title: Cardiac phenotype and long-term prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with late presentation.
abstract: The clinical profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients with late presentation is unknown.
  
  
  
  The purpose of this study was to characterize the genotype, cardiac phenotype, and long-term outcomes of ARVC/D patients with late presentation (age ≥50 years at diagnosis).
  
  
  
  Five hundred two patients with an ARVC/D diagnosis from Johns Hopkins and Utrecht Registries were studied and long-term clinical outcomes ascertained.
  
  
  
  Late presentation was seen in 104 patients (21%; 38% PKP2 carriers); 3% were ≥65 years at diagnosis. Sustained ventricular tachycardia was the major (43%) mode of presentation in patients with late presentation, whereas cardiac syncope was infrequent (P <.001). Those with late presentation were significantly less likely to harbor a known pathogenic mutation (53%; P = .005), have less precordial T-wave repolarization changes (P <.001), and have lower ventricular ectopy burden (P = .026). Over median 6-year follow-up, 68 patients with late presentation (65%) experienced sustained ventricular arrhythmias, with similar arrhythmia-free survival at 5-year follow up (P = .48). Left ventricular dysfunction and heart failure were seen in 24 (32%) and 15 patients (14%), respectively, without need for cardiac transplantation. In the late presentation cohort, male sex, pathogenic mutation, right ventricular structural disease, lack of family history, and electrophysiologic study inducibility were associated with increased arrhythmic risk.
  
  
  
  One-fifth of all ARVC/D patients present after age 50 years, often with sustained ventricular tachycardia, and are less likely to have prior syncope, ECG changes, ventricular ectopy, or identifiable pathogenic mutation. In ARVC/D, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk.
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bhonsale
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anneline S J M
authors.initials: ASJM
authors.lastname: Te Riele
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Abhishek C
authors.initials: AC
authors.lastname: Sawant
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Groeneweg
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mast
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: van der Pols
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten J M
authors.initials: MJM
authors.lastname: Cramer
authors.affiliation: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: van der Heijden
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
authors.affiliation: Department of Clinical Genetics, Academic Medical Center Amsterdam, Amsterdam, The Netherlands; ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.affiliation: ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Richard N W
authors.initials: RNW
authors.lastname: Hauer
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: hcalkins@jhmi.edu.
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
mesh_terms: D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D051191:Plakophilins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014481:United States; D055815:Young Adult
chemical_list: C495337:PKP2 protein, human; D051191:Plakophilins
keywords: Arrhythmogenic right ventricular cardiomyopathy/dysplasia; Cardiomyopathy; Genotype; Late onset; Outcome