Metabolic Dysfunction-Associated Steatotic Liver Disease and Heart Failure with Preserved Ejection Fraction: A Bidirectional Relationship with Clinical and Therapeutic Implications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent and is the most common cause of chronic liver disease in the western world. It is considered the hepatic manifestation of metabolic syndrome and ultimately leads to cardiovascular diseases, which are the leading cause of death. Heart failure with preserved ejection fraction (HFpEF) appears to be a complication of MASLD and, conversely, seems to exacerbate its severity. This review focuses on the pathophysiological association between MASLD and HFpEF, as well as their clinical and therapeutic implications. Summary: The connection between MASLD and HFpEF is intricate and bidirectional, involving several pathophysiological mechanisms, such as insulin resistance, overactivation of the renin-angiotensin-aldosterone and sympathetic nervous systems, systemic and hepatic inflammation, and gut dysbiosis. MASLD is an independent risk factor for diastolic dysfunction and HFpEF, increasing the risk of hospitalization and death in those with established heart failure. Conversely, HFpEF exacerbates the severity of MASLD. Screening for MASLD and liver fibrosis should be conducted in stable and euvolemic patients with HFpEF, utilizing liver ultrasonography and the Fibrosis-4 index. Screening for heart failure in MASLD patients should be performed with the measurement of natriuretic peptides; however, these may have a lower sensitivity in these patients and echocardiography may be needed. Therapeutic strategies for both MASLD and HFpEF are limited, but certain interventions studied for MASLD may also benefit the cardiovascular system. Lifestyle interventions, such as adherence to a Mediterranean diet and weight loss, have proven beneficial for both diseases. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and incretin mimetics show promise in treating patients with both conditions and may have synergistic effects. Key Messages: MASLD increases the risk of incident HFpEF and worsens the prognosis of patients with HFpEF. Given the high prevalence of MASLD in patients with stable HFpEF, screening for MASLD is crucial. Screening for heart failure in MASLD should begin with the measurement of natriuretic peptides when there is clinical suspicion. Therapeutic interventions such as SGLT2i and glucagon-like peptide-1 receptor agonists may offer synergistic benefits for patients with both diseases.