What is the management approach for patients with Ischemia with No Obstructive Coronary Artery (INOCA) and Myocardial Infarction with No Obstructive Coronary Artery (MINOCA)?

Management of INOCA and MINOCA

For MINOCA, immediately follow a systematic diagnostic algorithm starting with cardiac magnetic resonance (CMR) imaging to identify the underlying cause, then treat according to the specific etiology identified; for INOCA, perform invasive coronary function testing to determine the mechanism of ischemia and guide targeted therapy. 1

MINOCA: Diagnostic Approach

Initial Working Diagnosis

• All patients with suspected MINOCA must follow a structured diagnostic algorithm to differentiate true MINOCA from alternative diagnoses (Class I recommendation). 1
• Confirm diagnostic criteria: evidence of acute MI with troponin elevation AND non-obstructive coronary arteries (<50% stenosis) on angiography. 1, 2
• Immediately assess left ventricular wall motion using either LV angiography or echocardiography in the acute setting to identify regional wall motion abnormalities. 1

Essential Diagnostic Testing

• Perform CMR in all MINOCA patients without an obvious underlying cause (Class I, Level B recommendation). 1
• CMR can identify the underlying cause in up to 87% of MINOCA cases, differentiating between Takotsubo syndrome, myocarditis, or true MI. 1
• Perform CMR within 2 weeks of symptom onset to maximize diagnostic accuracy. 1
• Consider intracoronary imaging with IVUS or OCT when thrombus, plaque rupture/erosion, or spontaneous coronary artery dissection (SCAD) are suspected. 1

Exclude Alternative Diagnoses

• Rule out pulmonary embolism with D-dimer testing, BNP, and/or CT pulmonary angiography as appropriate. 1
• Consider supply-demand mismatch conditions: hypertensive crisis, tachyarrhythmias, sepsis, severe anemia, and cardiac contusion. 1, 2
• Exclude non-cardiac causes of troponin elevation before finalizing MINOCA diagnosis. 2

MINOCA: Treatment Strategy

Mechanism-Based Treatment

• Treat according to the specific underlying cause identified (Class I recommendation). 1
• For vasospastic angina: calcium channel blockers and nitrates. 1, 2
• For plaque disruption/thromboembolism: aspirin plus consideration of dual antiplatelet therapy (DAPT) based on pathophysiological considerations, though evidence is limited. 1
• For Takotsubo syndrome: supportive care and beta-blockers. 2
• For myocarditis: anti-inflammatory treatment as appropriate. 2

Unknown Etiology (8-25% of cases)

• When the cause remains undetermined despite optimal workup, target the most probable mechanisms: vasospastic angina, coronary plaque disruption, and thromboembolism. 1
• Consider treatment according to secondary prevention guidelines for atherosclerotic disease (Class IIb, Level C recommendation). 1
• The benefit of DAPT should be considered based on pathophysiological reasoning, recognizing that evidence is scarce. 1

INOCA: Diagnostic Approach

Recognition and Initial Evaluation

• INOCA occurs in 30-50% of patients undergoing invasive coronary angiography, with higher prevalence in women (50-70%) than men (30-50%). 1
• Consider INOCA early during cardiovascular risk stratification and throughout the diagnostic workup. 1
• Recognize that multiple mechanisms frequently contribute to ischemia; the presence of coronary stenosis does not exclude other pathways. 1

Non-Invasive Testing

• Prefer PET imaging over SPECT for initial non-invasive testing, as PET quantifies myocardial blood flow and provides information about both CMD and CAD with low radiation exposure. 1
• Consider stress CMR or transthoracic Doppler of the LAD during stress echocardiography to determine coronary flow reserve (Class IIb, Level B). 1
• Consider ambulatory ECG monitoring in patients with suspected vasospastic angina (Class IIa, Level B), though absence of ST elevation during symptoms does not rule out spasm. 1

Invasive Coronary Function Testing (CFT)

• Perform invasive coronary angiography with availability of invasive functional assessment in patients with uncertain diagnosis after non-invasive testing (Class I, Level B recommendation). 1
• Alert the invasive cardiologist to the need for CFT at the time of referral to ensure comprehensive evaluation during the procedure. 1
• Invasive comprehensive testing is preferred when there is low-threshold angina. 1
• In persistently symptomatic patients with poor quality of life despite medical therapy, perform invasive CFT after considering patient preferences (Class I, Level B). 1
• Comprehensive CFT includes assessment of intracoronary pressure and flow (coronary flow reserve, index of microcirculatory resistance) and provocative testing for coronary artery spasm. 1

Prevalence of Mechanisms

• Among ANOCA patients tested with acetylcholine, 80% show endothelial dysfunction, 60% have microvascular angina/vasospastic angina, and 50% have impaired coronary flow reserve and/or high microvascular resistance. 1
• This emphasizes the importance of testing all ANOCA patients to determine the specific endotype for appropriate treatment. 1

INOCA: Treatment Strategy

Mechanism-Based Therapy

• Use a patient-centered, mechanism-based approach to medical treatment based on CFT results to improve symptoms and quality of life. 1
• Target the specific mechanisms identified: coronary microvascular disease, epicardial coronary artery spasm, myocardial bridging, or diffuse non-obstructive atherosclerosis. 1
• Recognize that coronary microvascular dysfunction and coronary artery spasm are frequent causes of residual angina after coronary revascularization. 1

Current Treatment Limitations

• Current treatments remain largely empirical, representing a major unmet need. 1
• Benefits of antithrombotic therapy in INOCA are uncertain. 1
• Adjunctive non-pharmacologic treatments (neuromodulation, therapeutic angiogenesis, coronary sinus reducer therapy) require further study. 1

Common Pitfalls to Avoid

• Do not assume normal coronary arteries exclude ischemic heart disease—consider structural and functional abnormalities at all levels of the vasculature. 1
• Do not delay CMR in MINOCA patients—perform within 2 weeks to maximize diagnostic yield. 1
• Do not fail to perform comprehensive diagnostic workup—failure to identify the underlying cause results in inappropriate treatment and inadequate counseling. 3
• Do not overlook the need for CFT at the time of initial angiography—alert the invasive cardiologist beforehand to avoid repeat procedures. 1
• Do not assume absence of ST elevation on ambulatory monitoring rules out coronary spasm—provocative testing may still be positive. 1