Epidemiology of inherited arrhythmias

Offerhaus, Joost A.; Bezzina, Connie R.; Wilde, Arthur A.M.

doi:10.1038/s41569-019-0266-2

Cited by 40 publications

(34 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In humans, the prevalence of J-waves in ECGs varies between 5% and 19% (Offerhaus, Bezzina and Wilde, 2020). In the majority of cases these J-waves are benign.…”

Section: Discussionmentioning

confidence: 99%

The mechanism underlying J-waves and T-waves in the electrocardiogram of mice and zebra finches

Offerhaus

Snelderwaard

Faber

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Brief cardiac cycles are required to achieve high heart rates as seen in endothermic animals. A main determinant of the cardiac cycle is the repolarization phase of the cardiac action potential, which is visible in the ECG as a T-wave. In mammals with high heart rates – such as rodents – the repolarization phase is short and the ECG is characterized by a positive deflection following the QRS-complex, the J-wave. It is unclear whether birds with high heart rates show similar ECG characteristics. Here we study cardiac repolarization and the ECG in the zebra finch which has high heart rates. In ex vivo hearts of zebra finch (N=5) and mouse (N=5), pseudo-ECGs and optical action potentials were measured. In both species, total ventricular activation was fast with QRS durations shorter than 10ms. Ventricular activation progressed from the left to the right ventricle in zebra finch whereas the activation pattern was apex-to-base in mouse. In both species, phase 1 early repolarization followed the activation front, causing a positive J-wave in the pseudo-ECG. In zebra finch, late repolarization was directed from the right ventricle to the left ventricle, whereas late repolarization was directed opposite in mouse. Accordingly, on the zebra finch ECG, the J-wave and the T-wave have the same direction, whereas in the mouse the J-wave and the T-wave are discordant. Our findings demonstrate early repolarization and the associated J-wave are not restricted to mammals and that they also occur within birds. Early repolarization may have evolved by convergence in association with high heart rates.Summary statementZebra finches are small birds with high heart rates. Similar to small rodents, the zebra finch ECG contains a J-wave, which is caused by early repolarization

show abstract

“…In humans, the prevalence of J-waves in ECGs varies between 5% and 19% (Offerhaus, Bezzina and Wilde, 2020). In the majority of cases these J-waves are benign.…”

Section: Discussionmentioning

confidence: 99%

The mechanism underlying J-waves and T-waves in the electrocardiogram of mice and zebra finches

Offerhaus

Snelderwaard

Faber

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Founder mutations are mutations shared by a (large) number of individuals who have a common origin and all share a unique chromosomal background (haplotype) on which the mutation occurred. They appear to be frequent in the Netherlands, both in the cardiovascular domain [4][5][6][7][8][9], and in other domains [10]. Within the cardiovascular domain well-studied examples are HCM with three founder mutations being responsible for an estimated 40% of Dutch HCM patients [4,11], the 1795insD mutation in the cardiac sodium channel (SCN5A) associated with a SCN5Aoverlap syndrome (i.e., a disease entity with both gain of function (LQTS) and loss of function characteristics (progressive cardiac conduction disease and Brugada syndrome)) [7], a haplotype on chromosome 7 associated with idiopathic ventricular fibrillation [6], and the PLN Argdel14 mutation [8].…”

Section: Founder Mutationsmentioning

confidence: 99%

Cardiogenetics, 25 years a growing subspecialism

2020

Self Cite

View full text Add to dashboard Cite

The cardiology and clinical genetics subspecialty of cardiogenetics has experienced a tremendous growth in the past 25 years. This review discusses examples of the progress that has been made as well as new challenges that have arisen within this field, with special focus on the Netherlands. A significant number of Dutch founder mutations, i.e. mutations shared by a number of individuals who have a common origin and all share a unique chromosomal background on which the mutation occurred, have been identified and have provided unique insights into genotypephenotype correlations in inherited arrhythmia syndromes and inherited cardiomyopathies. Cardiological and genetic screening of family members of young victims of sudden cardiac death combined with genetic testing in the deceased individual have turned out to be rewarding. However, the interpretation of the results of genetic testing in this setting and in the setting of living patients with a (suspected) phenotype is now considered more challenging than previously anticipated, because the introduction of high-throughput sequencing technologies has resulted in the identification of a significant number of variants of unknown significance. Interpretation of genetic and clinical findings by experienced multidisciplinary teams are key to ensure a high quality of care to the patient and the family.

show abstract

“…As a result, the normal physiological functioning of these channels is altered, which disturbs the ionic homeostasis inside the cardiomyocytes (CMs) and affects the cardiac action potential (AP). Hence, an arrhythmogenic substrate arises which increases the risk of life-threatening arrhythmias and consequent sudden cardiac death, even in prior asymptomatic young patients [1,2]. Long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic Hearts 2020, 1 182 ventricular tachycardia (CPVT) are the four major channelopathies.…”

Section: Introductionmentioning

confidence: 99%

“…Long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic Hearts 2020, 1 182 ventricular tachycardia (CPVT) are the four major channelopathies. The reported prevalence of channelopathies is often an underestimation because of the presence of asymptomatic mutation carriers, low penetrance, variable expressivity within and between families and diagnostic difficulties as changes in electrocardiogram (ECG) patterns are transient [1][2][3]. Due to this, elucidating the pathophysiological mechanisms behind the ICAs and identifying patients remains challenging.…”

Section: Introductionmentioning

confidence: 99%

Optical Mapping in hiPSC-CM and Zebrafish to Resolve Cardiac Arrhythmias

Vandendriessche

Sieliwonczyk

Alaerts

et al. 2020

Hearts

View full text Add to dashboard Cite

Inherited cardiac arrhythmias contribute substantially to sudden cardiac death in the young. The underlying pathophysiology remains incompletely understood because of the lack of representative study models and the labour-intensive nature of electrophysiological patch clamp experiments. Whereas patch clamp is still considered the gold standard for investigating electrical properties in a cell, optical mapping of voltage and calcium transients has paved the way for high-throughput studies. Moreover, the development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) has enabled the study of patient specific cell lines capturing the full genomic background. Nevertheless, hiPSC-CMs do not fully address the complex interactions between various cell types in the heart. Studies using in vivo models, are therefore necessary. Given the analogies between the human and zebrafish cardiovascular system, zebrafish has emerged as a cost-efficient model for arrhythmogenic diseases. In this review, we describe how hiPSC-CM and zebrafish are employed as models to study primary electrical disorders. We provide an overview of the contemporary electrophysiological phenotyping tools and discuss in more depth the different strategies available for optical mapping. We consider the current advantages and disadvantages of both hiPSC-CM and zebrafish as a model and optical mapping as phenotyping tool and propose strategies for further improvement. Overall, the combination of experimental readouts at cellular (hiPSC-CM) and whole organ (zebrafish) level can raise our understanding of the complexity of inherited cardiac arrhythmia disorders to the next level.

show abstract

Epidemiology of inherited arrhythmias

Cited by 40 publications

References 162 publications

The mechanism underlying J-waves and T-waves in the electrocardiogram of mice and zebra finches

The mechanism underlying J-waves and T-waves in the electrocardiogram of mice and zebra finches

Cardiogenetics, 25 years a growing subspecialism

Optical Mapping in hiPSC-CM and Zebrafish to Resolve Cardiac Arrhythmias

Contact Info

Product

Resources

About