2026 PART 6 Disorders of the Cardiovascular System

pain, syncope, congestive heart failure (CHF), murmurs,

arrhythmias, conduction disturbances, pericardial effusion,

and pericardial tamponade. Additionally, embolic phenomena and constitutional symptoms may occur.

Myxoma Myxomas are the most common type of primary cardiac tumor in adults, accounting for one-third

to one-half of all cases at postmortem examination, and

approximately three-quarters of the tumors treated surgically. They occur at all ages, most commonly in the third

through sixth decades, with a female predilection. Approximately 90% of myxomas are sporadic; the remainder

are familial with autosomal dominant transmission. The

familial variety often occurs as part of a syndrome complex

(Carney complex) that includes (1) myxomas (cardiac,

skin, and/or breast), (2) lentigines and/or pigmented nevi,

and (3) endocrine overactivity (primary nodular adrenal

cortical disease with or without Cushing’s syndrome, testicular tumors, and/or pituitary adenomas with gigantism or

acromegaly). Certain constellations of findings have been

referred to as the NAME syndrome (nevi, atrial myxoma,

myxoid neurofibroma, and ephelides) or the LAMB syndrome (lentigines, atrial myxoma, and blue nevi), although

these syndromes probably represent subsets of the Carney

complex. The genetic basis of this complex has not been elucidated

completely; however, inactivating mutations in the tumor-suppressor

gene PRKAR1A, which encodes the protein kinase A type I-α regulatory

subunit, have been identified in ~70% of patients with Carney complex.

Pathologically, myxomas are gelatinous structures that consist of

myxoma cells embedded in a stroma rich in glycosaminoglycans.

Most sporadic tumors are solitary, arise from the interatrial septum

in the vicinity of the fossa ovalis (particularly in the left atrium), and

are often pedunculated on a fibrovascular stalk. In contrast, familial

or syndromic tumors tend to occur in younger individuals, are often

multiple, may be ventricular in location, and are more likely to recur

after initial resection.

Myxomas commonly present with obstructive signs and symptoms.

The most common clinical presentation mimics that of mitral valve

disease: either stenosis owing to tumor prolapse into the mitral orifice

or regurgitation resulting from tumor-induced valvular trauma or

distortion. Ventricular myxomas may cause outflow tract obstruction

similar to that caused by subaortic or subpulmonic stenosis. The

symptoms and signs of myxoma may be sudden in onset or positional

in nature, owing to the effects of gravity on tumor position. A characteristic low-pitched sound, a “tumor plop,” may be appreciated on

auscultation during early or mid-diastole and is thought to result from

the impact of the tumor against the mitral valve or ventricular wall.

Myxomas also may present with peripheral or pulmonary embolic

phenomenon (resulting from embolization of tumor fragments or

tumor-associated thrombus) or with constitutional signs and symptoms, including fever, weight loss, cachexia, malaise, arthralgias, rash,

digital clubbing, and Raynaud’s phenomenon. These constitutional

symptoms are likely the result of cytokines (e.g., interleukin 6) secreted

by the myxoma. Laboratory abnormalities, such as hypergammaglobulinemia, anemia, polycythemia, leukocytosis, thrombocytopenia or

thrombocytosis, elevated erythrocyte sedimentation rate, and elevated

C-reactive protein level are often present. These features account for

the frequent misdiagnosis of patients with myxomas as having endocarditis, collagen vascular disease, or a paraneoplastic syndrome.

Two-dimensional and three-dimensional transthoracic and/or

transesophageal echocardiography are useful in the diagnosis of

cardiac myxoma and allow for assessment of tumor size and determination of the site of tumor attachment, both of which are important

considerations in the planning of surgical excision (Fig. 271-1). Computed tomography (CT) and magnetic resonance imaging (MRI) may

provide important additional information regarding size, shape, composition, and surface characteristics of the tumor (Fig. 271-2) and may

identify extracardiac intrathoracic involvement in patients in whom

metastatic disease is suspected.

A B

FIGURE 271-1 Transthoracic echocardiogram demonstrating a large atrial myxoma. The myxoma

(Myx) fills the entire left atrium in systole (A) and prolapses across the mitral valve and into the

left ventricle (LV) during diastole (B). RA, right atrium; RV, right ventricle. (Courtesy of Dr. Michael

Tsang; with permission.)

FIGURE 271-2 Cardiac magnetic resonance imaging demonstrating a rounded

mass (M) within the left atrium (LA). Pathologic evaluation at the time of surgery

revealed it to be an atrial myxoma. LV, left ventricle; RA, right atrium; RV, right

ventricle.

Although cardiac catheterization and angiography were previously

performed routinely before tumor resection, they no longer are considered mandatory when adequate noninvasive information is available and other cardiac disorders (e.g., coronary artery disease) are not

considered likely. Additionally, catheterization of the chamber from

which the tumor arises carries the risk of tumor embolization. Because

myxomas may be familial, echocardiographic screening of first-degree

relatives is appropriate, particularly if the patient is young and has

multiple tumors or features of a myxoma syndrome.

TREATMENT

Myxoma

Surgical excision using cardiopulmonary bypass is indicated

regardless of tumor size and is generally curative. Myxomas recur in

12–22% of familial cases but in only 1–2% of sporadic cases. Tumor

Atrial Myxoma and Other Cardiac Tumors

2027CHAPTER 271

recurrence most likely results from multifocal lesions in the former

setting and incomplete tumor resection in the latter.

Other Benign Tumors Cardiac lipomas, although relatively common, are usually incidental findings at postmortem examination; however, they may grow as large as 15 cm, may present as an abnormality of

the cardiac silhouette on chest x-ray, and should be resected if they produce symptoms owing to mechanical interference with cardiac function, arrhythmias, or conduction disturbances. Papillary fibroelastomas

are friable tumors with frond-like projections that are usually solitary

and are the most common tumors of the cardiac valves. Remnants

of cytomegalovirus have been recovered from these tumors, raising

the possibility that they arise as a result of chronic viral endocarditis.

Although usually clinically silent, they can cause valve dysfunction and

may embolize distally, resulting in transient ischemic attacks, stroke,

or myocardial infarction. In general, these tumors should be resected

even when asymptomatic, although a more conservative approach may

be considered for small, right-sided lesions. Rhabdomyomas and fibromas are the most common cardiac tumors in infants and children and

usually occur in the ventricles, where they may produce mechanical

obstruction to blood flow, thereby mimicking valvular stenosis, CHF,

restrictive or hypertrophic cardiomyopathy, or pericardial constriction.

