Hospital Medicine

Acute pericarditis

I. Problem/Condition.

Acute pericarditis results from acute inflammation of the pericardium, which can be the result of an isolated event (i.e., viral infection) or part of a more generalized systemic disorder (i.e., systemic lupus erythematosus). It is differentiated from chronic pericarditis by the patient’s symptoms having been present for less than 3 months.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The differential diagnosis of a patient with possible acute pericarditis will typically fall into the following categories:

  • Cardiac (acute ischemic heart disease, aortic dissection, coronary dissection)

  • Pulmonary (pulmonary embolism, pneumothorax, pleuritis, lung cancer)

  • Infectious (pneumonia, mediastinitis)

  • Gastrointestinal (esophagitis, esophageal spasm, peptic ulcer disease, esophageal or gastric carcinoma)

  • Musculoskeletal (costochondritis, Tietze’s syndrome)

  • Miscellaneous conditions like mediastinal tumors or herpes zoster

The etiology of a patient’s acute pericarditis will fall into one the following categories:

  • Idiopathic

  • Infectious

    • Bacterial, tuberculous, viral, fungal, rickettsial, mycoplasma, leptospiral, listeria, parasitic, and others

  • Connective tissue disease

    • Rheumatoid arthritis, rheumatic fever, systemic lupus erythematosus, systemic sclerosis, Sjogren’s syndrome, Reiter’s syndrome, ankylosing spondylitis, Wegener’s granulomatosis, giant cell arteritis, polymyositis/dermatomyositis, Behcet’s syndrome, familial Mediterranean fever, polyarteritis nodosum, Churg-Strauss syndrome, and others

  • Diseases of adjacent structures

    • Myocardial infarction, aortic dissection, pneumonia, pulmonary embolism, empyema

  • Metabolic causes

    • Myxedema, uremia, dialysis related, gout, scurvy

  • Neoplastic

    • Primary (mesothelioma, sarcoma, lipoma, fibroma, and others)

    • Secondary due to metastasis or direct spread (carcinomas, lymphomas, carcinoid, and others)

  • Trauma

    • Direct (pericardial perforation like penetrating injury, esophageal or gastric perforation or cardiac injury from cardiac surgery or percutaneous procedure-related)

    • Indirect (radiation treatment, non-penetrating chest injury)

  • Drug induced

    • Procainamide, hydralazine, isoniazid, penicillins, others

  • Bleeding diathesis

    • Severe thrombocytopenia or coagulopathic disorders

  • Miscellaneous (postmyocardial infarction/Dressler’s syndrome, inflammatory bowel disease, Loeffler’s syndrome, Stevens-Johnson syndrome, hypereosinophilic syndrome, acute pancreatitis-related)

B. Describe a diagnostic approach/method to the patient with this problem

The diagnostic approach to identifying a patient with acute pericarditis requires attention to the patient’s history, identifying key characteristics on the physical examination and importantly analyzing the patient’s electrocardiogram.

1. Historical information important in the diagnosis of this problem.

Since over 90% of patients with acute pericarditis present with chest pain, carefully asking about the characteristics that are most suggestive of acute pericarditis associated with chest discomfort is vital.

  • When did the chest pain/discomfort first begin?

  • What is the location of the chest pain/discomfort?

  • What is the character of the chest pain/discomfort?

  • Where does the chest pain/discomfort radiate to?

  • What makes the chest pain/discomfort better or worse?

  • Have you ever experienced this type of chest pain/discomfort before?

The chest pain/discomfort of acute pericarditis is typically described as a left-sided or retrosternal pain or discomfort that is often characterized as positional and/or pleuritic in nature. The pain characteristically improves when the patient sits upright and worsens when supine.

The chest pain/discomfort may radiate to the neck, arms or left shoulder but importantly can radiate to the patient’s back in the region of the trapezius ridge because both the pericardium and the trapezius muscle are innervated by the phrenic nerve. This differs from the chest pain associated with myocardial ischemia or aortic dissection, which might radiate to the back but is usually interscapular in nature.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

The most important physical examination questions to answer in a patient with suspected acute pericarditis are:

  • Does the patient look toxic or ill (suggesting underlying life threatening infectious or malignant cause of pericarditis)?

  • If the blood pressure is around 90/60 millimeters mercury (mmHg), does the patient also have an elevated central venous pressure and muffled heart sounds suggesting Beck’s triad or could the patient have constrictive pericarditis?

