Diagnosing Type 2 Myocardial Infarction
The ability to measure cardiac troponin, either cardiac troponin T (cTnT) or cardiac troponin I (cTnI), marked a paradigm shift in the use of cardiac biomarkers for the diagnosis of myocardial infarction (MI). For the first time, a totally cardiac-specific test was available that would detect myocardial injury even in the presence of concomitant skeletal muscle injury. Comparison with the existing cardiac biomarkers creatine kinase and creatine kinase-myocardial band (CK-MB) showed diagnostic equivalence for detection of classical MI. More importantly, a large proportion of patients with a diagnosis of unstable angina were found to have an elevated cardiac troponin, and those patients were found to have a worse prognosis compared with those who did not have elevated cardiac troponin.1 These findings provided the impetus to shift to the use of cardiac troponin as the cardiac biomarker of choice and the proposed redefinition of MI.
There are some caveats that must be remembered. At this point in time, the diagnostic "gold standard" biochemical test for diagnosis of MI was measurement of CK-MB. Second, the usual threshold was a CK-MB twice the upper reference limit, which reduced diagnostic sensitivity. It had previously been demonstrated that minor rises in CK-MB about the upper reference limit but below the diagnostic limit were associated with an adverse prognosis. It is therefore unsurprising that cardiac troponin, a cardiac-specific test, was both more sensitive and, because the diagnostic discriminant was optimised against CK-MB, more specific.
The use of troponin as biochemical "gold standard" had an immediate result of increasing the number of patients who had a final diagnosis that excluded MI who were noted to have an elevated troponin. Chronic elevation of both cTnT and cTnI had been noted in renal failure early in the introduction of troponin testing.1 The recommendation to use the 99th percentile as diagnostic discriminant and the progressive improvements in assay sensitivity further increased the range of clinical conditions with concomitant cardiac troponin elevation. This is illustrated in the list included in the most recent iteration of the universal definition of MI.2 In addition, new clinical entities that mimic MI, such as spontaneous coronary artery dissection and Takotsubo (stress) cardiomyopathy, have been identified.3 As it has been sardonically observed by Bob Jesse, "when troponin was a lousy assay it was a great test, but now that it's becoming a great assay, it's getting to be a lousy test."4 Therefore, in an attempt to address the problem of troponin elevation outside of traditional MI, the concept of type 2 MI was introduced in the universal definition of MI.5
Type 2 MI is defined as "myocardial infarction secondary to ischaemia due to either increased oxygen demand or decreased supply, e.g. coronary artery spasm, coronary embolism, anaemia, arrhythmias, hypertension or hypotension."
The definition of type 2 MI is unsatisfactory because it is not really defined by what it is but rather what it is not.6 Nevertheless, the clinical problem remains: to distinguish acute MI (associated with plaque rupture or erosion, traditional or type 1 MI)for which there is evidence-based treatmentfrom acute secondary ischaemic cardiac injury, including type 2 MI, where such treatments are not evidence based and may even be harmful.
The role of troponin measurement is in the differential diagnosis of suspected non-ST-segment elevation MI (NSTEMI). Patients presenting with ST-segment elevation MI require immediate intervention based on current guidelines and thus should not wait for troponin results.
The first stage is to assess the probability that the patient has underlying acute coronary artery disease (CAD) from the clinical history and that the symptoms are caused by cardiac ischemia. The assessment of the probability that the patient has underlying CAD may be an informal classification into high, medium, or low risk or a more formal risk score. Cardiac ischemia is assessed by the electrocardiogram (ECG) and interpretation of the symptoms. An initial troponin measurement should be made as well as assessment of renal function and other appropriate laboratory tests and investigations guided by the clinical presentation of the patient.
