Reverse Remodelling by Sacubitril/Valsartan Predicts the Prognosis in Heart Failure with Reduced Ejection Fraction

Figures

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  Figure 1. Study population flow chart. The study population, comprised 415 patients with HFrEF treated with ARNI (sacubitril/valsartan cohort), were matched to patients in a separate HF registry (STRATS‐AHF registry). 5 , 6 Patients with follow‐up echocardiography within 6 months (n = 289) and 12 months (n = 371) of ARNI treatment initiation were also matched. In the STRATS‐AHF registry, 1178 patients with HFrEF without sacubitril/valsartan treatment were identified for 1:1 propensity score matching. EF, ejection fraction; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular.

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  Figure 2. Trajectories of cardiac function and NT‐proBNP level in patients with HFrEF treated with sacubitril/valsartan. Serial measurements of (A) LV‐EDVi, (B) LV‐ESVi, (C) LV‐EF, (D) mitral E/e′ ratio, (E) LAVI, and (F) NT‐proBNP level are shown according to the occurrence of the study outcome (cardiovascular death or HHF). Measurements in patients without an outcome event are shown in blue dots with spline curves; those in patients with an outcome event are shown in red dots with spline curves; and those in the matched control group are shown in green dots with spline curves. EDVi, end‐diastolic volume index; EF, ejection fraction; ESVi, end‐systolic volume index; HFrEF, heart failure with reduced ejection fraction; LAVI, left atrial volume index; LV, left ventricular; NT‐proBNP, N‐terminal pro B‐type natriuretic peptide.

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  Figure 3. Changes in the severity of MR. The severity of MR was assessed at baseline (before ARNI treatment) and at last echocardiography (after ARNI treatment), according to the occurrence of outcome events. In patients without an outcome event, the severity of MR was decreased after ARNI treatment, whereas the patients with an outcome event did not show reduction in MR amount. Notably, the prevalence of severe MR was further increased in patients who experienced an outcome event. MR, mitral regurgitation.

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  Figure 4. Survival curves according to the achievement of LV reverse remodelling. Event‐free survival curves according to the occurrence of LV reverse remodelling (A) within 6 months and (B) 12 months of sacubitril/valsartan treatment initiation are shown. Landmark analyses counting the outcome events after the determination of LV reverse remodelling (C) within 6 months and (D) within 12 months of treatment initiation are also shown. Survival curves of patients who achieved LV reverse remodelling are shown in blue, and those without LV reverse remodelling are shown in red. The overall survival in the study population was compared to that for propensity‐score matched patients with HFrEF who were not treated with sacubitril/valsartan (green colour), identified from a separate registry (STRATS‐AHF registry). 5 , 6 CI, confidence interval; HR, hazard ratio; LV, left ventricular.

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  Figure 5. Subgroup analyses for LV reverse remodelling within 12 months of treatment initiation. The adjusted HRs are shown for the composite of CV death or HHF in subgroups based on clinical features and LV‐EF. Using propensity‐score matched patients with HFrEF without ARNI treatment as a reference (green), the HRs of patients treated with ARNI who did (blue) and did not (red) achieve reverse remodelling within 12 months are summarized. Comparisons between patients with and without reverse remodelling, and P‐values for the interaction, are also shown in the rightmost column of the table. BP, blood pressure; CI, confidence interval; CV, cardiovascular; GFR, glomerular filtration rate; HHF, hospitalization for heart failure; HR, hazard ratio; LV‐EF, left ventricular ejection fraction.