Abstract 17725: Prognostic Implications and the Impact of Empagliflozin on Bone Morphogenetic Protein-10 in Heart Failure: Results from the EMPEROR Program

Abstract

Background: Bone morphogenetic protein (BMP)-10 is upregulated in response to cardiac injury and exerts a protective role via activating transforming growth factor β/Smad and STAT3-pathways preserving normal cardiac function by inhibiting cell death and fibrosis. Aim: To assess association of baseline characteristics and prognostic significance of BMP-10 in patients with heart failure (HF) with reduced or preserved ejection fraction, and the effect of empagliflozin on BMP-10 level. Methods: Serum BMP-10 (Elecsys®, Roche Diagnostics) was assessed in 1127 patients from the EMPEROR-Reduced and Preserved trials, categorized by tertiles of baseline BMP-10 (<2.35; ≥2.35-<3.11; ≥3.11 ng/mL). Results: Median baseline BMP-10 was 2.71 ng/mL. Patients in higher tertiles tended to be older, women, NYHA class III-IV, with obesity, atrial fibrillation, and worse renal function (all P<0.05). Baseline BMP-10 level correlated with N-terminal pro B-type natriuretic peptides and high-sensitivity troponin T levels (Spearman rho=0.41, 0.26 respectively). Higher baseline BMP-10 was associated with increased risk for adverse outcomes ( Table 1 ). For each 2-fold increase in BMP-10, the adjusted hazard ratio (HR) for cardiovascular death (CV) or HF hospitalization was 2.85 (95% CI 1.99, 4.09, P<0.0001). Empagliflozin treatment was associated with reduction in BMP-10 at week 12 (adjusted gMean ratio 0.94 [0.91-0.97], P<0.001) but not week 52 (1.00 [0.96-1.04], P=0.86). Empagliflozin reduced the risk of CV death or HF hospitalization, particularly for patients at highest baseline BMP-10 level (<1 st tertile HR 1.03 [0.56-1.88]; ≥1 st and <2 nd tertile HR 0.74 [0.40-1.35]; ≥2 nd tertile HR 0.61 [0.40-0.92], P-trend=0.15). Conclusion: BMP-10 levels were associated with worse disease severity and outcomes in patients with HF. Empagliflozin was associated with reduction of BMP-10 at week 12. The benefit of empagliflozin on outcomes was more pronounced with higher BMP-10 levels.