Pericarditis
Acute pericarditis is defined as symptoms or signs resulting from pericardial inflammation lasting no more than 1 to 2 weeks. It can occur in various diseases.
The most common cause of acute pericarditis is idiopathic, meaning that no specific cause can be identified through routine diagnostic testing. Most cases of acute idiopathic pericarditis are thought to be of viral origin. However, specific virus testing is not typically conducted because of the associated costs and because this information usually does not impact treatment decisions.
The incidence of acute pericarditis is challenging to quantify due to likely undiagnosed cases. At autopsy, its frequency is about 1%—additionally, 5% of patients with nonischemic chest pain present to the emergency room.
Idiopathic pericarditis is estimated to occur in 80-90% of cases, influenced by demographic factors as well as regional and seasonal variations in viral infections.
Tuberculous pericarditis is a cause of acute pericarditis, but it typically presents with more chronic symptoms.
Patients with bacterial pericarditis are usually critically ill, with other aspects of their illness—such as pericardial effusions, sepsis, and pneumonia—often taking precedence in their clinical presentation.
Pericarditis can occur 24 to 72 hours after a transmural myocardial infarction (MI) as a result of localized inflammation. In the past, delayed pericarditis linked to Dressler syndrome was quite common; however, its incidence has significantly decreased with the introduction of early reperfusion techniques.
Causes of pericarditis
Idiopathic
Infection
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Viral (echovirus, coxsackievirus, adenovirus, cytomegalovirus, hepatitis B, infectious mononucleosis, HIV)
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Bacterial (pneumococcus, staphylococcus, streptococcus, mycoplasma, Lyme disease, Haemophilus influenzae, Neisseria meningitidis, and others)
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Mycobacterial* (Mycobacterium tuberculosis, Mycobacterium avium-intracellulare)
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Fungal (histoplasmosis, coccidioidomycosis) Protozoal
Immune-inflammatory Connective tissue disease
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systemic lupus erythematosus, rheumatoid arthritis, scleroderma, mixed)
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Arteritis (polyarteritis nodosa, temporal arteritis)
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Inflammatory bowel disease
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Early post– myocardial infarction Late post– myocardial infarction (Dressler syndrome),
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late post-cardiotomy/ thoracotomy
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Late post-trauma
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Drug induced (procainamide, hydralazine, isoniazid, cyclosporine, others)
Neoplastic disease
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Primary: mesothelioma, fibrosarcoma, lipoma, others
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Secondary*: breast and lung carcinoma, lymphomas, Kaposi sarcoma
Radiation induced
Early post– cardiac surgery and post– orthotopic heart transplantation
Hemopericardium
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Trauma
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Post– myocardial infarction
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free wall rupture
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Device and procedure related: Percutaneous coronary procedures, implantable defibrillators, pacemakers, post– arrhythmia ablation, post– atrial septal defect closure, post– valve repair or replacement
Dissecting aortic aneurysm
Trauma
Blunt and penetrating, post– cardiopulmonary resuscitation
Congenital
Cysts, congenital absence
Miscellaneous
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Cholesterol (“ gold paint” pericarditis)
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Chronic renal failure, dialysis related
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Chylopericardium
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Hypothyroidism and hyperthyroidism
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Amyloidosis
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Aortic dissection
Differential diagnosis that mimic acute pericarditis
Takotsubo cardiomyopathy
Symptom: Chest pain, dyspnea, syncope, arrhythmias, sudden cardiac death. Usually, in older female patients, it is triggered by an emotional event or exertion.
ECG: ST-segment elevation, T-wave inversion, QTc segment prolongation.
Echocardiography: Apical, midventricular, basal, or focal hypokinesia/akinesia.
Coronary angiography: Absence of obstructive CAD
Myocardial infarction
Symptom: Chest pain, dyspnea, arrhythmias, sudden cardiac death.
ECG: ST-segment elevation, ST-segment depression, and/or T-wave inversion.
Echocardiography: Regional wall motion abnormalities according to epicardial coronary artery distribution.
Coronary angiography: Coronary artery disease with acute plaque rupture, thrombus formation, and coronary dissection.
Myocarditis
Symptom: Chest pain, dyspnea, acute heart failure, sudden cardiac death. Usually in young or middle-aged populations, often preceded by an upper respiratory infection or enteritis.
ECG: Nonspecific ST-segment and T-wave changes (diffuse ST-segment elevation is usually seen in myopericarditis/perimyocarditis).
Echocardiography: Global systolic dysfunction (sometimes regional or segmental). Pericardial involvement may also be present.
Coronary angiography: Absence of obstructive CAD or angiographic evidence of acute plaque rupture.
Acute pericarditis
Symptom: Chest pain, with changes according to position (worse leaning back), pericardial rub, pericardial effusion.
ECG: PR-segment depression, concave ST-segment elevation, T-wave inversion.
Echocardiography: Pericardial effusion, cardiac tamponade, constrictive physiology.
Coronary angiography: Absence of obstructive CAD or angiographic evidence of acute plaque rupture.
Symptom
Patients with uncomplicated acute pericarditis often seem uncomfortable and anxious; they may present with low-grade fever and sinus tachycardia.
Patients may experience sharp, pleuritic retrosternal chest pain that can radiate to the back or trapezius ridge. The pain typically worsens when lying down and improves with leaning forward.
Complications of acute pericarditis include effusion, tamponade, and constriction. As noted earlier, small effusions are common.
Myocarditis is better described as an associated condition rather than a complication.
Pericarditis and myocarditis frequently occur together, and the terms used to describe this phenomenon are perimyocarditis (predominant myocarditis with pericardial involvement) or myopericarditis (predominant pericarditis with myocardial involvement).
Definitions of Pericarditis According to the Time of Presentation
Definition
Acute Event lasting <4 to 6 weeks
Incessant Event lasting >4 to 6 weeks without remission
Recurrent New signs and symptoms of pericardial inflammation after a symptom-free interval of 4 to 6 weeks
Chronic Pericarditis lasting >3 months
Physical examination
The only abnormal physical finding is the friction rub caused by contact between visceral and parietal pericardium.
A pericardial friction rub is pathognomonic, often described as similar to "walking on crunchy snow." It occurs in three phases: ventricular systole, ventricular diastole, and atrial systole.
However, in atrial fibrillation, atrial systole is absent. Place the stethoscope's diaphragm at the left lower sternal border, leaning forward, to listen for this sound.
The pericardial friction rub can vary in intensity and may become more or less audible at different times during the day. It is important to listen to a patient suspected of having pericarditis regularly, even if the rub is not initially detectable.
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Electrocardigraphy
ECG content you are viewing is a Creative Commons work, credited to James Heilman, MD.
The ST-segment vector usually points leftward, anteriorly, and inferiorly, with ST-segment elevation observed in all leads except aVR and often V1. The ST segment typically appears coved upward, resembling the current of injury seen in acute, transmural ischemia.
PR-segment depression is common. It can occur without ST elevation and may be the initial or only electrocardiographic manifestation of acute pericarditis.
Subsequent electrocardiographic changes:
In patients who present late after the onset of symptoms, these electrocardiographic changes may be difficult to distinguish from ischemia.
days to weeks
weeks to months
Echocardiography
The echocardiogram is typically normal in cases of acute idiopathic pericarditis and is primarily used to rule out the presence of silent effusions.
The size of the echo-free space between the pericardial layers at the end of diastole is categorized semiquantitatively as follows: trivial (only noted during systole), small (less than 10 mm), moderate (10 to 20 mm), large (21 to 25 mm), and very large (greater than 25 mm). A significant amount of pericardial fluid can help identify patients with acute pericarditis who are at a higher risk of complications.
Echocardiography is essential for guiding pericardial drainage in cases of severe pericardial effusion or cardiac tamponade.
Moreover, echocardiography plays a crucial role in identifying complications such as tamponade or constrictive pericarditis. It is also valuable for monitoring pericardial effusion and evaluating the treatment response. It also assists in assessing whether associated myocarditis affects ventricular function and is useful in detecting myocardial infarction (MI).
