9: Chest Pain

A patient with chest pain poses one of the most complicated diagnostic challenges. The differential diagnosis is extensive and includes diagnoses that can be imminently life-threatening. The initial pivotal points are the acuity of onset of the pain and the presence of vital sign abnormalities. Later in the evaluation, the presence of ECG or chest film abnormalities, symptoms consistent with aortic dissection, and the presence or absence of pleuritic pain (pain that worsens with inspiration) are important pivotal points. An algorithm to guide the consideration of the patient with chest pain is shown in Figure 9-1.

The differential diagnosis of chest pain is best remembered using an anatomic approach. Consideration needs to be given to the structures from the skin to the internal organs. The differential below is organized anatomically.

1. Skin: Herpes zoster

2. Breast

   1. Fibroadenomas

   2. Mastitis

   3. Gynecomastia

3. Musculoskeletal

   1. Costochondritis

   2. Precordial catch syndrome

   3. Pectoral muscle strain

   4. Rib fracture

   5. Cervical or thoracic spondylosis (C4–T6)

   6. Myositis

4. Esophageal

   1. Spasm

   2. Rupture

   3. Esophagitis

      1. Reflux

      2. Medication-related

   4. Neoplasm

5. Gastrointestinal (GI)

   1. Peptic ulcer disease

   2. Gallbladder disease

   3. Liver abscess

   4. Subdiaphragmatic abscess

   5. Pancreatitis

6. Pulmonary

   1. Pleura

      1. Pleural effusion

      2. Pneumonia

      3. Neoplasm

      4. Viral infections

      5. Pneumothorax

   2. Lung

      1. Neoplasm

      2. Pneumonia

   3. Pulmonary vasculature

      1. Pulmonary embolism

      2. Pulmonary hypertension

7. Cardiac

   1. Pericarditis

   2. Myocarditis

   3. Myocardial ischemia (stable angina, myocardial infarction, or unstable angina)

8. Vascular: Thoracic aortic aneurysm or aortic dissection

9. Mediastinal structures

   1. Lymphoma

   2. Thymoma

10. Psychiatric

Mr. W is a middle-aged man with chronic, nonpleuritic chest pain and risk factors for coronary artery disease (CAD). His symptoms are consistent with stable angina. The pivotal points in this case are the chronicity, exertional nature, and substernal location of the pain. Given the seriousness and prevalence of CAD, it must lead the differential diagnosis. Gastroesophageal reflux disease (GERD) and musculoskeletal disorders are common causes of chest pain that can mimic angina (exacerbated by activity, sensation of pressure) and thus should be considered. The chronicity of his symptoms argues against many other worrisome diagnoses (eg, pulmonary embolism [PE], pneumothorax, pericarditis, or aortic dissection). Pain from a mediastinal abnormality is possible. Table 9-1 lists the differential diagnosis.

Leading Hypothesis: Stable Angina

Textbook Presentation

Although atypical presentations are common, stable angina usually presents with symptoms of substernal chest discomfort precipitated by exertion. These symptoms resolve promptly with rest or nitroglycerin and do not change over the course of weeks. Affected patients usually have risk factors for CAD.

Disease Highlights

1. Stable angina is a chest pain syndrome caused by a mismatch between myocardial oxygen supply and demand.

   1. The mismatch is most often caused by coronary artery stenoses.

   2. It can also occur in the setting of normal or nearly normal coronary arteries and

      1. Anemia

      2. Tachycardia of any cause (atrial fibrillation, hyperthyroidism)

      3. Aortic stenosis

      4. Hypertrophic cardiomyopathy

      5. Heart failure (HF) (the result of high filling pressures)

         It is important to consider causes of angina other than CAD.

2. Stable angina is a common presentation for CAD.

3. Although exertional chest pain is the most common symptom of stable angina, other presentations are possible. Presentations may vary by what elicits the pain and what the symptoms are.

   1. Eliciting factors other than exercise

      1. Cold weather

      2. Extreme moods (anger, stress)

      3. Large meals

   2. Symptoms other than chest pain

      1. Dyspnea

      2. Nausea or indigestion

      3. Pain in areas other than the chest (eg, jaw, neck, teeth, back, abdomen)

      4. Palpitations

      5. Syncope

      6. Weakness and fatigue

4. The risk factors for CAD are important to elicit when the patient’s history is suspicious. The traditional risk factors follow:

   1. Male sex

   2. Age > 55 years in men and > 65 years in women

   3. Tobacco use

   4. Diabetes

   5. Hypertension

   6. Family history of premature cardiovascular disease (younger than age 55 in men and younger than age 65 in women).

   7. Abnormal lipid profile

      1. Elevated low-density lipoprotein (LDL)

      2. Elevated triglycerides

      3. Elevated cholesterol/high-density lipoprotein (HDL) ratio (normal < 5:1, ideally < 3.5:1).

      4. Low HDL

5. Other risk factors

   1. Other vascular diseases (peripheral, cerebral)

   2. Hyperhomocysteinemia

   3. Elevated levels of inflammation (C-reactive protein)

   4. Chronic kidney disease

   5. Cocaine use should be asked about because, although it is not a risk factor for CAD, it can cause both angina and myocardial infarction (MI).

      Asking about the traditional cardiac risk factors should be a part of the history for any patient with chest pain.

6. Stable angina and CAD in women

   1. Although the pathophysiology of stable angina is the same in men and women, it raises some unique issues in women that deserve comment.

   2. Stable angina presents differently in women than in men.

      1. Because angina usually presents in women at an older age than in men, there are more comordid diseases to confuse the presentation.

      2. Women describe their chest pain differently, using terms like “burning” and “tender” more frequently.

   3. There is good evidence that the diagnostic tests used for CAD, which are discussed later in this chapter, are less accurate in women than in men.

   4. Because there is a lower prevalence of disease among women,

      1. Physicians often do not consider the diagnosis.

      2. Lower pretest probability leads to worse positive predictive value of diagnostic tests (there are more false-positive results on noninvasive tests).

Evidence-Based Diagnosis

1. History

   1. The first step in diagnosing CAD is taking an accurate history of the patient’s chest pain.

   2. There are reliable data on the prevalence of disease in patients with typical angina, atypical angina, nonanginal chest pain, and in patients who are asymptomatic. The answers to the following questions categorize the patient’s chest pain:

      1. Is your chest discomfort substernal? (“Where is your pain?”)

      2. Are your symptoms precipitated by exertion? (“Does your pain come on or get worse when you walk, walk fast, or climb stairs?”)

      3. Does rest provide prompt relief of your symptoms (within 10 minutes)? (“Does your pain get better with rest?”)

         Use the patient’s own words when taking a history (eg, pressure, burning, aching, squeezing, piercing).

   3. Patients who answer yes to all 3 questions are classified as having typical angina, 2 positive answers as atypical angina, and 1 positive as nonanginal chest pain. A patient who answers no to all questions is asymptomatic.

