A5005320768- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Ion channel regulation and function
- Cardiovascular Effects of Exercise
- Heart Rate Variability and Autonomic Control
- ECG Monitoring and Analysis
- Viral Infections and Immunology Research
- Cardiovascular Function and Risk Factors
- Congenital heart defects research
- Receptor Mechanisms and Signaling
- Blood Pressure and Hypertension Studies
- Lipoproteins and Cardiovascular Health
- Cardiac Arrhythmias and Treatments
- Atrial Fibrillation Management and Outcomes
- Neuroscience and Neural Engineering
- scientometrics and bibliometrics research
- Academic Writing and Publishing
- Cardiac Imaging and Diagnostics
- Genetics, Aging, and Longevity in Model Organisms
- Cardiac pacing and defibrillation studies
- Cancer, Lipids, and Metabolism
- RNA Research and Splicing
- Electrochemical Analysis and Applications
- Obsessive-Compulsive Spectrum Disorders
- Ion Transport and Channel Regulation
Stellenbosch University
2015-2025
Netcare Jakaranda Hospital
2022
Tygerberg Hospital
1993-2021
Western Cape Department of Health
2020
University of Pavia
2001-2016
University of Helsinki
2004-2016
Istituti di Ricovero e Cura a Carattere Scientifico
2004-2016
IRCCS Istituto Auxologico Italiano
2009-2016
Helsinki University Hospital
2016
German Centre for Cardiovascular Research
2016
Background —The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding the electrophysiological consequences these opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that conditions (“triggers”) associated with events may in large part be gene specific. Methods and Results —We identified 670 LQTS patients known genotype (LQT1, n=371; LQT2,...
The management of long-QT syndrome (LQTS) patients who continue to have cardiac events (CEs) despite beta-blockers is complex. We assessed the long-term efficacy left sympathetic denervation (LCSD) in a group high-risk patients.We identified 147 LQTS underwent LCSD. Their QT interval was very prolonged (QTc, 543+/-65 ms); 99% were symptomatic; 48% had arrest; and 75% those treated with remained symptomatic. average follow-up periods between first CE LCSD post-LCSD 4.6 7.8 years,...
BACKGROUND X-linked cardiomyopathy (XLCM) is a rapidly progressive primary myocardial disorder presenting in teenage males as congestive heart failure. Manifesting female carriers have later onset (fifth decade) and slower progression. The purpose of this study was to localize the XLCM gene locus two families using molecular genetic techniques. METHODS AND RESULTS Linkage analysis 60 X-chromosome-specific DNA markers performed previously reported large pedigree smaller new pedigree....
Progressive familial heart block type I (PFHBI) is a progressive cardiac bundle branch disease in the His-Purkinje system that exhibits autosomal-dominant inheritance. In 3 branches of large South African Afrikaner pedigree with an form PFHBI, we identified mutation c.19G-->A transient receptor potential cation channel, subfamily M, member 4 gene (TRPM4) at chromosomal locus 19q13.3. This predicted amino acid substitution p.E7K TRPM4 terminus. encodes Ca2+-activated nonselective (CAN)...
A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine characteristics LQTS receiving ICD, indications, and aftermath.The study population included 233 patients. Beginning 2002, data were collected prospectively. Female (77%) LQT3 (22% genotype positive) overrepresented; mean QTc was 516±65 milliseconds; age at implantation 30±17 years; known...
Background— In congenital long-QT syndrome (LQTS), a genetically heterogeneous disorder that predisposes to sudden cardiac death, genetic factors other than the primary mutation may modify probability of life-threatening events. Recent evidence indicates common variants in NOS1AP are associated with QT-interval duration general population. Methods and Results— We tested hypothesis risk clinical manifestations degree prolongation South African LQTS population (500 subjects, 205 carriers)...
Background— In the congenital long-QT syndrome (LQTS), there can be a marked phenotypic heterogeneity. Founder effects, by which many individuals share mutation identical descent, represent powerful tool to further understand underlying mechanisms and predict natural history of mutation-associated effects. We are investigating one such founder effect, originating in South Africa approximately ad 1700 segregating same KCNQ1 (A341V). Methods Results— The study population involved 320 subjects,...
Background— The impressive clinical heterogeneity of the long-QT syndrome (LQTS) remains partially unexplained. In a South African (SA) founder population, we identified common LQTS type 1 (LQT1)–causing mutation ( KCNQ1 -A341V) associated with high severity. We tested whether arrhythmic risk was caused directly by A341V or its presence in specific ethnic setting SA families. Methods and Results— Seventy-eight patients, all single -A341V mutation, from 21 families 8 countries were compared...
Progressive familial heart block type I (PF-HBI) is a dominantly inherited cardiac bundle-branch conduction disorder that has been traced through nine generations of large South African kindred. Similar disorders have reported elsewhere; however, the cause these diseases unknown. The aim present study was to determine by linkage analysis approximate chromosomal position gene causing PFHBI, thereby allowing family-based diagnosis and development positional cloning strategies identify...
Background— Long-QT syndrome (LQTS), a cardiac arrhythmia disorder with variable phenotype, often results in devastating outcomes, including sudden death. Variable expression, independently from the primary disease-causing mutation, can partly be explained by genetic modifiers. This study investigates variants known LQTS-causative gene, AKAP9 , for potential LQTS-type 1–modifying effects. Methods and Results— Members of South African 1 founder population (181 noncarriers 168 mutation...
Mutation type, location, dominant-negative IKs reduction, and possibly loss of cyclic adenosine monophosphate (cAMP)-dependent stimulation via protein kinase A (PKA) influence the clinical severity long QT syndrome type 1 (LQT1). Given malignancy KCNQ1-p.A341V, we assessed whether mutations neighbouring p.A341V in S6 channel segment could also increase arrhythmic risk.Clinical genetic data were obtained from 1316 LQT1 patients [450 families, 166 unique KCNQ1 mutations, including 277...
Familial hypertrophic cardiomyopathy (HCM) is caused by mutations in 9 sarcomeric protein genes. The most commonly affected beta-myosin heavy chain (MYH7), where missense cluster the head and neck regions directly affect motor function. Comparable have not been described light meromyosin (LMM) region of myosin rod, nor would these be expected to We studied 82 probands with HCM whom no had found MYH7 exons encoding other frequently implicated disease Primers were designed amplify 24 40 MYH7....
Familial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in young. Recent application restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian 14 (US and French-Canadian two (National Institutes Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one...
The study assesses complexity of the cardiac control directed to sinus node and ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over beat-to-beat variability series heart period (HP) interval. HP interval were approximated respectively as temporal distance between two consecutive R-wave peaks apex T-wave end. Both measures automatically taken from 24-hour electrocardiographic Holter traces...
Abstract Aims Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) LQTS type 3. We aimed investigate whether SGK1-Inh could similarly APD types and 2. Methods results Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)...
Background: Long QT syndrome (LQTS) is a life-threatening condition characterized by prolonged intervals on electrocardiograms and increased susceptibility to drugs affecting cardiac repolarization. Congenital forms are mostly associated with variants in the KCNQ1 KCNH2 genes. Among pathogenic or likely (P/LP) variants, some significantly higher incidence of events compared others. While therapies such as beta-blockers have reduced mortality, patients unresponsive intolerant these...