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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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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. |
format | Online Article Text |
id | pubmed-5887247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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