Author + information
- Received October 2, 2017
- Revision received January 31, 2018
- Accepted January 31, 2018
- Published online April 9, 2018.
- Andrea Mazzanti, MDa,b,
- Riccardo Maragna, MDa,
- Gaetano Vacanti, MDa,
- Nicola Monteforte, MDa,
- Raffaella Bloise, MDa,
- Maira Marino, RNa,
- Lorenzo Braghieri, MDa,
- Patrick Gambelli, BSca,
- Mirella Memmi, BSca,
- Eleonora Pagan, MScc,
- Massimo Morini, DEnga,d,
- Alberto Malovini, BSca,
- Martin Ortiz, MDe,
- Luciana Sacilotto, MDa,
- Riccardo Bellazzi, PhDd,
- Lorenzo Monserrat, MD, PhDe,
- Carlo Napolitano, MD, PhDa,
- Vincenzo Bagnardi, PhDc and
- Silvia G. Priori, MD, PhDa,b,f,∗ ()
- aMolecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy
- bDepartment of Molecular Medicine, University of Pavia, Pavia, Italy
- cDepartment of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
- dDepartment of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
- eHealth in Code, La Coruña, Spain
- fMolecular Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
- ↵∗Address for correspondence:
Dr. Silvia G. Priori, Molecular Cardiology, IRCCS ICS Maugeri, Via Maugeri, 10, 27100 Pavia, Italy.
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.
- inherited arrhythmias
- life-threatening arrhythmic events
- long QT syndrome
- sudden cardiac death
This work was supported by the Ricerca Corrente funding scheme of the Italian Ministry of Health. Dr. Ortiz has received personal fees from Health in Code, SL. Dr. Monserrat is a shareholder in Health in Code, SL. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper.
- Received October 2, 2017.
- Revision received January 31, 2018.
- Accepted January 31, 2018.
- 2018 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.