Myocardial injury with nonobstructive coronary arteries (MINOCA)

Article written and reviewed by Dr Luca Moretti

MINOCA, updated as myocardial injury with non-obstructive coronary arteries, identifies a working diagnosis in patients with clinical features of possible infarction in whom coronary angiography shows no epicardial stenosis of 50% or greater. The term does not describe a single disease and is not equivalent to “normal coronary arteries”: it is a working diagnosis encompassing patients in whom the work-up may identify coronary, noncoronary cardiac, or noncardiac causes. The working diagnosis of MINOCA applies to a patient with clinical features of possible infarction and nonobstructive coronary arteries, meaning no stenosis of 50% or greater; it does not require the definitive criteria for myocardial infarction to have already been met. It is therefore an operational diagnosis that must be converted into an etiological diagnosis, not a label with which to conclude hospitalization.

The angiographic threshold of 50% is conventional. A 30% or 40% stenosis may contain a vulnerable plaque, a partially lysed thrombus, or an intramural dissection; angiography depicts the luminal contour but does not precisely characterize the wall, endothelium, or microcirculation. The same image does not exclude vasospasm, a recanalized embolism, or microvascular dysfunction. The expression “absence of coronary disease” is therefore inappropriate until the coronary mechanism, myocardium, and possible extracoronary causes of imbalance have been assessed.
Myocarditis, Takotsubo syndrome, and other cardiomyopathies may mimic infarction with pain, ECG abnormalities, and troponin elevation. They fall under suspected MINOCA at the time of angiography but not under the final diagnosis if imaging demonstrates nonischemic injury; this distinction is essential: myocarditis does not require DAPT for a nonexistent plaque, while plaque erosion must not be discharged as a stress reaction. Cardiac magnetic resonance, combined when necessary with intracoronary imaging and functional tests, is the cornerstone of reclassification.

Under the previous definition, MINOCA accounted for approximately 5-10% of infarctions undergoing angiography and was relatively more frequent in women and younger patients; these estimates cannot be transferred directly to the new definition as a working diagnosis of myocardial injury. Nevertheless, it includes men, older people, and patients with numerous atherosclerotic risk factors. Prognostic estimates based on the previous MINOCA definition cannot be transferred directly to the new diagnostic construct; prognosis depends on the final diagnosis and the patient’s condition. Defining the etiology avoids both undertreatment of an ischemic cause and indiscriminate exposure to unjustified drugs.

Etiology, risk factors, pathogenesis, and pathophysiology

Plaque disruption includes cap rupture, endothelial erosion, and calcified nodules. The thrombus may transiently occlude the vessel, embolize distally, or dissolve before angiography, leaving modest stenosis. OCT identifies cap discontinuity, cavities, thrombus, and surface loss; IVUS penetrates more deeply but has lower resolution for superficial abnormalities. If infarction is confirmed and acute coronary pathology identified, the mechanism falls under primary myocardial infarction even when residual narrowing is below 50%. Smoking, LDL, diabetes, and inflammation retain their significance, so the absence of obstruction does not negate atherosclerotic prevention.

Spontaneous coronary artery dissection separates layers of the wall through an intramural hematoma or intimal tear, compressing the true lumen. Long smooth forms may be mistaken for a small vessel or spasm; focal forms mimic atherosclerosis. It is more frequent in women, is associated with fibromuscular dysplasia, and may be favored by physical or emotional stress, pregnancy, and the puerperium, although these conditions are not required. Intracoronary imaging clarifies selected cases, but instrumentation may extend the dissection; a convincing angiographic diagnosis does not require routine invasive confirmation.

