Publications

OBJECTIVES

The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.

BACKGROUND

CI-AKI is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality. The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during coronary injection.

METHODS

The AVERT trial was a prospective, multicenter, 1:1 randomized clinical trial in 578 subjects with either baseline estimated glomerular filtration rate 20 to 30 ml/min/1.73 m or estimated glomerular filtration rate 30 to 60 ml/min/1.73 m and at least 2 additional risk factors for CI-AKI. Patients undergoing coronary angiography with planned or possible percutaneous coronary intervention (PCI) were randomized to hydration plus the AVERT system (n = 292) or hydration only (n = 286). The primary effectiveness endpoints were: 1) the total CMV used; and 2) the incidence of CI-AKI, defined as a ≥0.3 mg/dl increase in serum creatinine within 5 days post-procedure.

RESULTS

Patient demographics were well balanced between the groups, with mean baseline serum creatinine of 1.6 ± 0.4 mg/dl and 64.9% patients with diabetes mellitus. PCI was performed in 42.2% of procedures, with coronary angiography in the remainder. Use of AVERT resulted in a 15.5% relative reduction in CMV overall (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml; p = 0.02) and a 22.8% relative reduction in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml; p = 0.001). The maximum relative reduction in CMV was 46% (124 ± 48 ml vs. 232 ± 97 ml; p = 0.01) when ≥3 lesions were treated. There were no differences in the rates of CI-AKI (27.0% vs. 26.6%; p = 0.70) between the study groups.

CONCLUSIONS

Use of the AVERT system was feasible and safe, with acceptable image quality during coronary angiography and PCI. AVERT significantly reduced CMV, with the extent of CMV reduction correlating with procedural complexity. No significant differences in CI-AKI were observed with AVERT in this trial. (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN [AVERT]; NCT01976299).

CD160 promotes NK cell cytotoxicity and IFN-γ production, but the function of CD160 on CD8 T cells remains unclear with some studies supporting a coinhibitory role and others a costimulatory role. In this study, we demonstrate that CD160 has a costimulatory role in promoting CD8 T cell effector functions needed for optimal clearance of oral infection. CD160 mice did not clear oral as efficiently as wild type (WT) littermates. WT RAG and CD160 RAG mice similarly cleared , indicating that CD160 on NK cells does not contribute to impaired clearance. Defective clearance is due to compromised intraepithelial lymphocytes and CD8 T cell functions. There was a reduction in the frequencies of granzyme B-expressing intraepithelial lymphocytes in -infected CD160 mice as compared with WT littermate controls. Similarly, the frequencies of granzyme B-expressing splenic CD8 T cells and IFN-γ and TNF-α double-producer CD8 T cells were significantly reduced in -infected CD160 mice compared with WT littermates. Adoptive transfer studies showed that RAG recipients receiving CD160 CD8 T cells had a higher mortality, exhibited more weight loss, and had a higher bacterial burden compared with RAG recipients receiving WT CD8 T cells. These findings demonstrate that CD160 provides costimulatory signals to CD8 T cells needed for optimal CD8 T cell responses and protective immunity during an acute mucosal bacterial infection.