Ordóñez‐Llanos, Jordi

Abstract The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.

Abstract The IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has directives and initiatives focused on providing evidence-based educational resources to aid and improve understanding around key analytical and clinical aspects of cardiac biomarkers used in clinical practice and the research setting. As a task force, we have previously published position statements and recommendations focused on use and analytical aspects of high-sensitivity cardiac troponin assays. The current educational document is the first from the C-CB highlighting important biochemical, analytical, and clinical aspects as they relate to the natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), with a focus on heart failure.

Abstract This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB,8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: (a) quality control (QC) utilization, (b) validation of the lower reportable analytical limits, (c) units to be used in reporting measurable concentrations for patients and QC materials, (d) 99th percentile sex-specific upper reference limits to define the reference interval; (e) criteria required to define hs-cTn assays, (f) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, (g) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, (h) harmonizing and standardizing assay results and the role of commutable materials, (i) time to reporting of results from sample receipt and sample collection, and (j) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.

AbstractBACKGROUNDB-type natriuretic peptides (BNPs) are used clinically to diagnose and monitor heart failure and are present in the circulation as multiple proBNP-derived fragments. We investigated the specificity of BNP immunoassays with glycosylated and nonglycosylated BNP, N-terminal proBNP (NT-proBNP), and proBNP peptides to probe the cross-reactivity of each assay.METHODSNine B-type natriuretic peptides were studied,including synthetic and recombinant BNP (Shionogi, Scios, Mayo), human and synthetic glycosylated and nonglycosylated NT-proBNP (HyTest, Roche Diagnostics), and human glycosylated and nonglycosylated proBNP (HyTest, Scios). Five BNP [Abbott, Abbott POC, Alere, Beckman Coulter, Siemens (Centaur)], 9 NT-proBNP [Ortho-Clinical Diagnostics, Roche, Response, bioMerieux, Siemens (Dimension, Immulite, Stratus CS), Mitsubishi] and 3 research-use-only proBNP immunoassays [Biosite (Alere), Bio-Rad, Goetze] were evaluated. Specificity was assessed by calculating the recovery between baseline and peptide-spiked human plasma pools at target concentrations of 100 ng/L BNP, 300 ng/L proBNP, or 450 ng/L NT-proBNP. All assays were performed in duplicate.RESULTSBNP and NT-proBNP assays demonstrated substantial cross-reactivity with proBNP peptides. NT-proBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1–32 peptide and have minimal cross-reactivity with BNP peptides and glycosylated proBNP.CONCLUSIONSBNP or NT-proBNP results are not transferable among the current existing immunoassays owing to their differences in cross-reactivity and ability to detect various glycosylated forms of proBNP-derived fragments. Opportunities remain to standardize and harmonize BNP and NT-proBNP assays, as well as to develop specific proBNP assays, to widen their clinical scope of use.

Abstract BACKGROUND Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) determinations are fixtures in clinical practice and research. Cardiac troponin testing has been the standard of practice for the diagnosis of acute myocardial infarction (AMI), early rule-out, risk stratification, and outcomes assessment in patients presenting with acute coronary syndrome (ACS) and non-ACS myocardial injury. We recognize from reading the literature over the past several years how poorly understood the analytical characteristics are for cTnI and cTnT assays by laboratorians, clinicians, and scientists who use these assays. CONTENT The purposes of this mini-review are (a) to define limit of blank, limit of detection, limit of quantification, and imprecision, (b) overview the analytical characteristics of the existing cardiac troponin assays, (c) recommend approaches to define a healthy (normal) reference population for determining the 99th percentile and the appropriate statistic to use for this calculation, (d) clarify how an assay becomes designated as “high sensitivity,” and (e) provide guidance on determining delta (Δ) change values. SUMMARY This review raises important educational information regarding cTnI and cTnT assays, their 99th percentile upper reference limits (URL) differentiated by sex, and specifically addresses high-sensitivity (hs)-assays used to measure low concentrations. Recommendations are made to help clarify the nomenclature and analytical and clinical characteristics to define hs-assays. The review also identifies challenges for the evolving implementation of hs-assays into clinical practice. It is hoped that with the introduction of these concepts, laboratorians, clinicians and researchers can develop a more unified view of how these assays should be used worldwide.