RT Journal Article
SR Electronic
T1 β-Adrenergic blockade combined with subcutaneous B-type natriuretic peptide: a promising approach to reduce ventricular arrhythmia in heart failure?
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 833
OP 841
DO 10.1136/heartjnl-2013-305167
VO 100
IS 11
A1 Jérôme Thireau
A1 Sarah Karam
A1 Stéphanie Roberge
A1 Julien Roussel
A1 Franck Aimond
A1 Cécile Cassan
A1 Arnaud Gac
A1 Dominique Babuty
A1 Jean-Yves Le Guennec
A1 Alain Lacampagne
A1 Jérémy Fauconnier
A1 Sylvain Richard
YR 2014
UL http://heart.bmj.com/content/100/11/833.abstract
AB Aims Clinical studies failed to prove convincingly efficiency of intravenous infusion of neseritide during heart failure and evidence suggested a pro-adrenergic action of B-type natriuretic peptide (BNP). However, subcutaneous BNP therapy was recently proposed in heart failure, thus raising new perspectives over what was considered as a promising treatment. We tested the efficiency of a combination of oral β1-adrenergic receptor blocker metoprolol and subcutaneous BNP infusion in decompensated heart failure. Methods and results The effects of metoprolol or/and BNP were studied on cardiac remodelling, excitation–contraction coupling and arrhythmias in an experimental mouse model of ischaemic heart failure following postmyocardial infarction. We determined the cellular and molecular mechanisms involved in anti-remodelling and antiarrhythmic actions. As major findings, the combination was more effective than metoprolol alone in reversing cardiac remodelling and preventing ventricular arrhythmia. The association of the two molecules improved cardiac function, reduced hypertrophy and fibrosis, and corrected the heart rate, sympatho-vagal balance (low frequencies/high frequencies) and ECG parameters (P to R wave interval (PR), QRS duration, QTc intervals). It also improved altered Ca2+ cycling by normalising Ca2+-handling protein levels (S100A1, SERCA2a, RyR2), and prevented pro-arrhythmogenic Ca2+ waves derived from abnormal Ca2+ sparks in ventricular cardiomyocytes. Altogether these effects accounted for decreased occurrence of ventricular arrhythmias. Conclusions Association of subcutaneous BNP and oral metoprolol appeared to be more effective than metoprolol alone. Breaking the deleterious loop linking BNP and sympathetic overdrive in heart failure could unmask the efficiency of BNP against deleterious damages in heart failure and bring a new potential approach against lethal arrhythmia during heart failure.