What is stable angina?
Stable angina is a discomfort or pain in the chest due to a transient inadequate blood supply to the heart; typically aggravated by physical exertion, emotion or stress and promptly relieved by rest or nitroglycerin.
Cause and pathophysiology:
Coronary atherosclerosis is the principal cause of stable angina. In stable angina, fixed or stable atherosclerotic plaques are formed within the coronary artery. Coronary artery supply oxygen rich blood to the heart. When the demand of oxygen in the heart is increased that occurs with physical exertion, emotion or stress; the fixed or stable atherosclerotic plaques within the coronary artery impede the blood flow. As a result, transient myocardial ischemia occurs and person feels chest discomfort or pain. If the person takes rest, his myocardial oxygen demand decreases, or if he intake nitroglycerin, his heart get more oxygen (nitroglycerin increases blood flow by dilating the coronary artery) and ultimately relief chest discomfort or pain.
The main symptom of stable angina is central chest pain or discomfort. Pain is precipitated by physical exertion or other forms of stress, particularly intense emotion, cold exposure, heavy meals and rarely vivid dreams, and is promptly relieved by rest or nitroglycerin. Most attacks typically lasts 2-5 minutes, duration is seldom less than 30 seconds or more than 15 minutes, although a vague sensation of discomfort may persist after pain has stopped. Pain usually located in the centre of the chest, but may radiate to neck, jaw, shoulder, back, and arms (most commonly left arm). Some persons may also feel breathing difficulty accompanying chest pain.
New York Heart Association (NYHA) has developed a functional classification for classifying the severity of angina. This classification guides the plan of treatment and also helps the physician to comparison the patient symptoms from one visit to the next. A progression from one class to next may need more aggressive evaluation.
Class I: No limitation during ordinary activities such as walking, climbing stairs. Chest discomfort or pain only occurs with prolonged or strenuous or rapid exertion.
Class II: Slight limitation during ordinary activities. Patient feels chest discomfort or pain during walking, walking uphill, climbing stairs or under emotional stress.
Class III: Marked limitation of ordinary activities without symptoms at rest.
Class IV: Patient is unable to carry on any physical activities without chest discomfort or pain; angina may be present at rest.
Stable angina is diagnosed by clinical symptoms with following investigations-
ECG is often normal in between attacks of stable angina. If ECG is done during an attack, horizontal or downward sloping ST-segment depression may be found.
Exercise tolerance test (ETT)
ETT can be used to confirm or refute the diagnosis of stable angina. ETT is usually performed using a standard treadmill or bicycle ergometer while monitoring the person’s ECG, blood pressure, and general condition. Planar (horizontal) or down-sloping ST segment depression of one millimeter or more is indicative of ischemia. Up-sloping ST segment depression is less specific and often founds in normal persons.
Myocardial perfusion scanning
Myocardial perfusion scanning is done when ETT cannot evaluate the stable angina or those who are unable to perform exercise for ETT. We can detect the ischemic area in the heart muscle by this myocardial perfusion scanning during stress (stress can be achieved by exercise or by controlled infusion of dobutamine). An intravenous radioactive isotope such as 99 technetium-labelled tetrofosmin is used for scanning procedure.
Stress echocardiography is an alternative to myocardial perfusion scanning. Here, echocardiography is performed during physical stress (achieved by exercise) or during pharmacological stress (achieved by controlled infusion of dobutamine). In stable angina, reversible contractility defect in the heart muscle is found on stress echocardiography.
Coronary angiography is an imaging technique used to visualize the lumen of coronary arteries of the heart by using a fluoroscopy. It provides detailed information about the extent and nature of coronary artery disease. This procedure is done under local anaesthesia and requires specialized equipment, cardiac monitoring and experienced operating team.
Risk stratification is important in stable angina. It helps in choosing appropriate treatment and identifies patients who require invasive therapy such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). It also gives an idea about patient’s prognosis.
Low risk group
1. Patients with good effort tolerance
2. Predictable exertional angina – It means that the same amount of physical exertion can cause chest pain and pain go away when the person stop the work.
3. Ischemia only at high workload – Ischemic change develops in the heart muscle on ETT only at heavy exercise.
4. Single vessel or two vessel disease – Atherosclerotic plaque is deposited within one or two coronary arteries and block the artery partially which produces symptoms. Usually, coronary angiography is done to detect the plaque.
5. Good left ventricular function – Heart has four chambers. Left ventricle is the main chamber that pumped out oxygen rich blood in the whole body. Good left ventricular function means that the left ventricle pump out an amount blood that is adequate for the needs of the body. Physical findings of good left ventricular function are normal pulse rate, normal blood pressure, no crackles at the lung base and so on. Left ventricular function is usually assessed by echocardiography; ejection fraction more than 60% indicates good left ventricular function.
High risk group
1. Patients with poor effort tolerance
2. Ischemia at low workload – Ischemic change appears in the heart muscle on ETT at minimum exercise.
3. Left main vessel or three vessel disease – Atherosclerotic plaque is deposited within left main coronary artery or three coronary arteries and produces symptoms.
4. Poor left ventricular function – Physical findings of poor left ventricular function are high pulse rate, low blood pressure, crackles at the lung base and so on .Ejection fraction less than 35% indicates poor left ventricular function.
5. Post-infarct angina – It means that a person feels chest pain again who had a history of previous myocardial infarction (heart attack).
Patients may fall between these two groups.
Following complications may develop in stable angina:
1. Unstable angina – The atherosclerotic plaque of stable angina may inflamed or ruptured that triggers platelet aggregation to form a non-occlusive thrombus (blood clot) that partially obstructs a coronary artery and develops unstable angina.
2. Myocardial infarction – Sometimes the ruptured or eroded atherosclerotic plaque triggers platelet aggregation to form an occlusive thrombus (blood clot) that completely obstructs a coronary artery and develops myocardial infarction.
3. Chronic heart failure – In chronic stable angina, the heart muscle get inadequate blood supply that may lead to a reduction in ventricular contractility and causes chronic heart failure.
4. Heart arrhythmias – Heart arrhythmia is a disturbance of the electrical rhythm of the heart. In stable angina, ischemic heart muscle may disrupts electrical signals and may produces arrhythmia in which heartbeat may be too fast, too slow or irregular.
The goals of treatment are to eliminate or reduce symptoms and prevent long-term complications. Patient’s advice, drug therapy and revascularization are all employed in the treatment of stable angina.
(A) Patient’s advice:
1. Patients should be stopped cigarette smoking.
2. They maintain an ideal body weight.
3. They take a regular exercise up to, but not beyond, the point of chest discomfort. Exercise can create collateral arteries in the heart.
4. Patients should avoid severe unaccustomed physical exertion, and also heavy exercise in very cold weather or after a heavy meal.
5. They should eat a Mediterranean style diet (diet rich in monounsaturated fatty acids and omega-3 fatty acids, but low in saturated fatty acids).
6. They should intake sublingual nitrate before undertaking physical exertion.
7. Patients with diabetes and hypertension should achieve well control.
(B) Drug therapy:
All patients with stable angina should be given oral aspirin 75 mg daily for life long. Aspirin reduces the risk of complications such as myocardial infarction. 75 mg of clopidogrel is equally effective if aspirin causes troublesome side effects.
Glyceryl trinitrate (nitroglycerine, trinitrin) is standard drug in stable angina. It is given sublingually (under tongue) either in tablet form or as an aerosol spray. Usual dose is 0.2-0.3 mg. It will relief anginal pain in about 2-3 minutes. All patients should be encouraged to use sublingual nitrate before undertaking physical exertion that may induce anginal chest pain.
