ArticleCirculation. Arrhythmia and electrophysiology2011
Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia.
Article in Circulation. Arrhythmia and electrophysiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 155 citations in OpenAlex.
- A Mechanistic Clinical Trial Using (Circulation. Arrhythmia and electrophysiology · 2022Trial
- Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial.JAMA cardiology · 2017Trial
- Long-Term Serial Exercise Stress Testing in Catecholaminergic Polymorphic Ventricular Tachycardia on Beta-Blocker and Flecainide Therapy.Journal of cardiovascular electrophysiology · 2026Article
- Case Report: Overlap of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia in two Chinese children withFrontiers in pediatrics · 2026Article
- Introduction of a single carboxylic acid converts the cyclic oligomeric depsipeptide ent-verticilide from a ryanodine receptor 2 (RyR2) inhibitor to RyR2 activator.Molecular pharmacology · 2025Article
- Practical compendium of antiarrhythmic drugs: a clinical consensus statement of the European Heart Rhythm Association of the European Society of Cardiology.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 · 2025Review
- Preventing the phosphorylation of RyR2 at canonical sites reduces CaNature cardiovascular research · 2025Article
- Catecholaminergic Polymorphic Ventricular Tachycardia: Advancing From Molecular Insights to Preclinical Models.Journal of the American Heart Association · 2025Review
- Flecainide Specifically Targets the Monovalent Countercurrent Through the Cardiac Ryanodine Receptor, While a Dominant Opposing CaInternational journal of molecular sciences · 2024Article
- An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.Stem cell research & therapy · 2024Article
- Enhanced CaJACC. Clinical electrophysiology · 2024Article
- Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies.Journal of clinical medicine · 2024Review
- A dual-targeted drug inhibits cardiac ryanodine receptor CaLife science alliance · 2024Article
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients.International journal of molecular sciences · 2023Review
- Store-Operated CaJournal of clinical medicine · 2023Review
- Sarcospan Deficiency Increases Oxidative Stress and Arrhythmias in Hearts after Acute Ischemia-Reperfusion Injury.International journal of molecular sciences · 2023Article
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Development of Ryanodine Receptor (RyR) Inhibitors for Skeletal Muscle and Heart Diseases.Juntendo Iji zasshi = Juntendo medical journal · 2023Article
- JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias.Journal of arrhythmia · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) and can be difficult to treat. The class Ic antiarrhythmic drug flecainide blocks RyR2 channels and prevents CPVT in mice and humans. It is not known whether other class I antiarrhythmic drugs also block RyR2 channels and to what extent RyR2 channel inhibition contributes to antiarrhythmic efficacy in CPVT. METHODS AND
resultsWe first measured the effect of all class I antiarrhythmic drugs marketed in the United States (quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, and propafenone) on single RyR2 channels incorporated into lipid bilayers. Only flecainide and propafenone inhibited RyR2 channels, with the S-enantiomer of propafenone having a significantly lower potency than R-propafenone or flecainide. In Casq2(-/-) myocytes, the propafenone enantiomers and flecainide significantly reduced arrhythmogenic Ca(2+) waves at clinically relevant concentrations, whereas Na(+) channel inhibitors without RyR2 blocking properties did not. In Casq2(-/-) mice, 5 mg/kg R-propafenone or 20 mg/kg S-propafenone prevented exercise-induced CPVT, whereas procainamide (20 mg/kg) or lidocaine (20 mg/kg) were ineffective (n=5 to 9 mice, P<0.05). QRS duration was not significantly different, indicating a similar degree of Na(+) channel inhibition. Clinically, propafenone (900 mg/d) prevented ICD shocks in a 22-year-old CPVT patient who had been refractory to maximal standard drug therapy and bilateral stellate ganglionectomy.
conclusionsRyR2 cardiac Ca(2+) release channel inhibition appears to determine efficacy of class I drugs for the prevention of CPVT in Casq2(-/-) mice. Propafenone may be an alternative to flecainide for CPVT patients symptomatic on β-blockers.
Indexed as
Identifiers
What OpenQuestion holds
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.