BACKGROUND: Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist. OBJECTIVE: The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events. METHODS: A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10-18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups. RESULTS: A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3-11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10- and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on β-blocker or flecainide alone vs 10% (5/48) in patients on β-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001). CONCLUSION: Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors.

• MeSH
• dítě MeSH
• komorová tachykardie epidemiologie   terapie   MeSH
• lidé MeSH
• mladiství MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• stupeň závažnosti nemoci MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Kanada MeSH
• Spojené státy americké MeSH

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.

• MeSH
• amiodaron aplikace a dávkování   škodlivé účinky   MeSH
• Andersenův syndrom komplikace   genetika   terapie   MeSH
• antiarytmika aplikace a dávkování   škodlivé účinky   MeSH
• beta blokátory terapeutické užití   MeSH
• databáze faktografické MeSH
• defibrilátory implantabilní MeSH
• dítě MeSH
• dospělí MeSH
• draslíkové kanály dovnitř usměrňující genetika   MeSH
• elektrokardiografie MeSH
• genetické testování MeSH
• hodnocení rizik * MeSH
• kojenec MeSH
• komorová tachykardie etiologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• náhlá srdeční smrt epidemiologie   MeSH
• předškolní dítě MeSH
• srdeční arytmie etiologie   terapie   MeSH
• svalová slabost etiologie   MeSH
• synkopa etiologie   terapie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH