Definition and pathophysiology
Myocardial infarction (MI) is a clinical diagnosis that integrates myocardial injury, evidence of acute myocardial ischaemia, electrocardiographic findings, cardiac biomarkers, imaging, angiography, and, occasionally, pathological examination. Pathologically, infarction represents myocardial cell death caused by prolonged ischaemia.
The first cellular abnormalities of ischaemia include depletion of glycogen, relaxation of myofibrils, and disruption of the sarcolemma. These changes may appear within 10–15 minutes of ischaemia. Mitochondrial abnormalities can occur even earlier after coronary occlusion and progress over time. Experimentally, necrosis advances from the subendocardium towards the subepicardium over several hours. The extent and tempo of injury are influenced by collateral flow, myocardial oxygen consumption, and intermittent occlusion with reperfusion. Prompt reperfusion, when appropriate, reduces myocardial ischaemic injury.
Myocardial injury
Myocardial injury is defined by at least one cardiac troponin (cTn) concentration above the assay-specific 99th percentile upper reference limit (URL). It is considered acute when there is a rise and/or fall in cTn values. An elevated cTn alone does not establish MI, because myocardial injury may occur without myocardial ischaemia.
Non-ischaemic myocardial injury may accompany numerous cardiac and systemic disorders, including:
| Cardiac causes | Systemic causes |
|---|---|
| Heart failure | Sepsis |
| Myocarditis | Chronic kidney disease |
| Cardiomyopathy | Stroke or subarachnoid haemorrhage |
| Takotsubo syndrome | Pulmonary embolism |
| Recent coronary revascularization | Infiltrative disease, such as amyloidosis or sarcoidosis |
| Other cardiac procedures | Chemotherapeutic agents |
| Catheter ablation | Critical illness |
| Defibrillator shocks | Strenuous exercise |
| Cardiac contusion |
The diagnosis should therefore distinguish isolated myocardial injury from infarction caused by acute ischaemia.
Acute myocardial infarction
Acute MI requires both:
Acute myocardial injury, demonstrated by a rise and/or fall in cTn with at least one value above the 99th percentile URL; and
Clinical evidence of acute myocardial ischaemia, demonstrated by at least one of the following:
New ischaemic ECG changes.
New pathological Q waves.
Imaging evidence of new loss of viable myocardium or a new regional wall-motion abnormality in an ischaemic pattern.
Identification of a coronary thrombus by angiography or autopsy, except in type 2 and type 3 MI.
A diagnosis of MI should not be made solely from an abnormal cTn concentration in the absence of evidence of ischaemia.
Classification of myocardial infarction
The Fourth Universal Definition separates MI into five principal types.
| Type | Mechanism or setting |
|---|---|
| Type 1 | Acute atherothrombotic MI, usually related to plaque rupture or erosion |
| Type 2 | MI caused by oxygen supply–demand imbalance unrelated to acute atherothrombosis |
| Type 3 | Cardiac death with suspected acute ischaemia before biomarker confirmation |
| Type 4a | MI associated with percutaneous coronary intervention (PCI) |
| Type 4b | MI caused by stent or scaffold thrombosis |
| Type 4c | MI caused by restenosis |
| Type 5 | MI associated with coronary artery bypass grafting (CABG) |
Types 4b and 4c fulfil the criteria for type 1 MI because they represent coronary atherothrombotic events in the setting of a stent thrombosis or restenosis.
Type 1 myocardial infarction
Definition and pathophysiology
Type 1 MI results from acute coronary atherothrombosis. It is usually precipitated by disruption of an atherosclerotic plaque through rupture or erosion. The relative contributions of plaque disease and thrombus vary considerably. Thrombotic material may embolize distally and cause additional myocyte necrosis. Plaque disruption may also be accompanied by haemorrhage into the plaque.
The diagnosis is supported by the general criteria for acute MI together with evidence of acute coronary atherothrombosis. Post-mortem demonstration of an atherothrombus in the artery supplying the infarcted myocardium meets the criteria for type 1 MI regardless of the cTn concentration.
Type 1 MI should be classified electrocardiographically as ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), because this classification guides treatment according to current acute coronary syndrome recommendations.
Clinical presentation
The clinical presentation is determined by the presence of acute myocardial ischaemia and may include symptoms suggestive of ischaemia, new ischaemic ECG abnormalities, pathological Q waves, or new imaging evidence of myocardial injury. The supplied material does not provide a detailed symptom profile or physical-examination description specific to type 1 MI.
Evaluation and diagnosis
Evaluation requires integration of:
The clinical context and symptoms.
Serial cTn measurements.
ECG findings, including assessment for new ischaemic changes.
Imaging for new loss of viable myocardium or a new regional wall-motion abnormality.
