Chronic stable angina

Cardiology Review® Online, March 2004, Volume 21, Issue 3

From the Department of Medicine, University of Arizona Health Sciences Center, Tucson, Arizona

Coronary artery disease (CAD) is the leading cause of death in adults in the United States, accounting for about one third of all deaths in subjects older than 35 years.1 The prevalence of this disease is approximately one third to one half that of all cardiovascular disease. The lifetime risk of CAD for individuals at age 40 years is 49% for men and 32% for women; the lifetime risk is also appreciable in those free of this disease at age 70 years, at 35% for men and 24% for women. The death rate from CAD is higher in men than in women, declining from three times higher at ages 25 to 34 years to 1.6 times higher at ages 75 to 84 years, and in blacks than in whites, an excess that disappears by age 75 years. Among the Hispanic population, mortality from CAD is not as high as it is among blacks or whites.1

Mortality rates for cardiovascular disease and CAD in men and women and in blacks and whites have fallen in most countries by 24% to 28% since 1975, although the decline has slowed since 1990.1 Approximately 45% of this reduction is attributable to improvement in medical therapy for coronary disease; the remaining 55% is the result of risk-factor reduction, particularly to a decline in smoking and from treatment of hypertension.

Data from 44 years of follow-up of the original Framingham Heart

Study1 cohort and 20 years of surveillance of their offspring have allowed the incidence of initial coronary events to be ascertained, including both

recognized and clinically unrecognized myocardial infarction (MI), angina pectoris, unstable angina, and sudden and nonsudden coronary deaths. For 40-year-olds, the lifetime risk of developing CAD is 49% in men and 32%

in women. For those reaching age 70 years, it is 35% for men and 24% for women. For the more serious manifestations of CAD, such as MI and sudden death, women lag behind men in incidence by 20 years, but the sex ratio for incidence narrows progressively with advancing age. The incidence at ages 65 to 94 years compared with ages 35 to 64 years more than doubles

in men and triples in women. In premenopausal women, serious man-

ifestations of CAD, such as MI and sudden death, are relatively rare. Be-

yond menopause, the incidence and severity of coronary disease increases abruptly. The male predominance of CAD is least striking for angina pectoris. Before age 75 years, the initial presentation of coronary disease in women is more likely to be angina pectoris than MI. Furthermore, angina in women is more likely to be uncomplicated (80% of cases), whereas angina in men often occurs after an MI (66%).1 Infarction predominates at virtually all ages in men, in whom only 20% of infarctions are preceded by long-standing angina, with the percentage being even lower if the MI is silent or unrecognized.

General principles

Angina is caused by myocardial ischemia that occurs whenever myocardial oxygen demand exceeds oxygen supply. An understanding of the pathophysiology of angina first requires a brief review of the determinants of oxygen demand and supply.

Myocardial oxygen demand. Four major factors determine myocardial work and therefore myocardial oxygen demand: (1) heart rate; (2) systolic blood pressure (the clinical marker of afterload); (3) myocardial wall tension or stress (the product of ventricular end-diastolic volume or preload and myocardial muscle mass); and (4) myocardial contractility.

Clinical conditions associated with an increase in oxygen demand affect one or more of these parameters. Examples include increased catecholamine levels, as with vigorous exertion or mental-stress tachycardia of any etiology; hypertension; and left ventricular hypertrophy. Individuals consistently experience angina during exercise testing when asked to exceed a defined angina threshold or absolute double-product value.

Myocardial oxygen supply. The major determinants of oxygen supply are the oxygen-carrying capacity of the blood. This is determined by oxygen tension and hemoglobin level; the degree of oxygen unloading from hemoglobin to the tissues, which is related to red blood cell 2,3-diphosphoglycerate levels; and coronary artery blood flow, which is influenced by: (1) coronary artery diameter and vessel tone (resistance); (2) collateral flow; (3) perfusion pressure, which is determined by the pressure gradient from the aorta to the coronary end-arterial vessels and by the left ventricular end-diastolic pressure (because the direction of blood flow is from epicardium to endocardium); and (4) heart rate and diastolic period (because coronary artery blood flow occurs primarily during diastole).

The most frequent cause of myocardial ischemia is coronary arterial atherosclerosis. Other causes include coronary artery vasospasm, fibrosis, and embolism. In addition, stimulation of the esophagus by acid can cause coronary artery vasoconstriction and a reduction in coronary blood flow via a neural cardio-esophageal reflex.

