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troponin-I in serum/plasma

Indications: - assessment/diagnosis of myocardial infarction in emergency department or hospital setting - single troponin-I levels should not be used for the diagnosis of acute myocardial infarction (a significant increase is used) - serial samples should be drawn & tested at sequential intervals - high-sensitivity serum troponin-I at presentation & 1 hour later suggested in protocol for rule out NSTEMI [15,16] - for nonischemic clinical conditions, routine testing is not advised, except for cardiac prognosis in patients with chronic kidney disease & patients undergoing chemotherapy who have drug-induced cardiac injury [7] * it seems measurement of serum creatine kinase (CK) & serum CK-MB isozymes no longer used much if at all Reference interval: - < 0.9 ng/mL (Opus) - < 0.5 ng/mL (Abbott AxSYM) - < 0.2 ng/mL (DPC Immulite) - < 0.1 ng/ml (Bayer Centaur) [9] ng/mL (Beckman Access) - published reference intervals seem to vary widely Clinical significance: - elevated cardiac-specific troponin-I indicates myocardial injury due to myocardial ischemia &/or myocardial infarction [9] - cardiac-specific troponin-I is measurable in the serum within 3 hours after onset of an acute MI [5]; earlier assays 4-6 hours - levels < 0.05 ng/mL using high-sensitivity assay with 99.6% negative predictive value for type 1 MI on presentation or type 1 MI or cardiac death within 30 days [8] - high-sensitivity cardiac troponin I concentration of < 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days [11,18] - high-sensitivity troponin I levels normal at presentation & not increased 1 hour later can rule out MI [10] - high-sensitivity troponin I levels elevated at presentation & not increased 1 hour later warrant inpatient observation but not coronary angiography [10] - high sensitivity troponin I identifies more patients with acute coronary syndrome, but does not improve outcomes [14] - peak concentrations are reached in approximately 12-18 hours after infarction - levels may remain elevated for several days prior to returning to normal - transient elevations in serum troponin I in hospitalized patients is associated with increased all-cause mortality & major cardiovascular complications [2] - lower thresholds may better identify patients with acute coronary syndrome [4] - levels < 2.5 pg/mL may identify patients with stable CAD at low risk for inducible myocardia ischemia [17] - manufacturers' upper limit of normal for high-sensitivity cardiac troponin may be too low [19] Increases: - myocardial injury due to myocardial ischemia &/or myocardial infarction [9] - high-sensitivity troponin I levels elevated at presentation & not increased 1 hour later warrant inpatient observation but not coronary angiography (see troponin T cardiac in serum/plasma) - heart failure - asymptomatic patients with levels in the top 1/3 with higher risk for incident heart failure than those in the bottom 1/3 (RR=2.1) [13] - aortic stenosis - due to left ventricular wall stress & myocardial ischemia - sepsis Principle: The Opus Troponin I is a 2 site sandwich immunoassay. The assay uses 2 goat polyclonal antibodies which recognize 2 different polypeptide segments unique to the cardiac-specific isoform of troponin-I. One of these antibodies is immobilized onto glass fiber. A 2nd antibody is conjugated to alkaline phosphatase. After washing the glass fiber, bound Troponin-I is measured by alkaline phosphatase activity using the fluorescent substrate 4-methylumbelliferyl phosphate. 3 levels of troponin-I controls are used. Interferences: 1) Improperly handled samples containing any type of particulate matter may result in falsely elevated results 2) bilirubin levels > 5 mg/dL may cause falsely low values 3) heterophilic antibodies. 4) high intake of biotin make result in falsely low value [12]

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troponin-I

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troponin I in serum/plasma/blood

