Pneumococcal pneumonia and pulmonary tuberculosis are the archetypical pneumonias associated with pleural involvement. The onset of symptoms in pneumococcal pneumonia (fever, chills, cough, sputum production, pleuritic chest pain) may be acute and mimic pulmonary embolization (see Chapter 52).

Pulmonary embolization can cause pleuritic pain, especially when embolization leads to parenchymal infarction and pleural reaction. Pleural rub, effusion, low-grade fever, and hemoptysis also herald pulmonary infarction with pleural involvement. However, in some instances, the pain may be less clearly pleuritic and is often absent; it is estimated that fewer than 10% of all embolic episodes are accompanied by chest pain. The classic cardiopulmonary manifestations of embolization—dyspnea, tachypnea, and tachycardia—are nearly universal but may be
short-lived. Hypoxemia and oxygen desaturation may or may not be present, depending on the degree of mismatch between ventilation and perfusion. Severe embolization can cause acute pulmonary hypertension manifested by systemic hypotension, jugular venous distention, an accentuated pulmonic component of the second heart sound, acute tricuspid regurgitation, chest x-ray abnormalities, and electrocardiographic manifestations of acute right heart strain (see later discussion).

Spontaneous pneumothorax stretches the pleura and results in acute onset of pleuritic pain and dyspnea. The condition occurs in young persons and those with emphysema, in which there can be rupture of a bleb. If the pneumothorax is large, deviation of the trachea may be observed.

Pleurodynia is a self-limited source of pleuritic pain, most commonly in children and young adults, and is associated with a respiratory viral infection, such as that due to coxsackie virus B. A typical viral syndrome precedes the acute onset of chest pain. Chest pain in the setting of a viral upper respiratory infection may also occur from cough-initiated injury to the chest wall or from bronchospasm. Young healthy persons sometimes note a sudden sharp pleuritic episode relieved by taking a deep breath, referred to as the precordial catch syndrome. Its mechanism is unclear, but a transient folding of the pleura on itself is hypothesized.

Angina pectoris due to occlusive coronary artery disease is the most important cardiac source of chest pain. Coronary perfusion may be similarly compromised by critical aortic stenosis leading to angina (see Chapter 33). The classic hallmarks of angina are its sudden onset with exertion, emotional stress, or eating (usually a very large meal) and its relief within minutes by rest or nitroglycerin. Patients usually describe their chest pain as a squeezing, heaviness, or pressure, although it may be burning or sharp. The quality of the pain is not diagnostic, and many patients state the sensation is more a “discomfort” than a true pain. Radiation to the jaw, neck, shoulder, arm, back, or upper abdomen is common and may present in the absence of chest symptoms. At times, the arm is reported to feel numb or tingling. Autonomic epiphenomena such as diaphoresis and nausea may accompany the episode, as may dyspnea if there is transient pump failure or marked anxiety. Episodes last 2 to 20 minutes. Prompt response to nitroglycerin is characteristic; relief is usually obtained within 5 minutes. Often, patients make gestures in describing their chest pain. Those traditionally associated with ischemia include the Levine sign (clenched fist brought to the chest), the palm sign (extended palm touching the chest), and the arm sign (touching the left arm with the right hand). Prevalences in prospective observational study of patients presenting to the ER with chest pain were 11%, 35%, and 16%, respectively; sensitivities for coronary artery disease were low (9%, 38%, and 16%, respectively), and specificities were higher (84%, 67%, and 78%, respectively), but positive predictive values were modest (50%, 65%, and 55%, respectively) and contributed little to refining the pretest probability.

Gender and racial differences in presentation have been explored. The clinical presentation of myocardial ischemia in women, particularly women younger than the age of 60 years, can differ from that in men. Chest pain is more likely to be absent or atypical (see later discussion) and may be overshadowed by exertional fatigue, shortness of breath, diaphoresis, arm tingling, jaw discomfort, nausea, or other epiphenomena of ischemia that are easy to dismiss as “noncardiac.” Diabetes mellitus is a major risk factor for the early onset of ischemic heart disease in women. With regard to the effect of race on presentation, acute chest pain presentations appear to be similar among whites and African Americans.