    • If concerned for cardiac tamponade does the patient have pulsus paradoxus?

    • If concerned for constrictive pericarditis does the patient have signs of right heart failure greater than left heart failure and have any of the following?

      • Decreased apical impulse?

      • Early diastolic heart sound (pericardial knock)?

      • Bilateral pleural effusions?

      • Elevated central venous pressure with:

      • Elevation or failure to fall with inspiration (Kussmaul’s sign)?

      • Prominent y descent or Friedreich’s sign?

      • Hepatomegaly, a pulsatile liver, clinical ascites, and bilateral lower extremity edema?

  • Does the patient have a pericardial friction rub? This can be a 1, 2 or 3 component rub occurring in atrial systole, ventricular systole and early diastole. This is a high-pitched, scratchy heart sound best heard at the left lower sternal border with the patient at end of expiration and leaning forward. Importantly, unlike a pleural friction rub, its presence continues despite having the patient hold their breath.

  • Does the patient have dullness under the left scapula suggesting possible compression of the base of the left lung by the presence of a large pericardial effusion or Bamberger-Pins-Ewart sign?

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

There are no pathognomonic laboratory tests in patients with acute pericarditis. Depending on the possible underlying etiology of the acute pericarditis the following tests might be useful:

  • White blood cell and differential.

  • Chemistry panel (evaluating for advanced kidney disease or the presence of systemic illness affecting other organs).

  • Troponin testing:

    • Because acute pericarditis leads to a superficial epicardial "myocarditis" a significant number of patients will have an elevated troponin test.

    • Importantly the pattern of troponin elevation, peak and resolution can closely mimic that of an acute myocardial infarction patient.

    • Unlike cases of acute coronary syndrome (ACS), the presence of troponin elevation in acute pericarditis is not associated with a negative prognosis.

  • Platelet count, prothrombin time (PT), internationalized normalized ratio (INR) and partial thromboplastin time (PTT) (to rule out an underlying bleeding diathesis that might have caused a hemorrhagic pericarditis).

  • Selected use of antinuclear antibody (ANA) testing, rheumatoid factor and anti-neutrophil cytoplasmic antibody (ANCA) tests depending on the suspicions of an underlying connective tissue disease.

  • Thyroid-stimulating hormone (TSH).

The key diagnostic test in the evaluation of a patient with suspected acute pericarditis is the electrocardiogram (ECG). Importantly there are potentially four ECG stages of acute pericarditis and depending on the underlying etiology the speed at which a patient’s ECG will change is highly variable. Usually a daily ECG is enough to capture changes over time in a hospitalized patient.

  • Stage 1 (concave ST segment elevation notably in the epicardial leads I, II, aVL, aVF, V3-V6. No true reciprocal ST segment depressions except in cavity pattern leads such as aVR, V1 and occasionally in V2).

  • Stage 2 (ST junctions return to baseline with little T wave changes, PR segment depression in epicardial leads which can give the false impression of continued ST segment elevation if the T-P interval is used as the baseline).

  • Stage 3 (diffuse T wave inversions).

  • Stage 4 (ECG resolution to baseline normal).

Some patients with acute pericarditis and an associated pericardial effusion will manifest an overall lowering of their ECG voltage or have evidence of QRS electrical alternans (beat to beat in the amplitude of the QRS voltage). Either finding when not present does not rule out either a pericardial effusion and/or cardiac tamponade.

The chest radiograph is helpful in the evaluation of a patient with suspected acute pericarditis in a number of ways:

  • In most cases of uncomplicated acute pericarditis the chest radiograph will reveal no abnormalities in the cardiac size or lung parenchyma.

  • The presence of cardiomegaly and pulmonary congestion in a patient with acute pericarditis suggests the patient has a myopericarditis or could have constrictive pericarditis.

  • The presence of a "water bottle" shaped cardiac silhouette suggests a large pericardial effusion of at least 250cc of pericardial fluid.

  • The presence of pericardial calcification suggests recurrent pericarditis and possibly constrictive pericarditis (although the sensitivity of pericardial calcification on chest radiography is very low).

While the transthoracic echocardiogram has been recommended for all patients with suspected acute pericarditis by the American College of Cardiology/American Heart Association (ACC/AHA) and the American Society for Echocardiography (ASE), the presence of a significant pericardial effusion only adds pertinent information to the clinical diagnosis of acute pericarditis while a normal result does not rule out acute pericarditis.

