Abstract
Brain natriuretic peptide (BNP) levels are increased in both patients with heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF), but the reasons for this remain unclear. Our purpose was to examine whether serum-induced BNP (iBNP) expression partly contributes to increased BNP in patients with HFpEF. BNP reporter cardiomyocytes from pBNP-luc-KI mice were stimulated with serum from patients with HFpEF or HFrEF (n = 114 and n = 82, respectively). Luciferase activity was examined as iBNP and the iBNP-to-BNP ratio was evaluated. Patient characteristics and clinical parameters were compared, and multivariate regression analysis was performed to determine independent predictors of the iBNP-to-BNP ratio. Female sex and frequencies of atrial fibrillation, hypertension and the use of a calcium channel blocker (CCB) were higher in HFpEF. The iBNP-to-BNP ratio was significantly higher in HFpEF (26.9) than in HFrEF (16.1, p < 0.001). Multivariate regression analysis identified the existence of HFpEF as an independent predictor of the iBNP-to-BNP ratio after adjusting for all other measurements (β = 0.154, p = 0.032). Age, hemoglobin, CCB usage and deceleration time were also independent predictors (β = 0.167, p = 0.025; β = 0.203, p = 0.006; β = 0.138, p = 0.049; and β = 0.143, p = 0.049, respectively). These results indicate that the elevated BNP in patients with HFpEF is partly due to iBNP from the heart.
Highlights
Introduction iationsThe number of patients with heart failure with preserved ejection fraction (HFpEF) is increasing, representing a growing burden as a health problem around the world [1,2]
Significant differences between groups were observed in sex, systolic and diastolic blood pressures, heart rate, left ventricular ejection fraction (LVEF), Brain natriuretic peptide (BNP), number of hospitalizations for HF during the past 12 months, and prevalences of atrial fibrillation, coronary artery disease, hypertension, chronic kidney disease, diabetes mellitus, ever-smoker status, and uses of medications including angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB), beta-blocker, calcium channel blockers (CCB), mineralocorticoid receptor antagonists (MRA) and diuretic
RV5 + SV1 from electrocardiography, interventricular septal wall thickness, posterior wall thickness, LVEF, A wave, and deceleration time of mitral E-wave velocity from echocardiography were significantly higher in the HFpEF group than in the HF with reduced ejection fraction (HFrEF) group
Summary
The number of patients with heart failure with preserved ejection fraction (HFpEF) is increasing, representing a growing burden as a health problem around the world [1,2]. Prognosis is poor for patients with HFpEF, similar to that of patients with HF with reduced ejection fraction (HFrEF) [1,3]. Neurohormonal antagonists, including angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB), mineralocorticoid receptor antagonists (MRA), beta-blockers and angiotensin receptor neprilysin inhibitors (ARNI). Have been shown to improve survival and hospitalization in patients with HFrEF. All these agents have failed to improve mortality in patients with HFpEF [3–5]. The trials of sodium/glucose cotransporter 2 inhibitors (SGLT2i) for the treatment of HFpEF are ongoing [6]. Pathological mechanisms underlying HFpEF should be clarified and new agents and/or devices to improve the prognosis of HFpEF developed [7]
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