Ischemic heart disease: a stable and unstable angina pectoris, MI

Ischemic heart disease: a stable and  unstable angina pectoris, MI. Treatment. Differentiation of the chest pain causes.

Background: Angina pectoris is the result of myocardial ischemia caused by an imbalance between myocardial blood supply and oxygen demand. Angina is a common presenting symptom (typically, chest pain) among patients with coronary artery disease. A comprehensive approach to diagnosis and to medical management of angina pectoris is an integral part of the daily responsibilities of physicians.

Pathophysiology: Myocardial ischemia develops when coronary blood flow becomes inadequate to meet myocardial oxygen demand. This causes myocardial cells to switch from aerobic to anaerobic metabolism, with a progressive impairment of metabolic, mechanical, and electrical functions. Angina pectoris is the most common clinical manifestation of myocardial ischemia. It is caused by chemical and mechanical stimulation of sensory afferent nerve endings in the coronary vessels and myocardium. These nerve fibers extend from the first to fourth thoracic spinal nerves, ascending via the spinal cord to the thalamus, and from there to the cerebral cortex.

Fig. 1 Heart anatomy

Recent studies have shown that adenosine may be the main chemical mediator of anginal pain. During ischemia, ATP is degraded to adenosine, which, after diffusion to the extracellular space, causes arteriolar dilation and anginal pain. Adenosine induces angina mainly by stimulating the A1 receptors in cardiac afferent nerve endings.

Heart rate, myocardial inotropic state, and myocardial wall tension are the major determinants of myocardial metabolic activity and myocardial oxygen demand. Increases in the heart rate and myocardial contractile state result in increased myocardial oxygen demand. Increases in both afterload (ie, aortic pressure) and preload (ie, ventricular end-diastolic volume) result in a proportional elevation of myocardial wall tension and, therefore, increased myocardial oxygen demand. Oxygen supply to any organ system is determined by blood flow and oxygen extraction. Because the resting coronary venous oxygen saturation is already at a relatively low level (approximately 30%), the myocardium has a limited ability to increase its oxygen extraction during episodes of increased demand. Thus, an increase in myocardial oxygen demand (eg, during exercise) must be met by a proportional increase in coronary blood flow.

The ability of the coronary arteries to increase blood flow in response to increased cardiac metabolic demand is referred to as coronary flow reserve (CFR). In healthy people, the maximal coronary blood flow after full dilation of the coronary arteries is roughly 4-6 times the resting coronary blood flow. CFR depends on at least 3 factors: large and small coronary artery resistance, extravascular (ie, myocardial and interstitial) resistance, and blood composition.

Myocardial ischemia can result from (1) a reduction of coronary blood flow caused by fixed and/or dynamic epicardial coronary artery (ie, conductive vessel) stenosis, (2) abnormal constriction or deficient relaxation of coronary microcirculation (ie, resistance vessels), or (3) reduced oxygen-carrying capacity of the blood.

Atherosclerosis is the most common cause of epicardial coronary artery stenosis and, hence, angina pectoris. Patients with a fixed coronary atherosclerotic lesion of at least 50% show myocardial ischemia during increased myocardial metabolic demand as the result of a significant reduction in CFR. These patients are not able to increase their coronary blood flow during stress to match the increased myocardial metabolic demand, thus they experience angina. Fixed atherosclerotic lesions of at least 90% almost completely abolish the flow reserve; patients with these lesions may experience angina at rest.

 

Fig 1a. Structure of cardio-vascular system

 

 

 

Coronary spasm can also reduce CFR significantly by causing dynamic stenosis of coronary arteries. Prinzmetal angina is defined as resting angina associated with ST-segment elevation caused by focal coronary artery spasm. Although most patients with Prinzmetal angina have underlying fixed coronary lesions, some have angiographically normal coronary arteries. Several mechanisms have been proposed for Prinzmetal angina: focal deficiency of nitric oxide production, hyperinsulinemia, low intracellular magnesium levels, smoking cigarettes, and using cocaine.

 

 

 

Approximately 30% of patients with chest pain referred for cardiac catheterization have normal or minimal atherosclerosis of coronary arteries. A subset of these patients demonstrates reduced CFR that is believed to be caused by functional and structural alterations of small coronary arteries and arterioles (ie, resistance vessels). Under normal conditions, resistance vessels are responsible for as much as 95% of coronary artery resistance, with the remaining 5% being from epicardial coronary arteries (ie, conductive vessels). The former is not visualized during regular coronary catheterization. Angina due to dysfunction of small coronary arteries and arterioles is called microvascular angina. Several diseases, such as diabetes mellitus, hypertension, and systemic collagen vascular diseases (eg, systemic lupus erythematosus, polyarteritis nodosa), are believed to cause microvascular abnormalities with subsequent reduction in CFR.

The syndrome that includes angina pectoris, ischemialike ST-segment changes and/or myocardial perfusion defects during stress testing, and angiographically normal coronary arteries is referred to as syndrome X. Most patients with this syndrome are postmenopausal women, and they usually have an excellent prognosis. Syndrome X is believed to be caused by microvascular angina. Multiple mechanisms may be responsible for this syndrome, including (1) impaired endothelial dysfunction, (2) increased release of local vasoconstrictors, (3) fibrosis and medial hypertrophy of the microcirculation, (4) abnormal cardiac adrenergic nerve function, and/or (5) estrogen deficiency.

A number of extravascular forces produced by contraction of adjacent myocardium and intraventricular pressures can influence coronary microcirculation resistance and thus reduce CFR. Extravascular compressive forces are highest in the subendocardium and decrease toward the subepicardium. Left ventricular (LV) hypertrophy together with a higher myocardial oxygen demand (eg, during tachycardia) cause greater susceptibility to ischemia in subendocardial layers.

Myocardial ischemia can also be the result of factors affecting blood composition, such as reduced oxygen-carrying capacity of blood, as is observed with severe anemia (hemoglobin, <8 g/dL), or elevated levels of carboxyhemoglobin. The latter may be the result of inhalation of carbon monoxide in a closed area or of long-term smoking.

Recently, ambulatory ECG monitoring has shown that silent ischemia is a common phenomenon among patients with established coronary artery disease. In one study, as many as 75% of episodes of ischemia (defined as transient ST depression of >1 mm persisting for at least 1 min) occurring in patients with stable angina were clinically silent. Silent ischemia occurs most frequently in early morning hours and may result in transient myocardial contractile dysfunction (ie, stunning). The exact mechanism(s) for silent ischemia is not known. However, autonomic dysfunction (especially in patients with diabetes), a higher pain threshold in some individuals, and the production of excessive quantities of endorphins are among the more popular hypotheses.

Fig. Heart structure

Frequency: In the US: Approximately 6.3 million Americans are estimated to experience angina. An estimated 350,000 new cases of angina occur every year. Each year, 1.1 million new and recurrent cases of an acute coronary event occur in this country, of which more than 40% are fatal. Roughly, more than 12 million Americans had a history of myocardial infarction (MI) and/or angina pectoris in the year 2000.

Mortality/Morbidity: Coronary artery disease is the single most common cause of death in the United States, accounting for almost one death per minute. More than half of those who die suddenly from coronary artery disease have no previous symptoms.

Race: The rate of angina pectoris in women older than 20 years ranges from 3.9% ion-Hispanic white women to 6.2% ion-Hispanic black women and 5.5% in Mexican American women. The rates of angina pectoris for men in the same ethnic groups are 2.6%, 3.1%, and 4.1%, respectively. Among American Indians aged 65-74 years, the rates (per 1000 persons) of new and recurrent heart attacks are 25.1% for men and 9.1% for women.

Sex: Angina pectoris is more often the presenting symptom of coronary artery disease in women than in men, with a female-to-male ratio of 1.7:1. It has a prevalence of 3.9 million in women and 2.3 million in men. The frequency of atypical presentations is also more common among women compared with men. Women have a slightly higher rate of mortality from coronary artery disease compared with men, in part because of an older age at presentation and a frequent lack of classic anginal symptoms. The estimated age-adjusted prevalence of angina is greater in women than in men.

Age: The prevalence of angina pectoris increases with age. Age is a strong independent risk factor for mortality.

 

CLINICAL

History: Most patients with angina pectoris report of retrosternal chest discomfort rather than frank pain. The former is usually described as a pressure, heaviness, squeezing, burning, or choking sensation. Anginal pain may be localized primarily in the epigastrium, back, neck, jaw, or shoulders. Typical locations for radiation of pain are arms, shoulders, and neck. Typically, angina is precipitated by exertion, eating, exposure to cold, or emotional stress. It lasts for approximately 1-5 minutes and is relieved by rest or nitroglycerin. Chest pain lasting only a few seconds is not usually angina pectoris. The intensity of angina does not change with respiration, cough, or change in position. Pain above the mandible and below the epigastrium is rarely anginal iature.

Fig.3 Coronarographia

Ask patients about the frequency of angina, severity of pain, and number of nitroglycerin pills used during angina episodes.

Angina decubitus is a variant of angina pectoris that occurs at night while the patient is recumbent. Some have suggested that it is induced by an increase in myocardial oxygen demand caused by expansion of the blood volume with increased venous return during recumbency.

The Canadian Cardiovascular Society grading scale is used for classification of angina severity, as follows:

Class I – Angina only during strenuous or prolonged physical activity

Class II – Slight limitation, with angina only during vigorous physical activity

Class III – Symptoms with everyday living activities, ie, moderate limitation

Class IV – Inability to perform any activity without angina or angina at rest, ie, severe limitation

The New York Heart Association classification is also used to quantify the functional limitation imposed by patients’ symptoms, as follows:

Class I – No limitation of physical activity (Ordinary physical activity does not cause symptoms.)

Class II – Slight limitation of physical activity (Ordinary physical activity does cause symptoms.)

Class III – Moderate limitation of activity (Patient is comfortable at rest, but less than ordinary activities cause symptoms.)

Class IV – Unable to perform any physical activity without discomfort, therefore severe limitation (Patient may be symptomatic even at rest.)

Unstable angina is defined as new-onset angina (ie, within 2 mo of initial presentation) of at least class III severity, significant recent increase in frequency and severity of angina, or angina at rest.

Fig. Angiography

Physical:

For most patients with stable angina, physical examination findings are normal. Diagnosing secondary causes of angina, such as aortic stenosis, is important.

A positive Levine sign (characterized by the patient’s fist clenched over the sternum when describing the discomfort) is suggestive of angina pectoris.

Look for physical signs of abnormal lipid metabolism (eg, xanthelasma, xanthoma) or of diffuse atherosclerosis (eg, absence or diminished peripheral pulses, increased light reflexes or arteriovenous nicking upon ophthalmic examination, carotid bruit).

Examination of patients during the angina attack may be more helpful. Useful physical findings include third and/or fourth heart sounds due to LV systolic and/or diastolic dysfunction and mitral regurgitation secondary to papillary muscle dysfunction.

Pain produced by chest wall pressure is usually of chest wall origin.

Causes:

Decrease in myocardial blood supply due to increased coronary resistance in large and small coronary arteries

Significant coronary atherosclerotic lesion in the large epicardial coronary arteries (ie, conductive vessels) with at least a 50% reduction in arterial diameter

Coronary spasm (ie, Prinzmetal angina)

Abnormal constriction or deficient endothelial-dependent relaxation of resistant vessels associated with diffuse vascular disease (ie, microvascular angina)

Fig. 4 Pathogenesis of atherosclerosis

Syndrome X

Systemic inflammatory or collagen vascular disease, such as scleroderma, systemic lupus erythematous, Kawasaki disease, polyarteritis nodosa, and Takayasu arteritis

Increased extravascular forces, such as severe LV hypertrophy caused by hypertension, aortic stenosis, or hypertrophic cardiomyopathy, or increased LV diastolic pressures

Reduction in the oxygen-carrying capacity of blood, such as elevated carboxyhemoglobin or severe anemia (hemoglobin, <8 g/dL)

Congenital anomalies of the origin and/or course of the major epicardial coronary arteries

Structural abnormalities of the coronary arteries

Congenital coronary artery aneurysm or fistula

Coronary artery ectasia

Coronary artery fibrosis after chest radiation

Coronary intimal fibrosis following cardiac transplantation

Risk factors

Major risk factors for atherosclerosis: These include a family history of premature coronary artery disease, cigarette smoking, diabetes mellitus, hypercholesterolemia, or systemic hypertension.

Other risk factors: These include LV hypertrophy, obesity, and elevated serum levels of homocysteine, lipoprotein (a), plasminogen activator inhibitor, fibrinogen, serum triglycerides, or low high-density lipoprotein (HDL).

Fig. 5 Pathogenesis of atherosclerosis

 

Metabolic syndrome: This has recently been characterized by the presence of hyperinsulinemia (fasting glucose level, >110 mg/dL), abdominal obesity (waist circumference, >40 in for men or >35 in for women), decreased HDL cholesterol levels (<40 mg/dL for men or <50 mg/dL for women), hypertriglyceridemia (>150 mg/dL), and hypertension (>130/85 mm Hg). Based on data from the 2000 US census, an estimated 47 million Americans have the metabolic syndrome. Patients with the metabolic syndrome have a 3-fold increased risk for coronary atherosclerosis and stroke compared with those without this syndrome.

Precipitating factors: These include factors such as severe anemia, fever, tachyarrhythmias, catecholamines, emotional stress, and hyperthyroidism, which increase myocardial oxygen demand.

Preventive factors: Factors associated with reduced risk of atherosclerosis are a high serum HDL cholesterol level, physical activity, estrogen, and moderate alcohol intake (1-2 drinks/d).

 

DIFFERENTIALS

Anemia, Anxiety Disorders , Aortic Dissection ,Aortic Stenosis ,Biliary Colic ,Cardiomyopathy, Hypertrophic ,Cholecystitis ,Coronary Artery Atherosclerosis ,Coronary Artery Vasospasm ,Diabetes Mellitus, Type 1 ,Diabetes ,ellitus, Type 2 ,Gastric Ulcers ,Gastritis, Acute ,Gastroesophageal Reflux Disease ,Hiatal Hernia ,Hypercholesterolemia, Familial ,Hypercholesterolemia, Polygenic ,Hypertension ,Hyperthyroidism ,Isolated Coronary Artery ,nomalies ,Kawasaki Disease ,Mitral Regurgitation ,Mitral Valve Prolapse ,Panic Disorder ,Pericarditis, Acute ,Pleurodynia ,Pneumothorax ,Polyarteritis Nodosa ,Pott Disease (Tuberculous Spondylitis) ,Pulmonary Embolism ,Pulmonary Hypertension, Primary ,Pulmonary Hypertension, Secondary ,Scleroderma ,Systemic Lupus Erythematosus ,Takayasu Arteritis ,Toxicity, Cocaine ,Varicella-Zoster Virus

Imaging Studies:

Chest radiograph findings are usually normal in patients with angina pectoris. However, they may show cardiomegaly in patients with previous MI, ischemic cardiomyopathy, pericardial effusion, or acute pulmonary edema. Calcification of coronary arteries frequently correlates with major coronary artery disease.

 

 

 

 

 

Graded exercise stress testing is the most widely used test for the evaluation of patients presenting with chest pain. In patients with established stable angina pectoris, it also can provide prognostic information about the extent of disease.

Exercise stress testing can be performed alone and in conjunction with echocardiography or myocardial perfusion scintigraphy tests. Stress echocardiography has an overall sensitivity of 78% and specificity of 86%; myocardial perfusion scintigraphy has an overall sensitivity of 83% and specificity of 77%. Exercise stress testing alone generally has somewhat lower sensitivity and specificity, but it is cheaper and therefore is a reasonable choice in those with a low probability of disease.

Fig. Cells which take part in atherosclerosis

 

 

These test results must be interpreted in the context of the likelihood of the presence of coronary artery disease determined from the patient’s history and physical examination findings. In a population with low prevalence, the predictive abilities of these tests are low; however, in patients with a high likelihood of coronary artery disease, the predictive value is much higher.

Stress echocardiography can be used to evaluate segmental wall motion during exercise. It detects changes in regional wall motion that occur during myocardial ischemia. Normal myocardium becomes hyperdynamic during exercise; ischemic segments become hypokinetic or akinetic.

Stress echocardiography has the advantage of simultaneous evaluation of LV function, cardiac dimensions, and valvular disease. It is especially useful in patients with baseline ECG abnormalities and those with systolic murmurs suggestive of aortic stenosis or hypertrophic cardiomyopathy.

It is also helpful for localizing ischemia and evaluating its severity.

Signs of severe coronary artery disease during exercise stress echocardiography include LV dilation, a decrease in global systolic function, and new or worsening mitral regurgitation. However, with dobutamine stress echocardiography, even in patients with severe coronary artery disease, the LV cavity may not dilate and global systolic function may improve.

A major problem with stress echocardiography is the technical difficulty with obtaining adequate images in some patients.

Thallium Tl 201 and technetium Tc 99m sestamibi are the most frequently used myocardial perfusion scintigraphy tests. These tests are especially useful in patients with baseline ECG abnormalities, to localize the region of ischemia, and as prognostic indicators. The presence of increased lung uptake upon thallium imaging is associated with a poor prognosis. Increased lung uptake, together with poststress dilation of the LV and multiple perfusion defects, is suggestive of either left main coronary artery disease or severe 3-vessel disease. The number of affected myocardial segments is predictive of long-term survival. Smaller perfusion defects are usually associated with peripheral coronary artery lesions, which are associated with a better prognosis. The absence of perfusion defects even in the presence of symptoms indicates an excellent prognosis.

 

 

Fig. 9 Pathogenesis of atherosclerosis

The frequency of infarction or death is 1 case per 10,000 stress tests. Absolute contraindications include symptomatic cardiac arrhythmias, severe aortic stenosis, acute MI within the previous 2 days, acute myocarditis, or pericarditis. Discontinue the exercise stress test in the presence of chest pain, a drop in systolic blood pressure of more than 10 mm Hg, severe shortness of breath, fatigue, dizziness or near syncope, ST depression of more than 2 mm, ST elevation of at least 1 mm without diagnostic Q waves, or development of ventricular tachyarrhythmia.

Fig. 10 Pathogenesis of atherosclerosis

 

Other Tests:

ECG is useful for evaluating persons with angina pectoris; however, findings are variable among patients.

Approximately 50% of patients with angina pectoris have normal findings after a resting ECG. However, abnormalities such as evidence for prior MI, intraventricular conduction delay, various degrees of atrioventricular block, arrhythmias, or ST-T–wave changes may be seen.

During an attack of angina pectoris, 50% of patients with normal findings after resting ECG show abnormalities. A 1-mm or greater depression of the ST segment below the baseline, measured 80 milliseconds from the J point, is the most characteristic change. Reversible ST-segment elevation occurs with Prinzmetal angina. Some patients with coronary artery disease may show pseudonormalization of the resting ECG ST-T–wave abnormalities during episodes of chest pain.

 

 

 

 

Fig 11. Subendocardial ischemia

 

Exercise with ECG monitoring alone is the initial procedure of choice in patients without baseline ST-segment abnormalities or in whom anatomic localization of ischemia is not a consideration.

Horizontal or down-sloping ST-segment depression of at least 1 mm, measured 80 milliseconds from the J point, is considered the characteristic ischemic response.

ST-segment depression of more than 2 mm at a low workload or that persists for more than 5 minutes after termination of exercise and a failure of blood pressure to rise or an actual drop in blood pressure are signs of severe ischemic heart disease and a poor prognosis.

Withhold beta-blockers for approximately 48 hours before the stress test, whenever possible. Patients on digoxin and those with LV hypertrophy with repolarization abnormalities more often show positive results. Exercise stress tests have lower sensitivity and specificity in women and in patients with left bundle-branch block.

Pharmacologic agents (eg, dobutamine, dipyridamole, adenosine) can be used in patients who are unable to exercise.

Ambulatory ECG monitoring can be used for diagnostic purposes in patients with chest pain suggestive of Prinzmetal angina but is primarily used to evaluate the frequency of silent ischemia. Silent ischemia has been shown to be an independent predictor of mortality in patients with angina pectoris.

Several studies have shown that calcium in the coronary arteries as detected by electron-beam computed tomography is an important indicator of coronary artery stenosis. In these studies, the sensitivity of a positive electron-beam computed tomography scan ranged from 85-100% and the specificity varied from 41-76%, while the positive predictive value varied from 55-84% and the negative predictive value varied from 84-100%. However, several studies have shown inconsistent reproducibility in repeated measures of coronary calcium with electron-beam computed tomography. Thus, its proper role at this time remains controversial.

Procedures:

Selective coronary angiography is the definitive diagnostic test for evaluating the anatomic extent and severity of coronary artery disease.

Consider coronary angiography in symptomatic patients with inconclusive noninvasive study results, in survivors of sudden cardiac death, in those who are considered to have a poor prognosis based on the results of noninvasive studies, in those with occupational requirements for a definite diagnosis (eg, pilots), or in patients with coronary artery disease who are severely symptomatic despite maximal medical therapy.

In patients in whom Prinzmetal angina is suggested, provocative testing with ergonovine maleate during coronary angiography may be useful.

Intra-aortic balloon counterpulsation can be used in patients who continue to have unstable angina pectoris despite maximal medical treatment. This procedure should be followed promptly by coronary angiography with possible coronary revascularization.

In patients whose angina is refractory to medical therapy who are not suitable candidates for either percutaneous or surgical revascularization, enhanced external counterpulsation is a safe and noninvasive alternative therapy. It increases coronary perfusion and reduces myocardial oxygen demand by diastolic augmentation of the central aortic pressure. Several studies have shown that patients treated with enhanced external counterpulsation have a significantly reduced number of anginal episodes, improved exercise tolerance, and decreased daily use of nitroglycerin tablets. Its therapeutic effects on quality of life are noted to remain at 1-year follow-up.

Fig. Vessels atherosclerosis

 

TREATMENT

Medical Care: The main goals of treatment in angina pectoris are to relieve the symptoms, slow the progression of disease, and reduce the possibility of future events, especially MI and premature death.

General measures

Smoking cessation results in a significant reduction of acute adverse effects on the heart and may reverse, or at least slow, atherosclerosis. Strongly encourage patients to quit smoking, and take an active role in helping them to achieve this goal.

Treat risk factors, including hypertension, diabetes mellitus, obesity, and hyperlipidemia.

Several clinical trials have shown that in patients with established coronary artery disease, reduction of low-density lipoprotein (LDL) level with a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor (ie, statin) is associated with significant reductions in both mortality rate and major cardiac events.

These benefits are present even in patients with mild-to-moderate elevations of LDL cholesterol level.

Recent trials with cholesterol-lowering agents have confirmed the benefits of the therapeutic LDL lowering in older persons.

Angiographic studies demonstrate that a reduction of the LDL level in patients with coronary artery disease could cause slowing of progression, stabilization, or even regression of coronary artery lesions.

A recent study demonstrates a significant reduction of symptomatic myocardial ischemia in patients with unstable angina or non–Q-wave infarction with the administration of a statin during the early acute phase.

In a more recent study of 10,001 patients with stable coronary artery disease, an aggressive cholesterol-lowering approach with atorvastatin 80 mg daily (mean cholesterol level of 77 mg/dL) compared to a less-aggressive approach with atorvastatin 10 mg daily (mean cholesterol level of 101 mg/dL) resulted in a 2.2% absolute reduction and a 22% relative reduction in the occurrence of a first major cardiovascular event (defined as death from coronary heart disease; nonfatal, non–procedure-related myocardial infarction; resuscitation from cardiac arrest; or fatal or nonfatal stroke).This occurred with a greater incidence of elevated aminotransferase levels with the aggressive cholesterol-lowering approach (1.2% vs 0.2%, p<0.001).

On the basis of several recent studies that have demonstrated the benefits of more aggressive LDL-lowering therapies in high-risk patients with coronary artery disease, the Committee of the National Cholesterol Education Program recently made the following modifications to the Adult Treatment Panel III (ATP III) guidelines.

In high-risk patients, a serum LDL cholesterol level of less than 100 mg/dL is the goal.

Fig. Vessels atherosclerosis

 

In very high-risk patients, an LDL cholesterol level goal of less than 70 mg/dL is a therapeutic option. Patients in the category of very high risk are those with established coronary artery disease with one of the following: multiple major risk factors (especially diabetes), severe and poorly controlled risk factors (especially continued cigarette smoking), multiple risk factors of the metabolic syndrome (especially high triglyceride levels [>200 mg/dL] plus non-HDL cholesterol level [>130 mg/dL] with low HDL cholesterol level [<40 mg/dL]), and patients with acute coronary syndromes.

For moderately high-risk persons (2+ risk factors), the recommended LDL cholesterol level is less than130 mg/dL, but an LDL cholesterol level of 100 mg/dL is a therapeutic option.

Some triglyceride-rich lipoproteins, including partially degraded very LDL levels, are believed to be independent risk factors for coronary artery disease. In daily practice, non-HDL cholesterol level (ie, LDL + very LDL cholesterol [total cholesterol – HDL cholesterol]) is the most readily available measure of the total pool of these atherogenic lipoproteins. Thus, the ATP III has identified non-HDL cholesterol level as a secondary target of therapy in persons with high triglyceride levels (>200 mg/dL). The goal for non-HDL cholesterol level (for persons with serum triglyceride levels >200 mg/dL) is 30 mg/dL higher than the identified LDL cholesterol level goal.

Patients with established coronary disease and low HDL cholesterol levels are at high risk for recurrent events and should be targeted for aggressive nonpharmacological (ie, dietary modification, weight loss, physical exercise) and pharmacological treatment.

A recent study demonstrated that in patients with established coronary artery disease who have low HDL and low-risk LDL levels, drug therapy with medications that raise HDL cholesterol levels and lower triglyceride levels but have no effect on LDL cholesterol levels (eg, gemfibrozil) could significantly reduce the risk of major cardiac events.

Currently, the accepted approach to the management of patients with coronary artery disease and low HDL levels is as follows:

In all persons with low HDL cholesterol levels, the primary target of therapy is to achieve the ATP III guideline LDL cholesterol level goals with diet, exercise, and drug therapy as needed.

After reaching the targeted LDL level goal, emphasis shifts to other issues. That is, in patients with low HDL cholesterol levels who have associated high triglyceride levels (>200 mg/dL), the secondary priority is to achieve the non-HDL cholesterol level goal of 30 mg/dL higher than the identified LDL cholesterol level goal. In patients with isolated low HDL cholesterol levels (triglycerides <200 mg/dL), drugs to raise the HDL cholesterol level (eg, gemfibrozil, nicotinic acid) can be considered.

Exercise training results in improvement of symptoms, increase in the threshold of ischemia, and improvement of patients’ sense of well-being. However, before enrolling a patient in an exercise-training program, perform an exercise tolerance test to establish the safety of such a program.

Consider enteric-coated aspirin at a dose of 80-325 mg/d for all patients with stable angina who have no contraindications to its use. In patients in whom aspirin cannot be used because of allergy or gastrointestinal complications, consider clopidogrel.

Although early observational studies suggested a cardiovascular protective effect with the use of hormone replacement therapy, recent large randomized trials failed to demonstrate any benefit with hormone replacement therapy in the primary or secondary prevention of cardiovascular disease.

Fig. Patient with IHD

 

In fact, these studies even demonstrated an increased risk of coronary artery disease and stroke in patients on hormone replacement therapy.

The Women’s Health Initiative study demonstrated that the use of hormone replacement therapy for 1 year in 10,000 healthy postmenopausal women is associated with 7 more instances of coronary artery disease, 8 more strokes, 8 more pulmonary emboli, 8 more invasive breast cancers, 5 fewer hip fractures, and 6 fewer colorectal cancers.

Based on these data, the risks and benefits of hormone replacement therapy must be assessed on an individual basis for each patient.

Sublingual nitroglycerin has been the mainstay of treatment for angina pectoris. Sublingual nitroglycerin can be used for acute relief of angina and prophylactically before activities that may precipitate angina. No evidence indicates that long-acting nitrates improve survival in patients with coronary artery disease.

Beta-blockers are also used for symptomatic relief of angina and prevention of ischemic events. They work by reducing myocardial oxygen demand and by decreasing the heart rate and myocardial contractility. Beta-blockers have been shown to reduce the rates of mortality and morbidity following acute MI.

Long-acting heart rate–slowing calcium channel blockers can be used to control anginal symptoms in patients with a contraindication to beta-blockers and in those in whom symptomatic relief of angina cannot be achieved with the use of beta-blockers, nitrates, or both. Avoid short-acting dihydropyridine calcium channel blockers because they have been shown to increase the risk of adverse cardiac events.

Anginal symptoms in patients with Prinzmetal angina can be treated with calcium channel blockers with or without nitrates. In one study, supplemental vitamin E added to a calcium channel blocker significantly reduced anginal symptoms among such patients.

In patients with syndrome X and hypertension, ACE inhibitors may normalize thallium perfusion defects and increase exercise capacity.

Surgical Care:

Revascularization therapy (ie, coronary revascularization) can be considered in patients with left main artery stenosis greater than 50%, 2- or 3-vessel disease and LV dysfunction (ejection fraction, <45%), poor prognostic signs during noninvasive studies, or severe symptoms despite maximum medical therapy. The 2 main coronary revascularization procedures are percutaneous transluminal coronary angioplasty, with or without coronary stenting, and coronary artery bypass grafting.

Patients with 1- or 2-vessel disease and normal LV function who have anatomically suitable lesions are candidates for percutaneous transluminal coronary angioplasty and coronary stenting. Restenosis is the major complication, with symptomatic restenosis occurring in 20-25% of patients. Restenosis mostly occurs during the first 6 months after the procedure and can be managed by repeat angioplasty. Several recent trials have demonstrated that the use of drug-eluting stents (eg, sirolimus-eluting stents, paclitaxel-coated stents) can remarkably reduce the rate of in-stent restenosis. Recently, with the introduction of these drug-coated stents, patients with multivessel coronary artery disease are more frequently treated with percutaneous revascularization as opposed to the surgical revascularization.

Patients with single-vessel disease and normal ventricular function treated with percutaneous transluminal coronary angioplasty show improved exercise tolerance and fewer episodes of angina compared with those who receive medical treatment. However, no difference in the frequency of MI or death has been shown between these two groups.

Fig. Pathgenesis of atherosclerosis

Patients with significant left main coronary artery disease, 2- or 3-vessel disease and LV dysfunction, diabetes mellitus, or lesions anatomically unsuitable for percutaneous transluminal coronary angioplasty have better results with coronary artery bypass grafting. The overall operative mortality rate for coronary artery bypass grafting is approximately 1.3%. The rate of graft patency 10 years after surgery is less than 50% for vein grafting, although more than 90% of grafts using internal mammary arteries are patent at 10 years. In recent years, interest has increased regarding surgery without cardiopulmonary bypass (ie, off-pump) in an attempt to avoid the morbidity associated with cardiopulmonary bypass. A recent randomized study demonstrated that off-pump coronary surgery was as safe as on-pump surgery and caused less myocardial damage. However, the graft-patency rate was lower at 3 months in the off-pump group than in the on-pump group.

Recently, laser transmyocardial revascularization has been used as an experimental therapy for the treatment of severe, chronic, stable angina refractory to medical or other therapies. This technique has been performed with either an epicardial surgical technique or by a percutaneous approach. In both approaches, a series of transmural endomyocardial channels are created to improve myocardial perfusion. The surgical transmyocardial revascularization technique has been associated with symptomatic relief for end-stage chronic angina in the short term. However, no published data address the long-term efficacy of surgical transmyocardial revascularization. Nonetheless, this technique appears to provide at least symptomatic relief for end-stage chronic angina in the short term.

Diet: A diet low in saturated fat and dietary cholesterol is the mainstay of the Step I and Step II diet from the American Heart Association.

Activity: The level of activity that aggravates anginal symptoms is different for each patient. However, most patients with stable angina can avoid symptoms during daily activities simply by reducing the speed of activity.

 

MEDICATION

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antiplatelet agents — Prevent thrombus formation by inhibiting platelet aggregation. Aspirin is proven beneficial in primary and secondary prevention of coronary artery disease. In patients with aspirin intolerance, use clopidogrel. Clopidogrel is also used in combination with aspirin after coronary stent placement. Recently, clopidogrel use in addition to aspirin has been shown to be significantly superior to aspirin alone in patients with acute coronary syndrome without ST-segment elevation MI.

 

 

 

 

 

Drug Category: Beta-adrenergic blocking agents — Work by competing with endogenous catecholamines for beta-adrenergic receptors. Reduce myocardial oxygen consumption via several effects, including decrease in resting and exercise heart rates and reductions in myocardial contractility and afterload. Classified as nonselective, beta-1 selective, and having intrinsic sympathomimetic effects.

 

 

 

 

Drug Category: Calcium channel blockers — Reduce transmembrane flux of calcium via calcium channels. Cause smooth muscle relaxation, resulting in peripheral arterial vasodilation and afterload reduction. Indicated when symptoms persist despite treatment with beta-blockers or when beta-blockers are contraindicated. Also indicated in patients with Prinzmetal angina with or without nitrates.

 

 

 

 

Drug Category: Short-acting nitroglycerins — Suitable for immediate relief of exertional or rest angina. Can also be used for prophylaxis several minutes before planned exercise to avoid angina. Reduce myocardial oxygen demand by reduction of LV and arterial pressure, primarily by reducing preload.

 

 

 

Drug Category: Long-acting nitroglycerins — Reduce LV preload and afterload by venous and arterial dilation, which subsequently reduces myocardial oxygen consumption and relieves angina. Also cause dilation of epicardial coronary arteries, which is beneficial in patients with coronary spasm. In addition, nitroglycerin has antithrombotic and antiplatelet effects in patients with angina pectoris. No evidence suggests that nitrates improve survival or slow progression of coronary artery disease.

 

Drug Category: Angiotensin-converting enzyme inhibitors — Recently shown to reduce rates of death, MI, stroke, and need for revascularization procedures in patients with coronary artery disease or diabetes mellitus and at least one other cardiovascular risk factor, irrespective of the presence of hypertension or heart failure.

 

Fig Thrombosis of coronary artery

Drug Category: Anti-ischemic agents, miscellaneous — Ranolazine elicits action unlike beta-blockers, calcium antagonists, or nitrates. It does not affect hemodynamics or contractile and conduction parameters.

 

FOLLOW-UP

Deterrence/Prevention:

Coronary atherosclerosis is the main preventable cause of mortality in the United States. A rigorous effort to address correctable risk factors is the mainstay of preventive cardiovascular medicine.

Smoking cessation is the single most effective preventive intervention to reduce coronary atherosclerosis prevalence. It has been associated with a coronary artery disease reduction of 7-47% in primary prevention settings.

Aggressive treatment of diabetes mellitus, hypertension, LV hypertrophy, hyperlipidemia, and obesity has an important role in the prevention of coronary artery disease.

The most important recent development in coronary atherosclerosis risk modification is the introduction of inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Reductions of total and LDL cholesterol levels by 25% and 35%, respectively, can achieve a similar reduction in rates of total and coronary mortality, MI, and need for coronary revascularization.

Complications:

Complications of angina pectoris include unstable angina, MI, and death.

Prognosis:

Important prognostic indicators in patients with angina pectoris include LV function, severity and location of atherosclerotic lesions, and response of symptoms to medical treatment.

LV function is the strongest predictor of long-term survival. Elevated LV end-diastolic pressure and volume along with reduced LV ejection fraction (<40%) are poor prognostic signs.

Critical lesions of left main and proximal left anterior descending coronary arteries are associated with a greater risk. Mortality rates are also directly associated with the number of epicardial arteries involved.

Unstable angina, recent MI, or both is a sign of atherosclerotic plaque instability, which is a strong predictor of increased risk of short-term coronary events.

A number of signs during noninvasive testing are predictive of a higher risk of coronary events, including ST-segment depression of more than 2 mm at a low workload, ST-segment depression that persists for more than 5 minutes after termination of exercise, and failure of blood pressure to rise or an actual drop in blood pressure.

Patients who continue to smoke after an MI have a 22-47% increased risk of reinfarction and death.

In general, Prinzmetal angina and syndrome X are associated with excellent long-term prognoses.

Patient Education:

Educating patients about the benefits of smoking cessation, a low-cholesterol diet, physical activity, and periodic screening for diabetes mellitus and hypertension is the prime component of a long-term management plan.

For excellent patient education resources, visit eMedicine’s Circulatory Problems Center, Cholesterol Center, Heart Center, and Statins Center. Also, see eMedicine’s patient education articles Angina Pectoris, High Cholesterol, Understanding Your Cholesterol Level, Lifestyle Cholesterol Management, Understanding Cholesterol-Lowering Medications, Chest Pain, Coronary Heart Disease, and Heart Attack.

 

MISCELLANEOUS

Medical/Legal Pitfalls:

In patients with stable angina pectoris, even the most carefully performed history and physical examination have limitations. Classification of these patients solely on the basis of history and physical examination findings may lead to serious mistakes. Some type of stress testing is usually indicated to confirm the diagnosis and quantitate the severity of ischemia.

In women, elderly persons, and diabetic patients, coronary artery disease may manifest with atypical presentations other than angina pectoris, such as silent ischemia or infarction. Physicians should use a careful approach when evaluating these patients.

Classical and untypical variants of the acute myocardial infarction, criteria for diagnosis. Differential programs of  treatment of the uncomplicated myocardial infarction, physical rehabilitation

 

Background: Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to prolonged ischemia. This usually results from an imbalance of oxygen supply and demand. The appearance of cardiac enzymes in the circulation generally indicates myocardial necrosis. MI is considered, more appropriately, part of a spectrum referred to as acute coronary syndromes (ACSs), which also includes unstable angina and non–ST-elevation MI (NSTEMI). Patients with ischemic discomfort may or may not have ST-segment elevation. Most of those with ST-segment elevation will develop Q waves. Those without ST elevations will ultimately be diagnosed with unstable angina or NSTEMI based on the presence of cardiac enzymes.

Fig. Pathogenesis of MI

MI may lead to impairment of systolic function or diastolic function and to increased predisposition to arrhythmias and other long-term complications.

Pathophysiology: Atherosclerosis is the disease primarily responsible for most ACS cases. Approximately 90% of MIs result from an acute thrombus that obstructs an atherosclerotic coronary artery. Plaque rupture is considered to be the major trigger of coronary thrombosis.

Following plaque rupture, platelet activation and aggregation, coagulation pathway activation, and endothelial vasoconstriction occur and lead to coronary thrombosis and occlusion.

Atherogenesis

 

Consider nonatherosclerotic causes of acute MIs in younger patients or if no evidence of atherosclerosis is noted. Such causes include coronary emboli from sources such as an infected cardiac valve, coronary occlusion secondary to vasculitis, primary coronary vasospasm (variant angina), cocaine use, or other factors leading to mismatch of oxygen supply and demand, as may occur with a significant GI bleed.

Fig. Atherogenesis

 

Frequency:  In the US: Approximately 1.5 million cases of MI occur each year. Internationally: Cardiovascular diseases cause 12 million deaths throughout the world each year, according to the third monitoring report of the World Health Organization, 1991-93. They cause half of all deaths in several developed countries and are one of the main causes of death in many developing countries; they are the major cause of death in adults everywhere.

Mortality/Morbidity: Cardiovascular disease is the leading cause of death in the United States; approximately 500,000-700,000 deaths related to the coronary artery occur each year.

Ischemic heart disease is the leading cause of death worldwide. Approximately 6.3 million deaths due to heart disease occurred in 1990 worldwide, which represents 29% of all deaths. The prevalence of coronary artery disease (CAD) is increasing rapidly ionindustrialized countries.

Race: Cardiovascular disease is the leading cause of morbidity and mortality among African American, Hispanic, and white populations in the United States.

Sex: A male predominance in incidence exists up to approximately age 70 years, when the sexes converge to equal incidence.

Premenopausal women appear to be somewhat protected from atherosclerosis, possibly owing to the effects of estrogen.

Age:Incidence increases with age. Most patients who develop an acute MI are older than 60 years. Elderly people also tend to have higher rates of morbidity and mortality from their infarcts.

CLINICAL

History:

Chest pain

This is usually described as a substernal pressure sensation that also may be described as squeezing, aching, burning, or even sharp pain.

Prolonged chest discomfort lasting longer than 30 minutes is most compatible with infarction.

Radiation to the left arm or neck is common.

The sensation is precipitated by exertion and relieved by rest and nitroglycerin.

Chest pain may be associated with nausea, vomiting, diaphoresis, dyspnea, fatigue, or palpitations.

Atypical chest pain is common, especially in patients with diabetes and in elderly patients. However, any patient may present with atypical symptoms. These symptoms are considered the anginal equivalent for that patient.

Shortness of breath

Shortness of breath may be the patient’s anginal equivalent or a symptom of heart failure.

It is due to elevated end-diastolic pressures secondary to ischemia, which may then lead to elevated pulmonary pressures.

Fig. ECG changes in MI

Atypical presentations

Atypical presentations are common and frequently lead to misdiagnoses.

A patient may, for example, present with abdominal discomfort or jaw pain as his or her anginal equivalent.

An elderly patient may present with altered mental status.

Low threshold should be maintained when evaluating high- and moderate-risk patients, as their anginal equivalents may mimic other presentations.

Women tend to present more commonly with atypical symptoms such as sharp pain, fatigue, weakness, and other nonspecific complaints.

 

Physical: Physical examination findings can vary; one patient may be comfortable in bed, with normal examination results, while another may be in severe pain with significant respiratory distress requiring ventilatory support.

Low-grade fever may be present.

Hypotension or hypertension can be observed depending on the extent of the MI.

Fourth heart sound (S4) may be heard in patients with ischemia. With ischemia, diastolic dysfunction is the first physiologically measurable effect and this can then cause a stiff ventricle and an audible S4.

Dyskinetic cardiac bulge (in anterior wall MI) can occasionally be palpated.

Systolic murmur can be heard if mitral regurgitation (MR) or ventricular septal defect (VSD) develops.

Other findings include cool, clammy skin and diaphoresis.

Signs of congestive heart failure (CHF) may be found, including the following:

Third heart sound (S3) gallop

Pulmonary rales

Lower extremity edema

Elevated jugular venous pressure

Fig Stages of MI

Causes: Atherosclerosis with occlusive or partially occlusive thrombus formation, Nonmodifiable risk factors for atherosclerosis, Age, Sex, Family history of premature coronary heart disease, Modifiable risk factors for atherosclerosis, Smoking or other tobacco use, Diabetes mellitus, Hypertension, Dyslipidemia, Obesity, New and other risk factors for atherosclerosis, Elevated homocysteine levels, Male pattern baldness. Sedentary lifestyle and/or lack of exercise, Psychosocial stress, Presence of peripheral vascular disease, Poor oral hygiene, Nonatherosclerotic causes, Vasculitis , Coronary emboli , Congenital coronary anomalies, Coronary trauma, Coronary spasm, Drug use (cocaine), Factors that increase oxygen requirement, such as heavy exertion, fever, or hyperthyroidism , Factors that decrease oxygen delivery, such as hypoxemia of severe anemia

Other Problems to be Considered:

Pneumonia

Pancreatitis

Lab Studies:

Cardiac enzymes: In patients with suspected MI, obtain cardiac enzymes at regular intervals, starting upon admission and serially for as long as 24 hours.

Creatine kinase level

Creatine kinase comprises 3 isoenzymes, including creatine kinase with muscle subunits (CK-MM), which is found mainly in skeletal muscle; creatine kinase with brain subunits (CK-BB), predominantly found in the brain; and myocardial muscle creatine kinase (CK-MB), which is found mainly in the heart.

Serial measurements of CK-MB isoenzyme levels were previously the standard criterion for diagnosis of MI. CK-MB levels increase within 3-12 hours of onset of chest pain, reach peak values within 24 hours, and return to baseline after 48-72 hours. Levels peak earlier (wash out) if reperfusion occurs. Sensitivity is approximately 95%, with high specificity. However, sensitivity and specificity are not as high as for troponin levels, and the trend has favored using troponins for the diagnosis of MI.

Troponin levels

Troponin levels are now considered the criterion standard in defining and diagnosing MI, according to the American College of Cardiology (ACC)/American Heart Association (AHA) consensus statement on MI (Braunwald, 2000).

Cardiac troponin levels (troponin-T and troponin-I) have a greater sensitivity and specificity than CK-MB levels in detecting MI. They have important diagnostic and prognostic roles. Positive troponin levels are considered virtually diagnostic of MI in the most recent ACC/AHA revisions, as they are without equal in combined specificity and sensitivity in this diagnosis.

Serum levels increase within 3-12 hours from the onset of chest pain, peak at 24-48 hours, and return to baseline over 5-14 days.

Myoglobin levels

Urine myoglobin levels rise within 1-4 hours from the onset of chest pain.

Myoglobin levels are highly sensitive but not specific, and they may be useful within the context of other studies and in early detection of MI in the ED.

Complete blood cell count

Obtain a CBC count if MI is suspected to rule out anemia as a cause of decreased oxygen supply and prior to giving thrombolytics.

Leukocytosis is also common, but not universal, in the setting of acute MI.

A platelet count is necessary if a IIb/IIIa agent is considered; furthermore, the patient’s WBC count may be elevated modestly in the setting of MI, signifying an acute inflammatory state.

Chemistry profile

In the setting of MI, closely monitor potassium and magnesium levels.

Creatinine level is also needed prior to initiating treatment with an angiotensin-converting enzyme (ACE) inhibitor.

Lipid level profile: This may be helpful if obtained upon presentation because levels can change after 12-24 hours of an acute illness.

C-reactive protein (CRP) levels: Consider measuring CRP levels and other markers of inflammation upon presentation if an ACS is suspected.

Imaging Studies:

Chest radiography

Upon presentation, obtain a chest radiograph to assess the patient’s heart size and the presence or absence of decompensated CHF with or without pulmonary edema.

A chest radiograph may also assist in diagnosing concomitant disease, such as pneumonia in an elderly patient, as a precipitating cause for MI.

Echocardiography

An echocardiogram may play an important role in the setting of MI.

Regional wall motion abnormalities can be identified, which are especially helpful if the diagnosis is questionable.

An echocardiogram can also define the extent of the infarction and assess overall left ventricle (LV) and right ventricle (RV) function. In addition, an echocardiogram can identify complications, such as acute MR, LV rupture, or pericardial effusion.

Myocardial perfusion imaging

Prior to discharge, obtain myocardial perfusion imaging to assess the extent of residual ischemia if the patient has not undergone cardiac catheterization. The extent of ischemia can guide further therapy as to whether to proceed with catheterization or to continue conservative therapy.

Myocardial perfusion has been shown to be a valuable method for triage of patients with chest pain in the ED. Significant variability exists among centers, and the results of the trials can be applied only to those centers with proven reliability and experience.

Cardiac angiography

Cardiac catheterization defines the patient’s coronary anatomy and the extent of the disease. Most investigators recommend that all patients with MI should undergo cardiac catheterization, if it is available.

Patients with cardiogenic shock, intractable angina despite medications, or severe pulmonary congestion should undergo cardiac catheterization immediately.

Other Tests:

The electrocardiogram (ECG) is the most important tool in the initial evaluation and triage of patients in whom an ACS is suspected (see Images 1-3). It is confirmatory of the diagnosis in approximately 80% of cases.

Obtain an ECG immediately if MI is considered or suspected.

 

 

 

 

 

 

Video Localization of MI

 

In patients with inferior MI, record a right-sided ECG to rule out RV infarct.

Qualified personnel should review the ECG as soon as possible.

Perform ECGs serially upon presentation to evaluate progression and assess changes with and without pain.

Obtain daily serial ECGs for the first 2-3 days and additionally as needed.

Convex ST

-segment elevation with upright or inverted T waves is generally indicative of MI in the appropriate clinical setting.

ST depression and T-wave changes may also indicate evolution of NSTEMI.

 

 

        

TREATMENT

Medical Care: Initial therapy for acute MI is directed toward restoration of perfusion in order to salvage as much of the jeopardized myocardium as possible. This may be accomplished through medical or mechanical means, such as angioplasty or coronary artery bypass grafting.

Further treatment is based on (1) restoration of the balance between the oxygen supply and demand to prevent further ischemia, (2) pain relief, and (3) prevention and treatment of any complications that may arise.

Thrombolytic therapy has been shown to improve survival rates in patients with acute MI if administered in a timely fashion in the appropriate group of patients. If PCI capability is not available or will cause a delay greater than 90 minutes, then the optimal approach is to administer thrombolytics within 12 hours of onset of symptoms in patients with ST-segment elevation greater than 0.1 mV in 2 or more contiguous ECG leads, new left bundle-branch block (LBBB), or anterior ST depression consistent with posterior infarction. Tissue plasminogen activator (t-PA) is superior to streptokinase in achieving a higher rate of coronary artery patency; however, the key to efficacy lies in the speed of the delivery of therapy. Recent trials show a high patency rate if a IIb/IIIa receptor antagonist is combined with a half dose of a thrombolytic agent as the initial reperfusion strategy. The reduced dose of a thrombolytic agent combined with a potent platelet inhibitor may prove to be the preferred method for medical

reperfusion. Larger clinical trials are pending.

Aspirin and/or antiplatelet therapy Aspirin has been shown to decrease mortality and re-infarction rates after MI. Administer aspirin immediately, which the patient should chew if possible upon presentation. Continue aspirin indefinitely unless an obvious contraindication, such as a bleeding tendency or an allergy, is present. Clopidogrel may be used as an alternative in cases of a resistance or allergy to aspirin. Recent data from the CLARITY trial (CLopidogrel as Adjunctive ReperfusIon Therapy Thrombolysis in Myocardial Infarction [TIMI] 28) suggest that adding clopidogrel to this regimen is safe and effective. The clopidogrel dose used was 300 mg.

Administer a platelet glycoprotein (GP) IIb/IIIa-receptor antagonist, in addition to acetylsalicylic acid and unfractionated heparin (UFH), to patients with continuing ischemia or with other high-risk features and to patients in whom a percutaneous coronary intervention (PCI) is planned. Eptifibatide and tirofiban are approved for this use. Abciximab also can be used for 12-24 hours in patients with unstable angina or NSTEMI in whom a PCI is planned within the next 24 hours.

Beta-blockers reduce the rates of reinfarction and recurrent ischemia and possibly reduce the mortality rate if administered within 12 hours after MI. Administer routinely to all patients with MI unless a contraindication is present.

Heparin (and other anticoagulant agents) has an established role as an adjunctive agent in patients receiving t-PA but not with streptokinase. Heparin is also indicated in patients undergoing primary angioplasty. Little data exist with regard to efficacy in patients not receiving thrombolytic therapy in the setting of acute MI. Low–molecular-weight heparins (LMWHs) have been shown to be superior to UFHs in patients with unstable angina or NSTEMI.

Nitrates have no apparent impact on mortality rate in patients with ischemic syndromes. Their utility is in symptomatic relief and preload reduction. Administer to all patients with acute MI within the first 48 hours of presentation, unless contraindicated (ie, in RV infarction).

ACE inhibitors reduce mortality rates after MI. Administer ACE inhibitors as soon as possible as long as the patient has no contraindications and remains in stable condition. ACE inhibitors have the greatest benefit in patients with ventricular dysfunction. Continue ACE inhibitors indefinitely after MI. Angiotensin-receptor blockers may be used as an alternative in patients who develop adverse effects, such as a persistent cough, although initial trials need to be confirmed.

Surgical Care:

Percutaneous coronary intervention

PCI is the treatment of choice in most patients with STEMI, assuming a door to needle time of less than 90 minutes. PCI provides greater coronary patency (>96% thrombolysis in myocardial infarction [TIMI] 3 flow), lower risk of bleeding, and instant knowledge about the extent of the underlying disease. Studies have shown that primary PCI has a mortality benefit over thrombolytic therapy.

The choice of primary PCI should be individualized to each institution and to the patient’s presentation and timing.

The widespread use of stenting and adjunctive IIb/IIIa therapy are improving the results of primary PCI. A recently published trial showed that, in patients with acute MI, coronary stenting and abciximab lead to a greater degree of myocardial salvage and a better clinical outcome than fibrinolysis with thrombolytic therapy. Improvement of long- and short-term outcomes, however, depends highly on the speed with which reperfusion is achieved.

Primary PCI is also the treatment of choice in patients with cardiogenic shock, patients in whom thrombolysis failed, and those with high risk of bleeding or contraindications to thrombolytic therapy.

Only an experienced operator should perform primary PTCA, and PTCA should be performed only where the appropriate facilities are available. Operators should have at least 75 cases per year, while the center should perform at least 200 cases per year as per the recommendations of the ACC.

Emergent or urgent coronary artery graft bypass surgery is indicated in patients in whom angioplasty fails and in patients who develop mechanical complications such as a VSD, LV, or papillary muscle rupture.

Consultations:

ED personnel should initiate evaluation and treatment, including administering a thrombolytic agent.

Obtain cardiology consultation immediately if primary PCI is considered. Otherwise, cardiology consultation may be obtained as needed and upon admission. Consultation may be obtained sooner if the patient presents with significant heart failure, mechanical complications, arrhythmias, or other complicating factors.

Diet: Initially, keep the patient oothing by mouth (NPO) until his or her condition has been stabilized and treated. Following initial therapy and admission, a dietitian should instruct the patient regarding appropriate diet, as recommended by the AHA.

A low-salt, low-fat, and low-cholesterol diet is generally recommended.

Activity: Confine patients to bed rest to minimize oxygen consumption until reperfusion and initial therapy are complete. This usually lasts about 24-48 hours; after that, the patient’s activity may be accelerated slowly as tolerated and as the clinical situation allows.

Initiate cardiac rehabilitation prior to discharge.

MEDICATION

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Salicylates — The antiplatelet effects of these agents may improve mortality rate.

 

Drug Category: Vasodilators — These agents relieve chest discomfort by improving myocardial oxygen supply, which in turn dilates epicardial and collateral vessels, improving blood supply to the ischemic myocardium.

Drug Category: Analgesics — Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.

Drug Category: Anticoagulants — Unfractionated intravenous heparin and fractionated low molecular weight subcutaneous heparins are the two choices for initial anticoagulation therapy.

 

Drug Category: Thrombolytics — The main objective is to restore circulation through a previously occluded vessel by the rapid and complete removal of a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system.

 

 

 

Drug Category: Beta-adrenergic blockers — This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

 

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors — These agents may prevent conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Drug Category: Platelet aggregation inhibitors — These agents prevent acute cardiac ischemic complications in unstable angina unresponsive to conventional therapy.

 

 

        

FOLLOW-UP

Further Inpatient Care: Admit patients with MI to a coronary care unit. Monitor patients carefully for arrhythmia, recurrent ischemia, and other possible complications. The patient may be transferred to a telemetry unit 24-48 hours after admission if no complications occur. Hospitalize the patient for approximately 4-5 days after MI. Patients who undergo primary PCI or have an immediate cardiac catheterization may be discharged sooner if their hospital course is without incident.

Perform a coronary angiography on high-risk patients prior to discharge to evaluate their need for revascularization.

In the case of patients who have not had a cardiac catheterization and have no complications, perform a submaximal stress test prior to discharge to assess their subsequent risk.

Further Outpatient Care:

Arrange for follow-up within 2 weeks of discharge.

Arrange for cardiac rehabilitation.

In/Out Patient Meds:

The long-term use of aspirin in patients who have had an MI results in significant reduction in subsequent mortality rate.

Beta-blocker therapy has confirmed therapeutic benefit in survivors of acute MI. This therapy is most beneficial in patients with the highest risk.

ACE inhibitor use in patients with known CAD has been shown to reduce mortality rate.

Many trials have shown a clear benefit of lipid-lowering therapy in the secondary and primary prevention of CAD. The National Cholesterol Education Panel has set guidelines for target cholesterol levels. In general, patients who have experienced MI should achieve low-density lipoprotein (LDL) level less than 100 mg/dL, high-density lipoprotein (HDL) level greater than 40 mg/dL, and triglyceride level less than 200 mg/dL. High-risk patients should be treated to a target LDL level of less than 70 mg/dL.

Schwartz et al recently showed in the MIRACL trial that initiating atorvastatin during hospitalization for an ACS, irrespective of lipid levels, reduces the frequency of recurrent ischemic events. This treatment significantly reduced the frequency of the combined end point of death, recurrent death, MI, or worsening unstable angina requiring hospitalization.

Clopidogrel should be prescribed for a year following discharge if the patient has no contraindications and cost is not prohibitive. To reduce the risk of bleeding, the aspirin dose can be reduced to 81 mg.

Transfer: A patient in whom thrombolytic therapy fails should be transferred to a facility where cardiac catheterization and angioplasty facilities are available.

Deterrence/Prevention:

Smoking cessation Cigarette smoking is a major risk factor for CAD. Risk of recurrent coronary events decreases 50% at 1 year after smoking cessation.

Provide all patients who smoke with guidance, education, and the support needed to avoid smoking.

Bupropion has been shown to increase the chances of patients’ success in achieving smoking cessation.

Alcohol consumption

Mild alcohol consumption has been associated with a decreased risk of stroke and MI.

Cautiously consider recommending and discussing alcohol use on a case-by-case basis.

Antioxidant therapy, including vitamin E, has not shown clear benefit in the prevention of coronary events.

Do not use long-term anticoagulant (ie, warfarin) therapy routinely in post-MI patients but as an alternative in patients who cannot take antiplatelet agents. Patients with known LV thrombus, atrial fibrillation, or severe wall motion abnormalities have shown benefit from long-term anticoagulation, maintaining the international normalized ratio (INR) between 2 and 3.

Do not start post-MI patients on postmenopausal hormone therapy (HRT). Patients already taking HRT for more than 1 year may be continued on this therapy without increased risk.

COMPLICATIONS:

A number of arrhythmias occur after MI, ranging from benign to fatal. Arrhythmias are common in the setting of MI and are a major cause of morbidity and mortality. Close monitoring and immediate treatment of arrhythmias may be the most important part of the treatment of a post-MI patient within the first 48 hours. Pay close attention to exacerbating factors, such as electrolyte disturbances (especially potassium and magnesium), hypoxemia, drugs, or acidosis, and correct them accordingly.

Ventricular fibrillation and/or ventricular tachycardia occurring within the first 48 hours may be due to ischemia; however, if ventricular arrhythmias occur later, then further workup is indicated. Immediate cardioversion is the treatment of choice. Accelerated idioventricular arrhythmia is a ventricular arrhythmia that may occur in response to reperfusion. This rhythm has a benign prognosis and usually does not require therapy.

Supraventricular arrhythmias are also common. Sinus bradycardia may be due to drugs, ischemia, or a vagal response. Sinus tachycardia may be due to pain, anxiety, drugs, or other causes. Atrial fibrillation and other atrial tachycardias may also occur. Treat any tachycardia by correcting the cause first or by pharmacotherapy, because persistent tachycardias may lead to further ischemia.

Conduction abnormalities may result from ischemia, necrosis, or chronotropic drugs, or as a vagal response. Recognition and treatment of these abnormalities are important in short- and long-term outcomes. Possible therapies include medications, such as atropine, or even placement of a transvenous pacemaker if indicated. Conduction disturbances are seen more commonly in the setting of inferior MI but are more ominous when seen with an anterior infarct.

Recurrent ischemia may be due to incomplete reperfusion. Postinfarct angina occurs in 20-30% of patients. This is an indication to proceed to cardiac catheterization followed by mechanical revascularization as needed.

CHF can be due to systolic dysfunction or diastolic dysfunction in the setting of MI. The severity of the heart failure and systolic dysfunction depends on the extent of the infarct and the presence of any other complications, such as acute mitral regurgitation. Aggressive treatment is indicated to avoid worsening of the situation. Treatment may include any or all of the following: nitrates, morphine, diuretics, ACE inhibitors, and other vasodilators if needed. Digoxin has no role in the setting of acute CHF due to ischemia.

Cardiogenic shock is defined as a systolic BP less than 90 mm Hg in the presence of organ hypoperfusion. The mortality rate due to cardiogenic shock is as high as 70% in some series. Patients usually require inotropic agents, such as dopamine or dobutamine, and occasionally an intraaortic balloon pump is required. Patients presenting with cardiogenic shock should proceed directly to the catheterization lab, if available, for mechanical revascularization.

Acute MR is most common in the setting of an inferoposterior MI. This is secondary to ischemia, necrosis, or rupture of the LV papillary muscle (especially the posteromedial papillary muscle). This can lead to mild-to-severe MR with CHF. Diagnosis can be made on physical examination, but an echocardiogram is necessary to confirm the diagnosis and assess the severity, which helps in the choice of therapy. Treatment consists of aggressive afterload reduction, intraaortic balloon pump insertion, and immediate surgical repair.

 

Video Rupture of chorda

 

Ventricular rupture occurs in the interventricular septum or the LV free wall. Both are catastrophic events with mortality rates greater than 90%. Prompt recognition, stabilization, and surgical repair are crucial to any hope of survival. Ventricular rupture is more common in women, patients with hypertension, and those receiving NSAIDs or steroids. An echocardiogram can usually define the abnormality, and a right heart catheterization can show an oxygen saturation step-up in the case of a septal rupture.

Other complications include pericarditis, ventricular aneurysms, mural thrombi, and hypertension. Recognition and treatment can be life saving.

Prognosis:

Acute MI is associated with a 30% mortality rate; half of the deaths occur prior to arrival at the hospital.

An additional 5-10% of survivors die within the first year after their MI.

Approximately half of all patients with an MI are rehospitalized within 1 year of their index event.

Overall, prognosis is highly variable and depends largely on the extent of the infarct, the residual LV function, and whether the patient underwent revascularization.

Patient Education:

Diet

Diet plays an important role in the development of CAD. Educate post-MI patients about the role of a low-cholesterol and low-salt diet.

Educate patients about the AHA dietary guidelines regarding a low-fat, low-cholesterol diet.

A dietitian should see and evaluate all post-MI patients prior to their discharge.

Smoking cessation

Educate all post-MI patients regarding the critical role of smoking in the development of CAD.

Smoking cessation classes should be offered to help patients avoid smoking after their MI.

For excellent patient education resources, visit eMedicine’s Cholesterol Center. Also, see eMedicine’s patient education articles High Cholesterol, Understanding Your Cholesterol Level, Lifestyle Cholesterol Management, Understanding Cholesterol-Lowering Medications, Chest Pain, Coronary Heart Disease, and Heart Attack.

MISCELLANEOUS

Medical/Legal Pitfalls:

Failure to make the diagnosis of an MI is the leading cause of litigation against ED physicians and cardiologists.

Consider atypical presentations in elderly patients, patients with diabetes, and women. Assess all patients carefully, especially if they have significant cardiac risk factors.

Review all ECGs that are obtained in a prompt fashion because time is crucial.

Obtain cardiology consultation whenever the diagnosis is questionable.

Consider an echocardiogram to assess wall motion abnormalities in difficult cases with nondiagnostic ECGs, such as with an LBBB.

Special Concerns:

Right ventricular infarction

Approximately one third of patients with inferior MI develop RV infarction. RV infarction presents a special challenge because the adjunctive therapy, other than reperfusion, is somewhat different.

A right-sided ECG with greater than 1 mm ST elevation in V3R or V4R leads describes an RV infarct. An echocardiogram may be helpful in confirming the diagnosis. On physical examination, signs of right heart failure, such as elevated jugular venous pulsation, right-sided S3, Kussmaul sign, or hypotension, may be present, and the patient may have clear lung fields.

The patient becomes volume dependent to maintain adequate LV and RV filling. Occasionally, dobutamine may be needed, or even an intraaortic balloon pump for hemodynamic support.

Avoid nitrates or any medications that lower preload in this setting. A pulmonary artery catheter can be helpful in guiding therapy.

Elderly patients

Elderly patients with acute MI are at increased risk of developing complications. Treat these patients aggressively.

Elderly patients have an increased risk of bleeding with thrombolytic therapy, but they also have the most to gain from this therapy.

Very elderly patients should undergo primary angioplasty if available, but they should receive thrombolytics if excessive delay is anticipated before angioplasty can be performed.

 

LITERATURE

Antman EM, McCabe CH, Gurfinkel EP, et al: Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. Circulation 1999 Oct 12; 100(15): 1593-601.

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 Manag. J Am Coll Cardiol 2000 Sep; 36(3): 970-1062.

Califf RM: Acute myocardial infarction and other acute ischemic syndromes. In: Braunwald E, ed. Atlas of Heart Disease. 8th ed. St. Louis, Mo: Mosby; 1996: 1.1-15.13.

Ornato JP: Chest pain emergency centers: improving acute myocardial infarction care. Clin Cardiol 1999 Aug; 22(8 Suppl): IV3-9.

Schwartz GG, Olsson AG, Ezekowitz MD, et al: Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001 Apr 4; 285(13): 1711-8[Medline].

Tavazzi L: Clinical epidemiology of acute myocardial infarction. Am Heart J 1999 Aug; 138(2 Pt 2): S48-54.

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Підготував Доброродній А.В.