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https://www.readbyqxmd.com/read/28630169/patient-specific-drug-screening-using-a-human-induced-pluripotent-stem-cell-model-of-catecholaminergic-polymorphic-ventricular-tachycardia-type-2
#1
Leonid Maizels, Irit Huber, Gil Arbel, Anke J Tijsen, Amira Gepstein, Asaad Khoury, Lior Gepstein
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) results from autosomal recessive CASQ2 mutations, causing abnormal Ca(2+)-handling and malignant ventricular arrhythmias. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of CPVT2 and to use the generated hiPSC-derived cardiomyocytes to gain insights into patient-specific disease mechanism and pharmacotherapy. METHODS AND RESULTS: hiPSC cardiomyocytes were derived from a CPVT2 patient (D307H-CASQ2 mutation) and from healthy controls...
June 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28560722/effectiveness-of-drugs-in-routine-care-a-model-for-sequential-monitoring-of-new-medicines-using-dronedarone-as-example
#2
Thomas Cars, Lars Lindhagen, Rickard Malmström, Martin Neovius, Jonas Schwieler, Björn Wettermark, Johan Sundström
Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different from those treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases from a well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care...
May 30, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28552278/assessments-of-the-qt-qrs-restitution-in-perfused-guinea-pig-heart-can-discriminate-safe-and-arrhythmogenic-drugs
#3
Oleg E Osadchii
INTRODUCTION: Drug-induced arrhythmia remains a matter of serious clinical concern, partly due to low prognostic value of currently available arrhythmic biomarkers. METHODS: This study examined whether arrhythmogenic risks can be predicted through assessments of the rate adaptation of QT interval, ventricular effective refractory period (ERP), or the QT/QRS ratio, in perfused guinea-pig hearts. RESULTS: When the maximum restitution slope was taken as a metric of proarrhythmia, neither QT interval nor ERP measurements at progressively increased pacing rates were found to fully discriminate arrhythmogenic drugs (dofetilide, quinidine, flecainide, and procainamide) from those recognized as safe antiarrhythmics (lidocaine and mexiletine)...
May 24, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28534245/flecainide-induced-left-ventricular-dysfunction-fact-or-fiction
#4
Umair Khalid, Francia Rojas, Nasser Lakkis
No abstract text is available yet for this article.
May 22, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28521022/management-of-untreatable-ventricular-arrhythmias-during-pharmacologic-challenges-with-sodium-channel-blockers-for-suspected-brugada-syndrome
#5
Stefano Poli, Mauro Toniolo, Massimo Maiani, Davide Zanuttini, Luca Rebellato, Igor Vendramin, Ermanno Dametto, Guglielmo Bernardi, Flavio Bassi, Carlo Napolitano, Ugolino Livi, Alessandro Proclemer
Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears...
May 17, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28492868/efficacy-of-flecainide-in-the-treatment-of-catecholaminergic-polymorphic-ventricular-tachycardia-a-randomized-clinical-trial
#6
Prince J Kannankeril, Jeremy P Moore, Marina Cerrone, Silvia G Priori, Naomi J Kertesz, Pamela S Ro, Anjan S Batra, Elizabeth S Kaufman, David L Fairbrother, Elizabeth V Saarel, Susan P Etheridge, Ronald J Kanter, Michael P Carboni, Matthew V Dzurik, Darlene Fountain, Heidi Chen, E Wesley Ely, Dan M Roden, Bjorn C Knollmann
Importance: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal genetic arrhythmia syndrome characterized by polymorphic ventricular tachycardia with physical or emotional stress, for which current therapy with β-blockers is incompletely effective. Flecainide acetate directly suppresses sarcoplasmic reticulum calcium release-the cellular mechanism responsible for triggering ventricular arrhythmias in CPVT-but has never been assessed prospectively. Objective: To determine whether flecainide dosed to therapeutic levels and added to β-blocker therapy is superior to β-blocker therapy alone for the prevention of exercise-induced arrhythmias in CPVT...
May 10, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28491792/flecainide-treats-a-novel-kcnj2-mutation-associated-with-andersen-tawil-syndrome
#7
Hanora A Van Ert, Elise C McCune, Kate M Orland, Kathleen R Maginot, Nicholas H Von Bergen, Craig T January, Lee L Eckhardt
No abstract text is available yet for this article.
