A Simplified Proposal to Redefine Acute Myocardial Infarction versus Acute Myocardial Injury

The first consensus definition of myocardial infarction (MI) was published almost twenty years ago and was widely recognized as a landmark achievement.¹ The latest iteration, the 2018 “Fourth Universal Definition of Myocardial Infarction”², is the result of hundreds of hours of work by a cadre of international experts and differentiates MI into multiple subtypes based on clinical context and pathophysiological mechanism.

The Fourth Universal Definition of Myocardial Infarction is very complex. It defines seven distinct subtypes of myocardial infarction (type 1, type 2, type 3, type 4a, type 4b, type 4c, and type 5), and the related category of myocardial injury (cardiac biomarker release without evidence for myocardial ischemia). Due to the complexity, clinicians and experts alike – both in the community and academia – struggle to consistently and correctly apply the Universal Definition of MI in everyday clinical practice. The biggest challenge relates to appropriately diagnosing type 2 MI and distinguishing type 2 MI from acute myocardial injury.^3–5 Confusion abounds and, personally, I am afraid that the Universal Definition of MI has become too complicated for everyday clinical practice.

But could the diagnosis of MI be simplified without sacrificing the underlying biological concepts? I would argue yes. I believe that we only need a single definition of acute MI that is both conceptually and mechanistically distinctly different from acute myocardial injury (Table 1).

Table 1.

Criteria for the Definition of Acute Myocardial Infarction versus Acute Myocardial Injury

	Acute Myocardial Infarction*	Acute Myocardial Injury*
Mechanism	Coronary Occlusion	Extra-coronary
Common Examples	Coronary thrombosis Coronary vasospasm Coronary embolism Coronary artery dissection In-stent thrombosis	Supply and demand mismatch Atrial fibrillation with RVR Pulmonary Embolism Shock Sepsis Takotsubo CMP Acute anemia/hemorrhage
Treatment Goal	Restoring coronary blood flow	Identifying and treating the underlying cause

^*For patients who meet criteria for both conditions (e.g. an acute extra-coronary event triggering acute myocardial ischemia in the setting of critical obstructive coronary artery disease), it will be at the discretion of the clinical team to decide whether acute myocardial infarction or acute myocardial injury is more appropriate.

Under the proposed concept, acute myocardial infarction would include all conditions where an acute coronary artery occlusion results in myocardial necrosis regardless of the underlying cause. Coronary occlusion may be the result of an acute coronary plaque rupture, coronary embolism, vasospasm, or acute coronary artery dissection. Central to the definition is the acute interruption of coronary blood flow, and its diagnosis and therapy are directed at restoring coronary blood flow. On the other hand, acute myocardial injury would denote a condition where there is evidence of acute myocardial necrosis due to non-coronary causes. Examples are atrial fibrillation with rapid ventricular response, pulmonary embolism, sepsis, strenuous exercise, exposure to potent vasoactive drugs, causing an acute elevation of cardiac troponin. Central to the diagnosis of acute myocardial injury is that the primary underlying cause of myocardial necrosis is external to the coronary arteries. Thus, diagnosis and treatment of acute myocardial injury would be directed at identifying and treating the underlying, non-coronary cause.

The astute reader might point out that some cases may meet both criteria and myocardial necrosis may be due to a combination of coronary and extra-coronary pathophysiology. For instance, a patient with a stable but high-grade coronary stenosis who develops atrial fibrillation, acute anemia, or sepsis, triggering acute myocardial ischemia. In these cases, where coronary and extra-coronary pathology overlap, it would be at the discretion of the clinician to classify the event as either acute myocardial infarction or acute myocardial injury. We must accept that there are circumstances that may fit both criteria and that we will need to allow clinicians to exercise discretion in choosing the appropriate diagnosis.

Of note, the proposed simplified definition into only two conditions – myocardial infarction or myocardial injury – does not predicate specific diagnostic criteria or treatment. Rather, the definition focuses solely on the taxonomy, i.e. what we understand as myocardial infarction versus myocardial injury, and not how we delineate diagnostic criteria or recommended treatment. ECG presentation (ST-elevation or non-ST-elevation) or the exact level of cardiac troponin elevation or change values of high-sensitivity cardiac troponin, are fundamentally important for the diagnosis of MI (and myocardial injury) but immaterial for the definition of MI. Importantly, the proposed definition does also not specify the severity of the condition.

Similarly, the proposed simplified definition of acute MI does not predicate any treatment modality. Because the criterion for MI involves the clinical suspicion of a coronary event, most patients who meet the proposed definition of acute MI will likely undergo coronary angiography or imaging. It is not automatic, however, that those patients will require a coronary intervention. Conversely, patients with suspected acute myocardial injury may require a coronary intervention when an acute extra-coronary event, such as atrial fibrillation, causes acute myocardial ischemia in the setting of stable obstructive coronary artery disease. Naturally, differentiated treatment guidelines will need to be developed for both acute MI and acute myocardial injury. Acute MI caused by acute coronary thrombosis due to a plaque rupture event will require different guidelines than coronary vasospasm or coronary artery dissection. Similarly – and reminiscent of the 5 Hs and 5Ts in the non-shockable cardiac arrest algorithm – treatment recommendations for acute myocardial injury will need to focus on the underlying cause. Treatment guidelines for acute myocardial injury in the setting of atrial fibrillation with a rapid ventricular response rate will obviously differ from myocardial injury due to sepsis or anemia.

The proposed simplified definition would have several advantages. First, it would align the underlying mechanism of myocardial damage – coronary versus extra-coronary – with the definition, myocardial infarction versus injury. Second, it would also help our patients who wonder whether they actually had a heart attack. Aligning the colloquial term “heart attack” with “acute MI” will provide clarity to both clinician and patient and avoid much of the confusion that exists now. Third, by refocusing the definition of MI on the actual taxonomy (“what is an acute MI”) rather than combining it with diagnostic criteria (rise or fall pattern of cardiac troponin, specific ECG changes, clinical symptoms, etc.), we will provide more clarity for clinicians to correctly apply the definition.

Simplifying the diagnosis of acute MI may also have several disadvantages. First, further revisions to the Universal Definition will cause more confusion among clinicians, not less, at least initially. Second, the proposal would potentially require coronary imaging in most patients in order to make the diagnosis of myocardial infarction, which is not feasible in many parts of the world. This requirement would make adjudication for clinical trials more challenging and would potentially have implications for drug development. Also, some diagnostic stratification would still be required to guide therapy (e.g. spontaneous coronary dissection, coronary vasospasm). Third, there is a potential risk of this approach that patients with acute myocardial injury would be even less likely to undergo thorough investigation and treatment as those currently classified as having type 2 myocardial infarction, despite having a high rate of cardiovascular morbidity and mortality. It is important to highlight that irrespective of how these patients are classified, they require careful clinical evaluation to understand the mechanism of myocardial injury in order to provide the best treatment and care.

The proposed simplified definition of acute MI is not meant as a critique of the work of the committee developing the 4^th Universal Definition of MI, for whom I have deep respect. I fully recognize the immense challenge they have taken on and the amount of work that went into developing the Universal Definition. Rather, it offers a suggestion to simplify and resolve the confusion now present among clinicians trying to correctly diagnose acute myocardial infarction.