Pulmonary pressure-flow responses to exercise in heart failure treated with angiotensin receptor neprilysin inhibitor

Background: The role of the angiotensin receptor neprilysin inhibitor (ARNI) in cardiac function, particularly its impact on pulmonary circulation, remains underexplored. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (CO) responses as having the potential to assess the disease state. The aim of this study was to assess the effects of ARNI on pulmonary circulation in heart failure. We measured echocardiographic parameters post 6-min walk (6 MW) and compared the changes with baseline and follow-up. Our hypothesis was that pulmonary pressure-flow relationship of the pulmonary circulation obtained by 6 MW stress echocardiography would be improved with treatment. Methods: We prospectively enrolled 39 heart failure patients and conducted the 6 MW test indoors. Post-6 MW echocardiography measured echocardiographic variables, and CO was derived from electric cardiometry. Individualized ARNI doses were optimized, with follow-up echocardiographic evaluations after 1 year. Results: Left ventricular (LV) volume were significantly reduced (160.7 +/- 49.6 mL vs 136.0 +/- 54.3 mL, P < 0.001), and LV ejection fraction was significantly improved (37.6 +/- 11.3% vs 44.9 +/- 11.5%, P < 0.001). Among the 31 patients who underwent 6 MW stress echocardiographic study at baseline and 1 year later, 6 MW distance increased after treatment (380 m vs 430 m, P = 0.003). The Delta mPAP/Delta CO by 6 MW stress decreased with treatment (6.9 mmHg/L/min vs 2.8 mmHg/L/min, P = 0.002). The left atrial volume index was associated with the response group receiving ARNI treatment for pulmonary circulation. Conclusions: Initiation of ARNI was associated with improvement of left ventricular size and LVEF. Additionally, the 6 MW distance increased and the Delta mPAP/Delta CO was improved to within normal range with treatment.