Pericarditis and Myocarditis 13

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From: Contemporary Cardiology: Heart Disease Diagnosis and Therapy:

A Practical Approach, Second Edition

Edited by: M. Gabriel Khan © Humana Press Inc., Totowa, NJ

13 Pericarditis and Myocarditis

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PERICARDITIS

In more than 90% of patients with acute pericarditis the cause of the disease is unknown (idiopathic: viral). The common causes of pericarditis are listed in Table 13.1. The clas- sification into:

• causes based on the presence of an easily recognizable underlying disease.

• those caused by adverse reactions (easily excluded by history).

• and due to viral or unknown (idiopathic) causes, provides for easy recall.

Clinical Hallmarks Chest pain is typically:

• Retrosternal or left precordial.

• Occasionally radiates to one or both trapezius ridges (a radiation that does not occur with angina); may radiate to the neck or left arm and may simulate angina or myocardial infarc- tion (MI).

• At times localized to the epigastrium or left upper quadrant.

• Sharp, pleuritic, but may be described as an oppressive, dull, vague ache.

• Increased by deep inspiration, coughing, swallowing, recumbency.

• Relieved by sitting and leaning forward.

Genuine shortness of breath, forced shallow breathing owing to pain, and palpitations are common features. Underlying infection may cause fever and myalgia. A pericardial friction rub observed in about 85% of patients is characteristically:

• Heard between the lower left sternal edge and apex.

• Localized to any area or over most of the precordium.

• Heard with the diaphragm pressed firmly against the chest wall, with the patient leaning forward with the breath held at end expiration.

• Variable in intensity from minute to minute and can be missed (this calls for repeated auscultation).

• Triphasic in about half of patients, biphasic in one-third.

• High-pitched scratchy or squeaky.

Electrocardiogram Findings

The four stages of the electrocardiographic abnormalities are given in Table 13.2.

Because tachycardia is common, it may be the only electrocardiographic finding if supraventricular tachycardia (ST) elevation has resolved and the T-waves remain normal.

• The electocardiogram (ECG) obtained at the earliest stage of acute pericarditis usually reveals (PR) segment depressions in most leads and PR segment elevation in aVR, occasionally in V₁ (Fig. 13.1.,Table 13.2.). Typical ECG changes are observed in more than 80% of patients with pericarditis.

• Some patients manifest only PR segment depressions, which are misinterpreted as ST elevations, normal variant. Spodick points out that marked and widespread PR depres- sions are virtually never observed in early repolarization pattern, and sometimes only ST (J-point) deviations occur in acute pericarditis without PR deviations and these may resemble those observed in early repolarization; in such ECGs and in most patients with acute pericarditis, the J-point height in lead V₆ measures more than 25% of the height of the T-peak from the baseline.

• ST-segment elevation, when present, is a J-point ST elevation concave upward (anormal shape) with no T-wave inversion, whereas with MI, the ST segment is convex, often with emerging Q-waves present and the T-waves begin to invert before the ST segment nor- malizes. The ST segment is depressed in lead aVR and sometimes minimally in V₁. T^ROPONIN L^EVELS

Imazio et al. have shown that in viral or idiopathic acute pericarditis troponin elevation is frequently observed and is associated with male gender, magnitude of the ST-segment elevation, and pericardial effusion at presentation. The increase in troponin observed in

Table 13.1.

Causes of Pericarditis 1. Underlying diseases

Viral infections: Coxsackie B₅ B₆, echovirus, HIV, Epstein-Barr, Influenza, mumps, varicella, rubella; mycoplasma

Post-MI: early, late Aortic dissection

Cardiotomy, thoracic surgery Renal failure

Neoplastic Tuberculosis

Septicemia (purulent) Endocarditis

Collagen disease: vasculitis, rheumatic fever, rheumatoid arthritis, lupus, scleroderma (>30 individual forms)

Myxedema

Trauma: iatrogenic: surgery, catheter, pacemaker 2. Adverse reactions easily excluded by history

Drugs: anticoagulants, cromolyn, daunorubicin, dantrolene, hydralazine, isoniazid, methysergide, minoxidil, procainamide, phenytoin; radiation

3. Idiopathic: probable viral (specific diagnosis unidentified)

more than 45% of patients is roughly related to the extent of myocardial inflammatory involvement; unlike acute coronary syndromes, elevated levels do not predict an adverse outcome. Elevated levels usually returned to normal within 1 to 2 weeks and myocarditis should be suspected if these persist beyond 2 weeks.

