Definition and clinical concept
Myocardial infarction with non-obstructive coronary arteries (MINOCA) describes a clinical presentation in which the patient has symptoms suggestive of acute coronary syndrome (ACS), biochemical evidence of myocardial injury with corroborating evidence of infarction caused by ischaemia, and no obstructive stenosis in a major epicardial coronary artery. Non-obstructive disease is generally defined as the absence of a stenosis of 50% or more in any potential infarct-related artery.
MINOCA is not a definitive disease diagnosis. It is a descriptive and provisional classification that should trigger further investigation. The underlying mechanism may be coronary, myocardial, or systemic, and treatment is inappropriate or incomplete if the mechanism is not established. Myocarditis and takotsubo syndrome can produce myocardial injury and troponin elevation but are non-ischaemic mimics rather than MINOCA when identified as the final diagnosis.
Reported prevalence varies according to the population and diagnostic criteria. MINOCA accounts for approximately 1–14% of ACS presentations in different series and approximately 5–10% of patients presenting with myocardial infarction in other reports. It is more frequent in women and in patients presenting with NSTEMI than in those presenting with STEMI. Approximately one-third of patients with MINOCA may present with STEMI.
Pathophysiology and causes
MINOCA encompasses several distinct mechanisms. These may be broadly divided into coronary causes, myocardial causes, and extracardiac or systemic causes producing myocardial oxygen supply–demand imbalance.
Coronary mechanisms
Coronary mechanisms include:
Plaque rupture or plaque erosion with thrombosis, despite the absence of an angiographically obstructive lesion
Coronary embolism or thrombus
Epicardial coronary vasospasm
Coronary microvascular dysfunction
Spontaneous coronary artery dissection (SCAD)
Standard angiography may fail to demonstrate plaque disruption, intraluminal thrombus, or dissection. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can reveal lesions that are not apparent on conventional angiography.
Coronary vasomotor disorders may involve epicardial spasm or abnormalities of the coronary microcirculation. Microvascular angina reflects myocardial ischaemia caused by structural or functional microvascular abnormalities, impaired coronary flow reserve, reduced microcirculatory conductance, or abnormal arteriolar vasoconstriction. More than one mechanism may coexist.
Supply–demand mismatch
MINOCA may result from a mismatch between myocardial oxygen supply and demand. The clinical history should therefore be examined for potential physiological or systemic stressors, with treatment directed at the precipitating condition.
Myocardial and non-ischaemic mimics
Takotsubo syndrome, myocarditis, and cardiomyopathies may present with symptoms, ECG changes, and troponin elevation resembling acute myocardial infarction. These disorders require distinction from true MINOCA because their management is different. Takotsubo syndrome and myocarditis should not be classified as MINOCA when they are established as the explanation for the presentation.
Clinical presentation and symptoms
Patients typically present with symptoms suggestive of ACS and troponin elevation. The clinical and electrocardiographic manifestations of STEMI may otherwise resemble those of STEMI associated with obstructive atherosclerotic disease. Patients with MINOCA tend to be younger and more often female than patients with atherosclerotic-mediated myocardial infarction. A history of cigarette smoking may be present despite relatively few other conventional atherosclerotic risk factors.
A substantial proportion present with NSTEMI, although STEMI occurs in approximately one-third. Patients with MINOCA-related STEMI generally do not have a prodrome before infarction.
The clinical presentation may also reflect the underlying mechanism:
Supply–demand mismatch: a history of a potential precipitating stressor is important.
Coronary vasospasm: the history may identify migraine medications or cocaine exposure; resolution with vasodilators may provide a diagnostic clue.
Coronary embolism or thrombosis: the clinical context may suggest an underlying thrombotic disorder.
SCAD: angiographic review is central to diagnosis.
Takotsubo syndrome, cardiomyopathy, or myocarditis: the presentation may be clarified by contrast cardiac magnetic resonance imaging (CMR) and, where appropriate, left ventricular angiography.
Evaluation and physical examination
MINOCA should be approached as an ACS presentation requiring immediate assessment and stabilization, followed by systematic clarification of the mechanism.
The initial evaluation should establish:
Whether the presentation fulfils criteria for myocardial infarction rather than isolated myocardial injury.
Whether the coronary angiogram genuinely demonstrates non-obstructive disease.
Whether a lesion such as SCAD, plaque disruption, or thrombus has been overlooked.
Whether a cardiac or extracardiac alternative diagnosis explains the troponin elevation and clinical presentation.
The source material does not provide a detailed, mechanism-specific physical examination or a defined examination protocol. Physical findings should therefore be interpreted in relation to the suspected precipitating condition and the patient’s haemodynamic status.