The transthoracic echocardiogram is most helpful in patients with acute pericarditis who might have the following additional clinical circumstances:

  • Suspicion of cardiac tamponade

  • Suspicion of constrictive pericarditis

  • Suspicion of myopericarditis-associated acute heart failure

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

The diagnosis of acute pericarditis is clinical and is diagnosed by the presence of at least two out of three of the following criteria:

  • A classic history of acute pericardial pain

  • Physical examination evidence of a pericardial rub

  • ECG consistent with stage 1 changes or serial ECG changes consistent with resolving pericarditis (stage 1 to 2 to 3 to 4; stage 1 to 2 or 4; stage 2 to 3 and/or 4)

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

N/A

III. Management while the Diagnostic Process is Proceeding

A. Management of acute pericarditis.

Identifying the low risk acute pericarditis patient

The focus of the management of patients with acute pericarditis first requires determining that they do not have any of the following emergent conditions that will often require hospital admission and both a specific diagnostic as well as therapeutic plan:

  • Cardiac tamponade⇒emergent echocardiography⇒pericardiocentesis, diagnostic work-up

  • Suspected purulent pericarditis⇒emergent echocardiography⇒pericardiocentesis, diagnostic work-up for infectious etiologies⇒surgery?

  • Myopericarditis⇒echocardiography⇒heart failure management

  • Constrictive pericarditis⇒echocardiography⇒pericardectomy

  • Myocardial infarction related pericarditis⇒coronary angiography⇒ACS treatment

  • Uremic pericarditis⇒emergent hemodialysis

  • Trauma-related pericarditis⇒echocardiography⇒close observation⇒surgical intervention?

  • Oral anticoagulant-related pericarditis⇒echocardiography⇒correct coagulopathy

  • Suspected neoplastic pericarditis⇒echocardiography⇒pericardiocentesis, diagnostic work-up for cancer

  • Suspected large pericardial effusion⇒echocardiography⇒diagnostic work-up for autoimmune, infectious or neoplastic etiologies

  • Febrile pericarditis⇒echocardiography⇒diagnostic work-up for autoimmune or infectious etiologies

  • Immunosuppression-related pericarditis⇒echocardiography⇒diagnostic work-up for infectious etiologies

Patients that do not have any of the above conditions can be characterized as having low-risk acute pericarditis and managed safely as an outpatient with close clinical follow-up.

Treatments for acute pericarditis

First line treatment for low-risk acute pericarditis should include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine or combined therapy with colchicine and aspirin or ibuprofen.

Non-steroidal anti-inflammatory drugs

  • Aspirin

  • Ibuprofen

  • Naproxen

  • Indomethacin

Patients that have risk factors of gastrointestinal toxicity from NSAIDs (history of peptic ulcer disease (PUD), use of anticoagulants or glucocorticoids and aged more than 65 years old) should be placed on concomitant use of proton pump inhibitors when placed on NSAIDs.

Colchicine use with or without aspirin

Use of colchicine alone or in combination with aspirin or ibuprofen has been shown to lead to a reduction in symptoms and prevention of acute as well as recurrent pericarditis among low risk patients.

Glucocorticoids

Patients with acute pericarditis are candidates for glucocorticoid therapy if the following apply:

  • They are refractory to NSAID therapy and/or colchicine treatment and adequately have no clear established etiology for their pericarditis.

  • They have suspected connective tissue disease-related pericarditis.

  • They have uremic pericarditis not responding to aggressive hemodialysis.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

Therapy for acute pericarditis should always address the underlying etiology and careful consideration of its follow-up and management. For example, acute purulent pericarditis requires immediate pericardiocentesis and appropriate antimicrobial therapy.

The most common areas of mismanagement relate to knowing when it is appropriate to do a therapeutic and/or a diagnostic pericardiocentesis and when is it appropriate to consider an aggressive diagnostic evaluation including pericardiocentesis and pericardial biopsy.

Indications for immediate pericardiocentesis

  • Clinical tamponade

  • Suspected purulent pericarditis

  • Suspected neoplastic pericarditis

Contraindications to pericardiocentesis include aortic dissection-associated pericardial effusion, coagulopathy, platelet count less than 50,000 cells/microliter, or a small, posterior or loculated pericardial effusion.