Epicardial vasospasm is intense, transient, reversible constriction that may cause prolonged ischemia, arrhythmias, and necrosis. Smoking, cocaine and other sympathomimetics, autonomic abnormalities, and vascular smooth-muscle hyperreactivity contribute; mild atherosclerosis may coexist. Microvascular spasm causes ischemic symptoms and signs without visible epicardial constriction. Acetylcholine provocation testing, performed in an experienced laboratory after contraindications have been excluded, distinguishes phenotypes and guides calcium-channel blockers and nitrates; spontaneous response to nitrates alone is not diagnostic.
Coronary embolism may arise from atrial fibrillation, intracardiac thrombi, prosthetic valves or vegetations, tumors, paradoxical embolism, or iatrogenic material. A clot may migrate distally or lyse, leaving nearly normal angiography; occlusion of multiple branches or absence of plaque in the culprit vessel increases suspicion. In situ thrombosis may be favored by thrombophilia, cancer, antiphospholipid syndrome, or hormonal states, but indiscriminate testing has a low yield. Investigation is guided by age, thrombotic history, miscarriages, family history, and angiographic findings.

Secondary myocardial infarction may initially present as MINOCA when severe anemia, hypoxemia, tachyarrhythmia, shock, or a hypertensive crisis causes ischemia with nonobstructive coronary arteries; if confirmed, the final diagnosis must then be classified as secondary myocardial infarction. The systemic cause must be intense enough to explain the imbalance, and evidence of ischemia, not merely elevated troponin, must be present. Myocardial injury from sepsis or heart failure without ischemic evidence may initially enter the MINOCA pathway if the presentation suggests possible infarction and angiography shows nonobstructive arteries; once the nonischemic cause is defined, the final diagnosis is not myocardial infarction. The final diagnosis must state the identified cause; if secondary myocardial infarction is confirmed, it must be classified as such, optionally specifying that the patient initially presented with a working diagnosis of MINOCA.

Coronary microvascular dysfunction limits the ability to increase flow or causes arteriolar constriction. In acute presentations it may contribute to ischemia and necrosis, but reduced flow reserve immediately after infarction may also result from edema and does not prove causality. PET, quantitative CMR, and invasive assessment of CFR and microvascular resistance describe the phenotype and must be interpreted in the temporal context. Overlap with spasm, plaque disease, and cardiomyopathies is possible; a single abnormal result must not replace overall reconstruction.
Some cases remain indeterminate even after a complete pathway because the phenomenon resolves, imaging is delayed, or technical limitations intervene. Uncertainty must be documented together with hypotheses that remain plausible and why they were not confirmed; automatically attributing a psychogenic cause in the presence of nonobstructive coronary arteries is incorrect, as is prescribing full atherothrombotic infarction therapy indefinitely to everyone. Managing uncertainty requires therapy proportionate to the probable mechanism, reassessment, and clear instructions about symptoms.

Pathological anatomy, classification, and evolution

The working diagnosis of MINOCA requires clinical features of possible infarction and absence of obstruction of 50% or greater in every major epicardial vessel; it does not require infarction to have already been confirmed. The cutoff does not measure functional significance and does not exclude diffuse plaque disease; an intermediate lesion may require physiological assessment when stability permits. The term MINOCA must not be applied to chronic troponin elevation, contusion, ablation, kidney failure without ischemia, or separately classified procedural necrosis.

Operational criteria for suspected MINOCA

• Rise or fall in cardiac troponin with at least one value above the sex-specific 99th percentile.
• At least one item of evidence of acute ischemia: symptoms, new ECG changes, Q waves, ischemic imaging, or coronary thrombus.
• No angiographic stenosis of 50% or greater in a major epicardial artery.
• No clinically evident alternative explanation for the presentation at initial assessment.
• Subsequent exclusion of nonischemic mimics and definition of the mechanism whenever possible.