Unstable angina is one of the acute coronary syndromes, along with non-Q-wave myocardial infarction and Q-wave myocardial infarction. All are important causes of coronary chest pain and result from acute plaque rupture, which triggers platelet activation, thrombin clot formation, and active vasoconstriction. The clinical presentations of unstable angina include onset of new chest pain within the last 2 months severe enough to inhibit activity; established angina now increasing in frequency, severity, and duration (crescendo angina) and occurring with progressively less provocation; and development of rest pain or nocturnal angina in a person with a previously stable anginal pattern. Immediate mortality risk is high (up to 4%) but declines after 1 to 2 weeks. Clinical features associated with greatest risk include rest pain in excess of 20 minutes, signs of pump failure (hypotension, rales, S₃), new or worsening mitral regurgitation, and 1 mm or more of ST-segment change with pain.

Women with unstable angina are less likely than are men to present with acute ST-segment elevation indicative of vessel-occluding infarction. Compared with men presenting with unstable angina, they are older and more likely to have diabetes, hypertension, and prior heart failure, and they typically present hours later into the episode.

Myocardial infarction is typically heralded by chest pain exceeding that of unstable angina, but the presentation is often more subtle or even silent, particularly in diabetics, the elderly, and women. Bad prognostic signs include heart failure, hypotension, mitral regurgitation, ST-segment elevation, and a new left bundle-branch block. Onset of postinfarction angina is also associated with high risk.

Variant angina, as originally described by Prinzmetal, refers to anginal pain occurring exclusively at rest in conjunction with transient ST-segment elevation on electrocardiogram (ECG). Classically, this syndrome was associated with coronary artery spasm at the site of high-grade proximal fixed stenosis. However, other forms of coronary disease may produce a similar clinical picture, and vasospasm of the large coronary arteries may present in ways other than Prinzmetal’s description. Patients typically demonstrate inducible coronary vasospasm at angiography in response to vasoactive stressors. Cocaine abuse can trigger ischemia by precipitating coronary vasoconstriction, increasing myocardial oxygen demand, and enhancing platelet aggregation. It may present as angina in a young person with no other coronary heart disease (CHD) risk factors. Patients with vasospasm of large coronary arteries are at risk for ischemic events.

Atypical angina is a term used to denote angina-like chest pain that differs in location, quality, or other characteristics from more typical angina yet is still suggestive by virtue of similar precipitants, timing, or other features. Some define the term more precisely, indicating the presence of any two of angina’s
three cardinal features (substernal location, exercise precipitation, prompt relief by rest or nitroglycerin). As many as 50% of such patients who come to angiography prove to have coronary disease. Among the remainder, there appear to be increased incidences of panic disorder, major depression, esophageal disease, and coronary microcirculatory dysfunction. The mechanisms for many of these causes are not well-understood, but recent interest has focused on the coronary microcirculation.

The microvasculature is responsible for regulating coronary blood flow to myocytes through both endothelial and nonendothelial regulatory mechanisms. Endothelial dysfunction of the coronary microvasculature has been noted among more than half of patients who present with typical angina, an ischemic response to exercise stress testing, but absence of occlusive coronary disease at angiography. Sometimes referred to as having microvascular angina, or coronary syndrome X, these patients (most of whom are women in their 40s) are thought to exhibit abnormal coronary microvascular responses to autonomic and biochemical stimuli. The preponderance of cases occurring among women raises the question of a hormonal contribution to pathophysiology. At angiography, in response to intracoronary infusion of adenosine or acetylcholine, these patients often manifest reductions in subendocardial perfusion and may experience anginal chest pain. Such endothelial dysfunction is now recognized as a marker of early coronary artery disease and an important risk factor for adverse cardiac events (e.g., myocardial infarction, heart failure, sudden death)—a 5-year event risk of 7.9% in those with no occlusive disease. Symptomatic relief and event-risk reduction are achievable with use of beta-blockers, statins, and ACE inhibitors; nitrates and calcium channel blockers can provide symptomatic relief (see Chapter 30).

Mitral valve prolapse is notorious for its association with atypical chest pain. The commonly held view of a link between the two has been challenged by recent studies controlling more stringently for selection bias. Some argue that the apparent association is due to an increased frequency of underlying psychopathology, such as panic disorder (see later discussion), which may trigger chest pain. Symptoms of autonomic dysfunction (e.g., palpitations, sweating, dizziness) may sometimes accompany the chest pain and simulate an ischemic attack.

