2018 PART 6 Disorders of the Cardiovascular System

FIGURE 269-11 A. Fontan surgery creates a unique circulation in which deoxygenated blood is directed to the PAs from the SVC and IVC in a fashion that bypasses any

pumping chamber. The SVC and IVC are connected (*) via either an internal “tunnel” or an extracardiac conduit that guides flow to the PA. Pulmonary venous (oxygenated)

return courses from PV to LA to LV to aorta. In contrast to physiology in normal adults (where pressure is generated by an RV to propel blood flow from a lower pressure RA

to a higher pressure LA), in Fontan circulation, by definition, due to the absence of a pumping chamber to the PA, RA pressure is greater than LA pressure, permitting flow

through the lungs. Ao, aorta; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; PA, pulmonary arteries; PV, pulmonary veins; SVC, superior vena cava; *, Fontan baffle.

B. Diagrammatic representation of the location of various types of Fontan operations. (Part B used with permission from Emily Flynn McIntosh, illustrator.)

PA

SVC

*

* *

IVC

A

LV

Ao

RA

RA

LA

RV

Fontan

Extracardiac conduit

IVC

SVC

PA Ao

LV

LA

PV

Extracardiac

Fontan

Lateral tunnel

Fontan

B

Atriopulmonary

Fontan

Classic Fontan

Pericardial Disease

2019CHAPTER 270

sufficient knowledge and competency so as to be able both to engage

in patient care provision as well as to seek greater expertise, guidance,

and support, when such is appropriate. Across the globe, lifelong care

for adults with CHD typifies this growing demand. Care for adults with

CHD within medical care centers that contain an ACHD specialty care

program has been associated with improved overall survival. However,

current analyses suggest that the majority of adults with CHD seek

and receive their medical care outside of such ACHD specialty care

centers and within the hands of the general practitioner, internist,

and cardiologist. Under a surface of adaptability and determination,

adults with CHD present a wide spectrum of cognitive and functional

performance, multiple organ system comorbidities, abnormalities of

systemic and pulmonary vasculature, and a near universal presence

of heart failure of one stage or another, all over a lifetime. It appears

incumbent on the ACHD specialist and ACHD specialty care centers to

serve as a hub for partnering practitioners, encouraging engagement to

the level of highest competencies, and providing education, oversight,

and support, so as to achieve optimal outcomes.

■ FURTHER READING

Gilboa SM et al: Congenital heart defects in the United States: Estimating the magnitude of the affected population in 2010. Circulation

134:101, 2016.

Gurvitz M et al: Emerging research directions in adult congenital

heart disease: A report from an NHLBI/ACHA Working Group. J Am

Coll Cardiol 67:1956, 2016.

Regitz-Zagrosek V et al; and Group ESCSD: 2018 ESC guidelines

for the management of cardiovascular diseases during pregnancy. Eur

Heart J 39:3165, 2018.

Silversides CK et al: Pregnancy outcomes in women with heart disease: The CARPREG II Study. J Am Coll Cardiol 71:2419, 2018.

Stout KK et al: 2018 AHA/ACC guidelines for the management

of adults with congenital heart disease: A report of the American

College of Cardiology/American Heart Association Task Force on

Clinical Practice Guidelines. Circulation 139:e698, 2019.

■ NORMAL FUNCTIONS OF THE PERICARDIUM

The normal pericardium is a double-layered sac of the visceral pericardium and parietal pericardium. The visceral pericardium is a serous

membrane that is separated from the fibrous parietal pericardium

by a small quantity (15–50 mL) of fluid, an ultrafiltrate of plasma.

The normal pericardium, by exerting a restraining force, prevents

sudden dilation of the cardiac chambers, especially the right atrium

and ventricle, e.g., during exercise. It also restricts the anatomic position of the heart and likely retards the spread of infections from the

lungs and pleural cavities to the heart. Nevertheless, total absence of

the pericardium, either congenital or after surgery, does not produce

obvious clinical disease. In partial left pericardial defects, the main

pulmonary artery and left atrium may bulge through the defect; very

rarely, herniation and subsequent strangulation of the left atrium may

cause sudden death.

ACUTE PERICARDITIS

Acute pericarditis, by far the most common pathologic process involving the pericardium (Table 270-1), has four principal diagnostic

features:

1. Chest pain is usually present in acute infectious pericarditis and

in many of the forms presumed to be related to hypersensitivity,

270 Pericardial Disease

Joseph Loscalzo

TABLE 270-1 Classification of Pericarditis

Clinical Classification

I. Acute pericarditis (<6 weeks)

A. Fibrinous

B. Effusive (serous or sanguineous)

II. Subacute pericarditis (6 weeks to 6 months)

A. Effusive-constrictive

B. Constrictive

III. Chronic pericarditis (>6 months)

A. Constrictive

B. Adhesive (nonconstrictive)

Etiologic Classification

I. Infectious pericarditis

A. Viral (coxsackievirus A and B, echovirus, herpesviruses, mumps,

adenovirus, hepatitis, HIV)

B. Pyogenic (pneumococcus, Streptococcus, Staphylococcus, Neisseria,

Legionella, Chlamydia)

C. Tuberculous

D. Fungal (histoplasmosis, coccidioidomycosis, Candida, blastomycosis)

E. Other infections (syphilitic, protozoal, parasitic)

II. Noninfectious pericarditis

A. Acute idiopathic

B. Renal failure

C. Neoplasia

1. Primary tumors (benign or malignant, mesothelioma)

2. Tumors metastatic to pericardium (lung and breast cancer, lymphoma,

leukemia)

D. Trauma (penetrating chest wall, nonpenetrating)

E. Aortic dissection (with leakage into pericardial sac)

F. Acute myocardial infarction

G. Postirradiation

H. Familial Mediterranean fever and other periodic fever syndromes

I. Familial pericarditis

1. Mulibrey nanisma

J. Metabolic (myxedema, cholesterol)

III. Pericarditis presumably related to autoimmunity

A. Rheumatic fever

B. Collagen vascular disease (systemic lupus erythematosus, rheumatoid

arthritis, ankylosing spondylitis, scleroderma, acute rheumatic fever,

granulomatosis with polyangiitis [Wegener’s])

C. Drug-induced (e.g., procainamide, hydralazine, phenytoin, isoniazid,

minoxidil, anticoagulants, methysergide)

D. Postcardiac injury

1. Postpericardiotomy

2. Posttraumatic

3. Postmyocardial infarction (Dressler’s syndrome)

a

An autosomal recessive syndrome characterized by growth failure, muscle

hypotonia, hepatomegaly, ocular changes, enlarged cerebral ventricles, mental

retardation, ventricular hypertrophy, and chronic constrictive pericarditis.

autoimmunity, or of unknown cause (idiopathic). The pain of acute

pericarditis is often severe, retrosternal and/or left precordial, and

referred to the neck, arms, or left shoulder. Frequently the pain is

pleuritic, consequent to accompanying pleural inflammation (i.e.,

sharp and aggravated by inspiration and coughing); however, at

times, it is steady, radiates to the trapezius ridge or into either arm,

and resembles that of myocardial ischemia. For this reason, confusion with acute myocardial infarction (AMI) is common. Characteristically, pericardial pain may be intensified by lying supine and

relieved by sitting up and leaning forward (Chap. 14). Pain is often

absent in slowly developing tuberculous, postirradiation, neoplastic,

and uremic pericarditis.

The differentiation of AMI from acute pericarditis may be challenging when, with the latter, serum biomarkers of myocardial

damage such as troponin and creatine kinase-MB rise, presumably

2020 PART 6 Disorders of the Cardiovascular System

because of concomitant involvement of the epicardium in the

inflammatory process (an epi-myocarditis) with resulting myocyte

necrosis. If they occur, however, these elevations are quite modest

compared to those in AMI, given the extensive electrocardiographic

ST-segment elevation in pericarditis. This dissociation is useful in

differentiating between these conditions.

2. A pericardial friction rub is audible at some point in the illness in

about 85% of patients with acute pericarditis. The rub may have up

to three components per cardiac cycle and is described as rasping,

scratching, or grating (Chap. 239); it is heard most frequently at end

expiration with the patient upright and leaning forward.

3. The electrocardiogram (ECG) in acute pericarditis without massive

effusion usually displays changes secondary to acute subepicardial

inflammation (Fig. 270-1A), and typically evolves through four

stages. In stage 1, there is widespread elevation of the ST segments,

often with upward concavity, involving two or three standard limb

leads and V2

–V6

, with reciprocal depressions only in aVR and

occasionally V1

. In addition, there is depression of the PR segment

below the TP segment, reflecting atrial involvement, an early change

that may occur prior to ST segment elevation. Usually there are no

significant changes in QRS complexes unless a large pericardial

effusion develops (see below). After several days, the ST segments

return to normal (stage 2), and only then, or even later, do the T

waves become inverted (stage 3). Weeks or months after the onset

of acute pericarditis, the ECG returns to normal (stage 4). In contrast, in AMI, ST elevations are upwardly convex, and reciprocal

FIGURE 270-1 A. Acute pericarditis. There are diffuse ST-segment elevations in leads I, II, aVF, and V2

–V6

). There is PR-segment depression due to a concomitant atrial injury

current. B. Electrical alternans. This tracing was obtained from a patient with a large pericardial effusion with cardiac tamponade.

I

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

PR

ST

ST

PR

A

aVR V1 V4 I

aVL V2 V5 II

aVF V3 V6 III

II

B

depression is usually more prominent; these changes may return

to normal within a day or two. Q waves may develop, with loss of

R-wave amplitude, and T-wave inversions; by contrast, with acute

pericarditis, these changes are usually seen within hours before the

ST segments have become isoelectric (Chaps. 274 and 275).

4. Pericardial effusion is usually associated with pain and/or the ECG

changes mentioned above and, if the effusion is large, with electrical

alternans (Fig. 270-1B). Pericardial effusion is especially important

clinically when it develops within a relatively short time because it

may lead to cardiac tamponade (see below). Differentiation from

cardiac enlargement on physical examination may be difficult, but

heart sounds may be fainter with large pericardial effusion. The

friction rub and the apex impulse may disappear. The base of the

left lung may be compressed by pericardial fluid, producing Ewart’s

sign, a patch of dullness, increased fremitus, and egophany beneath

the angle of the left scapula. The chest roentgenogram may show

enlargement of the cardiac silhouette, with a “water bottle” configuration, but may be normal in patients with small effusions.

