Frontiers in Cardiovascular Medicine (Jul 2022)

Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium

  • Uwe Primessnig,
  • Uwe Primessnig,
  • Uwe Primessnig,
  • Peter M. Deißler,
  • Peter M. Deißler,
  • Paulina Wakula,
  • Paulina Wakula,
  • Khai Liem Tran,
  • Khai Liem Tran,
  • Felix Hohendanner,
  • Felix Hohendanner,
  • Felix Hohendanner,
  • Dirk von Lewinski,
  • Florian Blaschke,
  • Florian Blaschke,
  • Christoph Knosalla,
  • Christoph Knosalla,
  • Volkmar Falk,
  • Volkmar Falk,
  • Volkmar Falk,
  • Burkert Pieske,
  • Burkert Pieske,
  • Burkert Pieske,
  • Burkert Pieske,
  • Herko Grubitzsch,
  • Herko Grubitzsch,
  • Frank R. Heinzel,
  • Frank R. Heinzel

DOI
https://doi.org/10.3389/fcvm.2022.859014
Journal volume & issue
Vol. 9

Abstract

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BackgroundAlthough 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 ResultsRight 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).ConclusionBNP 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.

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