Andrea Mazzanti1, Riccardo Maragna2, Gaetano Vacanti2, Nicola Monteforte2, Raffaella Bloise2, Maira Marino2, Lorenzo Braghieri2, Patrick Gambelli2, Mirella Memmi2, Eleonora Pagan3, Massimo Morini4, Alberto Malovini2, Martin Ortiz5, Luciana Sacilotto2, Riccardo Bellazzi6, Lorenzo Monserrat5, Carlo Napolitano2, Vincenzo Bagnardi3, Silvia G Priori7. 1. Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy. 2. Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy. 3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 4. Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy; Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy. 5. Health in Code, La Coruña, Spain. 6. Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy. 7. Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Molecular Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Electronic address: silvia.priori@icsmaugeri.it.
Abstract
BACKGROUND: 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). OBJECTIVES: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: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). OBJECTIVES: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Authors: Kyung Jin Ahn; Mi Kyoung Song; Sang Yun Lee; Ja Kyoung Yoon; Gi Beom Kim; Seil Oh; Eun Jung Bae Journal: Korean Circ J Date: 2022-10 Impact factor: 3.101
Authors: Jason D Roberts; S Yukiko Asaki; Andrea Mazzanti; J Martijn Bos; Izabela Tuleta; Alison R Muir; Lia Crotti; Andrew D Krahn; Valentina Kutyifa; M Benjamin Shoemaker; Christopher L Johnsrude; Takeshi Aiba; Luciana Marcondes; Anwar Baban; Sharmila Udupa; Brynn Dechert; Peter Fischbach; Linda M Knight; Eric Vittinghoff; Deni Kukavica; Birgit Stallmeyer; John R Giudicessi; Carla Spazzolini; Keiko Shimamoto; Rafik Tadros; Julia Cadrin-Tourigny; Henry J Duff; Christopher S Simpson; Thomas M Roston; Yanushi D Wijeyeratne; Imane El Hajjaji; Maisoon D Yousif; Lorne J Gula; Peter Leong-Sit; Nikhil Chavali; Andrew P Landstrom; Gregory M Marcus; Sven Dittmann; Arthur A M Wilde; Elijah R Behr; Jacob Tfelt-Hansen; Melvin M Scheinman; Marco V Perez; Juan Pablo Kaski; Robert M Gow; Fabrizio Drago; Peter F Aziz; Dominic J Abrams; Michael H Gollob; Jonathan R Skinner; Wataru Shimizu; Elizabeth S Kaufman; Dan M Roden; Wojciech Zareba; Peter J Schwartz; Eric Schulze-Bahr; Susan P Etheridge; Silvia G Priori; Michael J Ackerman Journal: Circulation Date: 2020-01-16 Impact factor: 29.690
Authors: Giulio Conte; Arthur Wilde; Elijah R Behr; Daniel Scherr; Radoslaw Lenarczyk; Estelle Gandjbachkh; Lia Crotti; Georgia Brugada-Sarquella; Tatjana Potpara Journal: Circ Genom Precis Med Date: 2021-04-02
Authors: Lee L Eckhardt; Elizabeth S Kaufman; Michael J Ackerman; Peter F Aziz; Elijah R Behr; Marina Cerrone; Mina K Chung; Michael J Cutler; Susan P Etheridge; Andrew D Krahn; Steven A Lubitz; Marco V Perez; Silvia G Priori; Jason D Roberts; Dan M Roden; Eric Schulze-Bahr; Peter J Schwartz; Wataru Shimizu; M Benjamin Shoemaker; Raymond W Sy; Jeffrey A Towbin; Sami Viskin; Arthur A M Wilde; Wojciech Zareba Journal: Circ Arrhythm Electrophysiol Date: 2021-07-09