Contemporary Diagnosis and Management of Patients With MINOCA

Authors, Journal, Affiliations, Type, DOI

• Authors: Jacqueline E. Tamis-Holland (Chair), Hani Jneid (Vice Chair), Harmony R. Reynolds, Stefan Agewall, Emmanouil S. Brilakis, Todd M. Brown, Amir Lerman, Mary Cushman, Dharam J. Kumbhani, Cynthia Arslanian-Engoren, Ann F. Bolger, John F. Beltrame; on behalf of AHA Interventional Cardiovascular Care Committee
• Journal: Circulation. 2019;139:e891–e908
• Affiliations: Multiple US academic centers
• Type: AHA Scientific Statement
• DOI: 10.1161/CIR.0000000000000670

Overview

MINOCA (Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease) occurs in 5–6% of all angiography-referred AMI patients and disproportionately affects younger women. This AHA Scientific Statement provides an updated formal definition anchored to the 4th Universal Definition of MI and a "traffic light" three-step diagnostic algorithm (exclude overt mimics → advanced imaging to exclude myocarditis/takotsubo → MINOCA confirmed). Six mechanistic causes are systematically catalogued — plaque disruption, epicardial vasospasm, coronary microvascular dysfunction, coronary embolism/thrombosis, SCAD, and supply-demand mismatch — each with targeted diagnostic and therapeutic recommendations. SWEDEHEART registry data (n=9,138, mean 4.1 years) provide the principal evidence base for medical management, showing benefit for statins and ACE inhibitors/ARBs but not for dual antiplatelet therapy.

Keywords

MINOCA, myocardial infarction, nonobstructive coronary artery disease, coronary vasospasm, microvascular disease, spontaneous coronary artery dissection, angiography

Key Takeaways

Epidemiology

• Prevalence: 5–6% of AMI (range 5–15% depending on population); confirmed in a large meta-analysis (n=6% of AMIs without obstructive CAD)
• Demographics: mean age 58 years (vs 61 years in AMI-CAD); women constitute ~50% of MINOCA vs ~25% in AMI-CAD; women with AMI are >2× as likely as men to have MINOCA
• Higher prevalence in Black, Maori, Pacific, and Hispanic populations
• Lower prevalence of traditional CAD risk factors (dyslipidemia, hypertension, diabetes, smoking) compared to AMI-CAD, though not uniformly

Definition and Diagnostic Criteria (Table 1)

Three criteria must all be met:

1. Acute MI per 4th Universal Definition: rise/fall of cTn with ≥1 value >99th percentile + corroborative clinical evidence (symptoms, ECG changes, new wall motion abnormality, imaging evidence, or coronary thrombus on angiography/autopsy)
2. Nonobstructive coronaries: no stenosis ≥50% in any major epicardial vessel on angiography (includes normal arteries, <30% irregularities, and 30–49% moderate atherosclerosis)
3. No specific alternate diagnosis: excludes sepsis, PE, myocarditis, and other non-ischemic causes

• Distinction from myocardial injury (nonischemic) vs myocardial infarction (ischemic) is fundamental
• Takotsubo syndrome is categorized separately (mechanism uncertain; no myocardial necrosis on CMR; 4th Universal MI Definition does not classify it as MI)
• FFR >0.80 in 30–49% lesions: still classifies as MINOCA

Traffic Light Diagnostic Algorithm (Figure 1)

• Red (stop — exclude overt causes): Clinically obvious alternate diagnoses (sepsis, PE, myocarditis) — no MINOCA label
• Yellow (caution — exclude subtle mimics): Re-review angiogram for overlooked obstructive CAD or SCAD; CMRI to exclude myocarditis, takotsubo, cardiomyopathy; intracoronary imaging (OCT/IVUS) if atherosclerosis present
• Green (go — MINOCA confirmed): Working diagnosis established; further mechanistic testing in specialized centres (provocative spasm testing, microvascular functional assessment, thrombophilia screen)
• CMRI strongly encouraged but absence of necrosis on CMR does not exclude MINOCA

Cause 1 — Plaque Disruption (Atherosclerotic)