   4. The prevalence of CAD in each group is shown in Table 9-2.

   5. It is also useful to think of these data in terms of low-, intermediate-, and high-risk groups.

      1. Patients with a low pretest probability of CAD (< 15%) are all asymptomatic patients, men with nonanginal chest pain who are younger than 50 years and women with nonanginal chest pain who are younger than 60 years. Women under age 50 with atypical angina are also low risk.

      2. Patients with intermediate pretest probability (15–85%) are men over age 50 and women over age 60 with nonanginal chest pain, any man and any woman over age 50 with atypical angina as well as men under age 40 and women under age 60 with typical angina.

      3. Men older than 40 years and women older than 60 years with typical angina have a high (>85%) pretest probability.

   6. It is important to recognize that comorbidities can markedly influence the probability of disease. As an example, the rate of CAD in a 55-year-old woman with atypical angina goes from about 32% with no risk factors to 47% with 1 risk factor (eg, diabetes, tobacco use, hypertension).

   7. The remainder of the history should be aimed at collecting evidence that makes the diagnosis of CAD more likely, such as

      1. Cardiac risk factors

      2. Past history of cardiac disease

      3. Symptoms classic for other causes of chest pain

   8. Factors that make the diagnosis of CAD less likely include

      1. Unremitting pain of prolonged duration

      2. Other explanations for the patient’s symptoms

   9. Initial tests that should be done at the initial presentation include

      1. Glucose and lipid profile to identify diseases that increase the likelihood of chest pain being ischemic in origin.

      2. Hgb and thyroid-stimulating hormone (TSH) to identify other diseases that may cause angina.

      3. Resting electrocardiogram (ECG), looking for evidence of previous infarction.

      4. Troponin, if recent anginal symptoms had been particularly severe or long lasting.

2. Exercise testing

   1. Except in very rare cases, patients with symptoms of stable angina should have an exercise test.

   2. The test is used for 2 purposes: to diagnose CAD and for risk stratification (determining whether patients should be treated with medication only, percutaneous coronary intervention (PCI), or bypass surgery.

   3. Decisions about treatment are based on a number of factors, many coming from the results of exercise testing:

      1. The extent and severity of ischemia (most important)

      2. Other prognostic variables, such as aerobic ability, blood pressure and heart rate response to exercise, and inducible left ventricular dysfunction.

   4. All exercise tests attempt to induce and detect myocardial ischemia.

      1. Myocardial ischemia may be induced by exercise, dobutamine, adenosine, or dipyridamole.

      2. Myocardial ischemia may be detected by ECG, echocardiogram, or nuclear imaging.

      3. The sensitivity of an exercise test will fall if the patient does not reach an adequate degree of exercise, as measured by the rate-pressure product.

   5. Exercise electrocardiography is the simplest and least expensive test.

      1. It requires a normal resting ECG.

      2. The sensitivity of the exercise stress test can be improved (at the cost of lower specificity) by reducing the degree of ST depression needed for a positive test.

   6. The sensitivity, specificity, and LRs of some of the various tests are shown in Table 9-3. (It should be noted that the test characteristics of stress thallium and dobutamine echocardiography vary among healthcare centers.)

   7. The decision whether to order a routine exercise test or one with imaging is difficult. In general, reasons to obtain imaging are

      1. Abnormal resting ECG

      2. Previous coronary artery bypass grafting (CABG) surgery or PCI

      3. A more sensitive test is required to rule out CAD, such as in patients with a high likelihood of CAD.

         Because of the relatively low sensitivity of ECG stress tests, these should only be used to exclude the diagnosis of CAD in low-risk patients.

   8. Means of increasing coronary demand other than exercise (pharmacologic stress tests) are indicated for patients who are unable to exercise. They may also be more accurate in patients with a left bundle-branch block.

   9. A patient with stable angina might not undergo an exercise test if he has a high likelihood of disease (a test therefore does not need to be done for diagnostic purposes) and would not benefit from determining the distribution or severity of the disease (usually because he would not, or could not, undergo revascularization).

3. Angiography

   1. The gold standard for diagnosing CAD.

   2. The indications for patients with stable angina to undergo angiography include

      1. Abnormal stress indicating substantial ischemia.

      2. Ischemia at a low workload on an exercise test.

      3. Diagnostic uncertainty after an exercise test.

   3. Patients may undergo angiography without first having an exercise test in 2 circumstances when they will almost certainly require invasive therapy (PCI or CABG).

      1. When their symptoms are disabling despite therapy.

      2. When they have HF.

Treatment

1. The goal of treatment in patients with stable angina is to decrease symptoms and inhibit disease progression. Patients with stable angina have about a 3%/year risk of both MI and death.

2. Nonpharmacologic

   1. Smoking cessation

   2. Exercise (intensity guided by exercise testing)

   3. Low fat, low cholesterol diet

3. Pharmacologic

   1. Symptomatic treatment. It is important to recognize that patients often need a combination of medicines to control their symptoms.

      1. Decrease oxygen demand: beta-blocker or the calcium channel blockers verapamil or diltiazem

      2. Increase oxygen supply: long-and short-acting nitrates

      3. Ranolazine, a sodium channel blocker, is an effective antianginal, usually used in combination with a beta-blocker.

   2. Inhibit disease progression

      1. Aspirin

      2. Clopidogrel in patients who are intolerant of aspirin or who have had PCI.

      3. Risk factor modification

         • (1) BP control in patients with hypertension.

         • (2) High intensity HMG-CoA reductase inhibitor (statin) therapy.

         • (3) Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in patients at the highest risk, such as those with diabetes or HF.

         • (4) Glycemic control in patients with diabetes

4. Interventional therapy (either via PCI or bypass surgery) is the mainstay of treatment for the acute coronary syndromes discussed below. For stable angina, it plays a role in the care of patients with more advanced disease. An overview of the data is below.

   1. In low-risk patients (such as those with single vessel disease)

      1. There is no difference in mortality between medical management and PCI.

      2. Patients who undergo a PCI tend to have better control of their symptoms but undergo more procedures.

   2. In moderate-risk patients (such as those with multivessel disease but an otherwise normal heart)

      1. PCI and CABG are about equal in terms of mortality and both are superior to medical therapy.

      2. PCI leads to more procedures.

   3. In high-risk patients (such as those with disease of the left main coronary artery, 3 vessel disease, or 2 vessel disease involving the proximal left anterior descending artery)

      1. Bypass surgery has a survival benefit compared with medical therapy.

      2. For selected patients, PCI can have a similar outcome to surgery.

      3. Bypass surgery is superior in patients with diabetes.

The results of the patient’s exercise test are surprising. Stable angina remains high in the differential despite the normal stress test but alternative diagnoses must be considered. The intermittent nature of the pain and the lack of constitutional symptoms both make a mediastinal lesion unlikely. The absence of a recent injury, change in activity or reproducible pain on physical exam moves musculoskeletal pain down on the differential. GERD is a common cause of chest pain and should be considered.

