Heart failure with preserved ejection fraction (HFpEF) has long been considered a stubborn cardiac condition defined by diastolic dysfunction. However, a paradigm shift is underway, reframing it as a systemic metabolic disorder driven by inflammation.
The emerging cardio-hepato-pancreas axis theory posits that venous congestion triggers a dangerous loop. Hepatic congestion from right-sided heart pressure doesn't just cause liver stiffness; it actively drives disease progression through hypoxia, fibrosis, and a surge of inflammatory cytokines that further damage the myocardium.
This systemic view also incorporates the pancreas. Splanchnic hypoperfusion and congestion can trigger pancreatic exocrine insufficiency (PEI), leading to malabsorption, sarcopenia, and cachexia-complicating the cardiac prognosis. Conditions like metabolic dysfunction-associated steatotic liver disease and insulin resistance amplify inflammatory adipokines, increasing ventricular stiffness.
Therapeutic strategies are shifting accordingly. The success of SGLT2 inhibitors and GLP-1 receptor agonists supports this model, as their benefits likely stem from pleiotropic anti-inflammatory and metabolic effects rather than direct cardiac mechanics. Experts now advocate for interdisciplinary care that combines cardiology, hepatology, and nutrition to break the inflammatory tri-organ loop.