STABLE ANGINA

Angina pectoris is the symptom complex caused by transient myocardial ischaemia and constitutes a clinical syndrome rather than a disease; it may occur whenever there is an imbalance between myocardial oxygen supply and demand (Box 18.54). Coronary atheroma is by far the most common cause of angina; however, the symptom may also be a manifestation of other forms of heart disease, particularly aortic valve disease and hypertrophic cardiomyopathy. This section describes the features of 'stable' angina pectoris which occurs when coronary perfusion is impaired by fixed or stable atheroma of the coronary arteries. page 581 page 582 18.54 FACTORS INFLUENCING MYOCARDIAL OXYGEN SUPPLY AND DEMAND Oxygen demand Cardiac work Heart rate Blood pressure Myocardial contractility Left ventricular hypertrophy Valve disease, e.g. aortic stenosis

Oxygen supply

Coronary blood flow Duration of diastole Coronary perfusion pressure (aortic diastolic minus coronary sinus or right atrial diastolic pressure) Coronary vasomotor tone Oxygenation Haemoglobin Oxygen saturation

N.B. Coronary blood flow occurs mainly in diastole.

18.55 ACTIVITIES PRECIPITATING ANGINA

Common

Physical exertion Cold exposure Heavy meals Intense emotion

Uncommon

Lying flat (decubitus angina) Vivid dreams (nocturnal angina)

Clinical features

The history is by far the most important factor in making the diagnosis; the features of cardiac pain and the differential diagnosis of chest pain are discussed on pages 534-539.

Stable angina is characterised by central chest pain, discomfort or breathlessness that is precipitated by exertion or other forms of stress (Box 18.55), and is promptly relieved by rest (Figs 18.15 and 18.16, pp. 535-536). Some patients find that the discomfort comes when they start walking, and that later it does not return despite greater effort ('warm-up angina').

Physical examination is frequently negative, but should include a careful search for evidence of valve disease (particularly aortic), important risk factors (e.g. hypertension, diabetes), left ventricular dysfunction (e.g. cardiomegaly, gallop rhythm), other manifestations of arterial disease (e.g. carotid bruits, peripheral vascular disease) and unrelated conditions that may exacerbate angina (e.g. anaemia, thyrotoxicosis).

Investigations

Resting ECG

The ECG may show evidence of previous myocardial infarction but is often normal even in patients with left main or severe three-vessel coronary artery disease. Occasionally, there is T-wave flattening or inversion in some leads, providing non-specific evidence of myocardial ischaemia or damage.

Figure 18.60 Forms of exercise-induced ST depression. Planar ST depression is usually indicative of myocardial ischaemia. Down-sloping depression also usually indicates myocardial ischaemia. Up-sloping depression, however, may be a normal finding.

18.56 A GUIDE TO RISK STRATIFICATION IN STABLE ANGINA

High risk	Low risk
Post-infarct angina	Predictable exertional angina
Poor effort tolerance	Good effort tolerance
Ischaemia at low workload	Ischaemia only at high workload
Left main or three-vessel disease	Single-vessel or minor two-vessel disease
Poor LV function	Good LV function
N.B. Patients may fall between these categories.

The most convincing ECG evidence of myocardial ischaemia is obtained by demonstrating reversible ST segment depression or elevation, with or without T-wave inversion, at the time the patient is experiencing symptoms (whether spontaneous or induced by exercise testing).

Exercise ECG

An exercise tolerance test (ETT) is usually performed using a standard treadmill or bicycle ergometer protocol (p. 528) while monitoring the patient's ECG, blood pressure and general condition. Planar or down-sloping ST segment depression of 1 mm or more is indicative of ischaemia (Fig. 18.60); up-sloping ST depression is less specific and often occurs in normal individuals.

Exercise testing can be used to confirm or refute a diagnosis of angina and is also a useful means of assessing the severity of coronary disease and identifying high-risk individuals (Box 18.56). For example, the amount of exercise which can be tolerated and the extent and degree of any ST segment change (Fig. 18.61) provide a useful guide to the likely extent of coronary disease.

Exercise testing is not infallible and may produce false positive results in the presence of digoxin therapy, left ventricular hypertrophy, left bundle branch block or Wolff-Parkinson-White syndrome. The predictive accuracy of exercise testing is lower in women than men. The test should be classed as inconclusive (and not negative) if the patient cannot achieve an adequate level of exercise because of locomotor or other non-cardiac problems.

