Requiem for a Heavyweight—The Demise of Creatine Kinase-MB

During the past year, I’ve received many questions at conferences or via email from emergency physicians regarding the utility of the CK-MB. “What do I do when the CK-MB is high but the TN is normal?” or “Why don’t the cardiologists care about the elevated CK-MB?” or “Why is my lab getting rid of the CK-MB?” For quite some time now, these questions have reminded me of the epic movie Titanic. Why, you ask?

You may recall the end of this bittersweet movie. James Cameron, after spending two hours building up the character of the movie’s hero Jack Dawson, callously sinks him to the bottom of the cold Atlantic (ignoring the fact that ice actually floats). All the while Rose floated on the makeshift raft (honestly, there wasn’t room for Jack on that thing?) repeating, “I’ll never let you go, Jack, I’ll never let you go!” My initial reaction to Jack’s predicament as Rose swam off to a new life was that maybe they were setting up for a sequel. They would rescue Jack and find him only mostly dead, thaw him and find that induced hypothermia does, in fact, lock in freshness. My second thought was, “That’s not fair! This movie stinks!” But the fact is, heroes often die, or at the very least get replaced, despite our transient infatuation with them and temporary promises that we’ll never let them go.

Enter our next hero and star of the long-running movie called “AMI, Interrupted.” The star’s name is “CK-MB.” For 15 years, this hero has been winning our hearts (so to speak) with its reliability at rooting out and diagnosing the “bad guys” …infarcted myocytes. We’ve been so reliant on this hero that for many years, if the CK-MB was positive we diagnosed an MI, and if the CK-MB was negative it ruled out the MI. Pretty simple, right? Well, maybe not. Over the years the tabloid literature has been dealing some major blows to our once-proud hero and now a lot of cardiologists are putting MB in a corner. Everyone is questioning whether CK-MB’s career is over. In fact, now we find CK-MB and TN trading places as the cardiac biomarker of choice for patients with cardiovascular issues. The authors of this expose provide the reasons. There are 81 references in this 4-page editorial. I’ll refer the interested reader to the manuscript for the specific references, and I’ll simply provide the summary of their comments:

TN is now the preferred marker of all of the organizations that are involved in creating the major guidelines for AMI: the ACC, AHA, ESC (European Society of Cardiology), and National Academy of Clinical Biochemistry. The World Health Organization has also adopted TN, not CK-MB, into its definition for MI.

Assays now detect TN elevations as quickly as they detect CK-MB.

TN is predictive of in-patient and long-term prognosis in patients with ACS and non-ACS cardiac conditions. This is not true for CK-MB.

In 10% of cases of ACS, CK-MB may be positive with a negative TN. However, the prognosis of these patients correlates with the negative TN, not with the positive CK-MB; so it appears that even in these cases, the presence of the positive CK-MB is not helpful.

TN predicts infarct size as good or better than CK-MB.

TN is more cardio-selective than CK-MB (though neither is perfect).

Quality control of CK-MB assays is waning, perhaps partly because industry also believes that there’s little future in CK-MB. As a result, there is greater machine-to-machine variability in CK-MB values.

Proper use of TN makes this test at least as useful, if not more, compared to CK-MB for detecting reinfarction and in evaluating patients post-PCI and post-CABG.

Overall, CK-MB appears to increase costs without providing any additional diagnostic or prognostic benefit.

The authors argue that one of the main reasons that CK-MB is still around is because physicians have been so accustomed to CK-MB that they simply are unwilling to give it up. CK-MB has certainly served its purpose well for many years. Perhaps now, however, it’s time to give CK-MB its star on the Hollywood Walk of Fame, a Lifetime Achievement Award, and a retirement home in Palm Springs. For those who want to continue to cling tightly… “I’ll never let you go, CK-MB!” Well, folks, you know how that movie ends. “Not good, Mav, not good.”


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