What is the role of CK‑MB (creatine‑kinase MB) in the diagnosis and management of acute coronary syndrome?

Role of CK-MB in Acute Coronary Syndrome

Cardiac troponin is the preferred biomarker for diagnosing acute coronary syndrome, and CK-MB should only be used when troponin is unavailable. 1

Primary Diagnostic Role

CK-MB serves as a second-choice marker for diagnosing myocardial infarction when troponin testing is not available. 1 While CK-MB by mass assay provides rapid, cost-efficient, and accurate results, it has been superseded by cardiac troponins due to troponin's superior sensitivity and specificity for myocardial injury. 1

Key Limitations of CK-MB for Initial Diagnosis

• CK-MB lacks cardiac specificity because it is present in skeletal muscle (1-3% of total CK), intestine, diaphragm, uterus, and prostate, leading to false positives in patients with skeletal muscle disease, injury, or surgery. 1, 2
• Low sensitivity in early presentation: CK-MB sensitivity is only 7-49% within 0-2 hours of symptom onset, 12-64% at 2-4 hours, and doesn't exceed 90% until 8-10 hours after symptoms begin. 1
• Troponin detects smaller areas of myocardial necrosis that CK-MB misses, identifying high-risk patients with unstable plaques who benefit from aggressive therapy. 1

Specific Clinical Situations Where CK-MB Remains Useful

Detection of Early Reinfarction

CK-MB is the preferred marker for detecting reinfarction within 48-72 hours of the index myocardial infarction. 1, 3 This represents CK-MB's most important contemporary role because:

• CK-MB returns to normal within 48-72 hours, making re-elevation easily detectable. 1
• Troponin remains elevated for 7-14 days after the initial MI, making it difficult to identify new myocardial injury during this window. 1
• Serial CK-MB measurements can discriminate new increases when recurrent symptoms occur between 72 hours and 2 weeks post-MI. 1

Assessment of Periprocedural Myocardial Injury

CK-MB remains useful for diagnosing MI extension and periprocedural MI following cardiac interventions. 1 The shorter half-life allows detection of new injury superimposed on recent events.

Very Early Presentation (< 6 Hours)

When combined with myoglobin, CK-MB enhances early detection in patients presenting within 6 hours of symptom onset. 1, 3 However, this multimarker approach still requires serial testing because:

• Initial CK-MB sensitivity at presentation is only 52% at median 240 minutes after symptom onset. 1
• Serial measurements over 8-12 hours are necessary to reliably exclude MI. 1

Diagnostic Testing Protocol

Timing of CK-MB Measurements

Draw CK-MB at hospital presentation and repeat at 6-9 hours after symptom onset, with consideration for additional sampling at 12-24 hours if initial tests are negative and clinical suspicion remains high. 3

• Baseline measurement: Obtain blood at presentation for all patients with suspected ACS. 3
• 6-9 hour repeat: This represents optimal timing given CK-MB kinetics, as sensitivity reaches 72-94% by 6-8 hours. 1, 3
• 12-24 hour sampling: If both earlier samples are negative but suspicion persists, repeat testing as sensitivity approaches 100% by this timepoint. 1, 3

Diagnostic Criteria

Two consecutive elevated CK-MB measurements above the 99th percentile with a rising and/or falling pattern are required for MI diagnosis. 3 This requirement exists because:

• Single elevated values lack specificity due to CK-MB presence in non-cardiac tissues. 1
• The characteristic rise/fall pattern confirms acute myocardial injury rather than chronic elevation. 3

Critical Caveats and Pitfalls

When CK-MB Elevation Does NOT Indicate MI

Always measure troponin when CK-MB is elevated to confirm true myocardial injury. 2 CK-MB can be falsely elevated in:

• Major skeletal muscle injury or disease (trauma, rhabdomyolysis, myopathies). 1
• Intestinal injury (e.g., acute appendicitis, bowel ischemia). 2
• Post-surgical states involving muscle or organ manipulation. 1

If troponin is below the 99th percentile when CK-MB is elevated, investigate non-cardiac sources before attributing the elevation to myocardial injury. 2

Time-Dependent Interpretation

If time of symptom onset is unknown or unreliable, reference timing to ED presentation rather than symptom onset. 1 This prevents misinterpretation of sensitivity data and inappropriate early discharge.

CK-MB should never be used alone to exclude MI in the first 6 hours after symptom onset due to inadequate sensitivity (< 60%). 1

Comparison with Troponin

The 2012 ACC/AHA guidelines establish clear hierarchy: 1

• Troponin advantages: Greater sensitivity and specificity, detection of minor myocardial damage, useful for risk stratification and therapy selection, remains elevated up to 2 weeks allowing late diagnosis. 1
• CK-MB advantages: Rapid return to normal (24-36 hours) enables early reinfarction detection, familiar to clinicians, cost-efficient. 1

Patients with elevated troponin but normal CK-MB are at increased 30-day risk of death or MI, demonstrating troponin's superior prognostic value. 1 Conversely, isolated CK-MB elevation without troponin elevation carries lower risk and should prompt investigation of non-cardiac sources. 1

Practical Algorithm for CK-MB Use

1. At presentation: Draw troponin (preferred) or CK-MB if troponin unavailable. 3
2. At 6-9 hours: Repeat measurement. 3
3. If both negative but suspicion persists: Repeat at 12-24 hours. 3
4. For recurrent chest pain: Obtain additional sample immediately. 3
5. For suspected reinfarction within 2 weeks: CK-MB is more useful than troponin due to troponin's prolonged elevation. 1, 3
6. If CK-MB elevated but clinical picture unclear: Always check troponin to confirm cardiac origin. 2