43 - 281 Pericardial Disease

281 Pericardial Disease

■ ■UNREPAIRED CYANOTIC CHD

Eisenmenger Syndrome  ES is felt to be the consequence of a long-standing high-volume or pressurized left-to-right shunt in which excessive blood flow to the pulmonary vasculature leads to severely increased pulmonary vascular resistance that eventually results in reversal of the shunt, creating bidirectional or right-to-left flow. ES is a multiple-organ condition and may occur with any CHD with an initial left-to-right shunt. The natural history of ES is variable, and although there is significant morbidity, in general, adults with ES appear to survive longer than those with other forms of pulmonary arterial hypertension. Medical care recommendations have included sustain­ ing adequate hydration, avoiding, and treating anemia including iron supplementation when appropriate, and anticoagulation (although this remains controversial due to predisposition to bleeding and occur­ rence of clinical hemoptysis, which has frequently been associated with pulmonary vascular thrombosis). Elevation of hematocrit above that considered appropriate for the degree of cyanosis can be managed in symptomatic patients by hydration alone or, on occasion, by perform­ ing phlebotomy with isovolumic replenishment. Routine phlebotomy in the asymptomatic adult with ES is contraindicated. Appropriate optimization of iron stores has been demonstrated to improve qual­ ity of life and functional performance in iron-deficient adults with ES. Contraception for women with ES who are of childbearing age is strongly recommended, avoiding use of estrogen, which may be throm­ bogenic. Pregnancy is contraindicated in these women due to the high risk of maternal mortality. PART 6 Disorders of the Cardiovascular System Selective pulmonary vasodilators, such as bosentan or sildenafil, are efficacious in ES. Select patients may be candidates for combined heart–lung transplantation or preferably lung transplantation with concomitant repair of the intracardiac defect, if feasible. The Role of Palliative Care in ACHD  In aggregate, adults with CHD demonstrate both quality-of-life–limiting comorbidities and premature mortality far in excess of age-matched controls. The reported prevalence of pain, anxiety, depression, dyspnea, and fatigue appears similar to that reported for adults who are decades older and engaged in palliative care for acquired cardiovascular disease at end of life (EOL). Similarly, at EOL with ACHD, frequencies of hospital­ ization, intensive care admission, 30-day readmission, and increased length of hospital stay appear greater (despite younger age) than for adults with cancer. In a retrospective study of ACHD patients who died during a hospital admission, only a minority had engaged in EOL discussions with their providers. Surveys of both adults with CHD and their providers suggest that the overwhelming majority of patients wish to participate in advanced care planning and discussion of palliative care; this contrasts with statements from ACHD care providers noting their uncertainties regarding EOL prognostication and concerns over discussion about EOL. Palliative care specialists who are embedded within or aligned with ACHD care teams can play an important and iterative role in defining and addressing alignment of patient and clini­ cian goals within the boundaries of frequently complex care decisions over the adult life span. Global Considerations  As survival patterns improve for all medically complex patients, the internist and general practitioner are faced with particular challenges and dilemmas; foremost is accrual of 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 perfor­ mance, 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 sup­ port, so as to achieve optimal outcomes. ■ ■FURTHER READING Gilboa SM et al: Congenital heart defects in the United States: Esti­ mating 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. Holzer R et al: PICS/AEPC/APPCS/CSANZ/SCAI/SOLACI: Expert consensus statement on cardiac catheterization for pediatric patients and adults with congenital heart disease. JACC Cardiovasc Interv 17:115, 2024. Regitz-Zagrosek V et al: 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 39:3165, 2018. Sachdeva R et al: ACC/AHA/ASE/HRS/ISACHD/SCAI/SCCT/ SCMR/SOPE 2020 Appropriate Use Criteria for non-invasive mul­ timodality imaging during the follow-up care of patients with con­ genital heart disease: A report of the American College of Cardiology Solution Set Oversight Committee and Appropriate Use Criteria Task Force, American Heart Association, American Society of Echo­ cardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomogra­ phy, Society for Cardiovascular Magnetic Resonance, and Society of Pediatric Echocardiography. J Am Coll Cardiol 75:657, 2020. Silversides CK et al: Pregnancy outcomes in women with heart dis­ ease: 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 Col­ lege of Cardiology/American Heart Association Task Force on Clini­ cal Practice Guidelines. Circulation 139:e698, 2019. Joseph Loscalzo