Diagnosis Echocardiography (Chap. 241) is the most widely used

imaging technique. It is sensitive, specific, simple, and noninvasive;

may be performed at the bedside; and allows localization and estimation of the quantity of pericardial fluid. The presence of pericardial

fluid is recorded by two-dimensional transthoracic echocardiography

as a relatively echo-free space between the posterior pericardium and

left ventricular epicardium and/or as a space between the anterior right

Pericardial Disease

2021CHAPTER 270

ventricle and the parietal pericardium just beneath the anterior chest

wall (Fig. 270-2).

The diagnosis of pericardial fluid or thickening may be confirmed

by computed tomography (CT) or magnetic resonance imaging (MRI).

These techniques may be superior to echocardiography in detecting

loculated pericardial effusions, and pericardial thickening, and in the

identification of pericardial masses. MRI is also helpful in detecting

pericardial inflammation (Fig. 270-3).

TREATMENT

Acute Pericarditis

There is no specific therapy for acute idiopathic pericarditis, but

bed rest should be recommended, and anti-inflammatory treatment

with aspirin (2–4 g/d) or nonsteroidal anti-inflammatory drugs

(NSAIDs), such as ibuprofen (600–800 mg tid) or indomethacin

(25–50 mg tid), should be administered along with gastric protection (e.g., omeprazole 20 mg/d). In responsive patients, these

doses should be continued for 1–2 weeks and then tapered over

several weeks. In addition, colchicine (0.5 mg qd [<70 kg] or

0.5 mg bid [>70 kg]) should be administered for 3 months. Colchicine enhances the response to NSAIDs and also aids in reducing

the risk of recurrent pericarditis. This drug is concentrated in and

interferes with the migration of neutrophils, may cause diarrhea

and other gastrointestinal side effects, and is contraindicated in

patients with hepatic or renal dysfunction. Glucocorticoids (e.g.,

prednisone 1 mg/kg per day) usually suppress the clinical manifestations of acute pericarditis in patients who have failed therapy

with or do not tolerate NSAIDs and colchicine. However, since they

increase the risk of subsequent recurrence, full-dose corticosteroids

should be given for only 2–4 days and then tapered. Anticoagulants

should be avoided because their use could cause bleeding into the

pericardial cavity and tamponade.

In patients with multiple, frequent, and disabling recurrences

that continue for >2 years, are not prevented by continuing colchicine and other NSAIDs, and are not controlled by glucocorticoids,

treatment with azathioprine or anakinra (an interleukin 1β receptor

antagonist) has been reported to be of benefit. Rarely, pericardial

stripping may be necessary; however, this procedure may not

always terminate the recurrences.

The majority of patients with acute pericarditis can be managed as outpatients with careful follow-up. However, when specific

causes (tuberculosis, neoplastic disease, bacterial infection) are suspected, or if any of the predictors of poor prognosis (fever >38°C,

subacute onset, or large pericardial effusion) are present, hospitalization is advisable.

■ CARDIAC TAMPONADE

The accumulation of fluid in the pericardial space in a quantity sufficient to cause serious obstruction of the inflow of blood into the

ventricles results in cardiac tamponade. This complication may be fatal

if it is not recognized and treated promptly. The most common causes

of tamponade are idiopathic pericarditis and pericarditis secondary to

neoplastic disease, tuberculosis, or bleeding into the pericardial space

after leakage from an aortic dissection, cardiac operation, trauma, or

treatment with anticoagulants.

The three principal features of tamponade (Beck’s triad) are hypotension, soft or absent heart sounds, and jugular venous distention with

a prominent x (early systolic) descent but an absent y (early diastolic)

descent. The limitations to ventricular filling are responsible for reductions of cardiac output and arterial pressure. The quantity of fluid

necessary to produce cardiac tamponade may be as small as 200 mL

when the fluid develops rapidly or be as much as >2000 mL in slowly

developing effusions when the pericardium has had the opportunity to

stretch and adapt to an increasing volume.

A high index of suspicion for cardiac tamponade is required

because in many instances no obvious cause for pericardial disease

is apparent. This diagnosis should be considered in any patient with

otherwise unexplained sudden enlargement of the cardiac silhouette,

hypotension, and elevation of jugular venous pressure. Reductions

in amplitude of the QRS complexes and electrical alternans of the P,

QRS, or T waves should also raise the suspicion of cardiac tamponade

(Fig. 270-1).

Table 270-2 lists the features that distinguish acute cardiac tamponade from constrictive pericarditis.

FIGURE 270-2 Two-dimensional echocardiogram in lateral view in a patient

with a large pericardial effusion. Ao, aorta; LA, left atrium; LV, left ventricle; pe,

pericardial effusion; RV, right ventricle. (Reproduced with permission from Imazio M:

Contemporary management of pericardial diseases. Curr Opin Cardiol 27:308, 2012.)

RV

A B

LV

LV

LA

AO

*

*

*

FIGURE 270-3 Pericardial inflammation by cardiac magnetic resonance imaging. A. Short axis view. The pericardium is thickened and enhanced on T2 magnetic images.

Note thickened white line denoted by arrow. B. Long axis view. Late gadolinium enhancement of thickened, inflamed pericardium. AO, aorta; LA, left atrium; LV, left ventricle;

RV, right ventricle. (From RY Kwong: Cardiovascular magnetic resonance imaging, in Braunwald’s Heart Disease, 10th ed, Mann DL et al [eds]. Philadelphia: Elsevier, 2015,

pp 320–40.)