Other forms of stress testing

Myocardial perfusion scanning

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Figure 18.61 A positive exercise test. The resting 12-lead ECG shows some minor T-wave changes in the inferolateral leads but is otherwise normal. After 3 minutes' exercise on a treadmill there is marked planar ST depression in leads II, V4 and V5 (right offset). Subsequent coronary angiography revealed critical three-vessel coronary artery disease.

This may be helpful in the evaluation of patients with an equivocal or uninterpretable exercise test and those who are unable to exercise; its predictive accuracy is higher than that of the exercise ECG. The technique involves obtaining scintiscans of the myocardium at rest and during stress after the administration of an inravenous radioactive isotope such as 99technetium tetrofosmin. It may be used in conjunction with conventional exercise testing or some form of pharmacological stress such as a controlled infusion of dobutamine. Thallium and tetrofosmin are taken up by viable perfused myocardium. A perfusion defect present during stress but not rest provides evidence of reversible myocardial ischaemia (Fig. 18.62), whereas a persistent perfusion defect seen during both phases of the study is usually indicative of previous myocardial infarction.

Stress echocardiography

This is an alternative to myocardial perfusion scanning and can achieve similar predictive accuracy (superior to exercise ECG). The technique uses transthoracic echocardiography to identify ischaemic segments of myocardium and areas of infarction. The former characteristically exhibit reversible defects in contractility during exercise or pharmacological stress with a dobutamine infusion; the latter typically do not contract at rest or during stress.

Coronary arteriography

In contrast to the functional information provided by stress testing, coronary arteriography provides detailed anatomical information about the extent and nature of coronary artery disease (Fig. 18.63), and is usually performed with a view to coronary bypass grafting or percutaneous coronary intervention (PCI-p. 586). In some patients, diagnostic coronary angiography may be indicated when non-invasive tests have failed to elucidate the cause of atypical chest pain. The procedure is performed under local anaesthesia and requires specialised radiological equipment, cardiac monitoring and an experienced operating team.

Management

The management of angina pectoris involves: a careful assessment of the likely extent and severity of arterial disease the identification and control of significant risk factors (e.g. smoking, hypertension, hyperlipidaemia) the use of measures to control symptoms the identification of high-risk patients and application of treatments to improve life expectancy.

Symptoms alone are a poor guide to the extent of coronary artery disease; exercise or pharmacological stress testing is therefore advisable in all patients who are potential candidates for revascularisation. An algorithm for the investigation and treatment of patients with stable angina is shown in Figure 18.64.

Treatment should start with a careful explanation of the problem and a discussion of the potential lifestyle and medical interventions that may relieve symptoms and improve prognosis (Box 18.57). Anxiety and misconceptions often contribute to disability; for example, some patients avoid all forms of exertion because they believe that each attack of angina is a 'mini heart attack' that results in permanent damage. Effective management of these psychological factors can make a huge difference to the patient's quality of life.

Antiplatelet therapy

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Figure 18.62 A technetium scan showing reversible anterior myocardial ischaemia. The images are cross-sectional tomograms of the left ventricle. The resting scans (right) show even uptake of technetium and look like doughnuts; during stress (in this case a dobutamine infusion) there is reduced uptake of technetium, particularly along the anterior wall (arrows), and the scans look like crescents (left).

Figure 18.63 Coronary angiogram from a patient with stable angina. There is severe stenosis of the left main stem (arrow).

Figure 18.64 A scheme for the investigation and treatment of stable angina on effort. (PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting)

18.57 ADVICE TO PATIENTS WITH STABLE ANGINA

Do not smoke Aim at ideal body weight Take regular exercise (exercise up to, but not beyond, the point of chest discomfort is beneficial and may promote collateral vessels) Avoid severe unaccustomed exertion, and vigorous exercise after a heavy meal or in very cold weather Take sublingual nitrate before undertaking exertion that may induce angina

Low-dose (75-150 mg) aspirin reduces the risk of adverse events such as myocardial infarction and should be prescribed for all patients with coronary artery disease indefinitely (Box 18.52). Clopidogrel (75 mg daily) is an equally effective antiplatelet agent that can be prescribed if aspirin causes troublesome dyspepsia or other side-effects.

