Abstract 8816: Asymmetric Dimethylarginine Predicts Appropriate Implanted Cardioverter Defibrillator Therapy in Patients With Severe Left Ventricular Dysfunction
Introduction: Patients with severely decreased left ventricular ejection fraction (LVEF<35%) are at high risk for the occurrence of malignant ventricular arrhythmias and sudden cardiac death (SCD). So far, besides LVEF, further risk stratification has failed to improve prediction of SCD. The aim of the present study was to evaluate, if biomarkers of nitric oxide metabolism can predict the occurrence of VT/VF in patients with primary prevention of SCD.
Methods: Plasma levels of asymmetric dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), monomethyl arginine (MMA), L-arginine, nitrite, nitrate, NT-proBNP, and hs-CRP were examined in 106 consecutive included patients (mean age 65.5±10.8 years, 97 male, mean LVEF 24±6%), with ischemic (n=82) or dilated cardiomyopathy, who had implanted an ICD for primary prevention. Patients were assessed for appropriate ICD therapy with a mean follow-up time of 344±86 days, and ICD therapy was correlated to biomarker levels.
Results: Appropriate ICD therapy was detected in 18 patients. Of note, these patients had higher plasmatic ADMA values (0.56±0.1μmol/l vs. 0.51±0.1μmol/l; p=0.02) and lower L-arginine/ADMA-ratios than patients without appropriate ICD therapy (n=88) (144.7±32.5 vs. 175.3±41.3; p=0.002). Levels of SDMA, MMA, nitrite, nitrate, NT-proBNP, and hs-CRP were not significantly different in both groups. Additionally, patients with inappropriate ICD therapy (n=5) did not have significant alterations in ADMA levels (0.53±0.05μmol/l vs. 0.52± 0.09μmol/l; p=ns), as well as in the L-arginine/ADMA-ratio (175.2±26.2 vs. 169.8±42.1; p=ns). Patients with an ADMA level above 0.501μmol/l were eightfold more likely to receive ICD therapy. In addition, an L-arginine/ADMA-ratio below 142.2 was associated with a sevenfold increased risk. Moreover, negative predictive values for ADMA and the L-arginine/ADMA-ratio were 96% and 91%, respectively.
Conclusions: In conclusion, our prospective study shows that ADMA and the L-arginine/ADMA-ratio are valuable biomarkers for the prediction of VT/VF and appropriate ICD therapy in patients with a LVEF<35%.
- © 2010 by American Heart Association, Inc.