Echocardiography

The finding of a pericardial effusion helps to confirm the diagnosis. Echocardiography is necessary to detect and quantitate associated pericardial effusion and in assessing tamponade (Fig. 13.2.).

Idiopathic and Viral Pericarditis

Most cases of so-called idiopathic pericarditis are caused by viral infections (Table

of tamponade is manifested by hemodynamic compromise, elevation of the jugular venous pressure (JVP), and pulsus paradoxus and hypotension; the latter may mask pulsus paradoxus.

Echocardiography is helpful to confirm the diagnosis or tamponade (Fig. 13.2.).

Pericardiocentesis is not done routinely, even with moderate-sized effusions, if tampon- ade is not present. Pericardiocentesis may be necessary for diagnosis, for example, viral, bacterial, or molecular biological studies. If pain is bothersome, the patient should rest in bed and chair for a few days, followed by slow ambulation over 1–2 weeks.

After a few days to 1 week of acute pericarditis, the ST segments return to the isoelec- tric level, there is widespread T-wave inversion, typical of the second stage of acute pericarditis. Occasionally, the ST-segment elevation resolves and there is no progression to the second stage.

MANAGEMENT OF P^{AIN IN} A^CUTE PERICARDITIS

• Physical activity may worsen nonsignificant myocarditis reflected by ST segment and T-wave changes; thus, activities should be curtailed for the first week and monitored depending on symptomatology, ECG, and echocardiographical findings.

• Pain is usually relieved by the nonsteroidal anti-inflammatory drugs (NSAIDs): 400–

800 mg of ibuprofen every 8 hours, the combination of ibuprofen and colchicine, have been shown to be rapidly effective, with symptomatic relief within 1–3 days if acute pericarditis is the correct diagnosis.

• 0.6 mg of colchicine twice daily has been shown to be effective, used alone or in com- bination. Most important colchicine has been shown to prevent recurrent pericarditis.

• Indomethacin usually controls pain but may reduce coronary low and has more adverse effects compared with ibubrofen.

• All NSAIDS (selective and nonselective) are contraindicated with acute MI, however, because myocardial healing and scar formation appear to be impaired by these agents.

Table 13.2.

ECG Clues to Pericarditis

Stage I (hours to days) Widespread ST-segment elevation 2–5 mm concave upward and PR depression in leads I, II, III, V₂–V₅; reciprocal depression aVR, V₁

Stage II (few days later) ST and PR segments isoelectric, upright, or flattened T

Stage III After normalization of ST segment, diffuse T-wave inversion occurs Stage IV (days to weeks) T-waves normalize, rarely remain inverted

Fig. 13.1. Acute pericarditis (ST stage) widespread ST-segment elevation with upward concavity in leads I, II, aVF, V2 to V6, with ST-segment depression in aVR. Note the PR segment depression in many leads, and PR depression in aVR.

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• Randomized clinical trials of NSAIDs are not available, but several reports indicate clearly that combined therapy is usually effective within 1–3 days. Combined therapy is advisable for 7–14 days then slow tapering of doses for 1 or 2 weeks to prevent early recurrence.

Corticosteroids. An oral corticosteroid should only be used if it is also indicated for

an underlying disease or if the patient’s syndrome is severe and resistant to the combi- nation of colchicines and ibuprofen. It is not advisable to commence corticosteroids solely for the relief of pain, because these agents may increase viral replication. Recur- rence of pericarditis and a bothersome, corticosteroid-dependent, and disabling syn- drome have been ascribed to corticosteroid therapy, albeit, rarely. Corticosteroids are indicated when there is total failure of high-dose NSAIDs and colchines used over several weeks and with relapsing pericarditis not controlled by NSAIDs and colchines.

Dexamethasone. A dosage of 4 mg intravenously (IV) may relieve pain in a few hours.

Predinisone. A dosage of 60 mg daily for a few days is used and decreased by 10 mg

every 3–5 days until a dose of 15 mg is reached. If symptoms are controlled, it is advisable to give 15 mg on alternate days for 5 days and then 10 mg alternate days for 5 days, 5 mg alternate days for 5 days, and discontinue. The course of prednisone should be tapered as quickly as feasible. NSAIDs are added at an adequate dosage, when the corticosteroid dose has reached 15 mg daily.

