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Mar.07.2022

Pericarditis

Synopsis

Key Points

  • Pericarditis describes inflammation of the pericardium with or without a pericardial effusion; may be acute, subacute, incessant, chronic, or recurrent r1
  • May be idiopathic or caused by viral or bacterial infections or noninfectious conditions (in particular, autoimmune/inflammatory, neoplastic, or metabolic diseases)
  • Suspect pericarditis in patients presenting with pleuritic chest pain (particularly if it is improved by sitting upright or leaning forward), pericardial friction rub, and characteristic ECG abnormalities
  • Initial diagnostic workup for all patients with suspected pericarditis includes ECG, chest radiograph, CBC with differential, inflammatory markers, cardiac troponin levels, and echocardiography r1r2r3
  • Additional testing is individualized and may not be necessary to identify the underlying cause in all patients; however, it is important to rule out certain causes (autoimmune disease, tuberculosis, malignancy) that require specific therapy r1
  • Treatment for acute and recurrent pericarditis includes restricted physical activity, and NSAIDs in combination with colchicine
    • NSAIDs are the first line of therapy for idiopathic or viral pericarditis in the absence of any contraindication to their use
    • Corticosteroids may be considered for refractory disease only if bacterial or viral infection can be excluded as causes
    • Treat the underlying pathology if known (other than viral infection)
    • In early 2021, the US Food and Drug Administration approved rilonacept injection for treatment of recurrent pericarditis and to reduce the risk of recurrence in adults and children 12 years and older r4

Urgent Action

  • Cardiac tamponade is a life-threatening complication that requires urgent pericardial drainage
  • Patients with suspected purulent pericarditis require urgent pericardiocentesis r1

Pitfalls

  • Although use of corticosteroids can provide rapid symptom relief in certain patients with acute and recurrent pericarditis, their use should be avoided as they can lead to chronic disease, increased recurrence, and adverse effects r1

Terminology

Clinical Clarification

  • Pericarditis describes inflammation of the pericardium with or without pericardial effusion r1
  • Inflammation may be acute, subacute, chronic, or recurrent r1
    • Acute pericarditis is the most common disease affecting the pericardium, responsible for 0.1% of all hospital admissions and 5% of all emergency department admissions for chest pain not caused by myocardial infarction r1

Classification

  • According to disease course
    • Acute pericarditis: newly onset disease r1
    • Subacute pericarditis: symptoms develop over several days without clear acute onset r1
    • Recurrent pericarditis: recurrence of disease after an acute episode and symptom-free interval of 4 to 6 weeks or longer r1
      • Incidence after first acute pericarditis episode ranges from 20% to 30% r5
      • Incidence after multiple recurrences ranges from 20% to 50%, particularly in patients not treated with colchicine r5
    • Incessant pericarditis: disease persists for longer than 4 to 6 weeks but less than 3 months without a clear remission period after the initial acute episode r1
    • Chronic pericarditis: disease lasting longer than 3 months r1
  • According to underlying cause r1
    • Idiopathic
    • Infectious
    • Noninfectious
      • Autoimmune/inflammatory
      • Neoplastic
      • Cardiac
      • Traumatic (including iatrogenic)
      • Metabolic
      • Radiation
      • Medication
  • Additional pericardial syndromes that may result from progression of pericarditis
    • Constrictive pericarditis r1
      • Impaired filling of the ventricles due to scarring and consequent loss of elasticity of the pericardial sac
      • May occur in less than 1% of acute pericarditis cases but is more common with pericarditis of specific causes; rarely occurs in recurrent pericarditis
      • Types
        • Transient constrictive pericarditis r1
          • Reversible pattern of constriction due to inflammation after spontaneous recovery or treatment
          • Temporary; may develop with pericarditis and mild effusion
        • Chronic constrictive pericarditis r1
          • Characterized by persistent symptoms (eg, limitation of physical activity, symptoms of heart failure at rest) lasting more than 3 to 6 months r1
    • Effusive-constrictive pericarditis (rare in the United States) r1
      • Constrictive pericarditis and concomitant pericardial effusion
      • Signs of pericardial effusion and cardiac tamponade are present; however, right atrial pressure remains elevated after pericardiocentesis
      • Uncommon
    • Purulent pericarditis r6
      • Life-threatening manifestation of bacterial pericarditis characterized by the accumulation of gross pus in the pericardial space
      • Very rare
    • Pericardial effusion
      • Accumulation of pericardial fluid
      • May occur without pericarditis
      • Variety of causes (eg, malignancy, infection, trauma, pericarditis) or may be idiopathic
    • Cardiac tamponade
      • Compression of the heart leading to impeded filling of the ventricles due to accumulation of a large amount of pericardial fluid under pressure
      • May occur without pericarditis

Diagnosis

Clinical Presentation

History

  • Sudden onset of retrosternal pleuritic chest pain is most common presenting symptom r7c1
    • Typically sharp and pleuritic c2c3
    • Often exacerbated by deep inspiration, coughing, or lying flat and relieved by sitting up and/or leaning forward c4
    • May radiate to the neck, arms, left shoulder, or 1 or both trapezius muscle ridges c5c6c7
    • Uncommon presentation in purulent pericarditis
  • Other symptoms and onset are influenced by underlying cause and disease course: r7
    • Fever (more common in children than adults) r1c8
      • Fevers due to bacterial pericarditis occur at regular intervals and are associated with frank rigors r7
    • Malaise and myalgia may be present r8c9c10
    • If pericardial effusion develops, dyspnea, dry cough, dysphagia, hiccups, and dysphonia may result r9c11c12c13c14
    • Symptoms of heart failure suggest progression to constrictive pericarditis r1
  • History may suggest an underlying cause of suspected pericarditis
    • Patients with viral or bacterial pericarditis may have a history of recent viral or bacterial illness, respectively r1
    • Patients may have known underlying autoimmune disease or history of lung or breast cancer, malignant melanoma, lymphoma, or leukemia r1
    • Bacterial pericarditis is always an acute disease
    • Fungal pericarditis evolves more slowly
    • Onset of tuberculous pericarditis is insidious

