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Fahima Syeda, Andrew P Holmes, Ting Y Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P Kucera, Florian Jousset, Joris R de Groot, Stephan Rohr, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs...
October 25, 2016: Journal of the American College of Cardiology
Naokata Sumitomo
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is induced by emotions or exercise in patients without organic heart disease and may be polymorphic or bidirectional in nature. The prognosis of CPVT is not good, and therefore prevention of sudden death is of utmost importance. Genetic variants of CPVT include RyR2, CASQ2, CALM2, TRD, and possibly KCNJ2 and ANK2 gene mutations. Hypotheses that suggest the causes of CPVT include weakened binding of FKBP12.6 and RyR2, a store overload-induced Ca(2+) release (SOICR), unzipping of intramolecular domain interactions in RyR2, and molecular and functional abnormalities caused by mutations in the CASQ2 gene...
October 2016: Journal of Arrhythmia
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
Martin Steinmetz, Georg Nickenig, Tilman Sauerbruch, Florian Eyer, Christian Rabe
No abstract text is available yet for this article.
October 12, 2016: Clinical Toxicology
Srinivasa Prasad, Narayanan Namboodiri, Anees Thajudheen, Gurbhej Singh, Mukund A Prabhu, S P Abhilash, Krishnakumar Mohanan Nair, Aamir Rashid, V K Ajit Kumar, Jaganmohan A Tharakan
BACKGROUND: Many subjects in community have non-type 1 Brugada pattern ECG with atypical symptoms, relevance of which is not clear. Provocative tests to unmask type 1 Brugada pattern in these patients would help in diagnosing Brugada Syndrome. However sensitivity and specificity of provocating drugs are variable. METHODS: We studied 29 patients referred to our institute with clinical presentation suggestive but not diagnostic of Brugada or with non-Type 1 Brugada pattern ECG...
March 2016: Indian Pacing and Electrophysiology Journal
Ana Santoveña, Irma Charola, Javier Suárez-González, Nuria Teigell-Pérez, Susana García-van Nood, Mabel Soriano, José B Fariña
There is as yet no commercialized preparation for oral administration of flecainide acetate (FA) to children. In such cases, manipulation of commercial tablets is the usual practice in pharmacy services of hospitals and compounding pharmacies, to provide a suitable dosage form for this vulnerable pediatric population group. In this study we have formulated FA as an oral solution, as an alternative to the suspension elaborated from commercial tablets. Due to this sensitivity of young patients, we have used the pure active pharmaceutical ingredient (API) and the lowest permitted levels of pediatric excipients...
September 23, 2016: Pharmaceutical Development and Technology
Shankar Sridharan, Ian Sullivan, Viktor Tomek, Joanne Wolfenden, Jan Škovránek, Robert Yates, Jan Janoušek, Troy E Dominguez, Jan Marek
BACKGROUND: The optimal treatment for fetal supraventricular tachycardia (SVT) with 1:1 atrioventricular relationship is unclear. OBJECTIVE: We compared the effectiveness of transplacental treatment protocols used in 2 centers. METHODS: Pharmacologic treatment was used in 84 fetuses. Maternal oral flecainide was the primary therapy in center 1 (n = 34) and intravenous maternal digoxin in center 2 (n = 50). SVT mechanism was classified by mechanical ventriculoatrial (VA) time intervals as short VA or long VA...
September 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Kosuke Doki, Yukio Sekiguchi, Keisuke Kuga, Kazutaka Aonuma, Masato Homma
OBJECTIVE: β1-Adrenergic receptor (β1-AR) stimulation modulates the antiarrhythmic activities of sodium channel blockers. The β1-AR Gly389 variant shows a marked decrease in agonist-stimulated cyclic AMP production compared with that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly polymorphism affects the efficacy of flecainide, a typical sodium channel blocker, in patients with or without coadministration of β-blockers. METHODS: The effects of the β1-AR Arg389Gly polymorphism on the antiarrhythmic efficacy of flecainide were compared between with and without coadministered β-blockers in 159 patients with supraventricular tachyarrhythmia...
October 2016: Pharmacogenetics and Genomics
Marcela K Preininger, Rajneesh Jha, Joshua T Maxwell, Qingling Wu, Monalisa Singh, Bo Wang, Aarti Dalal, Zachary T Mceachin, Wilfried Rossoll, Chadwick M Hales, Peter S Fischbach, Mary B Wagner, Chunhui Xu
Although β-blockers can be used to eliminate stress-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), this treatment is unsuccessful in ∼25% of cases. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these patients have potential for use in investigating the phenomenon, but it remains unknown whether they can recapitulate patient-specific drug responses to β-blockers. This study assessed whether the inadequacy of β-blocker therapy in an individual can be observed in vitro using patient-derived CPVT iPSC-CMs...
September 1, 2016: Disease Models & Mechanisms
Sridharan Rajamani, Gongxin Liu, Nesrine El-Bizri, Donglin Guo, Cindy Li, Xiao-Liang Chen, Kristopher M Kahlig, Nevena Mollova, Elfatih Elzein, Jeff Zablocki, Luiz Belardinelli
BACKGROUND AND PURPOSE: Enhanced late Na(+) current (late INa ) in the myocardium is pro-arrhythmic. Inhibition of this current is a promising strategy to stabilize ventricular repolarization and suppress arrhythmias. Here, we describe GS-6615, a selective inhibitor of late INa , already in clinical development for the treatment of long QT syndrome 3 (LQT3). EXPERIMENTAL APPROACH: The effects of GS-6615 to inhibit late INa , versus other ion currents to shorten the ventricular action potential duration (APD), monophasic APD (MAPD) and QT interval, and decrease to the incidence of ventricular arrhythmias was determined in rabbit cardiac preparations...
