What is the diagnosis and treatment for microvascular angina (cardiac syndrome X)?

From the Guidelines

Microvascular angina, also known as cardiac syndrome X, should be treated with a personalized approach, considering the underlying mechanisms of microcirculatory dysfunction, and typically includes medications such as beta-blockers, calcium channel blockers, and nitrates to reduce symptoms, as recommended by the 2024 ESC guidelines for the management of chronic coronary syndromes 1. The condition is characterized by chest pain due to reduced blood flow to the heart muscle through the small coronary blood vessels, despite normal-appearing major coronary arteries.

Diagnosis and Treatment

• The diagnosis of microvascular angina involves invasive coronary reactivity testing, including prognostic evidence from the WISE study, and PET measurement of peak myocardial blood flow and MBFR, when reduced, reflects abnormalities of flow 1.
• Treatment should address the dominant mechanism of microcirculatory dysfunction, and may include:
  • Beta-blockers, such as metoprolol 25-100 mg twice daily, to reduce symptoms and improve coronary flow reserve 1.
  • Calcium channel blockers, such as amlodipine 5-10 mg daily, to control symptoms and prevent ischemia 1.
  • Nitrates, such as isosorbide mononitrate 30-60 mg daily, to prevent recurrent episodes and reduce symptoms 1.
  • ACE inhibitors, such as ramipril 2.5-10 mg daily, to improve endothelial function and symptom control 1.
  • Statins, such as atorvastatin 10-40 mg daily, to improve vascular function and reduce cardiovascular risk 1.

Lifestyle Modifications

• Lifestyle modifications are crucial, including:
  • Regular exercise to improve cardiovascular health and reduce symptoms.
  • Smoking cessation to reduce cardiovascular risk and improve endothelial function.
  • Weight management to reduce cardiovascular risk and improve overall health.
  • Stress reduction techniques, such as meditation or yoga, to reduce stress and improve quality of life. The condition results from dysfunction of the small coronary blood vessels that fail to dilate properly in response to increased oxygen demand, leading to ischemia despite open major coronary arteries, and can significantly impact quality of life, though it generally has a better prognosis than obstructive coronary artery disease 1.

From the Research

Diagnosis of Microvascular Angina

• Microvascular angina (MVA) is defined as angina pectoris caused by abnormalities of small coronary arteries 2
• Diagnosis is typically characterized by angina attacks mainly caused by effort, evidence of myocardial ischemia on non-invasive stress tests, but normal coronary arteries at angiography 2
• The gold standard diagnostic test for microvascular coronary dysfunction (MCD) is the invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test endothelial-dependent and -independent microvascular and macrovascular coronary function 3

Treatment of Microvascular Angina

• Treatment of MVA is initially based on standard anti-ischemic drugs (beta-blockers, calcium antagonists, and nitrates), but control of symptoms is often insufficient 2
• Additional drugs with different potential anti-ischemic effects have been proposed, including ranolazine, ivabradine, angiotensin-converting enzyme (ACE) inhibitors, xanthine derivatives, nicorandil, statins, alpha-blockers, and estrogens in perimenopausal women 2
• Angiotensin-converting enzyme inhibition has been shown to lessen exercise-induced ischemia in patients with syndrome X and microvascular angina, probably by a direct modulation of coronary microvascular tone 4
• Current pharmacotherapy for MCD may include treatment of microvascular endothelial dysfunction (with statins, angiotensin-converting enzyme inhibitors, or low-dose aspirin), as well as treatment for angina and myocardial ischemia (with β-blockers, calcium channel blockers, nitrates, or ranolazine) 3
• A comprehensive treatment approach aimed at risk factor management, including lifestyle counseling regarding smoking cessation, nutrition, and physical activity, should be initiated 3
• Additional symptom management techniques may include tricyclic medication, enhanced external counterpulsation, hypnosis, and spinal cord stimulation 3

Treatment Efficacy and Enrolment Criteria

• Despite improvements in recognition and diagnosis, uncertainty remains around the most effective treatment strategy for MVA, and more data are needed 5
• A systematic review of treatment studies for MVA found that only a quarter of studies enrolled patients who met contemporary diagnostic criteria for definitive MVA 5
• Ranolazine is the most well-studied intervention drug, but double-blind randomized controlled trials have shown inconsistent improvements in Seattle Angina Questionnaire scores and coronary flow reserve with short-term follow-up 5
• Larger studies with robust selection criteria, blinded patient-reported outcomes, and long-term follow-up are needed to support any specific treatment intervention 5