title: Evaluation of Structural Progression in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
abstract: Considerable research has described the arrhythmic course of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, objective data characterizing structural progression, such as ventricular enlargement and cardiac dysfunction, in ARVD/C are relatively scarce.
  
  
  
  To define the extent of structural progression, identify determinants of structural progression, and determine the association between structural progression and electrocardiographic (ECG) changes in patients with ARVD/C.
  
  
  
  In this cohort study, first- and last-available echocardiograms of 85 patients with ARVD/C fulfilling 2010 Task Force diagnostic criteria (TFC) from a transatlantic ARVD/C registry were retrospectively compared to assess structural disease progression. Right ventricular (RV) size and systolic function between baseline and last follow-up were compared. The RV size was determined by RV outflow tract dimension, and RV and left ventricular (LV) systolic function were determined by RV fractional area change (RV-FAC) and LV ejection fraction (LVEF), respectively. Multivariable logistic regression was used to study associations between baseline characteristics and the occurrence of structural progression.
  
  
  
  The main outcome was the change in variables indicating structural progression. Secondary outcomes were the correlation with electrical progression and identification of the association between baseline characteristics and occurence structural progression.
  
  
  
  Among the 85 patients with ARVD/C, mean (SD) age at baseline was 42.8 (14.4) years and 47 (55%) were men. After a mean (SD) follow-up of 6.4 (2.5) years, RV outflow tract dimension increased from 35 mm (interquartile range [IQR], 31 to 39) to 37 mm (IQR, 33 to 41) (P < .001), RV-FAC decreased from 39% (IQR, 33% to 44%) to 34% (IQR, 24% to 42%) (P < .001) (rate -3.3% per 5 years; IQR, -8.9% to 1.2%), indicating large interpatient variability. The LVEF decreased from 55% (IQR, 52% to 60%) to 54% (IQR, 49% to 57%) (P = .001) (rate, -0.2% per 5 years; IQR, -6.5% to 1.7%). Forty examinations were reanalyzed to establish the measurement error. Patients exceeding the measurement error by ±2 SDs were identified with significant progressive disease for RV, with a decrease in RV-FAC greater than 10% (n = 21) and, for LV, a decrease in LVEF greater than 7% (n = 23). Progression of RV disease was associated with depolarization criteria at baseline (odds ratio [OR], 9.0; 95% CI, 1.1-74.2; P = .04), whereas progression of LV disease was associated with phospholamban (PLN) mutation (OR, 8.8; 95% CI, 2.1-37.2; P = .003). There was no association between progressive RV/LV structural disease and newly developed ECG TFC.
  
  
  
  Structural dysfunction in ARVD/C is progressive with substantial interpatient variability. Significant structural RV progression was associated with prior depolarization abnormalities, whereas LV progression is modified by genetic background. Structural progression was not associated with development of new ECG TFC. The results of this study pave the way for designing and launching trials aimed at reducing structural progression in patients with ARVD/C.
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mast
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Arco J
authors.initials: AJ
authors.lastname: Teske
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Loh
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Birgitta K
authors.initials: BK
authors.lastname: Velthuis
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Tedford
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: van der Heijden
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
authors.affiliation: Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Hauer
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Abraham
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands5Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands2Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland5Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Anneline S J M
authors.initials: AS
authors.lastname: Te Riele
authors.affiliation: Division of Cardiology, Department of Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Cramer
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis* / Q000503:physiopathology; D018450:Disease Progression; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D016278:Ventricular Function, Right / Q000502:physiology*