Prognostic Implications of Troponin T and Creatine Kinase

MB Elevation After Coronary Artery Bypass Grafting

Michael J. Domanski, MD

Disclosures

Am Heart J. 2012;164(5):636-637. 

Modest enzyme elevations resulting from myocardial damage are a frequent consequence of coronary artery bypass grafting (CABG).[1] These had frequently been dismissed as being without prognostic importance. Recent data demonstrate otherwise. Domanski et al reported a patient level meta-analysis of 18908 patients from 7 studies that examined the prognostic significance of creatine kinase–MB (CK-MB) or troponin elevation within 24 hours after CABG.[2] Patient follow-up varied form 3 months to 5 years in that study. A strong, graded, monotonically increasing, almost exponential relationship of CK-MB and mortality was present at all levels of serum CK-MB beyond the reference range. Mortality was doubled when the CK-MB level was 4.4 times the upper limit of normal. This association remained significant for patients from 30 days to 1 year (patients who survived at least 30 days), and there was a strong trend for significance of the association for patients from 1 to 5 years (ie, patients surviving for at least 1 year).The relationship of mortality and troponin elevation was qualitatively similar. Earlier, smaller studies are consistent with these findings.[3–6]

Myocardial enzyme elevation following percutaneous intervention has, similarly, been associated with worsened prognosis.[7–11] That different mechanisms underlie the myocardial damage in these 2 very different procedures suggests that any myocardial damage detriments prognosis regardless of the procedure that causes it.

The prognostic impact of myocardial damage assessed by enzyme elevation has at least two important implications. The first is that post-procedure enzyme elevation is a potentially important endpoint for clinical trials. Also of significance is the potential use of these enzyme elevations as a measure of procedure quality, including for the comparison of different centers and even individual operators.

A number of questions need to be addressed. What, for instance, is the cause of death in these patients. Certainly, for small elevations, arrhythmia caused or facilitated by the fibrosis consequent upon myocardial injury seems likely but this is unproven and should be studied. In addition, the most appropriate biomarker of myocardial damage needs to be determined.

Into this context comes the study of Sorras et al.[12] This is a single-center study that examined long-term mortality in 1350 consecutive patients who underwent isolated on-pump CABG and who had CK-MB and troponin T measured 7, 20, and 44 hours postoperatively. The authors examined mortality during a median follow-up was 6.1 years, comparing the association of mortality and troponin T vs the association of mortality and CK-MB. A total of 207 patients (15.7%) died during a median follow-up of 6.1 years. The study found that both CK-MB and troponin T were significant independent predictors of long-term mortality, similar to previous papers. In addition, the investigators were able to extend previous findings by demonstrating that troponin T is a better predictor of mortality than CK-MB; specifically by showing that CK-MB did not add to the prognostic information beyond that provided by troponin T. This adds important incremental information because it makes clear which biomarker would be most important in future studies. These findings comport with magnetic resonance imaging studies suggesting better quantification of myocardial necrosis with troponin than CK-MB.[1,13] From first principles, these findings are not surprising given the significant CK-MB content of skeletal muscle and the skeletal muscle trauma that occurs with CABG.

There are some limitations of this study. Factors not recognized and thus not accounted for in the multivariable analysis may have influenced the results. The known specificity of troponin T is reassuring in this regard as are the magnetic resonance imaging–based studies comparing CK-MB and troponin as metrics of necrosis. The study is relatively small and single center. Also, the study cannot take into consideration differences in treatment rendered over the full course of the follow-up. Nonetheless, the findings are consistent with what would be expected and with prior studies and, in aggregate, are convincing.

So, integrating the Sorras et al study into what we know about post-revascularization biomarker evidence of myocardial damage, we are in a position to draw some conclusions. The totality of available data clearly support that long-term survival following revascularization is reduced in proportion to the severity of enzyme elevation post-procedure. This conclusion is indisputable for CABG and sufficiently clear for percutaneous intervention to adopt the view for this procedure as well, at least when enzyme level is determined in patients who do not present with an acute or recent pre-procedure myocardial infarction as a cause for enzyme elevation. Both CK-MB and troponin T are useful biomarkers to quantify risk enhancement with troponin T being superior to CK-MB.

An important implication is that post-procedure enzyme rise is a reasonable metric for comparing programs and operators and so is a quality assurance parameter. Important in this regard will be standardizing the time post-procedure when enzyme level is determined given the known change of enzyme level over time.

Future effort should be directed to achieving a better understanding of the process variables that contribute to procedural myocardial necrosis, particularly ones that are under the control of the operator and thus potentially alterable. Also, a better understanding of the mechanism of death in these patients is needed, particularly one that explains the long-term prognostic impact of modest post-procedure enzyme elevations.

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