• Encompasses plaque rupture, plaque erosion, and calcified nodule
• Found in ~1/3 of MINOCA patients on IVUS (Reynolds: 38%; Ouldzein: 37%); OCT likely detects more (especially erosion, not seen by IVUS)
• Plaque erosion more common in women, smokers, younger patients; rupture associated with thin-cap fibroatheroma and non-culprit lesion disruption
• Plaque disruption found in angiographically normal-appearing segments in ~50% of cases — OCT/IVUS recommended for all MINOCA patients with any angiographic atherosclerosis
• Management: Aspirin (mainstay); high-intensity statin; consider second antiplatelet (clopidogrel/ticagrelor); ACEi/ARBs if LV dysfunction; routine stenting not recommended

Cause 2 — Epicardial Coronary Vasospasm (Nonatherosclerotic)

• Intense vasoconstriction (>90%) of an epicardial coronary artery compromising myocardial blood flow
• Diagnosed in 46% of MINOCA patients undergoing provocative testing (Montone et al.)
• Asian predilection: Japanese (81%) and Korean (61%) post-discharge vasospasm positivity vs whites (15%)
• Gold-standard test: intracoronary acetylcholine boluses (20–100 μg over 20 s), angiographic evaluation; arrhythmias in 5% (comparable to spontaneous episodes); no procedure-related deaths in contemporary series
• Management: Calcium channel blockers (cornerstone); nicorandil; cilostazol; long-acting nitrates (tolerance issue); dual CCB for refractory cases; avoid β-blockers

Cause 3 — Coronary Microvascular Dysfunction (Nonatherosclerotic)

• Coronary microcirculation (<0.5 mm diameter vessels) accounts for ~70% of coronary resistance
• Impaired coronary flow defined by: CFR <2.0 on adenosine, or microvascular spasm on acetylcholine provocation (symptoms + ECG changes without epicardial spasm), or coronary slow flow phenomenon (≥3 beats to fill vessel at rest)
• Detected in 30–50% of chest pain patients with nonobstructive CAD; more common in women and those with CV risk factors
• Distinguishing microvascular dysfunction as cause vs consequence of MINOCA is challenging; 2/3 of female MINOCA patients showed inducible perfusion defects on stress CMR
• MINOCA is distinct from INOCA (ischemia with nonobstructive CAD) — INOCA patients do not have acute MI
• Management: CCBs and β-blockers for symptoms; ranolazine, dipyridamole (microvascular vasodilation); l-arginine, enalapril (endothelial function); imipramine, aminophylline (visceral analgesia); limited evidence base

Cause 4 — Coronary Embolism/Thrombosis (Nonatherosclerotic)

• Thrombosis may involve microcirculation or cause transient epicardial obstruction with spontaneous lysis
• Inherited thrombophilia: Factor V Leiden (5% general population; 12% in MINOCA by meta-analysis); protein C/S deficiency (3%); prothrombin 20210A; factor VIII/vWF elevation; OR for AMI 3.7 for factor V Leiden in young women
• Acquired hypercoagulable states: antiphospholipid syndrome (AMI in ~5% of APS patients; 7.5% of coronary embolism cases); HIT (heparin-PF4 antibodies; platelet decline ≥50%); TTP (microangiopathic hemolytic anemia + thrombocytopenia; AMI in 5.6% of TTP hospitalizations); myeloproliferative neoplasms
• Testing preferably after acute illness resolution; hematology consultation recommended
• Management: Antiplatelet or anticoagulant depending on cause; condition-specific therapies (plasma exchange + rituximab for TTP; heparin avoidance for HIT)

Cause 5 — Spontaneous Coronary Artery Dissection (SCAD)

• Most common AMI cause in women <50 years (prevalence up to 35%)
• SCAD usually produces some obstruction but may appear near-normal on angiography (Type II SCAD — diffuse smooth tapering)
• Mechanism: intimal tear or spontaneous medial hemorrhage → intramural hematoma → luminal compression; associated with fibromuscular dysplasia, emotional/physical stress, pregnancy (antepartum, early/late postpartum)
• Diagnosis requires angiographic review ± intracoronary OCT (preferred) or IVUS; care to avoid hydraulic extension of dissection during OCT
• Management: Conservative in most (PCI only for left main, haemodynamic instability, refractory ischemia); aspirin + β-blocker; clopidogrel controversial; avoid strenuous exercise and future pregnancy (expert opinion)