The most useful classification separates coronary mechanisms from alternative diagnoses. The former include plaque disruption, dissection, embolism or thrombosis, spasm, and microvascular dysfunction; supply-demand imbalance is an extracoronary ischemic mechanism that may be associated with nonobstructive coronary arteries; myocarditis and Takotsubo syndrome are removed from the group once diagnosed. This taxonomy prevents the error of regarding MINOCA as a single anatomical variant and makes causal therapy verifiable during follow-up.
The histological pattern of infarction is ischemic necrosis, often subendocardial but sometimes transmural or multifocal. On CMR, ischemic late gadolinium enhancement begins at the subendocardium and follows a coronary territory; edema identifies recent injury; myocarditis more often shows nonterritorial subepicardial or intramural enhancement, while Takotsubo syndrome combines edema and typical wall-motion abnormalities with the usual absence of an ischemic scar. Patterns may be incomplete: a negative CMR does not exclude a small infarction, particularly when performed late or technically limited.

The culprit plaque may be eccentric and nonstenotic. Rupture exposes the lipid core; erosion preserves the cap but has adherent thrombus; a calcified nodule protrudes into the lumen. Distal microemboli produce small foci of necrosis not shown by angiography; in dissection, the wall contains blood and the true lumen is compressed without classic plaque. In embolism, the myocardium follows the occluded territory, while prolonged spasm may leave a scar similar to that from transient thrombosis.
The acute course ranges from a limited event to cardiogenic shock, arrhythmias, or cardiac arrest. Ischemic mass, the ventricle involved, and reperfusion delay matter more than the final nonobstructive appearance; SCAD may heal spontaneously but may also extend; spasm may recur during the first hours; an untreated embolic source may cause new coronary or cerebral events. Initial monitoring follows the clinical risk of infarction, not an assumed low risk derived from the word nonobstructive.

Over time, remodeling, ventricular dysfunction, scar-related arrhythmias, and recurrent ischemia may occur. Function often recovers when injury is small or transient, but not always; CMR distinguishes reversible edema from fibrosis; recurrence may reproduce the same mechanism or a different one, especially when plaque disease and abnormal vasomotion coexist. Follow-up reports must preserve the etiological diagnosis and avoid classifying every new pain generically as “previous MINOCA.”
Mortality estimates published using the previous MINOCA definition cannot be transferred directly to the new diagnostic construct; risk must be interpreted according to the final diagnosis. Prognosis is heterogeneous and depends on that diagnosis; if the work-up confirms infarction caused by plaque, SCAD, vasospasm, or embolism, the event must be classified as primary myocardial infarction according to the Fifth UDMI. Age, diabetes, kidney function, ejection fraction, and presentation with STEMI or shock retain prognostic value. Absence of a definitive diagnosis may reflect an incomplete pathway and be associated with less coherent prevention.

Clinical manifestations

The presentation may be indistinguishable from possible acute myocardial infarction: pressure-like retrosternal pain, radiation, dyspnea, nausea, sweating, syncope, or cardiac arrest. Nonclassic symptoms are more frequent in women, older people, and diabetes, but no profile identifies the mechanism; the tracing may show STEMI, ST-segment depression, T-wave inversion, or minimal abnormalities; troponin magnitude varies widely. Before angiography, treatment and triage follow the acute coronary syndrome pathway because the absence of obstruction is not yet known.
A history of rest pain at night, cyclical episodes, and rapid response to nitrates suggests vasospasm, particularly with transient ST-segment elevation; however, response to nitrates is nonspecific and esophageal pain may improve similarly. Cocaine, amphetamines, triptans, and other vasoconstrictors must be sought without judgment. Palpitations or syncope during the episode signal possible arrhythmias and increase the urgency of monitoring.

SCAD may occur during or after physical stress, emotional stress, pregnancy, or the puerperium, but many cases have no recognizable trigger. Headache, hypertension, or a history of arterial tortuosity may suggest an associated arteriopathy; absence of atherosclerotic risk factors is not required; pain may persist after healing and does not always indicate recurrence. Every new acute episode nevertheless requires ECG and troponin testing because recurrence cannot be excluded solely from symptom frequency.
An embolic source is suspected with atrial fibrillation, a prosthetic valve, endocarditis, recent cardioversion, ventricular thrombus, cancer, or systemic thromboembolism. Fever, peripheral phenomena, and a murmur suggest endocarditis; neurological deficits require parallel assessment. Paradoxical embolism requires venous thrombus and a right-to-left communication in the appropriate context, not merely the common finding of a patent foramen ovale. A history of miscarriages or thrombosis at a young age points toward antiphospholipid syndrome or another selected thrombophilia.

