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SHR Neuro Cancer Cardio Lipid Metab Microb
Primessnig, U; Deißler, PM; Wakula, P; Tran, KL; Hohendanner, F; von, Lewinski, D; Blaschke, F; Knosalla, C; Falk, V; Pieske, B; Grubitzsch, H; Heinzel, FR.
Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium.
FRONT CARDIOVASC MED. 2022; 9: 859014
Doi: 10.3389/fcvm.2022.859014
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- Leading authors Med Uni Graz
- Heinzel Frank
- Primessnig Uwe
- Co-authors Med Uni Graz
- Hohendanner Felix
- Pieske Burkert Mathias
- von Lewinski Dirk
- Wakula-Heinzel Paulina
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- Abstract:
- Background: Although the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan started a new era in heart failure (HF) treatment, less is known about the tissue-level effects of the drug on the atrial myocardial functional reserve and arrhythmogenesis. Methods and Results: Right atrial (RA) biopsies were retrieved from patients (n = 42) undergoing open-heart surgery, and functional experiments were conducted in muscle strips (n = 101). B-type natriuretic peptide (BNP) did not modulate systolic developed force in human myocardium during β-adrenergic stimulation, but it significantly reduced diastolic tension (p < 0.01) and the probability of arrhythmias (p < 0.01). In addition, patient's plasma NTproBNP positively correlated with isoproterenol-induced contractile reserve in atrial tissue in vitro (r = 0.65; p < 0.01). Sacubitrilat+valsartan (Sac/Val) did not show positive inotropic effects on atrial trabeculae function but reduced arrhythmogeneity. Atrial and ventricular biopsies from patients with end-stage HF (n = 10) confirmed that neprilysin (NEP) is equally expressed in human atrial and ventricular myocardium. RA NEP expression correlates positively with RA ejection fraction (EF) (r = 0.806; p < 0.05) and left ventricle (LV) NEP correlates inversely with left atrial (LA) volume (r = -0.691; p < 0.05). Conclusion: BNP ameliorates diastolic tension during adrenergic stress in human atrial myocardium and may have positive long-term effects on the inotropic reserve. BNP and Sac/Val reduce atrial arrhythmogeneity during adrenergic stress in vitro. Myocardial NEP expression is downregulated with declining myocardial function, suggesting a compensatory mechanism in HF.
- Find related publications in this database (Keywords)
- BNP
- sacubitrilat
- valsartan (Sac
- Val)
- atrial function
- arrhythmias
- heart failure
- neprilysin
- sacubitril
- valsartan