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- Lahrouchi, Najim, et al.
(author)
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Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
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Journal article (peer-reviewed)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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- Carrick, Richard T., et al.
(author)
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Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe
- 2024
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In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645.
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Journal article (peer-reviewed)abstract
- Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed.Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans.Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
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- Moons, Philip, 1968, et al.
(author)
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Placing patient-reported outcomes at the centre of cardiovascular clinical practice: implications for quality of care and management A statement of the ESC Association of Cardiovascular Nursing and Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Preventive Cardiology (EAPC), Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), European Association of Cardiovascular Imaging (EACVI), ESC Regulatory Affairs Committee, ESC Advocacy Committee, ESC Digital Health Committee, ESC Education Committee, and the ESC Patient Forum
- 2023
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In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645.
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Journal article (peer-reviewed)abstract
- Patient-reported outcomes (PROs) provide important insights into patients' own perspectives about their health and medical condition, and there is evidence that their use can lead to improvements in the quality of care and to better-informed clinical decisions. Their application in cardiovascular populations has grown over the past decades. This statement describes what PROs are, and it provides an inventory of disease-specific and domain-specific PROs that have been developed for cardiovascular populations. International standards and quality indices have been published, which can guide the selection of PROs for clinical practice and in clinical trials and research; patients as well as experts in psychometrics should be involved in choosing which are most appropriate. Collaborations are needed to define criteria for using PROs to guide regulatory decisions, and the utility of PROs for comparing and monitoring the quality of care and for allocating resources should be evaluated. New sources for recording PROs include wearable digital health devices, medical registries, and electronic health record. Advice is given for the optimal use of PROs in shared clinical decision-making in cardiovascular medicine, and concerning future directions for their wider application.
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