Background: Sacubitril/Valsartan (S/V) reduces the risk of cardiovascular mortality and heart failure (HF) hospitalisations in patients with HF and reduced ejection fraction. Information on the underlying hemodynamic effects of S/V, especially on left ventricular (LV) contractility, is still lacking.

Methods: We prospectively included consecutive patients with symptomatic HF and LV ejection fraction (EF) ≤40% in whom treatment with S/V was initiated. Non-invasive pressure volume loops were obtained from echocardiography with simultaneous arm-cuff blood pressure measurements. The primary endpoint was the change in LV end systolic elastance (Ees), effective arterial elastance (Ea) and the ventricular-arterial coupling (Ea/Ees) after six months of treatment with S/V. Here, we present the prespecified interim analysis of 50 patients with completed 3 and 6 months follow-up. The study is registered with ClinicalTrials.gov, NCT04498780.

Results: 38 of the 50 patients were females, mean age was 61.8 ±18.6 years. Ischaemic heart failure was present in 22 (44%), non-ischaemic aetiology in 24 (48%), and myocarditis in 4 (8%) patients. At six months, 34 (68%) patients were on the target dose of S/V. The percentage of patients with NYHA class III changed from 20% (n=10) to 8% (n=4), p<0.001. Median NT-proBNP level decreased from 2398 pg/ml (interquartile range (IQR), 1185-6034) to 813 pg/ml (IQR 299-1971, p<0.001). LV end-systolic elastance (Ees), arterial elastance (Ea) and the ventricular-arterial coupling ratio Ea/Ees remained similar at 6 months of follow-up compared to baseline (p=ns). LV end-diastolic volume (110±28 ml/m^{2 vs. 87±31 ml/m2, p<0.0001) and end-systolic volume (78±26 ml/m2 vs. 52±26 ml/m2, p<0.0001) were reduced, hence mean LVEF increased (30±7 % vs. 42±11%, p<0.0001). LV end diastolic pressure was significantly reduced (21±3.9 mmHg vs. 18±2.7 mmHg, p<0.0001).}

Conclusion: In heart failure patients with reduced ejection fraction, treatment with Sacubitril/Valsartan leads to reverse LV remodelling and reduced filling pressures while LV contractility and afterload did not change significantly.