Heart Failure and Tricuspid Regurgitation: The Role of SGLT2 Inhibitors in Improving Outcomes

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 categorized by baseline TR severity (significant: ≥moderate vs. non-significant) and further stratified by SGLT2 inhibitor use at follow-up initiation. 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 years (IQR: 1–7), 17,696 (61%) patients experienced the composite outcome. Significant TR was associated with a 67% and 20% increased risk of death or HF hospitalization in univariate and multivariate models, respectively (95% CI: 1.60–1.74 and 1.14–1.26, both p<0.001). SGLT2 inhibitor use was linked to a >50% reduction in composite outcome risk across the cohort, with no significant difference between patients with or without significant TR (HR 0.43 vs. 0.49, p for interaction = 0.7). Time-dependent analyses for TR and SGLT2 inhibitor use yielded consistent results.

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.