References

  1. Behring Diagnostics, Westwood MA (Opus procedure manual)
  2. Gudmundon GS, Kahn SE, Moran JF Association of mild transient elevation of troponin I levels with increased mortality and major cardiovascular events in the general patient population Arch Lab Med & Pathology 129:474, 2005
  3. Clinical Guide to Laboratory Tests, 4th edition, HB Wu ed, WB Saunders, Philadelphia, 2006
  4. Mills NL et al Implementation of a Sensitive Troponin I Assay and Risk of Recurrent Myocardial Infarction and Death in Patients With Suspected Acute Coronary Syndrome JAMA. 2011;305(12):1210-1216 PMID: 21427373 http://jama.ama-assn.org/content/305/12/1210.short
  5. Keller T et al. Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. JAMA 2011 Dec 28; 306:2684. PMID: 22203537
  6. Troponin-I Laboratory Test Directory ARUP: 90613
  7. Newby LK et al ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations J Am Coll Cardiol. Nov 2012 PMID: 23154053 http://content.onlinejacc.org/article.aspx?articleID=1389700
  8. Sadlowski C, Sadoughi S, Saitz R High-Sensitivity Cardiac Troponin Testing May Identify Low-Risk for Heart Attack. Physician's First Watch, Oct 8, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Shah AS, Anand A, Sandoval Y et al High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015 Dec 19;386(10012):2481-8. Epub 2015 Oct 8. PMID: 26454362 Free PMC Article
  9. Medical Knowledge Self Assessment Program (MKSAP) 17, 19. American College of Physicians, Philadelphia 2015, 2023
  10. Neumann JT et al Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I 1-Hour Algorithm. JAMA Cardiol. Jul 1;1(4):397-404, Published online June 01, 2016 PMID: 27438315 http://cardiology.jamanetwork.com/article.aspx?articleid=2526373 - Carlton E et al Evaluation of High-Sensitivity Cardiac Troponin I Levels in Patients With Suspected Acute Coronary Syndrome. JAMA Cardiol. Jul 1;1(4):405-12, Published online June 01, 2016 PMID: 27438316 http://cardiology.jamanetwork.com/article.aspx?articleid=2526374 - Morrow DA Evidence-Based Algorithms Using High-Sensitivity Cardiac Troponin in the Emergency Department. JAMA Cardiol. Jul 1;1(4):379-81, Published online June 01, 2016 PMID: 27438311 http://cardiology.jamanetwork.com/article.aspx?articleid=2526371
  11. Chapman AR, Lee KK, McAllister DA et al Association of High-Sensitivity Cardiac Troponin I Concentration With Cardiac Outcomes in Patients With Suspected Acute Coronary Syndrome. JAMA. Published online November 11, 2017 PMID: 29127948 https://jamanetwork.com/journals/jama/fullarticle/2662908 - Shah AS, Anand A, Sandoval Y et al High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015 Dec 19;386(10012):2481-8. Epub 2015 Oct 8. PMID: 26454362 Free PMC Article
  12. FDA MedWatch Nov 28, 2017 Biotin (Vitamin B7): Safety Communication - May Interfere with Lab Tests. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm586641.htm - FDA Safety Communcation. Nov 5, 2019 - UPDATE: The FDA Warns that Biotin May Interfere with Lab Tests: https://www.fda.gov/medical-devices/safety-communications/update-fda-warns-biotin-may-interfere-lab-tests-fda-safety-communication - Biotin Interference with Troponin Lab Tests - Assays Subject to Biotin Interference. https://www.fda.gov/medical-devices/vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference
  13. Evans JDW, Dobbin SJH, Pettit SJ et al High-Sensitivity Cardiac Troponin and New-Onset Heart Failure. A Systematic Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure Events. JACC: Heart Failure. January 2018 PMID: 29331272 http://heartfailure.onlinejacc.org/content/early/2018/01/02/j.jchf.2017.11.003 - Jaffe AS, Miller WL. Meta-Analyses and Interpretation of Troponin Values in Heart Failure. JACC: Heart Failure. January 2018 PMID: 29331273 http://heartfailure.onlinejacc.org/content/early/2018/01/02/j.jchf.2017.12.001
  14. Shah ASV, Anand A, Strachan FE et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: A stepped-wedge, cluster- randomised controlled trial. Lancet 2018 Aug 28; PMID: 30170853 Free Article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31923-8/fulltext
  15. Reichlin T, Twerenbold R, Wildi K et al Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ. 2015 May 19;187(8):E243-52 PMID: 25869867 Free PMC Article http://www.cmaj.ca/content/early/2015/04/13/cmaj.141349.full.pdf
  16. Twerenbold R, Neumann JT, Sorensen NA Prospective Validation of the 0/1-h Algorithm for Early Diagnosis of Myocardial Infarction. J Am Coll Cardiol. 2018 Aug 7;72(6):620-632. PMID: 30071991
  17. Hammadah M, Kim JH, Tahhan AS et al Use of High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia: A Cohort Study. Ann Intern Med. 2018. Nov 6. PMID: 30398528 http://annals.org/aim/article-abstract/2712482/use-high-sensitivity-cardiac-troponin-exclusion-inducible-myocardial-ischemia-cohort - Devereaux PJ The Potential for Troponin to Inform Prognosis in Patients With Stable Coronary Artery Disease. Ann Intern Med. 2018. Nov 6 PMID: 30398543 http://annals.org/aim/article-abstract/2712931/potential-troponin-inform-prognosis-patients-stable-coronary-artery-disease
  18. Januzzi JL Jr, Suchindran S, Hoffmann U et al. Single-molecule hsTnI and short-term risk in stable patients with chest pain. J Am Coll Cardiol 2019 Jan 29; 73:251. PMID: 30678753 https://www.sciencedirect.com/science/article/pii/S073510971839199X - Collinson P. Troponin in suspected coronary artery disease: Headed toward a new paradigm in cardiac biomarkers? J Am Coll Cardiol 2019 Jan 29; 73:261. PMID: 30678754 https://www.sciencedirect.com/science/article/pii/S0735109718392611
  19. Mariathas M, Allan R, Ramamoorth S et al True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study. BMJ 2019;364:l729 PMID: 30867154 Free Article https://www.bmj.com/content/364/bmj.l729
  20. Charitakis K, Nguyen TC. Severe Symptomatic Aortic Stenosis? Check Troponin, Too. J Am Heart Assoc. 2019 Mar 19;8(6):e012156. PMID: 30866695 PMCID: PMC6475068 Free PMC article.
  21. Julius BK, Spillmann M, Vassalli G, Villari B, Eberli FR, Hess OM. Angina pectoris in patients with aortic stenosis and normal coronary arteries. Mechanisms and pathophysiological concepts. Circulation. 1997 Feb 18;95(4):892-8. PMID: 9054747

Component-of

cardiac injury panel