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

Disclosures

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

In This Article

Application of Rapid, Troponin-based Triage Algorithms in the United States

In the spring of 2017, the Food and Drug Administration (FDA) approved the hs-cTnT assay as the first clinically available, more sensitive cTn assay in the United States.[114] The FDA-approved use of hs-cTnT differs in 2 important details from the contemporary use of hs-cTnT in most other countries. First, very low concentrations are only reported down to the limit of quantification (6 ng/l) as compared with the limit of blank (3 ng/l). Second, the FDA required the determination of the assay-specific 99th percentile upper-reference limit in an age-matched population to that of patients presenting to the ED with suspected MI, whereas the 99th percentile upper-reference limit for use outside the United States was determined in healthy and often younger individuals. As a consequence, the FDA-approved uniform 99th percentile upper-reference limit (19 ng/l) is slightly higher as compared with the 99th percentile upper-reference limit used outside the United States (14 ng/l). Both changes could potentially impact the safety and/or efficacy of rapid triage algorithms defined previously in a non-FDA setting.

A recent analysis aimed to quantify the impact of the FDA-approved use of hs-cTnT on the safety and efficacy of the 0/1h-ESC-algorithm in a large international diagnostic multicenter study enrolling 3,267 unselected patients presenting with suspected MI to the ED.[115] The original 0/1h-ESC algorithm was adapted to the FDA setting by lifting the direct rule-out criterion at presentation from <5 ng/l to <6 ng/l, because hs-cTnT levels are only reported down to 6 ng/l in the United States. Rule-out safety, as well as rule-in performance, of the original and the modified algorithm were very high and comparable (NPV 99.8% vs. 99.9%; p = 0.928; sensitivity 99.4% vs. 99.6%; p = 0.667; PPV 76.9% vs. 76.7%; p = 0.969; specificity 95.5% for both algorithms; p = 0.929) (Figure 5). Both algorithms allowed rapid rule-out and rule-in of MI in 3 of 4 patients. These findings confirm the concept of the 0/1h-ESC algorithms and suggest that the 0/1h algorithm using hs-cTnT as approved by the FDA seems to provide high safety and high efficacy for the triage toward rapid rule-out or rule-in of MI.

Figure 5.

Diagnostic Performance of the Original and Modified 0/1h-Algorithm
Diagnostic performance of (A) the original 0/1h-ESC-algorithm and (B) the 0/1h-ESC-algorithm modified according to the Food and Drug Administration (FDA) regulatory requirements for rapid rule-out and rule-in of NSTEMI using high-sensitivity cardiac troponin T (hs-cTnT). The underlying differences between the original and the modified algorithm are circled in green. @0h = based on 0-h blood sample obtained at presentation to the ED only (direct rule-out or direct rule-in); @1h = based on 0- and 1-h blood samples; 1h-change = absolute (unsigned) change of hs-cTnT within 1 h; NPV = negative predictive value; PPV = positive predictive value; Sens = sensitivity; Spec = specificity; other abbreviations as in Figures 1 and 3. Adapted with permission from Twerenbold et al.(115).

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