Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.

Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs)....

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Autores: Mazzanti, Andrea, Maragna, Riccardo, Vacanti, Gaetano, Monteforte, Nicola, Bloise, Raffaella, Marino, Maira, Braghieri, Lorenzo, Gambelli, Patrick, Memmi, Mirella, Pagan, Eleonora, Morini, Massimo, Malovini, Alberto, Ortiz, Martin, Sacilotto, Luciana, Bellazzi, Riccardo, Monserrat, Lorenzo, Napolitano, Carlo, Bagnardi, Vincenzo, Priori, Silvia G.
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10498
Acceso en línea:http://hdl.handle.net/20.500.12105/10498
Access Level:acceso abierto
Palabra clave:Cohort Studies
Female
Genotype
Heart
Humans
Long QT Syndrome
Male
Risk Assessment
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spelling Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.Mazzanti, AndreaMaragna, RiccardoVacanti, GaetanoMonteforte, NicolaBloise, RaffaellaMarino, MairaBraghieri, LorenzoGambelli, PatrickMemmi, MirellaPagan, EleonoraMorini, MassimoMalovini, AlbertoOrtiz, MartinSacilotto, LucianaBellazzi, RiccardoMonserrat, LorenzoNapolitano, CarloBagnardi, VincenzoPriori, Silvia G.Cohort StudiesFemaleGenotypeHeartHumansLong QT SyndromeMaleRisk AssessmentLong QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers. The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03). The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS.ElsevierMinistero della Salute (Italia)20202020-06-1920182018-04-0120182018-04-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/10498reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/104982026-06-12T12:43:37Z
dc.title.none.fl_str_mv Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
title Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
spellingShingle Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
Mazzanti, Andrea
Cohort Studies
Female
Genotype
Heart
Humans
Long QT Syndrome
Male
Risk Assessment
title_short Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
title_full Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
title_fullStr Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
title_full_unstemmed Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
title_sort Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.
dc.creator.none.fl_str_mv Mazzanti, Andrea
Maragna, Riccardo
Vacanti, Gaetano
Monteforte, Nicola
Bloise, Raffaella
Marino, Maira
Braghieri, Lorenzo
Gambelli, Patrick
Memmi, Mirella
Pagan, Eleonora
Morini, Massimo
Malovini, Alberto
Ortiz, Martin
Sacilotto, Luciana
Bellazzi, Riccardo
Monserrat, Lorenzo
Napolitano, Carlo
Bagnardi, Vincenzo
Priori, Silvia G.
author Mazzanti, Andrea
author_facet Mazzanti, Andrea
Maragna, Riccardo
Vacanti, Gaetano
Monteforte, Nicola
Bloise, Raffaella
Marino, Maira
Braghieri, Lorenzo
Gambelli, Patrick
Memmi, Mirella
Pagan, Eleonora
Morini, Massimo
Malovini, Alberto
Ortiz, Martin
Sacilotto, Luciana
Bellazzi, Riccardo
Monserrat, Lorenzo
Napolitano, Carlo
Bagnardi, Vincenzo
Priori, Silvia G.
author_role author
author2 Maragna, Riccardo
Vacanti, Gaetano
Monteforte, Nicola
Bloise, Raffaella
Marino, Maira
Braghieri, Lorenzo
Gambelli, Patrick
Memmi, Mirella
Pagan, Eleonora
Morini, Massimo
Malovini, Alberto
Ortiz, Martin
Sacilotto, Luciana
Bellazzi, Riccardo
Monserrat, Lorenzo
Napolitano, Carlo
Bagnardi, Vincenzo
Priori, Silvia G.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministero della Salute (Italia)
dc.subject.none.fl_str_mv Cohort Studies
Female
Genotype
Heart
Humans
Long QT Syndrome
Male
Risk Assessment
topic Cohort Studies
Female
Genotype
Heart
Humans
Long QT Syndrome
Male
Risk Assessment
description Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers. The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03). The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-04-01
2018
2018-04-01
2020
2020-06-19
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/10498
url http://hdl.handle.net/20.500.12105/10498
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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