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Angina pectoris
is a clinical syndrome of precordial discomfort or pressure due
to transient myocardial ischemia without infarction. It is typically precipitated
by exertion or psychologic stress and relieved by rest or sublingual
nitroglycerin. Diagnosis is by symptoms, ECG, and myocardial imaging.
Treatment may include nitrates, β-blockers, Ca
channel blockers, and coronary angioplasty or coronary artery bypass
graft surgery.
Etiology
and Pathophysiology
Angina pectoris occurs when cardiac workload and resultant myocardial O2 demand exceed the ability of coronary arteries to supply an adequate amount of oxygenated blood, as can occur when the arteries are narrowed. Narrowing usually results from atherosclerosis but may result from coronary artery spasm or, rarely, coronary artery embolism. Acute coronary thrombosis can cause angina if obstruction is partial or transient, but it usually causes MI.
Because myocardial O2 demand is determined mainly by heart rate, systolic wall tension, and contractility, narrowing of a coronary artery typically results in angina that occurs during exertion and is relieved by rest.
In addition to exertion, cardiac workload can be increased by disorders such as hypertension, aortic stenosis, aortic regurgitation, or hypertrophic cardiomyopathy. In such cases, angina can result whether atherosclerosis is present or not. These disorders can also decrease relative myocardial perfusion because myocardial mass is increased (causing decreased diastolic flow).
A decreased O2 supply, as in severe anemia or hypoxia, can precipitate or aggravate angina.
In stable angina, the relationship between workload or demand and ischemia is usually relatively predictable. However, atherosclerotic arterial narrowing is not entirely fixed; it varies with the normal fluctuations in arterial tone that occur in all people. Thus, more people have angina in the morning, when arterial tone is relatively high. Also, abnormal endothelial function may contribute to variations in arterial tone; eg, in endothelium damaged by atheromas, stress of a catecholamine surge causes vasoconstriction rather than dilation (normal response).
As the myocardium becomes ischemic, coronary sinus blood pH falls, cellular K is lost, lactate accumulates, ECG abnormalities appear, and ventricular function deteriorates. Left ventricular (LV) diastolic pressure usually increases during angina, sometimes inducing pulmonary congestion and dyspnea. The exact mechanism by which ischemia produces discomfort is unclear but may involve nerve stimulation by hypoxic metabolites.
Symptoms and Signs
Angina may be a vague, barely troublesome ache or may rapidly become a severe, intense precordial crushing sensation. It is rarely described as pain. Discomfort is most commonly felt beneath the sternum, although location varies. Discomfort may radiate to the left shoulder and down the inside of the left arm, even to the fingers; straight through to the back; into the throat, jaws, and teeth; and, occasionally, down the inside of the right arm. It may also be felt in the upper abdomen. The discomfort of angina is never above the ears or below the umbilicus.
Some patients have atypical angina (eg, bloating, gas, abdominal distress), often ascribing symptoms to indigestion; belching may even seem to relieve the symptoms. Others have dyspnea due to the sharp, reversible increase in LV filling pressure that often accompanies ischemia. Frequently, the patient's description is imprecise, and whether the problem is angina, dyspnea, or both may be difficult to determine. Because ischemic symptoms require a minute or more to resolve, brief, fleeting sensations rarely represent angina.
Between and even during attacks of angina, physical findings may be normal. However, during the attack, heart rate may increase modestly, BP is often elevated, heart sounds become more distant, and the apical impulse is more diffuse. The 2nd heart sound may become paradoxical because LV ejection is more prolonged during an ischemic attack. A 4th heart sound is common, and a 3rd heart sound may develop. A mid or late systolic apical murmur shrill—or blowing but not especially loud—may occur if ischemia causes localized papillary muscle dysfunction, producing mitral regurgitation.
Angina pectoris is typically triggered by exertion or strong emotion, usually persists no more than a few minutes, and subsides with rest. Response to exertion is usually predictable, but in some patients, exercise that is tolerated one day may precipitate angina the next because of variations in arterial tone. Symptoms are exaggerated when exertion follows a meal or occurs in cold weather; walking into the wind or first contact with cold air after leaving a warm room may precipitate an attack. Symptom severity is often classified by the degree of exertion resulting in angina (see Table 1: Coronary Artery Disease: Canadian Cardiovascular Classification System of Angina Pectoris ).
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Table 1
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Canadian
Cardiovascular
Classification System
of Angina Pectoris
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Class
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Activities Triggering Chest Pain
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1
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Strenuous, rapid, or prolonged exertion
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Not usual physical activities (eg, walking, climbing stairs)
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2
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Walking rapidly
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Walking uphill
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Climbing stairs rapidly
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Walking or climbing stairs after meals
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Cold
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Wind
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Emotional stress
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3
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Walking, even 1 or 2 blocks at usual pace and on level ground
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Climbing stairs, even 1 flight
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4
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Any physical activity
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Sometimes occurring at rest
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Adapted from Braunwald E, Antman EM, Beasley JW, et al: ACC/AHA Guidelines for the management of patients with unstable angina and non-ST segment elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the management of patients with unstable angina). Journal of American College of Cardiology 36:970–1062, 2000.
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Attacks may vary from several a day to symptom-free intervals of weeks, months, or years. They may increase in frequency (called crescendo angina) to a fatal outcome or gradually decrease or disappear if adequate collateral coronary circulation develops, if the ischemic area infarcts, or if heart failure or intermittent claudication supervenes and limits activity.
Nocturnal angina may occur if a dream causes striking changes in respiration, pulse rate, and BP. Nocturnal angina may also be a sign of recurrent LV failure, an equivalent of nocturnal dyspnea. The recumbent position increases venous return, stretching the myocardium and increasing wall stress, which increases O2 demand.
Angina may occur spontaneously during rest (called angina decubitus). It is usually accompanied by a modestly increased heart rate and a sometimes markedly higher BP, which increase O2 demand. These increases may be the cause of rest angina or the result of ischemia induced by plaque rupture and thrombus formation. If angina is not relieved, unmet myocardial O2 demand increases further, making MI more likely.
Unstable angina:
Because angina characteristics are usually predictable for a given patient, any changes (ie, rest angina, new-onset angina, increasing angina) should be considered serious. Such changes are termed unstable angina and require prompt evaluation and treatment.
Unstable angina is classified based on severity and clinical situation (see Table 2: Coronary Artery Disease: Braunwald Classification of Unstable Angina*). Also considered are whether unstable angina occurs during treatment for chronic stable angina and whether transient changes in ST-T waves occur during angina. If angina has occurred within 48 h and no contributory extracardiac condition is present, troponin levels may be measured to help estimate prognosis; troponin-negative indicates a better prognosis than troponin-positive.
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Table 2
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Braunwald
Classification of Unstable Angina*
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Classification
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Description
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Designation
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Severity
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I
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New onset of severe angina or increasing† angina
No angina during rest
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—
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II
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Angina during rest within past month but not within preceding 48 h
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Subacute angina at rest
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III‡
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Angina during rest within 48 h
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Acute angina at rest
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Clinical situation
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A
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Develops secondary to an extracardiac condition that worsens myocardial ischemia
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Secondary UA
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B‡
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Develops when no contributory extracardiac condition is present
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Primary UA
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C
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Develops within 2 wk of acute MI
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Post-MI UA
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*Basic classification consists of Roman numeral and a letter.
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†Angina occurs more frequently, is more severe, lasts longer, or is triggered by less exertion.
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‡For patients with class IIIB, troponin status (negative or positive) is determined to estimate prognosis.
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UA = unstable angina.
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Adapted from Hamm CW, Braunwald E: APACHE II: A classification of unstable angina revisited. Circulation 102:118–122, 2000.
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Diagnosis
Diagnosis is suspected if chest discomfort is typical and is precipitated by exertion and relieved by rest. Patients whose chest discomfort lasts > 20 min or occurs during rest or who have syncope or heart failure are evaluated for an acute coronary syndrome (see Coronary Artery Disease: Acute Coronary Syndromes (ACS)). Chest discomfort may also be caused by GI disorders (eg, reflux, esophageal spasm, indigestion, cholelithiasis), costochondritis, anxiety, panic attacks, hyperventilation, and other cardiac disorders (eg, pericarditis, mitral valve prolapse, supraventricular tachycardia, atrial fibrillation), even when coronary blood flow is not compromised (see Approach to the Cardiac Patient: Chest Pain).
ECG:
If typical exertional symptoms are present, ECG is indicated. Because angina resolves quickly with rest, ECG rarely can be done during an attack except during stress testing. If done during an attack, ECG is likely to show reversible ischemic changes: T wave discordant to the QRS vector, ST-segment depression (typically), ST-segment elevation, decreased R-wave height, intraventricular or bundle branch conduction disturbances, and arrhythmia (usually ventricular extrasystoles). Between attacks, the ECG (and usually LV function) at rest is normal in about 30% of patients with a typical history of angina pectoris, even those with extensive 3-vessel disease. In the remaining 70%, the ECG shows evidence of previous infarction, hypertrophy, or nonspecific ST-segment and T-wave (ST-T) abnormalities. An abnormal resting ECG alone does not establish or refute the diagnosis.
Stress
testing:
More specific tests include stress testing with ECG or with myocardial imaging (eg, echocardiography, radionuclide imaging) and coronary angiography. Further testing is needed to confirm the diagnosis, evaluate disease severity, determine appropriate exercise levels for the patient, and help predict prognosis.
Noninvasive tests are considered first. For coronary artery disease (CAD), the most accurate are stress echocardiography and myocardial perfusion imaging with single-photon emission computed tomography (SPECT) or PET. However, these tests are more expensive than simple stress testing with ECG.
If a patient has a normal resting ECG and can exercise, exercise stress testing with ECG is done. In men with chest discomfort suggesting angina, stress ECG testing has a specificity of 70%; sensitivity is 90%. Sensitivity is similar in women, but specificity is lower, particularly in women < 55 (< 70%). However, women are more likely than men to have an abnormal resting ECG when CAD is present (32% vs 23%). Although sensitivity is reasonably high, exercise ECG can miss severe CAD (even left main or 3-vessel disease). In patients with atypical symptoms, a negative stress ECG usually rules out angina pectoris and CAD; a positive result may or may not represent coronary ischemia and indicates need for further testing.
When the resting ECG is abnormal, false-positive ST-segment shifts are common on the stress ECG, so patients should have stress testing with myocardial imaging. Exercise or pharmacologic stress (eg, with dobutamine or dipyridamole infusion) may be used. The choice of imaging technique depends on institutional availability and expertise. Imaging tests can help assess LV function and response to stress; identify areas of ischemia, infarction, and viable tissue; and determine the site and extent of myocardium at risk. Stress echocardiography can also detect ischemia-induced mitral regurgitation.
Angiography:
Coronary angiography (see also Cardiovascular Tests and Procedures: Angiography) is the standard for diagnosing CAD but is not always necessary to confirm the diagnosis. It is indicated primarily to locate and assess severity of coronary artery lesions when revascularization (percutaneous intervention [PCI] or coronary artery bypass grafting [CABG]) is being considered. Angiography may also be indicated when knowledge of coronary anatomy is necessary to advise about work or lifestyle needs (eg, discontinuing job or sports activities). Obstruction is assumed to be physiologically significant when the luminal diameter is reduced > 70%. This reduction correlates well with the presence of angina pectoris unless spasm or thrombosis is superimposed.
Intravascular ultrasonography provides images of coronary artery structure. An ultrasound probe on the tip of a catheter is inserted in the coronary arteries during angiography. This test can provide more information about coronary anatomy than other tests; it is indicated when the nature of lesions is unclear or when apparent disease severity does not match symptom severity. Used with angioplasty, it can help ensure optimal placement of stents.
Imaging:
Electron beam CT can detect the amount of Ca present in coronary artery plaque. The Ca score (from 1 to 100) is roughly proportional to the risk of subsequent coronary events. However, because Ca may be present in the absence of significant stenosis, the score does not correlate well with the need for angioplasty or CABG. Thus, the American Heart Association recommends that screening with electron beam CT should be done only for select groups of patients and is most valuable when combined with historical and clinical data to estimate risk of death or non-fatal MI. These groups may include asymptomatic patients with an intermediate Framingham 10-yr risk estimate of 10 to 20% and symptomatic patients with equivocal stress test results.