Fig. 13.2. Cardiac tamponade in a patient with carcinoma of the lung. M-mode and two-dimen- sional echocardiogram reveal a large pericardial effusion with a swinging heart motion, diastolic collapse of the right ventricle and left atrium and electrical alternans. Note in the M-mode tracing that when the cardiac wall swings anteriorly, the QRS voltage is high (arrow) and low (arrow) when it swings posteriorly. Ao, aorta; RV, right ventricle; LV, left ventricle; LA, left atrium; PE, pericardial effusion; CW, continuous wave. From Gazes PC. Clinical cardiology. Philadelphia:

Lea & Febiger, 1990, p. 374. Reprinted with permission.

Recurrent Pericarditis

• Colchicine dosage: 2 mg loading dose, then 1 mg daily. Approximately 25% of patients experience recurrence; if effusion develops, the risk of tamponade is high in this subset.

In the absence of heart failure (HF) or tamponade, colchicine causes beneficial effects and is advisable.

• The salutary effects may be caused by colchicine binding to membrane proteins and interference with polymorph leukocyte function.

• Patients with chest pain unrelieved by adequate doses of NSAIDs and colchicines may require corticosteroids for control of pain, fever, and shortness of breath. Alternate-day therapy carries less risk of adverse effects.

• In patients with relapsing pericarditis who do not respond to drug therapy, particularly chronic colchicine use, peri-cardiocentesis may be required.

Specific Causes of Pericarditis

Acute pericarditis occurs in approximately 10% of patients within 10 hours–10 days after infarction. The pain may be confused with postinfarction angina, extension of infarction, or pulmonary embolism. Most cases occur on the third or fourth day postinfarction. Chest pain is best treated with aspirin. NSAIDs, such as indomethacin, ibuprofen, naproxen, and cyclooxygenase-2 (COX-2) inhibitors should be avoided be- cause they appear to interfere with the healing of infarcted tissue and have been shown to cause infarct expansion and accelerate remodeling.

Dressler’s syndrome occurs in less than 0.1% of patients, usually weeks or months after MI, and may be an immune reaction. This condition is currently no longer observed.

P^URULENT PERICARDITIS

Purulent pericarditis usually occurs during septicemia caused by pneumococcus,

indicated in patients suspected of purulent pericarditis to isolate micro-organisms and determine sensitivities and the appropriate choice of antibiotics. Cardiothoracic surgical assistance often is required for open pericardial drainage or creation of a pericardiopleural window.

T^UBERCULOUS PERICARDITIS

In Asia, Africa, the Middle East, Latin America, and some nonindustrialized countries, tuberculosis is the most common cause of pericarditis. In North America and Europe, tuberculosis is responsible for about 4%, 7%, and 6% of acute pericarditis, tamponade, and constrictive pericarditis, respectively.

Diagnosis requires isolation of mycobacterium tuberculosis in pericardial fluid or a histological examination of pericardial tissue or proven active tuberculosis in other organs.

Tuberculous pericarditis is more common in blacks, is commonly seen in patients with acquired immunodeficiency syndrome (AIDS), and has a peak incidence in patients between 30 and 60 years of age.

Symptoms and signs include the following:

• Cough; weight loss; dyspnea, occasionally orthopnea; fever, chills, and night sweats may be present for several months before signs of pericarditis occur; cardiomegaly; a pericar- dial friction rub plus signs of tamponade may develop; hepatomegaly occurs in over 90%

of patients; and ascites is fairly common.

Echocardiographic and computed tomography (CT) examination may reveal pericar- dial effusion and pericardial thickening. The patient should be hospitalized, observed for tamponade, and given therapy with isoniazid (300 mg), pyridoxine (50 mg), rifampin (600 mg), and ethambutol (15 mg/kg) daily for at least 9 months, allowing a minimum of 6 months of drug treatment after culture conversion. The combination of isoniazid (300 mg) and rifampin (600 mg) daily for 9 months has been shown to produce a satisfactory response in 95% of patients with extrapulmonary tuberculosis.

Corticosteroid Therapy

Corticosteroid therapy is indicated for recurrent or persistent pericardial effusion in patients receiving adequate courses of antituberculous therapy. This therapy may avoid constrictive pericarditis and pericardial resection, which appears to be required in 7–40%

of patients adequately treated with antituberculous drugs. Although some series show a high incidence of pericardial constriction, pericardiectomy is not routinely recommended.

In a study by Strang et al., only 17 of 240 patients treated with prednisolone in addition to antituberculous drugs for 11 weeks required pericardiectomy, and prednisolone therapy reduced overall mortality from 14 to 3%.

A 40–60 mg dosage of prednisone or prednisolone daily is given in two divided doses.