A clinical diagnosis of angina pectoris has a 90% predictive accuracy for the presence of CAD2; however, based on Bayesian principles, this depends upon the prevalence of CAD in population subgroups, such as men versus women and young versus old persons.

Atherosclerotic obstruction is the fundamental mechanism underlying exertional angina. Although a plaque causing a tight stenosis is more prone to cause complete obstruction and to result in unstable angina or MI, most MIs are characterized by rupture of plaque with less than 50% stenosis. This is true because nonobstructive plaques are so abundant. Why smaller lesions are more likely to cause acute ischemic events is incompletely understood. One possibility is that activation of foam cells (macrophages that contain lipids) at the margins of small plaques contributes to plaque rupture through these cells’ secretion of metalloproteinases that penetrate the thin fibrous cap of the plaque. In contrast, larger lesions are more likely to be calcified, with less inflammation and a thicker cap. Another possible explanation is that less obstructive plaques are subject to greater circumferential tensile stress on the fibrous cap. According to Laplace’s law, vascular wall tension is related to luminal pressure and the radius of the vessel, and less obstructive lesions therefore result in larger luminal diameters and greater wall stress. Also, individuals with tight stenoses are more likely to develop collateral circulation that can protect them from MIs in the face of a complete arterial occlusion.

Endothelial dysfunction

Endothelial dysfunction is one of the earliest signs of atherosclerosis. The endothelium consists of cells that line the walls of the vasculature and actively secrete substances that determine vascular tone as well as local balance of coagulation, anticoagulation, and cellular activity. These cells secrete substances such as ni-tric oxide, endothelin, prostacyclin, thromboxane, tissue plasminogen activator, heparin, platelet-derived growth factor, and macrophage colony-stimulating factor. Endothelial-dependent vasorelaxation depends upon the generation and preservation of nitric oxide—also known as endothelium-derived relaxing factor—a most potent endogenous vasodilator. Endothelial-independent vasorelaxation refers to dilatory capacity when a nitric-oxide precursor is given.

Endothelial function may be assessed invasively by measuring vasodilatory response to an infusion of acetylcholine. A normal response is dilation, whereas an abnormal response is constriction or no change. Noninvasive measurement of brachial artery dilation in response to

postocclusive hyperemia is the most common way to assess endothelial function in vivo.

The composition of atheroscle-rotic plaques is an important deter-minant of their susceptibility to instability and fissure, rupture, or dissection, with resulting thrombosis. In an angioscopic study of human coronary arteries, yellowish plaques with an increased lipid core and a thin fibrous cap were associ-ated with a high incidence of acute ischemic events, such as unstable angina or infarction. In comparison, white plaques, which have thicker fibrous caps overlying the lipid core, were primarily associated with stable angina. Ruptured yellow plaques and red or pink thrombi also were more common in patients with acute coronary syndromes.

Yellow plaques at angioscopy are also associated with higher serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B than is the case with white plaques. Among men with coronary disease who die suddenly, hypercholesterolemia appears to predispose vul-

nerable plaques to rupture, with subsequent sudden death. Why atherosclerotic plaques become disrupted is not fully understood. Two major factors thought to contribute to weakening of the fibrous cap of a plaque are inflammation and accelerated degradation of collagen and other matrix components.

The immediate site of plaque rupture or erosion is marked by an active inflammatory process consisting of activated monocytes and macrophages and, to a lesser degree, T cells. In addition, an inverse relationship has been noted between the extent of macrophage and T-cell

inflammation in culprit lesions and the clinical stability of the ischemic syndrome. Current data therefore support the concept that endothelial dysfunction and accelerated atherosclerosis are tightly intertwined and must be addressed together when developing therapeutic regimens

for CAD.

Risk factors

Both well-established traditional risk factors and poorly proven, nontraditional risk factors are associated with CAD and atherosclerosis.1,3-9

Sex and age. Male sex and older age put individuals at higher risk for atherosclerotic CAD.