Multidetector row CT (MDRCT) coronary angiography can accurately identify coronary stenosis and has a number of advantages. The test is noninvasive, can exclude coronary stenosis with high accuracy, can establish stent or by-pass graft patency, can visualize cardiac and coronary venous anatomy, and can assess calcified and noncalcified plaque burden. However, radiation exposure is significant, and the test is not suitable for those with heart rates > 65 beats/min, those with irregular heart beats, and pregnant women. Patients must also be able to hold their breath 15 to 20 sec, 3 to 4 times during the study.
Evolving indications for MDRCT coronary angiography include
Cardiac MRI has become invaluable in evaluating many cardiac and great vessel abnormalities. It may be used to evaluate CAD by several techniques, which enable direct visualization of coronary stenosis, assessment of flow in the coronary arteries, evaluation of myocardial perfusion and metabolism, evaluation of wall motion abnormalities during stress, and assessment of infracted myocardium vs viable myocardium.
Current indications for cardiac MRI include evaluation of cardiac structure and function, assessment of myocardial viability, and possibly diagnosis and risk assessment of patients with either known or suspected CAD.
Prognosis
The main adverse outcomes are unstable angina, MI, and sudden death due to arrhythmias. Annual mortality rate is about 1.4% in patients with angina, no history of MI, a normal resting ECG, and normal BP. However, women with CAD tend to have a worse prognosis. Mortality rate is about 7.5% when systolic hypertension is present, 8.4% when the ECG is abnormal, and 12% when both are present. Type 2 diabetes about doubles the mortality rate for each scenario.
Prognosis worsens with increasing age, increasingly severe anginal symptoms, presence of anatomic lesions, and poor ventricular function. Lesions in the left main coronary artery or proximal left anterior descending artery indicate particularly high risk. Although prognosis correlates with number and severity of coronary arteries affected, prognosis is surprisingly good for patients with stable angina, even those with 3-vessel disease, if ventricular function is normal.
Treatment
Reversible risk factors are modified as much as possible (see also Arteriosclerosis: Treatment). Smokers should stop smoking; ≥ 2 yr after stopping smoking, risk of MI is reduced to that for people who never smoked. Hypertension is treated diligently because even mild hypertension increases cardiac workload. Weight loss alone often reduces the severity of angina. Sometimes treatment of mild LV failure markedly lessens angina. Paradoxically, digitalis occasionally intensifies angina, presumably because increased myocardial contractility increases O2 demand, arterial tone is increased, or both. Aggressive reduction of total and LDL cholesterol (via diet plus drugs as necessary) slows the progression of CAD, may cause some lesions to regress (see Lipid Disorders: Prognosis and Treatment), and improves endothelial function and thus arterial response to stress. An exercise program emphasizing walking often improves the sense of well-being, reduces CAD risk, and improves exercise tolerance.
Drugs:
The main goals are to relieve acute symptoms, prevent or reduce ischemia (see Table 3: Coronary Artery Disease: Drugs for Coronary Artery Disease ), and prevent future ischemic events. For an acute attack, sublingual nitroglycerin is the most effective drug.
To prevent ischemia, all patients diagnosed with CAD or at high risk of developing CAD should take an antiplatelet drug daily. β-Blockers, unless contraindicated or not tolerated, are given to most patients. For some patients, prevention of symptoms requires Ca channel blockers or long-acting nitrates.
Antiplatelet
drugs inhibit platelet aggregation. Aspirin binds irreversibly to platelets and inhibits cyclooxygenase and platelet aggregation. Clopidogrel blocks adenosine diphosphate–induced platelet aggregation. Either drug can reduce risk of ischemic events (MI, sudden death), but the drugs are most effective when given together. Patients unable to tolerate one should receive the other drug alone.