2022 PART 6 Disorders of the Cardiovascular System

Paradoxical Pulse This important clue to the presence of cardiac

tamponade consists of a greater than normal (10 mmHg) inspiratory

decline in systolic arterial pressure. When severe, it may be detected by

palpating weakness or even disappearance of the arterial pulse during

inspiration, but usually sphygmomanometric measurement of systolic

pressure during slow respiration is required.

Because both ventricles share a tight incompressible covering, i.e.,

the pericardial sac, the inspiratory enlargement of the right ventricle

causes leftward bulging of the interventricular septum, reducing left

ventricular volume, stroke volume, and arterial systolic pressure. Paradoxical pulse also occurs in approximately one-third of patients with

constrictive pericarditis (see below), and in some cases of hypovolemic

shock, acute and chronic obstructive airway disease, and pulmonary

embolism. Right ventricular infarction (Chap. 275) may resemble

cardiac tamponade with hypotension, elevated jugular venous pressure,

an absent y descent in the jugular venous pulse, and occasionally, a

paradoxical pulse (Table 270-2).

Diagnosis Because immediate treatment of cardiac tamponade

may be lifesaving, prompt establishment of the diagnosis, usually by

echocardiography, should be undertaken. When pericardial effusion

causes tamponade, Doppler ultrasound shows that tricuspid and

pulmonic valve flow velocities increase markedly during inspiration,

whereas pulmonic vein, mitral, and aortic flow velocities decrease (as

in constrictive pericarditis, see below) (Fig. 270-4). In tamponade,

there is late diastolic inward motion (collapse) of the right ventricular

free wall and the right atrium. Transesophageal echocardiography,

CT, or cardiac MRI may be necessary to diagnose a loculated effusion

responsible for cardiac tamponade.

TREATMENT

Cardiac Tamponade

Patients with acute pericarditis should be observed frequently

for the development of an effusion. If a large effusion is present,

pericardiocentesis should be performed or the patient watched

closely for signs of tamponade with serial echocardiography and

monitoring of arterial and venous pressures.

PERICARDIOCENTESIS

If manifestations of tamponade appear, pericardiocentesis using an

apical, parasternal, or, most commonly, subxiphoid approach must

be carried out at once because if left untreated, tamponade may be

rapidly fatal. Whenever possible, this procedure should be carried

out under echocardiographic guidance. Intravenous saline may be

administered as the patient is being readied for the procedure, but

the pericardiocentesis must not be delayed. If possible, intrapericardial pressure should be measured before fluid is withdrawn, and

TABLE 270-2 Features That Distinguish Cardiac Tamponade from Constrictive Pericarditis and Similar Clinical Disorders

CHARACTERISTIC TAMPONADE

CONSTRICTIVE

PERICARDITIS

RESTRICTIVE

CARDIOMYOPATHY

RIGHT VENTRICULAR

MYOCARDIAL

INFARCTION

EFFUSIVE CONSTRICTIVE

PERICARDITIS

Clinical

Pulsus paradoxus +++ + + + +++

Jugular veins

Prominent y descent – ++ + + –

Prominent x descent +++ ++ +++ + +++

Kussmaul’s sign – +++ + +++ ++

Third heart sound – – + + +

Pericardial knock – ++ – – –

Electrocardiogram

Low ECG voltage ++ ++ + – +

Electrical alternans ++ – – – +

Echocardiogram

Thickened pericardium – +++ – – ++

Pericardial calcification – ++ – – _

Pericardial effusion +++ – – – ++

RV size Usually small Usually normal Usually normal Enlarged Usually normal

Exaggerated respiratory

variation in flow velocity

+++ +++ – +++ +

CT/MRI

Thickened pericardium – +++ – ++

Equalization of diastolic

pressures

+++ +++ – ++ ++

Abbreviations: +++, always present; ++, usually present; +, rare; –, absent; DC, diastolic collapse; ECG, electrocardiogram; RV, right ventricle.

Source: Reproduced with permission from GM Brockington et al: Constrictive pericarditis. Cardiol Clin 8:645, 1990.

E Septum

RV

RA

LA

LV

DIASTOLE DIASTOLE

E A

A

TV MV TV MV

Septum

Doppler

transvalvular

inflow patterns

Thickened

pericardium

Pulmonary

vein

IVC and hepatic veins

Inspiration Expiration

Apical 4-chamber views

FIGURE 270-4 Constrictive pericarditis. Doppler schema of respirophasic changes

in mitral and tricuspid inflow. Reciprocal patterns of ventricular filling are assessed

on pulsed Doppler examination of mitral valve (MV) and tricuspid valve (TV) inflow.

IVC, inferior vena cava; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right

ventricle. (Courtesy of Bernard E. Bulwer, MD.)

Pericardial Disease

2023CHAPTER 270

the pericardial cavity should be drained as completely as possible.

A small, multiholed catheter may be advanced over the needle

inserted into the pericardial cavity and left in place to allow draining of the pericardial space if fluid reaccumulates. Surgical drainage

through a limited (subxiphoid) thoracotomy may be required in

recurrent tamponade to remove loculated effusions and/or when it

is necessary to obtain tissue for diagnosis.

Pericardial fluid obtained from an effusion may have the physical

characteristics of an exudate. In developed nations, bloody fluid

is most commonly due to neoplasm, renal failure, or after cardiac

injury. In developing nations, tuberculosis, may also cause exudative and/or bloody effusion.