Long-acting nitrate preparations include isosorbide mono-nitrate, 10-40 mg orally twice a day or 60-120 mg once a day in a sustained-release tablet; isosorbide dinitrate, 10-40 mg orally three times a day; oral sustained-release nitroglycerine tablet, 6.25-12.5 mg two to four times a day; nitroglycerine ointment, 6.25-25 mg applied two to four times a day; and transdermal nitroglycerine patches.
Nitrates produce arteriolar and venous dilatation. Coronary artery dilatation leads to an increase in myocardial oxygen supply. Peripheral arterial dilatation causes a fall in afterload (resistance against which heart pump), and venous dilatation leads to a diminished preload (degree to which heart is stretched). Therefore, nitrares reduce myocardial oxygen supply by lowering preload and afterload.
Headache is a very common side effect, but tends to diminish with continued use. Continuous nitrate intake can cause tolerance. This can be avoided by an eight hour nitrate free period, best achieved at night when a person is inactive.
Now beta-blockers are routinely use in patients with stable angina. Beta-blockers reduce myocardial oxygen demand by reducing heart rate, blood pressure, and cardiac contractility. Oral cardioselective beta-blocker such as metoprolol 50-200 mg daily, or bisoprolol 5-15 mg daily are usually adequate. Beta-blockers should be avoided if there is bronchial asthma, heart failure, heart block, or bradycardia.
Calcium channel blockers:
These drugs inhibit the entry of extracellular calcium into cells, particularly cardiac and arteriolar smooth muscle cells, and reduce myocardial oxygen demand by lowering blood pressure and cardiac contractility. Calcium channel blockers fall into two main groups, the dihydropyridines such as amlodipine, nifedipine and the phenylalkylamines such as verapamil, diltiazem. Used alone, dihydropyridines often cause a reflex tachycardia that can be avoided by concomitant use of a beta-blocker. In contrast, phenylalkylamines can cause slow heart rate both at rest and during exercise and are effective anti-anginal drugs when beta-blockers are contraindicated.
Nicorandil is a potassium channel activator. It dilates both arteries and veins. It is given orally in a dose of 10-30 mg twice a day.
Ivabradine is new drug for angina that acts by blocking the If channel in the SA node, resulting in a slowing of the heart rate both at rest and during exercise. Usual dose is 5 mg two times daily.
Ranolazine is used as first line therapy in chronic stable angina. It decreases intracellular calcium overload by decreasing the late sodium current. The usual dose is 500 mg orally twice daily. It can cause QT prolongation. Therefore, it should not be given in patients with pre-existing QT prolongation and in patients talking QT prolonging drugs such as quinidine, sotalol, dofetilide. Ranolazine is contraindicated in patients with significant kidney and liver disease.
Statins such as atorvastatin, rosuvastatin, or simvastatin is required in patients with stable angina. It can reduce LDL (low density lipoprotein) cholesterol that is the main culprit for atherosclerotic plaque formation and raise HDL (high density lipoprotein) cholesterol that is beneficial for us.
It is conventional to start drug therapy with low-dose aspirin, sublingual glyceryl trinitrate, a beta-blocker and a statin, and then add a calcium channel blocker or a long acting nitrate or other later, if needed.
(C) Revascularization treatment:
High risk patients with stable angina are needed revascularization treatment.Appropriate combination drugs therapy is appropriate in low to medium risk patients, and revascularization is reserved for those who fail to settle with medical therapy. Revascularization may take in the form of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PCI is recommended for one or two-vessel disease and CABG for left main coronary arterial disease or severe three-vessel disease.
Prognosis depending on the number of vessels diseased, the extent of vessels obstruction, the status of left ventricular function, the presence of diabetes, the habit of smoking and the presence of arrhythmias. Mortality rates are gradually increasing in patients with one, two, and three-vessel disease and those with left main coronary artery disease; ranging from 1% per year to 25% per year. When the coronary arteries become 80% obstructed or more, the risk of thrombosis is greatly increased. Those whose ischemic change appears on ETT at minimum exercise and those with extensive ischemic change by exercise ECG or myocardial perfusion scanning have a poorer prognosis.