Pericardial Disease ■ ■NORMAL FUNCTIONS OF THE PERICARDIUM The normal pericardium is a double-layered sac of the visceral pericar­ dium 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 nor­ mal pericardium, by exerting a restraining force, prevents sudden dila­ tion 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 281-1), 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,

TABLE 281-1  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, post-acute COVID, mpox) 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 autoinflammatory syndromes I. Familial pericarditis
3. 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, IgG4 disease) C. Drug-induced (e.g., procainamide, hydralazine, phenytoin, isoniazid, minoxidil, anticoagulants, methysergide) D. Postcardiac injury
4. Postpericardiotomy
5. Posttraumatic
6. Postmyocardial infarction (Dressler’s syndrome) aAn autosomal recessive syndrome characterized by growth failure, muscle hypotonia, hepatomegaly, ocular changes, enlarged cerebral ventricles, intellectual disability, ventricular hypertrophy, and chronic constrictive pericarditis. Abbreviation: COVID, coronavirus disease. 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, confu­ sion with acute myocardial infarction (AMI) is common. Charac­ teristically, pericardial pain may be intensified by lying supine and relieved by sitting up and leaning forward (Chap. 15). Pain is often absent in slowly developing tuberculous, postirradiation, neoplastic, and uremic pericarditis. The differentiation of AMI from acute pericarditis may be chal­ lenging when, with the latter, serum biomarkers of myocardial damage rise, presumably 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 superficial (sub-)epicardial injury despite often 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

CHAPTER 281 approximately 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. 246); it is heard most frequently at end expiration with the patient upright and leaning forward. 3. The electrocardiogram (ECG) in acute pericarditis without massive Pericardial Disease effusion usually displays changes secondary to acute subepicardial inflammation (Fig. 281-1A), 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 effu­ sion 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 depression is usually more prominent; these changes may return to normal within a day or two (Chaps. 285 and 286). 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. 281-1B). 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 fric­ tion 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 egophony beneath the angle of the left scapula. The chest x-ray may show enlargement of the cardiac silhouette, with a “water bottle” configuration, but may be normal in patients with small effusions. Diagnosis  Echocardiography (Chap. 248) is the most widely used imaging technique. It is sensitive, specific, simple, and noninvasive; may be performed at the bedside; and allows localization and estima­ tion 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 ventricle and the parietal pericardium just beneath the anterior chest wall (Fig. 281-2). 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. 281-3). TREATMENT Acute Pericarditis There is no specific therapy for acute idiopathic pericarditis, but bed rest may be recommended, and anti-inflammatory treat­ ment with aspirin (2–4 g/d) or nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (600–800 mg tid) or indo­ methacin (25–50 mg tid), should be administered along with gastric protection (e.g., omeprazole 20 mg/d). In responsive

I aVR PR ST PART 6 Disorders of the Cardiovascular System II aVL III aVF A aVR V1 V4 I aVL V2 V5 II aVF V3 V6 III II B FIGURE 281-1  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. patients, these doses should be continued for 1–2 weeks and then tapered over several weeks. In addition, colchicine (0.5 to 0.6 mg qd [<70 kg] or 0.5 to 0.6 mg bid [>70 kg]) should be adminis­ tered for 3 months. Colchicine enhances the response to NSAIDs FIGURE 281-2  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.)

V1 V4 ST PR V2 V5 V3 V6 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 pericardi­ tis 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 pericar­ dial cavity and tamponade. In patients with multiple, frequent, and disabling recurrences that continue for >2 years, are not prevented by continuing colchi­ cine 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 man­ aged as outpatients with careful follow-up. However, when specific causes (tuberculosis, neoplastic disease, bacterial infection) are sus­ pected, or if any of the predictors of poor prognosis (fever >38°C, subacute onset, large pericardial effusion, immunosuppression, or evidence of pericardial tamponade) are present, hospitalization is advisable.