February 2017: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28491747/flecainide-induced-incessant-orthodromic-atrioventricular-reentrant-tachycardia-in-wolff-parkinson-white-syndrome-uneven-depression-of-accessory-pathway-conduction
#8
Oscar A Pellizzón, Manlio F Márquez, Mario D González, Sebastián Nannini, Rodolfo Leiva, Antonia Catalano, Pedro Iturralde
No abstract text is available yet for this article.
November 2016: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28481554/palladium-catalyzed-c-h-trifluoroethoxylation-of-n-sulfonylbenzamides
#9
Long Yang, Shangda Li, Lei Cai, Yongzheng Ding, Lei Fu, Zhihua Cai, Huafang Ji, Gang Li
The trifluoroethyl aryl ethers are important motifs in drug molecules. However, a report devoted specifically to the study of transition-metal-catalyzed C-H trifluoroethoxylation has not been reported to date. A protocol of Pd(II)-catalyzed o-C-H trifluoroethoxylation of a broad range of benzoic acid derivatives (i.e., N-sulfonylbenzamides) has been developed. This method is also applied to the formal synthesis of the drug molecule flecainide, wherein the first m-C-H trifluoroethoxylation is also exemplified...
May 8, 2017: Organic Letters
https://www.readbyqxmd.com/read/28466829/magnetocardiographic-evaluation-of-nonarrhythmogenic-flecainide-induced-electrocardiographic-t-wave-inversion
#10
Donatella Brisinda, Anna Rita Sorbo, Lara La Brocca, Riccardo Fenici
No abstract text is available yet for this article.
April 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28455405/respiration-driven-excessive-sinus-tachycardia-treated-with-clonidine
#11
Matthew Emile Li Kam Wa, Patricia Taraborrelli, Sajad Hayat, Phang Boon Lim
A 26-year-old man presented to our syncope service with debilitating daily palpitations, shortness of breath, presyncope and syncope following a severe viral respiratory illness 4 years previously. Mobitz type II block had previously been identified, leading to a permanent pacemaker and no further episodes of frank syncope. Transthoracic echocardiography, electophysiological study and repeated urine metanepherines were normal. His palpitations and presyncope were reproducible on deep inspiration, coughing, isometric hand exercise and passive leg raises...
April 28, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28421842/the-management-of-ventricular-dysrhythmia-in-aconite-poisoning
#12
REVIEW
James M Coulson, Thomas M Caparrotta, John P Thompson
INTRODUCTION: Aconite poisoning is relatively rare but is frequently complicated by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to the presence of an admixture of alkaloids present in all parts of the plant. The major target of these aconite alkaloids is the fast voltage-gates sodium channel, where they cause persistent activation. This blockade of the channel in the activated state promotes automaticity within the ventricular myocardium and the generation of ventricular arrhythmias...
June 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28369767/multiple-targets-for-flecainide-action-implications-for-cardiac-arrhythmogenesis
#13
REVIEW
Samantha C Salvage, Karthik H Chandrasekharan, Kamalan Jeevaratnam, Angela F Dulhunty, Andrew J Thompson, Antony P Jackson, Christopher L-H Huang
Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca(2+) -mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro-arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization...
April 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28339995/long-term-flecainide-therapy-in-type-3-long-qt-syndrome
#14
Ehud Chorin, Rivki Taub, Aron Medina, Nir Flint, Sami Viskin, Jesaia Benhorin
Aims: Type 3 long QT syndrome (LQT3) is caused by gain-of-function mutations in the cardiac sodium channel gene (SCN5A). Previous reports on the long-term use of sodium channel blockers in LQT3 are sparse. The objective of the current study was to evaluate the long-term safety and efficacy of flecainide therapy in patients with LQT3 who carry the D1790G SCN5A mutation. Methods and results: The study population comprised 30 D1790G carriers who were treated with flecainide and followed for 1-215 months (mean 145 ± 54 months, median 140 months)...