The pericardial fluid should be analyzed for red and white blood

cells and cytology for neoplastic cells. Cultures should be obtained.

The presence of DNA of Mycobacterium tuberculosis determined

by the polymerase chain reaction strongly supports the diagnosis

of tuberculous pericarditis; however, it is often necessary to obtain

pericardial tissue to make this diagnosis (Chap. 178).

■ VIRAL OR IDIOPATHIC ACUTE PERICARDITIS

In many instances, acute pericarditis occurs in association with or

following illnesses of known or presumed viral origin and probably is

caused by the same agent. There may be an antecedent infection of the

respiratory tract, but viral isolation and serologic studies are usually

negative. In some cases, Coxsackievirus A or B or the virus of influenza, echovirus, mumps, Herpes simplex, varicella/zoster, adenovirus,

or cytomegalovirus has been isolated from pericardial fluid, and/or

appropriate elevations in viral antibody titers have been observed.

Frequently, a viral cause cannot be established, and the term idiopathic

acute pericarditis is appropriate.

Viral or idiopathic acute pericarditis occurs at all ages but is most

common in young adult males and is often associated with pleural

effusion and pneumonitis. The almost simultaneous development of

fever and precordial pain, often 10–12 days after a presumed viral

illness, constitutes an important feature in the differentiation of acute

pericarditis from AMI, in which chest pain precedes fever. The constitutional symptoms are usually mild to moderate, and a pericardial

friction rub is often audible. The disease ordinarily runs its course in a

few days to 4 weeks. Elevations of C-reactive protein and of the white

blood cell count are common. The ST-segment alterations in the ECG

usually disappear after 1 or more weeks, but the abnormal T waves

may persist for as long as several years and be a source of confusion in

persons without a clear history of pericarditis. Accumulation of some

pericardial fluid is common, and both tamponade and constrictive

pericarditis are possible, but infrequent, complications.

The most frequent complication is recurrent (relapsing) pericarditis, which occurs in about one-fourth of patients with acute idiopathic pericarditis. A smaller number of individuals have multiple

recurrences.

Postcardiac Injury Syndrome Acute pericarditis may appear in

a variety of circumstances that have one common feature—previous

injury to the myocardium with blood in the pericardial cavity. The

syndrome may develop after a cardiac operation (postpericardiotomy

syndrome), after blunt or penetrating cardiac trauma (Chap. 272), or

after perforation of the heart with a catheter; rarely, it follows AMI.

The clinical picture mimics acute viral or idiopathic pericarditis.

The principal symptom is the pain of acute pericarditis, which usually

develops 1–4 weeks after the cardiac injury. Recurrences are common

and may occur up to 2 years or more following the injury. Fever, pleuritis, and pneumonitis are accompanying features, and the illness usually

subsides in 1 or 2 weeks. The pericarditis may be of the fibrinous variety, or it may be a pericardial effusion, which is often serosanguinous

and rarely causes tamponade. ECG changes typical of acute pericarditis

may also occur. This syndrome is probably the result of a hypersensitivity (or autoimmune) reaction to antigen(s) that originate from injured

myocardial tissue and/or pericardium.

Often no treatment is necessary aside from aspirin and analgesics. When the illness is severe or followed by a series of disabling

recurrences, therapy with another NSAID, colchicine, or a glucocorticoid, such as described for treatment of acute pericarditis, is usually

effective.

■ DIFFERENTIAL DIAGNOSIS

Because there is no specific test for acute idiopathic pericarditis, the

diagnosis is one of exclusion. Consequently, all other disorders that

may be associated with acute fibrinous pericarditis must be considered.

A common diagnostic error is mistaking acute viral or idiopathic pericarditis for AMI and vice versa.

Pericarditis secondary to postcardiac injury is differentiated from

acute idiopathic pericarditis chiefly by timing. If it occurs within a few

days or weeks of a chest blow, a cardiac perforation, a cardiac operation, or an AMI, the two are probably related.

It is important to distinguish pericarditis due to collagen vascular

disease from acute idiopathic pericarditis. Most important in the differential diagnosis is the pericarditis due to systemic lupus erythematosus

(SLE; Chap. 356) or drug-induced (hydralazine or procainamide)

lupus. When pericarditis occurs in the absence of any obvious underlying disorder, the diagnosis of SLE may be suggested by a rise in the

titer of antinuclear antibodies. Acute pericarditis is an occasional complication of rheumatoid arthritis, scleroderma, and polyarteritis nodosa,

and other evidence of these diseases is usually obvious at the time of

presentation with acute pericarditis.

Pyogenic (purulent) pericarditis is usually secondary to cardiothoracic operations, by extension of infection from the lungs or pleural

cavities, from rupture of the esophagus into the pericardial sac, or from

rupture of a valvular ring abscess in a patient with infective endocarditis. It may also complicate the viral, bacterial, mycobacterial, and fungal

infections that occur with HIV infection. It is generally accompanied

by fever, chills, septicemia, and evidence of infection elsewhere, and

generally has a poor prognosis. The diagnosis is made by examination

of the pericardial fluid. It requires immediate drainage as well as vigorous antibiotic treatment.

Pericarditis of renal failure (uremic pericarditis) occurs in up to

one-third of patients with severe renal dysfunction and is also seen

in patients undergoing chronic dialysis who have normal levels of

blood urea nitrogen (dialysis-associated pericarditis). These two forms

of pericarditis may be fibrinous and are generally associated with

serosanguinous effusions; frank hemorrhagic effusions may be seen

in some cases of uremic pericarditis prior to the onset of dialysis. A

pericardial friction rub is common, but pain is usually absent or mild.

