Abstract Body (Do not enter title and authors here): Background: Sacubitril/valsartan (Sac/Val) has been shown to reduce N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with acute heart failure (AHF), yet the therapeutic response may differ according to underlying cardiac phenotype.
Hypothesis: We hypothesized that specific baseline echocardiographic parameters may modify the NT-proBNP-lowering effect of Sac/Val in this population.
Aims: This study aimed to explore whether baseline echocardiographic markers could identify patients with AHF, who will experience greater reductions in NT-proBNP following Sac/Val therapy.
Methods: This was a sub-analysis of the multicenter, physician-initiated, prospective, randomized, open-label PREMIER study (NCT05164653), in which the clinical effects of early initiation of Sac/Val, compared to the standard renin-angiotensin system inhibitor therapy (control), were evaluated in Japanese inpatients stabilized after hospitalization for AHF. Participants were stratified according to echocardiographic characteristics at baseline, including LVEDVI, LVESVI, LVMI, LVOT-VTI, E/e′, LAVI, and TRV. The proportional change in geometric mean NT-proBNP from baseline to 8 weeks was compared between the Sac/Val and control groups within each stratum.
Results: Among 206 patients with echocardiographic data (median age, 76 years; 31% female; median left ventricular ejection fraction, 39%), 94 were assigned to the sacubitril/valsartan (Sac/Val) group and 112 to the control group. Overall, Sac/Val treatment led to a significantly greater reduction in NT-proBNP than control (group ratio 0.75; 95% CI, 0.60 to 0.93). Among the echocardiography-based subgroups, the treatment effect was more evident in subgroups with elevated LVMI (LVMI ≥123.7 g/m²; group ratio, 0.56; 95% CI, 0.40 to 0.77) and reduced LVOT-VTI (LVOT-VTI <13 cm; group ratio, 0.59; 95% CI, 0.43 to 0.80), compared to each corresponding counterpart (P for interaction = 0.009 and 0.045, respectively) (Figure). In contrast, no significant between-group differences in the treatment effect were observed in subgroups stratified by other echocardiographic parameters (all P for interaction >0.1).
Conclusions: Baseline LVMI and LVOT-VTI values may help identify the optimal patients who derive greater benefit from early initiation of Sac/Val therapy after an AHF episode, supporting a phenotype-guided approach to individualized treatment in this population.