November 2016: British Journal of Pharmacology
Carlos Acosta-Materán, Eloy Díaz-Oliva, Diego Fernández-Rodríguez, Julio Hernández-Afonso
A high percentage of patients having atrial fibrillation (AF) presents with paroxysmal AF. Flecainide, the prototypic class Ic anti-arrhythmic drug is the most effective drug to maintain sinus rhythm in this subgroup of patients, though the drug has potential pro-arrhythmic effects. Furthermore, the H1 receptor antagonists are the most commonly prescribed drugs for the symptomatic treatment of pruritus. Despite having low number of adverse effects, the H1 receptor antagonists have cardiotoxic effects. Flecainide and H1 receptor antagonists present arrhythmic complications including QT interval prolongation and torsade de pointes (TdP)...
April 2016: Journal of Pharmacology & Pharmacotherapeutics
Michael A Valentino, Andrew Panakos, Loheetha Ragupathi, Janna Williams, Behzad B Pavri
In the setting of flecainide toxicity, supraventricular tachycardia can manifest as a bizarre right or left bundle branch block, sometimes with a northwest axis, and can easily be mistaken for ventricular tachycardia leading to inappropriate therapy. We conducted a comprehensive literature review for cases of flecainide toxicity. We found 21 articles of flecainide toxicity in adult patients in which 22 ECG tracings were published. In patients with flecainide toxicity and QRS duration ≤ 200 ms, the ECGs were more likely to show RBBB, visible P waves (p = 0...
July 19, 2016: Cardiovascular Toxicology
Carl Hayward, Hitesh C Patel, Ketna Patel, Carlo Di Mario, Alexander R Lyon, Syed Y Ahsan, Edward Rowland
AIMS: An important decision in the management of patients with atrial fibrillation is whether to adopt a rate or rhythm control strategy. Options for the latter include oral membrane-active anti-arrhythmic drugs (AADs) or catheter ablation. Recent prescription trends may have been affected by the introduction of dronedarone and an increasing number of reports suggesting increased mortality in those taking AADs. We describe the trend in oral AAD prescriptions in England in the period 1998-2014...
April 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Krystien Vv Lieve, Arthur A Wilde, Christian van der Werf
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder, with symptoms including syncope and sudden cardiac death due to polymorphic VT or ventricular fibrillation typically triggered by exercise or emotions in the absence of structural heart disease. The cornerstone of medical therapy for CPVT is β-blockers. However, recently flecainide has been added to the therapeutic arsenal for CPVT. In this review we summarise current data on the efficacy and role of flecainide in the treatment of CPVT...
May 2016: Arrhythmia & Electrophysiology Review
Emre Oto, Sercan Okutucu, Deniz Katircioglu-Öztürk, Halil Altay Güvenir, Ergun Karaagaoglu, Martin Borggrefe, Günter Breithardt, Andreas Goette, Ursula Ravens, Gerhard Steinbeck, Karl Wegscheider, Ali Oto, Paulus Kirchhof
AIMS: Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death. METHODS AND RESULTS: The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset...
July 4, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Yu-Ichi Noto, Kazumoto Shibuya, Steve Vucic, Matthew C Kiernan
INTRODUCTION: Motor neuron hyperexcitability appears linked to the process of neurodegeneration in amyotrophic lateral sclerosis (ALS). As such, therapies that inhibit neuronal hyperexcitability may prove effective in arresting the progression of ALS. AREA COVERED: We searched MEDLINE and and selected randomised controlled trials that covered neuroprotective therapy. Riluzole has been established to reduce neuronal hyperexcitability. More recently, initial studies of Na(+) channel blockers (mexiletine and flecainide) have been trialled...
October 2016: Expert Review of Neurotherapeutics
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
Xiaoyu Zhang, Liang Guo, Haoyu Zeng, Stephen L White, Michael Furniss, Bharathi Balasubramanian, Edward Lis, Armando Lagrutta, Frederick Sannajust, Li Leyna Zhao, Biao Xi, Xiaobo Wang, Myrtle Davis, Yama A Abassi
INTRODUCTION: The ICH S7B guidelines recommend that all new chemical entities should be subjected to hERG repolarization screening due to its association with life-threatening "Torsades de Pointes" (TdP) arrhythmia. However, it has become evident that not all hERG channel inhibitors result in TdP and not all compounds that induce QT prolongation and TdP necessarily inhibit hERG. In order to address the limitations of the S7B/E14 guidelines, the FDA through a public/private partnership initiated the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative to examine the possible modification and refinement of the ICH E14/S7B guidelines...
September 2016: Journal of Pharmacological and Toxicological Methods
Mark L Bannister, Anita Alvarez-Laviada, N Lowri Thomas, Sammy A Mason, Sharon Coleman, Christo L du Plessis, Abbygail T Moran, David Neill-Hall, Hasnah Osman, Mark C Bagley, Kenneth T MacLeod, Christopher H George, Alan J Williams
BACKGROUND AND PURPOSE: Flecainide is a use-dependent blocker of cardiac Na(+) channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na(+) channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca(2) (+) -release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na(+) and/or RyR2 channels...
August 2016: British Journal of Pharmacology
James E Tisdale
Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval-prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration...
May 2016: Canadian Pharmacists Journal: CPJ, Revue des Pharmaciens du Canada: RPC
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