Highly sensitive troponin immunoassays: navigating between the scylla and charybdis

The recent development and introduction into clinical and laboratory practice of the novel highly sensitive cardiac troponin assays has contributed to improve the diagnosis and risk stratification of patients presenting with suspected myocardial injury and acute coronary syndrome at the emergency department (ED). The enhanced ability to detect very low amount of troponin in blood with the novel tests has also raised the challenge of intercepting values above the 99th percentile of the reference population in apparently healthy subjects as well as several patients with comorbidities different from myocardial infarction. As such, the diagnostic approach and the triage of chest pain patients need to be readjusted and, most probably, the role of clinical judgment will assume greater importance than with the old generation immunoassays. In this perspective, a strategy based on the "delta biomarker approach" rather than that based on the traditional "peak" value might be more viable, since the observation of a dynamic pattern of troponin values might help discriminating the timing of injury as well as distinguishing acute from chronic etiologies and thereby increasing both the specificity and the positive predictive value (PPV) of the test. Nevertheless, this approach would require an accurate definition of the reference ranges as well as the identification of the magnitude of increase or decrease during serial sampling. We are thereby navigating between the Scylla (i.e., definition of appropriate 99th percentile of the reference population) and Charybdis (i.e., identification of a reliable delta threshold) of the novel highly sensitive immunoassays. The aim of this article is to provide an overview on the clinical impact of the highly sensitive cardiac troponin immunoassays in the differential diagnosis of patients presenting to ED with thoracic pain suggestive for acute coronary syndrome.