Troponin T-Based Algorithm Rules AMI In or Out

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Algorithmic Approach Provides Important Step Forward

The algorithmic approach to ruling in and ruling out AMI in patients presenting with chest pain as presented by Dr. Reichlin and his colleagues provides an important step forward in the application of high-sensitivity cardiac troponin as a tool for the triage of emergency department patients with possible MI, and could – with continued development – substantially improve the evaluation of such patients, Dr. L. Kristin Newby wrote in an accompanying editorial.

"However, much work remains to develop the evidence to bring hsTn testing and the algorithms they have developed to use in clinical practice," she wrote (Arch. Intern. Med. 2012 Aug. 13 [doi: 10/1001/archinternmed.2012.1808]).

Most importantly, the algorithm requires validation in prospective studies that assess implications for clinical outcomes in addition to the sensitivity and negative predictive value, and specificity and positive predictive value, she noted.

Such studies will help confirm that the thresholds used in the current study are satisfactory across age groups, and help determine whether factors such as sex and time from symptom onset should also be considered.

"Finally, although touted as ‘simple’ by the authors, the need for multi-component algorithms that are different for rule-in and rule-out and that vary by age group or other parameters will challenge application by busy clinicians unlikely to remember or accurately process the proposed algorithm. As such, it will be imperative that hsTn algorithms, if validated, are built into clinical decision support layered onto electronic health records so that testing results are provided electronically to physicians along with the algorithmic interpretation to allow systematic application in triage and treatment," she wrote.

Dr. Newby is with the division of cardiology at the Duke Clinical Research Institute in Durham, N.C. She reported receiving personal income from consulting or other service, and/or support from research grants or contracts from Amgen, AstraZeneca, and other companies, as well as the National Heart, Lung, and Blood Institute.



A simple algorithm using baseline values and absolute changes in high-sensitivity cardiac troponin T allows for rapid rule-in and rule-out of acute myocardial infarction in most patients who present with chest pain, according to findings from a prospective, multicenter study.

The algorithm, which was developed in a randomly selected derivation cohort of 436 patients and validated in an additional 436 subjects from the APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study, safely ruled out and accurately ruled in acute myocardial infarction within 1 hour in 77% of patients with chest pain, Dr. Tobias Reichlin of University Hospital Basel (Switzerland) and his colleagues reported online Aug. 13 in Archives of Internal Medicine.

In the validation cohort, the algorithm had 100% sensitivity and negative predictive value for ruling out acute myocardial infarction, and 97% specificity and 84% positive predictive value for ruling in AMI, the investigators said (Arch. Intern. Med. 2012 Aug. 13 [doi: 10.1001/archinternmed.2012.3698]).

Use of the algorithm "may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients with chest pain," they noted.

APACE participants presented during April 2006-June 2009 with acute chest pain symptoms suggestive of AMI, and were tested at baseline and after 1 hour for serum levels of high-sensitivity cardiac troponin T (hs-cTnT), a highly specific biomarker of myocardial necrosis.

Baseline levels of hs-cTnT were significantly higher in patients with AMI, compared with patients having other final diagnoses, and the prevalence of AMI in those presenting with acute chest pain differed significantly based on quantitative levels of hs-cTnT.

"In patients with hs-cTnT levels lower than 14 ng/L (99th percentile of healthy individuals) at presentation, the incidence of AMI was 3.2%, and there was a rise to 21% in patients with levels between 14 and 49 ng/L, 65% in patients with levels between 50 and 99 ng/L, 88% in patients with levels between 100 and 199 ng/L, and 93% in patients with levels of 200 ng/L or higher," the investigators said.

The optimal rule-out threshold was determined to be a baseline hs-cTnT level lower than 12 ng/L, and an absolute change of less than 3 ng/L in the first hour; the optimal rule-in threshold for AMI was either a baseline hs-cTnT of 52 ng/L or higher at presentation, or an absolute change of 5 ng/L or higher in the first hour.

The cumulative 30-day survival rates among 259 patients in whom AMI was ruled out, 76 in whom AMI was ruled in, and 101 who did not meet criteria for rule-in or rule-out (those considered to be in an "observational zone") were 99.8%, 95.3%, and 98.6%, respectively.

The low 30-day mortality of 0.2% in patients ruled out for AMI "underscores the suitability of these patients for early discharge," the investigators wrote.

"Our findings extend and corroborate recent results regarding hs-cTnT assays and are of great clinical importance," they said, explaining that they provide some clarification about how to use the assays for decision making in daily clinical practice. Because the proportion of patients with AMI continuously increases with increasing hs-cTnT values, it is important to interpret levels as quantitative rather than qualitative, avoiding the terms positive and negative with respect to the levels.

Given the potential limitations of the study – including the fact that it was conducted in emergency department patients with symptoms suggestive of AMI (the pretest probability setting where the algorithm should be used), and the fact that the proportion of patients with MI (17%) was high compared with other chest pain studies – the algorithm requires confirmation and external validation in a second multicenter study in a lower-risk cohort, the investigators said.

This study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, Abbott, Roche, Siemens, and the department of internal medicine at University Hospital Basel. The hs-cTnT assay was donated by Roche. Dr. Reichlin and coauthor Dr. Christian Mueller each disclosed receiving speaker honoraria from Abbott, Biosite, and other companies. In addition, Dr. Reichlin disclosed receiving grant support from the Professor Max Cloetta Foundation, and Dr. Mueller reported receiving research support from the Novartis Foundation, the Krokus Foundation, Abbott, AstraZeneca, and other companies.

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