Rhabdomyomas are probably hamartomatous growths, are multiple in

90% of cases, occur in ~50% of children with tuberous sclerosis, and

are associated with mutations in the tumor-suppressor genes TSC1 and

TSC2 (Fig. 271-3). These tumors have a tendency to regress completely

or partially; only tumors that cause obstruction require surgical resection. Fibromas are usually single, universally ventricular in location,

often calcified, and may be associated with mutations in the tumorsuppressor gene PTCH1. Fibromas tend to grow and cause arrhythmias and obstructive symptoms and should be completely resected

when possible. Paragangliomas are rare chromaffin cell tumors that

represent extra-adrenal pheochromocytomas. Most are located in the

roof of the left atrium and can be identified on cardiac CT or MRI or

with nuclear scanning using 131-I-metaiodobenzylguanidine. They

are highly vascular and may be hormonally active, resulting in uncontrolled hypertension. Extensive surgical resection is usually required.

Hemangiomas and mesotheliomas are generally small tumors, most

often intramyocardial in location, and may cause atrioventricular (AV)

conduction disturbances and even sudden death as a result of their propensity to develop in the region of the AV node. Other benign tumors

arising from the heart include teratoma, chemodectoma, neurilemoma,

granular cell myoblastoma, and paraganglioma.

Malignant Tumors Almost all malignant primary cardiac tumors

are sarcomas, which may be of several histologic types; angiosarcomas

are the most common type in adults, whereas rhabdomyosarcomas

are the most common type in children. In general, sarcomas are characterized by rapid progression that culminates in the patient’s death

within weeks to months from the time of presentation as a result of

hemodynamic compromise, local invasion, or distant metastases.

Almost one-third are metastatic at the time of initial diagnosis, usually

involving the lungs. Sarcomas commonly involve the right side of the

heart, are rapidly growing, frequently invade the pericardial space, and

may obstruct the cardiac chambers or venae cavae. Sarcomas also may

occur on the left side of the heart and may be mistaken for myxomas.

Isolated cardiac lymphomas have been rarely described, but more

commonly occur in the context of systemic disease. They are more

common in men and in the elderly; usually involve the right heart; may

represent with arrhythmias, syncope, CHF, or constitutional symptoms; and are usually of the large B-cell type.

TREATMENT

Malignant Tumors

The optimal therapy for cardiac sarcoma is complete resection,

often with neoadjuvant and postoperative chemotherapy; however,

at the time of presentation, many of these tumors have spread too

extensively to allow for surgical excision. Although there are scattered reports of palliation with radiotherapy and/or chemotherapy,

the response of cardiac sarcomas to these therapies is generally

poor. The one exception appears to be cardiac lymphosarcomas,

which may respond to a combination of chemo- and radiotherapy.

Primary cardiac lymphoma is the most chemotherapy-sensitive

primary cardiac malignancy, with long-term survival achieved in

~40% of treated individuals.

■ TUMORS METASTATIC TO THE HEART

Metastatic cardiac tumors are much more common than primary

cardiac tumors, and their incidence is likely to increase as the life

expectancy of patients with various forms of malignant neoplasms is

extended by more effective therapy and improved imaging modalities

allow earlier identification of metastatic disease. Although cardiac

metastases may occur with any tumor type, the relative incidence is

especially high in malignant melanoma and, to a somewhat lesser

extent, leukemia and lymphoma (Fig. 271-4). In absolute terms, the

most common primary sites from which cardiac metastases originate

are carcinoma of the breast and lung, reflecting the high incidence of

these malignancies. Cardiac metastases almost always occur in the setting of widespread primary disease; most often, there is either primary

or metastatic disease elsewhere in the thoracic cavity.

RA

RV

LV

T

T

T T

FIGURE 271-3 Transthoracic echocardiogram revealing multiple tumors (T)

consistent with rhabdomyomas in a 1-day-old infant. The largest tumor (arrows)

was located in the left antrioventricular groove and measured 2 cm × 2 cm. LV, left

ventricle; RA, right atrium; RV, right ventricle.

RV

LV

LA

Met

FIGURE 271-4 Large metastatic lesion (Met) in the left ventricle (LV) of a patient

with diffusely metastatic bladder cancer. The mass arose from the interventricular

septum and prolapsed into the aortic outflow tract during systole.

2028 PART 6 Disorders of the Cardiovascular System

■ CARDIAC TRAUMA

Traumatic cardiac injury may be caused by either penetrating or nonpenetrating trauma; the latter is often referred to as blunt cardiac injury

(BCI). Penetrating injuries most often result from gunshot or knife

wounds, and the site of entry is usually obvious. Blunt cardiac injuries

most often occur during motor vehicle accidents, either from rapid

deceleration or from impact of the chest against the steering wheel, but

can also result from falls from heights, crush injuries, blast injuries, and

violent assault. Importantly, rapid deceleration following motor vehicle

accidents may be associated with significant cardiac injury even in the

absence of external signs of thoracic trauma.

■ BLUNT CARDIAC INJURY

Myocardial contusion is a nonspecific term that has been used to

describe a broad spectrum of nonpenetrating cardiac injuries that

result in abnormalities on electrocardiogram (ECG), elevation in

cardiac biomarkers, and acute structural cardiac abnormalities

(Table 272-1). Importantly, the cardiac injury may initially be overlooked in trauma patients as the clinical focus is directed toward other,

more obvious injuries. Unfortunately, there is no one sign or symptom that confirms the diagnosis of BCI, and clinical, laboratory, and

radiographic findings may be nonspecific in the setting of significant

trauma. The physical examination may be challenging in the setting of

chest wall injury; however, patients should be carefully examined to

detect pericardial rubs, cardiac murmurs, and evidence of pericardial

tamponade (Chap. 270). The mechanism of injury and the presence of

other chest trauma should be considered when determining the index

of suspicion for BCI; however, there is no proven association between

sternal or rib fractures and the presence of BCI, and significant cardiac

injury may be present in the absence of chest wall abnormalities.

Chest pain is common following thoracic trauma, and while it

could indicate cardiac ischemia or pericardial injury, it often reflects

musculoskeletal trauma. Nonetheless, myocardial necrosis may occur

as a direct result of the blunt injury or as a result of traumatic coronary laceration, dissection, or thrombosis. The injured myocardium is

pathologically similar to infarcted myocardium and may be associated

with atrial or ventricular arrhythmias, conduction disturbances including bundle branch block, or abnormalities on ECG resembling those of

infarction or pericarditis. Thus, it is important to obtain an ECG in all

patients presenting with chest trauma and consider BCI as a cause of

otherwise unexplained ECG abnormalities.

272 Cardiac Trauma

Eric H. Awtry

TABLE 272-1 Spectrum of Cardiac Abnormalities Following Blunt

Cardiac Injury

ABNORMALITY COMMENTS

ECG abnormalities Sinus tachycardia, RBBB, ST-T wave abnormalities,

atrial and ventricular arrhythmias

Elevated cardiac

biomarkers

Troponin I and T are most specific

Focal wall motion

abnormality or

hematoma

Most commonly involving RV free wall, LV apex, and

interventricular septum

Valvular insufficiency Most commonly involving mitral and tricuspid valves

and occasionally the aortic valve

Myocardial rupture Ventricular septal defect or free wall rupture

Coronary artery injury Most commonly involving the LAD, usually presents

as STEMI

Pericardial effusion and

tamponade

Resulting from free wall rupture or coronary artery

laceration

Abbreviations: ECG, electrocardiogram; LAD, left anterior descending coronary

artery; LV, left ventricle; RBBB, right bundle branch block; RV, right ventricle; STEMI,

ST-segment elevation myocardial infarction.

