Question 3

Compare and contrast the role of Troponin and CKMB in the management of myocardial ischaemia in the critically ill.

[Click here to toggle visibility of the answers]

College Answer

CKMB is creatine kinase dimer of M and B chains and exists as 4. It is found in a high ratio predominantly in myocardial cytosol, but is also present in skeletal muscle (especially in myopathies or after injury). Levels of CK MB rise within 4 to 12 hours of myocardial infarction (high sensitivity and specificity), peak at 18 to 24 hours and return to baseline by 36 to 40 hours. Diagnosis of MI may be enhanced by measuring MB isoforms (higher sensitivity) or use of MBfraction of total CK (problem if significant skeletal muscle damage [eg. surgery, cardioversion], hypothyroidism or renal failure [CKMB elevated in approximately 30 to 70 percent of dialysis patients]). Not increased in myocarditis. CKMB level is indicative of infarct size, and is independent prognostic marker. Rapid return of level to normal allows potential for diagnosis of reinfarction.

Cardiac troponins are cardiac regulatory proteins and exist as “T” and “I” forms. Early release is from cytosol, and subsequent release from damaged structural components. Many results from early studies hindered by variability in assays. More recent (second generation) assays are highly specific for cardiac troponins (both forms). Levels rise within 4 to 12 hours after myocardial infarction (high specificity but less sensitivity if rely on 6 hour specimen), peak at 18 to 24 hours, but levels stay elevated for up to 10 days (allows late diagnosis of MI, but not reinfarction). cTpI preferred in renal failure (false positive elevations of cTnT: in one study 82 percent of asymptomatic dialysis patients had elevated cTnT levels when the cutoff value was 0.01 µ g/L!). Elevations may occur in pulmonary embolism or myocarditis, but potentially better than CKMB for situations where skeletal muscle damage is present (eg. DCR, trauma, post-op). Level of troponin also associated with prognosis (? clinical relevance of subtle elevations).

Elevation of cardiac enzymes (if not a false positive) without ECG changes is now considered to represent a non-ST elevation myocardial infarction.

Discussion

This question had found a more detailed incarnation in a later paper - 2010 paper 2, question 27.

An answer to this question lends well to a table format.

Biomarker	Troponin	CKMB
Origin	Highly specific injured myocardium	Myocardium as well as skeletal muscle; MB isoform is more specific
Pharmacokinetics	Rise within 4-6hrs; Peak within 18-24 hrs Slow to clear (7-14 days)	Rise within 4-12 hrs; Peak within 18-24 hrs Rapidly cleared (2-3 days)
Use in critical care	More sensitive than CK for cardiac ischaemia Rapid rise allows earlier identification of ischaemia Correlate well with risk stratification Strongly associated with 30-day mortality	Less sensitive for cardiac ischaemia than TnT Rapid clearance allows the detection of reinfarction
Causes of elevation unrelated to coronary ischaemia	Pulmonary embolism Tachyarrhythmia Post-defibrillation Post-CPR Post-cardiotomy Cardiac trauma Myocarditis	Pulmonary embolism Tachyarrhythmia Post-defibrillation Post-CPR Post-cardiotomy Cardiac trauma
Non-cardiac causes of elevation	Sepsis Renal failure	Sepsis Renal failure Rhabdomyolysis Trauma Major surgery Burns (esp electrical)

References

McLean, Anthony S., and Stephen J. Huang. "Cardiac biomarkers in the intensive care unit." Ann Intensive Care 2.8 (2012): 1-11.

[Submit a comment or correction]