CardioBuzz is a blog by Todd Neale for readers with an interest in cardiology.
Earlier this week, an expert panel convened by the Society for Cardiovascular Angiography and Interventions (SCAI) released a consensus document detailing a new definition for clinically relevant myocardial infarctions occurring after coronary artery bypass grafting or percutaneous coronary intervention.
I interviewed one of the members of the writing group, , of Columbia University Medical Center and the Cardiovascular Research Foundation in New York City. My earlier story contained only a small sample of his comments, and I've included a fuller version of the interview here (edited for length and clarity).
Todd Neale: Why is there a need for a new definition for post-revascularization MI?
Gregg Stone, MD: There are multiple different definitions that are in widespread use to define periprocedural myocardial infarction, and this is beyond an academic exercise because these definitions have very practical relevance in terms of being able to evaluate the safety and efficacy of new drugs and devices, to be able to compare different studies to each other, to be able to assess quality metrics for individual operators and hospitals. So it's important to get this right.
When you look at the most widespread classifications of periprocedural myocardial infarction, interestingly, almost none of them are evidence-based. And by that I mean they haven't defined a periprocedural myocardial infarction using a definition based on factors that prior studies have suggested are strongly associated with subsequent outcomes after a myocardial infarction. We wanted to use the best evidence that was out there to define a clinically relevant myocardial infarction.
Neale: What impact will the release of this document have?
Stone: It will have several important implications if people accept this concept. And it's hard to argue with the need or desirability for a clinically relevant myocardial infarction classification scheme. No. 1, the incidence of periprocedural myocardial infarction will decrease. The bar is relatively high. Most studies have shown that most increases in either CK-MB or troponins do not have prognostic significance. And as a result, while they may be interesting to track and while they may generally correlate with the larger increases, they're really not prognostically important and therefore they shouldn't count adversely against a drug or a device or a physician or a hospital system. So the incidence will decrease, and I think it will more appropriately focus us on trying to prevent the infarcts that really matter.
At the same time, it may shift the balance between what's seen as efficacy and safety. For example, consider a drug or a device that would cause a relatively large number of periprocedural myocardial infarctions. If most of those are understood to have no prognostic significance or minimal prognostic significance, then the relationship between the drug and device and those events should be markedly reduced in importance.
It may also lead to a different assessment when we consider how physicians or hospital systems are compared. Efforts to reduce small periprocedural biomarker elevations may be impossible because they may just be a marker of diffuse atherosclerotic disease. And so physicians or hospital systems that are routinely treating more complex patients may have a higher incidence of small-to-moderate elevations of biomarkers. And that may just be a reflection, frankly, of clinical excellence rather than complications.
Neale: What difficulties do you anticipate in getting widespread use of this new definition?
Stone: Whenever you introduce a new concept, especially in a field that is already seen as being replete with numerous types of definitions and classification schemes, I think there will be some inertia that has to be overcome. All new studies, all new concepts, even new drugs and devices that are approved by FDA take years to diffuse throughout the medical infrastructure and subspecialties, and I suspect the same will be true here. However, I do think that along with the universal definition of myocardial infarction, which is frequently now reported, this clinically relevant definition of myocardial infarction will be relatively rapidly and in a widespread fashion adopted and reported. There's nothing wrong with looking at multiple types of different definitions of periprocedural myocardial infarction.
Neale: So this new definition won't fully supplant the universal definition?
Stone: Certainly not immediately. And I think the universal definition is excellent. There's been a lot of thought that's gone into that document and I think we recognize and emphasize that the new definition is also imperfect and needs to continually evolve. In particular, there's really a lack of appropriate databases to come up with the one perfect definition that is not going to change over time. We need to understand much more about patient-level, vessel-level, and angiographic characteristics, because it is very important when studying the relationship between biomarker elevations and subsequent prognosis to be able to correct or adjust for all of these different factors.
We also need standardization of the assays that are being used, and even the assays are changing over time from standard-sensitivity to high-sensitivity troponins. We need more clarification of troponin T versus troponin I. I think there's a general desirability to move to troponins, although when you look at the data that's out there, it's much stronger correlating CK-MB elevations to subsequent prognosis. I think a lot of the troponin elevations are just noise or troponins are just too sensitive. And so there's a lot more work that needs to be done.
So I do think that there's a role for both classification schemes. We would propose the clinically relevant definition be the one that is used to make most substantial decisions right now on tradeoffs between efficacy and safety for new drugs and devices, in judging hospital systems and physicians, etc. But I do think there's value in both, and they will both continue to evolve over time as new data become evident.
Neale: Aren't some hospitals moving away from CK-MB?
Stone: I think that to some extent that's true. When we've recently looked at this for some large trials that we've been doing, greater than 95% of hospitals currently -- this is within the last year -- still have access to CK-MBs. Although I do think there's been a move to troponins because of their ease, their greater specificity, and arguably in some cases lower cost without evidence. And that's one of the points that we're trying to make in our article: in some regard, the universal definition has gotten ahead of itself. It has recommended that troponins be the preferred biomarker without the evidence to support the fact that it has prognostic significance. Right now most of the evidence is with CK-MB. So I do think that right now we would strongly recommend that CK-MB -- if available, as it is in most hospitals -- be used as the primary biomarker to determine periprocedural significance of biomarker elevations. And in the future we need to develop more data with standardized troponin I and troponin T assays to be able to understand how to convert over to troponins, which I do agree ultimately may be preferable because of their greater specificity.
Neale: Final thoughts?
Stone: The one thing I will say is that this new classification is not meant to be in any way a competition with the universal definition. We're friends with the people who are on those writing committees and tremendously respect their work. I think the universal definition of MI was superb in being able to create a benchmark from which studies can be compared to each other, and as a starting point to look at important periprocedural complications. What we've really tried to emphasize in this classification scheme is the primary link between biomarker elevations and prognosis. And that's the main difference. In the universal definition of MI, they even acknowledged that their criteria were arbitrary. We've tried to reduce the arbitrariness of the cutoff values that we selected so that the researcher, academician, clinician, hospital administrator, etc., can be confident that these levels that we're recommending are the ones that are associated with a worse prognosis for patients suffering periprocedural complications.