Alternative Diagnosis: Gastroesophageal Reflux Disease (GERD)

Textbook Presentation

Heartburn (a burning, substernal, chest discomfort) is usually the presenting symptom in a patient with GERD. Other classic symptoms are regurgitation or dysphagia; chest pain is a common alternative presentation. Patients often report that their symptoms are worst at night and after large meals.

Although dysphagia is a common presentation of GERD, its presence raises the possibility of an obstructing lesion and thus mandates prompt evaluation, usually with upper endoscopy.

Disease Highlights

1. The symptoms of GERD are so well known that most patients diagnose themselves before visiting a physician.

2. GERD is a common cause of chest pain.

3. There are GI and non-GI complications of GERD.

   1. GI

      1. Esophagitis

      2. Stricture formation

      3. Barrett esophagus

      4. Esophageal adenocarcinoma

   2. Non-GI

      1. Chronic cough

      2. Hoarseness

      3. Worsening of asthma

4. Esophageal disorders, other than GERD, might also present as chest pain.

   1. Esophagitis or esophageal ulcer

      1. Odynophagia common

      2. Multiple causes include infection and pill esophagitis.

      3. Pill esophagitis is especially associated with certain medications:

         • (1) Bisphosphonates

         • (2) Tetracyclines

         • (3) Antiinflammatories

         • (4) Potassium chloride

   2. Esophageal cancer

      1. Often associated with dysphagia

      2. Smoking, alcohol use, and chronic reflux are risk factors.

   3. Esophageal rupture (Boerhaave syndrome). Often presents with acute pain after retching.

   4. Esophageal spasm and motility disorders. Often presents with intermittent chest pain and dysphagia.

Evidence-Based Diagnosis

1. GERD should be high in the differential diagnosis of chest pain when heartburn, regurgitation, or dysphagia is present or when other commonly associated symptoms or complications (eg, chronic cough and asthma) are present.

2. Identifying factors that exacerbate the symptoms of GERD is helpful both in diagnosis and management.

   1. Ingesting large (especially fatty) meals

   2. Lying down after a meal

   3. Using tobacco

   4. Eating any of the (delicious) foods that relax the lower esophageal sphincter

      1. Chocolate

      2. Alcohol

      3. Coffee

      4. Peppermint

3. Historical features help differentiate esophageal from cardiac chest pain.

   1. A small study analyzed the prevalence of several historical features in 100 patients in an emergency department with either esophageal or cardiac chest pain.

   2. The differences that reached statistical significance are listed in Table 9-4. Although the study was small, the data are instructive.

   3. From these data, it is clear that history cannot differentiate esophageal chest pain from pain due to cardiac ischemia. That said, pain that occurs with swallowing, is persistent, wakes the patient from sleep, is positional, and is associated with heartburn or regurgitation is more likely to be of esophageal origin.

   4. It is interesting that only 83% of patients with an esophageal cause of pain in this study had GI symptoms (ie, heartburn, regurgitation, dysphagia, or vomiting).

   5. Striking were some of the features not significantly different between the 2 groups:

      1. Radiation to the left arm

      2. Exacerbation with exercise

      3. Relief with nitroglycerin

   6. The effect of nitroglycerin in relieving chest pain has consistently been found to be useless in differentiating anginal chest pain from esophageal or other causes of chest pain.

      Response to nitroglycerin should not be used as a diagnostic test in the evaluation of chest pain.

4. Esophageal pH testing, the gold standard for the diagnosis of GERD, is seldom necessary.

5. The combination of a suspicious history and consistent endoscopic findings has a 97% specificity for GERD.

6. Suggestive symptoms and response to therapy is generally considered diagnostic.

7. Esophagogastroduodenoscopy (EGD) should be done when

   1. Patients have symptoms of complicated disease

      1. Dysphagia

      2. Extra-esophageal symptoms

      3. Bleeding

      4. Weight loss

      5. Chest pain of unclear etiology

   2. Patients are at risk for Barrett esophagus (long-standing symptoms of reflux).

   3. Patients require long-term therapy.

   4. Patients respond poorly to appropriate therapy.

8. Ambulatory pH monitoring is useful in 2 settings:

   1. In patients with symptoms of GERD and a normal endoscopy.

   2. To monitor therapy in refractory cases.

Treatment

1. Nonpharmacologic

   1. Elevate the entire head of the bed; adding extra pillows may actually worsen reflux.

   2. Avoid lying down for 3 hours after meals.

   3. Stop smoking.

   4. Stop ingesting foods and beverages that relax the lower esophageal sphincter or worsen symptoms of GERD.

2. Pharmacologic

   1. Antacids

   2. H₂-blockers

   3. Proton-pump inhibitors

      1. First-line therapy in patients with reflux severe enough to prompt a physician visit.

      2. Many patients require long-term therapy.

   4. Motility agents (such as metoclopramide) are useful in patients who need adjuvant therapy or who have significant symptoms of regurgitation.

   5. Surgery

      1. Antireflux surgery currently has only a very small role.

      2. May be warranted in some patients with particularly severe disease.

      3. One randomized trial has suggested that patients treated with surgery had a higher mortality rate than those treated medically at a mean follow-up of about 11 years (number needed to harm [NNH] = 8.3).

         Because GERD is a common cause of chest pain, if the suspicion of the disease is high, it is appropriate to prescribe an empiric course of proton-pump inhibitors after more ominous causes of chest pain have been ruled out.

Prior to the stress test, Mr. W’s probability of having CAD was at least 92% (see Table 9-2). It is important to understand why the exercise test was done in this case. The diagnosis of coronary disease was essentially made by the history and physical. The exercise test was meant to guide therapy. Considering a pretest probability of 92%, and a LR– of about 0.15 for the exercise test, the posttest probability is 60%. This is still well above the test threshold for a potentially fatal disease like CAD.

Despite the results of the stress test, stable angina was considered more likely than GERD. Mr. W was given aspirin and a beta-blocker and underwent an angiogram the week after the visit. He was found to have a 90% stenosis of the mid left anterior descending artery and underwent PCI with stent placement.

Before ordering an exercise test, ask yourself why you are doing it: Are you trying to diagnose CAD or determine the severity of the disease?

Mrs. G is experiencing acute, severe, nonpleuritic chest pain. This presentation is associated with multiple “must not miss” diagnoses. The acuity of the pain is a pivotal point in this history. MI with and without ST elevations and unstable angina, as a group referred to as acute coronary syndromes, are the most common life-threatening causes of acute chest pain and need to be considered first. Aortic dissection also needs to be considered given the severity of the pain, the history of hypertension, and the radiation of the pain to the back. PE is another possible cause even though the chest pain is not pleuritic. Other alternative causes of this type of pain are esophageal spasm and pancreatitis (though it would be atypical for pancreatitis to begin so acutely). Table 9-5 lists the differential diagnosis.

