Third universal definition of myocardial infarction: Update, caveats, differential diagnoses
ABSTRACTUpdated definitions of myocardial infarction (MI) reflect research on measuring cardiac troponin to diagnose MI. Elevations of this biomarker indicate cardiac injury but not always an acute coronary syndrome. Clinical judgment is needed to interpret increasingly sensitive biomarker assays appropriately. Here, we review the new MI definitions and the various causes of elevated troponin to enable physicians to differentiate acute coronary syndromes from other conditions.
KEY POINTS
- Because newer assays for troponin can detect this biomarker at lower concentrations than earlier ones could, they are more sensitive but less specific.
- The high sensitivity of troponin assays makes them valuable for ruling out MI, but less so for ruling it in. Therefore, additional signs are required for the diagnosis.
- MI is categorized into several types, depending on whether it is spontaneous (acute coronary syndromes), caused by supply-demand mismatch, associated with sudden cardiac death, or a complication of percutaneous coronary intervention or of coronary artery bypass grafting.
- In settings in which nonspecific troponin elevations are frequently seen, a less sensitive but more specific test such as creatine kinase MB or troponin using a higher threshold value may be useful.
Type 2: Due to ischemic imbalance
Type 2 MI is caused by a supply-demand imbalance in myocardial perfusion, resulting in ischemic damage. This specifically excludes acute coronary thrombosis, but can result from marked changes in demand or supply (eg, sepsis) or from a combination of acute changes and chronic conditions (eg, tachycardia with baseline coronary artery disease). Baseline stable coronary artery disease, left ventricular hypertrophy, endothelial dysfunction, coronary artery spasm, coronary embolism, arrhythmias, anemia, respiratory failure, hypotension, and hypertension can all contribute to a supply-demand mismatch sufficient to cause permanent myocardial damage.
The criteria for diagnosing type 2 MI are the same as for type 1: both elevated troponin levels and one of the clinical criteria (symptoms of ischemia, electrocardiographic changes, new wall-motion abnormality, or intracoronary thrombus) must be present.
Of importance, unlike those with type 1 MI, most patients with type 2 MI are unlikely to immediately benefit from antithrombotic therapy, as they typically have no acute thrombosis (except in cases of coronary embolism). Therapy should instead be directed at the underlying supply-demand imbalance and may include volume resuscitation, blood pressure support or control, or control of tachyarrhythmias.
In the long term, treatment to resolve or prevent supply-demand imbalances may also include revascularization or antithrombotic drugs, but these may be contraindicated in the acute setting.
Type 3: Sudden cardiac death from MI
The third type of MI occurs when myocardial ischemia results in sudden cardiac death before blood samples can be obtained. Before dying, the patient should have had symptoms suggesting myocardial ischemia and should have had presumed new ischemic electrocardiographic changes or new left bundle branch block.
This definition of MI is not very useful clinically but is important for population-based research studies.
Type 4a: Due to percutaneous coronary intervention
A rise in CK-MB levels after percutaneous coronary intervention has been associated with a higher rate of death or recurrent MI.10 Previously, type 4 MI was defined as an elevation of cardiac biomarker values (> 3 times the 99th percentile) after percutaneous coronary intervention in a patient who had a normal baseline value (< 99th percentile).11
Unfortunately, using troponin at this threshold, the number of cases is five times higher than when CK-MB is used, without a consistent correlation with the outcomes of death or complications.12 Currently, the increase in cardiac troponin after percutaneous coronary intervention is best interpreted as a marker of the patient’s atherothrombotic burden more than as a predictor of adverse outcomes.13
The updated definition of MI associated with percutaneous coronary intervention now requires an elevation of cardiac troponin values greater than 5 times the 99th percentile in a patient who had normal baseline values or an increase of more than 20% from baseline within 48 hours of the procedure. As this value has been arbitrarily assigned rather than based on an established threshold with clinical outcomes, a true MI must further meet one of the following criteria:
- Symptoms suggesting myocardial ischemia
- New ischemic electrocardiographic changes or new left bundle branch block
- Angiographic loss of patency of a major coronary artery or a side branch or persistent slow-flow or no-flow or embolization
- Imaging evidence of a new loss of viable myocardium or a new wall-motion abnormality.
Given that troponin levels may be elevated in up to 65% of patients after uncomplicated percutaneous coronary intervention and this elevation may be unavoidable,14 a higher troponin threshold to diagnose MI and the clear requirement of clinical correlates may resonate with physicians as a more appropriate definition. In turn, such guidelines may better identify those with an adverse event, while partly reducing unnecessary hospitalization and observation time in those for whom it is not necessary.
Type 4b: Due to stent thrombosis
Type 4b MI is MI caused by stent thrombosis. The thrombosis must be detected by coronary angiography or autopsy in the setting of myocardial ischemia and a rise or fall of cardiac biomarker values, with at least one value above the 99th percentile.
Type 4c: Due to restenosis
Proposed is the addition of type 4c MI, ie, MI resulting from restenosis of more than 50%, because restenosis after percutaneous coronary intervention can lead to MI without thrombosis.15
Type 5: After coronary artery bypass grafting
Similar to the situation after percutaneous coronary intervention, increased CK-MB levels after coronary artery bypass graft surgery are associated with poor outcomes.16 Although some studies have indicated that increased troponin levels within 24 hours of this surgery are associated with higher death rates, no study has established a troponin threshold that correlates with outcomes.17
The task force acknowledged this lack of prognostic value but arbitrarily defined type 5 MI as requiring biomarker elevations greater than 10 times the 99th percentile during the first 48 hours after surgery, with a normal baseline value. One of the following additional criteria must also be met:
- New pathologic Q waves or new left bundle branch block
- Angiographically documented new occlusion in the graft or native coronary artery
- Imaging evidence of new loss of viable myocardium or new wall-motion abnormality.
CHANGES FROM THE 2007 DEFINITIONS
Updates to the definitions of the MI types since the 2007 task force definition can be found in Table 1.
In type 1 and 2 MI, the finding of an intracoronary thrombus by angiography or autopsy was added as one of the possible criteria for evidence of myocardial ischemia.
In type 3 MI, the definition was simplified by deleting the former criterion of finding a fresh thrombus by angiography or autopsy.
In type 4a MI, by requiring clinical correlates, the updated definition in particular moves away from relying solely on troponin levels to diagnose an infarction after percutaneous coronary intervention, as was the case in 2007. Other changes from the 2007 definition: the troponin MI threshold was previously 3 times the 99th percentile, now it is 5 times. Also, if the patient had an elevated baseline value, he or she can now still qualify as having an MI if the level increases by more than 20%.
In type 5 MI, changes to the definition similarly reflect the need to address overly sensitive troponin values when diagnosing an MI after coronary artery bypass grafting. To address such concerns, the required cardiac biomarker values were increased from more than 5 to more than 10 times the 99th percentile.
The task force raised the troponin thresholds for type 4 and type 5 MI in response to evidence showing that troponins are excessively sensitive to minimal myocardial damage during revascularization, and the lack of a troponin threshold that correlates with clinical outcomes.12 Although higher, these values remain arbitrary, so physicians will need to exercise clinical judgment when deciding whether patients are experiencing benign myocardial injury or rather a true MI after revascularization procedures.