Cardiac metastases may occur via hematogenous or lymphangitic

spread or by direct tumor invasion. While they generally manifest as

small, firm nodules, diffuse infiltration also may occur, especially with

sarcomas or hematologic neoplasms. The pericardium is most often

involved, followed by myocardial involvement of any chamber and,

rarely, by involvement of the endocardium or cardiac valves.

Cardiac metastases are clinically apparent only ~10% of the time,

are usually not the cause of the patient’s presentation, and rarely are the

cause of death. The vast majority occur in the setting of a previously

recognized malignant neoplasm. As with primary cardiac tumors, the

clinical presentation reflects more the location and size of the tumor

than its histologic type. When symptomatic, cardiac metastases may

result in a variety of clinical features, including dyspnea, acute pericarditis, cardiac tamponade, ectopic tachyarrhythmias, heart block, and

CHF. Importantly, many of these signs and symptoms may also result

from myocarditis, pericarditis, or cardiomyopathy induced by radiotherapy or chemotherapy, and a high index of suspicion for cardiac

involvement should be maintained for patients with malignant disease

who develop these symptoms.

Electrocardiographic (ECG) findings are nonspecific but may reveal

features consistent with pericarditis or may demonstrate low QRS voltage and electrical alternans in the setting of a large pericardial effusion.

On chest x-ray, the cardiac silhouette is most often normal but may be

enlarged or exhibit a bizarre contour. Echocardiography is useful for

identifying and assessing the significance of pericardial effusions and

visualizing larger metastases, although CT and radionuclide imaging

may define the tumor burden more clearly. Cardiac MRI offers superb

image quality and plays a central role in the diagnostic evaluation of

cardiac metastases and cardiac tumors in general. Pericardiocentesis

may allow for a specific cytologic diagnosis in patients with malignant

pericardial effusions with a reported sensitivity of 67–92%. Angiography is rarely necessary but may help to delineate discrete myocardial

lesions.

TREATMENT

Tumors Metastatic to the Heart

Most patients with cardiac metastases have advanced malignant

disease; thus, therapy is generally palliative and consists of controlling symptoms and treatment of the primary tumor. Symptomatic

malignant pericardial effusions should be drained by pericardiocentesis. Prolonged drainage (3–5 days) and concomitant instillation of a sclerosing agent (e.g., tetracycline or bleomycin) may

delay or prevent reaccumulation of the effusion, and creation of a

pericardial window allows drainage of the effusion to the adjacent

pleural or peritoneal space. Given the overall poor prognosis of

these patients, discussions regarding goals of care and involvement

of palliative care services are often appropriate.

■ FURTHER READING

Bussani R et al: Cardiac metastases. J Clin Pathol 60:27, 2007.

Mousavi N et al: Assessment of cardiac masses by cardiac magnetic

resonance imaging: Histological correlation and clinical outcomes. J

Am Heart Assoc 8:e007829, 2019.

Shapira O et al: Tumors of the heart, in Sabiston and Spenser Surgery

of the Chest, 9th ed, FW Sellke et al (eds). Philadelphia, Elsevier, 2016,

pp 1849–1857.

Tamin SS et al: Prognostic and bioepidemiologic implications of papillary fibroelastomas. J Am Coll Cardiol 65:2420, 2015.

Young PM et al: Computed tomography imaging of cardiac masses.

Radiol Clin N Am 57:75, 2019.

Cardiac Trauma

2029CHAPTER 272

Serum creatine kinase, myocardial band (CK-MB) isoenzyme levels

are increased in ~20% of patients who experience blunt chest trauma

but may be falsely elevated in the presence of massive skeletal muscle

injury and should not be relied upon to confirm the diagnosis of BCI

in the setting of trauma. Cardiac troponin levels are more specific for

identifying cardiac damage; patients with normal serial troponin levels after chest trauma are very unlikely to have cardiac injury. When

combined with a normal ECG, a normal troponin level at 6–8 h after

chest trauma essentially excludes BCI. Echocardiography is the most

useful modality for the detection of structural and functional sequelae

of BCI, including regional wall motion abnormalities (most commonly

involving the right ventricle, interventricular septum, or left ventricular apex), pericardial effusion, valvular dysfunction, and ventricular

rupture. A transthoracic echocardiogram (TTE) should be performed

in all patients with suspected BCI, especially in those with an abnormal

ECG, elevated troponin, or hemodynamic instability; transesophageal

echocardiography should be considered for patients in whom adequate

TTE images cannot be obtained.

Traumatic rupture of the cardiac valves or their supporting structures, most commonly of the tricuspid or mitral valve, leads to acute

valvular incompetence. This complication is usually heralded by

the development of a loud murmur, may be associated with rapidly

progressive heart failure, and can be diagnosed by either TTE or

transesophageal echocardiography.

The most serious consequence of nonpenetrating cardiac injury is

myocardial rupture, which may result in hemopericardium and tamponade (free wall rupture) or intracardiac shunting (ventricular septal

rupture). Although generally fatal, up to 40% of patients with cardiac

rupture have been reported to survive long enough to reach a specialized trauma center. Hemopericardium also may result from traumatic

rupture of a pericardial vessel or a coronary artery. Additionally, pericarditis and/or pericardial effusion may develop weeks or even months

after blunt chest trauma as a manifestation of the post–cardiac injury

syndrome, an inflammatory condition that resembles the postpericardiotomy syndrome (Chap. 270).

Blunt, nonpenetrating, often innocent-appearing injuries to the

chest may trigger ventricular fibrillation even in the absence of structural myocardial damage. This syndrome, referred to as commotio

cordis, occurs most often in adolescents during sporting events (e.g.,

baseball, hockey, football, and lacrosse) and is an electrical phenomenon that probably results from an impact to the chest wall overlying

the heart during the susceptible phase of repolarization (just before

the peak of the T wave). Survival depends on prompt defibrillation.

Sudden emotional or physical trauma, even in the absence of direct

cardiac trauma, may precipitate a transient catecholamine-mediated

cardiomyopathy referred to as takotsubo syndrome or apical ballooning

syndrome (Chap. 259).

Rupture or transection of the aorta, usually just above the aortic

valve or at the site of the ligamentum arteriosum, is a common consequence of nonpenetrating chest trauma and is the most common

vascular deceleration injury. The clinical presentation may be similar

to that of aortic dissection (Chap. 280); the arterial pressure and pulse

amplitude may be increased in the upper extremities and decreased

in the lower extremities, and chest x-ray may reveal mediastinal widening. Aortic rupture into the left thoracic space is almost universally

fatal; however, the rupture may occasionally be contained by the aortic

adventitia, resulting in a false, or pseudo-, aneurysm that may be discovered months or years after the initial injury.

TREATMENT

Blunt Cardiac Injury

The treatment of BCI depends on the specific injury sustained.

