Abstract 12972: Serum-induced Expression of Brain Natriuretic Peptide Contributes to its Increase in Patients With HFpEF

Abstract

Introduction: Brain natriuretic peptide (BNP) levels are relatively higher in patients with heart failure with preserved ejection fraction (HFpEF) than heart failure with reduced ejection fraction (HFrEF); however, the mechanism remains unclear. BNP is induced by undetermined stretch-activated receptors including mechanically gated channels, which can be activated by a mechanical stimulus alone, and mechanically modulated channels, which require nonmechanical stimuli such as agonists. Thus it is possible that serum-induced expression of BNP may contribute to the increase of BNP in patients. Purpose: Our purpose is to examine whether serum-induced BNP expression (iBNP) partly contributes to the increase in BNP in patients with HFpEF. Methods: We generated the BNP reporter mice by knocking luciferase cDNA in the initiation site of NPPB . Neonatal cardiomyocytes were isolated and cultured from 2-day-old neonates. These cardiomyocytes were stimulated for 24 hours with 20% serum from patients with HFpEF or HFrEF (n=114 and 82, respectively) and the luciferase activity was examined as iBNP and the ratio of iBNP to BNP was measured. The patients’ characteristics and clinical parameters were compared and multivariate regression analysis was performed using SPSS version 25. Results: The mean ages were 71 yrs in HFpEF and 67 yrs in HFrEF. The female gender was higher in HFpEF (46% vs 32%). The prevalence of atrial fibrillation and hypertension and the use of calcium channel blocker (CCB) were higher in HFpEF than in HFrEF (31 vs 17%, 66 vs 43%, 28 vs 18%). The prevalence of coronary artery disease, chronic kidney disease and diabetes mellitus were lower in HFpEF than HFrEF (21 vs 42%, 44 vs 74%, 25 vs 44%). The ratio of iBNP to BNP was significantly higher in HFpEF than in HFrEF (26.9 vs 16.1, P<0.001). Multivariate regression analysis showed the existence of HFpEF was an independent predictor for the ratio of iBNP to BNP after adjusting all other measurements (β=0.154, P=0.032). Age, hemoglobin, the use of CCB and the deceleration time were also independent predictors (β=0.167, P=0.025; β=0.203, P=0.006; β=0.138, P=0.049; β=0.143, P=0.049, respectively). Conclusions: These results indicate the elevation of BNP in patients with HFpEF is partly due to the iBNP from heart.