Working Group of Molecular Electrophysiology, Faculty of Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
Int J Cardiol. 2013 Sep 20;168(1):255-60. doi: 10.1016/j.ijcard.2012.09.083. Epub 2012 Oct 10.
Patients (pts) with severely decreased left ventricular ejection fraction (LV-EF ≤ 35%) are at high risk for sudden cardiac death (SCD). We sought to investigate, if pts with primary prevention ICD hold alterations in enzyme-activities of the dipeptidyl-aminopeptidase IV (DPIV) and the renin-angiotensin system (RAS) before VT/VF occurrence.
57 Pts (53 male, mean age 64.9 [42-84] years, mean LV-EF 26 ± 5%) with ischemic (n=49) or non-ischemic cardiomyopathy (n=8) who had received an ICD/CRT-D for primary prevention, were included. Pts were assessed for appropriate ICD intervention for VT/VF during a mean follow-up of 365 ± 90 days. Serum levels of dipeptidyl-aminopeptidase IV (DPIV), aminopeptidase N (APN), aminopeptidase B (APB), insulin-regulated aminopeptidase (IRAP), and angiotensin-converting enzyme 2 (ACE2) were determined.
Pts with appropriate ICD intervention (n=16) had higher serum activities of IRAP (mean difference=12.681 pkat/mL; p=0.007), and DPIV (mean difference=117.557 pkat/mL; p=0.032) than pts without appropriate ICD intervention. Furthermore, ACE2 activity was significantly higher (median: 223.7 RFU/smL vs. 169.10 RFU/smL; p=0.037). A Cox regression analysis indicated DPIV activity >50th centile to have a hazard ratio (HR) of 5.955 (CI 95%: 1.670-21.241; p=0.006) for prediction of appropriate ICD intervention. In a multivariate Cox regression model, DPIV and IRAP >50th centile remained predictive for appropriate ICD intervention.
Our prospective study shows that pts with primary prevention ICD, who receive appropriate ICD intervention during follow-up, can be identified by elevated activities of DPIV and several RAS proteases. Hence, theses biomarkers seem to be of prognostic relevance in a primary prevention collective. Our data has to be proven in larger cohorts.
患有严重左心室射血分数降低（LV-EF≤35%）的患者（pts）发生心脏性猝死（SCD）的风险很高。我们试图研究原发性预防 ICD 的 pts 在 VT/VF 发生前是否存在二肽基氨基肽酶 IV（DPIV）和肾素-血管紧张素系统（RAS）的酶活性改变。
纳入 57 例（53 名男性，平均年龄 64.9[42-84]岁，平均 LV-EF 26±5%）因缺血性（n=49）或非缺血性心肌病（n=8）而接受 ICD/CRT-D 作为原发性预防的 pts。在平均 365±90 天的随访期间，评估 pts 是否因 VT/VF 而发生适当的 ICD 干预。测定二肽基氨基肽酶 IV（DPIV）、氨基肽酶 N（APN）、氨基肽酶 B（APB）、胰岛素调节氨基肽酶（IRAP）和血管紧张素转化酶 2（ACE2）的血清水平。
发生适当 ICD 干预的 pts（n=16）的血清 IRAP（平均差值=12.681 pkat/mL；p=0.007）和 DPIV（平均差值=117.557 pkat/mL；p=0.032）活性高于未发生适当 ICD 干预的 pts。此外，ACE2 活性显著升高（中位数：223.7 RFU/smL 与 169.10 RFU/smL；p=0.037）。Cox 回归分析表明，DPIV 活性>第 50 百分位数的 HR 为 5.955（95%CI：1.670-21.241；p=0.006），预测适当的 ICD 干预。在多变量 Cox 回归模型中，DPIV 和 IRAP>第 50 百分位数仍然可预测适当的 ICD 干预。
我们的前瞻性研究表明，在随访期间接受适当 ICD 干预的原发性预防 ICD 的 pts，可以通过 DPIV 和几种 RAS 蛋白酶的活性升高来识别。因此，这些生物标志物在原发性预防人群中似乎具有预后意义。我们的数据需要在更大的队列中得到验证。
