Definition and Pathophysiology
The conceptual understanding of myocardial infarction (MI) has evolved significantly over the past century. Initial post-mortem observations in the late 19th century first linked thrombotic occlusion of a coronary artery with myocardial necrosis. Although early clinical descriptions emerged at the dawn of the 20th century, widespread acceptance was delayed, partly due to autopsy studies demonstrating an absence of coronary thrombi in a significant proportion of deceased patients. Historically referred to as coronary thrombosis, the term myocardial infarction ultimately prevailed.
The need for a standardized global definition led to early efforts by the World Health Organization in the mid-20th century, relying primarily on electrocardiographic criteria for epidemiological purposes. With the advent of highly sensitive cardiac biomarkers, the European Society of Cardiology (ESC), American College of Cardiology (ACC), American Heart Association (AHA), and World Heart Federation (WHF) collaborated to redefine MI using a biochemical and clinical approach. This culminated in the Universal Definition of Myocardial Infarction Consensus Documents, with the Fourth Universal Definition published in 2018.
A fundamental prerequisite for diagnosing any MI is myocardial injury, defined by an elevated cardiac troponin (cTn) value with at least one value above the 99th percentile upper reference limit (URL). The injury is considered acute if there is a documented rise and/or fall of cTn values. However, myocardial injury alone is an entity in itself and may arise from non-ischaemic cardiac conditions (such as myocarditis) or non-cardiac conditions (such as renal failure). To establish a diagnosis of MI, acute myocardial injury must be coupled with clinical evidence of acute myocardial ischaemia.
The Fourth Universal Definition classifies MI into five distinct subtypes based on pathophysiology and clinical context:
Type 1 MI: Caused by atherothrombotic coronary artery disease, usually precipitated by atherosclerotic plaque disruption (rupture or erosion). The dynamic thrombotic component can vary in burden and may lead to distal coronary embolization, resulting in myocyte necrosis. Plaque rupture may be further complicated by intraluminal thrombosis or haemorrhage into the plaque through the disrupted surface.
Type 2 MI: Attributed to an imbalance between myocardial oxygen supply and demand, without the presence of acute atherothrombosis.
Type 3 MI: Describes cardiac death in patients with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes, occurring before cTn values become available or abnormal.
Type 4a MI: Represents a periprocedural myocardial infarction associated with percutaneous coronary intervention (PCI).
Type 4b MI: Denotes myocardial infarction related to stent thrombosis following PCI.
Type 4c MI: Denotes myocardial infarction related to restenosis following PCI. Both type 4b and 4c MIs meet the clinical criteria for a type 1 MI.
Type 5 MI: Represents a periprocedural myocardial infarction associated with coronary artery bypass grafting (CABG).
Clinical Presentation and Symptoms
The diagnosis of an acute MI remains a comprehensive clinical diagnosis based on patient symptoms, ECG changes, highly sensitive biochemical markers, and information gleaned from various imaging techniques. For types 1, 2, and 3 MI, clinical evidence of acute myocardial ischaemia is central. Symptoms of myocardial ischaemia are a primary diagnostic criterion for acute MI.
For procedural subtypes (types 4a and 5), the clinical presentation is inherently linked to the context of the index revascularization procedure, occurring within 48 hours after PCI or CABG. While the procedure itself provides the clinical context, the diagnosis requires evidence of new myocardial ischaemia, which may manifest through symptoms, ECG changes, or angiographic complications.
Evaluation and Physical Examination
The source material does not provide specific details regarding the physical examination findings for myocardial infarction.
Diagnostics (ECG, Imaging, Electrophysiology)
Diagnostic evaluation requires the integration of clinical findings, ECG patterns, laboratory data, imaging observations, and occasionally pathological findings, all interpreted within the time horizon of the suspected event.
Electrocardiography (ECG)
For types 1, 2, and 3 MI, new ischaemic ECG changes or the development of pathological Q waves are key diagnostic criteria. In type 1 MI, it is essential to integrate ECG findings to classify the event as either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) to guide appropriate treatment. In type 3 MI, patients present with presumed new ischaemic ECG changes before biomarker availability. For type 4a MI, new ischaemic ECG changes are a specific diagnostic criterion; however, this criterion is not applied to type 5 MI. The isolated development of new pathological Q waves meets the criteria for type 4a or type 5 MI if cTn values are elevated and rising, even if they do not reach the prespecified biomarker thresholds.
Imaging
Imaging evidence of new loss of viable myocardium, or a new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology, fulfils diagnostic criteria for types 1, 2, 4a, and 5 MI.