Myocarditis may follow a viral infection or be associated with fever, myalgia, palpitations, and pleuritic pain; Takotsubo syndrome is often preceded by emotional or physical stress. No historical feature is sufficient to distinguish them from a patient with a working diagnosis of MINOCA and possible infarction; pleuritic pain does not exclude infarction, and evident stress does not prove Takotsubo syndrome. Echocardiography and especially CMR convert clinical clues into a diagnosis, whereas a narrative explanation without imaging leaves the cause of myocardial injury unresolved.
Physical examination is often normal but may show congestion, hypotension, a new murmur, arrhythmia, or signs of systemic embolism. Pulse asymmetry and transfixing pain point toward aortic disease; hypoxia, tachycardia, and signs of venous thrombosis toward pulmonary embolism. These conditions may cause troponin elevation and ECG abnormalities without coronary infarction. Investigation is guided by clinical probability and must not delay urgent coronary angiography when signs of coronary occlusion persist.

After discharge, anxiety, uncertainty, and activity restriction are common. Saying “there is nothing wrong” contradicts the presence of myocardial injury requiring an etiological explanation and may impair adherence; conversely, presenting every pain as imminent reinfarction promotes repeated visits and fear of exertion. The patient must know the demonstrated mechanism, what has been excluded, and the warning signs. Rehabilitation, gradual return to activity, and psychological support are parts of recovery, particularly in SCAD and persistent symptoms.

Investigations and diagnosis

The initial pathway includes an ECG within minutes, serial tracings, high-sensitivity troponin, complete blood count, kidney function, electrolytes, glucose, and hemodynamic assessment. Biomarker dynamics confirm acute injury, but ischemia must be documented by symptoms, ECG, imaging, or thrombus; echocardiography identifies regional abnormalities, right and left ventricular function, valves, effusion, and complications. Nonterritorial wall-motion abnormalities do not exclude infarction; normal function does not exclude a small event.
Coronary angiography must be reviewed systematically for intermediate stenoses, thrombus, distal cutoff, occluded branches, tapering, staining, and features of dissection. Multiple projections reduce overlap; intracoronary nitrate distinguishes a spastic component and clarifies true caliber; a lesion between 30% and 50% may be causally relevant and, when appropriate, physiology assesses the gradient. Ventriculography may suggest Takotsubo syndrome but does not replace CMR or justify indiscriminate additional contrast.

Cardiac magnetic resonance should be performed early when available, ideally during hospitalization or within a few days. Cine imaging, T1 and T2 mapping, edema, and late enhancement distinguish infarction, myocarditis, Takotsubo syndrome, and cardiomyopathies while also measuring function and thrombi; a territorial subendocardial or transmural pattern confirms ischemia; a subepicardial or mid-wall pattern points toward myocarditis. Yield decreases as edema and transient abnormalities resolve; a late negative CMR does not retrospectively make every suspicion false.
OCT provides resolution suitable for erosion, rupture, thrombus, and small dissections; IVUS is useful for the deep wall, hematoma, and large vessels. Examination is focused on the territory suggested by ECG, wall motion, and CMR because multivessel imaging increases contrast use and manipulation; in SCAD, the indication is restrictive because of the risk of extension or entry into the false lumen. An intracoronary finding must correlate with the myocardial territory: an incidental plaque does not prove causality.