Cause 6 — Supply-Demand Mismatch (Type 2 MI)

• Secondary ischemic imbalance: tachyarrhythmias, anemia, hypotension, thyrotoxicosis; heterogeneous category
• Requires corroborating ischemic evidence beyond troponin alone — cannot be liberally applied to all elevated troponin in hypotension/tachycardia
• Management targets the underlying inciting cause; additional cardioprotective therapy individualized

Cardioprotective Therapy (SWEDEHEART Registry, n=9,138, mean 4.1 years)

• Statins: HR 0.77 (95% CI 0.68–0.87) — significantly lower composite outcome (mortality, reinfarction, heart failure, stroke)
• ACE inhibitors/ARBs: HR 0.82 (95% CI 0.73–0.93) — significantly lower composite outcome
• β-blockers: HR 0.86 (95% CI 0.74–1.01) — trend toward lower event rate, not significant
• Dual antiplatelet therapy: HR 0.90 (95% CI 0.74–1.08) — no significant benefit
• MINOCA-BAT trial (n≥3,500): prospective RCT comparing ACEi/ARBs + β-blockers vs placebo — results awaited at time of statement
• Standard AMI secondary prevention therapies should not be routinely applied to all MINOCA — individualize by underlying cause (e.g., CCBs for vasospasm, not β-blockers)

Prognosis

• MINOCA generally better prognosis than AMI-CAD, but outcome data are heterogeneous
• VIRGO study: similar 1-month and 1-year mortality rates to AMI-CAD in young patients
• ACTION-GWTG registry (n=19,000): in-hospital mortality 1.1%; no sex differences
• Meta-analysis: pooled in-hospital mortality 0.9%; 12-month mortality 4.7%
• ANZACS-QI: death or AMI in 4.6% at 2 years vs 2.2% in matched controls
• SWEDEHEART (mean 4.1 years): mortality 13.4%; re-MI 7.1%; ischemic stroke 4.3%; HF hospitalization 6.4%
• ~25% develop angina in the subsequent 12 months (comparable to AMI-CAD)
• Predictors of in-hospital mortality similar to AMI-CAD: age, troponin level, renal dysfunction; ST-elevation and shock/HF presentation are more strongly predictive in MINOCA than AMI-CAD

Limitations of the Document

• No prospective randomized controlled trials specifically in MINOCA patients at time of writing
• SWEDEHEART data are retrospective and observational; residual confounding possible
• Angiographic lesion severity assessment is highly subjective (substantial interobserver variability)
• CMR not universally available; absence of necrosis on CMR does not exclude MINOCA
• Asian data on vasospasm may not extrapolate to Western populations
• No specific ICD-10 code for MINOCA at time of writing (coded as I21.9 "other MI")
• MINOCA-BAT trial results not yet available

Key Concepts Mentioned

• concepts/MINOCA — central topic: definition, diagnostic algorithm, management
• concepts/Coronary-Vasospasm — epicardial vasospasm as cause of MINOCA; provocation testing
• concepts/Coronary-Microvascular-Dysfunction — microvascular angina/spasm/slow-flow as MINOCA cause
• concepts/Late-Gadolinium-Enhancement — CMRI role in MINOCA diagnosis; LGE to confirm myocardial necrosis and exclude myocarditis

Key Entities Mentioned

• entities/SCAD — spontaneous coronary artery dissection as MINOCA cause (not yet created)
• entities/Atrial-Fibrillation — tachyarrhythmia-associated supply-demand mismatch as Type 2 MI cause

Wiki Pages Updated

• wiki/sources/minoca-aha-2019.md (created)
• wiki/concepts/MINOCA.md (created)
• wiki/concepts/Coronary-Vasospasm.md (created)
• wiki/concepts/Coronary-Microvascular-Dysfunction.md (created)
• wiki/sources/cv-pregnancy-aha-2020.md (updated: MINOCA cross-link added)
• wiki/wikiindex.md (updated)
• wiki/sourceindex.md (updated)
• wiki/log.md (updated)