Dataset Information

Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations.

ABSTRACT: During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment strategy. Moreover, disease expressivity and sensitivity to therapeutic interventions often varies between mutations and/or patients, underlining the need for more individualized strategies. The development of the induced pluripotent stem cell (iPSC) technology now provides the opportunity for generating iPSC-derived cardiomyocytes (CMs) from human material (hiPSC-CMs), enabling patient- and/or mutation-specific investigations. These hiPSC-CMs may furthermore be employed for identification and assessment of novel therapeutic strategies for arrhythmia syndromes. However, due to their relative immaturity, hiPSC-CMs also display a number of essential differences as compared to adult human CMs, and hence there are certain limitations in their use. We here review the electrophysiological characteristics of hiPSC-CMs, their use for investigating inherited arrhythmia syndromes, and their applicability for identification and assessment of (novel) anti-arrhythmic treatment strategies.

SUBMITTER: Casini S

PROVIDER: S-EPMC5550530 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations.

Casini Simona S Verkerk Arie O AO Remme Carol Ann CA

Cardiovascular drugs and therapy 20170601 3

During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment stra ...[more]

PMID: 28721524

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Project description:Implantable loop recorders (ILRs) are conventionally utilized to elucidate the mechanism of atypical syncope. The objective of this study was to assess the impact of these devices on management of pediatric patients with known or suspected inherited arrhythmia syndromes.A retrospective chart review was undertaken of all pediatric patients with known or suspected inherited arrhythmia syndromes in whom an ILR was implanted from 2008 to 2015. Captured data included categorization of diagnosis, treatment, transmitted tracings, and the impact of ILR tracings on management. Transmissions were categorized as symptomatic, autotriggered, or routine. Actionable transmissions were abnormal tracings that directly resulted in a change of medical or device therapy. A total of 20 patients met the stated inclusion criteria (long QT syndrome, n=8, catecholaminergic polymorphic ventricular tachycardia,n=9, Brugada syndrome, n=1, arrhythmogenic right ventricular cardiomyopathy, n=2), with 60% of patients being genotype positive. Primary indication for implantation of ILR included ongoing monitoring +/- symptoms (n=15, 75%), suspicion of noncompliance (n=1, 5%), and liberalization of recommended activity restrictions (n=4, 25%). A total of 172 transmissions were received in patients with inherited arrhythmia syndromes, with 7% yielding actionable data. The majority (52%) of symptom events were documented in the long QT syndrome population, with only 1 tracing (5%) yielding actionable data. Automatic transmissions were mostly seen in the catecholaminergic polymorphic ventricular tachycardia cohort (81%), with 21% yielding actionable data. There was no actionable data in routine transmissions.ILRs in patients with suspected or confirmed inherited arrhythmia syndromes may be useful for guiding management. Findings escalated therapies in 30% of subjects. As importantly, in this high-risk population, the majority of symptom events represented normal or benign rhythms, reassuring patients and physicians that no further intervention was required.

Dataset Information

Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations.

Publications

Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations.

Similar Datasets

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