The International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) recently issued a position statement, “IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays.” The task force was formed in 2011, charged with providing evidence-based educational materials to assist users of biomarkers, including laboratorians, clinicians, researchers, and those working in in-vitro diagnostics and regulatory agencies. The goal was to help these professionals understand key analytical and clinical aspects of established and novel cardiac biomarkers for use in research and clinical practice.
In addition to the position statement, IFCC prepared two reference guides in extended and pocket form to assist laboratories in implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice.
The task force is composed of laboratory medicine scientists, emergency medicine physicians and cardiologists, and its goal was to address two key issues related to implementing hs-cTn assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accordance with the universal definition of acute myocardial infarction (AMI), according to the position statement.
The 99th percentile value is universally endorsed as the reference cut-off to aid in diagnosing AMI. Key components necessary to implement hs-cTn assays in practice include: determining the 99th percentile in a healthy population, considering the 99th percentile from either peer-reviewed literature or the manufacturer’s product information, measuring hs-cTn assays with an analytical imprecision of ≤10% coefficient of variation, having hs assays that measure cTn above the limit of detection in ≥50% of healthy subjects, and reporting 99th percentile values as whole numbers only in ng/L units.
Also, age—especially older than 60 years—affects cTn values, as does gender, with men having higher values than women. The 99th percentile should be determined individually for each assay because hs-cTn assays are not standardized, and the 99th percentile values should be established or confirmed with the appropriate statistical power for each sex (men and women) using a minimum of 300 male and 300 female subjects (by sex), or 20 subjects if confirming 99th percentiles, using an appropriate 1-tailed nonparametric statistical method.
“These analytical, educational suggestions proposed and endorsed by the IFCC TF-CB are the first of many steps to better harmonize the global use and reporting of hs-cTn assays in practice,” the task force said.
Evaluating the degree of serial changes in hs-cTn values is best for differentiating among patients who have any type of acute cardiac injury, according to the position statement. “This approach is necessitated because there often are elevations of cTn values, particularly with those assays that are more sensitive, i.e. the ‘high-sensitivity’ assays,” the task force wrote. “Key to this determination is the assumption that the timing of the patient's presentation allows for such an evaluation.”
Factors that affect developing criteria for this include timing of the evaluation, spontaneous change in patients who do not have acute cardiac injury, the patient’s anatomy that led to the acute problem, and whether you are trying to improve diagnostic sensitivity or specificity. “It is important to recognize that criteria that rely on more marked changes will improve specificity at the expense of sensitivity, whereas those that are less marked will improve sensitivity at the expense of specificity. Thus, considerable thought and interaction between the stakeholders who use these assays is suggested,” the task force said.