Uremic Pericarditis

Pericardiocentesis is required only if there is suspicion of purulent infection or tam- ponade. The condition usually subsides with more frequent dialysis. Recurrent effusions uncontrolled by dialysis may respond to instillation of triamcinolone into the pericardial sac.

The instillation of sclerosing agents is of benefit in some patients with neoplastic pericarditis.

CARDIAC TAMPONADE Tamponade may occur acutely secondary to the following:

• Cardiac surgery or chest trauma: an individual who has sustained recent chest trauma and appears in shock with increased venous pressure should be suspected of having cardiac tamponade.

• Acute MI with free-wall rupture (see Chapter 2).

• Dissecting aneurysm.

• Acute or subacute presentations occasionally occur with neoplastic involvement, non- specific pericarditis, and uremia or purulent infections

Diagnostic Hallmarks

Sudden progressive severe shortness of breath, chest tightness, dysphagia, and periph- eral cyanosis may herald the shock-like state. The JVP is usually elevated. Acute hemo- pericardium may cause jugular pulsations without much distention because there is not sufficient time for blood volume to increase. Dilation of veins in the forehead, scalp, and fundi, may be observed. Hypotension and tachycardia are usually present. A pericardia rub may be present particularly in patients with inflammatory effusions.

• Cardiac tamponade is a form of cardiogenic shock and the differential diagnosis includes causes of cardiogenic shock (see Chapter 3, Table 3.1.).

• Significant pulsus paradoxus is usually detectable except when severe hypotension or elevation of the diastolic pressure of either ventricle is present. Studies between 1991 and 1999 give its prevalence between 12 and 75%.

Thus, the physician should not be lulled into a sense of false security by the absence of paradoxus.

• Pulsus paradoxus is an exaggeration of the normal inspiratory decline of systemic arterial pressure and is therefore not actually “paradoxic.” To determine the presence of signifi- cant pulsus paradoxus, the patient’s respirations are observed while slowly deflating the blood pressure (BP) cuff. Initially, the Korotkoff sound is heard only on expiration, but as the cuff pressure is lowered, Korotkoff sounds are heard during inspiration; the dif- ference in systolic blood pressure (SBP) recorded at the commencement of the Korotkoff sounds in inspiration and expiration is an estimate of pulsus parodoxus.

• Normally, this difference is less than 10 mmHg. Pulsus paradoxus greater than 12 mmHg is significant.

In patients with a very low cardiac output pulsus paradoxus is often not detected by this method and a catheter is needed for it to be identified. Pulsus paradoxus may be palpable in muscular arteries.

Muffled heart sounds represent another characteristic feature, although not a diagnos- tic hallmark.

Pulsus paradoxus may be observed in several conditions, including the following:

• Severe chronic obstructive pulmonary disease (COPD), status asthmaticus.

• Pneumothorax.

• Massive pulmonary embolism.

• The many forms of severe hypotension including profound hemorrhagic shock.

In COPD and asthma, the JVP falls normally on inspiration. With right ventricular (RV) infarction, the venous pressure is high but increases on inspiration (Kussmaul’s sign), and pulsus paradoxus is absent. Massive pulmonary embolism may produce a shock-like state with markedly elevated JVP and represents a diagnostic challenge, but the clinical setting usually assists in differentiating the two conditions.

Severe HF causing marked elevation of JVP can be confused with cardiac tamponade.

It is important to differentiate the two conditions, because the use of diuretics is contrain- dicated in the presence of tamponade. Because the most common cause of right HF is left HF, pulmonary congestion is usually detectable with the presence of crackles, third heart sound, radiological evidence of pulmonary congestion, and left ventricular (LV) failure.

Pulsus paradoxus is not a feature of severe HF, and the presence of a V-wave in the venous pulse indicates tricuspid regurgitation.

Conditions that they cause in the absence of diagnostic pulsus paradoxus in patients with cardiac tamponade include the following:

• Cardiac regional tamponade causing hemodynamic deterioration may occur within the first 2 weeks of cardiac surgery or in conditions causing adhesions and local cardiac compression by loculated fluid. In these situations, pulsus paradoxus may be absent and the echocardiogram may fail to show effusion all around the heart.

• Extreme hypotension that may occur during severe tamponade may make respiration induced pressure changes.

• Unmeasurable pericardial adhesions particularly over the right heart that impede vol- ume changes.

• Acute LV failure caused by MI with effusion causing tamponade.

• Severe aortic regurgitation with or without severe LV failure may produce sufficient regurgitant flow to dampen respiratory fluctuations.

ECG Findings

Electrial alternans; combined P and QRS alternation is a diagnostic hallmark, virtually specific for cardiac tamponade (Fig. 13.2.).

Alternation confined to the QRS complex: every other QRS complex is of smaller voltage is more common than combined P and QRS alternation, but rare cases of very large effusions without tamponade may cause QRS alternans.

Chest X-Ray

• More than 200 mL of fluid must accumulate before the cardiac dimensions and silhouette are affected.

• The volume of most nonhemorrhagic effusions that cause tamponade is 300–600 mL.

Definite pericardial-fat lines observed on the lateral film indicate a large effusion.

• A large cardiac silhouette in a patient with clear lung fields associated with severe acute shortness of breath, elevated JVP and hypotension or cardiogenic shock state suggests tamponade. Although the chest X-ray is not diagnostic, it is often done initially in the workup of virtually all patients with a shocklike state.

Echocardiography

In patients with suspected cardiac tamponade, urgent echocardiography is mandatory.

Echocardiographic hallmarks are: diastolic chamber collapses of the right atrium, right ventricle, or both, occasionally the left atrium and rarely the left ventricle.

• An early finding of diastolic right atrial collapse, which occurs in most cases except regional tamponade, in which right or left atrial collapse may be observed (Fig. 13.2.);

right atrial collapse is more specific if inward movement occupies more than 30% of the cardiac cycle. Right atrial collapse is seen also in some patients with hypovolemia with- out tamponade; this may occur in patients with multiple trauma with chest and pericardial involvement because bleeding elsewhere depletes blood volume.

• Diastolic right ventricular collapse is a less sensitive, but specific finding.

• Left atrial collapse is highly specific, but occurs in less than 25% of patients.

• A swinging heart and electrical alternans may occur (Fig. 13.2.).

Management

Management of tamponade involves the maintenance of an adequate preload so as to generate stroke volume.

Thus, diuretics and preload-reducing agents, such as nitrates and angiotensin-converting enzyme (ACE) inhibitors, must be avoided. Volume expansion with saline and even trans- fusion with packed red cells may provide hemodynamic stability until pericardiocentesis is accomplished. It is important to maintain volume expansion so that right atrial pressure may be maintained above intrapericardial pressure to prevent right atrial or ventricular collapse.

The volume expansion strategy is controversial, however, and is instituted only as a

temporary measure until pericardiocentesis is done. A 16 or 18 gage polytetra-

fluoroethylene sheathed needle with a steel core is used, and the steel core withdrawn

when the pericardial-fluid area is reached.

Pericardiocentes should be carried out by an experienced cardiologist under echocardiographic control or by a cardiac thoracic surgeon.

A paraxiphoid needle insertion is advised. The needle should be aimed toward the left shoulder. Insert the needle between the xiphoid process and left costal margin, then angle the hub of the needle about 15° above the skin to bypass the costal margin. The hub is then depressed so the point of the needle is aimed toward the left shoulder and advanced to pierce the pericardium with echocardiographical guidance if an apical insertion is used the needle is aimed internally.

An indwelling pericardial catheter with multiple side holes (pigtail angiographic cath- eter) may be used for drainage and for installation of antibiotics, triamcinolone, or che- motherapeutic agents. Failure of pericardiocentesis is usually owing to a posteriorly located effusion. Reaccumulation of fluid and recurrent tamponade are indications for subxiphoid pericardial window drainage carried out by a cardiothoracic surgeon.

CONSTRICTIVE PERICARDITIS

The proper management of constrictive pericarditis begins with correct diagnosis.

Common causes include the following:

• Neoplastic disease, especially carcinoma of lung or breast, asbestosis and lymphoma.

• Mediastinal irradiation.

• Nonviral pericardial infections.

• Postviral pericarditis.

• Tuberculosis (the most common cause in third-world countries).

• Postcardiac surgery.

• Chest trauma.

• Connective tissue diseases, particularly rheumatoid arthritis.

• Chronic renal failure and dialysis.

Diagnostic Hallmarks

If the JVP is both markedly and chronically elevated and the patient’s history and physical examination fail to suggest an apparent cardiac cause in the presence of a small quiet heart, then a restrictive syndrome must be considered, the most common cause being constrictive pericarditis.

Neck vein examination should reveal Kussmaul’s sign, which may be difficult to elicit when the venous pressure is severely elevated. The venous pulse usually has a prominent y-descent (a major negative wave), coincident with the early rapid diastolic filling of the ventricle. A prominent x-descent, coincident with filling of the atrium, is often observed in patients with sinus rhythm. The exaggerated x- and y-descents give the venous pres- sure a characteristic M- or W-shaped pattern (Table 13.3).