Acetylcholine testing assesses epicardial and microvascular vasospasm. Epicardial spasm requires marked constriction associated with symptoms and ischemic changes; symptoms and ECG changes without epicardial narrowing support microvascular spasm in the appropriate context. Testing is deferred until after the unstable phase and performed at experienced centers with the ability to reverse the response rapidly. Noninvasive perfusion or CFR tests may document dysfunction but do not always replace invasive phenotyping.
The embolic work-up includes ECG and monitoring for atrial fibrillation, transthoracic echocardiography, and, when indicated, transesophageal echocardiography to assess the atrial appendage, valves, vegetations, and shunts. Blood cultures precede antibiotics when endocarditis is suspected. CT or ultrasound assesses systemic emboli; venous Doppler is targeted to suspected thrombosis. Antiphospholipid antibodies and inherited thrombophilia tests are requested in selected patients, recognizing that the acute phase and anticoagulants may alter results and require delayed confirmation.

The differential diagnosis includes myocarditis, Takotsubo syndrome, pulmonary embolism, aortic dissection, sepsis, heart failure, tachyarrhythmia, and kidney injury. MINOCA now indicates myocardial injury with nonobstructive coronary arteries as a working diagnosis, not necessarily an already confirmed infarction. Pulmonary embolism is investigated using clinical probability, D-dimer in appropriate contexts, and CT pulmonary angiography; the aorta with urgent imaging when signs require it. The conclusive diagnosis must state the mechanism and final diagnosis; if infarction is confirmed, it must be classified as primary, secondary, or procedure-related, avoiding the generic phrase “normal coronary arteries.”

Treatment and prognosis

During the initial phase, the patient is treated as having an acute coronary syndrome until anatomy and diagnosis are clarified. Aspirin, anticoagulation, and invasive reperfusion follow presentation and risk; fibrinolysis is reserved for STEMI within 12 hours of onset when primary PCI is expected to be unavailable within 120 minutes of diagnosis and no contraindications exist, but it may be harmful if the mechanism is SCAD or aortic dissection. After angiography, therapy must be reassessed rather than continued by inertia. Oxygen is indicated for hypoxemia, nitrates if tolerated, and analgesia should avoid masking instability.

With documented plaque disruption, management follows atherothrombotic prevention: antiplatelet therapy, high-intensity statin therapy, and intensive risk-factor control. DAPT duration depends on thrombus, any PCI, and ischemic and bleeding risks; specific evidence in MINOCA without stenting is limited. An ACE inhibitor or ARB is indicated with dysfunction, hypertension, or other conditions and may be considered in the overall vascular risk. PCI is reserved for a causally important lesion because stenting a nonobstructive plaque without need adds procedural risk.
In stable SCAD, a conservative strategy is preferred because of the high spontaneous healing rate and difficulty of PCI. Revascularization is considered for persistent ischemia, instability, arrhythmias, left main involvement, or high-risk anatomy; bypass surgery is selective; aspirin is often used, while intensity and duration of a second antiplatelet agent without stenting are individualized because randomized trials are lacking. A statin is not prescribed for SCAD itself but only for dyslipidemia or another indication; beta-blockade may reduce wall stress and is observationally associated with fewer recurrences.

Vasospasm requires calcium-channel blockers at an effective dose, sometimes combining classes, and long-acting nitrates for persistent symptoms. Smoking and vasoconstrictive substances must be stopped; a nonselective beta-blocker may aggravate pure vasospasm and is avoided unless otherwise needed with appropriate coverage. Microvascular dysfunction is treated according to phenotype with a beta-blocker, calcium-channel blocker, ACE inhibitor or ARB, ranolazine, and rehabilitation, recognizing that evidence is less robust. Control of blood pressure, lipids, and lifestyle remains central.
In embolism, aspiration or PCI may restore flow if thrombus persists; long-term anticoagulation depends on the source, not on the name MINOCA. Atrial fibrillation, ventricular thrombus, mechanical prosthetic valves, and antiphospholipid syndrome require different regimens; endocarditis requires antibiotics and cardiac surgical assessment. An incidental patent foramen ovale does not automatically justify closure. In secondary myocardial infarction, anemia, hypoxia, arrhythmia, or shock is corrected; DAPT and PCI are not automatic treatments for systemic imbalance.

