Microvascular angina

Synonyms: microvascular angina

What is microvascular angina?

Microvascular Angina (previously known as Cardiac syndrome X (CSX)) is characterised by angina-like chest discomfort, ST-segment depression during exercise, and normal coronary arteries at angiography. CSX is much more common in women than in men. CSX is not necessarily benign and is linked to adverse cardiovascular outcomes and a poor quality of life.^{1 2 3}

There is no standard agreed definition for CSX.⁴ There are numerous causes for chest pain in patients with CSX that range from non-cardiac to coronary microvascular dysfunction (CMD).⁵ However, the term CSX is often used synonymously with CMD.

Myocardial ischaemia may result from different types of functional disease involving the coronary arteries (eg, coronary artery vasospasm), the coronary microcirculation or both. An accurate assessment of these components after exclusion of organic coronary artery disease (CAD) is very important because a correct diagnosis has relevant prognostic and therapeutic implications.²

There is a separate Coronary Artery Vasospasm article. The remainder of this article is mainly focused on CMD. The cause of microvascular angina seems very likely to be organic and functional abnormalities of the small arteries of the heart.⁶

Diabetes mellitus, coronary artery spasm, left ventricular hypertrophy and cardiomyopathy preclude the diagnosis of CMD.⁷

How common is microvascular angina? (Epidemiology)⁸

The prevalence of microvascular angina appears to have increased over the past few years because of increased diagnostic imaging, with a recent study reporting that of 400,000 individuals undergoing diagnostic angiography for suspected coronary artery disease, over 50% were found to have either no coronary artery disease or non-obstructive coronary artery disease.

Recent studies also showed that coronary microvascular dysfunction is identified in 4 in 5 patients with suspected microvascular angina or vasospastic angina.

Coronary microvascular dysfunction can occur in both men and women but recent reports and studies indicate that it is more prevalent in women (especially post-menopause).

Risk factors

These are in common with CAD and include:⁹

• Hypercholesterolaemia.

• Smoking.

• Obesity.

• Hypertension.

• Insulin resistance or overt diabetes mellitus.

• Low-grade chronic inflammation.

Microvascular angina symptoms (presentation)⁸

Patients with microvascular angina can present with exertional retrosternal chest pain/pressure or discomfort or have exertional dyspnoea. Symptoms may also develop during exercise, after exercise or even at rest and are relatively less likely to be relieved by nitrates compared with obstructive coronary artery disease.

Duration of symptoms are variable, tend to be prolonged and may differ in nature, ie stabbing pain, jaw pain or back pain.

Although symptoms can be the initial presentation in microvascular angina, there is a high prevalence of silent ischaemia in women with coronary microvascular dysfunction.

Signs

There are no characteristic clinical signs but examination may reveal underlying cardiovascular risk factors - eg, hypertension and obesity.

See also the article on Stable Angina.

Differential diagnosis¹⁰

The whole spectrum of causes of chest pain must be considered. See the separate Chest Pain and Cardiac-type Chest Pain Presenting in Primary Care articles. However, possible differential diagnoses for special consideration are:

• CAD.

• Coronary artery vasospasm.

• Cardiomyopathy.

Investigations⁸

Investigations should be as for CHD:

• FBC (to exclude anaemia or polycythaemia).

• U&E (if starting an angiotensin-converting enzyme (ACE) inhibitor).

• LFTs (before starting a statin).

• Fasting lipids (with a view to adjustment by diet or drugs).

• Fasting blood glucose (may show impaired glucose tolerance or overt diabetes).

Non-cardiac aetiologies of chest pain, including musculoskeletal, psychiatric, gastrointestinal and pulmonary disorders, must be excluded. Those with angina-like chest pain and even some with atypical features, including more frequent or persistent pain and inconsistent response to sublingual nitrates, should undergo stress testing.

Investigations for microvascular angina include non-invasive methods such as:

• Transthoracic Doppler, contrast echocardiography.

• Cardiac positron emission tomography (PET).

• Cardiac MRI.

• Cardiac CT.

Invasive testing¹¹

Coronary microvascular function in patients with angina and non-obstructive coronary artery disease should be evaluated invasively. The two tools that could be used are an intracoronary Doppler wire or an intracoronary thermodilution-derived method that measure the response of coronary blood flow under vasoactive stimuli. The most used is the thermodilution method.

Adenosine is the drug usually used for this aim at the dose of 140 μg/Kg/min that could be administered intravenously or intracoronary. However, the diagnostic accuracy is improved by the use of intracoronary acetylcholine that induces in normal patients a microvascular dilation.

Technical innovations have enabled the measurement of absolute coronary flow and minimal microvascular resistance by continuous thermodilution through the use of a dedicated microcatheter and dual-sensor intracoronary guidewires.

Microvascular angina treatment and management⁸

Treatment of CSX includes lifestyle modification and anti-anginal, anti-atherosclerotic and anti-ischaemic medications.

Non-pharmacological options include cognitive behavioural therapy, enhanced external counterpulsation, neurostimulation and stellate ganglionectomy.¹

Effective treatment of microvascular angina requires aggressive risk factor modification (exercise is one of the most effective treatment modalities). Several other treatment strategies have been shown to relieve anginal symptoms as well as improve vascular function, including beta-blockers, ACE inhibitors, ranolazine, L-arginine and statins. Oestrogen replacement therapy may also have a role for affected women. Nitrates may be effective for symptom relief.¹²

Other treatments include relaxation techniques, hypnotherapy and cognitive behavioural therapy.

General measures

• Exercise regimes have a beneficial effect.¹³

• Weight loss reduces insulin resistance.

• Stop smoking if applicable.

Pharmacological¹¹

The current medical therapy for angina in patients with obstructive coronary artery disease, like beta-blockers and calcium channel blockers, is the standard treatment for microvascular angina.

• Medications for the control of blood pressure, like ACE inhibitors, are demonstrated to improve coronary flow reserve in coronary microvascular disfunction and can be easily combined with other antianginal drugs like beta-blockers and calcium antagonists.

• Beta-blockers with vasodilatory properties like nebivolol and carvedilol have been shown to be the most effective.

• Calcium channel blockers like amlodipine, verapamil and diltiazem, induce vascular smooth muscle cell relaxation by blocking the influx of calcium and reduce the myocardial oxygen consumption.

• Ranolazine may improve exercise capacity and symptoms, decreasing calcium and sodium overload in cardiac cells, due to the inhibition of late inward sodium.

Other treatments⁵

Spinal cord stimulators and enhanced external counterpulsation (EECP) have been studied in patients with chest pain without obstructive CAD. Spinal stimulation is believed to modulate pain-related nerve signals and increase myocardial blood flow though effects on sympathetic tone. EECP increases diastolic blood flow to the heart.

Prognosis¹⁴

Patients with coronary microvascular disfunction have been reported to have a poor prognosis due to several factors like impaired quality of life and higher risk of major cardiovascular adverse events, especially in the postmenopausal women.

Patients with microvascular angina have a 1.5-fold increase in mortality compared with those without any evidence of myocardial ischaemia. In addition, more than 40% of patients are re-admitted to the hospital for chest pain and 30% undergo repeat coronary angiography. They also have a worse quality of life when compared to healthy counterparts.

Therefore, many patients with chest pain, without significant obstruction on coronary angiography, are often inappropriately reassured and remain untreated.

Prevention

The risk factors for coronary microvascular disfunction are similar to those for obstructive coronary artery disease. Therefore see also the article on Prevention of Cardiovascular Disease.