Flecainide ≈ Flecainide
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Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia Open
Background— Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder causing life-threatening arrhythmias whenever sympathetic activity increases. β-Βlockers are the mainstay of therapy; when they fail, implantabl…
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Catecholaminergic Polymorphic Ventricular Tachycardia in Children Open
Background— Catecholaminergic polymorphic ventricular tachycardia is an uncommon, potentially lethal, ion channelopathy. Standard therapies have high failure rates and little is known about treatment in children. Newer options such as flec…
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Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia Open
clinicaltrials.gov Identifier: NCT01117454.
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Cross-Site Reliability of Human Induced Pluripotent stem cell-derived Cardiomyocyte Based Safety Assays Using Microelectrode Arrays: Results from a Blinded CiPA Pilot Study Open
Recent in vitro cardiac safety studies demonstrate the ability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to detect electrophysiologic effects of drugs. However, variability contributed by unique approaches, …
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RYR2 Channel Inhibition Is the Principal Mechanism of Flecainide Action in CPVT Open
Rationale: The class Ic antiarrhythmic drug flecainide prevents ventricular tachyarrhythmia in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease caused by hyperactive RyR2 (cardiac ryanodine receptor) me…
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Current topics in catecholaminergic polymorphic ventricular tachycardia Open
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 p…
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The Mechanism of Flecainide Action in CPVT Does Not Involve a Direct Effect on RyR2 Open
Rationale: Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It …
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Flecainide: Current status and perspectives in arrhythmia management Open
Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conver…
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First‐Line Antiarrhythmic Transplacental Treatment for Fetal Tachyarrhythmia: A Systematic Review and Meta‐Analysis Open
Background There is no consensus on the most effective and best tolerated first‐line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta‐analysis was to compare the efficacy, safety, and fetal…
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Predicting cardiac electrical response to sodium-channel blockade and Brugada syndrome using polygenic risk scores Open
Aims Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (Br…
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NavAb Voltage-gated Sodium Channel, I217C, in Complex with Class 1C Anti-arrhythmic Flecainide Open
Potency of drug action is usually determined by binding to a specific receptor site on target proteins. In contrast to this conventional paradigm, we show here that potency of local anesthetics (LAs) and antiarrhythmic drugs (AADs) that bl…
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CPVT: Arrhythmogenesis, Therapeutic Management, and Future Perspectives. A Brief Review of the Literature Open
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a primary electrical disease characterized by a normal resting electrocardiogram and induction of malignant arrhythmias during adrenergic stress leading to syncope or sudden c…
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Molecular basis of hERG potassium channel blockade by the class Ic antiarrhythmic flecainide Open
The class Ic antiarrhythmic drug flecainide inhibits KCNH2-encoded "hERG" potassium channels at clinically relevant concentrations. The aim of this study was to elucidate the underlying molecular basis of this action. Patch clamp recording…
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Multiple targets for flecainide action: implications for cardiac arrhythmogenesis Open
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 tachyc…
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Impact of Astroglial Connexins on Modafinil Pharmacological Properties Open
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Post-Translational Modifications and Diastolic Calcium Leak Associated to the Novel RyR2-D3638A Mutation Lead to CPVT in Patient-Specific hiPSC-Derived Cardiomyocytes Open
Background: Sarcoplasmic reticulum Ca2+ leak and post-translational modifications under stress have been implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT), a highly lethal inherited arrhythmogenic disorder. Human i…
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Chronic intermittent tachypacing by an optogenetic approach induces arrhythmia vulnerability in human engineered heart tissue Open
Aims Chronic tachypacing is commonly used in animals to induce cardiac dysfunction and to study mechanisms of heart failure and arrhythmogenesis. Human induced pluripotent stem cells (hiPSC) may replace animal models to overcome species di…
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<i>In silico</i>prediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia Open
Key points The mechanism of therapeutic efficacy of flecainide for catecholaminergic polymorphic ventricular tachycardia (CPVT) is unclear. Model predictions suggest that Na + channel effects are insufficient to explain flecainide efficacy…
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Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs Open
Results suggest that obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers. These findings may have implications for the management of A…
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Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes Open
Andersen-Tawil syndrome (ATS) is a rare inherited channelopathy. The cardiac phenotype in ATS is typified by a prominent U wave and ventricular arrhythmia. An effective treatment for this disease remains to be established. We reprogrammed …
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Intravenous vernakalant in comparison with intravenous flecainide in the cardioversion of recent-onset atrial fibrillation Open
Background: Pharmacological cardioversion of atrial fibrillation is a reasonable alternative for electrical cardioversion in acute atrial fibrillation. We compared the efficacy and safety of intravenous vernakalant and intravenous flecaini…
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Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort Open
Objectives To establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases. Setting Suspected proarrhythmia …
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Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients Open
Multifocal atrial tachycardia (MAT) has a well‐known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan sy…
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An infrared optical pacing system for screening cardiac electrophysiology in human cardiomyocytes Open
Human cardiac myocytes derived from pluripotent stem cells (hCM) have invigorated interest in genetic disease mechanisms and cardiac safety testing; however, the technology to fully assess electrophysiological function in an assay that is …
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The novel late Na<sup>+</sup> current inhibitor, GS‐6615 (eleclazine) and its anti‐arrhythmic effects in rabbit isolated heart preparations Open
Background and Purpose Enhanced late Na + current (late I Na ) 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‐6…
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Allosteric Modulation of K <sub>v</sub> 11.1 (hERG) Channels Protects Against Drug-Induced Ventricular Arrhythmias Open
Background— Ventricular arrhythmias as a result of unintentional blockade of the K v 11.1 (hERG [human ether-à-go-go–related gene]) channel are a major safety concern in drug development. In past years, several highly prescribed drugs have…
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Long-term flecainide therapy in type 3 long QT syndrome Open
These data suggest that long-term flecainide therapy is relatively safe and effective among LQT3 patients who carry the D1790G SCN5A mutation.
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Channel Activity of Cardiac Ryanodine Receptors (RyR2) Determines Potency and Efficacy of Flecainide and R-Propafenone against Arrhythmogenic Calcium Waves in Ventricular Cardiomyocytes Open
Flecainide blocks ryanodine receptor type 2 (RyR2) channels in the open state, suppresses arrhythmogenic Ca2+ waves and prevents catecholaminergic polymorphic ventricular tachycardia (CPVT) in mice and humans. We hypothesized that differen…
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In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2 Open
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a major cause of stroke and morbidity. Recent genome-wide association studies have shown that paired-like homeodomain transcription factor 2 (Pitx2) to be stro…
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Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial Open
This pilot study indicated that flecainide was safe and potentially biologically effective in ALS. There was evidence that flecainide stabilized peripheral axonal membrane function in ALS. While the study was not powered to detect evidence…