Prognostic role of sarcopenia and effect of SGLT2-inhibitors on MACE in heart failure patients

Abstract Background Chronic Heart Failure (CHF) is associated with sarcopenia in 20% of cases, resulting in a poorer prognosis. CHF and sarcopenia share several pathophysiological mechanisms, including increased oxidative stress, inflammation, insulin resistance, and connective tissue infiltration into muscle tissue. These conditions are further complicated by malabsorption due to gastrointestinal congestion and physical inactivity, which result in enhanced protein catabolism and subsequent muscle mass loss. This bidirectional connection suggests potential benefits of CHF pharmacological treatments for patients with both conditions. Notably, SGLT2-inhibitors (SGLT2i) are strongly recommended for CHF treatment across the left ventricular ejection fraction (LVEF) spectrum and regardless of type 2 diabetes mellitus (T2DM) status. Purpose The aim of this study is to evaluate the association of sarcopenia and the potential role of SGLT2i with the incidence of MACE in outpatients with CHF. Methods In this retrospective observational study we enrolled 670 Caucasian outpatients, 369 were males and the average age was 65.6±12.5 years; 452 are affected by HFpEF while 218 by HFmrEF and HFrEF, 340 patients were sarcopenic, while 330 patients were not sarcopenic. The mean follow-up was 4.7±2.8 years. Study endpoint was MACE incidence and total mortality was also evaluated. We used AUC to evaluate the accuracy of sarcopenia in predicting MACE. Data was processed with Cox univariance and multivariate analysis model to define independent MACE predictors. Results A total of 245 (7.8 events/100 patient-year) MACE were observed; 213 in sarcopenia group and 32 in the no sarcopenia group (13.3 vs 2.1 events/100 patient-year) (p0.0001). Non-CV mortality was not significantly different between the sarcopenia and no sarcopenic group (18 vs 24 events, 1.1 vs 1.5 events/100 patient-year) (p = 0.291). Total mortality was higher in the sarcopenia group compared to the no sarcopenia group (102 vs 28 events, 6.4 vs 1.8 events/100 patient-year) (p0.0001). The ROC curve and his relative AUC demonstrated the accuracy of sarcopenia as a predictor of the occurrence of MACE (AUC 0.78; 95% CI 0.749–0.821; p0.0001). The multivariate analysis model demonstrates that SGLT2i reduces the risk of MACE by 89%. In contrast, sarcopenia increases the risk of MACE by a factor of almost six (HR 5.82). Conclusion This study provides evidence of association between sarcopenia and incidence of MACE in a population of CHF. Early detection and treatment are imperative to improve patient outcomes. SGLT2i reduced the composite endpoint of non-fatal stroke, non-fatal coronary event and cardiovascular death due to CHF by 89%. Total mortality was also reduced.