SGLT-2 inhibitors in moderate-to-severe functional mitral regurgitation: a meta-analysis of randomized controlled trials
F Stabile, M Dandamudi, S Jaramillo, B Hakkeem, J Khater, L A de Lucena, N Schettino Samad, M Nino Lopez, C Madaudo, D Di Lisi, G Vadala, V Sucato, E Corrado, A R Galassi, G NovoAbstract
Background
Functional mitral regurgitation (FMR) is associated with adverse outcomes, including heart failure hospitalizations (HFH) and mortality. Despite guideline-directed medical therapy (GDMT), patients with moderate-to-severe FMR often have poor prognosis. While sodium–glucose cotransporter-2 inhibitors (SGLT2i) are established in GDMT for HF with reduced (HFrEF), mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction, their impact on FMR is unclear. We aimed to perform a systematic review and meta-analysis to assess whether adding SGLT2i to GDMT reduces FMR severity and improves outcomes in patients with HFrEF or HFmrEF.
Methods
PubMed, Scopus, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing SGLT2i versus placebo in patients with moderate-to-severe FMR and HF on GDMT. Echocardiographic outcomes included effective regurgitant orifice area (EROA), regurgitant volume (RVol), and left ventricular ejection fraction (LVEF), while clinical outcomes were cardiovascular (CV) mortality and HFH. Pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs) were calculated using a random-effects model.
Results
Three RCTs including 472 patients were analyzed, of whom 275 (58%) received SGLT2i. Compared with placebo, SGLT2i was associated with significant reduction in EROA (MD –0.09 cm²; 95% CI –0.15 to –0.02; p=0.008) and RVol (MD –10.89 mL; 95% CI –17.34 to –4.44; p=0.0009), and increase in LVEF (MD +3.59%; 95% CI 1.12–6.06; p=0.004). Clinically, SGLT2i were associated with fewer HFH (RR 0.45; 95% CI 0.28–0.73; p=0.001) and reduced CV mortality (RR 0.26; 95% CI 0.12–0.57; p=0.0008).
Conclusion
In patients with moderate-to-severe FMR and HF, SGLT2i on top of GDMT was associated with significant improvements in MR severity and LVEF, together with a significant reduction in HFH and CV mortality.EROA+RVOLHFH+CV MORTALITY