RV LV LV A B FIGURE 281-3  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.) ■ ■CARDIAC TAMPONADE The accumulation of fluid in the pericardial space in a quantity suf­ ficient 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 hypo­ tension, 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 reduc­ tions 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. TABLE 281-2  Features That Distinguish Cardiac Tamponade from Constrictive Pericarditis and Similar Clinical Disorders CONSTRICTIVE PERICARDITIS CHARACTERISTIC TAMPONADE 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; CT, computed tomography; ECG, electrocardiogram; MRI, magnetic resonance imaging; RV, right ventricle. Source: Reproduced with permission from GM Brockington et al: Constrictive pericarditis. Cardiol Clin 8:645, 1990.

LA AO CHAPTER 281 * * Pericardial Disease * 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, hypoten­ sion, 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. 281-1). Table 281-2 lists the features that distinguish acute cardiac tamponade from constrictive pericarditis. 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 RIGHT VENTRICULAR MYOCARDIAL INFARCTION RESTRICTIVE CARDIOMYOPATHY EFFUSIVE CONSTRICTIVE PERICARDITIS

Inspiration Expiration Septum E Septum E A A TV TV MV MV LV RV PART 6 Disorders of the Cardiovascular System Doppler transvalvular inflow patterns Thickened pericardium RA Pulmonary vein LA DIASTOLE DIASTOLE IVC and hepatic veins Apical 4-chamber views FIGURE 281-4  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.) causes leftward bulging of the interventricular septum, reducing left ventricular volume, stroke volume, and arterial systolic pressure. Para­ doxical 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. 286) may resemble cardiac tamponade with hypotension, elevated jugular venous pres­ sure, a slow y descent in the jugular venous pulse, and, occasionally, a paradoxical pulse (Table 281-2). 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. 281-4). 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, peri­ cardiocentesis should be performed or the patient watched closely for signs of tamponade with serial echocardiography and monitor­ ing 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, intraperi­ cardial pressure should be measured before fluid is withdrawn, and 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 drain­ ing 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 cardiac trauma. 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 and/or of an elevated adenosine deaminase strongly supports the diagnosis of tuberculous pericar­ ditis; however, it is often necessary to obtain pericardial tissue to make this diagnosis (Chap. 183). ■ ■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, adeno­ virus, 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 effu­ sion 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 pericar­ ditis 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 dis­ appear 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 pos­ sible, but infrequent, complications. The most frequent complication is recurrent (relapsing) pericardi­ tis, which occurs in approximately 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. 283), 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, pleuri­ tis, and pneumonitis are accompanying features, and the illness usually subsides in 1 or 2 weeks. The pericarditis may be of the fibrinous vari­ ety, 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 hypersensitiv­ ity (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 recur­ rences, 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 peri­ carditis 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 opera­ tion, 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 dif­ ferential diagnosis is the pericarditis due to systemic lupus erythemato­ sus (SLE; Chap. 368) or drug-induced (hydralazine or procainamide) lupus. When pericarditis occurs in the absence of any obvious under­ lying disorder, the diagnosis of SLE may be suggested by a rise in the titer of antinuclear antibodies. Acute pericarditis is an occasional com­ plication 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 cardiotho­ racic 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 endocardi­ tis. 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 vigor­ ous 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 persis­ tent, 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 281-1). ■ ■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 chyloperi­ cardium 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. Pericar­ dial fluid 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 pericar­ diectomy may be required in patients with recurrence. Intrapericardial instillation of sclerosing agents may be used to prevent reaccumula­ tion of fluid, most commonly in recurrent neoplastic effusions.

CHRONIC CONSTRICTIVE PERICARDITIS This disorder results when the healing of an acute fibrinous or serofi­ brinous 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.

CHAPTER 281 Pericardial Disease The basic physiologic abnormality in patients with chronic constric­ tive 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 pres­ sures 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 pro­ cess 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 the characteristic “square root” sign during diastole. These hemodynamic changes, although characteristic, are not pathognomonic of constrictive pericarditis and may also be observed in restrictive cardiomyopathies (Chaps. 266–270, Table 266-1). ■ ■CLINICAL AND LABORATORY FINDINGS Weakness, fatigue, weight gain, increased abdominal girth, abdominal discomfort, and edema are common. The patient often appears chroni­ cally ill, and in advanced cases, anasarca, skeletal muscle wasting, and cachexia may be present. Exertional dyspnea is common, and orthop­ nea 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 cessa­ tion 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