Echocardiographically defined haemodynamic categorization predicts prognosis in ambulatory heart failure patients treated with sacubitril/valsartan

Aim Echo-derived haemodynamic classification, based on forward-flow and left ventricular (LV) filling pressure (LVFP) corre- lates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prog- nostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. Methods and results In our multicentre, open-label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m 2 ) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e′: ≥ or <15): Profile-A: normal-flow, normal-pressure; Profile-B: low-flow, normal-pressure; Pro- file-C: normal-flow, high-pressure; Profile-D: low-flow, high-pressure. Patients were started on sacubitril/valsartan and followed-up for 12.3 months (median). Rates of the composite of death/HF-hospitalization were assessed by multivariable Cox proportional-hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile-D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile-A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event-rate (per 100 patients per year) progressively increased from Profile-A to Profile-D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariate- adjusted Cox model, profiles with low forward-flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC-score and natriuretic peptides, provided significant continuous net reclassification improve- ment (0.329; P < 0.001). Intermediate and high-dose sacubitril/valsartan reduced the event’s risk independently of haemodynamic profile. Conclusions Echocardiographically-derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real-world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemody- namic profiles.