Combined ARNI and SGLT2i impacts on peak tricuspid regurgitant velocity and echocardiographic probability of pulmonary hypertension

Abstract Background In heart failure with reduced ejection fraction (HFrEF), the development of pulmonary hypertension (PH) is associated with poor prognosis. Recent medical advancements have substantially improved both survival rates and HF hospitalization. However, the impact of combining angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) on peak tricuspid regurgitant velocity (TRV) and PH echocardiographic probability remains unexplored. Purpose We aimed to evaluate the effect of ARNI alone versus ARNI combined with SGLT2i on peak TRV and PH probability in a real-life population of outpatients with HFrEF. Methods This was an observational monocentric study including patients treated with either ARNI alone or with SGLT2i on top of ARNI. Echocardiographic examinations were performed by fully accredited operators and all parameters were analysed offline by expert operators blinded to clinical data. We performed echocardiographic evaluation in all patients before initiating treatment and at 12 months follow-up. We excluded patients who discontinued ARNI within 6 months of introduction and those who did not complete at least 6 months of follow-up with both drugs. Results 80 HFrEF patients were included, 41 receiving ARNI+SGLT2i and 39 receiving ARNI alone. Baseline mean peak TRV was similar between the two groups (280±44 cm/s and 259±48 cm/s respectively, p=0.09). At follow-up, mean peak TRV was 232±32 cm/s in ARNI+SGLT2i group and 258±45 cm/s in ARNI alone group (p=0.02). The decrease in peak TRV was significant in ARNI+SGLT2i group, p=0.0004 (Table). At baseline the echocardiographic probability of PH was comparable between both groups, p=0.53 (Figure). Nevertheless, during follow-up, the proportion of patients with high probability of PH decreased in the ARNI+SGLT2i group (from 22% to 2%), while in the ARNI alone group it did not change (Figure). Conclusions In HFrEF the combination of ARNI+SGLT2i demonstrates high effectiveness in TRV reduction, downgrading PH probability class. In our population, this evidence is primarily driven by the decrease TRV. These results may suggest the positive effect of SGLT2i on pulmonary vascular remodelling and right heart hemodynamic worth of full investigation in further studies aimed at targeting left-sided PH and its prevention strategies.