This is TRAPID-AMI, a prospective Roche hs-TnT (99th percentile 14ng/L) study for patients presenting within 6 hours of peak chest pain symptoms. Samples were drawn on arrival, then serially over the next two hours, and a final sample drawn 4-14h after presentation. The primary outcome was acute MI, as adjudicated by a panel of cardiologists blinded to the hs-TnT result but aware of a Siemens conventional troponin I (99th percentile 40ng/L) result. Interestingly, they powered their study specifically for a negative predictive value, rather than a specific sensitivity result – certainly an easier enrollment target, but also potentially more difficult to generalize.
All told, they included 1,282 patients in the study and there were 213 patients ultimately diagnosed with AMI on their initial presentation. In 30-day follow-up, 11 patients could not be contacted, and an additional 18 patients not originally diagnosed with AMI met their combined MACE endpoint, 15 of which were revascularlization. Of these 213 patients with initial diagnosis of AMI, there were four false-negatives with respect to the troponin assays being below the limit of detection. For their primary outcome, then, sensitivity was 98.1% (95.3-99.5) with specificity 52.0% (49.0-55.0). The authors go on to present several different strategies based on various cut-offs and various EKG findings, the effect of which are various trade-offs between number of patients eligible for a zero-hour rule-out, the sensitivity, and the specificity. Negative predictive values, of course, generally ran >99%, owing the the relative infrequency of AMI diagnoses.
This study, like most before it, provides little additional insight. Sensitive troponin assays are, indeed, more sensitive. The sensitivity comes at a cost of specificity. We are also encountering a sort of Zeno’s Paradox with regard to our evaluation of these strategies. We employ more sensitive assays both to detect AMI up-front, but also as our gold-standard for adjudicated final outcome. The increased sensitivity, then, cuts both ways – as we detect tinier and tinier nSTEMI as a sort of ceiling for our sensitivity of any rapid rule-out strategy. Is it reasonable to suggest the occasional 1-in-200 tiny myocardial injury missed is unlikely to have serious clinical consequences? If so, the best question to address is how to continue the care of these patients after they leave the Emergency Department such that those who would benefit from additional medical and endovascular intervention are not lost.
“The use of very low concentrations of high sensitivity troponin T to rule out acute myocardial infarction using a single blood test”
http://www.ncbi.nlm.nih.gov/pubmed/27178492