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Marta Varela, Michael A Colman, Jules C Hancox, Oleg V Aslanidi
Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed...
December 2016: PLoS Computational Biology
Gregory N Beatch, Kiran Bhirangi, Steen Juul-Moller, Jörg Rustige
Atrial fibrillation (AF) is a common clinically significant cardiac arrhythmia. This phase 3 randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of vernakalant hydrochloride for the pharmacological conversion of AF to sinus rhythm (SR) in patients with recent-onset (>3 hours-≤7 days) symptomatic AF from the Asia-Pacific region. Patients received an infusion of vernakalant (3 mg/kg) or placebo over 10 minutes. If AF had not been terminated 15 minutes later, a second infusion of vernakalant (2 mg/kg) or placebo 15 minutes was administered...
November 7, 2016: Journal of Cardiovascular Pharmacology
Maximilian D Hien, Fernando Benito Castro, Philippe Fournier, Anne Filleron, Tu-Anh Tran
OBJECTIVES: We report on a rare but severe complication of adenosine use in a child with reentry tachycardia. METHODS AND RESULTS: Treatment with adenosine, which is the standard medical therapy of atrioventricular reentry tachycardia, led to the development of an irregular wide complex tachycardia, caused by rapid ventricular response to atrial fibrillation. The girl was finally stabilized with electrical cardioversion. We analyze the pathomechanism and discuss possible treatment options...
October 8, 2016: Pediatric Emergency Care
Gerrit Frommeyer, Catharina Clauss, Christian Ellermann, Harilaos Bogossian, Dirk G Dechering, Simon Kochhäuser, Florian Reinke, Christian Pott, Lars Eckardt
AIMS: The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS). METHODS AND RESULTS: Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 µM, n = 15) or veratridine (0...
October 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Caiyou Chen, Shicheng Jin, Zhefan Zhang, Biao Wei, Heng Wang, Kai Zhang, Hui Lv, Xiu-Qin Dong, Xumu Zhang
The first interrupted asymmetric hydroaminomethylation reaction was developed. The challenging trans-1,2-disubstituted olefins were employed as substrates, and a series of valuable chiral pyrrolidinones and pyrrolidines were obtained in high yields with high regioselectivities and excellent enantioselectivities. Several synthetic transformations were conducted, demonstrating the high synthetic utility of our method. A creative route for the synthesis of vernakalant and Enablex was also developed.
July 27, 2016: Journal of the American Chemical Society
R Kriz, M K Freynhofer, T W Weiss, F Egger, S C Gruber, P Eisenburger, J Wojta, K Huber, J Koch
BACKGROUND AND AIM: The management of patients with recent-onset atrial fibrillation (AF) presenting at emergency departments (EDs) varies widely. Our aim was to describe the management of patients with recent-onset (<48 hours) AF, to determine safety and efficacy of pharmacological cardioversion at the ED, and to evaluate the incidence of thromboembolism or death at 30 days. METHODS: In a prospective, observational, single-center study, 236 subjects with recent-onset AF were consecutively enrolled from January 2011 until January 2013...
August 2016: American Journal of Emergency Medicine
Gerrit Frommeyer, Christian Ellermann, Dirk G Dechering, Simon Kochhäuser, Nils Bögeholz, Fatih Güner, Patrick Leitz, Christian Pott, Lars Eckardt
BACKGROUND: Ranolazine has been reported to have an antiarrhythmic potential. The aim of this study was to assess the electrophysiologic effects of ranolazine and to compare its effects to vernakalant in an experimental whole-heart model of short-QT syndrome. METHODS: Rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IKATP channel opener, was administered (1 μM). RESULTS: Endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (- 34 milliseconds, P < 0...
June 10, 2016: Journal of Cardiovascular Electrophysiology
Justo Juliá, María López-Gil, Lola Villagraz, Álvaro Lozano, Adolfo Fontenla, Fernando Arribas
No abstract text is available yet for this article.
July 2016: Revista Española de Cardiología
Gregory N Beatch, Brian Mangal
BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with significant health risks. One strategy to mitigate the risks associated with long-term AF is to convert AF to sinus rhythm (SR). This study assessed the efficacy and safety of vernakalant hydrochloride for the pharmacological conversion of AF to SR. METHODS: Patients with recent-onset (duration >3 h- ≤ 7 days) symptomatic AF and no evidence or history of congestive heart failure were randomized in a 2:1 ratio to receive vernakalant or placebo...
May 28, 2016: BMC Cardiovascular Disorders
Juan Cosin-Sales, Armando Loscos, Ana Peiró, M Rosa Sorando, Francisco Buendía, Luis Ruescas
No abstract text is available yet for this article.
June 2016: Revista Española de Cardiología
Toshiki Chiba, Naoto Kondo, Akira Takahara
Electrical remodeling plays a pivotal role in maintaining the reentry during atrial fibrillation. In this study, we assessed influence of electrical remodeling on pharmacological manipulation of the atrial refractoriness in rabbits. We used an atrial electrical remodeling model of the rabbit, subjected to rapid atrial pacing (RAP; 600 beats/min) for 2-4 weeks, leading to shortening of atrial effective refractory period (AERP). Intravenous administration of dl-sotalol (6 mg/kg), bepridil (1 mg/kg), amiodarone (10 mg/kg) or vernakalant (3 mg/kg) significantly prolonged the AERP both in the control and RAP rabbits...