Family history. Family history is

a significant independent risk fac-

tor for CAD, particularly among younger individuals with a family history of premature disease. A paternal MI in those younger than

60 years is associated with a greater risk than is infarction at a later age; in comparison, any maternal history of infarction is associated with greater risk.3,4

Lipids. The serum total cholesterol and the LDL and high-density lipoprotein (HDL) cholesterol concentrations are clear risk factors for CAD, with the risk increasing progressively with higher values. The following lipid abnormalities are associated with increased CAD risk: elevated LDL, low HDL, increased ratio of total cholesterol to HDL, hypertriglyceridemia, increased lipoprotein a (Lp[a]), increased non-HDL, increased apo B, and decreased apo A-I.

The prevalence of dyslipidemia

is increased in patients with premature CAD, ranging as high as 75% to 85% as compared with approximately 40% to 48% in age-matched controls without CAD. The disturbance in lipoprotein metabolism is often familial.

Proof of the pathogenic importance of serum cholesterol in CAD has come from randomized trials in which reductions in levels of total and LDL cholesterol led to a reduced frequency of coronary events and reduced mortality.

Hypertension. Hypertension is a well-established risk factor for adverse cardiovascular outcomes, including CAD-related mortality and stroke. Systolic blood pressure is at least as powerful a coronary risk factor as diastolic blood pressure. Isolated systolic hypertension is now established as a major hazard for CAD and stroke. There is also evidence that pulse pressure (the difference between the systolic and diastolic blood pressures) is determined primarily by large-artery stiffness and is a predictor of risk.

Diabetes mellitus. Insulin resistance, hyperinsulinemia, and glucose intolerance are associated with atherosclerotic cardiovascular disease. In the Framingham Heart Study, for example, diabetes was an independent predictor of cardiovascular disease, especially in women. In addition to the importance of diabetes as a risk factor for CAD, diabetics have a greater burden of other atherogenic risk factors than nondiabetics, including hypertension, obesity, increased ratios of total to HDL cholesterol, hypertriglyceridemia, and an elevated plasma fibrinogen level.5

Obesity. Obesity is associated with hypertension, insulin resistance, glucose intolerance, hypertriglyceridemia, reduced HDL cholesterol, and an elevated fibrinogen level. Obesity is also associated with an increased risk of cardiovascular disease and mortality.6

Metabolic syndrome. Patients with the constellation of abdominal obesity, hypertension, diabetes, and dyslipidemia are considered to have the metabolic syndrome. These individuals have a much higher risk of CAD than the general population.

C-reactive protein. Among apparently healthy men and women, the baseline level of systemic inflammation, as assessed from the plasma concentration of C-reactive protein (CRP), predicts the long-term risk of a first MI, ischemic stroke, or peripheral vascular disease. Measurement of CRP levels, along with an analysis of the lipid profile, improves risk stratification of patients.

Lifestyle factors. A diet high in calories, saturated fat, and cholesterol contributes to other risk factors that predispose to CAD. Epidemiologic data indicate that moderate alcohol intake has a protective effect against this disease.

Diet. In addition to the role of dietary lipids in the development

of CAD, there is growing evidence that fruit and vegetable consumption and a diet with a high-fiber content are inversely related to the risk of developing this condition. High-fiber intake is associated with a 40% to 50% lower risk of CAD and stroke than a low-fiber intake.

Exercise. Even a moderate amount of exercise has a protective effect against CAD and all-cause mortality. In addition to the amount of ex-ercise, the degree of cardiovascular fitness (a measure of physical activ-ity), as determined by duration of exercise and maximal oxygen uptake during exercise on a treadmill, is associated with a reduction in CAD risk and overall cardiovascular mortality.

Cigarette smoking. Cigarette smoking is an important and reversible risk factor for CAD. The incidence of MI is 6-fold greater in women and 3-fold greater in men who smoke at least 20 cigarettes per day than in respective subjects who never smoke.10 CAD risk increases with greater levels of tobacco consumption in both men and women, and is higher in inhalers than in noninhalers. Similarly, the risk of recurrent infarction in a study of smokers who had had an MI decreased by 50% within 1 year of smoking cessation, and normalized to that of nonsmokers within 2 years. The benefits of smoking cessation are seen regardless of how long or how much the patient has previously smoked.