β-Blockers limit symptoms and prevent infarction and sudden death better than other drugs. β-Blockers block sympathetic stimulation of the heart and reduce systolic BP, heart rate, contractility, and cardiac output, thus decreasing myocardial O2 demand and increasing exercise tolerance. They also increase the threshold for ventricular fibrillation. Most patients tolerate these drugs well. Many β-blockers are available and effective. Dose is titrated upward as needed until limited by bradycardia or adverse effects. Patients who cannot tolerate β-blockers are given a Ca channel blocker with negative chronotropic effects (eg, diltiazem , verapamil ). Those at risk for β-blocker intolerance (eg, those with asthma) may be tried on a cardioselective β-blocker (eg, carvedilol ), perhaps with pulmonary function testing before and after drug administration to detect drug-induced bronchospasm.
Nitroglycerin is a potent smooth-muscle relaxant and vasodilator. Its main sites of action are in the peripheral vascular tree, especially in the venous or capacitance system, and in coronary blood vessels. Even severely atherosclerotic vessels may dilate in areas without atheroma. Nitroglycerin lowers systolic BP and dilates systemic veins, thus reducing myocardial wall tension, a major determinant of myocardial O2 need. Sublingual nitroglycerin is given for an acute attack or for prevention before exertion. Dramatic relief usually occurs within 1.5 to 3 min, is complete by about 5 min, and lasts up to 30 min. The dose may be repeated q 4 to 5 min up to 3 times if relief is incomplete. Patients should always carry nitroglycerin tablets or aerosol spray to use promptly at the onset of an angina attack. Patients should store tablets in a tightly sealed, light-resistant glass container, so that potency is not lost. Because the drug deteriorates quickly, small amounts should be obtained frequently.
Long-acting
nitrates (oral or transdermal) are used if symptoms persist after the β-blocker dose is maximized. If angina occurs at predictable times, a nitrate is given to cover those times. Oral nitrates include isosorbide dinitrate and mononitrate (the active metabolite of the dinitrate). They are effective within 1 to 2 h; their effect lasts 4 to 6 h. Sustained-release formulations of isosorbide mononitrate appear to be effective throughout the day. For transdermal use, cutaneous nitroglycerin patches have largely replaced nitroglycerin ointments primarily because ointments are inconvenient and messy. Patches slowly release the drug for a prolonged effect; exercise capacity improves 4 h after patch application and wanes in 18 to 24 h. Nitrate tolerance may occur, especially when plasma concentrations are kept constant. Because MI risk is highest in early morning, an afternoon or early evening respite period from nitrates is reasonable unless a patient commonly has angina at that time. For nitroglycerin , an 8- to 10-h respite period seems sufficient. Isosorbide may require a 12-h respite period. If given once/day, sustained-release isosorbide mononitrate does not appear to elicit tolerance.
Ca
channel blockers may be used if symptoms persist despite use of nitrates or if nitrates are not tolerated. Ca channel blockers are particularly useful if hypertension or coronary spasm is also present. Different types of Ca channel blockers have different effects. Dihydropyridines (eg, nifedipine , amlodipine , felodipine ) have no chronotropic effects and vary substantially in their negative inotropic effects. Shorter-acting dihydropyridines may cause reflex tachycardia and are associated with increased mortality in CAD patients; they should not be used to treat stable angina. Longer-acting formulations of dihydropyridines have fewer tachycardic effects; they are most commonly used with a β-blocker. In this group, amlodipine has the weakest negative inotropic effects; it may be used in patients with LV systolic dysfunction. Diltiazem and verapamil , other types of Ca channel blockers, have negative chronotropic and inotropic effects. They can be used alone in patients with β-blocker intolerance or asthma and normal LV systolic function but may increase cardiovascular mortality in patients with LV systolic dysfunction.
Revascularization:
Revascularization, either with PCI (eg, angioplasty, stenting) or CABG should be considered if angina persists despite drug therapy and worsens quality of life or if anatomic lesions (noted during angiography) put a patient at high risk of mortality. The choice between PCI and CABG depends on extent and location of anatomic lesions, the experience of the surgeon and medical center, and, to some extent, patient preference.
