High sensitivity Troponin I

High sensitivity cTnI results are used to assist in the diagnosis of acute myocardial infarction and to aid in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality [1-6].

Precision at low concentrations

The imprecision profile at low concentrations was determined by using plasma samples. The within-run and total standard deviations were calculated by CLSI EP5-A2 guidelines. The following results were obtained:

Sensitivity and measurable normal value

The limit of blank (LoB) and the limit of detection (LoD) of the PATHFASTTM hs-cTnI assay were determined, where LoB was 1.23 ng/L and LoD was 2.33 ng/L. The limit of quantitation (LoQ) at 20% coefficient of variation (CV) was determined to be 4 ng/L. The limit of quantitation (LoQ) at 10% coefficient of variation (CV) was determined to be 15 ng/L. These results were obtained from plasma samples.
The measurable number of healthy subjects between LoD and 99th percentile was 487 from 734 healthy subjects, in whom cardiovascular diseases were excluded by the following criteria: age <18; HbA1c ≥6.5%; NTpro-BNP ≥125 ng/L <75; NTpro-BNP ≥450 ng/L ≥75 years; eGFR <60 mL/min/1.73m².
PATHFASTTM hs-cTnI was classified as a high sensitive assay according to IFCC guidelines. With PATHFASTTM hs-cTnI assay classified as a high sensitivity assay, the gender specific 99th percentile and the measurable number of healthy subjects between LoD and 99th percentile were identified [7].

Reference ranges

The reference interval for the PATHFASTTM hs-cTnI assay was determined by testing 490 healthy individuals. The 99th percentile of the reference interval is 29 ng/L. The CV value at the 99th percentile concentration is 6.1% [7].

 

Diagnostic performance criteria

cTnI concentrations were measured by using the PATHFASTTM hs-cTnI assay in EDTA plasma samples obtained at 0 hour, 1 hour and 3 hours after admission to the chest pain unit (CPU) from 993 patients with suspicion of acute coronary syndrome. The final diagnosis identified 219 AMI patients (23.5%). The ROC analysis revealed AUC values for the discrimination between AMI and non-AMI patients including the clinical sensitivity and specificity, as well as the positive (PPV) and negative (NPV) predictive values based on the 99th percentile upper reference limit (URL) of 27.0 ng/L [8].

Publications

  1. Thygesen K, Alpert JS, White HD. Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J. 2007;28:2525-382)The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary
  2. Syndromes of the European Society of Cardiology. Guidelines for the diagnosis and treatment of non-ST-elevation acute coronary syndromes. Eur Heart J 2007;28:1598-1660.
  3. Apple FS. High-sensitivty cardiac troponin assays: what analytical and clinical issues need to be addressed before introduction into clinical practice? Clin Chem 2010;56:886-91.
  4. Peetz D et al. Method comparison of cardiac marker assays on PATHFAST, StratusCS, Axsym, Immulite 2000, Triage, Elecsys and Cardiac reader. Clin Lab 2006;52:605-14.
  5. Sandoval Y, Smith SW, Love SA, Sexter A, et al. Single high-sensitivity cardiac troponin I to rule-out acute myocardial infarction. Am J Med. 2017;130(9):1076-83.
  6. Sandoval Y, Smith SW, Shah ASV, Anand A, et al. Rapid Rule-Out of Acute Myocardial Injury Using a Single High-Sensitivity Cardiac Troponin I. Clin Chem 2017; 63:369-76.
  7. Cristenson et al. High-Sensitivity Cardiac Troponin I Assay for Point-of-Care or Laboratory Measurement: Pathfast® TnI-II System. TnI-II : in preparation.
  8. Neuman JT, Sörensen NA, Schwemer T, et al. Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I 1-Hour Algorithm. JAMA Cardiol. 2016;1:397-404.