Vitamins and homocysteine. Moderately high levels of plasma homocysteine are associated with subsequent risk of MI independently of other coronary risk factors. Because high levels can often be easily treated with vitamin supplements, homocysteine may be an independent, modifiable risk factor for CAD.8

Microalbuminuria. Microalbuminuria reflects renal vascular damage and may be a marker of early systemic arterial disease. Its presence can be regarded as an index of increased vulnerability to cardiovascular disease and a signal for vigorous efforts at correcting known risk factors.9

Left ventricular hypertrophy. Left ventricular hypertrophy is one of the less common but ominous risk

factors for CAD, stroke, and heart failure. The chief determinants of this condition, aside from age, are elevated blood pressure, obesity, height, and glucose intolerance. Downward trends in the prevalence of left ventricular hypertrophy over four decades indicate that it is preventable, and this has coincided with improved control of hyper-

tension. When evidence of this condition disappears, the risk of mor-tality from all-causes, cardiovascular disease, and CAD is substantially reduced.

Evaluation of patients with suspected CAD

General principles. Patients with stable chest-pain syndromes should undergo a thorough clinical evaluation, including classification of chest-pain type into definite or probable angina or nonspecific chest pain. Evaluation should also include identification of risk factors, such as age, tobacco use, dyslipidemia, hypertension, family history of premature CAD, activity profile, obesity, postmenopausal status, and diabetes.2-9,11 The physical examination usually detects evidence of other types of heart disease that can cause angina (aortic stenosis, hypertrophic cardiomyopathy, severe pulmonary

hypertension, and others). An assessment of contraindications to coronary angiography should be part

of this clinical assessment. Severe symptoms suggest severe CAD and are an indication for cardiac catheterization. The American College of Cardiology/American Heart Association (ACC/AHA) 2002 guidelines recommend evaluating hemoglobin and doing a fasting glucose determination and fasting lipid panel for new patients presenting with angina. Comorbid conditions that may precipitate functional angina should be considered. These include anemia, hyperthyroidism, tachyarrhythmias, cocaine abuse, or uncontrolled hypertension.

Disease prevalence affects the positive predictive value of a test; low disease prevalence results in a higher false-negative rate. Thus, a 50-year-old man with atypical chest pain has a 30% likelihood of disease, whereas a 65-year-old woman with typical angina has a 90% likelihood. The greatest increase in predictive value with the addition of a diagnostic test comes from the evaluation of a population with an in-

termediate prevalence of disease (commonly defined as 10%—90%). A diagnostic test in a population with low prevalence of a disease provides little added benefit because the test will have a high false-positive rate and a low positive predictive value. The ACC/AHA 2002 guidelines rely heavily on initial clinical assessment and data regarding disease prevalence in different populations to guide testing in individual patients.

Exercise stress testing. Exercise electrocardiographic testing has become increasingly important in evaluating patients with known or suspected CAD and in assessing the therapeutic effects of cardiac drugs. Exercise electrocardiography also provides significant prognostic information for patients with known CAD. Despite this, a great deal of controversy surrounds the use of exercise electrocardiographic testing in screening for “silent” coronary ischemia in asymptomatic individuals without known coronary disease.

Radionuclide imaging. Once the decision is made to perform a stress test to obtain diagnostic or prognostic information, or both, the use

of myocardial perfusion imaging may be of critical importance. The ACC/AHA 2002 guidelines for exercise testing and for the clinical use of radionuclide imaging strongly recommend an imaging study as part of the evaluation in the following groups of patients: (1) those who are unable to exercise to a level high enough to produce meaningful results on exercise electrocardiographic testing; and (2) those with baseline electrocardiographic abnormalities that interfere with interpretation

of the exercise electrocardiogram (ECG). These abnormalities include pre-excitation, a paced ventricular rhythm, more than 1 mm of resting ST-segment depression, and complete left bundle branch block. The use of digoxin and the presence of left ventricular hypertrophy also reduce the specificity of exercise electrocardiographic testing, although its sensitivity may remain unaffected.

Several other subsets of patients benefit incrementally from the use of radionuclide imaging. These include patients with previous MI or coronary revascularization procedures (percutaneous coronary intervention or coronary artery bypass graft [CABG] surgery), known significant CAD (for identification of the culprit lesion causing ischemia), diabetes, or a previous positive radionuclide imaging study.

For many years, planar imaging and single-photon emission computed tomography (SPECT) with thallium 201 constituted the only scintigraphic techniques available for detecting CAD and assessing prognosis. A major limitation of imaging with this method is the

high false-positive rate attributed to image-attenuation artifacts, such as breast tissue in women and diaphragmatic attenuation in obese patients, and occasionally to variants of normal. These limitations prompted the development of new radionuclides for cardiac imaging.

