ArticleCirculation research2021
RYR2 Channel Inhibition Is the Principal Mechanism of Flecainide Action in CPVT.
Article in Circulation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 111 citations in OpenAlex.
- Flecainide reduces exercise-induced arrhythmic burden in PKP2-related arrhythmogenic cardiomyopathy.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Long-Term Serial Exercise Stress Testing in Catecholaminergic Polymorphic Ventricular Tachycardia on Beta-Blocker and Flecainide Therapy.Journal of cardiovascular electrophysiology · 2026Article
- Conventional Antiarrhythmics Class I-IV, Late INa Inhibitors, IKs Enhancers, RyR2 Stabilizers, Gap Junction Modulators, Atrial-Selective Antiarrhythmics, and Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Therapy in Arrhythmias.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Aberrant myocardial calcium cycling: pathogenic mechanisms and targeted therapeutics for heart failure.Frontiers in cardiovascular medicine · 2026Review
- Calcium release deficiency syndrome: an emerging ryanodinopathy.Frontiers in molecular biosciences · 2026Review
- Case Report: Overlap of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia in two Chinese children withFrontiers in pediatrics · 2026Article
- Decreased RYR2 Cluster Size and Abnormal SR CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Arrhythmogenic Cardiomyopathy: Towards Genotype Based Diagnoses and Management.Journal of cardiovascular electrophysiology · 2025Review
- RYR2 Variants in Catecholaminergic Polymorphic Ventricular Tachycardia Patients: Insights From Protein Structure and Clinical Data.Circulation. Arrhythmia and electrophysiology · 2025Review
- Catecholaminergic polymorphic ventricular tachycardia: A narrative review of recent advances in genetics, mechanisms, diagnosis, and treatment.Asian heart journal · 2025Review
- Pharmacological Enhancement of Small Conductance CaCirculation research · 2025Article
- End-to-End Backbone Cyclization Enhances Passive Permeability of bRo5 Oligomeric Depsipeptides with Nonlinear Size Dependence.ACS medicinal chemistry letters · 2025Article
- Catecholaminergic Polymorphic Ventricular Tachycardia: Advancing From Molecular Insights to Preclinical Models.Journal of the American Heart Association · 2025Review
- Case Report: High efficacy of low-dose flecainide as an add-on therapy to a beta-blocker for treating a high burden of idiopathic ventricular arrhythmias in a juvenile athlete.Frontiers in cardiovascular medicine · 2025Article
- Simultaneous optical recording of action potentials and calcium transients in cardiac single cells differentiated from type 1 CPVT-iPS cells.Frontiers in physiology · 2025Article
- Unveiling catecholaminergic polymorphic ventricular tachycardia: A case of type 2 ryanodine receptor exon 3 deletion mimicking long QT syndrome type 1.HeartRhythm case reports · 2025Article
- Flecainide Specifically Targets the Monovalent Countercurrent Through the Cardiac Ryanodine Receptor, While a Dominant Opposing CaInternational journal of molecular sciences · 2024Article
- Treatment Outcomes in Children With Catecholaminergic Polymorphic Ventricular Tachycardia: A Single Institutional Experience.Korean circulation journal · 2024Article
- Enhanced CaJACC. Clinical electrophysiology · 2024Article
- Novel variants inLife science alliance · 2024Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleThe 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) mediated calcium (Ca) release. Although flecainide inhibits single RyR2 channels in vitro, reports have claimed that RyR2 inhibition by flecainide is not relevant for its mechanism of antiarrhythmic action and concluded that sodium channel block alone is responsible for flecainide's efficacy in CPVT.
objectiveTo determine whether RyR2 block independently contributes to flecainide's efficacy for suppressing spontaneous sarcoplasmic reticulum Ca release and for preventing ventricular tachycardia in vivo. METHODS AND
resultsWe synthesized N-methylated flecainide analogues (QX-flecainide and
conclusionsFlecainide remains an effective inhibitor of RyR2-mediated arrhythmogenic Ca release even when cardiac sodium channels are blocked. In mice with CPVT, sodium channel block alone did not prevent ventricular tachycardia. Hence, RyR2 channel inhibition likely constitutes the principal mechanism of antiarrhythmic action of flecainide in CPVT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.