This form of transient cardiomyopathy, typically associated with an emotionally stressful event, results in hypercontractility of basal segments of the left ventricle and severe anteroapical hypokinesis producing a characteristic “ballooning” of the left ventricle. It occurs predominantly in middle-aged women and may mimic acute coronary syndrome by producing chest pressure, shortness of breath, LV dysfunction (heart failure in 50%), ischemic anterior wall electrocardiographic changes, and even mild troponin elevations; however, troponin elevations are much more modest than would be expected from acute MI causing LV wall motion abnormalities. Purported mechanisms include catecholamine toxicity, aborted MI due to sudden clot lysis, coronary vasospasm, and microvascular dysfunction. Clinical differentiation from acute coronary syndrome and acute myocardial infarction can be very difficult; only at cardiac angiography can the diagnosis be made with certainty, finding “clean” coronary arteries and a ballooning left ventricle.

Pericarditis may present with pleuritic pain, resulting from spread of the inflammatory process from the relatively insensitive pericardium to the adjacent pain-sensitive parietal pleura. The pain is sharp, aggravated by respiratory activity, and sometimes precipitated by swallowing if the posterior aspect of the heart is involved. When the diaphragmatic surface of the pericardium is involved, pain will be referred to the tip of the shoulder. Change in position may alter the pain. Patients often note a lessening of pain on sitting up and leaning forward. Pericarditis can also produce a second type of pain that mimics angina. Its most diagnostic physical finding is a two- or three-component friction rub. A vexing pericardial problem is the development of chest pain after coronary bypass surgery. The return of typical angina raises the specter of graft occlusion, but pleuritic pain suggests the postpericardiotomy syndrome.

Myocarditis usually occurs in the context of a viral infection, classically heralded by prodromal symptoms of fever, myalgias, and respiratory or gastrointestinal complaints. Subsequently, the patient may present with cardiac manifestations ranging from chest pain (in about 1/3 of patients) to shortness of breath (in 2/3); about 1/5 note palpitations. Mechanisms include an associated pericarditis causing pleuritic chest pain; inflammation-induced coronary vasospasm resulting in ischemic pain, and a dilated cardiomyopathy compromising ejection fraction and triggering electrical instability.

A careful chest pain description is critical. The prevalence of angiographically confirmed CHD approaches 90% in persons with a classic story for angina (see prior discussion). Prevalence declines to less than 15% in those coming to catheterization who have nonanginal chest pain. In the Framingham Study, patients presenting with new onset of definite angina had a relative risk of a coronary event over 2 years of 3.7 for men and 5.9 for women. Relative risk for those with possible angina fell to 3.0 for men and 2.9 for women, and it fell to 1.3 for men and 0.8 for women with nonanginal chest pain.

Among the features of the chest pain description with the greatest discriminant value are its timing in relation to precipitating and alleviating factors. Quality, location, radiation, and intensity of pain are notoriously nonspecific. Precordial pain radiating down the left arm can occur with almost any cause of chest pain. A common pitfall in taking the history is to provide classic descriptions of chest pain to the patient who cannot give a quick, crisp account of his or her chest pain. Under the duress of the physician’s interrogation, the patient may agree to one of these neat descriptions, leading to a falsepositive diagnosis. A vaguely described chest pain may have important diagnostic meaning. As noted earlier, gestures traditionally associated with coronary disease, such as the Levine sign, have only modest predictive value that is usually insufficient to change the probability of coronary disease based on more-predictive clinical features.

Care is needed not to dismiss a story suggestive of ischemic pain because it is occurring in an atypical patient group, such as women in their 40s, who are at increased risk for coronary microvascular disease/syndrome X and its attendant adverse sequelae, especially if they have cardiac risk factors. Similarly, listening carefully to the chest pain story and checking for cardiovascular risk factors in patients with underlying psychiatric illness is essential, because there is frequently an overlay of distracting somatic symptoms and emotional responses.

Past medical history is reviewed for major cardiac risk factors (e.g., hypertension, diabetes, smoking, hypercholesterolemia, and obesity). Inquiry into cocaine use is essential, especially in young persons presenting with ischemia-like chest pain. Family history is checked for premature coronary disease. Note is also taken of patient age and gender. Postmenopausal women with coronary artery disease have an especially poor prognosis. Awareness of the potential biasing effects of gender and race on clinical thinking is critical to avoiding them. Race and gender have been found to be independent determinants of how patients are assessed. Because there are no differences in acute chest pain presentations among whites and African Americans, the chest pain presentation can be evaluated without the need to adjust for race. However, differences in CHD presentation between sexes need to be kept in mind. Women are often underdiagnosed, in part because the story may be atypical or vague (e.g., exertional fatigue, arm tingling, nausea, shortness of breath). A high index of suspicion for CHD is required in women younger than the age of 60 years presenting with chest pain, especially if they have preexisting diabetes (which negates the beneficial effects of estrogen).