Clinical Use of High-sensitivity Cardiac Troponin in Patients With Suspected Myocardial Infarction

Raphael Twerenbold, MD; Jasper Boeddinghaus, MD; Thomas Nestelberger, MD; Karin Wildi, MD; Maria Rubini Gimenez, MD; Patrick Badertscher, MD; Christian Mueller, MD


J Am Coll Cardiol. 2017;70(8):996-1012. 

In This Article

High-sensitivity Cardiac Troponin

The clinical assessment, even combined with an electrocardiogram (ECG), is not sufficient to diagnose or exclude non–ST-segment-elevation myocardial infarction (NSTEMI) in most patients, and thus the addition of blood tests to measure the concentration of cardiac troponin (cTn) T or I form the cornerstone for the early diagnosis of MI. Clinicians use cTn values to estimate the likelihood of MI and the short-term risk of death.

Advances in assay technology have led to a refinement in the clinical ability to detect and quantify cardiomyocyte injury.[9,10,12–40] These assays increased diagnostic accuracy at presentation, substantially reduced the sensitivity deficit of cTn at presentation for MI and the associated "troponin-blind" interval, and allowed the recent development of several novel strategies for the early rule-out or early rule-in of MI.[9,10,12–40] These improved assays are labeled "sensitive" when able to detect cTn in ~20% to 50% of healthy individuals and "high-sensitivity" if they detect a cTn level in >50% of reference (apparently healthy) subjects, and if they have a coefficient of variation of <10% at the 99th percentile upper-reference limit of the assay.[10] High-sensitivity assays can accurately detect cTn at lower levels than older-generation assays, giving them higher sensitivity for the detection of MI at presentation, which means that the time interval to the second measurement of high-sensitivity cTn (hs-cTn) can be significantly shortened, thereby reducing the time to diagnosis and improving efficiency in the ED.[9,10,12–41]

Although hs-cTn assays have been used in Europe, Australia, New Zealand, Canada, and many other developed countries since 2010, the first hs-cTn assay has just received approval for clinical use in the United States in the spring of 2017. By contrast, sensitive cTn (s-cTn) assays are widely used in the United States.

cTnT and -I are structural proteins unique to the heart. Thereby, cTnT and -I are organ-specific, but not disease-specific markers. High-sensitivity and s-cTnT and -I assays exactly quantify the amount of cardiomyocyte injury.[12,27,41,42] They ought to be interpreted as quantitative variables and not in a binary fashion (negative/positive) like a pregnancy test. From a diagnostic perspective, it is highly inappropriate to label a patient as "cTn-positive," as this would lump together patients with only mildly elevated cTn levels barely above the 99th percentile and an associated positive predictive value (PPV) for MI of only about 40% to 50% with patients with markedly elevated cTn levels (e.g., about 5 times above the 99th percentile) and an associated PPV of 90%. The higher the cTn level, the higher is the likelihood for the presence of MI. When referring to levels in the normal range, the same concept applies: the lower the cTn blood concentration, the lower the likelihood for MI. Continuous medical education and training of physicians in these concepts is essential to avoid inappropriate interpretation of chronic mild elevations of cTn associated with, for example, heart failure or other structural cardiac disorders such as valvular heart disease and left ventricular hypertrophy as signs of MI.