Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect.

To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome.

In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/m²) were combined to determine 4 hemodynamic profiles: profile-A (normal-flow/normal-pressure); profile-B (low-flow/normal-pressure); profile-C: (normal-flow/high-pressure); profile-D: (low-flow/high-pressure). Changes among categories were recorded, and their associations with rates of the composite of death/HF-hospitalization were assessed by multivariable Cox analysis.

At baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P < 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4–16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0–37.3) or worsened (31.2%, 20.7–46.9, P < 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45–0.95, P < 0.05).

In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.