Physical examination

  • Patient is typically normotensive r8c15
  • Sinus tachycardia may be evident and associated with fever c16
  • Patient may be febrile if cause is infectious c17
  • Clinical signs of sepsis (eg, fever, hypotension) may accompany purulent pericarditis r7c18
  • Pericardial friction rub may be audible on auscultation over the left sternal border (35% of patients) r7c19
    • Pericardial rub is triphasic (early diastole, late diastole, and systole) in 50% of patients, biphasic in 33% of patients, and monophasic in 13% of patients r3
    • Typically high-pitched, scratchy, or squeaky and may vary in intensity over time
    • Often varies throughout the day; it is important to evaluate patient multiple times and in different positions r2
  • Clinical signs that acute pericarditis has progressed to constrictive pericarditis include: r1
    • Elevated jugular venous pressure r10c20
      • Kussmaul sign (elevation of jugular venous pressure on inspiration) c21
        • May not be visible in milder forms of constrictive pericarditis
        • When visible, it can be seen at the upper neck or angle of the jaw when the patient is sitting; extremely high venous pressure may not be visible unless the patient is standing
    • Altered venous waveforms: a brisk collapse of the neck veins may be apparent, representing prominent x and y descents r10
    • Pericardial knock on auscultation; may be difficult to distinguish from an S₃ r7c22
    • Hyperdynamic apical impulse identified on palpation r10c23
    • Signs of right-sided heart failure: leg edema, abdominal distention, hepatomegaly, and ascites r10c24c25c26c27
  • Pulsus paradoxus and Kussmaul sign with elevated jugular venous pressure suggest disease is complicated by cardiac tamponade; other signs include: r7
    • Hypotension c28
    • Tachycardia c29
    • Muffled heart sounds c30

Causes and Risk Factors

Causes

  • Pericarditis may be categorized by infectious or noninfectious causes r1
    • Infectious causes
      • Viral (most common)
        • Majority of idiopathic cases of pericarditis are presumed to be viral; causes include:
          • Enteroviruses c31
          • Herpesviruses c32
          • Adenoviruses c33
          • Human parvovirus B19 c34
      • Bacterial
        • Mycobacterium tuberculosis is most common bacterial cause c35
          • Tuberculous pericarditis accounts for 4% or less of pericardial disease in developed countries but accounts for a significant portion of pericardial disease (50%-90%) in tuberculosis-endemic countries r1
        • Other bacteria include Coxiella burnetii and Borrelia burgdorferic36c37
        • Rarely, caused by:
          • Pneumococcus c38
          • Meningococcus c39
          • Gonococcus c40
          • Providencia stuartiic41
          • Streptococcus species c42
          • Staphylococcus species c43
          • Haemophilus species c44
          • Chlamydia species c45
          • Mycoplasma species c46
          • Legionella species c47
          • Leptospira species c48
          • Listeria species c49
      • Fungal (rare)
        • Infections with Histoplasma species are more likely in immunocompetent patients c50
        • Infections with Aspergillus, Blastomyces, and Candida species are more likely in immunocompromised patients c51c52c53
      • Parasitic causes are very rare but include infection with species of the genera Echinococcus and Toxoplasma c54c55
    • Noninfectious causes
      • Autoimmune (common)
        • Systemic autoimmune or inflammatory conditions
          • Systemic lupus erythematosus c56
          • Sjögren syndrome c57
          • Rheumatoid arthritis c58
          • Scleroderma c59
        • Systemic vasculitides
          • Takayasu disease c60
          • Eosinophilic granulomatosis with polyangiitis c61
        • Sarcoidosis c62
        • Familial Mediterranean fever c63
        • Inflammatory bowel disease c64
        • Still disease c65
      • Neoplastic
        • Typically caused by secondary metastatic tumors; lung cancer, breast cancer, and lymphoma are most common c66
        • Rarely, caused by primary tumors (primarily pericardial mesothelioma) c67
      • Metabolic
      • Traumatic
        • Early onset (rare)
          • Direct injury (eg, penetrating thoracic injury, esophageal perforation) c71c72
          • Indirect injury (eg, nonpenetrating thoracic injury, radiation injury) c73c74
            • Most radiation injury cases are secondary to radiation for Hodgkin lymphoma or breast or lung cancer
        • Delayed onset (common) c75
          • Post–myocardial infarction syndrome
            • Dressler syndrome: early infarct-associated (postinfarction) pericarditis
              • Typically occurs a few days after acute myocardial infarction
              • Rare and often transient
            • Late pericarditis (postcardiac injury): typically occurs 1 to 2 weeks after acute myocardial infarction
          • Postpericardiotomy syndrome c76
          • Posttraumatic (may include those occurring after iatrogenic trauma) c77
          • Late onset of pericardial disease is also common after radiation (20% within 2 years) and typically consists of effusive-constrictive pericarditis or classic constrictive pericarditis c78
      • Drug related (rare)
        • Drug-induced lupus syndrome secondary to use of procainamide, hydralazine, methyldopa, and phenytoin c79c80c81c82
        • Chemotherapy agents including doxorubicin, daunorubicin, cyclophosphamide, and 5-fluorouracil c83c84c85c86
        • Other drugs include penicillins, amiodarone, methysergide, mesalazine, clozapine, minoxidil, dantrolene, phenylbutazone, thiazides, streptomycin, thiouracils, streptokinase, p-aminosalicylic acid, sulfa drugs, cyclosporine, bromocriptine, granulocyte-macrophage colony-stimulating factor, and anti–tumor necrosis factor agents c87c88c89c90c91c92c93c94c95c96c97c98c99c100c101c102c103c104
      • Other
        • Amyloidosis c105
        • Aortic dissection c106
        • Pulmonary arterial hypertension c107
        • Chronic heart failure c108

