Cardiac electrophysiology and arrhythmias

Probabilistic Cardiac Digital Twins for Robust Patient-Specific Modeling

This paper introduces a framework for probabilistic cardiac digital twins that enables uncertainty quantification through joint probability density learning and conditional regression.

Sex-specific amplification of IKr-blocker-induced action potential prolongation by reduced female IKs repolarization reserve: a computational study using the O'Hara-Rudy human ventricular model

This paper uses a computational model to show that reduced IKs conductance in female cardiomyocytes amplifies the effect of IKr blockers, leading to greater action potential prolongation and increased risk of arrhythmia.

A New Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor Abundance and Superclustering

This paper uses dSTORM to visualize RyR clusters in rabbit SANCs and develops a model showing superclustering and RyR density changes modulate APCL during βAR stimulation.

Increased calcium spark frequency and variability of action potential duration precede early after depolarisations in isolated ventricular myocytes

This study shows that increased action potential duration variability and calcium sparks precede early afterdepolarisations in ventricular myocytes, suggesting calcium handling instability as a key mechanism for drug-induced arrhythmias.

Wave propagation enhances extracellular signal strength in small excitable tissues

The paper shows that localized stimulation generating traveling waves enhances extracellular signal strength in hiPSC-CMs compared to uniform stimulation.

MeTAL enables multiparametric risk prediction for human KCNH2 variants

MeTAL links KCNH2 variant biophysical properties to ECG phenotypes, revealing nonlinear relationships and improving risk prediction for inherited arrhythmia syndromes.

A Novel Mechanism of Cardiomyopathy: Toxic Peptides Dysregulate Calcium Transport

The paper identifies toxic transmembrane peptides that inhibit SERCA function in DCM, offering a new mechanism for calcium mishandling in heart failure.

A novel RyR2-selective stabilizer prevents stress-induced ventricular arrhythmias without impairing cardiac function

Ryanozole, a RyR2-selective stabilizer, prevents stress-induced arrhythmias without impairing cardiac function in CPVT mouse models.

Endurance exercise remodels pulmonary vein sleeve myocytes and promotes a proarrhythmic atrial substrate

This study shows endurance exercise increases proarrhythmic remodeling in pulmonary vein sleeve myocytes and the PV-LA junction, contributing to atrial fibrillation susceptibility in athletes.

Myocardial STIM1 deficiency triggers mitochondrial fission to impair electrophysiological function and exacerbate post-MI remodeling

This study shows that reducing STIM1 in cardiomyocytes causes mitochondrial fragmentation and metabolic changes, leading to electrical instability and worsened heart function after a heart attack.

Rapid functional classification of cardiac genetic variants directly informs precision cardiology

This paper introduces REVi-SCOPE, a platform that rapidly characterizes cardiac variants' functional impact, enabling precision cardiology by analyzing VUSs in 10 days.

Programmed electrical stimulation in human iPSC-derived cardiomyocytes reveals mechanisms of lethal arrhythmias in Calcium Release Deficiency Syndrome

This study uses hiPSC-derived cardiomyocytes to model CRDS, showing that programmed electrical stimulation induces arrhythmias through EADs and re-entry, which can be suppressed by flecainide.

Cardiac Calsequestrin is a Physiological Dimer that Polymerizes through a Ca2+-Triggered Cooperative Switch

This study shows cardiac Calsequestrin (CASQ2) is an intrinsic dimer that polymerizes via a Ca2+-triggered cooperative switch, with K+ ions modulating this process.

Structured local mismatch placement and internal packaging in cardiomyocytes during hyperthermal sarcomeric oscillations

This paper shows that local nonuniformity in cardiomyocytes during hyperthermal sarcomeric oscillations is structured at multiple mesoscale levels, with a shared rephasing compass organizing mismatch-pocket placement and internal redistribution routes.

In silico assessment of arrhythmic risk following the implantation of engineered heart tissues in porcine hearts with varying infarct locations

This study assesses arrhythmic risk from engineered heart tissue implantation in porcine hearts with different infarct locations using computational models.

