What are the American College of Emergency Physicians (ACEP) recommended testing strategies for cardiac markers?

Updated: Nov 20, 2018
  • Author: Donald Schreiber, MD, CM; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
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In patients with definite or possible ACS, serial evaluation of cardiac markers is essential to diagnosing acute MI.

The American College of Emergency Physicians (ACEP) recommends 3 different testing strategies for ruling out NSTEMI in the ED. [38] One strategy is to use a single negative CK-MB, TnI, or TnT measured 8-12 hours after symptom onset.

Another strategy is to use negative myoglobin in conjunction with a negative CK-MB mass or negative TnI measured at baseline and at 90 minutes in patients presenting less than 8 hours after symptom onset.

A third approach is to use a negative 2-hour delta CK-MB in conjunction with a negative 2-hour delta TnI in patients presenting less than 8 hours after symptom onset.

Note that ACEP does not specify whether to use the 99th percentile cutoff, the 10% CV cutoff, or the WHO acute MI cutoffs for troponin.

The 90-minute rule-out with myoglobin recommended by ACEP was based on a study that used myoglobin in conjunction with either CK-MB or TnI. [39] The CK-MB/myoglobin protocol yielded a sensitivity of 92% at 90 minutes, and the myoglobin/TnI combination yielded a sensitivity of 97% at 90 minutes.

ACEP acknowledges the relative lack of specificity for myoglobin and that many of the myoglobin studies did not define MI per the ACC/ESC guidelines. Nevertheless, it is difficult to comprehend the ACEP clinical policy that accepts a missed MI rate of 3-8%.

ACEP’s recommendations on the use of delta CK-MB and delta TnI are based on determining the change in the level of TnI or CK-MB on samples drawn 2 hours apart. However, the delta TnI evaluation is partially based on the use of older TnI assays and outdated WHO acute MI cutoffs in a retrospective study. Therefore, ACEP’s recommendation to use a delta TnI in conjunction with a delta CK-MB may not be generalizable to other commercially available troponin assays. Caution must be used when using ACEP’s recommendations in ED patients with chest pain and suspected ACS.

The following table outlines the recommended sampling frequency after ED admission for the different cardiac markers.

Table 1. Sampling Frequency of Cardiac Markers (Open Table in a new window)



3-4 h

6-9 h

12-24 h

>24 h

CK-MB isoforms, myoglobin











(only if very high risk)


Late presenters

(TnI, TnT)






The sample time at 3-4 hours is useful in the ED or chest pain observation unit where rapid triage and early diagnosis are essential. In other patients admitted for ACS, biomarkers drawn at the 3- to 4-hour interval are not as important as they are at the 6- to 9-hour mark. The ACC/AHA guidelines for the treatment of patients with unstable angina and NSTEMI recommend a baseline sample upon ED arrival and a repeat sample 6-9 hours after presentation.

Few studies on the "time to positivity" have been performed, but serial samples that become positive in the 12- to 24-hour window are considered unlikely, unless the patient has ongoing symptoms of ischemia after admission. Acute MI can therefore be ruled out in patients with negative serial marker results through the 6- to 9-hour period after presentation.

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