Treatment with an NSAID and intensification of dialysis are usually

adequate. Occasionally, tamponade occurs and pericardiocentesis is

required. When the pericarditis of renal failure is recurrent or persistent, a pericardial window should be created or pericardiectomy may

be necessary.

Pericarditis due to neoplastic diseases results from extension or

invasion of metastatic tumors (most commonly carcinoma of the

lung and breast, malignant melanoma, lymphoma, and leukemia)

to the pericardium. The pain of pericarditis, tamponade, and atrial

arrhythmias are complications that occur occasionally. Diagnosis is

made by pericardial fluid cytology or pericardial biopsy. Mediastinal

irradiation for neoplasm may cause acute pericarditis and/or chronic

constrictive pericarditis. Unusual causes of acute pericarditis include

syphilis, fungal infection (histoplasmosis, blastomycosis, aspergillosis,

and candidiasis), and parasitic infestation (amebiasis, toxoplasmosis,

echinococcosis, and trichinosis) (Table 270-1).

■ CHRONIC PERICARDIAL EFFUSIONS

Chronic pericardial effusions are sometimes encountered in patients

without an antecedent history of acute pericarditis. They may cause

few symptoms per se, and their presence may be detected by finding

an enlarged cardiac silhouette on a chest roentgenogram. Tuberculosis

and myxedema may be causal. Neoplasms, SLE, rheumatoid arthritis,

mycotic infections, radiation therapy to the chest, and chylopericardium may also cause chronic pericardial effusion and should be considered and specifically sought in such patients. Aspiration and analysis

of the pericardial fluid are often helpful in diagnosis. Pericardial fluid

2024 PART 6 Disorders of the Cardiovascular System

should be analyzed as described under pericardiocentesis. Grossly

sanguineous pericardial fluid results most commonly from a neoplasm,

tuberculosis, renal failure, or slow leakage from an aortic dissection.

Pericardiocentesis may resolve large effusions, but pericardiectomy

may be required in patients with recurrence. Intrapericardial instillation of sclerosing agents may be used to prevent reaccumulation of

fluid, most commonly in recurrent neoplastic effusions.

CHRONIC CONSTRICTIVE PERICARDITIS

This disorder results when the healing of an acute fibrinous or serofibrinous pericarditis or the resorption of a chronic pericardial effusion

is followed by obliteration of the pericardial cavity with the formation

of granulation tissue. The latter gradually contracts and forms a firm

scar encasing the heart, which may become calcified. In developing

nations, a high percentage of cases are of tuberculous origin, but this

is now an uncommon cause in North America or Western Europe.

Chronic constrictive pericarditis may follow acute or relapsing viral or

idiopathic pericarditis, trauma with organized blood clot, or cardiac

surgery of any type, or results from mediastinal irradiation, purulent

infection, histoplasmosis, neoplastic disease (especially breast cancer,

lung cancer, and lymphoma), rheumatoid arthritis, SLE, or chronic

renal failure treated by chronic dialysis. In many patients, the cause

of the pericardial disease is undetermined, and in these patients, an

asymptomatic or forgotten bout of viral pericarditis, idiopathic or

acute, may have been the inciting event.

The basic physiologic abnormality in patients with chronic constrictive pericarditis is the inability of the ventricles to fill owing to

the limitations imposed by the rigid, thickened pericardium. Ventricular filling is unimpeded during early diastole but is reduced abruptly

when the elastic limit of the pericardium is reached, whereas in cardiac

tamponade, ventricular filling is impeded throughout diastole. In both

conditions, ventricular end-diastolic and stroke volumes are reduced

and the end-diastolic pressures in both ventricles and the mean pressures in the atria, pulmonary veins, and systemic veins are all elevated

to similar levels (i.e., within 5 mmHg of one another). Despite these

hemodynamic changes, systolic function may be normal or only

slightly impaired at rest. However, in advanced cases, the fibrotic process may extend into the myocardium and cause myocardial scarring

and atrophy, and venous congestion may then be due to the combined

effects of the pericardial and myocardial lesions.

In constrictive pericarditis, the right and left atrial pressure pulses

display an M-shaped contour, with prominent x and y descents. The

y descent, which is absent or diminished in cardiac tamponade, is the

most prominent deflection in constrictive pericarditis; it reflects rapid

early filling of the ventricles. The y descent is interrupted by a rapid

rise in atrial pressure during early diastole, when ventricular filling is

impeded by the constricting pericardium. These characteristic changes

are transmitted to the jugular veins, where they may be recognized by

inspection. In constrictive pericarditis, the ventricular pressure pulses

in both ventricles exhibit characteristic “square root” signs during

diastole. These hemodynamic changes, although characteristic, are not

pathognomonic of constrictive pericarditis and may also be observed

in restrictive cardiomyopathies (Chap. 259, Table 259-2).

■ CLINICAL AND LABORATORY FINDINGS

Weakness, fatigue, weight gain, increased abdominal girth, abdominal

discomfort, and edema are common. The patient often appears chronically ill, and in advanced cases, anasarca, skeletal muscle wasting, and

cachexia may be present. Exertional dyspnea is common, and orthopnea may occur, although it is usually not severe. The neck veins are

distended and may remain so even after intensive diuretic treatment,

and venous pressure may fail to decline during inspiration (Kussmaul’s

sign). The latter is common in chronic pericarditis but may also occur

in tricuspid stenosis, right ventricular infarction, and restrictive

cardiomyopathy.

The pulse pressure is normal or reduced. A paradoxical pulse can

be detected in about one-third of cases. Congestive hepatomegaly is

pronounced, may impair hepatic function, and may cause jaundice;

ascites is common and is usually more prominent than dependent

edema. Pleural effusions and splenomegaly may also be present. The

apical pulse is reduced and may retract in systole (Broadbent’s sign).

The heart sounds may be distant; an early third heart sound (i.e., a pericardial knock) occurring at the cardiac apex with the abrupt cessation

of ventricular filling is often conspicuous.

The ECG frequently displays low voltage of the QRS complexes

and diffuse flattening or inversion of the T waves. Atrial fibrillation is

present in about one-third of patients. The chest roentgenogram shows

a normal or slightly enlarged heart. Pericardial calcification is most

common in tuberculous pericarditis. Pericardial calcification may,

however, occur in the absence of constriction, and constriction may

occur without calcification.

Inasmuch as the common physical signs of cardiac disease (murmurs, cardiac enlargement) may be inconspicuous or absent in chronic

constrictive pericarditis, hepatic enlargement and dysfunction associated with jaundice and intractable ascites may lead to a mistaken diagnosis of hepatic cirrhosis. This error can be avoided if the neck veins

are inspected and found to be distended.

The transthoracic echocardiogram often shows pericardial thickening, dilation of the inferior vena cava and hepatic veins, and a sharp

halt to rapid left ventricular filling in early diastole, with normal

ventricular systolic function and flattening of the left ventricular posterior wall. There is a distinctive pattern of transvalvular flow velocity

on Doppler echocardiography (Fig. 270-4). During inspiration, there

is an exaggerated reduction in blood flow velocity in the pulmonary

veins and across the mitral valve, and a leftward shift of the ventricular septum; the opposite occurs during expiration. Diastolic flow

velocity in the inferior vena cava into the right atrium and across the

tricuspid valve increases in an exaggerated manner during inspiration

and declines during expiration. However, echocardiography cannot

definitively establish or exclude the diagnosis of constrictive pericarditis; CT and MRI are more accurate, with the latter useful in evaluating

myocardial involvement.

■ DIFFERENTIAL DIAGNOSIS

As with chronic constrictive pericarditis, cor pulmonale (Chap. 257)

may be associated with marked systemic venous hypertension, little

pulmonary congestion, a (left) heart that is not enlarged, and a paradoxical pulse. However, in cor pulmonale, advanced parenchymal

pulmonary disease is usually apparent and venous pressure falls during inspiration (i.e., Kussmaul’s sign is negative). Tricuspid stenosis

(Chap. 266) may also simulate chronic constrictive pericarditis with

congestive hepatomegaly, splenomegaly, ascites, and venous distention.

However, the characteristic murmur and that of accompanying mitral

stenosis are usually present.

Because it can be corrected surgically, it is important to distinguish chronic constrictive pericarditis from restrictive cardiomyopathy

(Chap. 259), which has a similar pathophysiologic underpinning (i.e.,

restriction of ventricular filling). The differentiating features are summarized in Table 270-2. When a patient has progressive, disabling, and

unresponsive congestive heart failure and displays any of the features of

constrictive heart disease, Doppler echocardiography to record respiratory effects on transvalvular flow (Fig. 270-4) should be performed and

an MRI or CT scan should be obtained to detect or exclude constrictive

pericarditis because the latter is usually correctable.

TREATMENT

Constrictive Pericarditis

Pericardial resection is the only definitive treatment of constrictive pericarditis and should be as complete as possible. Coronary

arteriography should be carried out preoperatively in patients aged

>50 years to exclude unsuspected accompanying coronary artery

disease. The benefits derived from cardiac decortication are usually

progressive over a period of months. The risk of this operation

depends on the extent of penetration of the myocardium by the

Atrial Myxoma and Other Cardiac Tumors

2025CHAPTER 271

fibrotic and calcific process, the severity of myocardial atrophy, the

extent of secondary impairment of hepatic and/or renal function,

and the patient’s general condition. Operative mortality is in the

range of 5–10% even in experienced centers; the patients with

the most severe disease, especially secondary to radiation therapy,

are at highest risk. Therefore, surgical treatment should, if possible,

be carried out as early as possible.

Subacute Effusive-Constrictive Pericarditis This form of

pericardial disease is characterized by the combination of a tense

effusion in the pericardial space and constriction of the heart by thickened pericardium. As such, it shares a number of features with both

chronic pericardial effusion producing cardiac compression and with

pericardial constriction. It may be caused by tuberculosis (see below),

multiple attacks of acute idiopathic pericarditis, radiation, traumatic

pericarditis, renal failure, scleroderma, and neoplasms. The heart is

generally enlarged, and a paradoxical pulse is usually present. After

pericardiocentesis, the physiologic findings may change from those

of cardiac tamponade to those of pericardial constriction. Furthermore, the intrapericardial pressure and the central venous pressure

may decline, but not to normal. The diagnosis can be established

by pericardiocentesis followed by pericardial biopsy. Wide excision

of both the visceral and parietal pericardium is usually effective

therapy.

