The MASLD–Heart Axis: Biological Mechanisms, Cardiac Remodeling, and Clinical Implications

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of cardiometabolic dysfunction, is closely linked to atherosclerosis, heart failure, and adverse cardiovascular outcomes. This review summarizes current evidence on the biological basis of the MASLD–heart axis, with particular emphasis on vascular injury and adverse cardiac remodeling. Methods: A narrative review of contemporary literature was conducted, including experimental studies, observational cohorts, meta-analyses, randomized clinical trials, and current guideline recommendations addressing the cardiohepatic axis. Results: The interaction between the liver and the heart involves interconnected mechanisms, including insulin resistance, lipotoxicity, oxidative stress, chronic inflammation, endothelial dysfunction, and neurohormonal activation. Experimental and translational evidence supports biologically plausible links between MASLD-related metabolic and inflammatory pathways and vascular or myocardial injury, while clinical studies consistently associate MASLD with arterial stiffness, microvascular dysfunction, atherosclerotic disease, adverse cardiac remodeling, heart failure, atrial fibrillation, and cardiovascular events. Several of these associations persist after adjustment for conventional cardiometabolic risk factors, although residual confounding and shared risk determinants limit causal inference. Non-invasive tools, including the Fibrosis-4 (FIB-4) score and transient elastography, may help identify patients at higher risk of advanced fibrosis and cardiometabolic complications. Lifestyle interventions remain the cornerstone of management, while glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and fibroblast growth factor-21 analogs may provide combined hepatic and cardiovascular benefits. Conclusions: The cardiohepatic axis is an important component of cardiometabolic disease, linking hepatic dysfunction with vascular and myocardial injury through shared biological pathways. Incorporating hepatic assessment into cardiovascular risk evaluation may support earlier identification of high-risk patients.