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

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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

References

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