Leading Hypothesis: Acute MI

Textbook Presentation

The classic presentation of an acute MI is crushing substernal chest pressure, diaphoresis, nausea, shortness of breath, and a feeling of impending doom in a middle-aged man with risk factors for CAD. Even more than other “textbook presentations,” this description is often inaccurate because it does not take into account the frequency of MIs in women, younger and older patients, and the frequency of atypical presentations.

Disease Highlights

1. MI occurs when there is a prolonged failure to perfuse an area of myocardium leading to cell death.

2. Most commonly occurs when a coronary plaque ruptures causing thrombosis and subsequent blockage of a coronary artery.

3. The universal definition of MI describes 5 subtypes of MI based on their clinical presentation:

   1. Spontaneous MI due to a primary coronary event.

   2. MI secondary to ischemia due to either increased oxygen demand or decreased supply, eg, coronary artery spasm, anemia, or arrhythmias.

   3. Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischemia.

   4. MI associated with PCI or stent thrombosis.

   5. MI associated with CABG.

4. Acute MIs are classified as either ST segment elevation MI (STEMI) or non–ST segment elevation MI (NSTEMI).

   1. ST elevations signify transmural ischemia or infarction.

   2. NSTEMI

      1. Are less severe, usually injuring only subendomyocardial tissue

      2. Have a higher subsequent risk for STEMI than for patients who have had a STEMI

   3. These 2 types of MI are managed differently. The discussion of STEMI is covered in this section while the management of NSTEMI is discussed in the next section on unstable angina.

Evidence-Based Diagnosis

1. The diagnostic criteria for acute MI have been clearly established. There are 5 criteria that vary somewhat, based partly on the subtype of MI. They are shown in Table 9-6.

2. Clinical findings suggestive of MI

   1. Pretest probability

      1. About 15% of patients who arrive at the emergency department complaining of chest pain are having an MI.

      2. About 33% of patients admitted to the hospital with suspicion of an MI are found to be having one.

      3. About 50% of patients admitted to the CCU with suspicion of an MI are found to be having one.

   2. Historical and physical exam features are never sufficient to diagnose an MI and only (nearly) exclude MI in the lowest risk patients. Test characteristics for some common signs and symptoms appear in Table 9-7.

   3. Types of chest pain that decrease the likelihood of MI include pleuritic pain, sharp or stabbing pain, or positional pain.

3. ECG findings suggestive of MI

   1. All guidelines recommend an ECG be performed within 10 minutes of a patient’s arrival at a healthcare facility when an MI is suspected.

      Patients with chest pain should have an ECG within 10 minutes of arriving at a healthcare facility.

   2. Prevalence rates of MI among emergency department patients with chest pain and various ECG findings follow:

      1. New ST elevation of 1 mm: 80%

      2. New ST depression or T wave inversion: 20%

      3. No new changes in a patient with known CAD: 4%

      4. No new changes in a patient without known CAD: 2%

   3. Table 9-8 shows the test characteristics for ECG findings in patients with acute chest pain. (Because numbers vary from study to study, these likelihood ratios should be treated as estimates.)

      A patient with chest pain and ≥ 1-mm ST elevations in 2 contiguous leads or a new left bundle-branch block is having an acute MI and should receive immediate therapy.

4. Cardiac enzymes

   1. As is clear from the diagnostic criteria, abnormal levels of cardiac enzymes define the presence of MI.

   2. When an MI is suspected, creatine kinase MB subunit (CK-MB) and troponin should be ordered and processed immediately.

   3. These tests are highly reliable in diagnosing MI. (Note that the definition of MI is based on enzyme results whenever they are available.)

      1. Troponin: sensitivity, 95%; specificity, 98%; LR+, 47; LR-, 0.3.

      2. Serial CK-MB: in the first 24 hours—sensitivity, 99%; specificity, 98%; LR+, 50; LR-, 0.1.

   4. Troponin levels in patients with kidney disease

      1. Patients with kidney disease often have elevated troponin levels raising the risk of false-positive tests for MI.

      2. Patients with elevated troponin levels at baseline will still have a diagnostic rise and fall with MI.

      3. In patients with chronic kidney disease, higher baseline troponin levels are predictive of poor cardiovascular outcomes.

5. MI in women

   1. Presentation

      1. Acute MIs present differently in women than in men.

      2. Women often report prodromal symptoms such as fatigue, dyspnea, and insomnia.

      3. Women are more likely to present without chest pain than men (42% vs 30.7%). This difference becomes less pronounced as patients age (as both men and woman present more frequently without chest pain).

         Just under half of women suffering an MI have a chief complaint other than chest pain.

      4. Dyspnea, weakness, and fatigue are the other common presenting symptoms.

   2. Outcomes

      1. Women who suffer an MI are more likely to die. Recent data show an in-hospital mortality rate of 14.6% for women and 10.3% for men.

      2. The cause of this disparity is multifactorial but includes the fact that patients without chest pain receive delayed and less aggressive care.

      3. The mortality difference becomes less pronounced and eventually reverses as patients age.

6. Unrecognized MI

   1. Although the combination of symptoms, ECG findings, and enzymes make most MIs easy to diagnose, about 2% of patients with acute MI are not diagnosed and are discharged from the emergency department.

   2. Failure to recognize an MI results in worse outcomes for patients and serious medicolegal issues.

   3. MIs most commonly go unrecognized when they present in unusual ways or in people not expected to have MI.

   4. A patient with an MI or unstable angina who is mistakenly discharged is most likely to:

      1. Be a woman younger than age 55

      2. Be non-white

      3. Have a chief complaint of shortness of breath

      4. Have a nondiagnostic ECG

   5. The most common alternative presentations of MI are listed below. MI should at least be considered in patients being discharged from the emergency department with 1 of these diagnoses:

      1. HF

      2. Stable angina

      3. Arrhythmia

      4. Atypical location of pain

      5. Central nervous system manifestations (symptoms of cerebrovascular accident)

      6. Nervousness, mania, or psychosis

      7. Syncope

      8. Weakness

      9. Indigestion

         MI can present in many different ways. A high index of suspicion should always be present. Certain groups of patients (elderly, women, minorities, diabetics) are most likely to be misdiagnosed.

Treatment

1. Once an MI is diagnosed, therapy must be initiated immediately. The following applies to the treatment of STEMI:

   1. Medications

      1. Antiplatelet agents: aspirin, P2Y12 receptor blockers (eg, clopidogrel) and, in patients undergoing primary PCI, a glycoprotein IIb/IIIa inhibitor

      2. Beta-blockers

      3. Oxygen

      4. Nitroglycerin

      5. High intensity HMG-CoA reductase inhibitors (statins)

      6. Other therapy based on presentation

         • (1) Opioids for patients in pain

         • (2) Atropine for patients with pathologic bradycardia

         • (3) Antiarrhythmic agents

2. Reperfusion with either systemic thrombolysis or primary PCI.

   1. Although not universally available, primary PCI is the preferred option.

   2. Primary PCI is associated with

      1. Lower mortality (even in patients who must be transferred—albeit quickly—to a hospital with the capability)

      2. Significantly lower risk of serious bleeding complication. Hemorrhagic stroke is not a potential complication as it is with systemic thrombolysis.

   3. The ability to do primary PCI depends on the presence of an interventional cardiology team who can rapidly (within 90 minutes) bring the patient to the catheterization laboratory.

   4. Primary PCI with stent placement is the most efficacious treatment.

   5. Both primary angioplasty and thrombolysis are most effective when completed within 12 hours of symptom onset.

3. Once the culprit vessel has been opened, various medications have been shown to improve survival after acute MI.

   1. Beta-blockers

   2. ACE inhibitors

   3. Aspirin

   4. P2Y12 receptor blockers (duration based on intervention and risk of bleeding)

   5. HMG-CoA reductase inhibitors, dosed to achieve an LDL < 70 mg/dL.

   6. Glycoprotein IIB/IIIA inhibitors are recommended for patients with MIs who undergo stenting.

4. An exercise test is also recommended within 3 weeks of an MI in patients not undergoing PCI or angiography for information on prognosis, functional capacity, and risk stratification.

The ST depression is consistent with cardiac ischemia but is less specific than ST elevation and does not conclusively make the diagnosis of an acute MI; the diagnosis will be confirmed when cardiac enzyme levels are available. The abnormal ECG certainly makes the alternative diagnosis, unstable angina, quite likely if an MI is excluded. Aortic dissections can cause cardiac ischemia, so this too must remain in the differential.

Alternative Diagnosis: Unstable Angina

Textbook Presentation

New or worsening symptoms of CAD are the presenting symptoms of unstable angina. Unstable angina and an acute MI without ST elevation (NSTEMI) may be identical in their presentation, only differentiated by the presence or absence of myocardial enzyme elevation.

Disease Highlights

1. Unstable angina is defined as angina that is new, worsening in severity or frequency, or occurs at rest.

2. Pathophysiology

   1. Primarily caused by acute plaque rupture followed by platelet aggregation

      1. 67% of episodes occur in arteries with < 50% stenosis.

      2. 97% occur in arteries with < 75% stenosis.

   2. Caused less commonly by changes in oxygen demand or supply (eg, hyperthyroidism, anemia, high altitude)

3. The diagnosis of unstable angina can be difficult, often depending on a careful history to differentiate stable from unstable angina.

4. The clinician seeing a patient with unstable angina or a NSTEMI must

   1. Recognize that the patient has an acute coronary syndrome

   2. Institute care

   3. Determine the patient’s risk of progressing to an MI or death

   4. Treat accordingly

5. Vasospastic angina

   1. Vasospastic angina (also called Prinzmetal or variant angina) is a phenomenon that presents in a similar way to unstable angina.

   2. Patients with vasospastic angina periodically have episodes of cardiac ischemia with ST elevation.

   3. The attacks

      1. Are often associated with chest pain or other ischemic symptoms

      2. Resolve spontaneously or with nitroglycerin

      3. May occur in normal or diseased coronary arteries

      4. Can result in MI or death (often secondary to arrhythmia)

      5. Often occur at the same time each day

   4. Vasospastic angina is usually diagnosed clinically but can also be diagnosed by inducing it with ergonovine infusion in the catheterization laboratory.

   5. Vasospastic angina is treated effectively with calcium channel blockers and nitrates.

      Vasospastic angina should be considered in patients whose symptoms are consistent with cardiac ischemia and occur at about the same time each day. The diagnosis should also be considered when transient ST elevations develop.

Evidence-Based Diagnosis

1. Diagnosis

   1. There are 3 presentations of unstable angina:

      1. Rest angina

      2. New-onset (< 2 months) angina

      3. Increasing angina

   2. The American College of Cardiology and American Heart Association have endorsed a number of findings that increase the likelihood that a patient’s symptoms represent an acute coronary syndrome. These include

      1. Chest or left arm pain that reproduces prior angina

      2. Known history of CAD

      3. Transient mitral regurgitation murmur

      4. Hypotension

      5. Diaphoresis

      6. Pulmonary edema

      7. Crackles

2. Risk stratification

   1. Appropriate risk stratification ensures that the patient is triaged to the proper location for care (ICU, inpatient ward, home) and receives the most beneficial therapy.

   2. Patients can be stratified by various validated scores. The TIMI score is probably most commonly used and is shown in Table 9-9.

   3. Other characteristics that portend high risk are

      1. Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy

      2. Elevated cardiac biomarkers (troponin)

      3. Signs or symptoms of HF or new or worsening mitral regurgitation

      4. High-risk findings from noninvasive testing

      5. Hemodynamic instability

      6. Sustained ventricular tachycardia

      7. PCI within 6 months

      8. Prior CABG

      9. Reduced left ventricular function

Treatment

1. The following treatments should be started as soon as unstable angina or a NSTEMI is suspected:

   1. Oxygen

   2. Antiplatelet agents aspirin and a P2Y12 receptor blocker

   3. Anticoagulation with enoxaparin, unfractionated heparin, or bivalirudin

   4. Beta-blockers

   5. Nitrates

   6. High doses of HMG-CoA reductase inhibitors are probably beneficial when given early in the course of the presentation.

2. Patients whose risk stratification identifies them as having a low risk of death or complications should undergo conservative management strategy.

   1. If the patient is stable (no ongoing ischemia, arrhythmias or decreased ejection fraction on echocardiogram), a stress test should be done to determine whether angiography is indicated.

   2. If the stress test finds the patient to be at low risk, the patient can be discharged with prescriptions for aspirin, clopidogrel, beta-blockers, and an HMG-CoA reductase inhibitor.

3. Patients found to be at higher risk benefit from an early invasive strategy. These patients undergo angiography to determine further management (PCI, CABG, or medical therapy for coronary disease).

Alternative Diagnosis: Aortic Dissection

Textbook Presentation

The textbook presentation of an aortic dissection is an older man with a history of hypertension and possibly atherosclerotic disease who complains of “tearing” chest or back pain. The pain might be associated with vascular complications such as syncope, stroke, cardiac ischemia, or HF secondary to acute aortic regurgitation. On physical exam, there is asymmetry in the upper extremity BPs, and the chest radiograph shows a widened mediastinum.

Disease Highlights

1. Dissection begins with a tear in the aortic intima allowing blood to dissect the aorta between the intima and media.

2. Risk factors

   1. Hypertension, present in 72% of patients

   2. Atherosclerosis, present in 31% of patients

   3. Known aortic aneurysm, present in 16% of patients

      1. Aortic aneurysms are usually detected while they are asymptomatic on a chest radiograph.

      2. They may also present with aortic regurgitation, pain, or through impingement on other structures such as the trachea, esophagus, or recurrent laryngeal nerve.

   4. Prior aortic dissection (6%)

   5. Diabetes (5%)

   6. Marfan syndrome (5%)

3. An additional risk factor for aortic dissection is cocaine use. This is associated with dissections in younger patients (mean age 41).

   In addition to MI, thoracic aortic dissection should be considered in the differential of a young hypertensive patient who has chest pain after using cocaine.

4. The symptoms of dissection include pain as well as symptoms of vascular complications of the dissection. The type of complication depends on what type of dissection occurs.

5. Type A dissections involve the ascending aorta with or without the descending aorta.

   1. Account for about 60% of dissections

   2. Carry a mortality of about 35%

   3. May be associated with

      1. Acute aortic insufficiency

      2. Myocardial ischemia due to coronary occlusion

      3. Neurologic deficits

      4. Cardiac tamponade due to hemopericardium

6. Type B dissections involve only the descending aorta and are associated with a mortality rate of about 15%.

Evidence-Based Diagnosis

1. The diagnosis of aortic dissection is notoriously difficult. There are no signs or symptoms that are consistently associated with very high or very low LRs.

2. A study of 464 patients with aortic dissection helps describe the common presenting signs and symptoms of people with this diagnosis.

   1. Demographics:

      1. Mean age ≈ 63 years

      2. Hypertension in about three-quarters

   2. The presenting signs and symptoms were notable for the infrequency of some classic findings.

      1. Pulse deficit was noted in only 15% of patients, syncope in 9%, cerebrovascular accident in 5%, and HF in 7%.

      2. Some of the more common symptoms are shown in Table 9-10.

      3. Chest radiograph and ECG were found to be very insensitive diagnostic tools.

         The aorta is normal on the chest film in about 40% of patients with a dissection of the thoracic aorta.

3. Another study stratified patients by 3 independent predictors of aortic dissection: aortic type pain (pain of acute onset or tearing or ripping character), aortic or mediastinal widening on chest radiograph, and pulse or BP differentials.

   1. Low-risk patients had none of the characteristics.

      1. Only 7% of these patients had a dissection

      2. The test characteristics of these findings for excluding dissection were sensitivity, 96%; specificity, 48%; LR+, 1.85; LR−, 0.08.

   2. Intermediate-risk patients had only consistent pain or a consistent chest radiograph. Between 30% and 40% of these patients had a dissection.

   3. High-risk patients had pulse or both consistent pain and an abnormal chest film.

      1. > 84% of these patients had a dissection.

      2. The test characteristics of these findings for predicting dissection were sensitivity, 76%; specificity, 91%; LR+, 8.4; LR−, 0.26.

   4. The test characteristics for pulse or BP differentials in a patient in whom aortic dissection is suspected were sensitivity, 37%; specificity, 99%; LR+, 37; LR−, 0.64.

4. Summarizing the clinical diagnosis of aortic dissection

   1. Patients with dissections are likely to have a history of hypertension and experience severe, acute pain.

   2. Patients with chest pain are unlikely to have a dissection if they do not have any of the following:

      1. Acute or tearing or ripping pain

      2. Aortic or mediastinal widening

      3. Asymmetric pulse or BPs

5. The gold standard for diagnosis is angiography but most patients undergo noninvasive tests (CT or transesophageal echocardiography).

6. Both noninvasive tests have sensitivities and specificities above 95%.

7. Angiography is recommended to help guide therapy if there is evidence of organ ischemia.

Treatment

1. Because dissection is associated with extremely high mortality, the goal is to identify and repair the aneurysm prior to rupture.

2. Thoracic aortic dissection

   1. Dissection of the thoracic aorta is a medical emergency.

   2. Type A dissections generally are operated on immediately.

   3. Type B dissections usually are managed medically.

3. Thoracic aortic aneurysms (without dissection)

   1. When aneurysms are detected prior to rupture, the goal of therapy is to slow their growth and operate when the aneurysm reaches a certain size.

   2. Patients with aneurysms should have tight BP control.

   3. Patients should be closely monitored for increasing aneurysm size.

   4. Indications for surgery are based on the size of the aneurysm.

      1. 5.5 cm for ascending aneurysms

      2. 6.5 cm for descending aneurysms

      3. Rapid growth

The patient’s troponin and CK make the diagnosis of an acute MI. It should be realized that the presence of an MI does not rule out dissection of the thoracic aorta. Between 3% and 5% of patients with dissections have associated MIs. Even before the catheterization results, the subacute onset of the pain, the normal chest film, the lack of “tearing pain,” and symmetric pulses made aortic dissection unlikely.

This is a healthy young man with an acute illness. He reports pleuritic chest pain, cough, dyspnea, and fevers. The acuity of the symptoms as well as the pleuritic nature of the pain are pivotal points in this case. The first diagnoses to consider are infectious diseases that could cause pleuritic chest pain and fever. Pneumonia or pleural effusion could cause these symptoms, either individually or as part of the same process. (Pleural effusions will be discussed below while pneumonia will be discussed in Chapter 10.) Pericarditis can also cause pleuritic chest pain and can be associated with fevers. PE is a classic cause of pleuritic chest pain and shortness of breath and may be associated with fever (see Chapter 15). Intra-abdominal processes, such as subdiaphragmatic abscess should be kept in mind as causes of pleuritic chest pain. The combination of fever, dyspnea, and chest pain places pneumonia or pleural effusion at the top of the list. Table 9-11 lists the differential diagnosis.

Leading Hypothesis: Pleural Effusion

Textbook Presentation

Small effusions are usually asymptomatic while large effusions reliably cause dyspnea with or without pleuritic chest pain. The presentation depends on the cause of the effusion. Parapneumonic effusions will be accompanied by the signs and symptoms of pneumonia while effusions related to neoplasm, HF, PE or rheumatologic disease will be accompanied by signs of those underlying diseases.

Disease Highlights

1. Pathophysiology of pleural effusions vary by etiology but may be due to 1 or any combination of the following:

   1. Increased capillary permeability

   2. Increased hydrostatic pressure

   3. Decreased oncotic pressure

   4. Increased negative intrapleural pressure

   5. Disruption of pulmonary lymphatics

2. The most common causes of pleural effusions with their approximate yearly incidence are listed in Table 9-12.

3. The most useful way of organizing the differential diagnosis is by whether the effusion is exudative or transudative.

   1. Exudative effusions are caused by increased capillary permeability or disruption of pulmonary lymphatics.

   2. Transudative effusions are caused by increased hydrostatic pressure, decreased oncotic pressure, or increased negative intrapleural pressure.

4. Table 9-13 lists some common transudative and exudative effusions.

5. Exudative effusions commonly complicate the following diagnoses:

   1. Pneumonia

      1. Any effusion associated with pneumonia, lung abscess, or bronchiectasis is considered a parapneumonic effusion.

      2. Empyemas are parapneumonic effusions that have become infected.

      3. Empyemas, and certain parapneumonic effusions called complicated parapneumonic effusions, are more likely to form fibrotic, pleural peels. The diagnostic criteria for these types of effusions are described in the evidence-based diagnosis section.

      4. Parapneumonic effusions accompany 40% of all pneumonias while empyemas are rare complications.

      5. Effusions are more likely to form and are more likely to become infected if the treatment of the underlying pneumonia is delayed.

      6. The bacteriology of parapneumonic effusions is shown in Table 9-14.

   2. Malignancy

      1. Cancers most commonly associated with effusions are

         • (1) Lung

         • (2) Breast

         • (3) Lymphoma

         • (4) Leukemia

         • (5) Adenocarcinoma of unknown primary

      2. The effusion may occur as the presenting symptom of the cancer or occur in patients with a previously diagnosed malignancy.

      3. The presence of a malignant effusion is generally a very poor prognostic sign.

   3. PE

      1. Effusions are present in 26–56% of patients with PE.

      2. Effusions accompany PE most commonly in patients with pleuritic pain or hemoptysis.

   4. Viral infections

      1. Considered to be a common cause of effusions

      2. Difficult to diagnose; definitive diagnosis is rarely made

      3. Usually diagnosed in patients with febrile or nonfebrile illness with a transient effusion and negative evaluation for other causes.

      4. Other clues such as atypical lymphocytes, monocytosis, and leukopenia are helpful in diagnosing viral infection.

         A pleural effusion should only be diagnosed as viral in an appropriate clinical setting when more serious causes of effusion have been ruled out.

   5. CABG

      1. Pleural effusions develop in up to 90% of patients immediately following CABG.

      2. Can be left sided or bilateral

      3. Usually resolve spontaneously

   6. Other diseases that are not common causes of exudative pleural effusions include

      1. Uremia

      2. Tuberculosis (TB)

      3. Chylothorax

      4. Rheumatologic disease (eg, rheumatoid arthritis and systemic lupus erythematosus)

6. The most common causes of transudative effusions are

   1. HF

      1. Effusions are accompanied by other findings of left HF.

      2. Effusions are usually bilateral; unilateral effusions can occur, but they are less common.

   2. Cirrhosis with ascites

      1. About 6% of patients with ascites have pleural effusions.

      2. Effusion is thought to be secondary to ascites moving into the thorax via defects in the diaphragm.

      3. It is extremely rare to have pleural effusions on the basis of cirrhosis without ascites.

Evidence-Based Diagnosis

1. Detecting a pleural effusion

   1. The test characteristics for dullness to chest percussion are not well defined. The best estimates are sensitivity, 77%; specificity, 92%; LR+, 7.7; LR−, 0.27.

   2. There is often an area of egophony just superior to the effusion.

   3. Once detected, a pleural effusion is confirmed on chest radiograph, ultrasound, or other form of chest imaging.

2. Determining the etiology of a pleural effusion

   1. Any clinically significant effusion (> 1 cm on a chest film) should be sampled via thoracentesis.

   2. The only exception to this is in the case of HF. If the clinical suspicion for HF as the sole cause of the effusion is high, the effusion can be observed while the patient is treated. If the effusion persists or the diagnosis becomes unclear, the effusion should then be sampled.

      Pleural effusions are abnormal; any new pleural effusion should be evaluated.

   3. The first step in determining the cause of an effusion is to differentiate transudative from exudative effusions.

      1. Light criteria are the most widely used test for differentiating transudative from exudative effusions. By these criteria, an effusion is considered to be an exudate if any of the following are present:

         • (1) Pleural fluid protein/serum protein > 0.5

         • (2) Pleural fluid lactate dehydrogenase (LD)/serum LD > 0.6

         • (3) Pleural fluid LD > two-thirds upper limit of normal for serum LD

      2. The test characteristics for Light criteria are

         • (1) Sensitivity, 98%; specificity, 83%

         • (2) LR+, 5.76; LR−, 0.02

      3. The most specific test for an exudative effusion is a difference between the serum albumin and pleural fluid albumin of < 1.2 g/dL (LR+ 10.88).

   4. Once the diagnosis of a transudate or exudate is made, various other tests will help determine the exact diagnosis.

      1. Positive Gram stain or culture makes the diagnosis of an empyema.

      2. Fluid pH: A low pH (< 7.2) is commonly seen with

         • (1) Empyemas

         • (2) Malignant effusions

         • (3) Esophageal rupture

      3. Cell count

         • (1) Neutrophil count over 50% argues for an acute process

           • (a) Parapneumonic effusion (sensitivity = 91%)

           • (b) PE

         • (2) High neutrophil count is rarely seen in other diseases, such as TB and malignancy.

         • (3) Lymphocyte predominant exudative effusions are almost always caused by TB or malignancy (positive predictive value = 97%).

         • (4) Pleural fluid eosinophilia is a nonspecific finding. It is seen frequently with inflammatory diseases, pneumococcal pneumonia, viral pleuritis, TB, and even repeated thoracentesis.

         • (5) A low mesothelial cell count (< 5%) is highly suggestive of TB.

      4. Cytology

         • (1) Highly specific for the diagnosis of cancer

         • (2) Sensitivity is 70% at best, with significantly lower values for some cancers.

   5. Other tests for certain diseases are done if the clinical suspicion is high.

      1. Tuberculous effusions

         • (1) Usually suspected based on clinical presentation and pleural fluid lymphocytosis

         • (2) The sensitivity of commonly used tests for the diagnosis of tuberculous pleurisy are

           • (a) Pleural fluid culture, 42%

           • (b) Pleural biopsy culture, 64%

           • (c) Pleural biopsy histology (caseating granulomas), 70–80%

           • (d) Histology and pleural tissue culture > 90%

           • (e) Sputum culture, 20–50%

         • (3) Two newer tests, pleural fluid adenosine deaminase and interferon-gamma, are proving useful in the diagnosis of tuberculous effusions. Test characteristics from recent meta-analyses are

           • (a) Adenosine deaminase: sensitivity and specificity of 92.2%; LR+, 11.82; LR−, 0.08

           • (b) Interferon-gamma: sensitivity, 89%; specificity, 97%; LR+, 23.45; LR−, 0.11

      2. Glucose levels < 60 mg/dL are seen in

         • (1) Empyema

         • (2) TB

         • (3) Rheumatoid arthritis

         • (4) Systemic lupus erythematosus

      3. Triglycerides are > 110 mg/dL in patients with chylothorax. The fluid is also a milky white.

      4. Thoracoscopy with pleural biopsy is necessary when there is a suspicion for malignancy and cytology is negative.

         Pleural fluid testing should always include LD, protein, albumin, pH, and cell count. Other tests, such as cytology, are often sent.