Auscultation should reveal the presence of an early high-frequency third heart sound (S

) caused by abrupt cessation of early diastolic filling. This sound, referred to as a pericardial knock, occurs earlier than the conventional S

of HF and has a sharp high- pitched quality that is easily heard with the diaphragm and may mimic an opening snap or early filling sound heard in endomyocardial fibrosis.

Atrial fibrillation (AF) occurs in approximately 33% of cases of constrictive pericarditis.

The presence of marked ascites, occurring days to weeks before the presence of sig-

nificant edema, points strongly to constrictive pericarditis and serves to distinguish the

condition from HF, in which prominent edema occurs and is followed weeks later by mild

ascites. In a few patients with long-standing constriction and congestion, protein-losing gastroenteropathy may ensue.

Differential Diagnosis

Patients who present with noncalcific constrictive pericarditis pose a diagnostic problem.

H^EART F^AILURE

HF not caused by constrictive pericarditis can be difficult to differentiate. The pres- ence of a pericardial knock and marked ascites developing before leg edema favor the diagnosis of constrictive pericarditis. Also, severe HF causing chronically elevated JVP is invariably associated with tricuspid regurgitation and prominent V-waves. The heart size is usually normal with constrictive pericarditis, and calcification may be apparent, depending on the causation.

Constrictive Pericarditis vs Restrictive Cardiomyopathy

Constructive pericarditis Restrictive cardiomyopathy Clinical features

Heart size Usually normal Usually large

Heart impulse Quiet LV and/or right ventricular

dilatation

JVP M-pattern^a M-pattern

Kussmaul’s sign Present Present

Systolic (v) waves Absent Present (tricuspid regurgitation)

Systolic murmurs Rare Common

S₃ gallop^b Present Present (except in amyloid)

Chest X-ray Clear lung fields Similar

Normal heart size Similar or moderately enlarged Pericardial calcification (50%) Rare

Myocardial calcification not uncommon

ECG P-mitrale Uncommon

Atrial fibrillation 33% Common Conduction defects uncommon Common

Flat or inverted T-waves Widespread T-wave inversion common

May show low voltage Low voltage common

Q-waves very rare QS precordial leads pseudoinfarction pattern common

Echocardiogram Thickened pericardium

Calcified pericardium No pericardial calcification, myocardial calcification Normal septal motion

Systemic disease Tuberculosis Amyloid; sarcoid;

(associated) tuberculosis

CT or MRI Thickened pericardium Normal pericardium

aDue to exaggerated x- and y-descents.

bPericardial knock.

JVP, jugualr venous pressure; CT, computed tomography; MRI, magnetic resonance imaging; LV, left ventricular.

RV INFARCTION

RV infarction may produce a similar picture. RV infarction usually presents, however, in the setting of an acute MI and often with inferoposterior involvement. The condition is acute and presents with a high JVP associated with hypotension. Constrictive pericardi- tis is a chronic condition with insidious appearance of symptoms and signs.

R^IGHT A^TRIAL M^YXOMA

Myxoma should produce a prominent A-wave in the venous pulse, may mimic tricus- pid stenosis and requires echocardiographical exclusion.

RESTRICTIVE CARDIOMYOPATHY

Restrictive physiology owing to amyloid and endomyocardial fibrosis may mimic the hemodynamic findings of constrictive pericarditis. Table 13.3. gives diagnostic points for constrictive pericarditis versus restrictive cardiomyopathy. The presence of cardiac enlargement, prominent murmurs, and/or tricuspid regurgitation with prominent systolic V-waves supports the diagnosis of restrictive cardiomyopathy. ECG findings may be similar in both conditions, but pseudoinfarction pattern favors restrictive disease. Diag- nosis can be difficult if pericardial calcification or pericardial thickening is not observed on echocardiography or CT or in patients with LV diastolic pressures equal to RV dias- tolic pressures. MRI may be helpful in identifying thickening of the pericardium. In patients with suspected myocardial disease, endomyocardial biopsy is desirable.

Investigations

A few or all of the following investigations may be required to be certain of the diagnosis:

• Chest X-ray may show pericardial calcification, especially of the apex and posteriorly, which is best seen on lateral views, the heart size is usually normal.