Hemodynamically stable patients with a normal ECG and normal

serial troponin levels are at low risk for BCI and usually do not

require hospital admission for cardiac issues. Patients with an

abnormal ECG and/or elevated troponin but normal echocardiogram usually warrant 24–48 h of telemetry monitoring; however,

other specific cardiac treatment is not usually required in the

absence of the development of arrhythmias. Patients with mechanical complications (acute valvular insufficiency, myocardial rupture)

require urgent operative correction.

■ PENETRATING CARDIAC INJURY

Penetrating injuries of the heart produced by knife or bullet wounds

usually result in rapid clinical deterioration and frequently in death

as a result of hemopericardium/pericardial tamponade or massive

hemorrhage. Nonetheless, up to half of such patients may survive long

enough to reach a specialized trauma center if immediate resuscitation

is performed. Prognosis in these patients relates to the mechanism

of injury, the specific cardiac chamber(s) involved, and their clinical

condition at presentation. In general, gunshot wounds are associated

with a higher mortality than are knife wounds; up to 65% of stabbing

victims survive versus <20% of shooting victims. This is likely in part

because ballistic wounds are more frequently associated with multichamber cardiac injury. As a result of its anterior position in the chest,

the right ventricle (RV) is the most frequently injured cardiac chamber,

followed by the left ventricle (LV); isolated atrial injury is uncommon.

Some studies suggest that RV injuries may be associated with a better

prognosis than LV injuries, and most reports indicate that multichamber involvement carries a worse prognosis than single-chamber injury.

Patients who are in hemodynamic collapse at presentation to the emergency department have a particularly poor prognosis with a mortality

rate approaching 90%, whereas ~75% of patients who are stable enough

to be brought to the operating room will survive.

Cardiac perforation of the right atrium, the RV free wall, or the

interventricular septum may occur as a complication of cardiac procedures including during placement of central venous/intracardiac

catheters, insertion of pacemaker/defibrillator leads, or performance

of RV endomyocardial biopsies, and coronary arterial perforation can

occur during deployment of intracoronary stents. These iatrogenic

injuries are associated with a better prognosis than are other forms of

penetrating cardiac trauma, likely related to a more limited degree of

cardiac injury and the rapid availability of corrective therapies.

Traumatic rupture of a great vessel from penetrating injury is usually

associated with hemothorax and, less often, hemopericardium, both

of which are associated with significant mortality. Local hematoma

formation may compress adjacent vessels and produce ischemic symptoms, and arteriovenous fistulas may develop, occasionally resulting in

high-output heart failure.

Some patients with penetrating chest injuries are hemodynamically

stable at presentation and without symptoms to suggest cardiac injury;

however, as many as 20% of these patients will have occult penetrating

cardiac trauma. As a result, there should always be a high index of suspicion for cardiac injury in any patient with penetrating chest trauma,

irrespective of clinical stability. TTE should be performed in all of these

patients to assess for the presence of pericardial effusion or hematoma.

Occasionally, patients who survive penetrating cardiac injuries may

subsequently present days or weeks later with a new cardiac murmur

or heart failure as a result of mitral or tricuspid regurgitation or an

intracardiac shunt (i.e., ventricular or atrial septal defect, aortopulmonary fistula, or coronary arteriovenous fistula) that was undetected at

the time of the initial injury or developed subsequently (Fig. 272-1).

Therefore, trauma patients should be examined carefully several weeks

after the injury. If a mechanical complication is suspected, it can be

confirmed by echocardiography or cardiac catheterization.

TREATMENT

Penetrating Cardiac Injury

Penetrating cardiac injury associated with hemodynamic instability is a surgical emergency and requires immediate resuscitative measures including endotracheal intubation, establishment of

large-bore intravenous access to facilitate massive volume resuscitation, and immediate thoracotomy to allow for pericardial drainage

and repair of cardiac injuries. Occasionally, cross-clamping of the

2030 PART 6 Disorders of the Cardiovascular System

A B

RV

LV

FIGURE 272-1 Transthoracic echocardiogram demonstrating a traumatic ventricular septal defect. The patient underwent emergent repair of the right ventricle following

a self-inflicted stab wound to the chest. Subsequent two-dimensional imaging (A) revealed a laceration of the interventricular septum (arrow) with color flow Doppler (B)

demonstrating prominent left-to-right shunting across the defect. LV, left ventricle; RV, right ventricle.

descending aorta is required to preferentially perfuse the heart and

brain until hemodynamic stability can be achieved. Hemodynamically stable patients in whom echocardiography reveals even a small

pericardial effusion require urgent surgical exploration to evaluate

for occult cardiac perforation. Pericardiocentesis may be lifesaving

in patients with tamponade but is usually only a temporizing measure while awaiting definitive surgical therapy. In some survivors of

penetrating cardiac injury, the pericardial hemorrhage predisposes

to the development of constriction (Chap. 270), which may require

surgical decortication.

■ FURTHER READING

Crawford T et al: Thoracic trauma, in Sabiston and Spenser Surgery of

the Chest, 9th ed, FW Sellke et al (eds). Philadelphia, Elsevier, 2016,

pp 100–130.

Morse BC et al: Penetrating cardiac injuries: A 36-year perspective at

and urban level 1 trauma center. J Trauma Acute Care Surg 81:623,

2016.

Yousef R, Carr JA: Blunt cardiac trauma: A review of the current

knowledge and management. Ann Thorac Surg 98:1134, 2014.

Wu Y et al: Imaging of cardiac trauma. Radiol Clin N Am 57:795, 2019.

Section 5 Coronary and Peripheral

Vascular Disease

273 Ischemic Heart Disease

Elliott M. Antman, Joseph Loscalzo

Ischemic heart disease (IHD) is a condition in which there is an inadequate supply of blood and oxygen to a portion of the myocardium;

it typically occurs when there is an imbalance between myocardial

oxygen supply and demand. The most common cause of myocardial

ischemia is atherosclerotic disease of an epicardial coronary artery

(or arteries) sufficient to cause a regional reduction in myocardial

blood flow and inadequate perfusion of the myocardium supplied

by the involved coronary artery. This chapter focuses on the chronic

manifestations and treatment of IHD, while the subsequent chapters

address the acute phases of IHD.

■ EPIDEMIOLOGY AND GLOBAL TRENDS

IHD causes more deaths and disability and incurs greater economic

costs than any other illness in the developed world. IHD is the most

common, serious, chronic, life-threatening illness in the United States,

where 20.1 million persons have IHD. Although there is regional

variation, ~3–4% of the population has sustained a myocardial infarction. Genetic factors, a high-fat and energy-rich diet, smoking, and

a sedentary lifestyle are associated with the emergence of IHD. In

the United States and Western Europe, IHD is growing among lowincome groups, but primary prevention has delayed the disease to later

in life across socioeconomic groups. Despite these sobering statistics,

it is worth noting that epidemiologic data show a decline in the rate of

deaths due to IHD, about half of which is attributable to treatments and

half to prevention by risk factor modification.

