Abstract
AIMS: Despite well-established benefits of sacubitril/valsartan for cardiac reverse remodelling and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), there are some patients with limited therapeutic response, even with optimal therapy. We assessed the treatment response to sacubitril/valsartan in patients with HFrEF, focusing on the association between reverse remodelling and the prognosis. METHODS AND RESULTS: Using a retrospective cohort of consecutive patients with HFrEF treated with sacubitril/valsartan, we compared the time trajectory of cardiac function in 415 patients (1258 echocardiograms), according to the occurrence of cardiovascular death and hospitalization for HF during a median follow-up of 19.1 (interquartile range, 10.9-27.6) months. A higher sacubitril/valsartan dose was associated with a better prognosis, whereas advanced age, diabetes, left ventricular (LV) hypertrophy, left atrial enlargement, and pulmonary hypertension were associated with a worse prognosis. Patients without an event (n = 337; 81.2%) showed LV reverse remodelling (LV ejection fraction ≥45% or LV end-systolic volume reduction by 15% from baseline), which was typically observed within 6 months of sacubitril/valsartan treatment. Reverse remodelling achievement was significantly associated with a better prognosis. However, patients without reverse remodelling had a worse prognosis, as poor as that in patients with HFrEF not treated with sacubitril/valsartan. CONCLUSIONS: In patients with HFrEF treated with sacubitril/valsartan, LV reverse remodelling reflects the treatment response and predicts the prognosis, whereas a lack of reverse remodelling indicates the lack of treatment benefits. Prediction and assessment of reverse remodelling may facilitate the selection of patients with greater benefits by sacubitril/valsartan.