Division of Cardiology, Department of Internal Medicine, Otto-von-Guericke University, Magdeburg, Germany.
Europace. 2011 Oct;13(10):1428-35. doi: 10.1093/europace/eur171. Epub 2011 Jul 13.
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.
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).
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.
更精确地描述原发性预防植入式心脏复律除颤器（ICD）治疗患者发生室性心律失常的危险因素至关重要。我们旨在研究一氧化氮代谢生物标志物是否可以预测室性心动过速和室性心律失常的发生，并可能作为这些患者的风险标志物。
在 106 例连续患者（平均年龄 65 岁，97 例男性，平均左心室射血分数 24 ± 6%）中检查了血浆 l-精氨酸（Arg）、不对称二甲基精氨酸（ADMA）、对称二甲基精氨酸（SDMA）、单甲基 l-精氨酸和亚硝酸盐/硝酸盐的水平，这些患者患有缺血性（n=82）或非缺血性心肌病（n=24），并因心脏性猝死（SCD）的原发性预防而接受 ICD 植入。在平均 344 天的随访期间评估了适当的 ICD 干预，106 例患者中有 18 例（17%）发生了适当的 ICD 干预。与无任何 ICD 干预的患者相比，适当 ICD 干预的患者血浆 ADMA 水平显著升高（0.564 ± 0.083 μmol/L vs. 0.513 ± 0.088 μmol；P=0.027）。与无 ICD 干预的患者相比，适当 ICD 干预的患者 Arg/ADMA 比值较低（144.71 ± 32.50 vs. 175.29 ± 41.29；P=0.002）。单变量 Cox 回归显示，ADMA（P=0.028）和 Arg/ADMA 比值（P=0.003）与更高的适当 ICD 干预发生率相关。在多变量 Cox 回归分析中，ADMA 浓度高于第 50 百分位数与适当的 ICD 干预独立相关，显示危险比（HR）为 4.21（95%CI：1.14-15.63；P=0.028，表 4）。Arg/ADMA 比值低于第 25 百分位数的 HR 为 3.83（1.360-10.87；P=0.011）。
不对称二甲基精氨酸和 Arg/ADMA 比值似乎是预测左心室射血分数功能障碍（LV-EF≤35%）患者室性心动过速/心室颤动发作和适当 ICD 干预的新生物标志物，提示这些患者的风险分层有一定价值。