Cardiac rehabilitation, graded activity, blood-pressure control, smoking cessation, and sleep management improve recovery. In SCAD, exercise is individualized, avoiding extreme loads and Valsalva maneuvers without imposing permanent inactivity; follow-up reassesses ejection fraction, arrhythmias, angina, and adherence, coordinating cardiology, imaging, and specialists for the identified mechanism. Communication must distinguish residual risk from temporary restrictions because indefinite instructions impair quality of life and mental health.
Prognosis depends more on the cause than on angiographic diameter. Complicated plaque carries atherothrombotic risk; SCAD may recur in other segments; vasospasm predisposes to arrhythmias and new episodes; embolism recurs if the source persists; reduced ejection fraction, shock, age, diabetes, and kidney disease worsen outcomes. A follow-up program must include measurable goals and diagnostic review because a “universal MINOCA” therapy lacks the necessary precision.

Complications

Heart failure and cardiogenic shock may result from extensive necrosis, stunning, right ventricular involvement, or a mechanical complication. Urgent echocardiography distinguishes hypovolemia, ventricular dysfunction, mitral regurgitation, and tamponade; coronary angiography is reassessed if ischemia persists; hemodynamic support follows the phenotype, not the term MINOCA. Severe Takotsubo syndrome may cause shock with or without dynamic outflow-tract obstruction, but once identified it is no longer considered a complication of ischemic MINOCA.
Ventricular arrhythmias occur during ischemia, reperfusion, or because of scar. Defibrillation and correction of potassium, magnesium, and ischemia are immediate; bradyarrhythmias may accompany spasm or inferior infarction; late risk depends on ejection fraction, CMR scar, and documented arrhythmias, not on the absence of stenosis. The decision about an implantable defibrillator follows general indications after reassessment and is not advanced solely because of a treatable acute episode.

Reinfarction may result from new plaque disruption, recurrent SCAD, spasm, or embolism. Recurrent pain requires ECG and troponin testing, but interpretation recognizes that the biomarker may not yet have normalized; repeat angiography is urgent with instability or signs of occlusion; otherwise, imaging and tests consistent with the known mechanism are used. Attributing every recurrence to the same cause produces errors because multiple phenotypes may coexist.
Stroke and systemic emboli indicate a persistent source, atrial fibrillation, or ventricular thrombus. Brain imaging precedes antithrombotic decisions in an acute neurological event; echocardiography and monitoring complete the investigation; an apical thrombus may occur with extensive akinesia despite nonobstructive coronary arteries and require temporary anticoagulation. Bleeding risk increases when anticoagulants and antiplatelet agents are combined without a clear indication or for a duration that is not reassessed.

SCAD may be complicated by extension, occlusion, recurrent ischemia, or recurrence in a different vessel. PCI carries risks of hematoma propagation, loss of the true lumen, and the need for long stents; even bypass grafts may lose patency when the native vessel heals; an iatrogenic dissection during imaging must be recognized and managed immediately. Screening of extracoronary arteries for fibromuscular dysplasia and aneurysms is planned with techniques and timing that limit contrast and radiation.
Uncontrolled vasospasm may cause syncope, atrioventricular block, ventricular tachycardia, and sudden death. Adherence to calcium-channel blockers and removal of triggers are decisive; a device is considered only after the mechanism has been adequately treated and residual risk assessed. In microvascular dysfunction, persistent symptoms and repeated visits may cause substantial disability even without extensive necrosis. A specialist pathway reduces fragmentation and enables phenotype-based therapy.

Psychological complications include post-event anxiety, depression, hypervigilance, and fear of exercise. They are particularly common when the patient receives a vague or contradictory diagnosis; assessment must not convert ischemic symptoms into somatization but should integrate mental health and rehabilitation after the causal work-up is complete. Written information on medications, activity, contraception or pregnancy when relevant, and warning signs supports autonomy and reduces uncoordinated visits.