory circuit and improve outcomes in HFpEF.

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HFpEF Beyond the Heart: Exploring the Heart–Liver–Pancreas Axis

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