Traditional Cardiac Biomarkers Used in the Ed Ckmb Isoenzyme

CK-MB is predominantly found in the myocardium and is the most specific of the three CK isoenzymes for the detection of myocardial necrosis. Elevation of CK-MB occurs 4-6 h after the onset of myocardial necrosis and can remain for 24-48 h (10). The initial sensitivity of CK-MB for the detection of AMI has been reported to be 23-57% (11,12). Obtaining additional CK-MB measurements incrementally improves the sensitivity; repeat testing at 3 h after initial presentation improves the sensitivity to 88% (12), and sensitivity is maximized when CK-MB sampling is performed over a 9-h evaluation period (13).

CK-MB has excellent specificity, reported to be 97-99% (11,12). However, because up to 3% of the total CK in skeletal muscle is CK-MB, nonspecific elevations can occur in the setting of skeletal muscle damage (14). This limitation can be mitigated by calculating the CK-MB relative index, which is the proportion of CK-MB to total CK (15). A CK-MB relative index <2.5% indicates a skeletal muscle source for this enzyme.

Cardiac Troponin

With the development of assays for cardiac troponin, the definition of AMI has undergone a substantive transformation (see Chapter 3) (16). Similarly to CK-MB, troponin I and troponin T are detectable in the blood 4-12 h after the onset of myocardial necrosis and peak at 24-48 h. In contrast to CK-MB, elevated concentrations of cardiac troponin can persist for up to 7-10 d.

Cardiac troponin is more sensitive and specific than CK-MB for detecting myocardial necrosis and, thus, has become the preferred biomarker for the diagnosis of MI. Elevations in cardiac troponin in the absence of elevations in CK-MB suggest "microinfarctions," wherein a relatively small amount of myocardium undergoes necrosis (17). Additionally, the finding of elevated levels of cardiac troponin is a powerful predictor of future adverse cardiac events, including death and recurrent AMI, even when elevation of CK-MB or ST-segment deviation is absent (18-20). Identification of high-risk patients has allowed emergency physicians and cardiologists to determine which patients will derive the greatest benefit from aggressive ACS therapy. Patients with positive cardiac troponin results benefit more from antithrombotics (21), glycoprotein IIb-IIIa inhibitors (22), and early invasive revascularization than do patients with normal levels of cardiac troponin (23).

The sensitivity of initial measurement of cardiac troponin for the diagnosis of AMI has ranged from 4 to 66% (19,24-26). Serial measurement of cardiac troponin significantly improves the ability ofthis cardiac biomarker to detect AMI; Hamm et al. (19) performed troponin testing upon presentation and at 4 h, with improvement in the sensitivity from 51% to 94% for troponin T and 66% to 100% for troponin I in patients without ST-ele-vation. In that study, patients with negative serial troponin results drawn within 4 h had a 1.1% and 0.3% rate of MI and death, respectively, at 30 d (19). The specificity of cardiac troponin for the diagnosis of MI has been reported as 89-98% (19,25). The variability in reported specificity is reflective of differences in the "gold standard" used to define AMI in those studies.

Myoglobin

Myoglobin is a low-molecular-weight, unbound, cytosolic protein that is found in both myocardial and skeletal musculature. Because of its biochemical characteristics, myoglobin can be elevated in the serum within 1 to 2 h after the onset of symptoms in patients with an AMI (27). As a result, increased concentrations of myoglobin precede elevations of CK-MB and cardiac troponin, making it ideal for rapidly establishing a diagnosis of AMI (11). Ideally, myoglobin should be obtained in patients with symptoms less than 6 h in duration. Because myoglobin can rapidly disappear within 12-36 h after the onset of symptoms, its use is limited in patients with delayed presentations (27).

The sensitivity of myoglobin for diagnosing MI in patients presenting very early after the onset of symptoms is superior to that of CK-MB; sensitivities of 55% and 23% for myoglobin and CK-MB, respectively, have been reported from measurements obtained at presentation in the ED (11). Similarly to CK-MB and cardiac troponin, the sensitivity improves with serial measurement. For example, in one study, myoglobin was found to be 14%, 90%, and 100% sensitive at 0, 3, and 6 h, respectively (28). Elevated levels of myoglobin also appear to carry prognostic information. In a study of patients with non-ST-elevation ACS,

Fig. 1. Rapid rule-out protocol developed by Ng and colleagues at University of California at San Diego. Patients with ST-segment deviations or unresolved chest pain were excluded from this protocol. CCU, coronary care unit. (From ref. 32.)

elevated levels of myoglobin were associated with higher 6-mo mortality (29). Myoglobin is ubiquitous in skeletal muscle; therefore, elevated levels of myoglobin may be observed in patients with skeletal muscle damage (30). Because of myoglobin's limited specificity, confirmation with a definitive cardiac biomarker such as CK-MB or cardiac troponin is recommended (16).

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