Angiography or autopsy when coronary thrombus identification is relevant.
Type 2 myocardial infarction
Definition and pathophysiology
Type 2 MI is caused by an imbalance between myocardial oxygen supply and demand that is unrelated to acute coronary atherothrombosis. The diagnostic distinction is mechanistic: the event is attributed to supply–demand mismatch rather than acute plaque disruption with coronary thrombosis.
The presence or absence of coronary artery disease is relevant to prognosis and treatment, but the supplied material does not specify the individual precipitating conditions, therapeutic targets, or drug regimens for type 2 MI.
Differentiation from myocardial injury
A patient may have an acute rise and/or fall in cTn without clinical evidence of ischaemia. Such a presentation should be diagnosed as acute myocardial injury rather than type 2 MI. Type 2 MI requires acute myocardial injury plus clinical evidence of acute myocardial ischaemia.
Coronary thrombus identified by angiography or autopsy is not used as a defining criterion for type 2 MI.
Type 3 myocardial infarction
Definition
Type 3 MI refers to cardiac death in a patient with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes, occurring before cTn values become available or abnormal.
This category distinguishes presumed fatal acute ischaemic events from sudden cardiac death in which there is insufficient evidence to establish MI. The supplied material does not provide additional management or follow-up recommendations specific to type 3 MI.
Procedure-related myocardial injury and infarction
General principle
Coronary procedures frequently produce post-procedural cTn elevations. An isolated increase in cTn after PCI is sufficient to diagnose procedural myocardial injury, but not type 4a MI. A procedure-related MI requires both a specified degree of biomarker elevation and additional evidence of myocardial ischaemia or a procedure-related flow-limiting complication.
PCI-related MI is designated type 4a MI, whereas CABG-related MI is designated type 5 MI.
Type 4a myocardial infarction: PCI-related MI
Diagnostic criteria
For a type 4a MI occurring within 48 hours of PCI, the cTn threshold depends on the baseline concentration:
With normal baseline cTn: post-procedure cTn must exceed five times the 99th percentile URL.
With elevated baseline cTn that is stable, defined as ≤20% variation, or falling: the post-procedure value must rise by >20% and reach an absolute concentration more than five times the 99th percentile URL.
In addition, at least one of the following is required:
New ischaemic ECG changes.
New pathological Q waves.
Imaging evidence of newly lost viable myocardium or a new regional wall-motion abnormality in an ischaemic distribution.
Angiographic evidence of a flow-limiting procedural complication, such as:
Occlusion of a major epicardial artery.
Side-branch occlusion or thrombus.
Disruption of collateral flow.
Slow flow or no-reflow.
Distal embolization.
The development of new pathological Q waves may fulfil the criteria even when cTn is elevated and rising but remains below the specified biomarker threshold. Post-mortem demonstration of a procedure-related thrombus also meets the criteria for type 4a MI.
Practical interpretation
The distinction between procedural myocardial injury and type 4a MI is clinically important. Small, isolated biomarker elevations after an apparently successful PCI should not automatically be labelled MI. The diagnosis requires the combination of the specified cTn response and objective evidence of ischaemia or procedural coronary compromise.
A more stringent definition described in the supplied material identifies clinically relevant post-PCI MI using substantially higher cTn or creatine kinase-myocardial band thresholds, with additional ECG criteria in some cases. However, the Fourth Universal Definition criteria remain the principal framework described for classification.
Prognostic considerations
Post-PCI cTn and creatine kinase-myocardial band elevations occur more frequently than clinically apparent infarction. Small, asymptomatic enzyme increases may have limited clinical consequence, whereas larger degrees of myocardial necrosis are associated with higher one-year mortality. Spontaneous MI after PCI has greater prognostic importance than isolated periprocedural enzyme elevation.
Mortality after PCI is uncommon, approximately 1% in the supplied material, but is higher in patients undergoing PCI for STEMI, those with cardiogenic shock, and those with previously poor left-ventricular function in whom an occlusion develops.
Type 4b myocardial infarction: stent or scaffold thrombosis
Type 4b MI is caused by stent or scaffold thrombosis and fulfils the criteria for type 1 MI. Thus, the diagnosis requires acute myocardial injury with clinical evidence of myocardial ischaemia and the relevant evidence of an acute coronary thrombotic event. Post-mortem demonstration of a procedure-related thrombus meets type 4b criteria when the thrombus is associated with a stent.
The supplied material does not provide further information on the timing classification, angiographic definitions, antithrombotic treatment, or follow-up strategy for stent thrombosis.
Type 4c myocardial infarction: restenosis
Type 4c MI is associated with restenosis after PCI. It also meets the criteria for type 1 MI, reflecting the requirement for acute myocardial injury and clinical evidence of acute myocardial ischaemia in the context of a restenotic coronary lesion.
