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)....
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/10498 |
| Online Access: | http://hdl.handle.net/20.500.12105/10498 |
| Access Level: | Open access |
| Keyword: | Cohort Studies Female Genotype Heart Humans Long QT Syndrome Male Risk Assessment |
| _version_ | 1878735492152819712 |
|---|---|
| author | Mazzanti, Andrea |
| 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 |
| author_browse | Bagnardi, Vincenzo Bellazzi, Riccardo Bloise, Raffaella Braghieri, Lorenzo Gambelli, Patrick Malovini, Alberto Maragna, Riccardo Marino, Maira Mazzanti, Andrea Memmi, Mirella Monserrat, Lorenzo Monteforte, Nicola Morini, Massimo Napolitano, Carlo Ortiz, Martin Pagan, Eleonora Priori, Silvia G. Sacilotto, Luciana Vacanti, Gaetano |
| 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 |
| collection | Repisalud |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_7dbf3d20eb32fdcd831e1b157e5bdd8a |
| institution | Instituto de Salud Carlos III (ISCIII) |
| instname_str | Instituto de Salud Carlos III (ISCIII) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repisalud.isciii.es:20.500.12105/10498 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | Repisalud |
| spelling | Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome. 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. Cohort Studies Female Genotype Heart Humans Long QT Syndrome Male Risk Assessment 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. Elsevier http://hdl.handle.net/20.500.12105/10498 |
| 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 | 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_short | 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. |
| topic | Cohort Studies Female Genotype Heart Humans Long QT Syndrome Male Risk Assessment |
| topic_facet | Cohort Studies Female Genotype Heart Humans Long QT Syndrome Male Risk Assessment |
| url | http://hdl.handle.net/20.500.12105/10498 |