Heart failure and tricuspid regurgitation: the role of SGLT2 inhibitors in improving outcomes

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors have revolutionized heart failure (HF) management. While tricuspid regurgitation (TR) significantly affects HF prognosis, the role of SGLT2 inhibitors in improving outcomes in HF patients with concomitant TR remains unexplored. Methods This study included HF patients who underwent echocardiographic evaluation within 90 days of diagnosis. Patients were stratified by TR severity (significant: ≥moderate vs. non-significant) and the use of SGLT2 unhibitors at baseline and during follow-up. Baseline differences were adjusted using inverse probability treatment weighting. The primary outcome was a composite of all-cause mortality and HF hospitalizations. Results Among 28,940 HF patients (median age 75 IQR: 66–83, 43% women), 4,043 (14%) had significant TR, and 2,320 (8%) used SGLT2 inhibitors at baseline. During a median follow-up of 3.5 years (IQR: 1–7), 17,696 (61%) patients experienced the composite outcome. Significant TR was associated with a 67% increased risk in univariate analysis and a 20% higher risk in multivariate analysis (HR 1.67 95% CI: 1.60–1.74, p0.001 and HR 1.20 95% CI: 1.14–1.26, p0.001, respectively). SGLT2 inhibitors use was linked to a risk reduction of more than twofold for HF hospitalization and mortality, after adjusting for age, sex, comorbidities, echocardiographic parameters, and the use of other guideline-directed medical therapy for HF (HR 0.24 95% CI 0.15–0.36, p0.001 for HF hospitalization and HR 0.46 95% CI 0.40-0.54, p0.001 for mortality). Importantly, this benefit remained consistent across TR severity (HR 0.43 vs. 0.49, p for interaction=0.7). Time-dependent analyses confirmed similar results (HR 0.80 95% CI: 0.70–0.92, p=0.002 for non-significant TR and HR 0.78 95% CI: 0.64–0.95, p=0.014 for significant TR; p for interaction=0.6). Conclusions Baseline TR independently predicts worse outcomes in HF patients. This study is the first to show that SGLT2 inhibitors significantly reduce adverse outcomes in HF patients regardless of TR severity, further establishing their role as transformative prognostic agents.