Specific angiographic thresholds, treatment strategies, and surveillance recommendations for restenosis are not provided in the supplied material.
Type 5 myocardial infarction: CABG-related MI
Diagnostic criteria
CABG-related MI occurring within 48 hours of surgery requires:
With normal baseline cTn: cTn elevation greater than 10 times the 99th percentile URL.
With elevated baseline cTn that is stable, defined as ≤20% variation, or falling: a rise of >20% together with an absolute post-operative concentration greater than 10 times the 99th percentile URL.
In addition, at least one of the following must be present:
New pathological Q waves.
Imaging evidence of new loss of viable myocardium or a new regional wall-motion abnormality in an ischaemic pattern.
Angiographic evidence of a flow-limiting complication involving a native coronary artery or graft, including dissection, occlusion, side-branch occlusion or thrombus, disruption of collateral flow, or distal embolization.
New ischaemic ECG changes are an additional criterion for type 4a MI but are not listed as a criterion for type 5 MI in the supplied definition. Isolated new pathological Q waves may establish type 5 MI when cTn is elevated and rising but does not reach the specified threshold. Post-mortem demonstration of a procedure-related thrombus may also satisfy the criteria.
Diagnostic strategy
Clinical integration
Diagnosis should be based on the temporal relationship between symptoms, ECG abnormalities, biomarker changes, imaging findings, and any procedure or pathological observation. The relevant time horizon is essential, particularly for differentiating spontaneous MI from procedure-related injury.
The following sequence provides a structured diagnostic approach:
Establish whether cTn is elevated above the 99th percentile URL.
Determine whether the pattern is acute by identifying a rise and/or fall.
Search for clinical evidence of acute myocardial ischaemia.
Assess the ECG for new ischaemic changes or pathological Q waves.
Use imaging to identify new loss of viable myocardium or a new ischaemic regional wall-motion abnormality when appropriate.
Consider angiographic or pathological evidence of coronary thrombus or a procedure-related flow-limiting complication.
Assign the MI type according to mechanism and procedural context.
Electrocardiography
ECG findings may fulfil the criteria for acute MI when new ischaemic changes or pathological Q waves develop. ECG interpretation also contributes to classification of type 1 MI as STEMI or NSTEMI. The Fourth Universal Definition highlights several additional ECG considerations, including new non-rate-related right bundle branch block with specific repolarization patterns and ST-segment elevation in lead aVR with specific repolarization patterns as a STEMI equivalent. The supplied material does not provide the detailed ECG thresholds or lead-by-lead criteria for these findings.
In type 4a MI, new ischaemic ECG changes are specifically included among the required additional criteria. For procedure-related MI more generally, new pathological Q waves may independently satisfy the procedural criterion when the biomarker pattern is rising but below the specified threshold.
Imaging
Imaging contributes to the diagnosis by demonstrating:
New loss of viable myocardium.
A new regional wall-motion abnormality in a pattern consistent with ischaemia.
The Fourth Universal Definition places an enhanced emphasis on imaging, including cardiac magnetic resonance imaging, for diagnosing MI. No specific imaging protocols, sequences, or diagnostic thresholds are provided in the supplied material.
Angiography and pathology
Angiography may identify:
Acute coronary thrombus.
Coronary dissection.
Occlusion of a major epicardial artery or graft.
Side-branch occlusion or thrombus.
Disruption of collateral flow.
Distal embolization.
Slow flow or no-reflow after PCI.
Autopsy may demonstrate an acute atherothrombus in the artery supplying the infarcted myocardium, supporting type 1 MI. Post-mortem demonstration of procedure-related thrombus supports type 4a MI, or type 4b MI when associated with a stent.
Biomarkers and laboratory findings
Cardiac troponin
Cardiac troponin is the central biomarker for defining myocardial injury. At least one value above the assay-specific 99th percentile URL is required. Acute injury requires a rise and/or fall in serial measurements.
Interpretation must account for:
The assay used.
The assay-specific 99th percentile URL.
The complete sequence of biomarker measurements.
The baseline cTn concentration.
Whether the baseline value is stable, varying by ≤20%, or falling.
The clinical and ECG context.
High-sensitivity cTn assays have improved the detection of myocardial injury. Their dynamic ranges vary, and criteria may differ between assays. The use of high-sensitivity assays for defining type 4a and type 5 MI remains an area of active research; the five-fold threshold for type 4a MI is retained because the supplied material identifies no superior alternative.
