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

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/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.

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.