Risk factors and/or associations

Age
  • Mean age of acute pericarditis occurrence is 41 to 60 years r2
  • Advanced age is a risk factor for bacterial pericarditis r9c109
Sex
  • Men have a 2-fold higher risk for development of acute pericarditis r2c110
Other risk factors/associations
  • Idiopathic pericarditis is seasonal, occurring most often in the spring and fall r2
  • Risk factors for bacterial pericarditis include the following: r9
    • Diabetes mellitus c111
    • Untreated infection c112
    • Extensive burns c113
    • Immunosuppression c114
    • Cardiac surgery c115
    • Thoracic trauma c116
    • Preexisting pericardial effusion c117
  • IV drug use, indwelling venous catheter use, thoracic surgery, and prosthetic heart valves may increase the risk for fungal pericarditis r9c118c119c120c121
  • Purulent pericarditis occurs almost exclusively in patients with an underlying disease (eg, AIDS) or in patients being treated for an underlying disease (eg, in those who have undergone hemodialysis, thoracic surgery, or chemotherapy) r9c122
  • Recurrent pericarditis rates are higher in patients treated with steroid therapy r2c123

Diagnostic Procedures

Primary diagnostic tools

  • Suspect pericarditis in patients presenting with pleuritic chest pain, particularly if it is improved by sitting upright or leaning forward, and a pericardial friction rub
  • Initial workup for all patients with suspected pericarditis includes the following: r1
    • ECG c124
    • Chest radiography r3c125
    • Laboratory studies r2
      • CBC with differential c126
      • C-reactive protein and/or erythrocyte sedimentation rate c127c128
      • Cardiac troponin level c129
      • Renal function and liver tests c130c131
    • Transthoracic echocardiography c132
  • Additional diagnostic testing is individualized and may include: r1
    • Blood cultures in patients with suspected purulent pericarditis (eg, fever, signs of sepsis, concomitant bacterial infection) c133
    • Cardiac CT or MRI in patients with suspected constrictive pericarditis, nondiagnostic echocardiography, or complicated course c134c135
    • Tuberculosis testing (eg, interferon-γ release assay; culture of sputum, gastric aspirate, and/or urine for Mycobacterium tuberculosis) and chest CT in patients suspected of having tuberculous pericarditis (eg, those who reside in tuberculosis-endemic areas, immunocompromised patients) c136
    • HIV serology c137
    • Antinuclear antibodies in patients with suspected rheumatologic disorders
      • Additional tests may include antineutrophil cytoplasmic autoantibody, extractable nuclear antigens, ferritin level if Still disease is suspected, and PET if large vessel arteritis or sarcoidosis is suspected c138c139c140
    • Consider specific neoplastic markers and CT of chest and abdomen for patients with suspected neoplastic pericarditis c141c142
    • Pericardiocentesis for patients with suspected bacterial, neoplastic, or refractory pericarditis; perform therapeutically in patients with cardiac tamponade c143
    • Pericardial biopsy in patients suspected of having neoplastic pericarditis or in those suspected of having tuberculous pericarditis with more than 3 weeks of symptoms and no cause diagnosed by other methods c144
    • Cardiac catheterization can be used to diagnose constrictive pericarditis when other diagnostic methods are inconclusive r1c145
  • Although it is not necessary to identify the underlying cause for pericarditis in all patients, it is important to rule out causes that require targeted therapy; this may require additional testing r1
    • Pericarditis secondary to malignancy
    • Pericarditis associated with autoimmune disease
    • Tuberculous pericarditis
  • For patients with recurrent idiopathic pericarditis and symptom-free periods between episodes, it is unnecessary to perform a new search of disease cause with each recurrence unless new symptoms present r1
  • For patients with suspected constrictive pericarditis, also obtain B-type natriuretic peptide and evaluate for tuberculosis r1

Laboratory

  • CBC c146
    • Characterized by leukocytosis r1
  • Inflammatory markers
    • Characteristically associated with elevated erythrocyte sedimentation rate c147
    • C-reactive protein levels are elevated (greater than 3 mg/L) in 75% of cases; however, some patients may present with C-reactive protein levels within reference range that increase within the first week of disease r11c148
  • Cardiac troponin levels
    • Troponin I and T levels are elevated in 35% to 50% of acute pericarditis cases as a result of epicardial inflammation r9c149c150
    • Correlates with ST-segment elevation on ECG r9
    • Typically return to reference-range levels within 1 to 2 weeks
      • Elevated troponin levels lasting longer than 2 weeks suggest myocardial involvement and indicate worse prognosis r9

Imaging

  • Chest radiography r1c151
    • Recommended as an initial imaging technique for all suspected cases of acute or recurrent pericarditis; may detect mild to moderate pericardial effusions and identify potential causes (eg, tuberculosis, pneumonia, neoplasm)
    • May show normal findings in patients with acute pericarditis or may show pericardial effusion
    • Mediastinal irregularities indicate lymphadenopathy from tuberculous or fungal pericarditis r9
    • May show pericardial calcifications suggestive of constrictive pericarditis r1
  • Transthoracic echocardiography r1c152
    • Indicated as first line imaging modality for patients with suspected pericarditis; it is a primary method to detect pericardial effusion r1
    • Critical for evaluating hemodynamic effects on the heart if disease is suspected to be complicated by cardiac tamponade or progression to constrictive pericarditis r2
    • Able to identify disease complicated by myocardial involvement r3
    • The following findings are typical of acute or recurrent pericarditis:
      • Patients may have normal echocardiography findings r1
      • Pericardial effusion may be evident r1
        • Size of pericardial effusion can be assessed by determining end-diastolic distance of echo-free space between the epicardium and parietal pericardium on 2-dimensional echocardiography
          • Less than 10 mm: small
          • 10 to 20 mm: moderate
          • Greater than 20 mm: large
        • A large pericardial effusion with frondlike projections and thick, porridgelike fluid is suggestive of, but not specific for, tuberculous pericarditis
      • Thickened or hyperreflective pericardial layers (normal pericardial thickness is 0.7-2 mm) r1
      • Wall motion abnormalities may indicate myocardial involvement (myopericarditis) r1
      • Intrapericardial fibrinous strands may be evident r1
    • The following findings are consistent with constrictive pericarditis:
      • Septal motion abnormalities r10
      • Pericardial thickening or calcifications
      • Dilated atria r1
      • Dilation and diminished collapse of inferior vena cava is a universal finding in constrictive pericarditis r1
      • Premature opening of the pulmonary valve r1
      • Restrictive filling pattern of the right and left ventricles, suggesting stiff pericardium r1
      • Respiratory variation of the mitral peak E-wave velocity of greater than 25% on mitral inflow pulsed-wave Doppler echocardiography; 33% of patients may not present with this variation r10
      • Normal or increased mitral annular velocity (greater than 7 cm/second) r1
      • Decreased expiratory diastolic hepatic vein velocities with large reversals (highly specific for constrictive pericarditis) r10
      • Respiratory variation in the pulmonary venous peak D-wave velocity greater than 20% r1
      • Flow propagation velocity greater than 45 cm/second r1
      • Greater than 25% fall in mitral inflow velocity and greater than 40% rise in tricuspid velocity in the first beat after inspiration, with opposite changes observed after expiration r1
      • Normal or increased propagation velocity of early diastolic transmitral flow using color M-mode echocardiography r1
      • Annulus reversus (mitral lateral e′ velocity less than medial e′ velocity) r10
  • CT r1c153
    • Indicated as a second line imaging technique r1
      • Indicated to assess calcifications, pericardial thickness, and extent of pericardial involvement in patients with suspected constrictive pericarditis
      • Most accurate method to detect pericardial calcifications
    • The following findings are indicative of acute and recurrent pericarditis:
      • Evidence of pericardial inflammation (eg, edema, pericardial contrast enhancement) r1
      • Pericardial thickness greater than 3 to 4 mm r1
      • Findings may be more heterogeneous in recurrent pericarditis owing to fibrotic adhesions r1
      • Irregular pericardial delineation may present with recurrent disease r1
      • Typical pericarditis signs with mediastinal and tracheobronchial lymphadenopathy (greater than 10 mm with hypodense centers and matting visible) with sparing of hilar lymph nodes is suggestive of tuberculous pericarditis r1
    • The following findings are indicative of constrictive pericarditis:
      • Mild to moderate thickening of pericardial layers with or without calcificationsr1; 20% of patients with constrictive pericarditis may have normal pericardial thicknessr10
        • Usually most noticeable at the base of the ventricles, atrioventricular grooves, and atria
        • CT is the most accurate imaging modality to evaluate calcifications r1
      • Adjacent myocardium may be fibrotic and calcified r1
      • Compressed cardiac contents r1
      • Abnormally shaped ventricular septum r1
      • Dilated atria and caval/hepatic veins r1
      • Contrast reversal in caval/hepatic veins r1
      • Hepatic congestion r1
  • Cardiac MRI with gadolinium contrast material c154
    • Indicated as a second line imaging modality:
      • To diagnose atypical presentations of constrictive pericarditis, such as cases of transient or effusive-constrictive pericarditis or those with minimally thickened pericardium r1
      • To evaluate myocardial involvement and rule out ischemic myocardial necrosis in patients with pericarditis suspected to be complicated by myocardial disease r1
    • May identify fibrotic fusion of pericardial layers more easily than CT; however, pericardial calcifications are not visualized r1
    • The following findings are indicative of acute or recurrent pericarditis: r1
      • Strong pericardial late gadolinium enhancement after contrast r1
      • Inspiratory septal flattening on real-time cine cardiovascular MRI due to decreased pericardial compliance r1
      • Subepicardial/midwall myocardial late gadolinium enhancement indicates myopericarditis r1
      • Findings may be more heterogeneous in recurrent pericarditis owing to fibrotic adhesions r1
      • Irregular pericardial delineation may present with recurrent disease r1
    • The following findings are indicative of constrictive pericarditis:
      • Ventricular interdependence
      • Fibrocalcific process extending to the myocardium
      • Compressed cardiac contents
      • Dilated atria and caval/hepatic veins
      • Pleural fluid
      • Increased ventricular coupling as seen using real-time cine cardiac MRI or real-time phase contrast imaging
      • Fibrotic adhesion of pericardial layers

Functional testing

  • ECG c155
    • Recommended as part of initial workup of all patients with suspected acute or recurrent pericarditis; ECG changes are a criterion for diagnosis
      • However, pericarditis does not always cause ECG changes or may cause atypical ECG abnormalities
    • 4 stages of ECG abnormalities; patient may present with any of these findings, depending on timing of examination relevant to onset of disease r7
      • Stage 1: widespread ST-segment elevation (typically concave upward) with PR-segment depression suggests inflammation of the epicardium and is a hallmark sign of an acute episode of pericarditis (80% of patients with pericarditis) r1
        • Accompanied by reciprocal ST-segment depression in the aVR and V₁ leads r7
        • Typically seen within hours to days of chest pain onset r7
      • Stage 2: ST and PR segments normalize r7
        • Typically occurs within the first week of illness r2
      • Stage 3: symmetrical, widespread T-wave inversions r7
      • Stage 4: findings may appear normal or T-wave inversions persist indefinitely r7
    • Low-voltage, nonspecific ST/T changes, and atrial fibrillation are characteristic of constrictive pericarditis r1

Procedures

Pericardiocentesis c156
General explanation
  • Aspiration of pericardial fluid guided by fluoroscopy or echocardiography r1
Indication
  • Indicated for patients suspected of having bacterial, neoplastic, or purulent pericarditis r1
Contraindications r12
  • Aortic dissection
  • Myocardial rupture
  • Traumatic effusion with hemodynamic instability
Complications r1
  • Hepatic injury
  • Pneumopericardium
  • Pneumothorax
  • Hemothorax
  • Coronary artery or cardiac chamber puncture
  • Arrhythmias
Interpretation of results
  • For patients with suspected purulent pericarditis r9
    • Send pericardial fluid for Gram stain, acid-fast stain, and WBC count, neutrophil count, and serum glucose ratio
  • For patients with suspected neoplastic pericarditis, send pericardial fluid for cytology and tumor markers (eg, carcinoembryonic antigen, cytokeratin fragment 21-1)
  • For patients with suspected tuberculous pericarditis: r1
    • Culture for Mycobacterium tuberculosis
    • Perform quantitative polymerase chain reaction analysis to test for Mycobacterium tuberculosis nucleic acid
    • Send for WBC count and cytology
    • Perform interferon-γ assay r13
    • Stain for acid-fast bacilli
Pericardial biopsy c157
General explanation
  • Sample pericardial tissue for histologic examination using pericardioscopy r1
  • Obtain 7 to 10 tissue samples to reduce sampling error
Indication r1
  • Pericardial biopsy is indicated for patients with suspected tuberculous pericarditis and symptoms lasting longer than 3 weeks without identifiable cause
Complications
  • Transient fever r14
  • Pneumothorax
  • Nonsustained ventricular tachycardia has been reported to be caused by intrapericardial guidewire manipulation but is specific to patients with myocardial involvement r14

Other diagnostic tools

  • Acute pericarditis diagnosis requires that at least 2 of the following criteria be met: r1
    • Chest pain
      • Typically sharp and pleuritic
      • May be improved by sitting up and leaning forward
    • Pericardial friction rub
    • ECG changes
      • Typically new widespread ST elevation or PR depression
    • Pericardial effusion
  • Additional supporting findings include:
    • Elevated inflammatory markers
    • Evidence of pericardial inflammation on imaging

Differential Diagnosis

Most common

  • Myocardial infarction or ischemia c158c159d1
    • Presentation is often similar (ie, with chest pain)
    • Unlike pericarditis, chest pain is described as pressurelike, heavy, and squeezing and may resolve with administration of nitroglycerin
      • Pain does not vary with respiration or position changes and lasts minutes to hours rather than hours to days
    • Differentiated based on clinical features, ECG, cardiac biomarker assay, and echocardiography
  • Pneumonia c160d2
    • Presentation includes fever and productive cough; chest pain and dyspnea may occur
    • Differentiated based on clinical findings and chest radiograph
  • Pulmonary embolism c161d3
    • Chest pain has similar character but can be anterior, posterior, or lateral in location
    • Chest pain in phase with respiration (no chest pain when patient ceases breathing) and is not positional in nature
    • Differentiated based on clinical features, cardiac enzymes, ECG, and imaging findings; multidetector-row CT angiography is diagnostic for pulmonary embolism
  • Pneumothorax c162
    • Presentation includes acute dyspnea and pleuritic chest pain
    • Unlike pericarditis, may not be positional in nature and pericardial friction rub is absent
    • Differentiated based on clinical findings and chest radiograph
  • Pleuritis (pleurisy) c163
    • Often presents with pleuritic inspiratory chest pain, cough, and sometimes dyspnea
    • Unlike pericarditis, occurs in the setting of respiratory infection
    • Differentiated based on clinical features and presence of normal ECG and imaging tests
  • Costochondritis c164
    • Presents with pleuritic chest pain that may be exacerbated by movement
    • Unlike pericarditis, there is reproducible tenderness with palpation of the costochondral junctions
    • Patient is otherwise well with normal physical examination findings
    • Differentiated based on clinical features and presence of normal ECG and imaging findings

Treatment

Goals

  • Relieve pain and reduce inflammation r7
  • Prevent recurrence r2

Disposition

Admission criteria

Patients who present with confirmed or suspected pericarditis and at least 1 of the following risk factors for poor prognosis should be admitted to hospital for diagnosis and determination of cause: r1

  • Fever higher than 38 °C
  • Subacute disease course (symptoms developing over several days without clear-cut onset)
  • Large pericardial effusion
  • Cardiac tamponade
  • Failure to respond to NSAID therapy within 7 days
  • Disease in the context of immunosuppression or acute trauma
  • Currently taking oral anticoagulant therapy
  • Elevated cardiac troponin level (suggests myocarditis)

All other patients can be treated with outpatient care r1

Criteria for ICU admission
  • Hemodynamic instability (eg, owing to cardiac tamponade)

Recommendations for specialist referral

  • Patients with suspected pericarditis should be evaluated and managed in consultation with a cardiologist
  • Refer patients with infectious pericarditis to an infectious disease specialist r1
  • Refer to interventional cardiologist for management of moderate to large pericardial effusion or cardiac tamponade
  • Refer to cardiothoracic surgeon if pericardiotomy or pericardiectomy is required (eg, in constrictive pericarditis) r1

Treatment Options

For all patients with acute or recurrent pericarditis: r1

  • Treat underlying disorder in patients with an identified cause; this is especially important for preventing progression to constrictive pericarditis r1
    • Most cases in developed countries are viral or idiopathic and self-limited; treatment is supportive, and no particular therapy has been proven to prevent complications, which are rare
    • For most patients with post–myocardial infarction pericarditis, which is self-limited, supportive care is sufficient
  • Instruct all patients to restrict physical activity to only that required for average sedentary living r1
    • Activity should be restricted until symptoms resolve and C-reactive protein levels return to reference range
    • Athletes may return to competitive sports only after symptoms resolve and all diagnostic testing (ie, C-reactive protein levels and ECG and echocardiography results) shows normal findings (minimum of 3 months)
  • NSAIDs (aspirin or ibuprofen) and colchicine are the mainstays of treatmentr15 for most patients with idiopathic or viral pericarditis r1
    • Choice of NSAID is based on patient history, presence of comorbid disease, and physician preference
      • Aspirin should be used if it is already needed as part of antiplatelet therapy, if ischemic heart disease is a concern, or if pericarditis occurs early after an acute myocardial infarction
    • Use of colchicine in combination with NSAID therapy improves response to therapy and remission rates and prevents recurrence r1
    • Consider use of a proton pump inhibitor to protect against gastric damage for patients with high NSAID dosages or long periods of use r2
    • Treatment duration can be based on resolution of symptoms and normalization of inflammatory markers; treatment can be tapered once patient is symptom free and C-reactive protein is within reference range for at least 24 hours
  • Corticosteroids are a second line therapyr15 when infection has been excluded r1
    • Specific indications include: r1
      • Contraindications to NSAIDs
      • Systemic inflammatory diseases
      • Postpericardiotomy syndromes
      • Pregnancy
      • Uremic pericarditis
      • Persistent disease failing to respond to treatment with NSAIDs and colchicine
    • Use in low to moderate doses in combination with colchicine
    • May promote chronic disease and steroid dependence r1
    • Treatment can be tapered once patient is symptom free and C-reactive protein level is within reference range for at least 24 hours
  • Interleukin-1 receptor antagonist (ie, anakinra) r15
    • Data suggests it may be beneficial for treatment of recurrent pericarditis r15
    • Data for interleukin-1 blockade in acute pericarditis is not as robust r15

For patients with recurrent pericarditis:

  • In early 2021, the US Food and Drug Administration approved rilonacept injection for treatment of recurrent pericarditis and to reduce the risk of recurrence in adults and children 12 years and older r4
    • A Phase 3 Trial reported that, in patients with recurrent pericarditis, rilonacept resulted in rapid resolution of recurrent pericarditis and significantly reduced the risk of pericarditis recurrence r16
    • Interleukin-1 blockade with rilonacept may interfere with the body's natural immune response to infections; do not begin therapy in patients with acute or chronic infections
    • Avoid administration of live vaccines during rilonacept therapy; patients should receive all recommended immunizations before initiation of the therapy

Percutaneous or surgical therapy:

  • May be required for patients with any of the following:
    • Moderate to large pericardial effusion
    • Cardiac tamponade
    • Suspected bacterial or neoplastic cause for moderate to large pericardial effusion
    • Frequent recurrent pericarditis with effusion
    • Constrictive pericarditis (late sequelae)
  • Typically involves percutaneous drainage of pericardial effusion guided by fluoroscopy or echocardiography
  • Surgical removal of part of all of pericardium (pericardiectomy or pericardial window) is indicated in cases complicated by constrictive pericarditis or recurrent pericardial effusions r1

Drug therapy

  • NSAIDs c165c166c167
    • Aspirin r1
      • Acute
        • Aspirin Oral tablet; Adults: 750 to 1,000 mg PO every 8 hours for 1 to 2 weeks, then decrease dose by 250 to 500 mg/day every 1 to 2 weeks in combination with colchicine.
      • Recurrent
        • Aspirin Oral tablet; Adults: 500 to 1,000 mg PO every 6 to 8 hours for at least 2 to 4 weeks, then decrease dose by 250 to 500 mg/day every 1 to 2 weeks in combination with colchicine.  Dose range: 1.5 to 4 g/day.
    • Ibuprofen r1
      • Acute
        • Treatment duration is dependent on resolution of symptoms and the normalization of markers of inflammation (eg, C-reactive protein).
        • Ibuprofen Oral tablet; Adults: 600 mg PO every 8 hours for 1 to 2 weeks, then decrease dose by 200 to 400 mg/day every 1 to 2 weeks in combination with colchicine.
      • Recurrent
        • Ibuprofen Oral tablet; Adults: 600 mg PO every 8 hours for at least 2 to 4 weeks, then decrease dose by 200 to 400 mg/day every 1 to 2 weeks in combination with colchicine. Dose range: 1,200 to 2,400 mg/day.
    • Indomethacin
      • Acute
        • Indomethacin Oral capsule; Adults: 25 mg PO every 8 hours, initially; increase dose to 50 mg PO every 8 hours as tolerated and continue for 1 to 2 weeks, then decrease dose by 25 mg/day every 1 to 2 weeks in combination with colchicine.
      • Recurrent
        • Indomethacin Oral capsule; Adults: 25 mg PO every 8 hours, initially; increase dose to 50 mg PO every 8 hours as tolerated and continue for at least 2 to 4 weeks, then decrease dose by 25 mg/day every 1 to 2 weeks in combination with colchicine.
  • Colchicine r1c168
    • NOTE: The 0.5-mg tablet of colchicine is currently not available in the United States and many other countries. The 0.6-mg tablet or dose is used in place of the guideline-recommended 0.5-mg dosing.
      • Colchicine Oral tablet; Adults: 0.5 mg or 0.6 mg PO once daily for patients weighing less than 70 kg.
      • Colchicine Oral tablet; Adults: 0.5 mg or 0.6 mg PO twice daily for patients weighing 70 kg or more.
    • Use for 3 months for acute pericarditis, 6 months for recurrent pericarditis
    • After obtaining a complete response, may be tapered gradually over several weeks to several months; however, this is not mandatory r1
  • Corticosteroids
    • Prednisone r1c169
      • Prednisone Oral tablet; Adults: 0.25 to 0.5 mg/kg PO once daily. Corticosteroids are contraindicated in pericarditis after myocardial infarction; corticosteroids slow myocardial scar formation and incidence of rupture may increase
        • Maintain original dose until symptoms resolve and C-reactive protein levels normalize, then slowly taper.
          • Suggested taper:
            • For daily doses greater than 50 mg, taper by 10 mg/day every 1 to 2 weeks
            • For daily doses 25 to 50 mg, taper by 5 to 10 mg/day every 1 to 2 weeks
            • For daily doses 15 to 24 mg, taper by 2.5 mg/day every 2 to 4 weeks
            • For daily doses less than 15 mg, taper by 1.25 to 2.5 mg/day every 2 to 6 weeks
          • Only decrease dose if the patient is asymptomatic and C-reactive protein level is within reference range, particularly for doses less than 25 mg/day
  • Rilonacept r16c170
    • In early 2021, the US Food and Drug Administration approved rilonacept injection for treatment of recurrent pericarditis and to reduce the risk of recurrence in adults and children 12 years and older r4
    • Rilonacept Solution for injection; Children and Adolescents 12 to 17 years: 4.4 mg/kg/dose (Max: 320 mg/dose) subcutaneously (1 or 2 injections, Max: 160 mg/injection) once then, 2.2 mg/kg/dose (Max: 160 mg/dose) subcutaneously once weekly starting on day 8.
    • Rilonacept Solution for injection; Adults: 320 mg subcutaneously (two 160 mg-injections) once, then 160 mg subcutaneously once weekly starting on day 8.

Nondrug and supportive care

For athletes, restrict exercise for at least 3 months after symptom resolution and normalization of C-reactive protein levels and ECG and echocardiogram findings

For nonathletes, restrict exercise until resolution of symptoms and normalization of C-reactive protein level and ECG and echocardiogram findings r1

Procedures
Pericardiocentesis c171
General explanation
  • Drainage of pericardial fluid guided by fluoroscopy or echocardiography
Indication
  • Moderate to large pericardial effusion
  • Cardiac tamponade
Contraindications
  • Aortic dissection
  • Myocardial rupture
  • Traumatic effusion with hemodynamic instability
Complications
  • Arrhythmias
  • Coronary artery or cardiac chamber puncture
  • Hemothorax
  • Pneumothorax
  • Pneumopericardium
  • Hepatic injury

