title: Asymmetric dimethylarginine predicts appropriate implantable cardioverter-defibrillator intervention in patients with left ventricular dysfunction.
abstract: OBJECTIVE
  More precise characterization of risk factors for occurring ventricular arrhythmia in patients (pts) with primary prevention implantable cardioverter-defibrillator (ICD) therapy is critical. We sought to investigate whether biomarkers of nitric oxide metabolism can predict the occurrence of ventricular tachyarrhythmias and might be used as risk markers in these pts.
  
  
  RESULTS
  Plasma levels of l-arginine (Arg), asymmetric dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), monomethyl l-arginine, and nitrite/nitrate were examined in 106 consecutive pts (mean age 65 years, 97 male, mean LV-EF 24 ± 6%), with ischaemic (n= 82) or non-ischaemic cardiomyopathy (n= 24) who underwent ICD implantation for primary prevention of SCD. Appropriate ICD intervention was assessed during a mean follow-up of 344 days, and occurred in 18 of 106 (17%) pts. Asymmetric dimethylarginine plasma levels were significantly higher in pts with appropriate ICD intervention compared with those without any ICD intervention (0.564 ± 0.083 μmol/L vs. 0.513 ± 0.088 μmol; P= 0.027). The Arg/ADMA ratio was found lower in pts with appropriate ICD intervention than in those without ICD intervention (144.71 ± 32.50 vs. 175.29 ± 41.29; P= 0.002). Univariate Cox regression showed that ADMA (P = 0.028) and the Arg/ADMA ratio (P = 0.003) were associated with a higher incidence of appropriate ICD intervention. In a multivariable Cox regression analysis, an ADMA concentration above the 50th centile was independently associated with appropriate ICD intervention, revealing a hazard ratio (HR) of 4.21 (CI 95 %: 1.14-15.63; P = 0.028, Table 4). An Arg/ADMA ratio below the 25th centile had a HR of 3.83 (1.360-10.87; P = 0.011).
  
  
  CONCLUSIONS
  Asymmetric dimethylarginine and the Arg/ADMA ratio seem to be new biomarkers for the prediction of ventricular tachycardia/ventricular fibrillation episodes and of appropriate ICD intervention in pts with left ventricular ejection fraction dysfunction (LV-EF ≤ 35%), suggesting a value for risk stratification in these pts.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: H Immo
authors.initials: HI
authors.lastname: Lehmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammwöhner
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Röhl
authors.forename: Alicja
authors.initials: A
authors.lastname: Bukowska
authors.forename: Ali
authors.initials: A
authors.lastname: Ghanem
authors.forename: Helmut U
authors.initials: HU
authors.lastname: Klein
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D017147:Defibrillators, Implantable; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000628:therapy*
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine