Brad Stuart MD
Essentials of Diagnosis
Approximately six million Americans seek medical attention each year complaining of chest pain. Of these cases, only about 40% can be attributed to cardiac, pulmonary, or gastrointestinal disease.
The prevalence of diseases resulting in chest pain varies with the population. For ischemic heart disease, the presence of cardiac risk factors and the age of the patient are important. For example, coronary disease is diagnosed in less than 10% of persons with chest pain who are younger than 35 years of age. However, the incidence of cardiac diagnoses may exceed 50% in persons over 40 years of age.
The first priority in assessing a patient with chest pain is to determine whether the chest pain is due to coronary disease. About 11% of chest pain presentations are due to stable angina pectoris and another 1.5% signal acute coronary syndrome (ACS), consisting of myocardial infarction (MI) or unstable angina pectoris. Despite the best efforts of medical providers, approximately 20,000 patients with chest pain are sent home after ACS has been incorrectly ruled out. These missed diagnoses result in as many as one in five medical malpractice suits in the United States.
Once coronary disease has been excluded, other life-threatening causes of acute chest pain (eg, pulmonary embolus, aortic dissection, esophageal rupture, or tension pneumothorax) must also be considered; then, a specific cause of the pain can usually be identified and treatment begun. A targeted history and physical examination, combined with selected tests such as electrocardiogram (ECG) or chest radiograph, will usually allow the physician to arrive at an accurate diagnosis, avoiding unhelpful terms such as “noncardiac” or “atypical” chest pain. In addition, the clinical evaluation helps estimate the pretest probability of organic causes of chest pain before ordering diagnostic tests. Determining pretest probability helps interpret test results and also avoid unnecessary and expensive procedures.
The mechanisms of most causes of chest pain are poorly understood. However, it is understood that angina pectoris results from myocardial oxygen demand exceeding oxygen supply, leading to ischemic episodes.
The neural pathways that transmit chest pain, however, are well defined. Deep retrosternal or precordial pain is not diagnostic of cardiac disease or any other specific disease process; rather, it indicates pain stimuli in a portion of the anatomic regions supplied by the dermatomes T1 to T6. These spinal neuroanatomic levels innervate the thoracic region from the mid-neck to beneath the xiphoid process and also extend down the anteromedial arms and forearms. The thoracic viscera, including the myocardium, pericardium, aorta, pulmonary artery, mediastinum, and esophagus are all supplied by sensory afferent fibers originating from T1 through T4. Lesions in any of these structures tend to produce poorly localized, deep, visceral pain that is felt maximally in the retrosternal region or the precordium. This pain often radiates into the neck, the left or right hemithorax or the anteromedial aspects of one or both arms and forearms.
Sensory fibers from T5 and T6 innervate the lower thoracic wall, the diaphragmatic muscles and their peritoneal surfaces, the gallbladder, the pancreas, the duodenum, and the stomach. Injury to any of these structures causes poorly localized, deep, visceral pain identical in character to that mentioned above but localized to the xiphoid region and the right subscapular area. However, this pain may extend to the T1 T4 dermatomes through
posterior sympathetic connections, creating an anatomic pattern of pain indistinguishable from that originating from lesions above the diaphragm.
It has been said that pain from the umbilicus to the mandible is cardiac until proven otherwise. It is more accurate to state that visceral pain in the chest, like visceral pain elsewhere in the body, is not necessarily localized to the area of injury and its character is rarely specific for a particular lesion. However, a careful clinical evaluation and selected tests yield an accurate diagnosis in most cases.
Knowledge of risk factors for the various etiologies of chest pain provides important information, both for prevention of underlying disease and regarding disease likelihood, which may help guide the clinical evaluation.
Retrospective studies of patients under 40 years of age with acute MI show that up to 98% of patients had at least one conventional coronary risk factor. Following are some coronary risk factors that increase the likelihood of other diseases causing chest pain:
Following are clinically identifiable risk factors for the development of venous thrombosis and pulmonary embolism:
Clinicians must maintain diagnostic objectivity while evaluating a patient with chest pain. Studies have shown that patients were less likely to receive a cardiac workup if the physician viewed a histrionic portrayal of symptoms.
Furthermore, data suggest that women are not referred as often as men for appropriate diagnostic and therapeutic procedures for coronary disease, although this difference may be explained largely by the greater number of co-morbidities in women with ACS, resulting in a greater burden of procedural complications related to coronary reperfusion.
Acute, severe chest pain in men older than 60 years of age may be due to aortic dissection, whereas in younger men it may indicate spontaneous pneumothorax. A diagnosis of viral pleurisy is more common in younger adults of either sex.
Chest pain frequently recurs in such illnesses as peptic ulcer disease, gastroesophageal reflux, myocardial ischemia, cholecystitis and cholelithiasis that have not been treated surgically, cancer, and panic disorder. A diagnosis may be suggested if present pain is similar to that experienced in past exacerbations. A history of diabetes should raise the suspicion of an atypical presentation of myocardial ischemia. Recent blunt trauma to the chest may cause chest wall injury, pneumothorax, pulmonary or myocardial contusion, or a tear in the aorta, esophagus, or bronchus.
Patients with myocardial ischemia rarely complain of pain. Rather, they use such descriptors as squeezing, pressure, tightness, aching, constriction, burning, fullness, band-like sensation, lump in the throat, heavy weight (“elephant sitting on chest”), or toothache-like pain (with radiation to the mandible). In some cases, the patient places a closed fist over the sternum (the Levine sign). The quality of pain tends to be replicated in the same patient with repeated events of coronary ischemia. Coronary disease cannot be completely excluded in patients who describe the pain as sharp or stabbing, even though such qualities are not characteristic of myocardial ischemia.
The pain is less likely to be ischemic if it has a positional component, is reproducible by palpation, and if the patient has no history of angina or MI. The chest pain of myocarditis can be pleuritic in nature, but it can also be similar to pain typical of myocardial ischemia.
Ischemic pain is often diffuse and may be difficult or impossible to localize. Pain that is localized to a small area on the chest (particularly when the patient can point to it with a finger) is more likely due to a lesion of the chest wall or pleura.
Pain due to myocardial ischemia may radiate to the lower jaw, teeth, neck, throat, upper extremity, or shoulder on either side. The pain of MI may radiate to many of these areas at once, and particularly to the right arm.
Radiation to both arms may be an even stronger indicator of acute MI.
Acute cholecystitis can cause pain in the right shoulder, although concurrent pain in the epigastrium or right upper quadrant is more common than chest discomfort. The pain of aortic dissection often radiates between the scapulae.
Temporal elements may be used to help distinguish between different causes of chest pain.
Myocardial ischemia is most often gradual in onset, and its intensity increases over time. Esophageal disease may also exhibit a crescendo pattern. On the other hand, aortic dissection and pneumothorax usually cause pain of abrupt onset that is immediately of maximal intensity. Musculoskeletal chest pain is often insidious in onset, sometimes taking hours or days to reach a peak.
The duration of pain may differ by etiology as well. Chest discomfort that lasts only for a few seconds or that is constant over days to weeks is almost certainly not secondary to myocardial ischemia. Pain that is unchanging over years is most likely functional. Chest discomfort due to myocardial ischemia generally lasts for minutes; it may be more prolonged when due to an MI. Myocardial ischemia, as well as MI, may demonstrate a circadian pattern, occurring more frequently from 6 A.M. to noon then later in the day due to changes in sympathetic tone.
Pain on swallowing suggests an esophageal origin. Chest discomfort that occurs every time a patient eats is suggestive of upper gastroin testinal disease. However, it can also be seen in cases of severe coronary obstruction (eg, left main or three-vessel disease). Exertional chest pain is classic for angina, although occasionally esophageal spasm can present in a similar way. Myocardial ischemia can also be precipitated by exposure to cold, emotional stress, or sexual inter course. Musculoskeletal chest pain can be exacerbated by movement or by adopting certain body positions, as well as by deep breathing. True pleuritic chest pain is worsened by inspiration and often by lying down; causes may be pulmonary embolism and infarction, pneumothorax, pleurisy, pneumonia, or pericarditis.
Chest pain that is reliably palliated by eating food is probably caused by upper gastrointestinal disease. Neither nitroglycerin nor “GI cock-tails” (eg, antacid plus a viscous lidocaine) reliably distinguish the pain of myocardial ischemia from noncardiac pain. However, chest pain that is relieved by physical rest strongly suggests a cardiac etiology.
The magnitude of the patient's pain does not reliably discriminate between cardiac and noncardiac pain. However, in the setting of confirmed coronary disease, the pain of MI may be more severe than the pain of stable or unstable angina.
Cardiac and gastrointestinal causes of chest pain may coexist in up to one-third of patients with chest pain. Associated symptoms may not reliably distinguish between these etiologies. Painful swallowing, belching, or a bad taste in the mouth are suggestive of esophageal disease, although these symptoms may occur in patients with myocardial ischemia as well. Similarly, vomiting may occur secondary to myocardial ischemia or upper gastrointestinal problems such as peptic ulcer disease, cholecystitis, acute pancreatitis, and also diabetic ketoacidosis, which in turn may be triggered by acute MI.
Other associated symptoms, such as diaphoresis, may occur more often in the setting of myocardial ischemia and may suggest that diagnosis. Dyspnea on exertion may precede chest pain due to myocardial ischemia and may also be seen in heart failure. Dyspnea concurrent with chest pain may occur in myocardial ischemia or such pulmonary disorders as pneumonia or pulmonary embolus. Presyncope may be seen in myocardial ischemia, but may also accompany aortic dissection, pulmonary embolus or critical aortic stenosis. Exertional dyspnea is common in aortic stenosis as well. Palpitations may occur with myocardial ischemia secondary to ventricular ectopy, although some patients may have a hypersensitive awareness of their own normal sinus rhythm. New-onset atrial fibrillation is uncommon in acute MI but is seen frequently in chronic coronary disease. Pulmonary embolism may cause chest pain and palpitations due to new atrial fibrillation as well. Cough is a nonspecific symptom that may be due to heart failure, lung cancer, pulmonary embolus, pneumonia, or occasionally gastroesophageal reflux disease. Severe fatigue may be a presenting symptom of MI in elderly patients.
Clinicians must be alert for signs of circulatory compromise, including pallor and diaphoresis; these are associated with high early mortality. Although panic disorder may be present in up to one-third of patients with chest pain without coronary ischemia, it may also coexist with coronary disease. In some patients, their level of alarm can be a more accurate reflection of the seriousness of their disease than is the severity of their symptoms.
Systolic blood pressure below 90 mm Hg, especially in conjunction with physical signs of circulatory compromise, indicate a need for emergent care. An elevation in heart rate and blood
pressure may be seen in coronary ischemia secondary to sympathetic activation, but this is nonspecific. A marked difference in blood pressure between the two arms may suggest aortic dissection. A check for postural changes in heart rate and blood pressure is warranted, particularly in elderly patients with presyncope who may be volume depleted.
Chest wall tenderness that exactly replicates the patient's pain is extremely suggestive of noncardiac disease, although occasionally chest wall tenderness may be present together with myocardial ischemia. Hyperesthesia in a dermatomal distribution, particularly when associated with a vesicular or patchy erythematous rash, may be due to herpes zoster.
Auscultation in sitting and supine positions can detect murmurs of acute aortic stenosis or insufficiency as well as the pericardial friction rub of acute pericarditis. A mitral insufficiency murmur due to papillary muscle dysfunction or an S3 or S4 gallop may be caused by myocardial ischemia. Palpation at the apex may also detect an abnormal left ventricular heave, which is sometimes felt during ischemic episodes due to an area of dyskinesis secondary to occlusion of the left anterior descending coronary artery.
Asymmetric or absent lung sounds may indicate pneumothorax. Basilar rales may be heard in cases of myocardial ischemia that is severe enough to raise end-diastolic pressure. Evidence of consolidation may indicate pneumonia or cancer; dullness at one of the lung bases may be seen with pleural effusion.
Tenderness in the epigastrium may be consistent with peptic ulcer disease or pancreatitis, whereas right upper quadrant tenderness may indicate cholecystitis. A pulsatile epigastric mass may be an extension of a thoracic aortic aneurysm presenting with chest pain.
Ancillary studies including chest radiography and electrocardiography may provide further information supporting or disproving initial diagnostic hypotheses as well as reducing the chance of missing serious etiologies of chest pain. Additional studies-including but not limited to exercise electrocardiography, myocardial perfusion scanning, echocardiographic stress testing, diagnostic acid suppression, ventilation-perfusion lung scanning, or chest computed tomography (CT)-may sometimes be required to narrow diagnostic possibilities.
A chest radiograph aids in the diagnosis of chest pain due to cardiac or pulmonary causes, cancer, pneumothorax, or pneumomediastinum. The chest film may also be abnormal in aortic dissection, but other studies will usually be necessary for a definitive diagnosis. Up to one-quarter of chest radiographs done on patients with chest pain in an emergency setting yield information that influences therapy.
A 12-lead ECG provides critical information about the presence or absence of myocardial ischemia. A normal ECG significantly reduces the probability that chest pain is due to acute MI. However, up to one-third of patients with unstable angina have a normal ECG, and up to 4% of patients with normal ECGs will have had an acute MI. On the other hand, an abnormal ECG with specific findings (eg, ST-segment elevation, ST-segment depression or new Q waves) is not only compatible with ACS (acute MI or unstable angina) but also is correlated with the need for invasive therapy, a complicated hospital course, or death. Nonspecific ST-T wave abnormalities are commonly seen and may indicate heart disease; more than two-thirds are associated with noncoronary diagnoses.
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In evaluating the patient with chest pain, the clinician must first exclude life-threatening diagnoses and then provide emergent care if indicated. Once this has been accomplished, the next step is to establish a reasonable diagnosis that explains the patient's complaints. The list of potential diagnoses presented below appear in approximate order of prevalence seen in primary care practice, except that life-threatening diagnoses are discussed first. Table 18-1 summarizes the major causes of chest pain.
The first step in the evaluation of any patient with chest pain is to exclude coronary ischemia as the cause. Chest pain due to myocardial ischemia secondary to varying degrees of coronary artery obstruction includes a continuum of diagnoses including transmural MI, non-Q wave infarction, unstable angina pectoris, and stable angina. A careful history and physical examination accompanied by an ECG at rest furnishes a clinical diagnosis with 90% predictive accuracy for the presence of coronary disease. Other tests are rarely necessary to establish a working diagnosis of acute myocardial ischemia. However, up to 8% of cases of myocardial ischemia will be missed when clinical and ECG data alone are used to establish the diagnosis. If patients are discharged without treatment, the annual mortality rate is 6 to 8%. These patients tend to be women under the age
of 55, nonwhite, reporting dyspnea as the primary symptom, and with a normal or nondiagnostic ECG.
Table 18-1. Major Causes of Chest Pain.
The classic presentation of pain caused by coronary disease, most frequently seen in middle-aged men with risk factors for atherosclerosis, includes complaints of chest heaviness, pressure, tightness, and burning; patients often deny having pain and may have difficulty describing their discomfort. Typical anginal pain has a gradual onset, usually over several minutes, and does not change with respiration or position. It is diffuse, difficult to localize, and often radiates to other parts of the body, including the lower jaw and teeth (not the upper jaw), neck and throat, shoulders, inner aspects of upper arms and forearms, wrists, fingers, epigastric area, and occasionally to the interscapular region of the back. Ischemic pain almost always lasts more than 2 but less than 20 minutes, unless an MI is in progress, in which case the pain may last longer. Associated symptoms include dyspnea, nausea and vomiting, diaphoresis, lightheadedness, or palpitations.
Up to one-third of patients, especially women over 65 years of age who are obese as well as diabetics and the elderly, may not have chest pain but rather complain of such atypical symptoms as abdominal pain (in 33%), paroxysmal dyspnea (in over 15%), shortness of breath as a primary symptom, or fatigue. Patients with variant angina due to coronary vasospasm may have classic anginal pain precipitated by hyperventilation and occasionally by exercise. These patients are usually younger than 60 years of age and do not necessarily have classic cardiovascular risk factors. The rest ECG in these cases often shows transient ST-segment elevation. Life-threatening arrhythmias may occur.
Among patients considered to have acute coronary ischemia, several aspects of the primary presentation suggest the possibility of unstable angina or MI:
Chest pain that is more likely due to nonischemic problems is generally characterized as the following:
The clinician should remember that up to 25% of patients with sharp or stabbing pain may have ischemia. Also, patients with noncardiac pain may still have other potentially lethal conditions.
Information gathered from a 10-minute history and physical examination should allow the clinician to place the patient with suspected myocardial ischemia into one of four categories:
For those patients with definite or probable acute ischemia, an ECG and sequential cardiac enzymes (troponin T and I, creatine kinase CK-MB, and myoglobin) should be obtained to establish the diagnosis. Other routine measures include using supplemental oxygen, establishing continuous ECG monitoring, obtaining intravenous access, and giving 160-325 mg of aspirin (chewable if possible) as well as sublingual nitroglycerin for pain. Hospital admission should be arranged under the following circumstances:
sensitivity and negative predictive value at 90 minutes after onset of symptoms for the combination of myoglobin and troponin I are both high, myoglobin is not specific for myocardial necrosis; serum myoglobin levels may be elevated after recent cocaine use and in patients with impaired renal function. Elevated troponin levels, however, are highly specific for myocardial necrosis.
For patients who have persistent chest pain suggestive of acute myocardial ischemia but who have a nondiagnostic ECG and initially negative cardiac enzymes, rest imaging tests may help with the diagnosis. Acute rest myocardial perfusion imaging may be performed with one of several radiopharmaceutical agents that accumulate in the myocardium in concentrations proportional to blood flow. However, false-positive results may occur in patients with prior infarction, and false-negative results may be seen if chest pain has been resolved for more than 3 hours.
Echocardiography can detect regional left ventricular wall motion abnormalities within seconds of coronary artery occlusion; the sensitivity of this procedure is high but specificity is limited due to the large number of alternative causes of regional wall motion abnormalities. Thus, echocardiography may be used to exclude MI during or immediately after an episode of chest pain but not to diagnose it.
Patients with pain typical of ischemia in whom initial ECG and cardiac enzymes are normal or indeterminate can be monitored for 6-24 hours in a chest pain observation unit or in the emergency department. A repeat ECG and cardiac enzymes in 6 to 12 hours should be obtained; if either or both are positive, the patient should be admitted to the hospital.
Patients with typical anginal pain that resolves, and who are otherwise clinically stable, can undergo stress testing. Exercise testing has been shown to be both safe and predictive of good prognosis in patients who have a negative test result. Exercise ECG testing is not indicated in patients whose pain is probably noncardiac and who also have a nondiagnostic initial evaluation. There is a relatively low incidence of coronary disease in these patients.
The long-term outcome is more favorable for patients who are found not to have had an MI after being admitted for suspected MI than for those patients in whom MI is diagnosed. However, up to 15% of troponin-negative patients experience an adverse cardiac event at 1 year; in large series, 10-year mortality did not differ between the groups.
Chest pain caused by aortic dissection is often severe, bordering on catastrophic. Early diagnosis and treatment are critical for survival, particularly when hemodynamic compromise is present. Patients tend to be men ranging from 60 to 80 years of age; up to 75% have a prior history of hypertension. Less frequent predisposing factors include bicuspid aortic valve, Marfan or Turner syndrome, coarctation of the aorta, pregnancy, or prior coronary artery bypass surgery. Recently, high-intensity weight lifting and the abuse of crack cocaine have become more commonly associated with aortic dissection.
Pain is sudden in onset, often migratory, and often described as a ripping or tearing sensation. Pain is usually felt in the chest, anteriorly with dissections of the ascending aorta or posteriorly with dissections distal to the takeoff of the left subclavian artery. The pain may radiate anywhere in the thorax or abdomen. Painless dissection is uncommon.
Associated symptoms are usually caused by cerebral, spinal, coronary, or visceral ischemia due to occlusion of arterial branches at the site of dissection or propagation. Syncope heralds a worse prognosis because it is often due to cardiac tamponade from proximal dissection or stroke from occlusion of the subclavian artery. Other is-chemic symptoms include neurologic deficits or ischemia of the myocardium, gut, kidneys, or lower extremities. Acute heart failure may occur as a result of aortic insufficiency. Shock, hemothorax, or sudden death may occur if the aorta ruptures into the pericardial or pleural space.
The initial evaluation should include a check of pulses and blood pressures to ensure that they are symmetric bilaterally and in upper and lower extremities. Pulse deficits occur more commonly in proximal dissections but are present in <30% of patients. The examiner should check for a murmur of aortic insufficiency as well as a pulsatile epigastric mass and focal neurologic defects. The chest radiograph may show an abnormal aortic contour; this can also be seen in “unwinding” of the aorta, which is a normal variant often seen in the elderly. The mediastinum may be widened and the trachea displaced laterally. The ECG may be helpful, particularly in cases where chest pain is similar to that usually seen with angina; lack of ECG findings mitigates against myocardial ischemia, unless proximal dissection has compromised coronary arterial blood flow.
Definitive diagnosis is made by CT scan, magnetic resonance imaging (MRI) scan, or transesophageal echocardiography after the patient has been medically stabilized. Transthoracic echocardiography is not indicated because of its inability to visualize the transverse and descending aorta in most patients. Aortography is now performed in <5% of cases. Routine blood tests are nondiagnostic.
Abnormalities of the heart valves, including aortic stenosis, mitral stenosis, and mitral valve prolapse, may cause chest pain.
Aortic stenosis may present with anginal pain, dyspnea, and syncope. Cardiovascular examination in cases of critical aortic stenosis may show weakened and delayed peripheral arterial pulses, a sustained cardiac apical impulse, and a pronounced systolic murmur at the left sternal border that often radiates to the carotids. The pressure gradient across the valve as well as left ventricular function may be measured with an echocardiogram. Exercise stress testing may be contraindicated.
Mitral stenosis is an unusual cause of chest pain. The pain may be similar to angina, although it results from pulmonary hypertension and right ventricular hypertrophy. There may be associated coronary artery disease. Atrial tachyarrhythmias may be an additional cause of intermittent pain.
Mitral valve prolapse causes atypical chest pain, often fleeting and sharp in character, frequently in young women. It is often associated with a mid-systolic click and late systolic murmur. Hemodynamically significant mitral insufficiency rarely occurs.
Acute inflammation of the pericardium, often viral, idiopathic, orassociated with AIDS, induces pain that is often sharp, localized to the anterior chest, and usually made worse by inspiration. Less commonly, a dull pressure-like pain may occur that is sometimes difficult to distinguish from MI. Pain may radiate to the trapezius ridge, and it may decrease when the patient sits up. The pain is often accompanied by a pericardial friction rub that is heard best with the diaphragm of the stethoscope while the patient is sitting up, leaning forward, and holding his or her breath in full expiration.
Widespread ST-segment elevation may be seen on the ECG; these changes can be distinguished from those due to MI by experienced ECG interpreters. The chest radiograph is typically normal. The echocardiogram may show no pericardial effusion; this does not exclude acute pericarditis. Cardiac troponin I may be elevated in some cases, corresponding with the degree of myocardial inflammation and, coincidentally, with the degree of diffuse ST elevation, sometimes confounding the workup in patients with angina-like pain. Coronary angiograms have been negative in these patients, and the complication rate was not elevated at 1 year. Sustained arrhythmias are generally not seen in patients without coronary disease.
Inflammation of the myocardium is, in the United States at least, predominantly a viral illness. There is no gold standard for diagnosis; endomyocardial biopsy is performed in very few cases and generally yields only a lymphocytic infiltrate. Chest pain, if it occurs, is often associated with concomitant pericarditis and is therefore similar in character and location to that entity. Like pericarditis, myocarditis can produce substernal pain similar to that associated with angina pectoris. In some studies, the majority of patients with a clinical presentation consistent with MI but with normal coronary artery angiograms were found to have focal or generalized myocarditis.
Myocarditis may be responsible for up to 25% of sudden cardiac deaths in patients under 30 years of age, presumably due to lethal ventricular arrhythmias. However, premature atrial or ventricular extrasystoles are much more common than are any serious sustained arrhythmias. Myocarditis may be responsible for more cases of heart failure than of chest pain; up to 10% of patients with heart failure due to cardiomyopathy rather than is-chemic causes have cardiomyopathy on endomyocardial biopsy.
In severe cases, physical examination shows signs of fluid overload as well as an S3 or S4 gallop if heart failure is present. Routine blood tests are usually normal, except for cardiac enzymes, which may be elevated if there is associated myocardial necrosis. Cardiac troponin I or T may be more elevated than is CK-MB. Troponin elevations tend to occur early in the course of illness, probably reflecting a peak in myocardial necrosis within the first month.
ECG findings are variable, sometimes simulating those seen in MI or pericarditis. Chest film findings are usually consistent with whatever degree of heart failure is present. Serial echocardiography may reveal a spherical left ventricle early in the course of disease but a reversion to a more elliptical geometry as healing occurs. Wall motion abnormalities are usually global but occasionally segmental. Occasionally, mural thrombi may be seen, requiring anticoagulation. Echocardiography is also indicated to rule out valvular abnormalities and hypertrophic and restrictive cardiomyopathies as potential causes of heart failure. Endomyocardial biopsy may be indicated for patients with a rapidly deteriorating course or in those in whom a potentially reversible cause (eg, hemochromatosis or amyloidosis) is suspected.
This disorder has the following nonspecific characteristics:
The chest pain these patients experience is thought to be due to either myocardial ischemia of occult etiology, possibly due to clot with rapid lysis or microvascular disease, or to “hypersensitive heart syndrome.” Most patients are premenopausal women who are typically younger than those with coronary disease, and there is
a strong correlation between Syndrome X and panic attacks. About one-half of the patients have atypical pain, and those with angina-like pain experience it for unusually prolonged periods. Poor response to nitroglycerin is common. A significantly small number of patients labeled with Syndrome X have been found to suffer from associated rheumatologic diagnoses, esophageal dysfunction, or amyloidosis.
The ECG at rest may show no changes or nonspecific ST-T depression, but the exercise ECG typically shows horizontal or downsloping ST depression. Although an abnormal response to vasomotor stimuli (eg, adenosine) has been seen, myocardial perfusion and wall motion abnormalities are variable on imaging studies, leading some to suggest that ischemia, if present, may be limited to the subendocardium. A normal coronary angiogram is a necessary component of the diagnosis of Syndrome X. A positive response to ergonovine during catheterization confirms the alternative diagnosis of variant angina.
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Over half a million patients in the United States are diagnosed with pulmonary emboli each year; this probably understates the incidence of the disorder because it is an uncommon cause of chest pain in the primary care setting. Consequently, up to one-half of all cases go undiagnosed. Pulmonary emboli cause approximately 200,000 deaths in the United States each year. A high index of suspicion combined with rapid diagnosis and treatment are critical for survival. The mortality rate without treatment is approximately 30%; most deaths are due to recurrent emboli. However, with accurate diagnosis and effective anticoagulation, the mortality rate is reduced to 2 to 8%.
Up to 90% of pulmonary emboli arise from the deep veins of the lower extremities; the rest originate in pelvic, renal, or upper extremity veins, or from the right heart. Clinically significant pulmonary emboli usually result from ileofemoral thrombi. Calf vein thrombi resolve spontaneously in about 80% of cases; the remainder propagate to the popliteal, femoral, or iliac veins.
Clinical presentation depends on the size of the thrombus. Hemodynamic compromise results when large thrombi lodge at the bifurcation of the main pulmonary artery or the lobar branches. Pleuritic chest pain occurs when smaller thrombi travel distally and lodge in segmental veins, which presumably initiates an inflammatory response adjacent to the parietal pleura. Pulmonary infarction only occurs in about 10% of cases. Impairment of gas exchange results from the release of inflammatory mediators from platelets and other components of the thrombus and its surrounding vasculature, causing vascular permeability changes and intra-pulmonary shunting.
Predisposing factors to pulmonary emboli include immobilization, recent surgery, or malignancy. Up to 17% of patients with idiopathic venous thromboembolism have occult malignancy, particularly of the pancreas or prostate, although late-stage breast, lung, uterine, or brain cancers may also be associated with a hypercoagulable state.
Although most pulmonary emboli originate in the lower extremities, <30% of patients have leg symptoms at the time of diagnosis. On the other hand, patients with symptomatic deep venous thrombosis may have asymptomatic pulmonary emboli in over 25% of cases. When symptoms are present, they commonly include dyspnea, pleuritic pain, cough, and hemoptysis, which is usually characterized by blood-tinged sputum and is rarely massive. Physical signs include tachypnea, rales, tachycardia, a fourth heart sound, and an accentuated pulmonic component of the second heart sound. The most commonly recognized symptom complex, seen in approximately 67% cases, is pleuritic pain and hemoptysis. Cardiovascular collapse occurs in <10%. Unfortunately, no particular clinical finding is sensitive or specific for the diagnosis of pulmonary embolus.
Routine laboratory results are nonspecific, although arterial blood gases usually show hypoxemia, hypocapnia, and respiratory alkalosis. However, because typical arterial blood gas findings are not always seen, they should not be given excess weight in excluding or establishing the diagnosis. Similarly, pulse oximetry does not establish the diagnosis, although PA2>95% at the time of diagnosis may be seen in patients who are at increased risk for complications, including respiratory failure, car-diogenic shock, and death. Serum troponins I and T are elevated in up to 50% of patients with moderate to large pulmonary emboli, proportional to acute right heart overload; these findings are associated with poor outcomes. ECG changes are nonspecific, although T-wave inversions in the precordial leads may indicate severe right ventricular dysfunction. Chest film findings can include cardiomegaly, atelectasis, pulmonary parenchymal abnormality, or pleural effusion, but these findings are also nonspecific.
Clinical variables alone are not sufficient for the diagnosis of pulmonary embolism, although they do serve the important function of helping the clinician
formulate pretest probabilities of the likelihood of pulmonary embolus. Of the additional tests available, ventilation-perfusion lung scan is used most frequently. If the perfusion scan is completely normal, the diagnosis of pulmonary embolus is virtually excluded. Conversely, a high probability lung scan, particularly in a patient with a high pretest probability of pulmonary emboli, indicates a high likelihood of thromboembolic disease. Unfortunately, however, over 50% of lung scan defects are interpreted as intermediate or low probability. In addition, the false-positive rate of high probability scans approaches 15%, although it is reduced below 10% if patients with prior pulmonary emboli are excluded. Up to 75% of patients have combinations of clinical and lung scan probabilities that cannot finally confirm or exclude the diagnosis of pulmonary emboli. These patients may require pulmonary angiography for definitive diagnosis, although many series report that the majority of patients are treated without undergoing the test.
In patients with intermediate clinical and lung scan probabilities for pulmonary embolism, particularly those with leg symptoms, a positive lower-extremity venous ultrasound provides adequate rationale for anticoagulation, although up to 3% of results can be false-positive. In addition, thromboembolic disease is not completely excluded if a single leg study is negative, because the entire detectable clot burden may have already embolized, or emboli may have originated from a source other than the legs or from calf vein thrombi.
The sensitivity and negative predictive value of D-dimer, a degradation product of cross-linked fibrin, are both high, especially when the enzyme-linked immunosorbent assay (ELISA) method is used. A negative quantitative rapid ELISA result rules out venous thromboembolism, although a positive test lacks specificity because high d-dimer levels are commonly seen in patients with malignancy or who have recently undergone surgery; levels also rise with increasing age.
Helical CT scanning is used increasingly to rule out pulmonary embolus. Specificity of the procedure has been high in most studies; however, to avoid false-positive results, the radiologist should be experienced in interpreting helical CT scans. Sensitivity has been more variable; most studies show a higher likelihood of detecting clots in large proximal pulmonary veins than at the segmental level or in smaller vessels. However, patients with normal spiral CT studies experience subsequent embolic events in <2% of cases. In centers where radiologists are experienced, where multidetector row CT scanners with thin collimation are available, and particularly where additional images of pulmonary arteries and leg veins can be obtained without additional venipuncture or contrast administration, helical CT scanning can provide significant benefits. A recent study showed that a combination of d-dimer and multidetector-row CT scanning may rule out pulmonary embolus without lower extremity ultrasonography.
Pulmonary angiography, using four injections with four views, is the gold standard for diagnosing pulmonary emboli. If the order of vessel injection is prioritized based upon ventilation-perfusion scanning results, the contrast burden can be limited. A normal pulmonary angiogram with magnification excludes clinically significant pulmonary embolism. Procedure mortality is <0.5%, and only about 5% of patients experience complications, which are usually related to catheter insertion or contrast reactions.
To summarize, clinical assessment, ventilation-perfusion lung scanning, D-dimer testing, and venous ultrasound can be used to confirm or exclude the diagnosis of pulmonary emboli in many but not all patients:
Similar to acute pulmonary embolus, a clinical presentation including acute onset of pleuritic pain and respiratory distress should trigger consideration of spontaneous pneumothorax. Primary spontaneous pneumothorax usually occurs in young, tall, adult male smokers without prior history of lung disease; recurrence is common. Secondary spontaneous pneumothorax is superimposed on underlying lung disease, such as chronic obstructive pulmonary disease or Pneumocystis pneumonia. Although rare, tension pneumothorax is life-threatening unless diagnosed promptly and treated emergently. A “one-way valve” is created by a tissue flap from the injured lung, trapping air in the intrapleural space progressively with each inspiration. Compression of healthy lung can cause respiratory failure in minutes. Physical examination discloses
unilateral loss of breath sounds with hypertympany; the trachea is shifted away from the injured side and jugular venous distention can occur. The diagnosis must be based on history and physical examination; pneumothorax should be decompressed through the insertion of a large-bore needle into the second intercostal space in the midclavicular line on the affected side, prior to a confirmatory chest radiograph.
Primary pulmonary hypertension is rare. Patients with this condition who have chest pain on exertion may also experience syncope and edema; these are indicators of severe disease and impaired right heart function. In general, exertional dyspnea precedes exertional chest pain. Secondary pulmonary hypertension can occur in chronic obstructive pulmonary disease, chronic or diffuse pulmonary embolization, and some rheumatic diseases. Chest pain may be due to the underlying disease. Occasionally, chest pain is directly attributable to secondary pulmonary hypertension, but again this usually occurs later than dyspnea on exertion and also after fatigue and syncope with exertion. Patients who have concurrent mitral stenosis or congenital heart disease with corpulmonale may have typical exertional angina even with normal coronary arteries. Chest pain in these cases may be due to pulmonary artery stretching or ischemia of the right ventricle.
Approximately 80% of patients with bacterial pneumonia complain of sudden on-set of shaking chills followed by fever, pleuritic chest pain, and cough productive of purulent sputum. Chest pain, occurring in up to 33% of patients, is sharp or stabbing in character and worse on inspiration. For patients with severe pain, opioid analgesics may be necessary until antibiotics quell the vigorous anti-inflammatory response to bacterial infection.
Of the primary cancers causing pain in the chest, lung cancer is the most common; 90% of patients are symptomatic when they seekmedical attention. Chest pain in the absence of other symptoms is relatively rare in this disease. Up to 50% of patients with lung cancer have experienced chest pain in conjunction with cough, dyspnea, weight loss, and hemoptysis. Pain due to tumor involvement is usually dull and intermittent. More severe or persistent pain may indicate chest wall, bony, or mediastinal invasion. Neuropathic pain involving the shoulder or upper extremity in a C8 to T1 distribution can be a manifestation of Pancoast tumor, when a superior sulcus malignancy spreads upward into the brachial plexus; Horner syndrome can be an associated manifestation. Pleural or pericardial effusion, hoarseness, or superior vena cava syndrome can also be seen. Isolated pleural effusions present more often with dyspnea or vague chest discomfort than with typical pleuritic chest pain.
Chest pain is commonly seen in sarcoidosis, although it more commonly causes cough and dyspnea. Cardiac involvement by the granulomatous process may also lead to arrhythmias including heart block and sometimes sudden death; this event may be preceded by chest pain, palpitations, syncope, or light-headedness.
The acute onset of pleuritic pain in otherwise healthy young adults is usually due to viral pleurisy. However, underlying autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, or occasionally drug-induced lupus, may be responsible. Potential offending agents include procainamide, hydralazine, isoniazid, and others.
Goyle KK et al. Diagnosing pericarditis. Am Fam Physician. 2002;66:1695. [PMID: 12449268]
Kruip MJ et al. Diagnostic strategies for excluding pulmonary embolism in clinical outcome studies. A systematic review. Ann Intern Med. 2003; 138:941. [PMID: 12809450]
Laack TA et al. Pulmonary embolism: an unsuspected killer. Emerg Med Clin North Am. 2004;22:961. [PMID: 15474778]
Perrier A et al. Multi detector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005;352:1760. [PMID: 15858185]
Esophageal disease can cause visceral pain identical to that caused by myocardial ischemia because the heart and the esophagus share similar neurologic innervation. Esophageal pain, like myocardial ischemia, may cause chest pressure, may be provoked by exercise or a motion, may be palliated by rest or nitrates, or may exhibit a crescendo pattern. A single response of chest pain to therapy with an antacid and viscous lidocaine does not reliably distinguish cardiac from esophageal pain. Up to one-third of patients referred for cardiology evaluation after emergency assessment for chest pain may have esophageal symptoms; even experienced clinicians may have difficulty making the diagnosis on clinical grounds. Features that may suggest an esophageal source of chest pain include the following:
Severe straining from repeated vomiting can cause spontaneous perforation of the esophagus (Boerhaave syndrome). The patient complains of excruciating retrosternal and
upper abdominal pain. The diagnosis is usually clear, since tachypnea, cyanosis, fever, and shock develop rapidly. Esophageal perforation may also be seen after caustic ingestion, pill esophagitis, infectious ulcers in AIDS patients, or following dilation of esophageal stricture.
Ambulatory intraesophageal pH monitoring shows that about 50% of patients with recurrent chest pain and normal findings on coronary angiograms have abnormal esophageal acid exposure. Reflux esophagitis can result from the combination of excessive reflux of gastric contents, combined with impaired esophageal clearance. A therapeutic trial of acid suppression that eliminates pain helps with the diagnosis; ambulatory pH monitoring can also be used but may be less economical. Endoscopy is a low-yield procedure, since as little as 6% of patients have esophagitis.
Studies using intraesophageal balloon distention have shown that some patients with noncardiac chest pain have a low threshold for esophageal pain. A similar pattern has been seen in patients with functional dyspepsia and irritable bowel syndrome. Peripheral chemoreceptors, mechanoreceptors, thermoreceptors, or a problem with central processing may be involved. Numerous neuro transmitters have been implicated.
True esophageal spasm is an uncommon cause of chest pain; most of these patients will also have dysphagia. Esophageal spasm may be primary or associated with systemic disease, such as scleroderma or diabetes. Occasionally, spasm may be superimposed on chronic esophageal reflux disease. Esophageal manometry studies have shown diffuse spasm, hypertensive lower esophageal sphincter tone, or “nutcracker esophagus,” with distal esophageal pressure exceeding 180 mm Hg, although relevance to clinical patterns is uncertain.
Esophageal abnormalities may be linked to either local or systemic effects of drugs, including antibiotics (especially doxycycline), aspirin and nonsteroidal anti-inflammatory drugs, potassium chloride, quinidine, iron compounds, and others. Odynophagia may be so severe that patients cannot swallow their saliva. Such “pill esophagitis” may be associated with swallowing pills without water.
Chest pain may be due to radiating or referred visceral pain from peptic ulcer disease, cholecystitis or other causes of biliary colic, acute or chronic pancreatitis, renal stones or, occasionally, appendicitis.
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Over one-third of complaints of chest pain are due to a musculoskeletal cause. Patients seek medical attention more often from their primary care physicians than urgent or emergent care physicians. Characteristic features may alert the clinician to a musculoskeletal cause (see Table 18-1), but potentially life-threatening diagnoses should be excluded first. Examples of such features include unaccustomed vigorous repetitive motion, especially of arms and torso; slow, insidious onset of pain; pain worsened by motion or change of position; pain that lasts for hours to days; and pain may be localized or widespread. Serious underlying chronic systemic diseases may present with musculoskeletal chest pain (Table 18-2); these should be ruled out through appropriate clinical examination and testing. Finally, any patient whose chest pain occurs reliably with exertion; whose pain radiates to arms, neck, or jaw; whose pain is associated with numbness, fever, chills, cough, or dyspnea; or whose pain is localized to unusual areas, such as the axilla or thoracic spine, should be evaluated carefully for other associated diseases.
Isolated musculoskeletal chest pain may present with a number of characteristic syndromes. “Costochondritis” can cause multiple areas of tenderness where palpation
exactly reproduces the pain that the patient describes. Most frequently involved are the upper costal cartilages at the costochondral or sternocostal joints. These areas are never warm, erythematous, or swollen; if inflammation is present, this should alert the clinician to the possibility of underlying rheumatic disease. Chest wall pain may often occur after coronary artery bypass surgery as a result of incisional inflammation or sternal wiring. Posterior chest wall pain may be caused by costovertebral joint dysfunction; the pain can mimic that of pulmonary embolism. Thoracic disc herniation usually causes dermatomal, band-like pain accompanied by focal neurologic symptoms, but occasionally it can cause retrosternal pain. Finally, herpes zoster can present with dermatomal pain that is quite severe; the clinician should look for a vesicular rash, but pain may precede skin involvement. Postherpetic neuralgia may also be responsible.
Table 18-2. Systemic Illnesses Causing Symptoms Associated with Musculoskeletal Chest Pain.
Up to 20% of emergent presentations for chest pain are related to panic disorder; up to 50% of patients with noncardiac chest pain have psychiatric diagnoses. Hyperventilation, which is associated with panic disorder, can cause noncardiac chest pain accompanied by a nonspecific ST-T wave changes on ECG. Despite the high prevalence of psychogenic chest pain, clinicians must exclude organic disease before ascribing chest pain to a nonorganic cause.
Patients with Monchausen syndrome, or factitious disorder, frequently complain of retrosternal chest pain as well as syncope, dyspnea, and back pain. Many of these patients are males with a mean age in the forties; most report having “white-collar” jobs and a prior history of cardiac disease; further investigation often proved these data not to be true.
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An accurate diagnosis leads to specific treatment for the underlying disease process, which usually diminishes pain. Most chest pain caused by cardiac, pulmonary, or gastrointestinal disorders responds well to specific treatment. Pain that is refractory to disease-modifying treatment can be managed in almost all cases with the use of oral analgesics.
Even in end-stage disease, where opioid analgesics often play a major role, specific treatment can at least be opioid-sparing. When treatment is not practical or is no longer effective or when patients choose comfort care, pain should be managed aggressively using both disease-specific medications and analgesics. The highest-quality palliative care for seriously ill patients combines disease-modifying treatment and comfort measures.
ST-segment elevation MI is usually associated with complete thrombotic occlusion of a coronary artery; it is generally treated with immediate reperfusion therapy. An early invasive strategy is also advocated for patients with ACS who are at high risk for further decline.
The American College of Cardiology and the American Heart Association have published evidence-based guidelines for the management of patients with non-ST-segment elevation ACS. A simplified “ABCDEF” approach includes antiplatelet therapy, β-blockade, cholesterol treatment, diabetes management, exercise, and follow-up (Table 18-3).
Aspirin reduces mortality and recurrent infarction with only a 0.2% increased risk of major bleeding. All patients should receive 162 to 325 mg of aspirin initially, followed by 75 to 160 mg daily thereafter. Clopidogrel 75 mg daily should be substituted in patients who are intolerant of aspirin, and the same amount should be added to aspirin and continued for 12 months in patients who are at low risk for bleeding. GP IIb/IIIa inhibitors (currently available agents include abciximab, eptifibatide, or tirofiban) should be administered to any patients treated with an early invasive strategy. Anticoagulation with low-molecular-weight heparin, specifically enoxaparin, should be accomplished to reduce ischemia. Treatment with an angiotensin-converting enzyme (ACE) inhibitor should be started in patients with known atherosclerosis, diabetes, left ventricular systolic dysfunction, or heart failure, although their benefits in lower risk patients are not as clear. Angiotensin-receptor blockers can be used as an alternative to ACE inhibitors-but not in combination with them-in patients who experience side effects, usually cough.
β-Blockade reduces sympathetic tone and, consequently, cardiac workload and myocardial oxygen demand. Benefits are increased in patients with hypertension or left ventricular systolic dysfunction. Blood pressure control to 130/85 mm Hg, or slightly lower for stable patients, should be achieved with amlodipine if ACE inhibitors and β-blockers have not sufficed.
Therapy with 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) should be started and continued through outpatient treatment to reduce low-density lipoprotein-C levels below 70 mg/dL (1.8 mmol/L). Niacin or a fibrate should be added for patients
with high-density lipoprotein levels <40 mg/dL (1.0 mmol/L). Cigarette smoking cessation greatly lowers the risk of future coronary events; behavioral support, as well as bupropion with or without nicotine replacement, should be provided.
Table 18-3. “ABCDEF” Management of Non-ST Segment Elevation Acute Coronary Syndrome.
Treatment should bring glycosylated hemoglobin levels below 7.0%. Diet should be enriched with protein, complex carbohydrates, fruits, vegetables, nuts, and whole grains; saturated fat, cholesterol, and salt should be restricted.
All patients should be encouraged to participate in moderate levels of aerobic and weight-bearing exercise for at least 30 minutes on most days of the week, preferably within a cardiac rehabilitation program.
Close follow-up with a physician is recommended for all patients within 1 to 6 weeks after discharge, with regular follow-up thereafter. Patients of advanced age as well as those with heart failure, persistent ST-segment depression, renal insufficiency, and elevated enzyme levels tend to have a higher incidence
of recurrent cardiovascular events at 1 year. For all others, risk approaches that of similar patients with coronary disease, especially after 1 year. Coronary angiography is recommended for those in whom new or recurrent is-chemic symptoms or heart failure develops or who survive a cardiac arrest.
Chest discomfort in angina pectoris is caused by transient myocardial ischemia whenever myocardial oxygen demand exceeds oxygen supply. Treatment of angina is aimed at reducing the former and increasing the latter.
Underlying medical conditions, particularly hypertension, febrile illnesses, tachyarrhythmias, anemia or polycythemia, conditions causing hypoxemia, valvular heart disease or thyrotoxicosis, should be treated. The patient should be encouraged to reduce exercise in cold weather or after eating. All patients should take one baby aspirin (81 mg/d) or clopidogrel if aspirin is contraindicated; dipyridamole is ineffective. Patients should be encouraged to undertake a regular aerobic exercise program as recommended by the American College of Cardiology and the American Heart Association. Risk factor reduction, especially including treatment of hypertension, smoking cessation, lipid lowering, weight reduction, and glycemic control in diabetics, should be undertaken. Stress reduction as well as treatment of any underlying depression and anxiety are beneficial. An exercise ECG should be considered. Noninvasive measurement of global left ventricular systolic function is important for patients with documented MI or Q waves on ECG.
Nitrates, β-blockers, and calcium channel blockers are standard therapy for angina. High-risk patients with stable angina should probably be treated with an ACE inhibitor as well. Opioids (eg, oral morphine) are used for refractory angina in late-stage disease.
Nitrates decrease myocardial oxygen demand by producing both systemic arterial vasodilation that reduces left ventricular systolic wall stress, as well as coronary vasodilation to a lesser degree. No difference has been found among nitrate preparations. Sublingual nitroglycerin (0.3 mg [1/200 grains]) repeated every 5 minutes times two is standard therapy for acute anginal episodes as well as prophylaxis for activities known to precipitate angina. Onset of action is less than 5 minutes, and duration of action is 30 to 40 minutes. Oral or transdermal nitrate preparations can prevent or reduce the frequency of recurrent anginal episodes. However, nitrate tolerance dictates a 12- to 14-hour nitrate-free interval each day. A commonly used regimen uses isosorbide dinitrate 10 to 40 mg at 8 A.M., 1 P.M., and 6 P.M. Extended-release isosorbide mononitrate can be started at 30 mg once daily and titrated to 120 mg once daily if needed, but its effect is reduced after 12 hours, so supplementary nitrates or additional antianginal therapy may be required if nocturnal or rebound angina develops.
Table 18-4. Selected β-Blockers Used to Treat Angina.
β-Blockers both inhibit sympathetic stimulation of the myocardium and reduce systemic sympathetic tone. Although all types of β-blockers are equally effective in exertional angina, long-acting cardioselective agents (eg, atenolol or metoprolol) are preferred for the treatment of stable angina, because their diminished inhibition of β2-receptors minimizes side effects in patients with chronic obstructive pulmonary disease, asthma, peripheral vascular disease, diabetes, and depression (Table 18-4). Target resting heart rate is 50 to 60 beats per minute, not to exceed 100 beats per minute with ordinary activity. β-Blockers have the added advantage of preventing re-infarction and improving survival in patients who have had an MI, although they have not been shown to prevent first infarctions. They should be used with caution in patients with chronic obstructive pulmonary disease or peripheral vascular disease, and started in low doses in patients with heart failure who are well compensated. β-Blockers should be avoided in patients with variant angina.
Calcium channel blockers prevent calcium entry into vascular smooth muscle cells, initiating coronary and peripheral vasodilation, which reduces coronary and systemic vascular resistance and increases blood flow. Several types of calcium channel blockers are available. The dihydropyridines (eg, nifedipine, nicardipine, felodipine and amlodipine) have greater selectivity for vascular smooth muscle than for myocardium; they are potent vasodilators and cause less reduction in contractility and atrioventricular conduction. Verapamil has greater myocardial selectivity; it is a negative inotrope and chronotrope but a less potent peripheral vasodilator than are the dihydropyridines. Diltiazem has intermediate effects between the two. Of the available agents, short-acting dihydropyridines, especially nifedipine, should be avoided because they have been shown to increase post-MI mortality and to increase the incidence of infarction in patients with hypertension. Long-acting diltiazem or verapamil or a second-generation dihydropyridine (eg, amlodipine or felodipine) may be used alone, in combination with β-blockers, or substituted for them (Table 18-5). Calcium channel blockers are the preferred therapy for variant angina. Potential side effects include bradycardia,
which may proceed to heart block, aggravation of heart failure, constipation, flushing, headache, dizziness, and pedal edema. Calcium channel blockers tend to be discontinued more frequently than are β-blockers because of adverse reactions, but this difference is most marked with nifedipine.
Table 18-5. Selected Calcium Channel Blockers Used to Treat Angina.
Opioids (eg, oral morphine sulfate) are used to manage refractory angina in two settings: (1) at the time of presentation with ACS, when opioids are given intravenously for acute, severe chest pain; and near the end of life, when relief of symptoms is the highest priority, even if life may be shortened somewhat. Morphine diminishes sympathetic tone, reducing blood pressure and heart rate; oxygen consumption is also reduced, resulting in a decrease in chest pain. In addition, morphine reduces chemoreceptor sensitivity to CO2, thereby diminishing dyspnea. Although a large retrospective study has shown that administration of morphine for ACS was associated with an increase in mortality, patients who received morphine also were seen more often by a cardiologist, were more likely to receive evidence-based medicine, and were more likely to undergo invasive procedures; these patients might have had more severe underlying disease. Randomized trials of opioids in the setting of ACS are needed.
β-Blockers and calcium channel blockers are equally effective in the management of stable angina. If there is no contraindication, β-blockers should be given to all patients who have a history of prior MI or who have stable heart failure and are receiving optimal ACE inhibitor therapy. Nitrates, although universally used to relieve anginal symptoms, may have limited usefulness in their slow-release form as first-line therapy because tolerance to their effect usually develops. Combination therapy with a β-blocker and a calcium channel blocker, with or without the addition of long-acting nitrates, is indicated for patients who do not respond well to monotherapy. Opioids, such as oral morphine, should be used for angina that is refractory to other agents, particularly in terminal patients.
Cardiovascular diseases are the most common cause of death in women in the United States, accounting for 35% of all-cause mortality. Symptoms of some form of cardiovascular disease develop in one of three women over 65 years of age. Because women are underrepresented in clinical trials, data concerning the management of women with ACS are limited. Available data suggest that women are not referred as often as men for diagnostic and therapeutic procedures, although this is probably due to the fact that women present with more comorbidities than men and, therefore, experience predictably higher complication rates from revascularization procedures. Available evidence supports the use of the same standard medical therapy for women as for men. However, women are more likely to receive nitrates, calcium channel blockers, diuretics, and sedatives than are men, while some studies suggest that women are less likely to receive β-blockers and aspirin. Estrogen supplementation has not been shown to have a cardioprotective effect in women with coronary disease.
In ST-elevation MI, indications for thrombolysis or stenting are generally the same for women as for men. In most series, however, women are less likely than men to undergo both procedures and are likely to experience a greater delay in treatment as well. This finding has raised questions of gender bias. However, women are often older and have a greater burden of risk factors than men. After adjustment for clinical and coronary variables, evidence indicates that women probably have equivalent access to both catheterization and revascularization.
In non-ST elevation ACS, outcomes in high-risk men are improved with an invasive strategy of early catheterization and revascularization, but available data conflict as to whether this benefit extends to women for uncertain reasons.
Available data indicate that both optimal medical therapy and revascularization produce similar outcomes in quality of life, improvement in angina and death or nonfatal MI compared with younger patients. An invasive approach appears to be associated with greater risk, while medical therapy is associated with an almost 50% chance of later hospitalization and revascularization. Patient preference is an important determinant, since some patients will prefer to assume the risk of early revascularization to achieve better short-term outcomes, while others will
prefer the lower-risk approach and the avoidance of surgical morbidity.
Braunwald E et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST elevation myocardial infarction-2002: Summary article. Circulation. 2002; 106:1893. [PMID: 12383588]
Gibbons RJ et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina-Summary article. Circulation. 2003; 107:149. [PMID: 12570960]
Gluckman TJ et al. A simplified approach to the management of non-ST-segment elevation acute coronary syndromes. JAMA. 2005;293:349. [PMID: 15657328]
Tresch DD et al. Diagnosis and management of myocardial ischemia (angina) in the elderly patient. Am J Geriatr Cardiol. 2001; 10:337. [PMID: 11684918]
Yang EH et al. Current and future treatment strategies for refractory angina. Mayo Clin Proc. 2004;79:1284. [PMID: 15473411]
American College of Cardiology/American Heart Association 2002 Guideline Update for the Management of Patients With Chronic Stable Angina-Summary Article http://www.acc.org/clinical/guidelines/stable/summaryarticle.pdf
American College of Cardiology/American Heart Association 2002 Guideline Update for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction-Summary Article http://www.acc.org/clinical/guide-lines/unstable/summaryarticle.pdf
Patients with severe pleuritic pain secondary to pulmonary embolus can be treated with morphine, either oral or intravenous, while definitive treatment is started. Thrombolytics are used if there is hemodynamic compromise from a large embolus; otherwise heparin, either unfractionated or low-molecular-weight, is started concurrently with warfarin. Heparin and oral anticoagulation therapy should overlap for at least 5 days, or until the international normalized ratio (INR) has been therapeutic for more than 48 hours. Heparin may be continued longer in cases of massive pulmonary embolus, or for large-burden iliofemoral thrombosis. Anticoagulation should be continued for at least 12 weeks, keeping INR in the range of 2.0 to 3.0. Some patients with recurrent or multisite thrombosis, including some with multicentric thromboembolic disease related to malignancy, may require low-molecular-weight heparin instead of warfarin. Patients without reversible risk factors for first thromboembolic event should be treated for 6 months. Inferior vena cava filter placement is recommended under the following clinical circumstances:
Chest pain in lung cancer is almost always due to tumor growth. Therefore, it is best controlled by definitive antitumor treatment with surgery, chemotherapy, or radiation. However, pain should be treated as soon as it occurs, because pain left untreated recruits previously uninvolved central nervous system elements. As acute pain becomes chronic, anxiety, depression, and other nonpain phenomena can emerge to complicate treatment. In cases where antitumor therapy is not practical, or when patients place a higher priority on comfort than on disease treatment, symptom management becomes the highest priority, and it should be pursued aggressively, even if life may be shortened in the process. In these situations, issues such as informed consent and advanced directives should be discussed fully with the patient, family, and care-givers. Hospice care is frequently the best way to ensure that symptom management and family/caregiver support are provided effectively until the end of the patient's life.
The principles underlying rational and effective treatment of chest pain in lung cancer are identical to those outlined for the treatment of cancer pain in Chapter 8. The World Health Organization three-step approach to pain management should be followed for the management of chest pain secondary to cancer (see Figure 3-1). Pain assessment, including measurement of each location and type of pain on a 1 to 10 scale, should be performed on a regular basis. Nonopioid analgesics, particularly nonsteroidal anti-inflammatory drugs, should be used, but “strong” opioids (eg, morphine) should be added whenever pain is severe, which usually means once pain reaches 6 or higher on a 10-point scale. Clinicians should watch carefully for neuropathic pain, which may be partially refractive to opioids; methadone may provide particular benefit, and its low cost should be borne in mind as well.
Clinicians should not be deterred from providing adequate pain management in lung cancer because of irrational fears of respiratory depression. Available data indicates that morphine, started at low doses and increased until pain is controlled, does not depress respiration even in patients with coexistent chronic obstructive pulmonary disease. The key is to “start low and go slow” in patients with chronic obstructive pulmonary disease; although morphine reduces chemoreceptor sensitivity to CO2, patients become tolerant quickly. Pco2 returns to baseline within 24 hours, whereas relief of both pain and dyspnea persist.
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American College of Chest Physicians: Management of Spontaneous Pneumothorax http://www.chestnet.org/education/hsp/statements/pneumothorax/qrg
American College of Emergency Physicians: Critical issues in the Evaluation and Management of Patients Presenting with Suspected Pulmonary Embolism http://www.acep.org/library/pdf/cpPulEmbolism.pdf
Most cases of chest pain referable to the gastrointestinal tract result from gastroesophageal reflux disease. Reflux symptoms, including chest pain, are a function of the severity of esophageal epithelial injury, which in turn is related to the quantity of esophageal acid exposure. Effective treatment must be titrated to disease severity. Mild symptoms may be managed empirically by elevating the head of the bed; this is particularly important for patients with nocturnal or laryngeal symptoms. Patients should be encouraged to avoid reflux-inducing foods, which included chocolate, peppermint, fatty foods, and excessive alcohol. In addition, cola drinks, orange juice, cranberry juice, and red wine all have a pH below 3.5. Patients should also be counseled to avoid lying down shortly after meals, and to avoid eating large meals within 1 hour of bedtime. Smoking cessation is also useful, in part because it diminishes salivation; saliva neutralizes refluxed acid and speeds its clearance from the esophagus.
Gastric acid secretion can be reduced with either H2-blockers or proton pump inhibitors (PPIs). The latter are preferred, especially in severe cases, because they are much more effective in healing esophagitis (therapeutic gain of up to 75% relative to placebo, compared with approximately 60% therapeutic gain with H2-blockers). PPIs have also been shown to produce more rapid healing and symptom relief than H2-blockers. Most of the available PPIs appear to have similar efficacy when given in equivalent doses, although few large trials have directly compared them (Table 18-6). Both H2-blockers and PPIs work by raising intragastric pH; they do not prevent reflux.
Table 18-6. Selected Proton Pump Inhibitors to Treat Esophageal Reflux Disease.
In general, patients should be treated with the least potent regimen that relieves symptoms. An alternative is to start with a dose of PPI that is likely to relieve symptoms in most cases (eg, 60 mg/d of omeprazole), then to step down treatment at 2 to 4 week intervals, maintaining antisecretory treatment for 8 weeks. Patients whose symptoms are relieved can be given a trial off medication. Relapses that occur in less than 3 months can be managed with continuous therapy, while relapses that occur after 3 months can be managed with intermittent therapy. Patients on continuous PPI therapy should undergo endoscopy at least once to rule out Barrett esophagus, an atrophic condition that predisposes to esophageal cancer. In addition, atrophic gastritis, with attendant risk of gastric cancer, as well as vitamin B12 deficiency, may occur in some patients receiving long-term PPI therapy.
Patients whose symptoms are refractory to PPIs may be considered for a 24-hour pH study on medication or esophageal manometry to rule out esophageal motility disorder. Calcium channel blockers may be effective in managing documented esophageal spasm. Antireflux surgery may be considered for those patients who do not respond to other measures.
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