"Ultra-sensitive" cardiac troponins: Requirements for effective implementation in clinical practice

The measurement of cardiac troponins, either cardiac troponin I or T, has become the culprit of clinical decision making in patients with suspected acute coronary syndrome (ACS), especially in those with non-ST elevation myocardial infarction (NSTEMI). The leading analytical mainstays of cardiac troponin immunoassays include the limit of blank (LoB), limit of detection (LoD), functional sensitivity, the 99th percentile of a healthy reference population, along with the percentage of "ostensibly healthy" subjects displaying measurable values < 99th percentile. The latest generation of cardiac troponin immunoassays, conventionally defined as "high-sensitive" (HS), is characterized by a LoD over 100-fold lower compared to the first commercialized techniques and a percentage of measurable values consistently > 50% in the general healthy population. The very recent commercialization of methods with further improved analytical sensitivity (i.e., "ultra-sensitive" assays), which allow to measure cardiac troponin values in the vast majority of healthy subjects, is now challenging the diagnostic paradigm based on early rule-out of subjects with cardiac troponin values comprised between the 99th percentile and LoD. New diagnostic strategies, entailing assay-specific cut-offs, must hence be developed and validated in large multicenter studies. The aim of this article is to provide an update on commercially available HS and "ultra"-sensitive techniques for measuring cardiac troponins, along with possible implications of increasingly enhanced analytical sensitivity on diagnostic algorithms for evaluating patients with suspected ACS.