• ECG is virtually always abnormal but nonspecific and shows diffuse flat or inverted T- wave in over 75%; the depth of inversion of the T-waves is usually proportional to the degree of pericardial adherence to the myocardium, which may make stripping diffi- cult; low voltage is present in approximately 50% of cases, along with abnormal P-waves, P-mitrale if in sinus rhythm. AF is present in approximately 33% of patients.

• Echocardiography is of limited value in identifying thickened pericardium, unless calci- fication is present. Doppler echocardiography shows typical Doppler features in both mitral and hepatic vein flow in approximately 85% of patients with constriction amenable to surgery. In amyloid heart disease, the atrial septum is characteristically thickened, as also may be the case with valves.

• Ultrafast cine-CT and/or MRI give fairly accurate assessment of pericardial thickness, pericardial impingement on the right ventricle, and the degree of dilation of the vena cava and hepatic veins.

• Cardiac catheterization findings are listed in Table 13.4. Elevation and equalization of all diastolic pressures and the dip and plateau or square root sign are typical findings, but these may be observed in some patients with restrictive cardiomyopathy; as outlined above, MRI is useful in differentiating these two categories of patients.

• It is important to avoid diuretics before catheter studies, because sodium and water loss may cause equalization of LV and right ventricular filling pressures in patients with restrictive cardiomyopathy.

Therapy

If chest X-ray, CT, or MRI reveal a calcified pericardium and if endomyocardial biopsy is unavailable, surgery should be pursued in this setting.

Depending on findings on cardiac catheterization with left- and right-heart hemody- namics, the following is recommended:

• If CT or MRI imaging shows thickened pericardium and one or more hemodynamic criteria for constriction, a high probability of constriction is indicated and surgery is advisable.

• If discordant imaging and hemodynamic data are indeterminate, biopsy is advisable; if this shows infiltrative myopathy, medical therapy is advised, if the chest X-ray, CT, or MRI shows a calcified pericardium on a negative biopsy, surgery is advisable.

• If imaging shows a normal pericardium and less than 2 hemodynamic criteria for con- striction, there is a low probability of constriction and observation and medical therapy are rational strategies.

Surgical pericardiectomy is needed when medical therapy, with the judicious use of diuretics and digoxin for control of the ventricular response in patients with AF, fails to reduce markedly elevated JVP and when symptoms are persistent and bothersome. Early surgical mortality is approximately 5%. In patients with severe calcific disease, recovery may be delayed for weeks or months. If constriction and restriction are both present, pericardiectomy may not cause symptomatic improvement. If myocardial fibrosis is present also, improvement from operation will be limited.

Table 13.4.

Catheterization Data

Parameters Constrictive pericarditis Restrictive cardiomyopathy Diastolic pressure Equalization of early LV > right^a

and late diastolic pressures Rarely LV- right and resembles constrictive

Pericarditis

LVEDP-RVEDPⱕ6 mmHg Usual finding (few exceptions) Usually >6, but significant

(predictive value 87%)^b Overlap

LA pressure Equal right Higher than right; may equalize

with severe tricuspid regurgitation RV pressure square root Always present: early dip Present, but may disappear with

and plateau during diastole therapy regurgitation Sign

Pulmonary hypertension Mild Moderate or severe

RV systolic pressure Usual finding Wide range (30–85 mm Hg) ⱕ52 mmHg^b

(predictive value 71%)

RVEDP/RV systolic ⱖ0.38^b Usual finding Variable, significant overlap (predictive value 83%)

aBoth measured simultaneously.

bModified from Am heart J 1991;122:1431.

LV, left ventricular; RV, right ventricular; EDP, end diastolic pressure; LA, left atrial.

MYOCARDITIS

Acute myocarditis is a disease that can cause a fulminant illness that may result in functional impairment or death. Myocarditis appears to be a precursor in some patients with dilated cardiomyopathy. Confirmation of a diagnosis of myocarditis requires fulfill- ment of the Dallas criteria.

Etiology

It is clinically helpful to consider the etiology of myocarditis under six or more categories:

• Active viral: it appears that viruses may induce myocarditis in genetically susceptible individuals. In humans, viral involvement and a later immunological modulation appear to be important. Viral myocarditis can be induced in genetically susceptible mice by viruses and can be prevented by vaccines or by interferon. Enteroviruses of the Picornaviridae family, in particular Coxsackie B, are implicated in most cases. In ap- proximately 50% of patients with human immunodeficiency virus (HIV) who develop a dilated cardiomyopathy, associated myocarditis has been observed on biopsy. Also, 52%

of 71 AIDS patients was observed to have a myocarditis at autopsy. The HIV or cytome- galovirus appears to be the cause of myocarditis in patients with AIDS. Acute myocardi- tis has been associated with infection by Coxsackie B₃ and B₅, mumps, Epstein-Barr, influenza, and other viruses.

