title: Arrhythmic risk assessment in genotyped families with arrhythmogenic right ventricular cardiomyopathy.
abstract: Arrhythmogenic right-ventricular cardiomyopathy (ARVC) is a genetically determined disorder, mostly caused by mutations in genes encoding desmosomal proteins. We evaluated phenotype/genotype characteristics to predict the risk for the first major arrhythmic event in desmosomal-mutation-associated ARVC families.
  
  
  
  A cohort of 105 desmosomal-mutation carriers belonging to 39 consecutive ARVC families was evaluated. Serial clinical work-up consisting of history, physical examination, 12-lead/signal-averaged/24 h ambulatory ECG, and two-dimensional echocardiography was performed every 6-12 months. The predictive value of gender and genotype for the first major arrhythmic event was investigated within the cohort using time-to-event analysis. ECG/echocardiographic features were evaluated at the time of event and associated with the outcome using an age-matched nested case-control study within the cohort. Forty-three (41%) participants experienced the primary arrhythmic outcome at median age of 29 (21-46) years. The first event was sustained ventricular tachycardia in 31 and sudden cardiac death in 12. Definite diagnosis according to the 2010 Task Force criteria, showed 57% positive and 100% negative predictive value for the occurrence of arrhythmic outcome. Male gender (hazard ratio = 3.26, 95%CI, 1.63-6.51), predicted the first major arrhythmic event, independently of genotype, on multivariable analysis. Repolarization abnormalities and left-ventricular dysfunction independently associated with clinical disease profile at the time of event.
  
  
  
  Male gender, independently of genotype is an arrhythmic risk predictor in ARVC-associated desmosomal-mutation carriers. Repolarization abnormalities and left-ventricular dysfunction are important components of the first event-associated clinical disease profile.
authors.affiliation: Yannis Protonotarios Medical Centre, Naxos, Greece alexanderproton@gmail.com.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Protonotarios
authors.affiliation: 1st Department of Cardiology, University of Athens Medical School, Athens, Greece.
authors.forename: Aris
authors.initials: A
authors.lastname: Anastasakis
authors.affiliation: Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
authors.forename: Demosthenes B
authors.initials: DB
authors.lastname: Panagiotakos
authors.affiliation: Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus.
authors.forename: Loizos
authors.initials: L
authors.lastname: Antoniades
authors.affiliation: Institute of Cardiovascular Science, University College London and The Heart Hospital, University College London Hospitals Trust, London, UK.
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.affiliation: 1st Department of Cardiology, University of Athens Medical School, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Vouliotis
authors.affiliation: 1st Department of Cardiology, University of Athens Medical School, Athens, Greece.
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
authors.affiliation: Yannis Protonotarios Medical Centre, Naxos, Greece.
authors.forename: Adalena
authors.initials: A
authors.lastname: Tsatsopoulou
authors.affiliation: Institute of Cardiovascular Science, University College London and The Heart Hospital, University College London Hospitals Trust, London, UK.
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.affiliation: Yannis Protonotarios Medical Centre, Naxos, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Protonotarios
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D018572:Disease-Free Survival; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006115:Greece; D040941:Heredity; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D013997:Time Factors; D016277:Ventricular Function, Left; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: Arrhythmia; Arrhythmogenic right-ventricular cardiomyopathy; Risk factors; Sudden death
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