Creatine kinase-myocardial band
Creatine kinase-myocardial band elevation may occur after PCI and has been used in more stringent definitions of clinically relevant post-PCI MI. Small asymptomatic elevations below five times the upper limit of normal may occur after technically successful PCI and have little apparent clinical consequence. Troponin elevations are more frequent than creatine kinase-myocardial band elevations, although their additional prognostic significance over creatine kinase-myocardial band elevation is described as less established in this setting.
Haemodynamic and physical assessment in acute MI
The supplied haemodynamic classification uses clinical examination and invasive measurements.
Clinical classification
| Class | Clinical findings |
|---|---|
| I | No rales and no third heart sound |
| II | Crackles, third heart sound, or elevated jugular venous pressure |
| III | Frank pulmonary oedema |
| IV | Shock |
Invasive haemodynamic classification
| Subset | Definition |
|---|---|
| I | Normal haemodynamics: pulmonary capillary wedge pressure (PCWP) <18 and cardiac index (CI) >2.2 |
| II | Pulmonary congestion: PCWP >18 and CI >2.2 |
| III | Peripheral hypoperfusion: PCWP <18 and CI <2.2 |
| IV | Pulmonary congestion with peripheral hypoperfusion: PCWP >18 and CI <2.2 |
This classification helps describe the haemodynamic severity of acute MI. The supplied material does not provide a comprehensive physical-examination protocol or specific pharmacological treatment according to haemodynamic class.
Treatment and management
General principles
The diagnosis of MI has direct implications for further diagnostic testing, lifestyle advice, treatment, and prognosis. Management should be based on the specific MI type and its underlying mechanism. For type 1 MI, ECG classification into STEMI or NSTEMI is essential for selecting treatment according to current guidelines.
Prompt reperfusion, when clinically appropriate, limits ischaemic myocardial injury. For procedure-related events, management requires recognition of the distinction between isolated myocardial injury and true MI, together with assessment for flow-limiting procedural complications.
Type 1 MI
The supplied material establishes that type 1 MI should be managed according to current STEMI or NSTEMI guidelines, but does not provide specific reperfusion strategies, antiplatelet regimens, anticoagulant regimens, lipid-lowering therapy, doses, or secondary-prevention protocols.
Type 2 MI
Treatment should reflect the oxygen supply–demand imbalance and the presence or absence of coronary artery disease. However, the supplied material does not specify the individual precipitating conditions or provide drug treatment, dosing, or procedural recommendations.
Procedure-related MI
For type 4a and type 5 MI, the key management implications described are diagnostic:
Do not classify an isolated post-procedural cTn increase as MI.
Confirm the specified biomarker threshold.
Assess for new ischaemic ECG changes, pathological Q waves, new imaging abnormalities, or angiographic procedural complications.
Investigate and address flow-limiting complications when present.
No specific rescue PCI, surgical, antithrombotic, or supportive treatment protocol is provided.
Drugs and doses
The supplied material does not provide drug names, doses, dose adjustments, or practical prescribing instructions for the treatment of types 1–5 MI.
Guideline recommendations
The Fourth Universal Definition provides the following core recommendations:
Use the term myocardial injury when cTn exceeds the 99th percentile URL.
Call the injury acute when cTn demonstrates a rise and/or fall.
Diagnose acute MI only when acute myocardial injury is accompanied by clinical evidence of acute myocardial ischaemia.
Distinguish non-ischaemic myocardial injury from MI.
Classify MI mechanistically into types 1–5.
Distinguish procedural myocardial injury from procedure-related MI.
Use ECG findings to classify type 1 MI as STEMI or NSTEMI.
Interpret cTn results in relation to the assay, its URL, the serial pattern, and the clinical context.
Incorporate imaging, angiography, and, when available, pathological findings into the diagnostic process.
For healthcare documentation and data systems, record the assay used, its 99th percentile URL, and the complete cTn sequence so that acute biomarker kinetics can be evaluated reliably.
Prognosis and follow-up
Myocardial injury, whether or not it fulfils the criteria for MI, is associated with adverse prognosis. Larger degrees of post-PCI myocardial necrosis are associated with higher one-year mortality. Spontaneous MI occurring after PCI carries greater prognostic significance than an isolated periprocedural enzyme elevation.
Mortality after PCI is uncommon but increases in the setting of STEMI, cardiogenic shock, and previously poor left-ventricular function complicated by occlusion.
A diagnosis of MI also has important consequences beyond immediate clinical care. It may affect psychological well-being, life and health insurance, professional activities, driving and pilot licences, healthcare coding, reimbursement, public-health statistics, sick leave, and disability certification. Accurate classification is therefore important for both individual care and healthcare-system reporting.
The supplied material does not specify a structured schedule for outpatient follow-up, repeat imaging, rehabilitation, secondary prevention, or long-term pharmacotherapy.