Constrained neighboring-sarcomere phase topology relates to mean HSO amplitude in living cardiomyocytes

The paper analyzes sarcomere-length recordings in neonatal rat cardiomyocytes to show that hyperthermal sarcomeric oscillations (HSOs) exhibit a constrained neighboring-sarcomere phase topology and that the mean HSO amplitude can be described by the product of local amplitude and synchrony.

Beat-locked ATP microdomains in the sinoatrial node map a calcium-timed energetic hierarchy and regional pacemaker roles

The paper tracks beat-resolved ATP dynamics in mouse sinoatrial node myocytes, revealing distinct ATP-gain and -dip modes linked to regional pacemaker roles and energy supply.

PITX2C Deficiency Promotes Arrhythmogenic Remodeling via Oxidative Stress in Atrial Myocytes

This study shows that PITX2C deficiency leads to reduced oxidative metabolism and increased oxidative stress in atrial myocytes, causing arrhythmogenic remodeling and structural changes, which can be mitigated by antioxidants.

A Cohort-Based Global Sensitivity Benchmark of MRI-Derived Whole-Heart Electromechanical Models in Healthy Hearts

The paper benchmarks global sensitivity analysis of whole-heart electromechanical models across five healthy subjects, finding haemodynamic parameters dominate cardiac function despite anatomical variation.

Common Genetic Variants of The Cardiac Sodium Channel Alter Patient Response to Class 1b Antiarrhythmics

The paper shows that a common SCN5A variant, S1103Y, alters mexiletine's pharmacological response in induced pluripotent stem cell-derived cardiomyocytes, leading to proarrhythmic effects.

A biatrial digital twin integrating electrophysiology, mechanics, and circulation: from physiology to atrial fibrillation

This paper presents a multiscale atrial digital twin framework that integrates electrophysiology, mechanics, and circulation to simulate normal and pathological atrial function, showing how electrical changes affect mechanical and hemodynamic outcomes.

Novel insights into IKur modulation by Lgi3-4: Implications in atrial fibrillation

This study shows Lgi3-4 modulate IKur by interfering with KV1.5-KVβ interactions, contributing to atrial fibrillation pathophysiology.

CALM1, CALM2, and CALM3 expression and translation efficiency provide insight into the severity of calmodulinopathy

The paper compares the clinical impact of missense variants in CALM1, CALM2, and CALM3 genes by analyzing expression levels and translation efficiency in cardiac tissue.

Disruption of RBM20 causes atrial electrophysiological disturbances

This study examines the effects of RBM20-R636Q mutation on atrial electrophysiology and evaluates SGLT inhibitors as potential therapeutics for atrial remodeling and arrhythmias.

Integrated multi-modal data analysis for computational modeling of healthy and location-dependent myocardial infarction conditions in porcine hearts

The paper develops porcine ventricular digital twins using multi-modal data to study myocardial infarction effects on cardiac function and ECG patterns.

Recessive POPDC1 Truncation Causes Lethal Short-QT Pattern Arrhythmogenic Cardiomyopathy with Multi-Ion Channel Remodeling and Ankyrin-G Scaffold Disruption

Comparative transcriptomics analysis of histone deacetylases, transcription factors, and ion channel genes in human iPSC-cardiomyocytes vs. the adult human heart

The paper compares transcriptomes of HDACs, TFs, and ion channels in hiPSC-CMs and adult human heart to identify regulatory relationships and cardiotoxicity implications of HDAC inhibitors.

Voltage Gated Calcium Channel Dysregulation May Contribute to Neurological Symptoms in Calmodulinopathies

This study investigates how calmodulin mutations affect voltage-gated calcium channel regulation in neurons, linking these effects to neurological symptoms in calmodulinopathies.

A Deep Learning-Based Scoring Framework for Large-Scale Multi-Donor Cardiotoxicity Screening

This paper develops a deep learning framework to screen for cardiotoxicity using hiPSC-derived cardiomyocytes, identifying compounds with high toxicity scores and inter-donor variability.

Sex-specific electrophysiology and cholinergic responses underlie differential mechanisms of arrhythmia vulnerability in rabbit atria

This study examines sex differences in rabbit atrial electrophysiology and arrhythmia susceptibility, finding greater APD heterogeneity and cholinergic responses in females and males under different conditions.