title: Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations.
abstract: BACKGROUND
  Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.
  
  
  RESULTS
  We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24-32 (P<.001).
  
  
  CONCLUSIONS
  Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.
authors.affiliation: Department of Cardiology/Electrophysiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Aydin
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Baran A
authors.initials: BA
authors.lastname: Adsay
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Sheikhzadeh
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Keyser
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Rybczynski
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sondermann
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Detter
authors.affiliation: Department of Cardiology/Electrophysiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Steven
authors.affiliation: Institute of Human Genetics and Medical Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.affiliation: Department of Medical Biometry and Epidemiology, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of Cardiology/Electrophysiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Willems
authors.affiliation: Department of Cardiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Yskert
authors.initials: Y
authors.lastname: von Kodolitsch
authors.affiliation: Department of Cardiology/Electrophysiology, University Heart Center, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016757:Death, Sudden, Cardiac / Q000473:pathology; D015716:Electrocardiography, Ambulatory; D005091:Exons / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; C000605722:FBN1 protein, human; D054392:Adipokines; C109794:pro-brain natriuretic peptide (1-76)