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

Abstract

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 23 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.

Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: study protocol of a diagnostic RCT in the Netherlands (POB HELP)

“…The turn-around time from the application of the droplet of blood to the test result is approximately 8 min. The limit of detection is 1.6 ng/L and the limit of quantitation is 8.9 ng/L (at 10% CV) and 3.7 ng/L (at 20% CV) 22. The 99th percentile overall, for men and for women are, respectively, 23, 27 and 18 ng/L.…”

Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk

“…Recent analytical data have demonstrated that whole-blood and lithium-heparin plasma results correlated well in serial specimens from patients presenting to the ED. 23 We also acknowledge the need for future studies to address any potential bias or difference between plasma and whole-blood measurements that may or may not be clinically meaningful at concentrations close to the rule-out threshold. The present study supports the use of this hs-cTnI POC assay to facilitate early safe discharge without admission or urgent cardiac testing 1 but not in early presenters.…”

“…Fresh EDTA plasma and lithium-heparinized whole blood were concurrently measured: plasma on the clinically used hs-cTnI Abbott ARCHITECT i2000 SR analyzer 9,10 and whole blood on the hs-cTnI Siemens POC Atellica VTLi investigational assay. 22,23 The POC testing was performed by the same laboratory staff for both assays. The ARCHITECT hs-cTnI sex-specific 99th percentile upper reference limits (URLs) were 16 ng/L for female patients and 34 ng/L for male patients.…”

“…The Siemens POC Atellica VTLi assay had sex-specific 99 thpercentile URLs of 27 ng/L for male patients and 18 ng/L for female patients, with coefficients of variation ranging from 7.1% to 9.5% between 12.2 and 14.0 ng/L; 20% coefficients of variation for plasma and whole blood were 2.1 and 3.7 ng/L, respectively, with an LoD of 1.24 ng/L. 22,23 Event Adjudication (3) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; or (4) identification of an intracoronary thrombus by angiography or autopsy. 25 hs-cTnI assays used in clinical care (Abbott or Beckman) were used for patient adjudication.…”

Optimizing the Clinical Use of High-Sensitivity Troponin Assays: A Review

“…Pathfast and Triage lack studies on their clinical performance in AMI rule-in and rule-out. The most promising is the Atellica VTLi, with its analytical performance rigorously assessed in plasma and whole blood [ 79 ]. The Atellica’s clinical performance has been derived and validated in a US cohort (whole blood, n = 1086) against the Abbott hsTnI and in Australia (plasma, n = 1486) against the Beckman hs-cTnI [ 80 ].…”