March 2016: Journal of Pharmacological Sciences
Alexander Simon, Jan Niederdoeckl, Ekaterini Skyllouriotis, Nikola Schuetz, Harald Herkner, Christoph Weiser, Anton N Laggner, Hans Domanovits, Alexander O Spiel
AIMS: Ibutilide is a rapid-acting antiarrhythmic drug with worldwide use for conversion of recent-onset atrial fibrillation. Vernakalant, approved in the EU in 2010, is likewise used intravenously, with proven efficacy and safety compared with placebo and amiodarone in randomized clinical trials. The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent-onset atrial fibrillation treated with vernakalant or ibutilide. METHODS AND RESULTS: A randomized controlled trial registered at clinicaltrials...
March 22, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Arne van Hunnik, Dennis H Lau, Stef Zeemering, Marion Kuiper, Sander Verheule, Ulrich Schotten
BACKGROUND: Vernakalant inhibits several potassium currents and causes a rate- and voltage-dependent inhibition of the sodium current. OBJECTIVE: The aim of this study was to evaluate the antiarrhythmic mechanism of vernakalant in normal and electrically remodeled atria. METHODS: Fourteen goats were instrumented with electrodes on both atria. Drug effects on refractory period (ERP), conduction velocity (CV), and atrial fibrillation cycle length (AFCL) were determined in normal goats (control) and after 2 (2dAF) or 11 (11dAF) days of pacing-induced atrial fibrillation (AF) in awake goats...
April 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Maria Vittoria Matassini, Federico Guerra, Lorena Scappini, Loren Scappini, Alessia Urbinati, Alessandro Capucci
Atrial fibrillation (AF) is a common arrhythmia associated with increased mortality and morbidity. Different studies have shown no significant difference between rhythm and rate control strategies in terms of mortality. Moreover, the use of antiarrhythmic drugs is afflicted by cardiac and extracardiac toxicity and related costs of hospitalization. Nevertheless, some patients require a rhythm-control strategy and new anti-AF agents are being sought. Only few novel agents showed promising results in term of efficacy and safety...
2015: Future Cardiology
Leonardo Seoane, Adrián Baranchuk, Diego Conde
Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardioversion is considered one of the best treatments for recent onset AF, especially with drugs for avoiding sedation. Vernakalant is a novel antiarrhythmic that acts selectively in the atrium, and inhibits potassium currents, with minor blockade of IKr currents in the ventricle. It has been recently approved for pharmacological cardioversion of recent-onset AF in the European Union. The aim of this review is to analyze the pharmacokinetic and pharmacodynamic of vernakalant, and to show the efficacy and safety of this drug for the conversion of AF to sinus rhythm...
2015: Medicina
Shaojie Chen, Shaowen Liu, Helmut Purerfellner
The rising incidence of atrial fibrillation (AF) has stimulated researches to identify novel therapeutic options for such most common and refractory cardiac arrhythmia in clinical practice. Rhythm control strategy is shown to be associated with a lower risk of progression to permanent AF and greater clinical benefit as compared with rate control. Remarkable progress has been witnessed in rhythm control strategy particularly along with the development of mapping and ablation technology, while still should pharmacological cardioversion serve as an integrated approach for the management of AF especially in the emergency department or centers not equipped with ablation professionals...
2015: Current Pharmaceutical Design
Dnyaneshwar N Garad, Subhash D Tanpure, Santosh B Mhaske
Ammonium persulfate-dimethyl sulfoxide (APS-DMSO) has been developed as an efficient and new dehydrating reagent for a convenient one-pot process for the synthesis of miscellaneous cyclic imides in high yields starting from readily available primary amines and cyclic anhydrides. A plausible radical mechanism involving DMSO has been proposed. The application of this facile one-pot imide forming process has been demonstrated for a practical synthesis of vernakalant.
2015: Beilstein Journal of Organic Chemistry
Andreas Müssigbrodt, Silke John, Jedrzej Kosiuk, Sergio Richter, Gerhard Hindricks, Andreas Bollmann
AIMS: Electrical cardioversion is one cornerstone for the rhythm control strategy of atrial fibrillation (AF), which is, however, hampered by immediate AF recurrence (IRAF) or failed electrical cardioversion (FECV). We aimed to investigate the potential role of vernakalant for facilitated electrical cardioversion in cardioversion-resistant AF. METHODS AND RESULTS: The subjects of this study were 63 patients referred to the Heart Centre Leipzig between November 2011 and May 2014 for transthoracic electrical cardioversion of AF...
January 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
M Arrigo, D Bettex, A Rudiger
BACKGROUND: Atrial fibrillation is the most common arrhythmia in patients hospitalized in intensive care units and emergency departments and is associated with an increased morbidity and mortality. In critically ill patients, atrial fibrillation can cause hemodynamic instability and cardiogenic shock. The mechanisms and the management of atrial fibrillation are significantly different in critically ill patients compared to outpatients. DIAGNOSIS AND TREATMENT: The initial management includes the evaluation of the hemodynamic consequences of new-onset atrial fibrillation and the optimization of reversible causes...
November 2015: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Harsha D Devalla, Verena Schwach, John W Ford, James T Milnes, Said El-Haou, Claire Jackson, Konstantinos Gkatzis, David A Elliott, Susana M Chuva de Sousa Lopes, Christine L Mummery, Arie O Verkerk, Robert Passier
Drugs targeting atrial-specific ion channels, Kv1.5 or Kir3.1/3.4, are being developed as new therapeutic strategies for atrial fibrillation. However, current preclinical studies carried out in non-cardiac cell lines or animal models may not accurately represent the physiology of a human cardiomyocyte (CM). In the current study, we tested whether human embryonic stem cell (hESC)-derived atrial CMs could predict atrial selectivity of pharmacological compounds. By modulating retinoic acid signaling during hESC differentiation, we generated atrial-like (hESC-atrial) and ventricular-like (hESC-ventricular) CMs...
February 19, 2015: EMBO Molecular Medicine
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