Stable And Variant Angina
Angina pectoris is an episodic pain or crushing and/or squeezing sensation in the chest caused by reversible myocardial ischaemia. The discomfort may radiate into the neck, jaw and arms (particularly the left) and, more rarely, into the back. Other common symptoms include shortness of breath, abdominal pain and dizziness. Syncope (unconsciousness) occurs infrequently. Ischaemia can produce classic angina or may be totally silent without any symptoms. The clinical outlook from silent ischaemia is similar to symptomatic angina.
Three forms of angina are recognized. Stable and variant angina are discussed below, and unstable angina is described in Chapter 42.
Figure 40 shows the factors that determine myocardial O2 supply and demand. O2 demand is determined by heart rate, left ventricular contractility and systolic wall stress, and therefore increases with exercise, hypertension and left ventricular dilatation (e.g. during chronic heart failure). Myocardial O2 supply is primarily determined by coronary blood flow and coronary vascular resistance, which mostly occurs at the level of the intramyocardial arterioles. With exercise the coronary blood flow can increase to four to six times baseline, which is the normal coronary flow reserve (see Chapter 23).
Stable or exertional (typical) angina arises when the flow reserve of one or more coronary arteries is limited by a significant structural stenosis (>70%) resulting from atherosclerotic coronary heart disease. Stenoses typically develop in the epicardial region of arteries, within 6 cm of the aorta. Under resting conditions, cardiac O2 demand is low enough to be satisfied even by a diminished coronary flow. However, when exertion or emotional stress increases myocardial O2 demand, dilatation of the non-diseased areas of the artery cannot increase the supply of blood to the heart because the stenosis presents a fixed non-dilating obstruction. The resulting imbalance between myocardial O2 demand and supply causes myocardial ischaemia. Ischaemia develops mainly in the subendocardium, the inner part of the myocardial wall. This is because the blood flow to the left ventricular wall occurs mainly during diastole as a result of arteriolar compression during systole. The arterioles of the subendocardium are compressed more than those of the mid or subepicardial layers, so that the subendocardium is most vulnerable to a relative lack of O2.
In addition to causing pain, ischaemia causes a decline in myocardial cell high-energy phosphates (creatine phosphate and ATP). As a result, both ventricular contractility and diastolic relaxation in the territory of affected arteries are impaired. Consequences of these events may include a fall in cardiac output, symptoms of pulmonary congestion and activation of the sympathetic nervous system. Stable angina is almost always relieved within 5–10 min by rest or by nitroglycerin, which reduces cardiac O2 demand.
Some patients with stable angina may have excellent effort tolerance one day, but develop angina with minimal activity on another day. Contributing to this phenomenon of variable threshold angina is a dynamic endothelial dysfunction which often occurs in patients with coronary artery disease. The endothelium normally acts via nitric oxide to dilate coronary arteries during exercise. If this endothelium-dependent vasodilatation is periodically impaired, exercise may result in paradoxical vasoconstriction due to the unopposed vasoconstricting effect of the sympathetic nervous system on coronary α-receptors.
Variant angina, also termed vasospastic or Prinzmetal’s angina, is an uncommon condition in which myocardial ischaemia and pain are caused by a severe transient occlusive spasm of one or more epicardial coronary arteries. Patients with variant angina may or may not have coronary atherosclerosis, and in the former case, vasospasm often occurs in the vicinity of plaques. Variant angina occurs at rest (typically in the early morning hours) and may be intensely painful. It is exacerbated by smoking, and can be precipitated by cocaine use. About 30% of these patients show no evidence of coronary atherosclerotic lesions. Vasospasm is thought to occur because a segment of artery becomes abnormally over- reactive to vasoconstricting agents (e.g. noradrenaline, serotonin). There is also evidence that flow-mediated vasodilatation, a function of the endothelium, is impaired in the coronary arteries of patients with variant angina, and that this endothelial dysfunction may be due to oxidative stress (see Chapter 24).
Ischaemic heart disease and stable angina can be distinguished from other conditions causing chest pain (e.g. neuromuscular dis- orders, gastroesophageal reflux) based on characteristic anginal symptoms and several types of diagnostic investigation. Although resting ST/T wave changes indicate severe underlying coronary artery disease, the resting ECG is often normal. In this case, the presence of ischaemic heart disease can be unmasked by an exercise stress test, during which patients exercise at progressively increasing levels of effort on a stationary bicycle or treadmill. Development of cardiac ischaemia is revealed by chest pain, ECG changes including ST segment depression or elevation, arrhythmias, or a fall in blood pressure due to reduced ventricular contractility. The degree of effort at which these signs develop indicates the severity of ischaemia.
The exercise stress test is less useful in uncovering ischaemiarelated ECG changes if the baseline ECG is already abnormal due to factors such as left bundle branch block. In such patients, techniques designed to visualize ischaemic myocardium can be combined with the stress test to increase its specificity. Thallium-201 is an isotope that is taken up by normal but not ischaemic or previously infarcted myocardium. It is given intravenously during the stress test, and a gamma camera is used to image its distribution in the heart both immediately and also after the test, when ischaemia has subsided. A region of exercise-induced ischaemia will cause a ‘cold spot’ during but not after the stress test, because it will take up thallium-201 only when ischaemia has passed. Tech- netium-99m (99mTc)-labelled sestamibi (see Chapter 33) can also be used for this purpose. Coronary angiography (see Chapter 33) is used to provide direct radiographic visualization of the extent and severity of coronary artery disease, allowing risk assessment.
The hallmark of variant angina is ST segment elevation on the ECG. Cardiac ischaemia caused by variant angina can cause ventricular arrhythmias, syncope and even myocardial infarction during prolonged attacks. Variant angina can be provoked by intravenous administration of the vasoconstrictor ergonovine, forming the basis of a hospital test for this condition.
Uncomplicated stable angina has a good prognosis. Epidemiological studies show that cardiovascular mortality in patients with stable angina is approximately 1% per year. Mortality increases with the number of diseased arteries, especially if there is significant stenosis in the left coronary artery mainstem. Patients who have poor left ventricular function or diabetes are also at particular risk.
Patients without significant coronary artery disease have a benign prognosis; in a recent study only 4% of patients in this group died from a cardiac cause during an average follow-up period of 7 years. However, patients who also have severe coronary artery disease or who develop severe arrhythmias during vasospastic episodes are at greater risk.
The management of angina is designed to control symptoms, reduce underlying risk factors and improve prognosis. Control of symptoms involves the use of nitrovasodilators, β-adrenoceptor blockers and Ca2+ channel antagonists (see Chapter 41). Minimization of risk factors involves the use of low-dose aspirin, lipidlowering drugs and lifestyle changes, and is a vital component of treatment. Revascularization (see Chapter 43) can also be used to treat stable angina.