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Pericarditis
Veronica J. Ruston, DO, Capt, USAF, MC
Angela M. Riegel, DO
image BASICS
DESCRIPTION
Inflammation of the pericardium, with or without associated pericardial effusion. Myopericarditis or perimyocarditis refers to cases that have myocardial involvement in addition to the pericardial sac.
EPIDEMIOLOGY
Incidence
Epidemiologic studies are lacking. Exact incidence is unknown but occurs in up to 5% of patients evaluated in the ER for chest pain without myocardial infarction (MI); appears to be a slightly increased prevalence in men.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Inflammation of the pericardial sac can be acute or chronic (recurrent). Chronic/recurrent inflammation may result in constrictive pericarditis.
  • Can produce serous/purulent fluid/dense fibrinous material (depending on etiology), which may or may not lead to hemodynamic compromise
Genetics
No known genetic factors:
  • Idiopathic: 85-90% of cases; likely related to viral infection, which may trigger immune-related process
  • Infectious
    • Viral: coxsackievirus, echovirus, adenovirus, Epstein-Barr virus, cytomegalovirus, hepatitis viruses, influenza virus, HIV, measles, mumps, varicella
    • Bacterial: gram-positive and gram-negative organisms
    • Fungal (more common in immunocompromised populations): Blastomyces dermatitidis, Candida sp., Histoplasma capsulatum
    • Mycobacterial: Mycobacterium tuberculosis
    • Parasites: Echinococcus
  • Noninfectious causes
    • Acute MI (2 to 4 days after MI), Dressler syndrome (weeks to months after MI)
    • Aortic dissection
    • Renal failure, uremia, dialysis-associated
    • Malignancy (e.g., breast cancer, lung cancer, Hodgkin disease, leukemia, lymphoma)
    • Radiation therapy
    • Trauma
    • Postpericardiotomy
    • After cardiac procedures (e.g., catheterization, pacemaker placement, ablation)
    • Autoimmune disorders: connective tissue disorders, systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma, hypothyroidism, inflammatory bowel disease, spondyloarthropathies, Wegener granulomatosis
    • Sarcoidosis
  • Medication induced: dantrolene, doxorubicin, hydralazine, isoniazid, mesalamine, methysergide, penicillin, phenytoin, procainamide, rifampin
COMMONLY ASSOCIATED CONDITIONS
Depends on etiology
image DIAGNOSIS
PHYSICAL EXAM
  • Heart rate is usually rapid and regular.
  • Pericardial friction rub: coarse, high-pitched sound best heard during end expiration at left lower sternal border with patient leaning forward. Highly specific for diagnosis (but not sensitive); may be transient and mono-, bi-, or triphasic
  • New S3 may suggest myopericarditis.
  • Cardiac tamponade
  • Diagnostic clinical criteria
    • Acute pericarditis (at least two of four criteria)
      • Typical (pleuritic) chest pain
      • Pericardial friction rub
      • ECG changes with widespread ST elevation
      • New/increasing pericardial effusion
    • Myopericarditis
      • Definite pericarditis plus
      • Symptoms (dyspnea, chest pain, or palpitations) and ECG changes not previously documented (ST/T wave abnormalities, supraventricular/ventricular tachycardia) or focal/diffuse depressed left ventricular (LV) function documented on imaging study
      • Absence of evidence of other cause
      • One of the following: elevated cardiac enzymes (creatine kinase [CK]-MB, troponin I or T) or new focal/diffuse depressed LV function or abnormal imaging consistent with myocarditis (MRI with gadolinium, gallium-67 scanning, antimyosin antibody scanning)
    • Case definitions
      • Suspected myopericarditis: criteria 1, 2, and 3
      • Probable myopericarditis: criteria 1, 2, 3, and 4
      • Confirmed myopericarditis: histopathologic evidence of myocarditis by endomyocardial biopsy (EMB) or autopsy (Note: In the clinical setting, for self-limited cases with predominantly pericarditis, EMB is rarely indicated.)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • It is not necessary to order tests for uncomplicated cases or when the diagnosis is clear. Following labs may be helpful (1)[C]:
    • CBC: typically shows leukocytosis
    • Inflammatory markers: elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactodehydrogenase (LDH)
    • Cardiac biomarkers: typically elevated creatine kinase, troponins
      • Elevated troponins associated with younger age, male sex, pericardial effusion at presentation, and ST segment elevation on ECG
      • Adverse outcomes are not predicted by elevated troponin.
  • ECG: Findings include widespread upward concave ST segment elevation and PR segment depression that may evolve through four stages. ECG may be normal/show nonspecific abnormalities:
    • Stage 1: diffuse ST segment elevation and PR segment depression
    • Stage 2: Normalization of the ST and PR segments and T waves begin to flatten and invert.
