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Original Investigation | Health Care Reform

One-Hour Rule-out and Rule-in of Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T

Tobias Reichlin, MD; Christian Schindler, PhD; Beatrice Drexler, MD; Raphael Twerenbold, MD; Miriam Reiter, MD; Christa Zellweger, MD; Berit Moehring, MD; Ronny Ziller, MD; Rebeca Hoeller, MD; Maria Rubini Gimenez, MD; Philip Haaf, MD; Mihael Potocki, MD; Karin Wildi, MD; Cathrin Balmelli, MD; Michael Freese, RN; Claudia Stelzig, MSc; Heike Freidank, MD; Stefan Osswald, MD; Christian Mueller, MD, FESC
Arch Intern Med. 2012;172(16):1211-1218. doi:10.1001/archinternmed.2012.3698.
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Background  High-sensitivity cardiac troponin (hs-cTn) assays seem to improve the early diagnosis of acute myocardial infarction (AMI), but it is unknown how to best use them in clinical practice. Our objective was to develop and validate an algorithm for rapid rule-out and rule-in of AMI.

Methods  A prospective multicenter study enrolling 872 unselected patients with acute chest pain presenting to the emergency department. High-sensitivity cardiac troponin T (hs-cTnT) was measured in a blinded fashion at presentation and after 1 hour. The final diagnosis was adjudicated by 2 independent cardiologists. An hs-cTnT algorithm incorporating baseline values as well as absolute changes within the first hour was derived from 436 randomly selected patients and validated in the remaining 436 patients. The primary prognostic end point was death during 30 days of follow-up.

Results  Acute myocardial infarction was the final diagnosis in 17% of patients. After applying the hs-cTnT algorithm developed in the derivation cohort to the validation cohort, 259 patients (60%) could be classified as “rule-out,” 76 patients (17%) as “rule-in,” and 101 patients (23%) as in the “observational zone” within 1 hour. Overall, this resulted in a sensitivity and negative predictive value of 100% for rule-out, a 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% (P < .001) in patients classified as rule-out, observational zone, and rule-in, respectively.

Conclusions  Using a simple algorithm incorporating hs-cTnT baseline values and absolute changes within the first hour allowed a safe rule-out as well as an accurate rule-in of AMI within 1 hour in 77% of unselected patients with acute chest pain. This novel strategy may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients.

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Figures

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Figure 1. Levels of high-sensitivity cardiac troponin T (hs-cTnT) at presentation. Baseline hs-cTnT levels at presentation to the emergency department in all patients according to the adjudicated final diagnoses. Boxes represent interquartile ranges, while whiskers display ranges (without outliers further than 1.5 interquartile ranges from the respective end of the box). The proportion of patients above the 99th percentile were 88% for acute myocardial infarction (AMI), 36% for unstable angina (UA), 45% for cardiac but not coronary artery disease (CAD), 13% for noncardiac chest pain, and 31% for patients with unknown causes.

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Figure 2. Prevalence of acute myocardial infarction (AMI) according to absolute levels of high-sensitivity cardiac troponin T (hs-cTnT) at presentation.

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Figure 3. Algorithm for diagnosis of acute myocardial infarction (AMI) using high-sensitivity cardiac troponin T (hs-cTnT) in patients presenting with chest pain. Results are displayed for the validation cohort (n = 436). High-sensitivity cardiac troponin T (hs-cTnT) values are presented in nanograms per liter. 0h indicates hs-cTnT at presentation to the emergency department; Delta 1h, absolute change of hs-cTnT within the first hour; NPV, negative predictive value; and PPV, positive predictive value.

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Figure 4. Kaplan-Meier curves for the cumulative survival according to classification provided by the high-sensitivity cardiac troponin T (hs-cTnT) algorithm. Kaplan-Meier curves display the cumulative survival during 30 days of follow-up (A) and 2 years of follow-up (B) in all patients with chest pain (n = 872) according to the classification into “rule-out” (n = 491), “observational zone”(n = 212), and “rule-in” (n = 169) provided by the hs-cTnT 1-hour algorithm. Differences in survival were assessed using the log-rank test.

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References

Correspondence

March 25, 2013
Edward Watts Carlton, MBChB, MCEM; James Hugo Phillimore Gamble, MA, Cantab, BMBCh, MRCP; Kim Greaves, BSc, MD, FACC, FRCP
JAMA Intern Med. 2013;173(6):477-478. doi:10.1001/jamainternmed.2013.2273.
March 25, 2013
Tobias Reichlin, MD; Christian Mueller, MD, FESC
JAMA Intern Med. 2013;173(6):477-478. doi:10.1001/jamainternmed.2013.2787.
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