Microvascular angina:Diagnosis and treatment

Microvascular angina, also known as Cardiac Syndrome X, refers to a clinical syndrome characterized by typical symptoms of angina, positive electrocardiogram and/or exercise treadmill test results, with normal coronary angiography findings, and the exclusion of coronary artery spasm. Clinically, it can present as stable exertional angina or as unstable angina with increased frequency and intensity of attacks, which may occur at rest. Therefore, it is discussed in the guidelines for the diagnosis and treatment of stable coronary artery disease and non-ST elevation acute coronary syndrome (ACS).

Microvascular angina:Diagnosis and treatment
Microvascular angina:Diagnosis and treatment

The European Society of Cardiology guidelines for the management of stable coronary artery disease emphasize that microvascular angina should be considered when a patient has typical chest pain symptoms and the electrocardiogram and/or stress test suggest myocardial ischemia, but coronary angiography does not show fixed or dynamic obstructive epicardial coronary artery disease.

The diagnosis of microvascular angina primarily relies on patients having exercise-induced angina with normal coronary angiography or non-obstructive lesions (narrowing <50%), but with objective evidence of exercise-induced ST-segment depression or myocardial ischemia on stress imaging, with dobutamine stress echocardiography typically revealing wall motion abnormalities. This clinical situation is differentiated from coronary artery spasm-induced angina, which almost always occurs at rest, whereas the former, although it may also occur at rest, is more commonly related to physical activity.

The guidelines recommend the following objective tests for diagnosing microvascular angina:

  • 1.Consider exercise or dobutamine stress echocardiography to determine if there are segmental wall motion abnormalities consistent with angina and ST-segment changes;
  • 2.Transthoracic Doppler echocardiography may be considered to measure resting and post-adenosine intravenous left anterior descending artery diastolic flow, for non-invasive determination of coronary flow reserve (CFR);
  • 3.If coronary angiography is normal, intracoronary administration of acetylcholine or adenosine during the procedure can be considered, using Doppler techniques to assess endothelium-dependent and -independent coronary flow reserve, to detect microvascular or epicardial vessel spasm.

How is microvascular angina treated?

The treatment of microvascular angina emphasizes optimal control of coronary heart disease risk factors for all patients. Due to limited understanding of the etiology and lack of clinical studies showing improvement in outcomes, treatment is mainly aimed at symptom control. Among traditional anti-ischemic medications, short-acting nitrates are primarily used for relieving episodes of angina. As mentioned, the symptoms of microvascular angina are often related to exertion, thus beta-blockers are recommended as the first choice, especially effective in patients with increased heart rate at rest or during low-intensity exercise.

If beta-blockers do not fully control symptoms, calcium channel blockers and long-acting nitrates may be added. When there is significant variability in the pain threshold of exertional angina, which may be related to the state of vascular constriction, calcium channel blockers are considered for treatment. For patients whose symptoms persist despite optimal anti-ischemic treatment, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may be considered to counteract the vasoconstrictive effects of angiotensin II and improve microvascular function; small-scale studies have shown they can be beneficial in patients with hypertension or diabetes.

Nicorandil, which has both nitrate-like and potassium channel opening actions, selectively dilates microvessels and can improve exercise tolerance. Statins can alleviate angina symptoms by improving endothelial function. For patients with refractory angina who do not respond to the aforementioned combination therapy, xanthine derivatives like aminophylline or bamiphylline, which block adenosine receptors, can be considered to alleviate symptoms.

Due to the large variability in response to pharmacological treatment among patients with microvascular angina, it often requires repeated trials of different drug combinations to achieve an optimal effect. The guidelines recommend the following for the treatment of microvascular angina:

1.All patients should receive secondary prevention medications including aspirin and statins (Class I recommendation, Level B evidence);

2.Beta-blockers should be considered as first-line pharmacotherapy (Class I recommendation, Level B evidence);

3.If beta-blockers do not sufficiently control symptoms or are not tolerated, calcium channel blockers may be considered (Class I recommendation, Level B evidence);

4.In patients with refractory angina, the use of angiotensin-converting enzyme inhibitors or nicorandil may be considered (Class Ib recommendation, Level B evidence);

5.For patients who do not respond to the aforementioned pharmacotherapy, xanthine derivatives or neuromodulation techniques may be considered as non-pharmacological therapy (Class IIb recommendation, Level B evidence). Cardiac Syndrome X (also known as “microvascular angina”) is classified as a special type of stable angina. Its diagnosis also emphasizes the characteristics of exertion-induced chest pain, objective evidence of ischemia, or positive exercise tests, with normal coronary angiography, while also excluding coronary artery spasm.

The treatment principles proposed for microvascular angina similarly focus on controlling risk factors and actively improving symptoms through appropriate medication:

6.Use of nitrates, beta-blockers, and calcium channel blockers, either alone or in combination (Class I recommendation, Level B evidence);

7.Treatment with statins for patients with hyperlipidemia (Class I recommendation, Level B evidence);

8.Use of ACEIs for patients with hypertension or diabetes (Class I recommendation, Level B evidence);

9.Consideration of other anti-anginal medications, including nicorandil and metabolic agent trimetazidine (Class IIa recommendation, Level C evidence);

10.For persistent angina despite Class I recommended medications, a trial of aminophylline may be considered (Class Ib recommendation, Level C evidence);

11.For persistent angina despite Class I recommended medications, a trial of antidepressants may be considered (Class Ib recommendation, Level C evidence). Despite the various pharmacological treatments proposed for microvascular angina, including common medications for coronary artery disease, clinical efficacy has been suboptimal.

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