Ckmb

81.0 (58.1-94.5)

99.4 (96.8-100)

94.4 (72.7-99.9)

97.7 (94.2-99.4)

Combination

100 (83.2-100.0)

91.2 (85.9-95.0)

58.3 (39.3-73.7)

100 (97.6-100.0)

Presented as % (95% confidence intervals).

A positive serum myoglobin test is defined as a level 88.7 ng/mL or higher, and a positive serum CK-MB as 11.9 ng/mL or higher, at either the time of ED presentation or 3 h later. The combination test is defined as positive if either of the above two tests is positive. Adapted from ref. 42.

Presented as % (95% confidence intervals).

A positive serum myoglobin test is defined as a level 88.7 ng/mL or higher, and a positive serum CK-MB as 11.9 ng/mL or higher, at either the time of ED presentation or 3 h later. The combination test is defined as positive if either of the above two tests is positive. Adapted from ref. 42.

line and 3 h for diagnosis of acute MI in the ED (42). Considering a positive result if the marker was positive at either time point, myoglobin was more sensitive than CK-MB but less specific, and the combination of the results of both markers was most sensitive and specific. The sensitivity, specificity,and positive and negative predictive values of the individual markers and the combination of markers are shown in Table 6. In a similar study of 101 ED patients with chest pain, Kontos et al. showed that when patients with diagnostic ECGs were excluded, the sensitivity and specificity of a combination of myoglobin and CK-MB mass results at baseline were 80 and 84%, respectively, for the diagnosis of acute MI, and were superior to those for either marker alone (108). The combination of the markers' results on serial sampling at 0 and 4 h had both sensitivity and specificity of 100%, suggesting that a combination of markers could identify or exclude the diagnosis of acute MI as early as 4 h after ED presentation.

The Biochemical Markers of Acute Coronary Syndromes (BIOMACS) Study Group evaluated the use of serial testing of CK-MB, myoglobin, and cTnT alone or in combination, and at different discriminatory levels to confirm or exclude the diagnosis of acute MI within 6 h of presentation in 142 patients with chest pain and nondiagnostic ECGs (52). They concluded that no markers alone or in combination could safely

Fig. 5. Percentage of correctly and falsely excluded acute MI in all patients (59 with and 83 without infarction) 3 and 6 h after admission. Reproduced with permission from ref. 52.

exclude the diagnosis of acute MI with certainty on admission, but that by monitoring a combination of myoglobin with CK-MB or cTnT, MI could be excluded in up to 72% by 6 h with a low rate of patients falsely excluded (Fig. 5). For the diagnosis of MI, no single marker regardless of the discriminatory level used combined high sensitivity and specificity, but the combination of myoglobin and CK-MB or myoglobin and cTnT on serial testing had sensitivities of 92 and 82%, respectively, at 2 h, and 98% for both combinations at 6 h. Specificities of the combinations were 98 and 94%, respectively, at 2 h, and 93 and 82%, respectively, at 6 h.

Small studies have investigated the potential of some of the newer cardiac markers in diagnosis and risk stratification in the low to moderate risk Chest Pain Unit population. Puleo and colleagues showed that the use of CK-MB subforms in the evaluation of chest pain patients had excellent negative predictive value to rule-out MI (33). Trahey and colleagues reported that serial sampling of CK-MB subforms over a 6-h period followed by diagnostic exercise testing was sufficient to rule-out the diagnosis of MI in their Chest Pain Unit patients and to stratify patients with a negative stress test into a low-risk group with only a 1.3% risk of later MI or recurrent ischemia (109).

TnT testing also shows promise for risk stratification in the low to moderate risk Chest Pain Unit population. In a meta-analysis of published reports of cTnT testing in chest pain patients without documented MI, Wu and colleagues calculated an odds ratio for prediction of the need for coronary revascularization of 4.4 (95% confidence interval 3.0-6.5) in cTnT-positive patients (110). A similar meta-analysis revealed an odds ratio for death or infarction of 4.3 (95% confidence interval 2.8-6.8) in cTnT-positive patients (Fig. 6). In an analysis of439 consecutive patients assigned to observation in the Duke University Chest Pain Unit, 10% of patients were cTnT-positive on serial testing over 8 h (63). A positive cTnT result identified a group at higher risk for significant (>75% stenosis) underlying CAD (89%) and multivessel disease (67%) than those found in the cTnT-negative

No. of Running patients totals

Odds Ratio (log scale)

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