Diagnostic strategy
Coronary angiography
Invasive coronary angiography is the definitive diagnostic test in patients with ACS. In MINOCA, it demonstrates normal or near-normal coronary arteries, with no stenosis reaching the obstructive threshold.
Angiography alone, however, is insufficient to establish the cause in many patients. Careful re-review of the angiogram is important, particularly for suspected SCAD, plaque disruption, or thrombus.
Functional coronary angiography
Functional coronary angiography combines conventional angiography with adjunctive tests designed to identify coronary functional and structural abnormalities. Depending on the clinical context, assessment may include:
Left ventriculography
Measurement of left ventricular end-diastolic pressure
Intravascular imaging with IVUS or OCT
Assessment of coronary microvascular function
Testing of coronary reactivity and vasoreactivity
In patients with suspected endothelial dysfunction, invasive physiological assessment may be considered. The evidence base for such testing and for treatment of the resulting endotypes remains limited.
Intravascular imaging
IVUS and OCT may identify:
Plaque rupture
Plaque erosion
Intraluminal thrombus
Intracoronary plaque cavities
SCAD
These modalities are particularly useful when angiography shows no obstructive lesion but the clinical presentation strongly suggests an ischaemic coronary mechanism.
Cardiac imaging
If the cause remains unclear after angiography and functional coronary assessment, non-invasive imaging should be selected according to the clinical circumstances. Potential modalities include echocardiography, CMR, and computed tomography.
CMR is a key diagnostic investigation in patients with a working diagnosis of MINOCA. It can help distinguish infarction from myocarditis, takotsubo syndrome, cardiomyopathy, and other causes of myocardial injury. CMR should be obtained as early as possible, ideally during the index admission, because its diagnostic yield is greatest early after presentation. It can identify the underlying cause in up to 87% of patients with a working diagnosis of MINOCA.
Left ventricular angiography may assist in the assessment of takotsubo syndrome, particularly when combined with contrast-enhanced CMR.
Cause-oriented diagnostic assessment
| Suspected mechanism or disorder | Useful diagnostic assessment |
|---|---|
| Supply–demand mismatch | Clinical history and identification of potential stressors |
| Takotsubo syndrome | Left ventricular angiography and contrast CMR |
| Cardiomyopathy | Contrast CMR |
| Myocarditis | Contrast CMR |
| Plaque rupture or erosion | Review of angiography; IVUS or OCT |
| Coronary vasospasm | Response to vasodilators, provocation testing, and review of relevant drug or cocaine exposure |
| Microvascular dysfunction | Invasive or non-invasive assessment of coronary blood flow and coronary flow reserve; CMR |
| Coronary embolism or thrombus | Angiographic review, IVUS or OCT, and thrombophilia assessment or other thrombotic work-up |
| SCAD | Detailed angiographic review, with IVUS or OCT when appropriate |
ECG and biomarkers
Electrocardiography
The source material indicates that the ECG manifestations of MINOCA-related STEMI generally resemble those of STEMI caused by obstructive atherosclerotic coronary disease. It does not provide a separate ECG pattern, diagnostic threshold, or ECG-based algorithm specific to MINOCA.
Cardiac biomarkers
Troponin elevation is part of the clinical definition of MINOCA, but troponin elevation alone does not distinguish infarction from myocardial injury. Myocarditis and takotsubo syndrome can also produce substantial troponin elevation. Consequently, biomarker findings must be integrated with clinical evidence of ischaemia, angiography, and cardiac imaging.
The source material does not specify troponin thresholds, serial sampling intervals, or other laboratory markers. It does identify thrombophilia screening or other thrombotic evaluation as potentially useful when coronary embolism or thrombosis is suspected.
Treatment and management
General principles
Management is constrained by the absence of prospective randomized controlled trials evaluating treatment strategies for MINOCA as a whole or for its individual mechanisms. The immediate approach should therefore combine:
Emergency supportive care
Cardioprotective treatment during the acute presentation
Therapy directed at the suspected mechanism
Secondary prevention of atherosclerotic cardiovascular disease where appropriate
Risk-factor control
Treatment should be revised once the final diagnosis is established. The principal therapeutic principle is to manage the patient according to the underlying disease rather than according to the provisional label of MINOCA.
Acute management
Acute care should provide supportive treatment and cardioprotective therapy irrespective of the eventual mechanism, while investigation proceeds. Cause-directed therapy should be added when the likely mechanism becomes apparent.
The source material does not provide a universal acute drug regimen or doses for MINOCA. In particular, it does not specify doses or durations for aspirin, P2Y12 inhibitors, statins, beta-blockers, ACE inhibitors, calcium-channel blockers, nitrates, or anticoagulants. Treatment should therefore be individualized according to the final diagnosis and the relevant disease-specific recommendations.
