Cardiac electrophysiology and arrhythmias

Sinoatrial Node Impulses Emerge From Incessant, Unique Kinetic Transitions In Disordered Local Calcium Dynamics

The paper analyzes local calcium dynamics in mouse sinoatrial node cells to show how stochastic transitions in heterogeneous calcium oscillations generate rhythmic impulses.

A polygenic predictor of baseline QTc is associated with sotalol-induced QT prolongation

The paper develops a polygenic risk score for baseline QTc and shows it predicts sotalol-induced QT prolongation in a cohort of healthy subjects.

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes

The paper shows that TBX5 recruits CHD4 to regulate chromatin organization in atrial cardiomyocytes, affecting gene expression and atrial rhythm.

Geometrically-derived action potential markers for model development: a principled approach?

The paper investigates deriving action potential biomarkers from a linearised action potential function.

A Natural History Study of Timothy Syndrome

This study describes the first natural history of Timothy syndrome, identifying common extra-cardiac features beyond cardiac issues.

Data-driven insights into the association between oxidative stress and calcium-regulating proteins in cardiovascular disease.

The paper develops a data science pipeline to analyze interactions between Ca2+-regulating proteins and cardiovascular diseases, identifying associations with oxidative stress and cardiac arrhythmias.

Ephaptic coupling enables action potential conduction

This study demonstrates that ephaptic transmission can enable action potential conduction between cardiomyocytes, even in the presence of gap junctions, through shielded local domains.

Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells

This study examines the structure-function relationship of Ryanodine Receptor (RyR) clusters in sinoatrial node cells, showing how heterogeneities in cluster size and location influence calcium release and action potential firing rates.

Septins regulate heart contractility through modulation of cardiomyocyte store-operated calcium entry

This study shows septins regulate heart contractility by modulating store-operated calcium entry in cardiomyocytes, using Drosophila models and genetic manipulations.

CardioMEA: Comprehensive Data Analysis Platform for Studying Cardiac Diseases and Drug Responses

CardioMEA is a data-analysis platform for HD-MEA data from iPSC-CMs, enabling electrophysiological analysis of cardiac diseases and drug responses.

Gene Therapy with the N-terminal Fragment of Nav1.5 for Cardiac Channelopathies: A Novel Transcomplementation Mechanism Potentiating the Cardiac Sodium Current

This paper demonstrates that overexpressing the N-terminal fragment of Nav1.5 restores cardiac sodium current and electrical activity in models of Brugada syndrome.

Depleting trafficking regulator CASK promotes intercalated disc organization and ventricular function

This study shows that CASK depletion improves intercalated disc organization and ventricular function in multiple models, suggesting CASK as a repressor of ID structure and function in cardiac disease.

A rare non-coding enhancer variant in SCN5A contributes to the high prevalence of Brugada syndrome in Thailand

The paper identifies a rare non-coding enhancer variant in SCN5A associated with Brugada syndrome in Thailand, showing it disrupts a transcription factor binding site and reduces sodium current.

Mitochondrial reactive oxygen species cause arrhythmias in hypertrophic cardiomyopathy

This study shows that mitochondrial reactive oxygen species contribute to arrhythmias in hypertrophic cardiomyopathy by disrupting calcium handling and electrical conduction.

The fully activated open state of KCNQ1 controls the cardiac 'fight-or-flight' response

This paper identifies the fully activated open state of KCNQ1 as critical for β-adrenergic stimulation of IKs channels, showing that modulators enhancing this state can restore function in LQT1 mutants.

Functional characterization of QT interval associated SCN5A enhancer variants identify combined additive effects

The paper investigates the combined effects of SCN5A enhancer variants on gene expression and demonstrates their additive regulatory impact in vitro and in vivo.

Prognostic Value of Multiplexed Assays of Variant Effect and Automated Patch-clamping for KCNH2-LQTS Risk Stratification

This paper evaluates how functional variant data and penetrance estimates improve risk stratification for LQTS in KCNH2 missense variant carriers.

SGLT2 inhibitors protect against diabetic cardiomyopathy and atrial fibrillation through a CaMKII independent mechanism

This study shows SGLT2 inhibitors reduce diabetic cardiomyopathy and atrial fibrillation risk in T2D mice, but their effects are not dependent on CaMKII inhibition.

The Ithildin library for efficient numerical solution of anisotropic reaction-diffusion problems in excitable media

The paper introduces Ithildin, an open-source library for simulating excitable media, demonstrating its use in cardiac electrophysiology simulations.

TMPRSS6 cleaves KCNE1 and causes arrhythmias in iron overload disease

This study identifies TMPRSS6 cleavage of KCNE1 as a mechanism causing arrhythmias in iron overload disease using human iPSC-derived cardiomyocytes and computational models.

An autosomal dominant cardiac arrhythmia syndrome, ST Depression Syndrome, is caused by the de novo creation of a cardiomyocyte enhancer.

The paper identifies a de novo enhancer mutation in KCNB1 causing ST Depression Syndrome, a cardiac arrhythmia, and shows it can be predicted by a deep neural network.

Upstream alternative polyadenylation in SCN5A produces a short transcript isoform encoding a mitochondria-localized NaV1.5 N-terminal fragment that influences cardiomyocyte respiration

This study identifies an upstream alternative polyadenylation event in SCN5A that generates a short transcript encoding a mitochondria-localized NaV1.5 N-terminal fragment, which affects cardiomyocyte respiration.

Salidroside Mitigates Malignant Arrhythmias by Restoring Sodium Channel Function During Ultra-Acute Myocardial Infarction

This paper shows Salidroside reduces malignant arrhythmias in AMI by restoring sodium channel function and improving conduction uniformity.

Polygenic Risk Score predicts QTc-prolongation and Short-Term Mortality in Patients using QT-prolonging Psychoactive Medications

This study shows that a polygenic risk score for QTc (PRSQTc) predicts increased QTc interval and short-term mortality in patients starting QT-prolonging medications.

Sympathetic structural and electrophysiological remodeling in a rabbit model of reperfused myocardial infarction

This study investigates sympathetic remodeling in rabbit hearts after reperfused myocardial infarction, finding CSPGs correlate with reduced nerve density but preserved sympathetic responsiveness, leading to increased arrhythmia risk.

Polycystin-1 loss of function increases susceptibility to atrial fibrillation through impaired DNA damage response

Biallelic variants in POPDC2 cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy

Multi-site validation of a functional assay to adjudicate SCN5A Brugada Syndrome-associated variants

The paper validates an in vitro SCN5A Brugada Syndrome assay to reclassify variants of uncertain significance as pathogenic or benign.

S100A1's single cysteine is an indispensable redox-switch for the protection against diastolic calcium leakage in cardiomyocytes

This study identifies S100A1's C85 residue as a redox-switch critical for preventing diastolic calcium leakage in cardiomyocytes, without affecting inotropic function.

Identifying barriers to genetic testing in subspecialty cardiac care

This study identifies barriers to genetic testing in cardiac care by surveying providers, finding insurance issues and specialty differences affect testing uptake.