    • Stage 3: widespread T wave inversions
    • Stage 4: normalization of T waves; may have persistent inversions if chronic pericarditis
  • ECG may demonstrate low voltage and electrical alternans with tamponade.
  • Transthoracic echocardiogram is recommended to evaluate for the presence of pericardial effusion, tamponade, or myocardial disease (presence of effusion helps to confirm diagnosis of pericarditis) (1)[C].
  • Chest x-ray (CXR) is performed to rule out pulmonary/mediastinal pathology. Enlarged cardiac silhouette suggests large pericardial effusion (at least 200 mL).
  • CT and MRI allow visualization of pericardium to assess for complications or if initial workup is inconclusive (1)[C].
  • Additional testing (if clinically appropriate based on history or atypical presentation or course) may include tuberculin skin test, sputum cultures, rheumatoid factor, antinuclear antibody, and HIV serology (1)[C].
  • Viral cultures and antibody titers rarely clinically useful (1)[C]
Diagnostic Procedures/Other
  • Pericardiocentesis indicated for cardiac tamponade; for suspected purulent, tuberculous, or neoplastic pericarditis; and for effusions >20 mm on echocardiography (2)[C]
  • Surgical drainage with pericardial biopsy recommended if recurrent tamponade, ineffective pericardiocentesis, or hemodynamic instability (2)[C]
Test Interpretation
  • Microscopic examination may reveal hyperemia, leukocyte accumulation, or fibrin deposition.
  • Purulent fluid with neutrophilic predominance if bacterial etiology
  • Lymphocytic predominance in viral, tuberculous, and neoplastic pericarditis
image TREATMENT
  • Goal of treatment is to relieve pain and reduce complications (e.g., recurrence, tamponade, chronic restrictive pericarditis).
  • Outpatient therapy is reported to be successful in 85% patients with low-risk features.
GENERAL MEASURES
Specific therapy directed toward underlying disorder for patients with identified cause other than viral/idiopathic disease.
MEDICATION
First Line
  • NSAIDs are considered the mainstay of therapy for acute pericarditis:
    • Ibuprofen 400 to 800 mg TID for 1 to 2 weeks (2 to 4 weeks for recurrence) then taper (3)[C]
    • Aspirin 650 to 975 mg TID to QID for 1 to 2 weeks (2 to 4 weeks for recurrence) then taper; preferable for patients with recent MI because other NSAIDs impair scar formation in animal studies (4)[C]
    • Indomethacin 50 mg TID for 1 to 2 weeks (2 to 4 weeks for recurrence) then taper; should avoid in elderly due to flow restrictions to coronaries (3)[C]
    • Ketorolac 15 to 30 mg IV/IM q6h while inpatient; maximum duration of 5 days (3)[C]
    • GI protection should be provided (3)[C].
    • P.785

    • Tapering should be done only if the patient is asymptomatic and CRP/ESR are normal and are done every 1 to 2 weeks (3)[C].
    • Treatment duration using NSAIDs for initial attacks is 1 to 2 weeks, but for recurrences, consider 2 to 4 weeks of therapy (3)[C].
    • Monitoring: NSAIDs: CBC and CRP at baseline and weekly until CRP normalizes
    • Contraindications: hypersensitivity to aspirin or NSAIDs, active peptic ulcer/GI bleeding
    • Precautions: Use with caution in patients with asthma, 3rd-trimester pregnancy, coagulopathy, and renal/hepatic dysfunction.
  • Colchicine: common practice to use in combination with NSAIDs; 0.6 mg BID for up to 3 months (up to 6 months for recurrence); taper is not required. Efficacious as therapy for initial occurrence and if multiple recurrences. This is the only agent proven to prevent recurrences in RCTs. Adjunctive therapy can reduce rate of recurrence by 50% (2)[A]. Monitoring: Consider CBC, CRP, transaminases, creatine kinase, and creatinine at baseline and at least after 1 month.
  • Pregnant: <20 weeks' gestation: Aspirin is first choice, but NSAIDs and prednisone are also allowed; >20 weeks' gestation: Prednisone is allowed with avoidance of NSAIDs, aspirin, and colchicine (1)[C].
Second Line
  • Corticosteroid treatment is indicated in connective tissue disease, tuberculous pericarditis, or severe recurrent symptoms unresponsive to NSAIDs or colchicine; should be avoided in uncomplicated acute pericarditis. Corticosteroid use alone has been found to be an independent risk factor for recurrence (4)[C].
