Troponin Algorithm Rules MI in or Out in 77% of Chest-Pain Patients

August 14, 2012

August 13, 2012 (Basel, Switzerland) — Swiss researchers have published more details about what they say is a simple algorithm employing high-sensitivity (hs) cardiac troponin T that can safely rule in or rule out an acute MI (AMI) in three-quarters of patients presenting to the emergency department with chest pain [1]. Dr Tobias Reichlin (Brigham and Women's Hospital Boston, MA) and colleagues at University Hospital Basel, Switzerland, report their findings online August 13, 2012 in the Archives of Internal Medicine.

Reichlin et al provide an important step forward in application of high sensitivity troponin as a tool for triage of [emergency-department] patients with possible MI.

Reichlin et al say they developed the algorithm--which incorporates baseline values in hs-troponin T as well as absolute changes within the first hour--because it has been unclear how best to take advantage of the new high-sensitivity troponin tests in clinical practice. The findings, they say, "are of great clinical importance," although they acknowledge that confirmatory studies will be required. The preliminary findings with regard to this algorithm were first presented at the ESC meeting in Paris last year.

Writing in an accompanying editorial [2], Dr L Kristin Newby (Duke Clinical Research Institute, Durham, NC) agrees. "Reichlin et al provide an important step forward in application of [hs-troponin T] as a tool for triage of [emergency-department] patients with possible MI," she says. "However, much work remains to develop the evidence to bring [hs-troponin T] testing and the algorithms they have developed to use in clinical practice."

Four Major Novel Findings

In their prospective, observational multicenter study, Reichlin et al enrolled 872 unselected patients presenting to emergency departments with acute chest pain. High-sensitivity cardiac troponin T was measured in a blinded fashion using the Elecsys 2010 assay (Roche Diagnostics) at presentation and after one hour, with a final diagnosis adjudicated by two independent cardiologists.

An hs-cardiac-troponin-T algorithm incorporating baseline values as well as changes within the first hour was derived from 436 randomly selected patients and validated in the remaining 436. The primary prognostic end point was death during 30 days of follow-up.

AMI was the final diagnosis in 17% of patients. After the algorithm developed from the first 436 patients was applied to the remaining 436 for validation, 259 patients (60%) could be classified as "rule-out" and 76 patients (17%) as "rule-in," with 101 patients (23%) classified as being in the observational zone within one hour.

Overall, this resulted in a sensitivity and negative predictive value of 100% for rule-out, specificity and positive predictive value of 97% and 84%, respectively, for rule-in, and a prevalence of AMI of 8% in the observational-zone group. Cumulative 30-day survival was 99.8%, 98.6%, and 95.3% in patients classified as rule-out, observational zone, and rule-in, respectively.

With the use of this algorithm, a safe rule-out as well as an accurate rule-in of AMI can be performed within one hour in 77% of patients with chest pain.

Reichlin and colleagues say there are "four major novel findings" from this study. First, "with the use of this algorithm, a safe rule-out as well as an accurate rule-in of AMI can be performed within one hour in 77% of patients with chest pain."

Second, the proportion of patients with AMI continuously increases with increasing levels of hs-cardiac troponin T, so the latter should be interpreted quantitatively rather than qualitatively. That means avoiding the terms "positive" and "negative" troponin, they say. Third, "using this algorithm significantly shortens the time needed for rule-out and rule-in of AMI and may obviate the need for prolonged monitoring and serial blood sampling in three out of four patients with acute chest pain."

Finally, as 30-day mortality was 0.2% in those ruled out for AMI, the findings underscore "the suitability of these patients for early discharge," they observe.

Simple Applicability Will Be Required

Reichlin et al acknowledge that the proportion of patients with AMI that they found (17%) was high compared with other chest-pain studies and therefore validation of the outcome is required. Also, studies applying these data prospectively for clinical decision making are warranted, they note. And this algorithm used one specific hs-troponin T assay, so other algorithms will need to be developed for other assays.

Newby adds that it will be imperative that, if validated, this and other such algorithms will need to be easily interpretable and the results provided electronically to physicians to allow simple application in triage and treatment.

Reichlin has received speaker honoraria from Brahms and Roche. Disclosures for the coauthors are listed in the paper. Newby is supported by research grants from the following companies: Amgen, AstraZeneca, Biosite, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eli Lilly, Genentech, Johnson & Johnson, Merck, Mosby, Novartis, Proctor & Gamble, Regado Biosciences, Roche Diagnostic, Schering Plough, Scios, and Shionogi Pharma.


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