Point-of-Care: Roadmap for Analytical Characterization and Validation of a High-Sensitivity Cardiac Troponin I Assay in Plasma and Whole Blood Matrices.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays enable more precise use of traditional diagnostic strategies and earlier rule-out/rule-in at 0/1 h or 0/2 h after presentation of acute myocardial infarction (AMI). Availability of hs-cTn measurements at point-of-care (POC) can improve timely management of AMI patients. A roadmap for regulatory and analytical validation is exemplified with studies with the Atellica VTLi hs-cTnI at POC. METHODS: High-sensitivity performance was assessed with AACC/IFCC expert recommendations. Clinical Laboratory Standards Institute protocols were used for characterizing limit of blank, limit of detection (LoD), limit of quantitation (LoQ), 10% CV, precision, linearity, and analytic specificity with several reagent lots. Bland-Altman, Passing-Bablok, and hematocrit bias plots compared hs-cTnI measurement in lithium-heparin plasma (PL) and whole blood (WB) matrices. RESULTS: LoB was 0.55 ng/L; LoD and LoQ were 1.24 ng/L and 2.1 ng/Lm for PL and 1.60 ng/L and 3.7 ng/L for WB, respectively. The male 99th percentile is 27 ng/L, and female 99th percentile upper reference limit is 18 ng/L; 10% CVs were 6.7 ng/L for PL and 8.9 ng/L for WB. Also ≥50% of hs-cTnI values for healthy cohorts exceeded the LoD, confirming high-sensitivity performance. Linearity spanned from LoQ to 1250 ng/L. Specificity was >90% for 40 potential interferences; no hook effect was detected. WB and PL correlation was WB = 1.02*plasma + 0.3 ng/L (r = 0.996, n = 152). No hs-cTnI association with hematocrit was detected (R2 = 0.003). CONCLUSION: This analytical roadmap showed high-sensitivity performance, good analytic characteristics, and excellent PL and WB agreement for the Atellica VTLi hs-cTnI POC system. Essential clinical performance studies in patients by intended POC users may now commence.

Determination of sex-specific 99th percentile upper reference limits for a point of care high sensitivity cardiac troponin I assay.

OBJECTIVES: High sensitivity (hs) cardiac troponin (cTn) assays are defined per the IFCC Committee on Clinical Application of Cardiac Biomarker (C-CB) by the ability to measure ≥ 50% of concentrations greater than the limit of detection (LoD) with an impression of ≤10% at sex-specific 99th percentiles. Our study determined the sex-specific 99th percentile upper reference limits for males and females utilizing heparinized plasma from AACC universal sample bank for the Siemens point of care (POC) Atellica® VTLi hs-cTnI immunoassay. METHODS: Apparently healthy subjects, included overall 693, males 363, and females 330, following exclusionary surrogate biomarker use of hemoglobin A1c, NT-proBNP, and eGFR, along with statin medication. hs-cTnI was measured in a central laboratory, on multiple POC Atellica® VTLi immunoassay analyzers. The LoD was 1.24 ng/L and the 10%CV concentration was 6.7 ng/L. 99th percentile URLs were determined by the nonparametric (NP) method. RESULTS: Histograms of the hs-cTnI concentrations (ng/L) for males and females were used to visualize the distributions and concentrations in men and women and differed significantly (pre- and post-exclusion, both p <0.001). 99th percentile URLs were: overall 23 ng/L (90% CI 20-32 ng/L); male 27 ng/L (CI 21-37 ng/L); female 18 ng/L (CI 9-78 ng/L). The percentages of subjects having a measurable concentration ≥ the LoD were: overall 83.7%, male 87.3%, female 79.7%. CONCLUSIONS: Our findings show the novel POC Atellica® VTLi hs-cTnI assay meets the designation of a 'high-sensitivity' assay using heparinized plasma.