  • If steroids are used, consider low dose (0.25 to 0.5 mg/kg/day for 2 weeks for first attack; 0.25 to 0.5 mg/kg/day for 2 to 4 weeks for recurrence); then slow taper (if >50 mg: 10 mg/day every 1 to 2 weeks; if 25 to 50 mg: 5 to 10 mg/day every 1 to 2 weeks; if 15 to 25 mg: 2.5 mg/day every 2 to 4 weeks; if <15 mg: 1 to 2.5 mg/day every 2 to 6 weeks) following remission. Remember adequate prophylaxis treatment for osteoporosis prevention (4)[C].
  • If unable to taper from steroids, resume lowest steroid dose and begin slow taper of 1 to 2 mg every 2 to 4 weeks (3)[C].
  • Intrapericardial administration of steroids may be effective and limits systemic side effects.
ISSUES FOR REFERRAL
  • Refractory cases include those on unacceptably high long-term steroid doses (>25 mg/day).
  • Consider trial of aspirin and/or NSAIDs plus steroid and colchicine.
  • Uremic or dialysis-related cases require more frequent or urgent dialysis without significant benefit from pharmacologics (1)[C].
SURGERY/OTHER PROCEDURES
  • Pericardiocentesis is indicated in cases of cardiac tamponade, high likelihood of tuberculous/purulent/neoplastic pericarditis, and large symptomatic effusions refractory to medical therapy.
  • Pericardial biopsy may be considered for diagnosis in those with persistent worsening pericarditis without a definite diagnosis.
  • Pericardioscopy for targeted diagnostic imaging may be performed at experienced tertiary referral centers in refractory and difficult cases.
  • Pericardial window may be performed in cases of recurrent cardiac tamponade with large pericardial effusion despite medical therapy and severe symptoms.
  • Pericardiectomy can be considered. The 2004 European Society of Cardiology guidelines recommend pericardiectomy (Class IIa) for frequent and highly symptomatic recurrences of pericarditis refractory to medical therapy. However, this is rarely performed in the United States and has high morbidity and mortality (1)[C].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Inpatient therapy recommended for pericarditis associated with clinical predictors of poor prognosis:
  • Major predictors: fever >38°C, subacute onset, large pericardial effusion, cardiac tamponade, lack of response to NSAID/aspirin therapy after at least 1 week (5)[C]
  • Minor predictors: immunosuppressed state, trauma, oral anticoagulation therapy, myopericarditis (5)[C]
IV Fluids
IV fluids considered for hypotension or in the setting of pericardial tamponade
Discharge Criteria
  • Response to therapy with symptom improvement
  • Hemodynamic stability
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • 7 to 10 days to assess response to treatment
  • 1 month to check CBC and CRP and thereafter if symptoms continue to be present
  • Those with clinical predictors of poor prognosis may require closer follow-up based on lab data and echocardiographic findings.
Patient Monitoring
Myopericarditis
  • Use lower doses of anti-inflammatory drugs to control symptoms for 1 to 2 weeks while minimizing deleterious effects on myocarditic process.
  • Exercise restrictions for 4 to 6 weeks or until symptoms resolved and biomarkers normalized (2)[C].
  • Echocardiographic monitoring at 1, 6, and 12 months (especially in those with left ventricular dysfunction)
DIET
No restrictions
PROGNOSIS
Overall good prognosis; disease usually benign and self-limiting; purulent and tuberculosis pericarditis with high mortality
REFERENCES
1. Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the task force on the diagnosis and management of pericardial diseases of the European Society of Cardiology. Eur Heart J. 2004;25(7):587-610.
2. Imazio M, Brucato A, Belli R, et al. Colchicine for the prevention of pericarditis: what we know and what we do not know in 2014—systematic review and meta-analysis. J Cardiovasc Med (Hagerstown). 2014:15(12):840-846.
3. Lilly LS. Treatment of acute and recurrent pericarditis. Circulation. 2013;127(16):1723-1726.
4. Imazio M, Brucato A, Trinchero R, et al. Diagnosis and management of pericardial diseases. Nat Rev Cardiol. 2009;6(12):743-751.
5. Snyder MJ, Bepko J, White M. Acute pericarditis: diagnosis and management. Am Fam Physician. 2014:89(7):553-560.
Additional Reading
&NA;
  • Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.
  • Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of pericardial diseases. Circulation. 2010;121(7):916-928.
  • Khandaker MH, Espinosa RE, Nishimura RA, et al. Pericardial disease: diagnosis and management. Mayo Clin Proc. 2010;85(6):572-593.
Codes
&NA;
ICD10
  • I31.9 Disease of pericardium, unspecified
  • I30.9 Acute pericarditis, unspecified
  • I30.1 Infective pericarditis
Clinical Pearls
&NA;
  • Consider major and minor predictors in deciding which patients should be admitted.
  • Therapy aimed at symptomatic relief and NSAIDs are first-line treatment. Colchicine is recommended as an adjunct to NSAIDs.
  • Pericardiocentesis is recommended in the setting of cardiac tamponade or possible purulent pericarditis.