• Lymphocytic: also called postviral myocarditis, or idiopathic. The term lymphocytic appropriately describes the histological findings. The etiology of this form of myocardi- tis is unclear. It is believed to be the result of a pathological immune response to recent viral infection that is often subclinical. Two molecular biological techniques, polymerase chain reaction and in situ hybridization, have supported the etiological role of enterovi- ruses in human myocarditis.

• All other infectious causes: Chagas’ disease is the most common cause of myocarditis in Latin America. Other organisms implicated include toxoplasmosis and diphtheria.

• Autoimmune: associated with lupus erythematosus and Kawasaki syndrome.

• Giant cell: in this condition, investigators found large nucleated cells with the character- istics of macrophages next to myocytes. An autoimmune process appears likely because this condition has been seen in association with Sjögren’s syndrome, giant-cell arteritis, thymoma, myasthenia gravis, chronic active hepatitis, and ulcerated colitis. Patients with giant-cell myocarditis appear to have a prognosis worse than that of lymphocytic myo- carditis.

• Hypersensitivity to drugs and other exogenous agents.

Clinical Hallmarks

A viral illness in the preceding weeks is observed in over 85% of cases. Any one or more of the following may be manifest:

• Chest pain in over 20% of patients, associated with pericarditis and its signs and symp- toms; chest pain may occur suddenly and last for several hours without features of pericarditis and mimic acute MI (these patients may have recurrent or intractable chest pain over several days).

• Palpitations in approximately 33%.

• Symptoms and signs of HF with a small pericardial effusion.

• An easily heard S₃ gallop is commonly present with acute myocarditis and is an expected finding in patients with significant myocardial involvement; an S₃ may persist for several weeks.

• Subclinical illness is not uncommon.

• ECG shows ST-T-wave changes, often with low T-wave and QRS voltage. Conduction defects and atrial or ventricular arrhythmias commonly occur. The ECG may show Q-waves and a pattern simulating acute MI. Serial ECG tracings over the next few days, however, do not show the evolutionary changes that are hallmarks of acute MI.

• Creatine kinase (CK) and CK-MB may simulate MI, but with a different time course.

Myocardial biopsy is rarely required, except for research purposes or before prescribing immunotherapy. A negative gallium scan is reassuring, because it excludes myocarditis in over 96% of all cases. Also, a negative gallium predicts a negative myocardial biopsy.

In a multicenter study, only 9.4% of 2000 patients with presumed myocarditis had a positive biopsy. Antimyosin scintigraphy has a sensitivity of approximately 55% and a negative predictive value of 95%. A negative scan is usually associated with a biopsy negative for myocarditis. A diffused faint and heterogenous uptake indicates a positive scan for myocarditis. With MI, an intense localized myocardial uptake of antibody occurs in the region of the infarct-related coronary artery, but the scan basically reveals cardiac damage and does not necessarily indicate the cause.

Prediction of Outcome

More than 90% of patients recover completely over days, weeks, or months. In a few cases, HF is manifest and clears over weeks with conventional antifailure therapy. Rarely, HF becomes progressively worse and is unabated, except when corticosteroids or cyclosporin cause some amelioration.

Nonsustained ventricular arrhythmias should not be treated with antiarrhythmics, because these agents may cause deterioration owing to their negative inotropic and proarrhythmic effects. In the presence of lethal or potentially lethal arrhythmias, the use of amiodarone may be lifesaving.

HF Therapy Therapies for treating HF include the following:

• Modified bedrest: bed to chair for 1 week and then slow ambulation over weeks.

• Avoid digoxin because there is increased sensitivity; thus, the drug is used only for AF with a fast ventricular response or with severe HF along with furosemide and ACE inhibitors (see Chapter 5).

• Diuretics must be used judiciously, taking care to prevent potassium and magnesium depletion; ACE inhibitors are necessary to decrease afterload and appear to provide salutary effects.

• Corticosteroids are advisable if symptoms persist or continue to progress in an unabated fashion. Corticosteroids may be given a trial, especially if the illness is beyond 3 weeks.

During the first few weeks, there is a fear that corticosteroids may increase viral repli- cation and worsen myocarditis.

A multicenter randomized study using corticosteroids and cyclosporin in patients with biopsy-proven myocarditis showed no improvement in survival or LV function. Thus, a conservative approach is suggested, except where life appears to be threatened.

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