Monitoring SGLT2 inhibition effectiveness on pulmonary systolic pressure in heart failure with reduced ejection fraction

Background and aims: Pulmonary hypertension (pH) and right ventricular (RV) dysfunction worsen outcomes in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2-I) may influence pulmonary hemodynamics, yet their combined effects on tricuspid regurgitation velocity (TRV) and RV function remain matter of interest. We sought to evaluate the effects of ARNI alone versus ARNI+SGLT2-I on TRV, pH echocardiographic probability, and RV remodeling in HFrEF patients. Methods: This single-center observational study involved outpatients with HFrEF receiving optimal medical treatment (OMT), either with ARNI alone or a combination of ARNI+ SGLT2-I. Baseline and 12-month echocardiographic assessments included TRV, RV function parameters (TAPSE, FAC), and PH probability. Clinical outcomes were tracked for heart failure-related hospitalizations and mortality. Results: 179 HFrEF outpatients starting ARNI on top of OMT were included, with 58 receiving additional SGLT2-I. At follow-up, TRV significantly decreased in the ARNI+SGLT2-I group (from 276 ± 36 to 241 ± 46 cm/s, p = 0.0003) but not in the ARNI group. High PH probability declined from 23 % to 5 % (p < 0.001) in the ARNI+SGLT2-I group, with no significant change in the ARNI group. RV function improved significantly in the combination group (from 47 % to 19 %; p = 0.003) with greater TAPSE/sPAP and FAC increases (p = 0.03 and p = 0.01, respectively). Conclusions: Combining SGLT2-I with ARNI was associated with a specific modulating effect on TRV, improved RV coupling, and enhanced symptom relief compared to ARNI alone. These findings support the hypothesis that pulmonary vascular disease may be targeted by SGLT2-I, overall impacting on pulmonary hemodynamics and RV remodeling.