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Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients

BACKGROUND: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate ri...

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Autores principales: Koponen, Mikael, Havulinna, Aki S., Marjamaa, Annukka, Tuiskula, Annukka M., Salomaa, Veikko, Laitinen-Forsblom, Päivi J., Piippo, Kirsi, Toivonen, Lauri, Kontula, Kimmo, Viitasalo, Matti, Swan, Heikki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887247/
https://www.ncbi.nlm.nih.gov/pubmed/29622001
http://dx.doi.org/10.1186/s12881-018-0574-0
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author Koponen, Mikael
Havulinna, Aki S.
Marjamaa, Annukka
Tuiskula, Annukka M.
Salomaa, Veikko
Laitinen-Forsblom, Päivi J.
Piippo, Kirsi
Toivonen, Lauri
Kontula, Kimmo
Viitasalo, Matti
Swan, Heikki
author_facet Koponen, Mikael
Havulinna, Aki S.
Marjamaa, Annukka
Tuiskula, Annukka M.
Salomaa, Veikko
Laitinen-Forsblom, Päivi J.
Piippo, Kirsi
Toivonen, Lauri
Kontula, Kimmo
Viitasalo, Matti
Swan, Heikki
author_sort Koponen, Mikael
collection PubMed
description BACKGROUND: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. METHODS: A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18–40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. RESULTS: In mutation carriers, risk factors for cardiac events before initiation of β-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p < 0.001), a cardiac event before the age of 18 years (HR = 5.9, p < 0.001), and QTc ≥500 ms (vs < 470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0–3.9, p < 0.001–0.03) compared to G589D, c.1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c.453delC, L552S and R176W mutations associated with lower risk (HR = 0.11–0.23, p < 0.001) than other KCNH2 mutations. CONCLUSIONS: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0574-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-58872472018-04-09 Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients Koponen, Mikael Havulinna, Aki S. Marjamaa, Annukka Tuiskula, Annukka M. Salomaa, Veikko Laitinen-Forsblom, Päivi J. Piippo, Kirsi Toivonen, Lauri Kontula, Kimmo Viitasalo, Matti Swan, Heikki BMC Med Genet Research Article BACKGROUND: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. METHODS: A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18–40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. RESULTS: In mutation carriers, risk factors for cardiac events before initiation of β-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p < 0.001), a cardiac event before the age of 18 years (HR = 5.9, p < 0.001), and QTc ≥500 ms (vs < 470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0–3.9, p < 0.001–0.03) compared to G589D, c.1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c.453delC, L552S and R176W mutations associated with lower risk (HR = 0.11–0.23, p < 0.001) than other KCNH2 mutations. CONCLUSIONS: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0574-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-05 /pmc/articles/PMC5887247/ /pubmed/29622001 http://dx.doi.org/10.1186/s12881-018-0574-0 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Koponen, Mikael
Havulinna, Aki S.
Marjamaa, Annukka
Tuiskula, Annukka M.
Salomaa, Veikko
Laitinen-Forsblom, Päivi J.
Piippo, Kirsi
Toivonen, Lauri
Kontula, Kimmo
Viitasalo, Matti
Swan, Heikki
Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients
title Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients
title_full Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients
title_fullStr Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients
title_full_unstemmed Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients
title_short Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients: Koponen et al. Follow-up of adult LQTS patients
title_sort clinical and molecular genetic risk determinants in adult long qt syndrome type 1 and 2 patients: koponen et al. follow-up of adult lqts patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887247/
https://www.ncbi.nlm.nih.gov/pubmed/29622001
http://dx.doi.org/10.1186/s12881-018-0574-0
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