Obesity, insulin resistance, and type 2 diabetes mellitus are increasing and are powerful risk factors for IHD. These trends are occurring in

the general context of population growth and as a result of the increase

in the average age of the world’s population. With urbanization in

countries with emerging economies and a growing middle class, elements of the energy-rich Western diet are being adopted. As a result,

the prevalence of risk factors for IHD and the prevalence of IHD itself

are both increasing rapidly, so that in analyses of the global burden

of disease, there is a shift from communicable to noncommunicable

diseases, and it is estimated that globally 197.2 million people live with

IHD. Population subgroups that appear to be particularly affected are

men in South Asian countries, especially India and the Middle East.

IHD is a major contributor to the number of disability-adjusted lifeyears (DALYs) experienced globally.

■ PATHOPHYSIOLOGY

Central to an understanding of the pathophysiology of myocardial

ischemia is the concept of myocardial supply and demand. In normal

conditions, for any given level of a demand for oxygen, the myocardium

will control the supply of oxygen-rich blood to prevent underperfusion

of myocytes and the subsequent development of ischemia and infarction. The major determinants of myocardial oxygen demand (MVO2

)

are heart rate, myocardial contractility, and myocardial wall tension

(stress). An adequate supply of oxygen to the myocardium requires a

satisfactory level of oxygen-carrying capacity of the blood (determined

by the inspired level of oxygen, pulmonary function, and hemoglobin

concentration and function) and an adequate level of coronary blood

Ischemic Heart Disease

2031CHAPTER 273

flow. Blood flows through the coronary arteries in a phasic fashion,

with the majority occurring during diastole. About 75% of the total

coronary resistance to flow occurs across three sets of arteries: (1)

large epicardial arteries (Resistance 1 = R1

), (2) prearteriolar vessels

(R2

), and (3) arteriolar and intramyocardial capillary vessels (R3

). In

the absence of significant flow-limiting atherosclerotic obstructions,

R1

 is trivial; the major determinant of coronary resistance is found in

R2

 and R3 (Fig. 273-1). The normal coronary circulation is dominated

and controlled by the heart’s requirements for oxygen. This need is met

by the ability of the coronary vascular bed to vary its resistance (and,

therefore, blood flow) considerably while the myocardium extracts a

high and relatively fixed percentage of oxygen. Normally, intramyocardial resistance vessels demonstrate a great capacity for dilation (R2

 and

R3

 decrease). For example, the changing oxygen needs of the heart with

exercise and emotional stress affect coronary vascular resistance and,

in this manner, regulate the supply of oxygen and substrate to the myocardium (metabolic regulation). The coronary resistance vessels also

adapt to physiologic alterations in blood pressure to maintain coronary

blood flow at levels appropriate to myocardial needs (autoregulation).

By reducing the lumen of the coronary arteries, atherosclerosis

limits appropriate increases in perfusion when the demand for more

coronary flow occurs. When the luminal reduction is severe, myocardial perfusion in the basal state is reduced. Coronary blood flow also

can be limited by spasm (see Prinzmetal’s angina in Chap. 274), arterial

thrombi, and, rarely, coronary emboli as well as by ostial narrowing

due to aortitis. Congenital abnormalities such as the origin of the left

anterior descending coronary artery from the pulmonary artery may

cause myocardial ischemia and infarction in infancy, but this cause is

very rare in adults.

Myocardial ischemia also can occur if myocardial oxygen demands

are markedly increased and particularly when coronary blood flow

may be limited, as occurs in severe left ventricular hypertrophy (LVH)

due to aortic stenosis. The latter can present with angina that is indistinguishable from that caused by coronary atherosclerosis largely

owing to subendocardial ischemia (Chap. 261). A reduction in the

oxygen-carrying capacity of the blood, as in extremely severe anemia

or in the presence of carboxyhemoglobin, rarely causes myocardial

ischemia by itself but may lower the threshold for ischemia in patients

with moderate coronary obstruction.

Not infrequently, two or more causes of ischemia coexist in a

patient, such as an increase in oxygen demand due to LVH secondary

Segment

and size

Macrocirculation Microcirculation

Main stimulus

for vasomotion Flow Pressure Metabolites

Transport Regulation Exchange Main

function

Percentage of

total resistance

to flow

Epicardial arteries >400 µm Small arteries <400 µm Arterioles <100 µm Capillaries <10 µm

FIGURE 273-1 Macrocirculation and microcirculation across segments and sizes of the arteries. The location and size of the arteries supplying blood to the heart is shown

at the top. Vasomotion of the arterial segments occurs in response to the stimuli shown. The main function of each of the arterial segments is shown next, followed by a

depiction of the relative resistance to antegrade flow. (Reproduced with permission from B De Bruyne et al: Microvascular (dys)function and clinical outcome in stable

coronary disease. J Amer Coll Cardiol 67:1170, 2016.)

to hypertension and a reduction in oxygen supply secondary to coronary atherosclerosis and anemia. Abnormal constriction or failure

of normal dilation of the coronary resistance vessels also can cause

ischemia. When it causes angina, this condition is referred to as

microvascular angina.

CORONARY ATHEROSCLEROSIS

Epicardial coronary arteries are the major site of atherosclerotic disease. The major risk factors for atherosclerosis (high levels of plasma

low-density lipoprotein [LDL], cigarette smoking, hypertension, and

diabetes mellitus) vary in their relative impact on disturbing the normal functions of the vascular endothelium. These functions include

local control of vascular tone, maintenance of an antithrombotic

surface, and control of inflammatory cell adhesion and diapedesis.

The loss of these defenses leads to inappropriate constriction, luminal

thrombus formation, and abnormal interactions between blood cells,

especially monocytes and platelets, and the activated vascular endothelium. Functional changes in the vascular milieu ultimately result in

the subintimal collections of fat, smooth muscle cells, fibroblasts, and

intercellular matrix that define the atherosclerotic plaque. Rather than

viewing atherosclerosis strictly as a vascular problem, it is useful to

consider it in the context of alterations in the nature of the circulating

blood (hyperglycemia; increased concentrations of LDL cholesterol,

tissue factor, fibrinogen, von Willebrand factor, coagulation factor VII,

and platelet microparticles). The combination of a “vulnerable vessel”

in a patient with “vulnerable blood” promotes a state of hypercoagulability and hypofibrinolysis. This is especially true in patients with

diabetes mellitus.

Atherosclerosis develops at irregular rates in different segments of

the epicardial coronary tree and leads eventually to segmental reductions in cross-sectional area, i.e., plaque formation. There is also a

predilection for atherosclerotic plaques to develop at sites of increased

turbulence in coronary flow, such as at branch points in the epicardial

arteries. When a stenosis reduces the diameter of an epicardial artery

by 50%, there is a limitation of the ability to increase flow to meet

increased myocardial demand. When the diameter is reduced by ~80%,

blood flow at rest may be reduced, and further minor decreases in the

stenotic orifice area can reduce coronary flow dramatically to cause

myocardial ischemia at rest or with minimal stress.

