Clinical Progress Notes: Updates from the 4th Universal Definition of Myocardial Infarction

Elevated serum troponin clearly does not equal myocardial infarction (MI). This was the strong message in the 2018 publication of the Fourth Universal Definition of Myocardial Infarction¹ (4UDMI), the first update to the international consensus document since 2012.

Most clinicians have learned how to accurately diagnose the classic Type 1 MI (T1MI) due to atherosclerotic plaque rupture; however, elevated troponin in the absence of T1MI is increasingly common due to more frequent and less discriminate troponin testing.² Patients with elevated troponin in the absence of T1MI have traditionally created confusion and variability in diagnosis, management, and documentation. Interpretation and management of elevated troponin in the absence of T1MI has become difficult.

In this clinical practice update, we aim to review the updated definition of Type 2 MI (T2MI) and nonischemic myocardial injury (NIMI), since these are the two predominant diagnoses among patients with elevated troponin in the absence of T1MI. We also provide a clinical framework for clinicians to think through elevated serum cardiac troponin levels and identify opportunities for quality improvement around this critical issue.

The presence of an elevated serum troponin level is a critical component in determining the presence of cardiac myocyte injury and possible infarction. Myocardial injury is defined as the presence of serum troponin above the 99th percentile of the upper reference limit (URL), the absolute value of which varies by assay and which applies to traditional and highly sensitive subtypes. Myocardial injury can be confusing to assess, as it can be acute or chronic.

When troponin levels are elevated but stable, this is indicative of chronic (usually nonischemic) myocardial injury, as seen, for example, in patients who have end-stage renal disease. The presence of acute injury requires a change in the troponin value—specifically a rise and/or fall in troponin levels with serial measurements. What constitutes a significant “rise and/or fall” is a matter of some debate and is not precisely defined in the 4UDMI. The percent change in the troponin value over time (relative delta) is listed as part of the criteria for acute injury when the change is greater than or equal to 20%;¹ however, clinicians should be aware that absolute delta in troponin (the change in ng/dL) has better performance characteristics³ in diagnosing acute myocardial injury. Regardless of whether clinicians use relative or absolute changes in the serum troponin level, clinical evaluation of patients with acute injury is critical to establishing whether the injury is ischemic (MI) or nonischemic (NIMI). The presence of at least one of the following is necessary to meet the current criteria for myocardial ischemia according to the fourth universal definition: new ischemic symptoms (eg, chest pain, dyspnea, etc.), new ischemic changes in the patient’s electrocardiogram (eg, new ST segment depression in leads II, III, and aVF), or cardiac imaging changes consistent with ischemic injury (eg, new wall motion abnormality in the inferior wall on echocardiography).

Following diagnosis of MI based on elevated troponin and new symptoms or signs, the cause of MI should then be determined. Type 1 MI remains defined as MI caused by atherosclerotic plaque disruption in a patient with coronary artery disease (CAD). Type 2 MI is not caused by plaque disruption but is due to a mismatch between oxygen supply and demand unrelated to acute atherothrombosis. T2MI is an ischemic myocardial injury traceable to some other illness that leads to inadequate myocyte oxygenation. Causes of T2MI are numerous, can overlap with nonischemic injury, and can include severe anemia, septic shock, rapid atrial fibrillation, and coronary dissection. While CAD may be present in patients with T2MI, it is not a requirement, and an increased demand for, or reduced supply of, myocyte oxygen alone can be sufficient to cause MI.

In the absence of clinical signs or symptoms of cardiac ischemia, clinicians should categorize patients as having a nonischemic myocardial injury. There is significant overlap between causes of T2MI and NIMI, for example, sepsis could cause either T2MI or NIMI. What distinguishes these two entities is whether the signs and symptoms for myocardial ischemia as outlined above are present. If these signs or symptoms are present, the diagnosis is T2MI. If no clinical signs or symptoms of ischemia are present, the diagnosis is NIMI. The assessment of the clinician, using all available clinical information, is pivotal. The characteristics of the three major types of myocardial injury are depicted in the Figure.