Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

Adolescent Adrenergic beta-Antagonists / therapeutic use Adult Amiodarone / administration & dosage Andersen Syndrome / complications Anti-Arrhythmia Agents / administration & dosage Arrhythmias, Cardiac / etiology Child Child, Preschool Databases, Factual Death, Sudden, Cardiac / epidemiology Defibrillators, Implantable Electrocardiography Female Genetic Testing Humans Infant Male Middle Aged Muscle Weakness / etiology Mutation Potassium Channels, Inwardly Rectifying / genetics Risk Assessment Syncope / etiology Tachycardia, Ventricular / etiology Young Adult

KCNJ2 genetics inherited arrhythmias life-threatening arrhythmic events sudden cardiac death

Journal

Journal of the American College of Cardiology

ISSN: 1558-3597

Titre abrégé: J Am Coll Cardiol

Pays: United States

ID NLM: 8301365

Informations de publication

Date de publication:
21 04 2020

Historique:

received: 06 09 2019

revised: 25 01 2020

accepted: 11 02 2020

entrez: 18 4 2020

pubmed: 18 4 2020

medline: 29 12 2020

Statut: ppublish

Résumé

Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.

Sections du résumé

BACKGROUND

OBJECTIVES

This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1.

METHODS

Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis.

RESULTS

We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00).

CONCLUSIONS

Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.

Identifiants

DOI: 10.1016/j.jacc.2020.02.033 PMID: 32299589

pubmed: 32299589

pii: S0735-1097(20)34329-1

doi: 10.1016/j.jacc.2020.02.033

pii:

doi:

Substances chimiques

Adrenergic beta-Antagonists 0

Anti-Arrhythmia Agents 0

KCNJ2 protein, human 0

Potassium Channels, Inwardly Rectifying 0

Amiodarone N3RQ532IUT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1772-1784

Commentaires et corrections

Type : CommentIn