title: Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations.
abstract: The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene.
  
  
  
  The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives.
  
  
  
  We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with aRyR2mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope).As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10-33) vs 43 years (IQR, 25-54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43-175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32-139)). Multifocal atrial tachycardia was the predominant symptom in five patients.
  
  
  
  In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Anders Krogh
authors.identifier: 0000-0003-1662-4232
authors.initials: AK
authors.lastname: Broendberg
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Jens Cosedis
authors.initials: JC
authors.lastname: Nielsen
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Bjerre
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Lisbeth Noerum
authors.initials: LN
authors.lastname: Pedersen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Kristensen
authors.affiliation: Department of Cardiology, Odense University Hospital, DK-5000 Odense, Denmark.
authors.forename: Finn Lund
authors.initials: FL
authors.lastname: Henriksen
authors.affiliation: Department of Cardiology, The Heart Centre, Unit for Inherited Cardiac Diseases, Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
authors.affiliation: Department of Cardiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Henrik Kjaerulf
authors.initials: HK
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012189:Retrospective Studies; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D004247:DNA
keywords: Arrhythmias; CPVT; Implantable cardioverter defibrillator; genetics