Περίληψη:
Background: 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. 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. © 2020
Συγγραφείς:
Mazzanti, A.
Guz, D.
Trancuccio, A.
Pagan, E.
Kukavica, D.
Chargeishvili, T.
Olivetti, N.
Biernacka, E.K.
Sacilotto, L.
Sarquella-Brugada, G.
Campuzano, O.
Nof, E.
Anastasakis, A.
Sansone, V.A.
Jimenez-Jaimez, J.
Cruz, F.
Sánchez-Quiñones, J.
Hernandez-Afonso, J.
Fuentes, M.E.
Średniawa, B.
Garoufi, A.
Andršová, I.
Izquierdo, M.
Marinov, R.
Danon, A.
Expósito-García, V.
Garcia-Fernandez, A.
Muñoz-Esparza, C.
Ortíz, M.
Zienciuk-Krajka, A.
Tavazzani, E.
Monteforte, N.
Bloise, R.
Marino, M.
Memmi, M.
Napolitano, C.
Zorio, E.
Monserrat, L.
Bagnardi, V.
Priori, S.G.
Λέξεις-κλειδιά:
antiarrhythmic agent; beta adrenergic receptor blocking agent; amiodarone; antiarrhythmic agent; inwardly rectifying potassium channel; KCNJ2 protein, human, adult; Andersen Tawil syndrome type 1; Andersen Tawil syndrome type 1; Article; cohort analysis; disease association; drug efficacy; faintness; female; follow up; hazard ratio; heart arrhythmia; heart ventricle tachycardia; human; Italy; major clinical study; male; medical documentation; medical history; prediction; priority journal; risk assessment; adolescent; Andersen syndrome; child; complication; electrocardiography; factual database; faintness; genetic screening; genetics; heart arrhythmia; heart ventricle tachycardia; implantable cardioverter defibrillator; infant; middle aged; muscle weakness; mutation; preschool child; risk assessment; sudden cardiac death; young adult, Adolescent; Adrenergic beta-Antagonists; Adult; Amiodarone; Andersen Syndrome; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Child; Child, Preschool; Databases, Factual; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Genetic Testing; Humans; Infant; Male; Middle Aged; Muscle Weakness; Mutation; Potassium Channels, Inwardly Rectifying; Risk Assessment; Syncope; Tachycardia, Ventricular; Young Adult