Anti-anginal drug treatment

Four groups of drugs are used to help relieve or prevent the symptoms of angina: nitrates, β-blockers, calcium antagonists and potassium channel activators.

Nitrates

These drugs act directly on vascular smooth muscle to produce venous and arteriolar dilatation; their beneficial effects in angina are due to a reduction in myocardial oxygen demand (lower preload and afterload) and an increase in myocardial oxygen supply (coronary vasodilatation).

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Sublingual glyceryl trinitrate (GTN) administered from a metered-dose aerosol (400 μg per spray) or as a tablet (300 or 500 μg) allowed to dissolve under the tongue or crunched and retained in the mouth will usually relieve an attack of angina in 2-3 minutes. Unwanted side-effects include headache (which may be more distressing than the angina), symptomatic hypotension and, rarely, syncope. To avoid these symptoms the tablet may be spat out as soon as the angina is relieved.

Patients often need to be reassured that GTN is not habit-forming and will not lose its effect if used repeatedly. They should also be encouraged to use the drug prophylactically before engaging in exercise that is liable to provoke symptoms.

Sublingual GTN has a short duration of action (Box 18.58); however, a variety of alternative nitrate preparations can provide a more prolonged therapeutic effect. GTN can be given transcutaneously as a patch (5-10 mg daily), or as a slow-release buccal tablet (1-5 mg 6-hourly). GTN is subject to extensive first-pass metabolism in the liver and is therefore virtually ineffective when swallowed; however, other nitrates such as isosorbide dinitrate (10-20 mg 8-hourly) and isosorbide mononitrate (20-60 mg once or twice a day) can be given by mouth. Headache is common but tends to diminish if the patient perseveres with the treatment. Continuous nitrate therapy causes pharmacological tolerance and this should be avoided by using a regimen that includes a nitrate-free period of 6-8 hours every day. A variety of once-daily proprietary preparations with a built-in nitrate-free period are available. It is usually advisable to schedule the medication so that drug levels are low during the night when the patient is inactive; however, if nocturnal angina is a prominent symptom, long-acting nitrates can be given at the end of the day instead.

18.58 DURATION OF ACTION OF SOME NITRATE PREPARATIONS

Preparation	Peak action	Duration of action
Sublingual GTN	4-8 mins	10-30 mins
Buccal GTN	4-10 mins	30-300 mins
Transdermal GTN	1-3 hrs	Up to 24 hrs
Oral isosorbide dinitrate	45-120 mins	2-6 hrs
Oral isosorbide mononitrate	45-120 mins	6-10 hrs

Beta-blockers

These drugs lower myocardial oxygen demand by reducing heart rate, blood pressure and myocardial contractility. Unfortunately, they can exacerbate the symptoms of peripheral vascular disease and may provoke bronchospasm in patients with obstructive airways disease. The properties and side-effects of β-blockers are discussed above (p. 573).

In theory, non-selective β-blockers may aggravate coronary vasospasm by blocking the coronary artery β2-adrenoceptors and it is usually advisable to use a once-daily cardioselective preparation (e.g. atenolol 50-100 mg daily, slow-release metoprolol 50-200 mg daily, bisoprolol 5-10 mg daily).

A β-blocking drug should not be withdrawn abruptly because this may have a rebound effect and precipitate dangerous arrhythmias, worsening angina or myocardial infarction (the β-blocker withdrawal syndrome).

Calcium antagonists

These drugs inhibit the slow inward current caused by the entry of extracellular calcium through the cell membrane of excitable cells, particularly cardiac and arteriolar smooth muscle, and lower myocardial oxygen demand by reducing blood pressure and myocardial contractility.

Dihydropyridine calcium antagonists, such as nifedipine and nicardipine, often cause a reflex tachycardia; this may be counterproductive and it is often best to use these drugs in combination with a β-blocker. In contrast, verapamil and diltiazem are particularly suitable for patients who are not receiving a β-blocker because they inhibit conduction through the AV node and tend to cause a bradycardia or even atrioventricular block in susceptible individuals. The calcium antagonists may reduce myocardial contractility and can aggravate or precipitate heart failure. Other unwanted effects include peripheral oedema, flushing, headache and dizziness.

The dosage and some of the distinguishing features of these drugs are listed in Box 18.59.