Technetium-99m—labeled imaging agents and gated SPECT. Currently, two technetium-99m–labeled perfusion agents are primarily used for clinical purposes: technetium-99m–

sestamibi and technetium-99m—

tetrofosmin. These agents have improved imaging characteristics over those of thallium 201 because of

the higher photon energy and the

shorter half-life of technetium-99m. Perhaps most importantly, they allow easy ECG-gated acquisition (gated SPECT imaging), permitting the simultaneous evaluation of left ventricular systolic function and myocardial perfusion. The current consensus is that SPECT imaging has superior sensitivity, partly because of its ability to detect an individual stenosis on the basis of localization of stress-induced perfusion defects.

Pharmacologic stress testing. Stress testing through the intravenous use of pharmacologic agents has become the most widely accepted method of nonexercise-based cardiovascular stress testing. This is because such tests are quick and easy to perform.

Agents used for pharmacologic stress-testing are classified as either vasodilator or inotropic and chronotropic drugs. Vasodilators, which include adenosine, dipyridamole, and adenosine triphosphate ([ATP] a derivative of adenosine), produce primary coronary vasodilatation. Adenosine and dipyridamole are equally effective, but adenosine has the advantages of a very short half-life, rapid reversal of side effects after the test is completed, and possibly more predictable vasodilatation. Inotropic and chronotropic agents include dobutamine and arbutamine.

Combined exercise electrocardiography and pharmacologic stress testing. In many laboratories, submaximal treadmill exercise electrocardiographic testing is performed in conjunction with vasodilator stress imaging. This may be particularly helpful in preventing a test from being nondiagnostic as the result of a patient’s limited exercise capacity.

Coronary angiography. Coronary angiography is used to detect or exclude atherosclerotic disease in coronary arteries. This technique helps to assess the severity of an obstructive lesion. When combined with left ventricular angiocardiography, it also enables the investigator to evaluate global and regional function of the left ventricle.

Coronary arteriography is indi-cated in: (1) severely symptomatic patients with chronic stable angina pectoris who are being considered for revascularization; (2) patients with troublesome symptoms that present diagnostic difficulties and in whom there is need to confirm or rule out the diagnosis of ischemic heart disease; (3) patients with known or possible angina pectoris who have survived sudden cardiac death; and (4) patients judged to be at high risk for sustaining coronary events on the basis of having signs of severe ischemia on noninvasive testing, regardless of the presence or severity of symptoms.

Positron emission tomography. Positron emission tomography (PET) is a noninvasive alternative method to radionuclide imaging and pharmacologic stress testing for evaluating myocardial perfusion and viability. A potential major advantage of PET over SPECT as an imaging tech-

nique is its ability to identify and quantify specific metabolic cellular events. PET requires the use of positron-emitting isotopes (such as oxygen 15, carbon 11, nitrogen 13, and fluorine 18) that can be incorporated into physiologically active molecules.

Electron-beam computed tomography. Electron-beam computed to-mography (EBCT) can detect and quantify coronary calcification noninvasively, using serial and contig-uous electrocardiogram-triggered, 100-millisecond, thin-section (3 mm) tomograms from the aorta through the apex of the heart.12,13 Direct relationships have been established between coronary calcification as measured by EBCT and histological, ultrasonic, and angiographic measures of CAD on a heart-by-heart, vessel-by-vessel, and segment-by-segment basis.

Coronary calcification detected by EBCT is found in individuals who have significant angiographic CAD, with a sensitivity ranging from 90% to 100%, a specificity of 45% to 76%, a positive predictive accuracy of 55% to 84%, and a negative predictive accuracy of 84% to 100%.12,13 The finding of coronary calcification on EBCT can identify asymptomatic patients at high risk for CAD, but it is not certain whether this translates into the identification of patients with silent ischemia, which is important because silent ischemia is predictive of cardiac events.

Management

The short-term goal of therapy for chronic angina is improved symptoms. The long-term goal is reduced mortality and prevention of adverse cardiac events. The mainstay of management, however, is still risk-factor modification and patient education.

