Cardiac electrophysiology and arrhythmias

A bioelectrical phase transition patterns the first beats of a vertebrate heart

The paper identifies a bioelectrical phase transition as the mechanism initiating the first heartbeat in zebrafish, using optogenetic perturbations and all-optical electrophysiology.

Increased early sodium current causes familial atrial fibrillation and dampens effect of flecainide

This study investigates the effects of the Scn5a-M1875T mutation in mice, showing increased early sodium current and potential implications for atrial fibrillation treatment.

Junctophilin-2 promotes cardiomyocyte survival by blocking MURF1-mediated Junctin ubiquitination and proteasome-dependent degradation

This study shows junctophilin-2 protects cardiomyocytes from stress by preventing junctin ubiquitination and degradation, maintaining Ca2+ homeostasis and reducing apoptosis.

Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance

The paper reclassifies a variant in KCNH2 as a low penetrant likely pathogenic variant for LQTS2 based on biophysical effects and clinical variability.

A phenotype-based forward genetic screen identifies Dnajb6 as a sick sinus syndrome gene

This study identifies Dnajb6 as a gene causing sick sinus syndrome through a phenotype-based genetic screen in zebrafish.

Functional Assays Reclassify Suspected Splice-Altering Variants of Uncertain Significance in Mendelian Channelopathies

The paper uses functional assays to reclassify splice-altering variants in Brugada Syndrome and Long QT Syndrome genes, identifying pathogenic and benign classifications.

Novel Biosensor Identifies Ruxolitinib as a Potent and Cardioprotective CaMKII Inhibitor

The paper develops a CaMKII biosensor for high-throughput screening and identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor effective in preventing atrial fibrillation.

The Long Noncoding RNA Playrr Regulates Pitx2 Dosage and Protects Against Cardiac Arrhythmias

This study identifies Playrr, a lncRNA that regulates Pitx2 dosage and protects against cardiac arrhythmias by modulating cardiac gene expression and atrial substrate.

Interpretable machine learning of action potential duration restitution kinetics in single-cell models of atrial cardiomyocytes

The paper uses interpretable machine learning to analyze parameter-phenotype relationships in atrial cardiomyocyte models, identifying key ion channels influencing Smax.

Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization and repolarization

A polygenic risk score to predict sudden cardiac arrest in patients with coronary artery disease

This paper develops a polygenic risk score (metaPRS) to predict sudden cardiac arrest in patients with coronary artery disease using genetic and clinical data from two cohorts.

Numerical methods for the detection of phase defect structures in excitable media

This paper compares phase defect detection algorithms in cardiac arrhythmia data, finding that phase definition is more critical than algorithm choice for identifying phase defect lines.

A calibrated functional patch clamp assay to enhance clinical variant interpretation in KCNH2-related long QT syndrome

This study uses a high-throughput patch-clamp assay to reclassify KCNH2 variants of uncertain significance, providing evidence for clinical interpretation.

Functional heterogeneity of cell populations increases robustness of pacemaker function in a numerical model of the sinoatrial node tissue

The paper uses a computational model to show that functional heterogeneity in pacemaker cells enhances the robustness of SAN function by enabling cooperative interactions between firing and dormant cells.

Monogenic and Polygenic Contributions to QTc Prolongation in the Population

This study investigates how rare and common genetic variations contribute to QT interval duration, finding that both monogenic and polygenic factors influence QTc prolongation, with polygenic risk modulating the effect of rare variants.

Dominant negative effects of SCN5A missense variants

The paper shows that most SCN5A missense loss-of-function variants cause dominant negative effects and are associated with higher Brugada Syndrome risk.

Arrhythmia variant associations and reclassifications in the eMERGE-III sequencing study

The paper identifies pathogenic variants in arrhythmia genes in eMERGE-III participants and reclassifies variants of uncertain significance using functional studies.

In vivo identification and validation of novel potential predictors for human cardiovascular diseases

The paper identifies and validates 16 GWAS candidates with potential predictive power for human cardiovascular diseases using CRISPR/Cas9 in medaka.

Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications

The paper develops statistical translators to map cardiac myocyte electrophysiological responses across species, validated with experimental data and simulations.

A Novel Mice Model of Catecholaminergic Polymorphic Ventricular Tachycardia Generated by CRISPR/Cas9

This study creates a new CPVT mouse model by knocking out TECRL and shows it leads to cardiac arrhythmias and calcium handling defects.

Transcriptome profile of the zebrafish atrioventricular canal reveals molecular signatures of pacemaker and valve mesenchyme

The paper profiles the transcriptome of the zebrafish atrioventricular canal to identify molecular signatures of pacemaker and valve mesenchyme, revealing conserved features with mammalian AV node and cardiac valves.

CardIAP: Calcium images analyzer web application

CardIAP is a web application that automates the analysis of calcium fluorescence imaging data to identify spatio-temporal patterns and extract quantitative information on calcium dynamics.

Molecular Noise-Filtering in the β-adrenergic Signaling Network by Phospholamban Pentamers

The paper shows that PLN pentamers act as noise-filters in β-adrenergic signaling by regulating monomer phosphorylation and stabilizing SERCA activity despite PKA activity fluctuations.

The openCARP Simulation Environment for Cardiac Electrophysiology

The paper introduces openCARP, an open-source simulation environment for cardiac electrophysiology, and describes its capabilities and potential to improve reproducibility and standardization in the field.

Genetics of Unexplained Sudden Cardiac Death in Adult Caucasian and African American Individuals Living in the State of Maryland

This study examines the association between pathogenic or likely pathogenic genetic variants in cardiomyopathy and arrhythmia genes and unexplained sudden cardiac death in adults with no gross pathological findings.

Kinase independent function of PI3Kγ modulates calcium re-uptake by regulating phospholamban function

This study shows that PI3Kγ regulates calcium re-uptake in cardiomyocytes by modulating phospholamban phosphorylation through PP2A, independent of its kinase activity.

Piezo1 and BKCa channels in human atrial fibroblasts: interplay and remodelling in atrial fibrillation

This study identifies two stretch-activated ion channels, Piezo1 and BKCa, in human atrial fibroblasts and shows their differential regulation in atrial fibrillation.

Global approaches to postmortem genetic testing after sudden cardiac death in the young: A survey among healthcare professionals

This study surveys healthcare professionals on postmortem genetic testing practices for sudden cardiac death in young individuals, finding inconsistent access and variability in attitudes across regions.

Innervation and Neuronal Control of the Mammalian Sinoatrial Node: A Comprehensive Atlas

The paper creates a comprehensive neuroanatomic atlas of the RAGP-SAN complex in porcine and human hearts, showing how intrinsic cardiac neurons control SAN automaticity and cardiac function.

Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCa1.1, in Sinus Node Function and Arrhythmia Risk

The paper investigates the role of KCa1.1 in sinus node function and arrhythmia risk across species, finding conserved effects of its loss of function.