PCI is usually preferred for 1- or 2-vessel disease with suitable anatomic lesions. Lesions that are long or near bifurcation points are often not amenable to PCI. However, as stent technology improves, PCI is being used for more complicated cases.
CABG is very effective in selected patients with angina. The ideal candidate has severe angina pectoris and localized disease, or diabetes mellitus. About 85% of patients have complete or dramatic symptom relief. Exercise stress testing shows positive correlation between graft patency and improved exercise tolerance, but exercise tolerance sometimes remains improved despite graft closure.
CABG improves survival for patients with left main disease, those with 3-vessel disease and poor LV function, and some patients with 2-vessel disease. However, for patients with mild or moderate angina (class I or II) or 3-vessel disease and good ventricular function, CABG appears to only marginally improve survival. For patients with 1-vessel disease, outcomes with drug therapy, PCI, and CABG are similar; exceptions are left main disease and proximal left anterior descending disease, for which revascularization appears advantageous.
Variant
Angina
Variant angina
is angina pectoris secondary to epicardial coronary artery spasm
(Prinzmetal's angina).
Most patients with variant angina have significant fixed proximal obstruction of at least one major coronary artery. Spasm usually occurs within 1 cm of the obstruction (often accompanied by ventricular arrhythmia).
Symptoms are anginal discomfort occurring mainly during rest, often at night, and only rarely and inconsistently during exertion (unless significant coronary artery obstruction is also present). Attacks tend to occur regularly at certain times of day.
Diagnosis is suspected if ST-segment elevation occurs during the attack. Between anginal attacks, the ECG may be normal or show a stable abnormal pattern. Confirmation is by provocative testing with ergonovine or acetylcholine, which may precipitate coronary artery spasm, identified by significant ST-elevation or by observation of a reversible spasm during cardiac catheterization. Testing is done most commonly in a cardiac catheterization laboratory and occasionally in a coronary care unit.
Average survival at 5 yr is 89 to 97%, but mortality risk is greater for patients with both variant angina and atherosclerotic coronary artery obstruction. Usually, sublingual nitroglycerin promptly relieves variant angina. Ca channel blockers may effectively prevent symptoms. Theoretically, β-blockers may exacerbate spasm by allowing unopposed α-adrenergic vasoconstriction, but this effect has not been proved clinically. Oral drugs most commonly used are sustained-release diltiazem 120 to 540 mg once/day, sustained-release verapamil 120 to 480 mg once/day (dose must be reduced in patients with renal or hepatic dysfunction), or amlodipine 15 to 20 mg once/day (dose must be reduced in elderly patients and patients with hepatic dysfunction). In refractory cases, amiodarone may be useful. Although these drugs relieve symptoms, they do not appear to alter prognosis.
Syndrome
X
Syndrome X
is cardiac microvascular dysfunction or constriction causing angina
(microvascular angina).
Some patients with typical angina that is relieved by rest or nitroglycerin have normal coronary arteriograms (eg, no atherosclerosis, embolism, or inducible arterial spasm). Some of these patients have ischemia detected during stress testing; others do not. In some patients, the cause of ischemia seems to be reflex intramyocardial coronary constriction and reduced coronary flow reserve. Other patients have microvascular dysfunction within the myocardium: The abnormal vessels do not dilate in response to exercise or other cardiovascular stressors; sensitivity to cardiac pain may also be increased. Prognosis is good, although symptoms of ischemia may recur for years. In many patients, β-blockers relieve symptoms. This disorder should not be confused with variant angina due to epicardial coronary spasm or with another disorder called syndrome X, which refers to the metabolic syndrome (see Obesity and the Metabolic Syndrome: Metabolic Syndrome).
Silent
Ischemia
Patients with CAD (particularly diabetics) may have ischemia without symptoms. Ischemia is evidenced by transient asymptomatic ST-T abnormalities seen during 24-h Holter monitoring. Radionuclide studies can sometimes document asymptomatic myocardial ischemia during physical or mental stress (eg, mental arithmetic). Silent ischemia and angina pectoris may coexist, occurring at different times. Prognosis depends on severity of CAD.
Last full review/revision December 2007 by James Wayne Warnica, MD
Content last modified December 2007
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