Enzymatic activity of DPIV and renin–angiotensin system (RAS) proteases in patients with left ventricular dysfunction and primary prevention implantable cardioverter/defibrillator (ICD)

• Published in: International journal of cardiology 2013-09, Vol.168 (1), p.255-260
• Main Authors: Lehmann, H. Immo, Wolke, Carmen, Malenke, Wiebke, Röhl, Friedrich-Wilhelm, Hammwöhner, Matthias, Bukowska, Alicja, Lendeckel, Uwe, Goette, Andreas
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - blood; Cardiology. Vascular system; Cardiovascular; Cohort Studies; Defibrillators, Implantable; Dipeptidyl Peptidase 4 - blood; DPIV; Enzyme Activation - physiology; Female; Follow-Up Studies; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; ICD intervention; Male; Medical sciences; Middle Aged; Peptide Hydrolases - blood; Primary Prevention - methods; Prospective Studies; Renin angiotensin system (RAS); Renin-Angiotensin System - physiology; Risk marker for SCD; Ventricular Dysfunction, Left - enzymology
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2012.09.083

Abstract Background 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. Methods 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. Results 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/s mL vs. 169.10 RFU/s mL; 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. Conclusion 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.