• Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH, Cannon CP, Francis G, Morrow DA, Ravkilde J, Storrow AB, Tang W, IFCC Committee on Standardization of Markers of Cardiac Damage, Jaffe AS, Mair J, Ordonez-Llanos J, Pagani F, Panteghini M, Tate J, National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes. Clin Chem 2007 Apr;53(4):547-51. [23 references] PubMed



• Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH, National Academy of Clinical Biochemistry, IFCC Committee for Standardization of Markers of Cardiac Damage. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Circulation 2007 Apr 3;115(13):e352-5. [23 references] PubMed

This guideline updates a previous version: Wu AH, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes R Jr. National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem 1999 Jul;45(7):1104-21. [119 references] PubMed

• June 8, 2007, Troponin-I Immunoassay: Class I Recall of all lots of the Architect Stat Troponin-I Immunoassay. The assay may report falsely elevated or falsely decreased results at and near a low level, which may impact patient treatment.

• Chapter 1: Clinical characteristics and utilization of biochemical markers in acute coronary syndromes
• Chapter 3: Clinical utilization of cardiac biomarker testing in heart failure
• Chapter 4: Analytical issues for biomarkers of heart failure
• Chapter 5: Point of care testing, oversight and administration of cardiac biomarkers for acute coronary syndromes
• Chapter 6: Use of cardiac troponin and B-type natriuretic peptide or N-terminal proB-type natriuretic peptide for etiologies other than acute coronary syndromes and heart failure

Analytic Biomarker Issues

Recommendations: Analytical Aspects of Acute Coronary Syndrome (ACS) Biomarkers

All Class I

1. Reference decision-limits should be established for each cardiac biomarker based on a population of normal, healthy individuals without a known history of heart disease (reference population). For cardiac troponin I (cTnI) and T (cTnT), as well as for creatine kinase MB (CK-MB) mass, the 99th percentile of the reference population should be the decision-limit for myocardial injury. The Clinical Laboratory Standards Institute (CLSI; formerly NCCLS) recommends a minimum of 120 individuals per group of healthy individuals for appropriate statistical determination of a normal reference limit cutoff. Sex-specific reference limits should be used in clinical practice for CK-MB mass. For myoglobin, the 97.5th percentile (with sex-specific reference limits) should be the decision-limit for myocardial injury. (Level of Evidence: B)
2. One decision-limit, the 99th percentile, is recommended as the optimum cutoff for cTnI, cTnT, and CK-MB mass. ACS patients with cTnI and cTnT results above the decision-limit should be labeled as having myocardial injury and a high-risk profile. (Level of Evidence: B)
3. Assays for cardiac biomarkers should strive for a total imprecision (% coefficient of variation [CV]) of <10% at the 99th percentile reference limit. Before introduction into clinical practice, cardiac biomarker assays must be characterized with respect to potential interferences, including rheumatoid factors, human anti-mouse antibodies, and heterophile antibodies. Pre-analytical and analytical assay characteristics should include biomarker stability (over time and across temperature ranges) for each acceptable specimen type used in clinical practice and identification of antibody/epitope recognition sites for each biomarker. Analytical and pre-analytical specifications developed by professional groups such as the International Federation of Clinical Chemistry (IFCC) should be followed. (Level of Evidence: C)
4. Serum, plasma, and anticoagulated whole blood are acceptable specimens for the analysis of cardiac biomarkers. Choice of specimen must be based on sufficient evidence and the known characteristics of individual biomarker assays. (Level of Evidence: C)

Definitions:

Weight of Evidence

A - Data derived from multiple randomized or appropriately designed clinical trials that involved large numbers of patients

B - Data derived from a limited number of randomized or appropriately designed trials that involved small numbers of patients or from careful analyses of observational registries.

C - Expert Consensus was the primary basis for the recommendation

Summary of Indications

Class I: Conditions for which there is evidence and/or general agreement that a given laboratory procedure or treatment is useful and effective.

Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a laboratory procedure or treatment.

Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.

Class IIb: Usefulness/efficacy is less well established by evidence/opinion.

Class III: Conditions for which there is evidence and/or general agreement that the laboratory procedure/treatment is not useful/effective and in some cases may be harmful.

• Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH, Cannon CP, Francis G, Morrow DA, Ravkilde J, Storrow AB, Tang W, IFCC Committee on Standardization of Markers of Cardiac Damage, Jaffe AS, Mair J, Ordonez-Llanos J, Pagani F, Panteghini M, Tate J, National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes. Clin Chem 2007 Apr;53(4):547-51. [23 references] PubMed



• Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH, National Academy of Clinical Biochemistry, IFCC Committee for Standardization of Markers of Cardiac Damage. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Circulation 2007 Apr 3;115(13):e352-5. [23 references] PubMed

Financial Disclosures: The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines Committee for Utilization of Biomarkers in Acute Coronary Syndromes and Heart Failure reports all reported relationships within the 2 years previous to this publication that may be relevant to this guidelines document. A document of those relationships may be found in the online Data Supplement at http://www.clinchem.org/content/vol53/issue4.

This guideline updates a previous version: Wu AH, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes R Jr. National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem 1999 Jul;45(7):1104-21. [119 references] PubMed

Electronic copies: Available from the National Academy of Clinical Biochemistry (NACB) Web site.

Print copies: National Academy of Clinical Biochemistry publications are available through American Association for Clinical Chemistry (AACC) Press. To make a purchase or request a catalog, contact AACC Customer Service at 202-857-0717 or custserv@aacc.org.

Electronic copies: Available from the National Academy of Clinical Biochemistry (NACB) Web site.

Print copies: National Academy of Clinical Biochemistry publications are available through American Association for Clinical Chemistry (AACC) Press. To make a purchase or request a catalog, contact AACC Customer Service at 202-857-0717 or custserv@aacc.org.

Guidelines represented on the NGC Web site are submitted by guideline developers, and are screened solely to determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion.aspx .

NGC, AHRQ, and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover, the views and opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or hosting of guidelines in NGC may not be used for advertising or commercial endorsement purposes.

Readers with questions regarding guideline content are directed to contact the guideline developer.