A5045083789- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- ECG Monitoring and Analysis
- Cardiac pacing and defibrillation studies
- Cardiac Arrhythmias and Treatments
- Genetic Associations and Epidemiology
- Congenital heart defects research
- Neonatal Respiratory Health Research
- RNA and protein synthesis mechanisms
- Cardiac Valve Diseases and Treatments
- Cardiac Structural Anomalies and Repair
- Genomics and Rare Diseases
- Heart Failure Treatment and Management
- Cystic Fibrosis Research Advances
- RNA modifications and cancer
- Pulmonary Hypertension Research and Treatments
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Cardiac Arrest and Resuscitation
- RNA Research and Splicing
- Atrial Fibrillation Management and Outcomes
- Inhalation and Respiratory Drug Delivery
ERN GUARD-Heart
2018-2025
University of Amsterdam
2016-2025
Amsterdam University Medical Centers
2019-2025
Sequoia (United States)
2024
SEQUOIA (Italy)
2024
Oregon Health & Science University
2024
Netherlands Heart Institute
2009-2024
Chulalongkorn University
2024
Amsterdam Neuroscience
2019-2023
European Heart Network
2023
Background: Mutations in RBM20 (RNA-binding motif protein 20) cause a clinically aggressive form of dilated cardiomyopathy, with an increased risk malignant ventricular arrhythmias. is splicing factor that targets multiple pivotal cardiac genes, such as Titin (TTN) and CAMK2D (calcium/calmodulin-dependent kinase II delta). Aberrant TTN thought to be the main determinant RBM20-induced but not likely explain Here, we investigated extent which mutation carriers have arrhythmias explore...
AimsHeterozygous mutations in KCNQ1 cause type 1 long QT syndrome (LQT1), a disease characterized by prolonged heart rate-corrected interval (QTc) and life-threatening arrhythmias. It is unknown why penetrance expressivity so variable between individuals hosting identical mutations. We aimed to study whether this can be explained single nucleotide polymorphisms (SNPs) KCNQ1's 3′ untranslated region (3′UTR).
Catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome (SQTS) are inherited arrhythmogenic disorders that can cause sudden death. Numerous genes have been reported to these conditions, but evidence supporting gene-disease relationships varies considerably. To ensure appropriate utilization of genetic information for CPVT SQTS patients, we applied an evidence-based reappraisal previously genes.Three teams independently curated all published 11 9 implicated using...
Abstract Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality, with pathogenic variants found in about a third cases. Large-scale genome-wide association studies (GWAS) demonstrate that common genetic variation contributes to HCM risk. Here we derive polygenic scores (PGS) from GWAS genetically correlated traits test their performance the UK Biobank, 100,000 Genomes Project, clinical cohorts. We show higher PGS significantly increases risk general population,...
Background— Ventricular arrhythmia occurrence during exercise is reported in Brugada syndrome (BrS). Accordingly, experimental studies suggest that BrS-linked SCN5A mutations reduce sodium current more at fast heart rates. Yet, the effects of on BrS ECG phenotype have not been studied. We aimed to assess responses and determine whether these are affected by presence an mutation. Methods Results— ECGs baseline, peak exercise, recovery were analyzed from 35 male control subjects, 25 men...
Abstract Aims Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors ajmaline-induced PR and QRS changes Type I Brugada syndrome (BrS) electrocardiogram (ECG). Methods results In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements 26 721 ECGs, dose–response mixed modelling genotyping. calculated polygenic risk scores (PRS) interval (PRSPR),...
Stringent variant interpretation guidelines can lead to high rates of variants uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada (BrS). Quantitative disease-specific customization American College Medical Genetics Genomics/Association Molecular Pathology (ACMG/AMP) address this false negative rate.We compared rare frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) 3335 BrS (SCN5A) cases the International LQTS/BrS Consortia...
The pathogenic mutation p.Arg14del in the gene encoding Phospholamban (PLN) is known to cause cardiomyopathy and leads increased risk of sudden cardiac death. Automatic tools might improve detection patients with this rare disease. Deep learning currently state-of-the-art signal processing but requires large amounts data train algorithms. In situations relatively small data, like PLN, transfer may accuracy. We propose an ECG-based PLN using from a model originally trained for sex...
Type 2 congenital long QT syndrome (LQT-2) is linked to mutations in the human ether a-go-go-related gene (HERG) and characterized by rate-corrected interval (QTc) prolongation, ventricular arrhythmias, syncope, sudden death. Recognized triggers of these cardiac events include emotional acoustic stimuli. Here we investigated repeated occurrence fever-induced polymorphic tachycardia fibrillation LQT-2 patients with A558P missense mutation HERG. ECG analysis showed increased QTc fever both...
Conduction slowing of the electric impulse that drives heartbeat may evoke lethal cardiac arrhythmias. Mutations in SCN5A, which encodes pore-forming sodium channel alpha subunit, are associated with familial arrhythmia syndromes based on conduction slowing. However, disease severity among mutation carriers is highly variable. We hypothesized genetic modifiers underlie variability and severity. With aim identifying such modifiers, we studied Scn5a(1798insD/+) 2 distinct mouse strains, FVB/N...
Treatment with the anticancer drug taxol (TXL), which polymerizes cytoskeleton protein tubulin, may evoke cardiac arrhythmias based on reduced human sodium channel (Nav1.5) function. Therefore, we investigated whether enhanced tubulin polymerization by TXL affects Nav1.5 function and expression these effects are β1-subunit-mediated. Human embryonic kidney (HEK293) cells, transfected SCN5A cDNA alone or together SCN1B (Nav1.5 + β1), neonatal rat cardiomyocytes (NRCs) were incubated in...
Phospholamban (PLN) p.Arg14del mutation carriers are known to develop dilated and/or arrhythmogenic cardiomyopathy, and typical electrocardiographic (ECG) features have been identified for diagnosis. Machine learning is a powerful tool used in ECG analysis has shown outperform cardiologists.We aimed machine deep models diagnose PLN cardiomyopathy using ECGs evaluate their accuracy compared an expert cardiologist.We included 155 adult age- sex-matched control subjects. Twenty-one (13.4%) were...