Treatment

1. Pleural effusions are managed by treating the underlying disease (eg, pneumonia, uremia, HF).

2. Specific treatment of the effusion is necessary in certain circumstances.

   1. Complicated parapneumonic effusions

      1. Evacuation by chest tube drainage prevents pleural scarring and the development of restrictive pleural disease.

      2. Indications for chest tube placement are

         • (1) Purulent fluid or positive Gram stain

         • (2) pH < 7.2

         • (3) LD > 1000 units/L

         • (4) Glucose < 40 mg/dL

         • (5) Small effusions that are close to the above 3 cutoffs can sometimes be carefully monitored.

   2. Malignant pleural effusions

      1. Usually managed by treating the underlying disease and periodic therapeutic thoracentesis.

      2. If thoracentesis is required frequently and the patient’s life expectancy is long, there are a number of options among which are

         • (1) Pleurodesis, obliteration of the pleural space by the installation of a chemical irritant

         • (2) Catheter drainage, in which a semi-permanent catheter is placed to allow constant drainage of the effusion.

   3. Chylothorax

      1. Caused by nontraumatic (primarily lymphoma) or traumatic (usually surgical) disruption of the thoracic duct.

      2. In nontraumatic cases, the underlying disease is treated.

      3. In both nontraumatic and traumatic disease, the pleural space is evacuated with chest tube drainage.

      4. A diet of medium chain fatty acids or a trial of total parenteral nutrition is used to decrease flow through the thoracic duct.

      5. Pleurodesis and surgical management reserved for refractory cases.

Mr. H has a pleural effusion. Given the size of the effusion on the chest film, a thoracentesis was clearly indicated. The results of the aspirate are diagnostic. The fluid is an exudate and the low glucose, low pH, high WBC, and positive Gram stain make the diagnosis of an empyema.

It is worth noting that Mr. H’s previous diagnosis of musculoskeletal chest pain was incorrect. A chest radiograph done on his previous visit to the emergency department may have made the correct diagnosis and treatment could, potentially, have prevented the development of an empyema. There are many indications for chest films, one is to diagnose a cause for chest pain.

A chest film should be performed in any patient with chest pain and no clear diagnosis.

Alternative Diagnoses: Acute Pericarditis

Textbook Presentation

Acute pericarditis typically presents in young adults, with 1 week of viral symptoms and chest pain that improves with leaning forward. Physical exam reveals a 3-part friction rub. ECG reveals ST elevations and PR depressions in all leads.

Disease Highlights

1. Differential diagnosis

   1. Viral pericarditis is primarily caused by coxsackievirus, echovirus, and adenovirus.

   2. Other infectious causes of pericarditis include TB (historically the most common) and HIV.

   3. Pericarditis may occur after myocardial injury (post MI and postcardiac surgery).

   4. Rheumatologic causes include systemic lupus erythematosus and rheumatoid arthritis.

   5. Procainamide and hydralazine are among the drugs that can cause pericariditis.

   6. Neoplastic causes

      1. Malignancy metastatic to the pericardium

      2. Pericarditis can also be caused by chest irradiation.

   7. Uremia: approximately 50% of patients with uremia have pericardial effusions.

2. Although the differential diagnosis of pericarditis is long, 85–90% of cases are considered idiopathic or due to an undiagnosed virus.

Evidence-Based Diagnosis

1. Pericarditis is diagnosed when the characteristic pericardial friction is heard or when a patient with chest pain has characteristic ECG findings.

   1. History

      1. Chest pain is almost always present.

      2. The pain is usually pleuritic.

      3. It classically radiates to the trapezius ridge.

      4. Pain improves with sitting and worsens with reclining.

   2. Physical exam

      1. The pericardial friction rub is insensitive but nearly 100% specific; it is diagnostic of pericarditis.

      2. The rub is usually triphasic.

         • (1) Triphasic in 58% of cases

         • (2) Biphasic in 24% of cases

         • (3) Monophasic in 18% of cases

      3. Pericarditis is usually complicated by a pericardial effusion. Although the physical exam is insensitive for effusions, it is good for detecting tamponade.

         • (1) Sensitivity of jugular venous distention to detect tamponade is 100%.

         • (2) Sensitivity of tachycardia to detect tamponade is 100%.

         • (3) Pulsus paradoxus > 12 mm Hg

           • (a) Sensitivity, 98%; specificity, 83%

           • (b) LR+, 5.9; LR−, 0.03

      4. Beck triad (hypotension, jugular venous distention, and the presence of muffled heart sounds) is seldom seen but is very specific for tamponade.

   3. ECG

      1. The ECG most commonly shows widespread ST elevations and PR depressions. This finding is highly specific but the sensitivity is only about 60%.

      2. The differentiation of pericarditis from acute MI on ECG can be difficult. Some of the key differentiating factors are

         • (1) ST elevation in pericarditis is usually diffuse while in MI it is usually localized.

         • (2) ST elevations in MI are often associated with reciprocal changes.

         • (3) PR depression is very uncommon in acute MI.

         • (4) Q waves are not present with pericarditis.

         Pericarditis can mimic MI. The presence of a rub and careful analysis of the ECG should enable their distinction.

   4. Other diagnostic tests

      1. An echocardiogram is always done when pericarditis has been diagnosed to evaluate the presence of a significant pericardial effusion and exclude the presence of tamponade.

      2. Cardiac enzymes are frequently positive and are therefore not helpful for distinguishing the chest pain of pericarditis from that of cardiac ischemia.

2. Determining the etiology of pericarditis

   1. Because most pericarditis is either idiopathic or viral, requiring only supportive care, extensive work-up is generally not indicated.

   2. After a thorough history, most experts recommend only a few diagnostic tests.

      1. Chest radiograph

      2. Blood urea nitrogen and creatinine

      3. Purified protein derivative, interferon-gamma release assays (Quantiferon)

      4. Antinuclear antibodies

      5. Blood cultures

   3. More extensive evaluation is appropriate for patients with refractory or recurrent disease. Even the most invasive diagnostic studies, pericardiocentesis and pericardial biopsy, are generally not helpful. Their diagnostic yield is only about 20%.

Treatment

1. Because most patients have viral or idiopathic disease, the treatment of acute pericarditis is supportive.

   1. NSAIDs are the treatment of choice, usually providing good pain relief.

   2. The addition of colchicine may improve response to therapy and decrease rates of recurrent disease.

2. Prednisone is effective in patients with refractory disease but only after excluding the presence of diseases (such as TB) that could be worsened by corticosteroids.

3. Pericardiocentesis is required in patients with tamponade.

Empyemas are a medical emergency. They are closed space infections that need to be drained in order to cure them and preserve future lung function. As soon as one is detected, steps should be taken to drain it.