title: Prognostic Relevance of Gene-Environment Interactions in Patients With Dilated Cardiomyopathy: Applying the MOGE(S) Classification.
abstract: BACKGROUND
  The multifactorial pathogenesis leading to dilated cardiomyopathy (DCM) makes stratification difficult. The recent MOGE(S) (morphofunctional, organ involvement, genetic or familial, etiology, stage) classification addresses this issue.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the applicability and prognostic relevance of the MOGE(S) classification in patients with DCM.
  
  
  METHODS
  This study used patients from the Maastricht Cardiomyopathy Registry in the Netherlands and excluded patients with ischemic, valvular, hypertensive, and congenital heart disease. All other patients underwent a complete diagnostic work-up, including genetic evaluation and endomyocardial biopsy.
  
  
  RESULTS
  A total of 213 consecutive patients with DCM were included: organ involvement was demonstrated in 35 (16%) and genetic or familial DCM in 70 (33%) patients, including 16 (8%) patients with a pathogenic mutation. At least 1 cause was found in 155 (73%) patients, of whom 48 (23%) had more than 1 possible cause. Left ventricular reverse remodeling was more common in patients with nongenetic or nonfamilial DCM than in patients with genetic or familial DCM (40% vs. 25%; p = 0.04). After a median follow-up of 47 months, organ involvement and higher New York Heart Association functional class were associated with adverse outcome (p < 0.001 and p = 0.02, respectively). Genetic or familial DCM per se was of no prognostic significance, but when it was accompanied by additional etiologic-environmental factors such as significant viral load, immune-mediated factors, rhythm disturbances, or toxic triggers, a worse outcome was revealed (p = 0.03). A higher presence of MOGE(S) attributes (≥2 vs. ≤1 attributes) showed an adverse outcome (p = 0.007).
  
  
  CONCLUSIONS
  The MOGE(S) classification in DCM is applicable, and each attribute or the gene-environment interaction is associated with outcome. Importantly, the presence of multiple attributes was a strong predictor of adverse outcome. Finally, adaptation of the MOGE(S) involving multiple possible etiologies is recommended.
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands. Electronic address: mark.hazebroek@mumc.nl.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hazebroek
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Moors
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Dennert
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: van den Wijngaard
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Krapels
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Hoos
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Job
authors.initials: J
authors.lastname: Verdonschot
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Jort J
authors.initials: JJ
authors.lastname: Merken
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Vries
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Petra F
authors.initials: PF
authors.lastname: Wolffs
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Harry J G M
authors.initials: HJ
authors.lastname: Crijns
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
authors.affiliation: Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands; ICIN, Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000145:classification* / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index
keywords: autoimmune; etiology; toxic; virus