Therapy of ischemic heart disease can be classified as traditional or emerging and nontraditional. The traditional therapies are listed in the table. Nontraditional therapies include spinal cord stimulation, potassium channel blockers, external counterpulsation, transmyocardial laser revascularization, gene therapy, and heart transplantation.10,14-20

Spinal cord stimulation. Spinal cord stimulation is probably the most promising neurostimulatory mode of therapy for managing angina pectoris. In this technique, electrodes are used to stimulate thoracic nerve fibers. This therapy results in increased sympathetic nerve outflow, with consequent redistribution of myocardial blood flow to ischemic areas and a decrease in the sensation of pain (angina). Patients with refractory angina pectoris experience no adverse clinical rebound phenomenon when neuro-

stimulation is withheld.15,16 Spinal cord stimulation is effective in preventing hospital admissions of patients with refractory angina, without masking serious ischemic symptoms or lead-ing to silent infarction.

Potassium channel blockers. Potassium channel blockers are potent arterial and venous vasodilators. They also activate ATP-driven transmembrane potassium channels, leading to myocardial preconditioning that protects myocardial cells from ischemic injury. Relief of anginal symptoms is similar to that observed with nitrates.14 Nicorandil is the most commonly used potassium channel blocker. It has been used successfully in antianginal therapy outside the United States.

External counterpulsation. Enhanced external counterpulsation increases coronary perfusion pressure and thereby decreases anginal symptoms. External counterpulsation uses a timed sequential inflation of pressure cuffs placed on the legs. Inflation occurs during cardiac diastole, thereby increasing venous return, decreasing left ventricular afterload, and increasing diastolic filling pressures. Cuff pressure is abruptly discontinued just before the beginning of systole. Therapy with external counterpulsation in patients with refractory angina has been reported to improve coronary collateral circulation.

Enhanced external counterpulsation reduces angina and extends the time to exercise-induced ischemia in patients with symptomatic CAD. In most patients such treatment is relatively well tolerated and free of limiting side effects.17

Transmyocardial laser revascularization. Transmyocardial laser revascularization is a technique that uses laser ablation to create transmural channels in ischemic myocardium in areas where revascularization is not possible. Initially, these channels were thought to carry arterialized blood from the left ventricular cavity into the ischemic myocardium; however, it now appears that transmyocardial laser revascularization increases angiogenesis, thereby providing new collateral channels into the ischemic myocardial zone. This revascularization technique appears to be an excellent adjunct to CABG surgery for achieving improved myocardial revascularization in patients with vessels that can and cannot be grafted. Surgical experience has shown this procedure to

be safe. Postoperative follow-up studies of patients who underwent CABG surgery and transmyocardial laser revascularization showed significant improvement in myocardial function and perfusion in zones treated with the laser.18-20 Transmyocardial laser revascularization has also been used in patients with refractory angina who were receiving maximal medical therapy. In this setting, this therapy reduced angina and decreased the number of cardiac events during follow-up as compared with medical therapy alone given to similar patients.

Transmyocardial laser revascularization can be performed during open-heart surgery with a hand-held device, or can be done with a specially designed catheter during cardiac catheterization.

Gene therapy. The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function represents a new approach to the treatment of cardiovascular disease.10 Proof of concept for this approach has been demonstrated in animal models of myocardial ischemia, and it is currently undergoing clinical trials. A number of angiogenic growth factors have been shown to stimulate blood vessel growth under different circumstances. These include the following: members of the fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth families; angiopoietins; cytokines, such as interleukin-6 and interleukin-8; “master switch” genes, such as hypoxia-inducible factor-1a; and platelet-activating factor. Currently, it is unknown which of these methods offers the safest and most effective delivery strategy for inducing clinically important, therapeutic angiogenic responses in ischemic myocardium. Most strategies for transcatheter delivery of angiogenic factors have used an intracoronary route, a technique that may have limitations because of imprecise localization of genes or proteins as well as their systemic delivery to noncardiac tissue.

The effect of direct intraoperative, intramyocardial injection of angiogenic factors on collateral function has been reported in experimental models, and angiogenesis is being studied after direct intramyocardial injection of angiogenic peptides or plasmid vectors during human open-heart surgery. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without the need for surgery. Intrapericardial delivery of angiogenic factors is another potential route of delivery for these new therapeutic agents. This latter route offers the theoretical advantage of prolonged exposure of either coronary or myocardial tissue to the administered drug as a result of the reservoir function of the pericardium.15

Conclusion

Angina pectoris is one of the most common serious medical conditions seen in medical practice today. The evaluation and treatment of these patients has improved markedly over recent years. Newer treatments will soon find their way into daily practice.