October 16th, 2013

Redefining MI After Revascularization

James de Lemos reflects on a new definition of “clinically relevant myocardial infarction after coronary revascularization” from the Society for Cardiovascular Angiography and Interventions (SCAI). The SCAI proposal is published in JACC.


The new SCAI definition of MI after revascularization differs in several ways from the 2012 Universal Definition of procedural MI, which was authored by a joint task force representing the ESC, ACC, AHA, and World Heart Federation. Among the key differences are these:

1. The SCAI proposal recommends creatine kinase-MB, rather than troponin, elevation to define procedural MI.

2. The SCAI proposal requires a much larger amount of procedural injury to meet the definition of “clinically relevant MI”: 10x the upper limit of normal for CK-MB (or if CK-MB is not available, a 70-fold elevation in troponin) versus 5x ULN for troponin in the universal definition.

3. The SCAI proposal does not require associated evidence of ischemia, whereas the universal definition requires “ischemic context” (i.e., chest pain, ECG changes, angiographic evidence of a procedural complication or a new wall-motion abnormality) to meet the MI definition.


Virtually all of the pivotal modern trials leading to new drug approvals for antiplatelet and anticoagulant drugs have included procedural “myocardial infarctions” in the endpoint definition. In fact, the procedural MIs (the type 4a MIs that are the focus of a new SCAI consensus document and a related editorial by Harvey White) outnumber spontaneous MIs in most trials. If these procedural MIs had not been included, studies of GP IIb/IIIa inhibitors and prasugrel, for example, would be considered only marginally positive or null, and very different risk/cost/benefit interpretations for those drugs might have been made.

Before 2012, definitions of procedural MI had been based purely on modest elevation of biomarkers, typically creatine kinase-MB. In most cases, these are simply lab abnormalities, completely unrecognized by the patient and the treating physician. Moreover, those small periprocedural enzyme elevations are weighted in clinical trials (and by the FDA) as more important even than significant bleeding events. Most clinicians would agree that even a TIMI minor bleed is a much bigger deal to a patient than is an asymptomatic 3-fold biomarker elevation after PCI.

Although even modest CK-MB elevations have met criteria for procedural MI, it is clear that for all except the very large procedural MIs, the prognosis is not equivalent to a spontaneous MI. There is also a huge debate about whether these are true “events” that contribute directly to long-term outcomes or, rather, markers of sicker patients with worse atherosclerotic (or LV muscle) disease, in which case preventing the enzyme elevation would not improve long-term outcomes. The aggregate data suggest that except for very large procedural MIs, no causal association with poor long-term outcomes exists.

Both the universal definition and the SCAI recommendations improve on the earlier definitions, which were just way too wimpy. The addition of “clinical context” in the most recent universal definition attempts to raise the bar by requiring some mechanism for ischemia. This is a welcome change and at least elevates the diagnosis beyond a simple, minor lab abnormality. The problem is that tiny amounts of myocardial necrosis can meet the universal definition of MI. Because the reference range for troponin is so low, a 5-fold elevation is still a trivial amount of necrosis: 5 times nothing is still nothing! I think CK-MB is clearly preferable to troponin for definitions of procedural MI, particularly for drug-approval trials. Much more work is needed to define troponin thresholds that might be comparable with CK-MB, but a 5x ULN elevation in troponin is likely to be far too low a bar for procedural MI.

In my opinion, the use of troponin and the low threshold of elevation for procedural MIs was a mistake in the universal definition. The SCAI authors propose a more rigorous definition (CK-MB >10x ULN) and also allow the possibility of characterizing somewhat smaller MIs (CK-MB >5x ULN) if there is an ischemic mechanism. This is a sensible middle ground. They also provide a tentative troponin threshold for situations where CK-MB is not available, with the caveat that the evidence base to support these troponin thresholds is tenuous.

It would be interesting to reevaluate trials of GP IIb/IIIa inhibitors, cangrelor, and prasugrel using this more rigorous definition of procedural MI. It would not be surprising for the “benefit” of the antiplatelet therapies to be attenuated and for the trials to look quite different if a more clinically relevant definition of procedural MI were used.


Share your view of the SCAI’s new definition of MI after revascularization and of Dr. de Lemos’ assessment of it.

2 Responses to “Redefining MI After Revascularization”

  1. Until we have a marker of the precise moment of onset and consequent size of myocardial infarction which corresponds to a specific pertubation(atherothrombosis with Type I, supply/demand imbalance with Type II, side branch occlusion or distal embolization with Type IV) attribution will be confounded.

  2. Ajay J Kirtane, MD, SM says:

    Great commentary. Interesting as well that CMS/payors have already moved far beyond the universal definition by considering most PCIs as “outpatient procedures” for which enzymes aren’t even measured…