Venous Congestion in Metabolic Heart Disease: Potential Indirect Role of Dual Incretin Agonists

INTRODUCTION: Venous congestion is responsible for symptoms, organ dysfunction, and negative outcomes in heart failure. In obesity-related Heart Failure (HF) with preserved ejection fraction (HFpEF), metabolic dysfunction, inflammation, endothelial damage, and sodium retention might exacerbate venous congestion. METHOD: This structured narrative review provides an overview of the association between metabolic dysfunction, venous congestion, and incretin-based treatment in heart failure. Relevant literature was reviewed with special focus on original clinical trials, mechanism-of-action studies, and studies with venous congestion-related endpoints or surrogates. RESULTS: Beneficial effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists in obesity-related HFpEF patients have been shown in weight loss, symptom improvement, improvement in exercise tolerance, and reduced cardiovascular and heart failure outcomes. Nevertheless, there is still no evidence showing the direct effect of these agents in reducing venous pressure, preload, and systemic venous congestion. DISCUSSION: The current available literature can explain the indirect mechanism by which weight loss, hypotensive action, improved insulin resistance, reduction of ectopic fat, and antiinflammatory properties improve the cardiometabolic physiology of HFpEF patients. CONCLUSION: Although the use of dual incretin agonists represents a novel therapeutic approach for obesity-related HFpEF, the ability of these drugs to decongest the venous system directly is not yet proven. Further studies are required to evaluate venous congestion endpoints such as right-sided filling pressures, venous Doppler indices, natriuretic peptides, need for diuretics, and VExUS score.