Refractory acute pericarditis with pericardial effusion

Patients with acute pericarditis initially managed as low-risk who have notable pericardial effusion that is not improving or worsening should be considered for more aggressive diagnostic and therapeutic management that should include:

  • Pericardiocentesis with appropriate pericardial fluid studies to evaluate for infection or malignancy

  • Pericardial biopsy to evaluate for granulomatous pericarditis (i.e., tuberculosis) or a neoplastic cause

  • Empiric antituberculosis therapy if no clear diagnosis is made by pericardiocentesis and pericardial biopsy

Non-steroidal anti-inflammatory drug regimes (for acute and recurrent pericarditis)

  • Aspirin 650-1625 milligrams (mg) every 4 hours daily (sample regiment800 mg every 6-8 hours for 7-10 days if acute pericarditis with gradual aspirin dose tapering over 2-4 weeks if recurrent pericarditis)

  • Ibuprofen 200-1200 mg every 6 hours daily (sample regiment 600 mg every 8 hours for 7-14 days if acute pericarditis or with gradual dose tapering over 2-4 weeks in recurrent pericarditis)

  • Naproxen 200-500 mg every 12 hours daily

  • Indomethacin 25-50 mg every 8-12 hours, slow release (SR) 75 mg every 12 hours daily

Colchicine (to prevent recurrences used in combination with aspirin or ibuprofen)

  • Colchicine at doses of 0.2-0.5 mg twice daily for 3 months in acute pericarditis or 6 months for recurrent pericarditis. Dose colchicine once daily if weight < 70 kilograms (kg).

Glucocorticoids

  • Prednisone 0.5-1 mg/kg daily

IV. What’s the evidence?

Reviews

Maisch, B, Seferovic, PM, Ristic, AD, Erbel, R, Rienmuller, R, Adler, Y, Tomkowski, WZ, Thiene, G, Yacoub, MH. "Task Force on the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology. 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". European Heart Journal. vol. 25. 2004. pp. 587-610.

Mumoli, Nicola, Mancini, Antonio, Cei, Marco. "Clinical Practice. Acute Pericarditis". New England Journal of Medicine. vol. 371. 2014. pp. 2410-6.

Assessment

Zayas, R, Anguita, M, Torres, F, Gimenez, D, Bergillos, F, Ruiz, M, Ciudad, M, Gallardo, A, Valles, F. " Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis". American Journal of Cardiology. vol. 75. 1995. pp. 378-82.

Maisch, B, Ristic, AD. "The classification of pericardial disease in the age of modern medicine". Current Cardiology Reports. vol. 4. 2002. pp. 13-21.

Electrocardiography

Spodick, DH. "Pathogenesis and clinical correlations of the electrocardiographic abnormalities of pericardial disease". Cardiovascular Clinics. vol. 8. 1977. pp. 201-13.

Diagnostic tests

Soler-Soler, J, Permanyer-Miralda, G, Sagrista-Sauleda, J. "A systematic diagnostic approach to primary acute pericardial disease. The Barcelona experience". Cardiology Clinics. vol. 8. 1990. pp. 609-20.

Imazio, M, Demichelis, B, Cecchi, E, Belli, R, Ghisio, A, Bobbio, M, Trinchero, R. " Cardiac troponin I in acute pericarditis". Journal of the American College of Cardiology. vol. 42. 2003. pp. 2144-8.

Management

Schifferdecker, B, Spodick, DH. "Non-steroidal anti-inflammatory drugs in the treatment of pericarditis". Cardiology in Review. vol. 11. 2003. pp. 211-7.

Imazio, M, Demichelis, B, Parrini, I, Giuggia, M, Cecchi, E, Gaschino, G, Demarie, D, Ghisio, A, Trinchero, R. " Day-hospital treatment of acute pericarditis: a management program for outpatient therapy". Journal of the American College of Cardiology. vol. 43. 2004. pp. 1042-6.

Imazio, Massimo, Brucato, Antonio, Cemin, Roberto, Ferrua, Stefania, Belli, Riccardo, Maestroni, Silvia, Trinchero, Rita, Spodick, David H, Adler, Yehuda. "CORP (COlchicine for Recurrent Pericarditis) Investigators. Colchicine for recurrent pericarditis (CORP): a randomized trial". Ann Intern Med. vol. 155. 2011. pp. 409-414.

Imazio, M, Gaita, F, LeWinter, M. "Evaluation and Treatment of Pericarditis: A Systematic Review". JAMA. vol. 314. 2015. pp. 1498-1506.

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