Potassium channel activators

This class of drug has arterial and venous dilating properties but does not exhibit the tolerance seen with nitrates. Nicorandil (10-30 mg 12-hourly orally) is the only drug in this class currently available for clinical use.

18.59 CALCIUM ANTAGONISTS USED FOR THE TREATMENT OF ANGINA

Drug	Dose	Feature
Nifedipine	5-20 mg 8-hourly*	May cause marked tachycardia
Nicardipine	20-40 mg 8-hourly	May cause less myocardial depression than the other drugs in this group
Amlodipine	2.5-10 mg daily	Ultralong-acting
Verapamil	40-80 mg 8-hourly*	Commonly causes constipation; useful anti-arrhythmic properties (p. 573)
Diltiazem	60-120 mg 8-hourly*	Similar anti-arrhythmic properties to verapamil

* Once- or twice-daily slow-release preparations are available.

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Although each of these groups of drug has been shown to be superior to placebo in relieving the symptoms of angina, there is little convincing evidence that one group is more effective than another. Moreover, many commonly used combinations of anti-anginal drugs have not been evaluated in well-controlled clinical trials. Nevertheless, it is conventional to start therapy with low-dose aspirin, sublingual GTN and a β-blocker, and then add a calcium channel antagonist or a long-acting nitrate later, if necessary. The goal is the control of angina with minimum side-effects and the simplest possible drug regimen. There is little or no evidence that prescribing multiple anti-anginal drugs is of benefit, and revascularisation should be considered if an appropriate combination of two drugs fails to achieve a symptomatic response.

Invasive treatment

The most widely used invasive options for the treatment of ischaemic heart disease include percutaneous coronary intervention (PCI; including percutaneous transluminal coronary angioplasty, PTCA) and coronary artery bypass graft (CABG) surgery.

Percutaneous coronary intervention (PCI)

This is performed by passing a fine guidewire across a coronary stenosis under radiographic control and using it to position a balloon which is then inflated to dilate the stenosis (Fig. 18.14, p. 533 and Fig. 18.65). A coronary stent is a piece of coated metallic 'scaffolding' that can be deployed on a balloon and used to maximise and maintain dilatation of a stenosed vessel. The routine use of stents in appropriate vessels reduces both acute complications and the incidence of clinically important restenosis (Box 18.60).

PCI provides an effective symptomatic treatment but there is no evidence that it improves survival in patients with chronic stable angina. PCI is mainly used in single or two-vessel disease; stenoses in bypass grafts can be dilated as well as those in the native coronary arteries, and the technique is often used to provide palliative therapy for patients with recurrent angina after CABG. Coronary surgery is usually the preferred option in patients with three-vessel or left main disease, although recent trials have demonstrated that PCI is also feasible in such patients.

Figure 18.65 Percutaneous coronary intervention. A sequence of images from a 58-year-old woman with stable angina. Severe stenosis of the circumflex artery (arrow). A balloon has been advanced into the stenosis, over a guidewire, and has been inflated. (Note the waisting caused by the lesion.) Residual stenosis and dissection (tramline shadow-arrow) after balloon dilatation. A stent is deployed on a balloon. The stent is visible on plain fluoroscopy (arrow). Angiogram after stenting. A short balloon is used to dilate the stent at high pressure. Final result.

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18.60 ANGIOPLASTY AND INTRACORONARY STENTS IN ANGINA

'In comparison with simple balloon angioplasty, intracoronary stents afford superior acute and long-term clinical and angiographic results with lower rates of restenosis (e.g. 17% vs 40%) and recurrent angina (13% vs 30%).'

Versaci F, et al. N Engl J Med 1997; 336:817-822. Savage MP, et al. N Engl J Med 1997; 337:740-747.

For further information: http://www.nice.org.uk" target="_blank">www.nice.org.uk

18.61 PERCUTANEOUS CORONARY INTERVENTION VS MEDICAL THERAPY IN STABLE ANGINA

'PCI is more effective than medical therapy for alleviating angina pectoris and improving exercise tolerance but does not reduce mortality. It carries risks of procedure-related myocardial infarction, emergency coronary artery bypass grafting and repeat procedures for restenosis.'

Bucher HC, et al. BMJ 2000; 321:73-77. RITA-2 Trial participants. Lancet 1997; 350:461-468.

