Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

• Published in: Journal of cardiovascular electrophysiology 2016-12, Vol.27 (12), p.1420-1428
• Main Authors: BOURFISS, MIMOUNT, TE RIELE, ANNELINE S.J.M., MAST, THOMAS P., CRAMER, MAARTEN J., VAN DER HEIJDEN, JEROEN F., VAN VEEN, TOON A.B., LOH, PETER, DOOIJES, DENNIS, HAUER, RICHARD N.W., VELTHUIS, BIRGITTA K.
• Format: Article
• Language: English
• Subjects: Adult; arrhythmogenic right ventricular dysplasia; Arrhythmogenic Right Ventricular Dysplasia - diagnosis; Arrhythmogenic Right Ventricular Dysplasia - genetics; Arrhythmogenic Right Ventricular Dysplasia - physiopathology; Atria; atrial fibrillation; Atrial Fibrillation - diagnosis; Atrial Fibrillation - genetics; Atrial Fibrillation - physiopathology; Atrial Flutter - diagnosis; Atrial Flutter - genetics; Atrial Flutter - physiopathology; Atrial Function - genetics; Calcium-Binding Proteins - genetics; Cardiac arrhythmia; cardiac magnetic resonance imaging; Cardiomyopathy; Case-Control Studies; Cross-Sectional Studies; Defibrillators; Disruption; DNA Mutational Analysis; Echocardiography; EKG; Electrocardiography; Electrocardiography, Ambulatory; Female; Fibrillation; Genetic analysis; Genetic Predisposition to Disease; genotype; Genotype & phenotype; Heart; Heart Atria - diagnostic imaging; Heart Atria - physiopathology; Heart diseases; Humans; Incidence; Interrogation; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Phenotype; Phospholamban; Plakophilins - genetics; Registries; Right ventricular dysplasia; Risk Factors; Tachycardia; Ventricle; Vibration
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/jce.13094

Structural Atrial Involvement in ARVD/C Introduction 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. Objective To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype. Methods 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. Results 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%). Conclusion 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.