Tuberculous Pericardial Disease This chronic infection is a

common cause of chronic pericardial effusion, especially in the

developing world where active tuberculosis and HIV are endemic.

Tuberculous pericarditis may present as pericardial effusion, chronic

constrictive pericarditis, or subacute effusive-constrictive pericarditis

(see above). The clinical picture is that of a chronic, systemic illness

in a patient with pericardial effusion. It is important to consider this

diagnosis in a patient with known tuberculosis, with HIV, and with

fever, chest pain, weight loss, and enlargement of the cardiac silhouette

of undetermined origin. If the etiology of chronic pericardial effusion

remains obscure despite detailed analysis including culture of the pericardial fluid, a pericardial biopsy, preferably by a limited thoracotomy,

should be performed. If definitive evidence is still lacking but the specimen shows granulomas with caseation, antituberculous chemotherapy

(Chap. 178) is indicated.

If the biopsy specimen shows a thickened pericardium after

2–4 weeks of antituberculous therapy, pericardiectomy should be performed to prevent the development of constriction. Tubercular cardiac

constriction should be treated surgically while the patient is receiving

antituberculous chemotherapy.

Acknowledgment

Eugene Braunwald wrote this chapter in the 20th edition, and some

material from that chapter has been retained here.

■ FURTHER READING

Alraies MC et al: Usefulness of cardiac magnetic resonance-guided

management in patients with recurrent pericarditis. Am J Cardiol

115:542, 2015.

Bayes-Coenis A et al: Cotchicine in pericarditis. Eur Heart J 38:1706,

2017.

Garcia MJ: Constrictive pericarditis versus restrictive cardiomyopathy? J Am Coll Cardiol 67:2061, 2016.

LeWinter MM: Acute pericarditis. N Engl J Med 371:2410, 2014.

Lotan D et al: Usefulness of novel immunotherapeutic strategies for

idiopathic recurrent pericarditis. Am J Cardiol 117:861, 2016.

Mircanda WR, Oh JK: Effusive-constrictive pericarditis. Cardiol Clin

3:551, 2017.

Vistarini N et al: Pericardiectomy for constrictive pericarditis. Ann

Thorac Surg 100:107, 2015.

Welch TD: Constrictive pericarditis: diagnosis, management, and

clinical outcomes. Heart 104:725, 2018.

Cardiac tumors can be broadly classified into those that arise primarily

in the heart and those that reflect metastatic disease from a distant

primary source. Primary cardiac tumors can be further divided into

those that are pathologically benign and those that are malignant.

Overall, primary cardiac tumors are relatively uncommon, whereas

secondary involvement of the heart or pericardium occurs in as many

as 20% of patients with end-stage metastatic cancer. While patients

with cardiac tumors may present with a variety of symptoms, many

patients are asymptomatic at the time of diagnosis, the tumor being

identified incidentally on imaging studies performed for other reasons.

Cardiac tumors need to be differentiated from other cardiac masses

such as vegetation, thrombus, inflammatory myofibroblastic tumors,

or myocardial hypertrophy. Echocardiography is usually the initial

imaging modality used to evaluate cardiac tumors; however, a variety

of imaging modalities are now available, and a multimodality approach

is often necessary for accurate diagnosis and clarification of treatment

options (Table 271-1).

■ PRIMARY TUMORS

Primary tumors of the heart are rare, occurring in ~1 in 2000 patients

in autopsy series. Approximately three-quarters are histologically

benign, the majority of which are myxomas. Malignant tumors, almost

all of which are sarcomas, account for 25% of primary cardiac tumors.

All cardiac tumors, regardless of pathologic type, have the potential to

cause life-threatening complications. Many tumors are now surgically

curable; thus, early diagnosis is imperative.

Clinical Presentation Cardiac tumors may present with a wide

array of cardiac and noncardiac manifestations. These manifestations,

which depend in large part on the location and size of the tumor as well

as its impact on surrounding cardiac structures, are often nonspecific

features of more common forms of heart disease, and include chest

271 Atrial Myxoma and Other

Cardiac Tumors

Eric H. Awtry

TABLE 271-1 Imaging Modalities and Their Utility in the Evaluation of

Cardiac Tumors

MODALITY UTILITY IN CARDIAC TUMOR EVALUATION

Transthoracic

echocardiography (TTE)

(including two-dimensional,

three-dimensional, and

contrast)

Assessment of tumor location and size and its

impact on adjacent structures (e.g., valves,

pericardium).

Transesophageal

echocardiography (TEE)

Improved tumor characterization and spatial

resolution compared with TTE. May aid in

determining surgical approach.

Cardiac MRI with

gadolinium contrast

Improved tissue characterization, definition

of tumor size, and identification of local

invasion when compared with TTE or TEE. May

differentiate tumor from thrombus.

Gated cardiac CT Provides anatomic assessment and tissue

characterization of the tumor. Useful when

patients cannot tolerate MRI or when MRI is not

feasible (e.g., patients with implantable cardiac

devices). Allows for better assessment of calcified

lesions and evaluation of extracardiac tumor

involvement.

Nuclear imaging (including

18F-fluorodeoxyglucose

positron emission

tomography [FDG-PET])

Definition of extracardiac disease. May be

useful in diagnosis of certain cardiac tumors

(e.g., neuroendocrine tumors), but assessment

of smaller tumors may be limited by surrounding

myocardial FDG uptake.