For further information: http://www.sign.ac.uk" target="_blank">www.sign.ac.uk

The main acute complications of PCI are occlusion of the target vessel or a side branch by thrombus or a loose flap of intima (coronary artery dissection), and consequent myocardial damage. This occurs in about 2-5% of procedures and can often be corrected by deploying a stent; however, emergency CABG is sometimes required. Minor myocardial damage, as indicated by elevation of sensitive intracellular markers (troponins), occurs in up to 10% of cases. The main long-term complication of PCI is restenosis (Box 18.61), which occurs in up to one-third of cases; this is due to a combination of elastic recoil and smooth muscle proliferation (neo-intimal hyperplasia) and tends to occur within 3 months. Stenting substantially reduces the risk of restenosis, probably because it allows the operator to achieve more complete dilatation in the first place. Drug-eluting stents can reduce this risk even further by allowing an antiproliferative drug, such as sirolimus or paclitaxel, to elute slowly from the coating and prevent neo-intimal hyperplasia and in-stent restenosis. Recurrent angina (affecting up to 15-20% of patients receiving an intracoronary stent at 6 months) may require further PCI or bypass grafting.

The risk of complications and the likely success of the procedure are closely related to the morphology of the stenoses, the experience of the operator and the presence of important comorbidity (e.g. diabetes, peripheral arterial disease). A good outcome is less likely if the target lesion is complex, long, eccentric or calcified, lies on a bend or within a tortuous vessel, involves a branch or contains acute thrombus.

In combination with aspirin and heparin, adjunctive therapy with potent platelet inhibitors, such as clopidogrel or glycoprotein IIb/IIIa receptor antagonists, has been shown to improve the outcome of PCI, with lower short- and long-term rates of death and myocardial infarction.

Coronary artery bypass grafting (CABG)

The internal mammary arteries, radial arteries or reversed segments of the patient's own saphenous vein can be used to bypass coronary artery stenoses (Figs 18.66 and 18.67). This usually involves major surgery under cardiopulmonary bypass, but in some cases, grafts can be applied to the beating heart: 'off-pump' surgery. The operative mortality is approximately 1.5%, but risks are higher in elderly patients, those with poor left ventricular function and those with significant comorbidity, such as renal failure.

Figure 18.66 Coronary artery bypass graft surgery. Narrowed or stenosed arteries are bypassed using saphenous vein grafts connected to the aorta, or by utilising the internal mammary artery.

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Figure 18.67 Three-dimensional reconstruction of multislice computed tomography of the heart. The image shows the patent saphenous vein grafts (SVG) to the right coronary artery (RCA), obtuse marginal branch (OM) and diagonal branch (LADD), and left internal mammary artery graft (LIMA) to the left anterior descending (LAD) coronary artery.

18.62 CORONARY ARTERY BYPASS GRAFTING (CABG) FOR STABLE ANGINA

'CABG is superior to medical treatment for at least 10 years after surgery in terms of survival. Greatest benefit occurred in those with a significant stenosis in the left main coronary artery or those with three-vessel disease and impaired ventricular function.'

Yusuf S, et al. Lancet 1994; 344:563-570. Davies RF, et al. Circulation 1997; 95:2037-2043.

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Approximately 90% of patients are free of angina 1 year after surgery, but fewer than 60% of patients are asymptomatic 5 or more years after CABG. Early post-operative angina is usually due to graft failure arising from technical problems during the operation or poor 'run off' due to disease in the distal native coronary vessels. Late recurrence of angina may be due to progressive disease in the native coronary arteries or graft degeneration. Less than 50% of vein grafts are patent 10 years after surgery. However, arterial grafts have a much better long-term patency rate with more than 80% of internal mammary artery grafts patent at 10 years. This has lead many surgeons to consider total arterial revascularisation (TAR) during CABG surgery. Aspirin (75-150 mg daily) and clopidogrel (75 g daily) have both been shown to improve graft patency, and one or other should be prescribed indefinitely if well tolerated. Intensive lipid-lowering therapy has also been shown to slow the progression of disease in the native coronary arteries and bypass grafts, and to reduce clinical cardiovascular events; serum LDL cholesterol concentrations should therefore be reduced below 3.2 mmol/l (∼120 mg/dl). There is substantial excess cardiovascular morbidity and mortality in patients who continue to smoke after bypass grafting. Persistent smokers are twice as likely to die in the 10 years following surgery compared with those who give up at surgery.

