Simple Multimarker Approaches Combining Markers of Necrosis

No available biomarker of necrosis offers the ideal properties of a very rapid early rise in conjunction with very high sensitivity and specificity (see Chapter 1). Thus, investigators have proposed the combined assessment of a marker with very rapid kinetics, such as myoglobin, along with a more specific marker of necrosis, such as troponin, to facilitate the diagnosis of MI. For example, in a study of 1005 patients with possible myocardial ischemia admitted to chest pain units, simultaneous quantitative testing for myoglobin, creatine kinase-MB (CK-MB), and cardiac troponin I (cTnI) reduced the time to detection of marker elevation (2.5 h) compared to either a strategy using only CK-MB and troponin (2.8 h) or local laboratory-based testing of CK-MB (3.4 h) (20). In addition, this multimarker strategy using markers of necrosis was positive in a larger proportion of patients (19 vs 5%) at presentation (Fig. 2A) and showed a more robust discrimination of the risk of death or MI than the single-marker approach (Fig. 2B). In this data set, there was no clear prognostic advantage of a strategy that included myoglobin compared with one based on CK-MB and troponin. By contrast, when studied among a population with a high clinical probability of ACS, interestingly, an elevated level of myoglobin was independently associated with mortality, even after controlling for CK-MB and troponin (21).

Strategies employing multiple markers of myocardial necrosis may also enable accelerated exclusion of MI. Application ofbedside testing ofmyoglobin and cTnI among 817 patients being evaluated for possible AMI in the emergency department provided a sensi-itivity and a negative predictive value of 96.9 and 99.6%, respectively, by 90 min after presentation (22). Such data reinforce the potential for simultaneous testing of multiple markers to increase substantially the sensitivity of diagnostic and prognostic assessment of patients with possible ACS. Specific algorithms for clinical application are presented in Chapter 4.

Fig. 3. Risk of death through 14 d stratified by baseline testing for cTnT using a rapid qualitative assay and hsCRP (positive defined as ©15.5 mg/pL) in patients with non-ST elevation ACS enrolled in TIMI 11A trial.

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