Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium
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 (R...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.859014/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Uwe Primessnig |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T14:09:34Z |
| format | Article |
| id | doaj.art-3ab69dbeaf1246f5a94ad8f0519b684f |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-13T14:09:34Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-3ab69dbeaf1246f5a94ad8f0519b684f2022-12-22T02:43:49ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-07-01910.3389/fcvm.2022.859014859014Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human MyocardiumUwe Primessnig0Uwe Primessnig1Uwe Primessnig2Peter M. Deißler3Peter M. Deißler4Paulina Wakula5Paulina Wakula6Khai Liem Tran7Khai Liem Tran8Felix Hohendanner9Felix Hohendanner10Felix Hohendanner11Dirk von Lewinski12Florian Blaschke13Florian Blaschke14Christoph Knosalla15Christoph Knosalla16Volkmar Falk17Volkmar Falk18Volkmar Falk19Burkert Pieske20Burkert Pieske21Burkert Pieske22Burkert Pieske23Herko Grubitzsch24Herko Grubitzsch25Frank R. Heinzel26Frank R. Heinzel27Department of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyBerlin Institute of Health (BIH), Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyBerlin Institute of Health (BIH), Berlin, GermanyDepartment of Cardiology, Medical University of Graz, Graz, AustriaDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDepartment of Cardiothoracic and Vascular Surgery, German Heart Institute Berlin, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDepartment of Cardiothoracic and Vascular Surgery, German Heart Institute Berlin, Berlin, GermanyDepartment of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyBerlin Institute of Health (BIH), Berlin, GermanyDepartment of Internal Medicine and Cardiology, German Heart Center Berlin, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyDepartment of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, GermanyDepartment of Internal Medicine and Cardiology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDZHK (German Centre for Cardiovascular Research), Berlin, GermanyBackgroundAlthough 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.https://www.frontiersin.org/articles/10.3389/fcvm.2022.859014/fullBNPsacubitrilat/valsartan (Sac/Val)atrial functionarrhythmiasheart failureneprilysin |
| spellingShingle | 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 Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium Frontiers in Cardiovascular Medicine BNP sacubitrilat/valsartan (Sac/Val) atrial function arrhythmias heart failure neprilysin |
| title | Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium |
| title_full | Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium |
| title_fullStr | Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium |
| title_full_unstemmed | Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium |
| title_short | Effects of BNP and Sacubitrilat/Valsartan on Atrial Functional Reserve and Arrhythmogenesis in Human Myocardium |
| title_sort | effects of bnp and sacubitrilat valsartan on atrial functional reserve and arrhythmogenesis in human myocardium |
| topic | BNP sacubitrilat/valsartan (Sac/Val) atrial function arrhythmias heart failure neprilysin |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.859014/full |
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