CABG has been shown to improve survival in patients with left main coronary stenosis, and symptomatic patients with three-vessel coronary disease (i.e. involving left anterior descending, circumflex and right coronary arteries, Box 18.62) or two-vessel disease involving the proximal left anterior descending coronary artery. Improvement in survival is most marked in those with impaired left ventricular function or positive stress testing prior to surgery and those who have undergone left internal mammary artery grafting.

Neurological complications are common, with a 1-5% risk of perioperative stroke. Between 30% and 80% of patients develop short-term cognitive impairment that is often mild and typically resolves within 6 months. There are also reports of long-term cognitive decline that may be evident in more than 30% of patients at 5 years.

PCI and CABG are compared in Boxes 18.63 and 18.64.

Prognosis

Symptoms are a poor guide to prognosis; nevertheless, the 5-year mortality of patients with severe angina (NYHA class III or IV, p. 534) is nearly double that of patients with mild symptoms. Exercise testing and other forms of stress testing are much more powerful predictors of mortality; for example, in one study, the 4-year mortality of patients with stable angina and a negative exercise test was 1%, compared to more than 20% in those with a strongly positive test.

18.63 COMPARISON OF PERCUTANEOUS CORONARY INTERVENTION (PCI) AND CORONARY ARTERY BYPASS GRAFTING (CABG)

	PCI	CABG
Death	< 0.5%	< 1.5%
Myocardial infarction*	2%	10%
Hospital stay	12-36 hrs	5-8 days
Return to work	2-5 days	6-12 weeks
Recurrent angina	15-20% at 6 months	10% at 1 year
Repeat revascularisation	10-20% at 2 years	2% at 2 years
Neurological complications	Rare	Common (see text)
Other complications	Emergency CABG Vascular damage related to access site	Diffuse myocardial damage Infection (chest, wound) Wound pain

* Defined as CK-MB > 2 ×normal, pp. 93-594.

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18.64 COMPARISON OF PERCUTANEOUS CORONARY INTERVENTION (PCI) VS CORONARY ARTERY BYPASS GRAFT (CABG) SURGERY IN STABLE ANGINA

'Systematic reviews and meta-analyses have found similar rates of death, myocardial infarction and quality of life. PCI is associated with a greater need for repeat procedures, although this has been halved by the introduction of intracoronary stent implantation. For patients with multi-vessel disease or diabetes, CABG appears to confer better survival rates at 4-5 years.'

Pocock SJ, et al. Lancet 1995; 346:1184-1189. Bypass Angioplasty Revascularisation Investigation (BARI) Investigators. N Engl J Med 1996; 335:217-225. Hoffman SN, et al. J Am Coll Cardiol 2003; 41:1293-1304.

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In general, the prognosis of coronary artery disease is related to the number of diseased vessels (one-, two- or three-vessel coronary artery disease) and the degree of left ventricular dysfunction. A patient with single-vessel disease and good LV function has an excellent outlook (5-year survival > 90%), whereas a patient with severe LV dysfunction and extensive three-vessel disease has a poor prognosis (5-year survival < 30%) without revascularisation.

Spontaneous symptomatic improvement due to the development of collateral vessels is common.

ANGINA WITH NORMAL CORONARY ARTERIES

Approximately 10% of patients who report stable angina on effort will be found to have angiographically normal coronary arteries. Many of these patients are women and the mechanism of their symptoms is often difficult to establish. It is important to review the original diagnosis and explore other potential causes.

Coronary artery spasm

Vasospasm in coronary arteries may coexist with atheroma, especially in unstable angina (see below); occasionally (< 1% of all cases of angina), however, vasospasm may occur without angiographically detectable atheroma. This form of angina is sometimes known as variant angina and may be accompanied by spontaneous and transient ST elevation on the ECG (Prinzmetal's angina). Calcium antagonists, nitrates and other coronary vasodilators (e.g. nicorandil) are the most useful therapeutic agents but may be ineffective.

Syndrome X

The constellation of typical angina on effort, objective evidence of myocardial ischaemia on stress testing, and angiographically normal coronary arteries is sometimes known as syndrome X. This disorder is poorly understood but carries a good prognosis and may respond to treatment with anti-anginal therapy.