A holistic assessment is required at this point. This must assess the totality of the findings in a circular rather than linear fashion. It is important that the results of laboratory tests taken as a whole are consistent with the clinical features and the ECG. If the troponin is not elevated, then repeat testing is required before acute myocardial injury can be excluded with certainty. On the other hand, a single elevated troponin is not, on its own, diagnostic of MI. However, an elevated troponin along with other appropriate clinical and laboratory evidence raises the probability that the diagnosis is NSTEMI. The higher the troponin value, the greater the probability that the final diagnosis will be MI. It must be stressed that the data must be consistent. An elevated troponin plus a normal ECG or nonspecific changes should immediately raise suspicion of an alternate diagnosis. Similarly, there should be no other occult but acknowledged causes of minor troponin elevation, such as renal failure or significant age. Other potential acute causes of troponin elevation associated with CAD such as tachycardia or other conditions causing increased oxygen demand or reduced oxygen supply indicate a type 2 MI. However, even if the clinical probability of underlying CAD is high, a final diagnosis of MI requires demonstration of a changing troponin value. Contemporary sensitive assays are able to detect a significant troponin change on retesting if the initial value is elevated with a repeat test performed 2-3 hours later and with high sensitivity assays within 1 hour.
Repeat testing allows the immediate distinction between an acute myocardial injury and underlying chronic myocardial damage causing troponin elevation. This resolves the dilemma of the patient with renal disease (or high age). An elevated troponin in the first sample is to be expected in the patient with renal failure. A changing troponin indicates acute injury and may be due to an acute MI. In contrast, an elevated troponin that does not change significantly is due to chronic myocardial injury and may require further investigation but possibly not as an in-patient and not necessarily by a cardiologist.
The next phase of the evaluation is to distinguish between an acute troponin rise that is consistent with acute MI and one that is due to another cause. The diagnosis of acute MI should never be made on the basis of a troponin elevation alone. Again, a complete evaluation of the patient requires that the troponin rise is consistent with the clinical findings and the ECG. An elevated troponin with minimal ECG findings can occur with myocarditis or pulmonary embolism. The most important factor is to be aware that other clinical conditions can cause a troponin elevation. Troponin elevation is specific for myocardial injury, but not every troponin elevation is an MI. The presence of other clinical conditions such as pneumonia or pulmonary embolus should shift the clinical focus to an appreciation that the troponin elevation is an additional prognostic rather than diagnostic finding. If there is diagnostic uncertainty, cardiac imaging, either invasive or noninvasive, as well as other types of cross sectional imaging is necessary to provide additional information.
Therefore, the key features to diagnose a type 2 MI (more properly secondary ischaemic cardiac injury), can be summarised as follows:
- An elevated but changing troponin value
- Clinical features inconsistent with type 1 acute MI
- Clinical conditions known to increase the oxygen demand or decrease the oxygen supply like tachycardia
- Potentially confounding clinical conditions or comorbidities that are potentially associated or known to be associated with myocardial injury
- Absence of symptoms and/or signs indicating other nonischemic causes of troponin elevations like myocarditis.
Treatment of type 2 MI is to treat the underlying condition and hence remove the cardiac insult. To adequately assess the prognosis and determine appropriate further treatment in patients with type 2 MI, information about whether the patient has (or is likely to have) significant underlying CAD is essential.7 In addition, it is important to remember that elevated troponin in the patient with non-acute MI is not redundant information but also indicates an adverse prognosis (Figure 1).8
- Collinson PO, Garrison L, Christenson RH. Cardiac biomarkers - A short biography. Clin Biochem 2015;48:197-200.
- Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J 2012 ;33:2551-67.
- Lettieri C, Zavalloni D, Rossini R, et al. Management and Long-Term Prognosis of Spontaneous Coronary Artery Dissection. Am J Cardiol 2015;116:66-73.
- Jesse RL. On the relative value of an assay versus that of a test: a history of troponin for the diagnosis of myocardial infarction. J Am Coll Cardiol 2010;55:2125-8.
- Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction. Circulation 2007;116:2634-53.
- Collinson P, Lindahl B. Type 2 myocardial infarction: the chimaera of cardiology? Heart 2015;101:1697-703.
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