Segmental atherosclerotic narrowing of epicardial coronary arteries is caused most commonly by the formation of a plaque, which is

2032 PART 6 Disorders of the Cardiovascular System

subject to rupture or erosion of the cap separating the plaque from

the bloodstream. Upon exposure of the plaque contents to blood, two

important and interrelated processes are set in motion: (1) platelets

are activated and aggregate, and (2) the coagulation cascade is activated, leading to deposition of fibrin strands. A thrombus composed

of platelet aggregates and fibrin strands traps red blood cells and can

reduce coronary blood flow, leading to the clinical manifestations of

myocardial ischemia.

The location of the obstruction influences the quantity of myocardium rendered ischemic and determines the severity of the clinical

manifestations. Thus, critical obstructions in vessels, such as the

left main coronary artery and the proximal left anterior descending

coronary artery, are particularly hazardous. Chronic severe coronary

narrowing and myocardial ischemia frequently are accompanied by the

development of collateral vessels, especially when the narrowing develops gradually. When well developed, such vessels can by themselves

provide sufficient blood flow to sustain the viability of the myocardium

at rest but not during conditions of increased demand.

With progressive worsening of a stenosis in a proximal epicardial

artery, the distal resistance vessels (when they function normally)

dilate to reduce vascular resistance and maintain coronary blood

flow. A pressure gradient develops across the proximal stenosis, and

poststenotic pressure falls. When the resistance vessels are maximally

dilated, myocardial blood flow becomes dependent on the pressure in

the coronary artery distal to the obstruction. In these circumstances,

ischemia, manifest clinically by angina or electrocardiographically by

ST-segment deviation, can be precipitated by increases in myocardial

oxygen demand caused by physical activity, emotional stress, and/or

tachycardia. Changes in the caliber of the stenosed coronary artery

resulting from physiologic vasomotion, loss of endothelial control of

dilation (as occurs in atherosclerosis), pathologic spasm (Prinzmetal’s

angina), or small platelet-rich plugs also can upset the critical balance

between oxygen supply and demand and thereby precipitate myocardial ischemia.

■ EFFECTS OF ISCHEMIA

During episodes of inadequate perfusion caused by coronary atherosclerosis, myocardial tissue oxygen tension falls and may cause

transient disturbances of the mechanical, biochemical, and electrical

functions of the myocardium (Fig. 273-2). Coronary atherosclerosis is

a focal process that usually causes nonuniform ischemia. During ischemia, regional disturbances of ventricular contractility cause segmental

hypokinesia, akinesia, or, in severe cases, bulging (dyskinesia), which

can reduce myocardial pump function.

The abrupt development of severe ischemia, as occurs with total or

subtotal coronary occlusion, is associated with near instantaneous failure of normal muscle relaxation and then diminished contraction. The

relatively poor perfusion of the subendocardium causes more intense

ischemia of this portion of the wall (compared with the subepicardial

region). Ischemia of large portions of the ventricle causes transient

left ventricular (LV) failure, and if the papillary muscle apparatus is

involved, mitral regurgitation can occur. When ischemia is transient,

it may be associated with angina pectoris; when it is prolonged, it can

lead to myocardial necrosis and scarring with or without the clinical

picture of acute myocardial infarction (Chap. 275).

A wide range of abnormalities in cell metabolism, function, and

structure underlie these mechanical disturbances during ischemia.

The normal myocardium metabolizes fatty acids and glucose to carbon

dioxide and water. With severe oxygen deprivation, fatty acids cannot

be oxidized, and glucose is converted to lactate; intracellular pH is

reduced, as are the myocardial stores of high-energy phosphates, i.e.,

ATP and creatine phosphate. Impaired cell membrane function leads

to the leakage of potassium and the uptake of sodium by myocytes as

well as an increase in cytosolic calcium. The severity and duration of

the imbalance between myocardial oxygen supply and demand determine whether the damage is reversible (≤20 min for total occlusion in

the absence of collaterals) or permanent, with subsequent myocardial

necrosis (>20 min).

Ischemia also causes characteristic changes in the electrocardiogram

(ECG) such as repolarization abnormalities, as evidenced by inversion

of T waves and, when more severe, displacement of ST segments (Chap.

240). Transient T-wave inversion probably reflects nontransmural,

intramyocardial ischemia; transient ST-segment depression often

reflects patchy subendocardial ischemia; and ST-segment elevation is

thought to be caused by more severe transmural ischemia. Another

important consequence of myocardial ischemia is electrical instability,

which may lead to isolated ventricular premature beats or even ventricular tachycardia or ventricular fibrillation (Chaps. 254 and 255). Most

patients who die suddenly from IHD do so as a result of ischemiainduced ventricular tachyarrhythmias (Chap. 306).

■ ASYMPTOMATIC VERSUS SYMPTOMATIC IHD

Although the prevalence is decreasing, postmortem studies of accident victims and military casualties in Western countries show that

Systolic dysfunction

Regional wall motion

Decreased segmental perfusion

Diastolic dysfunction

Micro-infarction/myocardial fibrosis

Altered metabolism/abnormal ST segment

Decreased subendocardial perfusion

Endothelial and microvascular dysfunction

Exposure time of mismatch in myocardial oxygen supply/demand

Near term

Repetitive/progressive manifestations of ischemia

Prolonged

FIGURE 273-2 Cascade of mechanisms and manifestations of ischemia. (Reproduced with permission from LJ Shaw et al: Women and ischemic heart disease: Evolving

knowledge. J Am Coll Cardiol 54:1561, 2009.)

Ischemic Heart Disease

2033CHAPTER 273

coronary atherosclerosis can begin before age 20 and is present among

adults who were asymptomatic during life. Exercise stress tests in

asymptomatic persons may show evidence of silent myocardial ischemia, i.e., exercise-induced ECG changes not accompanied by angina

pectoris; coronary angiographic studies of such persons may reveal

coronary artery plaques and previously unrecognized obstructions

(Chap. 242). Coronary artery calcifications (CACs) may be seen on CT

images of the heart, can be quantified in a CAC score, and may be used

as adjunctive information to support a diagnosis of IHD. However,

they should not be used as the primary screening modality or as the

isolated basis on which to formulate therapeutic decisions. (See further

discussion below.) Postmortem examination of patients with such

obstructions without a history of clinical manifestations of myocardial

ischemia often shows macroscopic scars secondary to myocardial

infarction in regions supplied by diseased coronary arteries, with or

without collateral circulation. According to population studies, ~25%

of patients who survive acute myocardial infarction may not come to

medical attention, and these patients have the same adverse prognosis

as do those who present with the classic clinical picture of acute myocardial infarction (Chap. 275). Sudden death may be unheralded and is

a common presenting manifestation of IHD (Chap. 306).