Angiography and Pathology
The identification of a coronary thrombus by angiography or autopsy is diagnostic for type 1 MI (and is not applied to types 2 or 3). Post-mortem demonstration of acute atherothrombosis in the artery supplying the infarcted myocardium meets the criteria for type 1 MI. Similarly, post-mortem evidence of a procedure-related thrombus meets the criteria for type 4a MI, or type 4b MI if associated with a stent.
For procedure-related MIs (types 4a and 5), angiographic findings consistent with a procedural flow-limiting complication are diagnostic. These complications include:
Coronary dissection
Occlusion of a major epicardial artery or graft
Side-branch occlusion or thrombus
Disruption of collateral flow
Slow flow or no-reflow
Distal embolization
Biomarkers and Laboratory Findings
Cardiac troponin (cTn) values are the cornerstone of myocardial injury and infarction diagnosis. The threshold for injury is at least one cTn value above the 99th percentile URL. Acute injury requires a documented rise and/or fall of cTn values.
For coronary procedure-related MIs (types 4a and 5), specific biomarker thresholds are arbitrarily defined within 48 hours of the index procedure:
| MI Subtype | Procedure | Baseline cTn Status | Biomarker Threshold for Diagnosis |
|---|---|---|---|
| Type 4a | PCI | Normal baseline values | Post-procedure cTn > 5 × 99th percentile URL |
| Type 4a | PCI | Elevated but stable (≤ 20% variation) or falling | Rise > 20% from baseline to an absolute value > 5 × 99th percentile URL |
| Type 5 | CABG | Normal baseline values | Post-procedure cTn > 10 × 99th percentile URL |
| Type 5 | CABG | Elevated but stable (≤ 20% variation) or falling | Rise > 20% from baseline to an absolute value > 10 × 99th percentile URL |
The use of high-sensitivity cardiac troponin (hs-cTn) assays to diagnose type 4a and type 5 MI remains an area of active research. Because hs-cTn assays possess wide dynamic ranges, different criteria may be required for different assays. However, current data indicate that optimal hs-cTnT thresholds to predict cardiovascular events at 30 days and 1 year align closely with the five-fold increase threshold established by prior universal definitions; thus, these criteria have been retained.
Alternative definitions exist for periprocedural MI. The Society for Cardiovascular Angiography and Interventions (SCAI) defines a clinically relevant post-PCI MI as an elevation in creatine kinase-myocardial band (CK-MB) to ≥ 10 × upper limits of normal (ULN) or cTn to ≥ 70 × ULN. Alternatively, the SCAI definition is met with CK-MB ≥ 5 × ULN or cTn ≥ 35 × ULN if accompanied by new pathological Q waves in two or more contiguous leads or left bundle branch block. The Academic Research Consortium (ARC) has also proposed the ARC-2 definition for standardizing reporting in clinical trials. In routine clinical practice, asymptomatic CK-MB elevations (less than five times the ULN) occur in 3% to 11% of technically successful PCIs and carry little apparent clinical consequence. Troponin T and I elevations occur more frequently than CK-MB elevations, though their independent prognostic significance over CK-MB is less well established.
Guideline Recommendations
The Fourth Universal Definition of Myocardial Infarction (2018) provides the overarching framework for diagnosing and classifying MI. The document emphasizes that a consistent approach must be used when constructing a computable phenotype of MI in electronic medical records to reliably compare data across institutions and track epidemiological trends. Ideally, documentation should include the specific assay used, the 99th percentile URL, and the full sequence of biomarker values to accurately discern the rise and fall pattern.
Treatment and Management
The source material does not provide specific details regarding the pharmacological treatment, acute management strategies, or long-term therapeutic interventions for myocardial infarction.
Prognosis and Follow-up
The prognosis of MI is closely tied to its subtype and the magnitude of biomarker elevation. Myocardial injury, defined solely by elevated cTn values, is frequently encountered clinically and is associated with an adverse prognosis.
In the context of periprocedural events, larger degrees of myonecrosis are associated with higher 1-year mortality rates and should be considered a true periprocedural MI. Many of these clinically silent infarcts may reflect a higher overall atherosclerotic burden in the patient rather than being directly causal. Importantly, spontaneous MI occurring after a PCI carries much greater prognostic importance than periprocedural enzyme elevation.
The revision of the MI definition carries significant implications for patients, healthcare professionals, and society. A definitive diagnosis forms the basis for advice on further diagnostic testing, lifestyle changes, treatment, and prognosis. Furthermore, the diagnosis impacts psychological status, life and health insurance, professional careers, and driving or pilot licences. Societally, it influences diagnosis-related coding, hospital reimbursement, public health statistics, sick leave, and disability attestation. Educational materials and treatment guidelines must be appropriately adapted to ensure physicians are adequately informed of these diagnostic criteria.