February 28, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339646/transforming-growth-factor-%C3%AE-receptor-inhibition-prevents-ventricular-fibrosis-in-a-mouse-model-of-progressive-cardiac-conduction-disease
#15
Mickael Derangeon, Jérôme Montnach, Cynthia Ore Cerpa, Benoit Jagu, Justine Patin, Gilles Toumaniantz, Aurore Girardeau, Christopher L H Huang, William H Colledge, Andrew A Grace, Isabelle Baró, Flavien Charpentier
Aims: Loss-of-function mutations in SCN5A, the gene encoding NaV1.5 channel, have been associated with inherited progressive cardiac conduction disease (PCCD). We have proposed that Scn5a heterozygous knock-out (Scn5a+/-) mice, which are characterized by ventricular fibrotic remodelling with ageing, represent a model for PCCD. Our objectives were to identify the molecular pathway involved in fibrosis development and prevent its activation. Methods and results: Our study shows that myocardial interstitial fibrosis occurred in Scn5a+/- mice only after 45 weeks of age...
April 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28335638/incidence-and-clinical-predictors-of-subsequent-atrial-fibrillation-requiring-additional-ablation-after-cavotricuspid-isthmus-ablation-for-typical-atrial-flutter
#16
Alessandro De Bortoli, Li-Bin Shi, Ole-Jørgen Ohm, Per Ivar Hoff, Peter Schuster, Eivind Solheim, Jian Chen
OBJECTIVES: We sought to investigate the incidence of atrial fibrillation after catheter ablation for typical atrial flutter and to determine the predictors for symptomatic atrial fibrillation that required a further additional dedicated ablation procedure. DESIGN: 127 patients underwent elective cavotricuspid isthmus ablation with the indication of symptomatic, typical atrial flutter. The occurrence of atrial flutter, atrial fibrillation, cerebrovascular events and the need for additional ablation procedures for symptomatic atrial fibrillation was assessed during long-term follow-up...
June 2017: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/28321045/characterization-of-human-ips-cell-derived-cardiomyocyte-sheets-as-a-model-to-detect-drug-induced-conduction-disturbance
#17
Hiroko Izumi-Nakaseko, Yuji Nakamura, Takeshi Wada, Kentaro Ando, Yasunari Kanda, Yuko Sekino, Atsushi Sugiyama
In order to characterize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets as a model for detecting drug-induced conduction disturbance, we examined their electrophysiological and electropharmacological properties by using the multi-electrode array system with a programmed electrical stimulation protocol. At pre-drug control, the conduction speed, effective refractory period and field potential duration were 0.14 ± 0.01 m/sec, 453 ± 10 msec and 361 ± 9 msec, respectively at a cycle length of 1,000 msec (n = 18)...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28272074/when-potion-becomes-poison-a-case-report-of-flecainide-toxicity
#18
S Bajaj, M S Tullu, Zah Khan, M Agrawal
We report a 48-day-old female infant, who developed cardiac conduction abnormalities and seizures secondary to supratherapeutic doses of oral flecainide. Flecainide was started in this infant for treatment of supraventricular tachycardia. The drug was withdrawn with successful normalization of the QRS complex and no further recurrence of seizures. The Naranjo probability score for adverse drug reaction was 8, making the causality "probable." The case restates an important message that physicians should be aware of the side effects of the drugs that they prescribe, especially of those drugs which have a narrow therapeutic window...
March 3, 2017: Journal of Postgraduate Medicine
https://www.readbyqxmd.com/read/28270595/differential-responses-of-rabbit-ventricular-and-atrial-transient-outward-current-ito-to-the-ito-modulator-ns5806
#19
Hongwei Cheng, Mark B Cannell, Jules C Hancox
Transient outward potassium current (Ito) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of Ito may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine Ito This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular Ito Whole cell patch-clamp recordings of Ito and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28267896/treatment-of-supraventricular-tachycardia-in-a-horse
#20
Dorothy D Whelchel, Brett S Tennent-Brown, Amanda E Coleman, Gregg S Rapoport, Uriel Blas-Machado, Herbert W Maisenbacher, Brenton C Credille, Steeve Giguère
OBJECTIVE: To describe the treatment of persistent supraventricular tachycardia (SVT) in a young horse in endurance training. CASE SUMMARY: A 6-year-old Arab gelding in endurance training presented for a dysrhythmia and decreased performance. SVT was diagnosed and conversion to a normal sinus rhythm was achieved following administration of a constant rate infusion of amiodarone. However, reversion to SVT occurred shortly after initiation of ridden exercise. A second attempt to convert the dysrhythmia with amiodarone failed, but normal sinus rhythm was achieved with transvenous electrical cardioversion (TVEC)...
May 2017: Journal of Veterinary Emergency and Critical Care
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