Patients with IHD also can present with cardiomegaly and heart

failure secondary to ischemic damage of the LV myocardium that may

have caused no symptoms before the development of heart failure; this

condition is referred to as ischemic cardiomyopathy. In contrast to the

asymptomatic phase of IHD, the symptomatic phase is characterized

by chest discomfort due to either angina pectoris or acute myocardial

infarction (Chap. 275). Having entered the symptomatic phase, the

patient may exhibit a stable or progressive course, revert to the asymptomatic stage, or die suddenly.

STABLE ANGINA PECTORIS

This episodic clinical syndrome is a result of transient myocardial

ischemia. Various diseases that cause myocardial ischemia and the

numerous forms of discomfort with which it may be confused are discussed in Chap. 14. Males constitute ~70% of all patients with angina

pectoris and an even greater proportion of those aged <50 years. It

is, however, important to note that angina pectoris in women may be

atypical in presentation (see below).

■ HISTORY

The typical patient with angina is a man >50 years or a woman

>60 years of age who complains of episodes of chest discomfort, usually

described as heaviness, pressure, squeezing, smothering, or choking

and only rarely as frank pain. When the patient is asked to localize the

sensation, he or she typically places a hand over the sternum, sometimes with a clenched fist, to indicate a squeezing, central, substernal

discomfort (Levine’s sign). Angina is usually crescendo-decrescendo

in nature (typically with the severity of the discomfort not at its most

intense level at the outset of symptoms), typically lasts 2–5 min, and

can radiate to either shoulder and to both arms (especially the ulnar

aspects of the forearm and hand). It also can arise in or radiate to the

back, interscapular region, root of the neck, jaw, teeth, and epigastrium.

Angina is rarely localized below the umbilicus or above the mandible.

A useful finding in assessing a patient with chest discomfort is the fact

that myocardial ischemic discomfort does not radiate to the trapezius

muscles; that radiation pattern is more typical of pericarditis.

Although episodes of angina typically are caused by exertion (e.g.,

exercise, hurrying, or sexual activity) or emotion (e.g., stress, anger,

fright, or frustration) and are relieved by rest, they also may occur at

rest (Chap. 274) and while the patient is recumbent (angina decubitus).

The patient may be awakened at night by typical chest discomfort

and dyspnea. Nocturnal angina may be due to episodic tachycardia,

diminished oxygenation as the respiratory pattern changes during

sleep, or expansion of the intrathoracic blood volume that occurs with

recumbency; the latter causes an increase in cardiac size (end-diastolic

volume), wall tension, and myocardial oxygen demand that can lead to

ischemia and transient LV failure.

The threshold for the development of angina pectoris may vary by

time of day and emotional state. Many patients report a fixed threshold

for angina, occurring predictably at a certain level of activity, such as

climbing two flights of stairs at a normal pace. In these patients, coronary stenosis and myocardial oxygen supply are fixed, and ischemia

is precipitated by an increase in myocardial oxygen demand; they are

said to have stable exertional angina. In other patients, the threshold

for angina may vary considerably within any particular day and from

day to day. In such patients, variations in myocardial oxygen supply,

most likely due to changes in coronary vasomotor tone, may play an

important role in defining the pattern of angina. A patient may report

symptoms upon minor exertion in the morning yet by midday be

capable of much greater effort without symptoms. Angina may also be

precipitated by unfamiliar circumstances, a heavy meal, exposure to

cold, or a combination of these factors.

Exertional angina typically is relieved in 1–5 min by slowing or ceasing activities and even more rapidly by rest and sublingual nitroglycerin (see below). Indeed, the diagnosis of angina should be suspect if it

does not respond to the combination of these measures. The severity of

angina can be conveniently summarized by the Canadian Cardiac Society functional classification (Table 273-1). Its impact on the patient’s

functional capacity can be described by using the New York Heart

Association functional classification (Table 273-1).

Sharp, fleeting chest pain or a prolonged, dull ache localized to the

left submammary area is rarely due to myocardial ischemia. However,

especially in women and diabetic patients, angina pectoris may be

atypical in location and not strictly related to provoking factors. In

addition, this symptom may exacerbate and remit over days, weeks, or

months. Its occurrence can be seasonal, occurring more frequently in

the winter in temperate climates. Anginal “equivalents” are symptoms

of myocardial ischemia other than angina. They include dyspnea,

TABLE 273-1 Cardiovascular Disease Classification Chart

CLASS

NEW YORK HEART

ASSOCIATION FUNCTIONAL

CLASSIFICATION

CANADIAN CARDIOVASCULAR

SOCIETY FUNCTIONAL

CLASSIFICATION

I Patients have cardiac disease

but without the resulting

limitations of physical activity.

Ordinary physical activity

does not cause undue fatigue,

palpitation, dyspnea, or anginal

pain.

Ordinary physical activity, such

as walking and climbing stairs,

does not cause angina. Angina

present with strenuous or rapid

or prolonged exertion at work or

recreation.

II Patients have cardiac disease

resulting in slight limitation

of physical activity. They are

comfortable at rest. Ordinary

physical activity results in

fatigue, palpitation, dyspnea, or

anginal pain.

Slight limitation of ordinary

activity. Walking or climbing stairs

rapidly, walking uphill, walking

or stair climbing after meals, in

cold, or when under emotional

stress or only during the few

hours after awakening. Walking

more than two blocks on the level

and climbing more than one flight

of stairs at a normal pace and in

normal conditions.

III Patients have cardiac disease

resulting in marked limitation

of physical activity. They are

comfortable at rest. Less than

ordinary physical activity

causes fatigue, palpitation,

dyspnea, or anginal pain.

Marked limitation of ordinary

physical activity. Walking one

to two blocks on the level and

climbing one flight of stairs at

normal pace.

IV Patients have cardiac disease

resulting in inability to carry on

any physical activity without

discomfort. Symptoms of

cardiac insufficiency or of

the anginal syndrome may be

present even at rest. If any

physical activity is undertaken,

discomfort is increased.

Inability to carry on any physical

activity without discomfort—

anginal syndrome may be present

at rest.

Source: Reproduced with permission from L Goldman et al: Comparative

reproducibility and validity of systems for assessing cardiovascular functional

class: Advantages of a new specific activity scale. Circulation 64:1227, 1981.

2034 PART 6 Disorders of the Cardiovascular System

nausea, fatigue, and faintness and are more common in the elderly and

in diabetic patients.

Systematic questioning of a patient with suspected IHD is important to uncover the features of an unstable syndrome associated with

increased risk, such as angina occurring with less exertion than in the

past, occurring at rest, or awakening the patient from sleep. Since coronary atherosclerosis often is accompanied by similar lesions in other

arteries, a patient with angina should be questioned and examined for

peripheral arterial disease (intermittent claudication [Chap. 281]),

stroke, or transient ischemic attacks (Chap. 426). It is also important

to uncover a family history of premature IHD (<55 years in first-degree

male relatives and <65 in female relatives) and the presence of diabetes

mellitus, hyperlipidemia, hypertension, cigarette smoking, and other

risk factors for coronary atherosclerosis.