Comorbidities

  • Myocarditis shares a similar cause with pericarditis and therefore often occurs concurrently (15% of patientsr17) r1c172
    • Pericarditis with myocardial involvement is known as myopericarditis
      • Myocardial involvement may be subclinical but can be identified by increased markers of myocardial damage (ie, elevation of troponins or creatine kinase-MB) without newly developed left ventricular impairment r1
      • Risk factors for myocardial involvement include younger age, male sex, fever, arrhythmia, and ST-segment elevation r17
      • Management of myopericarditis is similar to that of pericarditis with the following exceptions: r1
        • There is insufficient evidence to recommend colchicine for patients with myopericarditis
        • Physical exercise should be restricted for at least 6 months from the onset of illness
      • Myopericarditis is not associated with increased risk of complications or recurrent pericarditis r17
  • Renal disease or end-stage renal disease r1c173c174
    • Uremic pericarditis describes pericarditis that occurs before renal replacement therapy or within 8 weeks of initiating renal replacement therapy
    • Dialysis pericarditis occurs after a patient is stabilized on dialysis (typically 8 or more weeks after initiation)
    • Constrictive pericarditis may complicate renal disease, although very rarely
  • Systemic autoimmune diseases
    • Common autoimmune comorbidities
      • Systemic lupus erythematosus c175
      • Sjögren syndrome c176
      • Rheumatoid arthritis c177
      • Scleroderma c178
    • Less common autoimmune comorbidities
      • Systemic vasculitides c179
      • Behçet syndrome c180
      • Sarcoidosis c181
      • Inflammatory bowel disease c182

Special populations

  • Pregnant and breastfeeding women
    • NSAIDs
      • Classic NSAIDs (ibuprofen or indomethacin) may be used during the first and second trimesters but should be withdrawn by gestational week 32
        • Indomethacin Oral capsule; Adults: Indomethacin 75 to 200 mg/day PO divided in 3 to 4 doses has been shown to be comparable to aspirin.
      • Aspirin (100 mg/day or less) should be used after gestational week 20 because other NSAIDs may cause impaired fetal renal function
    • Corticosteroids
      • Prednisone at the lowest effective dose may be used throughout pregnancy and breastfeeding but should be supplemented with calcium (1200-1500 mg/dayr5) and vitamin D (800-1000 international units/dayr5)
    • Colchicine is contraindicated during pregnancy and breastfeeding
  • Geriatric populations r1
    • Indomethacin is not recommended
    • Recommended to halve colchicine dose
    • Critically evaluate renal function and drug interactions before prescribing drug therapy
  • Tuberculous pericarditis r1
    • Consider adjunctive corticosteroids in patients without HIV infection r1
    • Administer intrapericardial urokinase to reduce risk of progression to constrictive pericarditis
    • For patients with constrictive tuberculous pericarditis who have not improved after 4 to 8 weeks of tuberculosis therapy, pericardiectomy is indicated
  • Recurrent pericarditis
    • Initially treat as for acute pericarditis
    • Treat those who do not respond to NSAIDs or who require very high doses of corticosteroids with azathioprine, IV immunoglobulin, or anakinra r1
    • Intrapericardial corticosteroid instillation may be an alternative to systemic corticosteroids r1
    • Consider pericardiectomy for patients with recurrent pericarditis refractory to all other medical therapy r1
  • Constrictive pericarditis r1
    • Late sequelae of pericarditis
    • Pericardiectomy is the mainstay of treatment
    • Antiinflammatory drugs should be used for those with newly diagnosed constrictive pericarditis who are hemodynamically stable r1
      • May be used in patients with elevated C-reactive protein and imaging evidence of pericardial inflammation or in patients for whom surgery is contraindicated
        • May resolve constriction in 10% to 20% of patients and prevent need for surgery
      • Do not use in patients with evidence of chronic constrictive pericarditis (eg, those with cachexia, atrial fibrillation, hepatic dysfunction, or pericardial calcification)

Monitoring

  • C-reactive protein levels should be used to assess response to treatment for patients with acute or recurrent pericarditis r1c183
  • Monitor patients with post–cardiac injury syndromes every 6 to 12 months using echocardiography to identify progression to constrictive pericarditis r1c184

Complications and Prognosis

Complications

  • Cardiac tamponade r1c185
  • Constrictive pericarditis c186
  • Recurrent episodes of acute pericarditis c187

Prognosis

  • Most patients with idiopathic acute or recurrentr1 pericarditis have good long-term prognosis r18
    • Acute viral pericarditis is often self-limiting, and most patients recover without complications r1
    • In-hospital mortality rate for acute pericarditis is 1.1% r1
      • This rate increases with age and severe complications
    • Approximately 15% to 30% of patients who have acute pericarditis and are not treated with colchicine develop incessant or recurrent pericarditis r1
      • Use of colchicine may halve the recurrence rate
  • Major risk factors for poor prognosis include: r1
    • Fever higher than 38 °C
    • Subacute disease course
    • Large pericardial effusion (diastolic echo-free space greater than 20 mm)
    • Cardiac tamponade
    • Failure to respond to NSAIDs within 7 days
  • Risk for progression to constrictive pericarditis is rare and determined by underlying cause r1
    • Low risk (less than 1%)
      • Idiopathic and presumed viral pericarditis
    • Intermediate risk (2%-5%)
      • Autoimmune or immune-mediated causes
      • Neoplastic causes
    • High risk (20%-30%)
      • Bacterial causes (especially tuberculous and purulent pericarditis)
  • Patients with tuberculosis pericarditis
    • Mortality rate for tuberculous pericarditis is 17% to 40% 6 months postdiagnosis (based on data available from patients in sub-Saharan Africa) r1
    • Approximately 50% of patients with tuberculous pericarditis progress to constrictive pericarditis if tuberculosis is not treated r1
      • Treatment of tuberculosis with rifampicin-based antituberculosis therapy reduces this progression rate to 17% to 40%
  • Untreated purulent pericarditis has a 100% death rate; treatment can lower the death rate to 15% and result in good long-term outcomes r1
    • Death from purulent pericarditis is primarily a result of cardiac tamponade, systemic toxicity, cardiac decompensation, or constriction r6
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