Management of Microvascular Angina and MINOCA

Diagnosis and Characterization

• Microvascular Angina (MVA) is characterized by angina due to dysfunction of the coronary microcirculation, with evidence of ischemia during stress testing and abnormal coronary microvascular function testing, including increased microvascular resistance (IMR ≥25), reduced coronary flow reserve (CFR <2.0), and reduced resistive reserve ratio (<2.0) 1
• MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) is defined as acute myocardial infarction with angiographically no obstructive coronary artery disease (stenosis ≤50%), with confirmation of MI criteria, absence of obstructive coronary disease, and no other overt cause for the clinical presentation 2

Treatment

• The American College of Cardiology recommends calcium channel blockers as first-line therapy for MVA and MINOCA, particularly for vasospastic forms, with a success rate of preventing spasm in ~90% of patients 3
• Beta-blockers are preferred for MVA with evidence of increased adrenergic activity, but are contraindicated in vasospastic angina as they can precipitate spasm by leaving α-mediated vasoconstriction unopposed 3
• Ranolazine is particularly beneficial in patients with impaired coronary flow reserve 3
• Baseline therapy for all patients includes aspirin, statins, ACE inhibitors, and sublingual nitroglycerin as needed, with consideration of smoking cessation and lifestyle modifications 1
• Long-acting nitrates are effective when used with calcium channel blockers for vasospastic angina, but require intermittent administration to prevent nitrate tolerance, with a recommended daily nitrate-free interval of 10-12 hours 3, 4, 5, 6
• Typical dosages for isosorbide mononitrate (ISMN) are 20 mg twice daily (standard) or 60-240 mg once daily (slow-release), and for isosorbide dinitrate (ISDN), 5-80 mg 2-3 times daily or 40 mg 1-2 times daily (slow-release) 6
• The European Heart Society recommends trimetazidine for microvascular angina, which can be used as part of initial treatment in properly selected patients, with a recommendation grade based on clinical evidence 7, 3
• Ivabradine improves coronary collateral flow and coronary flow reserve, with superior effects compared to bisoprolol despite similar degrees of heart rate reduction, and can be considered when beta-blockers are contraindicated 3, 7

Special Considerations

• Patients with atrioventricular conduction defects should avoid beta-blockers and non-dihydropyridine calcium channel blockers 3
• Patients with hyperthyroidism should consider non-selective beta-blockers or diltiazem/verapamil if beta-blockers are contraindicated 3
• Patients with enhanced pain perception should consider adenosine antagonists or tricyclic antidepressants (e.g., imipramine) 3
• For MINOCA patients, management should be guided by the identified underlying cause, with cardiac MRI recommended in all patients without an obvious underlying cause 2
• Concomitant use of nitrates with phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) is an absolute contraindication due to the risk of profound hypotension, and nitrates should be avoided within 24 hours of sildenafil and 48 hours of tadalafil 5, 8
• Common side effects of nitrates include headache, hypotension, and flushing, with ISMN being better tolerated, and monitoring of blood pressure is recommended, especially when initiating therapy or increasing doses 4, 5, 6
• Treatment response should be monitored closely, as microvascular angina often has a variable response to different drug treatments, and consideration should be given to tapering and discontinuing treatment 6-12 months after angina has disappeared, as spontaneous remission occurs in about half of patients, with a recommendation grade based on clinical evidence 3, 4

Treatment Approach

• For vasospastic angina, treatment should start with high-dose calcium channel blockers (preferably second-generation like amlodipine), followed by addition of long-acting nitrates if symptoms persist, with a recommended treatment approach based on clinical guidelines 3, 4
• For microvascular angina, treatment should start with ranolazine or trimetazidine, considering beta-blockers if evidence of increased adrenergic activity, and adding ivabradine if heart rate control is needed but beta-blockers are contraindicated, with a recommended treatment approach based on clinical guidelines 3, 7, 4