Mechanism-directed treatment
| Underlying mechanism | Potential treatment approach |
|---|---|
| Supply–demand mismatch | Treat the precipitating underlying condition |
| Takotsubo syndrome | Supportive care; guideline-directed heart-failure therapy, including ACE inhibitor therapy and beta-blockade when appropriate; mechanical circulatory support if required |
| Cardiomyopathy | Guideline-directed heart-failure therapy and treatment of the underlying cause |
| Myocarditis | Guideline-directed heart-failure therapy and myocarditis-specific management |
| Plaque erosion or rupture | Aspirin, high-intensity statin therapy, beta-blocker, ACE inhibitor; a P2Y12 inhibitor may be considered |
| Coronary vasospasm | Calcium-channel blocker, nitrates, or cilostazol; statin therapy may be considered |
| Microvascular dysfunction | Lifestyle modification, particularly exercise; statin, ACE inhibitor, beta-blocker, or L-arginine supplementation may be considered |
| Coronary embolism or thrombus | Consider anticoagulation and treat the underlying thrombotic condition |
| SCAD | Aspirin and beta-blocker; a P2Y12 inhibitor may be considered |
Secondary prevention
Secondary prevention should be considered in patients with evidence of coronary atherosclerotic disease and for control of cardiovascular risk factors. The ultimate choice of lipid-lowering, antiplatelet, vasoactive, or renin–angiotensin–aldosterone system therapy depends on the established cause.
MINOCA should not automatically be treated as a single uniform condition. For example, antithrombotic therapy may be appropriate for plaque disruption or embolism but not necessarily for a non-ischaemic diagnosis established by CMR. Similarly, calcium-channel blockers and nitrates are directed toward vasospastic disease, whereas heart-failure therapy is relevant to takotsubo syndrome or cardiomyopathy.
Psychosocial and lifestyle considerations
Psychological stress and depression may be relevant to patients with non-obstructive ischaemic syndromes and may contribute to endothelial dysfunction. Depression is associated with poor adherence and worse cardiovascular outcomes, while anxiety after myocardial infarction has been associated with poorer clinical outcomes in some studies. Exercise, psychotherapy, pharmacotherapy, and multidisciplinary care may improve symptoms and quality of life.
For patients with SCAD, particularly those in whom emotional or chronic stress may be contributory, rehabilitation should include stress management and attention to work–life balance. Psychological counselling may be appropriate in selected patients.
Guideline recommendations
The principal recommendations are:
| Recommendation | Class | Level of evidence |
|---|---|---|
| Follow a diagnostic algorithm in all patients with an initial working diagnosis of MINOCA to establish the final cause | I | C |
| Perform CMR after invasive angiography when the final diagnosis remains unclear | I | B |
| Manage MINOCA according to the final established underlying diagnosis and the relevant disease-specific guideline | I | B |
In patients with suspected endothelial dysfunction, invasive physiological assessment may be considered, although the cited ACC/AHA recommendation is less strong than the European recommendations for diagnostic algorithms and CMR.
Prognosis
A diagnosis of MINOCA does not imply a benign course. Compared with obstructive coronary disease, long-term mortality is lower overall, but clinically important mortality persists. In one meta-analysis, the relative risk of long-term mortality compared with obstructive coronary disease was 0.60. Reported long-term mortality was approximately 2.2% in MINOCA versus 5.0% in obstructive coronary disease. In another analysis, five-year mortality among patients with ST-elevation MINOCA was 20%.
Patients who survive STEMI without obstructive coronary disease generally have smaller infarcts and a better long-term outlook than those with atherosclerotic-mediated STEMI. In-hospital mortality was approximately 60% lower and one-year mortality approximately 40% lower in the cited comparison. These aggregate differences should not obscure the fact that prognosis depends substantially on the underlying mechanism and on comorbidities. Some MINOCA subgroups have outcomes similar to those of patients with atherosclerotic myocardial infarction.
Follow-up
Follow-up should be individualized according to the final diagnosis. It should include review of:
The completed diagnostic evaluation and established mechanism
Ventricular function and heart-failure status when relevant
Recurrent angina or vasomotor symptoms
Adherence to secondary prevention and risk-factor treatment
The need for ongoing antiplatelet, anticoagulant, vasoactive, lipid-lowering, or renin–angiotensin–aldosterone system therapy
Psychosocial health, exercise, and rehabilitation needs
Because MINOCA is a working diagnosis rather than a final disease label, early completion of the diagnostic pathway is central to safe longitudinal management. CMR is ideally performed during the index admission when the diagnosis remains uncertain, and subsequent therapy should be aligned with the final result. Persistent or recurrent symptoms in patients with non-obstructive arteries may warrant evaluation for coronary vasospasm, microvascular dysfunction, or another mechanism rather than repeated unstructured coronary angiography.
