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

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 ( = 42) undergoing open-heart surgery, and functional experiments were conducted in muscle strips ( = 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 ( < 0.01) and the probability of arrhythmias ( < 0.01). In addition, patient's plasma NTproBNP positively correlated with isoproterenol-induced contractile reserve in atrial tissue ( = 0.65; < 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 ( = 10) confirmed that neprilysin (NEP) is equally expressed in human atrial and ventricular myocardium. RA NEP expression correlates positively with RA ejection fraction (EF) ( = 0.806; < 0.05) and left ventricle (LV) NEP correlates inversely with left atrial (LA) volume ( = -0.691; < 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 . Myocardial NEP expression is downregulated with declining myocardial function, suggesting a compensatory mechanism in HF.