title: Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
abstract: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C.
  
  
  
  To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype.
  
  
  
  We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation.
  
  
  
  Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%).
  
  
  
  Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism.
authors: Faculty of Medicine (M.D. Program), University of Utrecht, Utrecht, the Netherlands.
authors: Mimount
authors: M
authors: Bourfiss
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Anneline S J M
authors: AS
authors: Te Riele
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Thomas P
authors: TP
authors: Mast
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Maarten J
authors: MJ
authors: Cramer
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Jeroen F
authors: JF
authors: VAN DER Heijden
authors: Department of Medical Physiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Toon A B
authors: TA
authors: VAN Veen
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Peter
authors: P
authors: Loh
authors: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Dennis
authors: D
authors: Dooijes
authors: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.|Netherlands Heart Institute, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Richard N W
authors: RN
authors: Hauer
authors: Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Birgitta K
authors: BK
authors: Velthuis
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001282:Atrial Flutter / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D016275:Atrial Function / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D015716:Electrocardiography, Ambulatory; D005260:Female; D020022:Genetic Predisposition to Disease; D006325:Heart Atria / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D051191:Plakophilins / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D051191:Plakophilins; D000099211:Phospholamban; C495337:PKP2 protein, human
keywords: arrhythmogenic right ventricular dysplasia; atria; atrial fibrillation; cardiac magnetic resonance imaging; cardiomyopathy; genotype