The Impact of SGLT2 Inhibitors on Pulmonary Artery Pressures and Pulmonary Hemodynamics in Patients With Heart Failure: A Systematic Review.

BACKGROUND

Heart failure is a major global health burden associated with high morbidity and mortality. Elevated pulmonary artery pressures (PAP) are linked to worse outcomes in heart failure patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for diabetes, have demonstrated cardiovascular benefits, but their specific effects on pulmonary hemodynamics remain unclear.

METHODS

This systematic review analyzed randomized controlled trials and observational cohort studies evaluating the effects of SGLT2 inhibitors on mean pulmonary artery pressure (mPAP) and pulmonary artery systolic pressure (PASP) in heart failure patients. A comprehensive search of PubMed, Embase, Cochrane Library, and Scopus databases was conducted until August 2024. Studies were appraised using PRISMA and AMSTAR guidelines, the Cochrane bias tool, and the Newcastle-Ottawa Scale.

HYPOTHESIS: SGLT2 inhibitors reduce PAPs in heart failure patients, leading to beneficial pulmonary hemodynamic effects.

RESULTS

Six studies (four RCTs and two observational; n = 346) were included. At rest, pooled analysis of three trials showed a significant reduction in mPAP (MD -1.41 mmHg; 95% CI -2.80 to -0.01; p = 0.05; I 2 = 12%). During exercise, two studies demonstrated a nonsignificant reduction in mPAP (MD -3.12 mmHg; 95% CI -7.60 to 1.36; p = 0.17; I 2 = 54%). For PASP, pooled analysis of four studies suggested a nonsignificant reduction (MD -6.72 mmHg; 95% CI -14.98 to 1.54; p = 0.11; I 2 = 96%), but sensitivity analysis excluding one outlier yielded a significant effect (MD -2.76 mmHg; 95% CI -4.99 to -0.53; p = 0.02; I 2 = 0%). Secondary outcomes included significant reductions in PCWP, PADP, and NT-proBNP.

CONCLUSION

SGLT2 inhibitors demonstrate beneficial effects on pulmonary pressures and hemodynamics in patients with heart failure, with consistent trends toward lower mPAP, PASP, and PCWP. Although results are influenced by study heterogeneity, the overall evidence suggests meaningful hemodynamic improvements. Larger, long-term randomized trials are warranted to clarify subgroup effects (HFrEF vs. HFpEF and dapagliflozin vs. empagliflozin) and establish clinical implications.