The history of typical angina pectoris establishes the diagnosis of

IHD until proven otherwise. Given the importance of the history,

clinicians should move beyond unstructured interviews with the

patient and consider using a validated questionnaire (e.g., Seattle

Angina Questionnaire) to establish the presence and severity of IHD.

The coexistence of advanced age, male sex, the postmenopausal state,

and risk factors for atherosclerosis increases the likelihood of hemodynamically significant coronary disease. A particularly challenging

problem is the evaluation and management of patients with persistent

ischemic-type chest discomfort but no flow-limiting obstructions in

their epicardial coronary arteries. This situation arises more often in

women than in men. Potential etiologies include microvascular coronary disease (detectable on coronary reactivity testing in response

to vasoactive agents such as intracoronary adenosine, acetylcholine,

and nitroglycerin) and abnormal cardiac nociception. Treatment of

microvascular coronary disease should focus on efforts to improve

endothelial function, including nitrates, beta blockers, calcium antagonists, statins, and angiotensin-converting enzyme (ACE) inhibitors.

Abnormal cardiac nociception is more difficult to manage and may be

ameliorated in some cases by imipramine.

■ PHYSICAL EXAMINATION

The physical examination is often normal in patients with stable

angina when they are asymptomatic. However, because of the increased

likelihood of IHD in patients with diabetes and/or peripheral arterial

disease, clinicians should search for evidence of atherosclerotic disease

at other sites, such as an abdominal aortic aneurysm, carotid arterial

bruits, and diminished arterial pulses in the lower extremities. The

physical examination also should include a search for evidence of risk

factors for atherosclerosis such as xanthelasmas and xanthomas. Evidence for peripheral arterial disease should be sought by evaluating the

pulse contour at multiple locations and comparing the blood pressure

between the arms and between the arms and the legs (ankle-brachial

index). Examination of the fundi may reveal an increased light reflex

and arteriovenous nicking as evidence of hypertension. There also may

be signs of anemia, thyroid disease, and nicotine stains on the fingertips from cigarette smoking.

Palpation may reveal cardiac enlargement and abnormal contraction of the cardiac impulse (LV dyskinesia). Auscultation can uncover

arterial bruits, a third and/or fourth heart sound, and, if acute ischemia or previous infarction has impaired papillary muscle function, an

apical systolic murmur due to mitral regurgitation. These auscultatory

signs are best appreciated with the patient in the left lateral decubitus

position. Aortic stenosis, aortic regurgitation (Chap. 261), pulmonary

hypertension (Chap. 283), and hypertrophic cardiomyopathy (Chap.

259) must be excluded, since these disorders may cause angina in the

absence of coronary atherosclerosis. Examination during an anginal

attack is useful, since ischemia can cause transient LV failure with

the appearance of a third and/or fourth heart sound, a dyskinetic

cardiac apex, mitral regurgitation, and even pulmonary edema. Tenderness of the chest wall, localization of the discomfort with a single

fingertip on the chest, or reproduction of the pain with palpation of the

chest makes it unlikely that the pain is caused by myocardial ischemia.

A protuberant abdomen may indicate that the patient has the metabolic syndrome and is at increased risk for atherosclerosis.

■ LABORATORY EXAMINATION

Although the diagnosis of IHD can be made with a high degree of

confidence from the history and physical examination, a number of

simple laboratory tests can be helpful. The urine should be examined for evidence of diabetes mellitus and renal disease (including

microalbuminuria) since these conditions accelerate atherosclerosis.

Similarly, examination of the blood should include measurements of

lipids (cholesterol—total, LDL, high-density lipoprotein [HDL]—and

triglycerides), glucose (hemoglobin A1C), creatinine, hematocrit, and, if

indicated based on the physical examination, thyroid function. A chest

x-ray may be helpful in demonstrating the consequences of IHD, i.e.,

cardiac enlargement, ventricular aneurysm, or signs of heart failure.

These signs can support the diagnosis of IHD and are important in

assessing the degree of cardiac damage. Evidence exists that an elevated

level of high-sensitivity C-reactive protein (CRP) (specifically, between

1 and 3 mg/L) is an independent risk factor for IHD and may be useful

in therapeutic decision-making about the initiation of hypolipidemic

treatment. The major benefit of high-sensitivity CRP is in reclassifying

the risk of IHD in patients in the “intermediate” risk category on the

basis of traditional risk factors.

■ ELECTROCARDIOGRAM

A 12-lead ECG recorded at rest may be normal in patients with typical angina pectoris, but there may also be signs of an old myocardial

infarction (Chap. 240). Although repolarization abnormalities, i.e.,

ST-segment and T-wave changes, as well as LVH and disturbances of

cardiac rhythm or intraventricular conduction, are suggestive of IHD,

they are nonspecific, since they also can occur in pericardial, myocardial, and valvular heart disease or, in the case of the former, transiently

with anxiety, changes in posture, drugs, or esophageal disease. The

presence of LVH is a significant indication of increased risk of adverse

outcomes from IHD. Of note, even though LVH and cardiac rhythm

disturbances are nonspecific indicators of the development of IHD,

they may be contributing factors to episodes of angina in patients

in whom IHD has developed as a consequence of conventional risk

factors. Dynamic ST-segment and T-wave changes that accompany

episodes of angina pectoris and disappear thereafter are more specific.

■ STRESS TESTING

Electrocardiographic The most widely used test for both the

diagnosis of IHD and the estimation of risk and prognosis involves

recording of the 12-lead ECG before, during, and after exercise, usually

on a treadmill (Fig. 273-3). The test consists of a standardized incremental increase in external workload (Table 273-2) while symptoms,

the ECG, and arm blood pressure are monitored. Exercise duration is

usually symptom-limited, and the test is discontinued upon evidence of

chest discomfort, severe shortness of breath, dizziness, severe fatigue,

ST-segment depression >0.2 mV (2 mm), a fall in systolic blood pressure >10 mmHg, or the development of a ventricular tachyarrhythmia.

This test is used to discover any limitation in exercise performance,

detect typical ECG signs of myocardial ischemia, and establish their

relationship to chest discomfort. The ischemic ST-segment response

generally is defined as flat or downsloping depression of the ST

segment >0.1 mV below baseline (i.e., the PR segment) and lasting

longer than 0.08 s (Fig. 273-2). Upsloping or junctional ST-segment

changes are not considered characteristic of ischemia and do not

constitute a positive test. Although T-wave abnormalities, conduction

disturbances, and ventricular arrhythmias that develop during exercise

should be noted, they are also not diagnostic. Negative exercise tests in

which the target heart rate (85% of maximal predicted heart rate for age

and sex) is not achieved are considered nondiagnostic.

In interpreting ECG stress tests, the probability that coronary

artery disease (CAD) exists in the patient or population under study

(i.e., pretest probability) should be considered. A positive result on

exercise indicates that the likelihood of CAD is 98% in males who are

>50 years with a history of typical angina pectoris and who develop

chest discomfort during the test. The likelihood decreases if the patient

has atypical or no chest pain by history and/or during the test.