ArticleCirculation. Arrhythmia and electrophysiology2014
Suppression of spontaneous ca elevations prevents atrial fibrillation in calsequestrin 2-null hearts.
Article in Circulation. Arrhythmia and electrophysiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02710669 (Comparison of), which is not on this map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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.
Comparison of (R) and (S) Propafenone for Prevention of Atrial Fibrillation Induction
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases.Nature genetics · 2025Pooled it
- A Mechanistic Clinical Trial Using (Circulation. Arrhythmia and electrophysiology · 2022Trial
- Predicting Sex-Specific Antiarrhythmic Strategies for Atrial Fibrillation through a Regression-Guided Computational Modeling Pipeline.bioRxiv : the preprint server for biology · 2026Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- The selective RyR2 inhibitor ent-verticilide suppresses atrial fibrillation susceptibility caused by Pitx2 deficiency.Journal of molecular and cellular cardiology · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Overview of programmed electrical stimulation to assess atrial fibrillation susceptibility in mice.Frontiers in physiology · 2023Review
- Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals.American journal of physiology. Heart and circulatory physiology · 2022Review
- Targeting the RyR2 to Prevent Atrial Fibrillation.Circulation. Arrhythmia and electrophysiology · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Emerging Antiarrhythmic Drugs for Atrial Fibrillation.International journal of molecular sciences · 2022Review
- The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.Biophysical reviews · 2022Review
- Optimizing transesophageal atrial pacing in mice to detect atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2022Article
- Research Priorities in the Secondary Prevention of Atrial Fibrillation: A National Heart, Lung, and Blood Institute Virtual Workshop Report.Journal of the American Heart Association · 2021Article
- Transcriptional factors in calcium mishandling and atrial fibrillation development.Pflugers Archiv : European journal of physiology · 2021Review
- The crosstalk between cardiomyocyte calcium and inflammasome signaling pathways in atrial fibrillation.Pflugers Archiv : European journal of physiology · 2021Review
- Genetic Complexity of Sinoatrial Node Dysfunction.Frontiers in genetics · 2021Review
- Ion Channel and Structural Remodeling in Obesity-Mediated Atrial Fibrillation.Circulation. Arrhythmia and electrophysiology · 2020Article
- Molecular and tissue mechanisms of catecholaminergic polymorphic ventricular tachycardia.The Journal of physiology · 2020Review
- Tetrodotoxin-Sensitive Neuronal-Type NaJournal of the American Heart Association · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAtrial fibrillation (AF) risk has been associated with leaky ryanodine receptor 2 (RyR2) Ca release channels. Patients with mutations in RyR2 or in the sarcoplasmic reticulum Ca-binding protein calsequestrin 2 (Casq2) display an increased risk for AF. Here, we examine the underlying mechanisms of AF associated with loss of Casq2 and test mechanism-based drug therapy. METHODS AND
resultsCompared with wild-type Casq2+/+ mice, atrial burst pacing consistently induced atrial flutter or AF in Casq2-/- mice and in isolated Casq2-/- hearts. Atrial optical voltage maps obtained from isolated hearts revealed multiple independent activation sites arising predominantly from the pulmonary vein region. Ca and voltage mapping demonstrated diastolic subthreshold spontaneous Ca elevations (SCaEs) and delayed afterdepolarizations whenever the pacing train failed to induce AF. The dual RyR2 and Na channel inhibitor R-propafenone (3 μmol/L) significantly reduced frequency and amplitude of SCaEs and delayed afterdepolarizations in atrial myocytes and intact atria and prevented induction of AF. In contrast, the S-enantiomer of propafenone, an equipotent Na channel blocker but much weaker RyR2 inhibitor, did not reduce SCaEs and delayed afterdepolarizations and failed to prevent AF.
conclusionsLoss of Casq2 increases risk of AF by promoting regional SCaEs and delayed afterdepolarizations in atrial tissue, which can be prevented by RyR2 inhibition with R-propafenone. Targeting AF caused by leaky RyR2 Ca channels with R-propafenone may be a more mechanism-based approach to treating this common arrhythmia.
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.