Screening the specific causes
It is important to screen for specific causes that may influence management, detect any effusion or other echocardiographic abnormalities, alleviate symptoms, and provide appropriate treatment if a specific cause is identified.
Initially, it is recommended to obtain the following laboratory data: ECG, CBC, chest radiograph, serum creatine kinase, troponin I, and echocardiogram.
In young women, testing for systemic lupus erythematosus (SLE) may be reasonable; however, it is worth noting that low antinuclear antibody (ANA) titers are often found in patients with recurrent idiopathic pericarditis who do not meet other criteria for SLE.
Treatment
Acute idiopathic pericarditis is a self-limited disease without significant complications or recurrence in 70% to 90% of patients.
Symptomatic treatment with a 2 week course of nonsteroidal anti-inflammatory drugs (NSAIDs) should be initiated.
NSAIDs (Anti-inflammatory dose)
Aspirin 750-1000 mg tid (prefer in patient with recent MI)
Ibuprofen 600-800 mg bid or tid
Naproxen 250-500 mg tid
Indomethacin 25-50 mg bid
Patients who do not respond well initially, have larger effusions, or have a suspected cause other than idiopathic pericarditis should be hospitalized for additional observation, diagnostic testing, and treatment as necessary.
Patients who respond slowly or inadequately to NSAIDs may require supplementary narcotic analgesics to allow time for a full response or a course of colchicine.
Hospitalization is recommended for patients with myocardial involvement. Studies in animal models of myocarditis have shown that non-steroidal anti-inflammatory drugs (NSAIDs) can increase mortality rates. Therefore, the European Society of Cardiology guidelines suggest using a lower dose of NSAIDs in these cases.
Colchicine
Colchicine is known for its anti-inflammatory effects, as it blocks tubulin polymerization, impairing microtubule assembly and inhibiting inflammasome formation and cytokine release in white blood cells, especially granulocytes. For acute pericarditis, it's recommended to use weight-adjusted dosing of colchicine alongside aspirin or another NSAID. While NSAIDs are usually stopped once pain subsides and CRP levels normalize, continuing colchicine may help prevent symptoms from persisting or recurring. Its benefits are well established for both acute and recurrent pericarditis.
The most common side effect of colchicine is gastrointestinal intolerance, which causes discontinuation in 5% to 8% of patients. Myelosuppression and aplastic anemia occur rarely at recommended doses (0.5 to 1.2 mg daily). The risk of neuromuscular toxicity increases with P-glycoprotein inhibitors. Patients over 70 years or weighing less than 70 kg should receive an adjusted dose.
1st episode of pericarditis
Colchicine in Addition to Conventional Therapy for Acute Pericarditis (COPE) trial: A prospective, randomized, open-label study involved 120 patients (mean age 56.9 ± 18.8 years; 54 males) experiencing their first episode of acute pericarditis. Patients were assigned to two groups: Group I received aspirin, while Group II received aspirin plus colchicine (1.0 to 2.0 mg on the first day, then 0.5 to 1.0 mg daily for three months). Corticosteroids were used only for those who could not tolerate aspirin.
The primary endpoint was the recurrence rate. After 2873 patient months of follow-up, colchicine significantly reduced recurrence rates at 18 months (10.7% vs. 32.3%; P = 0.004) and symptom persistence at 72 hours (11.7% vs. 36.7%; P = 0.003). Multivariate analysis identified corticosteroid use as an independent risk factor for recurrences (OR 4.30; P = 0.024). Colchicine was discontinued in 5 cases (8.3%) due to diarrhea, but no serious adverse effects were reported.
A multivariate logistic regression analysis identified corticosteroid use as an independent risk factor for recurrences, with an odds ratio of 4.30 (95% CI 1.21 to 15.25; P=0.024), after accounting for age, gender, pericardial effusion, severe pericardial effusion, cardiac tamponade, etiology, and colchicine therapy.
A Randomized Trial of Colchicine for Acute Pericarditis (ICAP) trial: In a multicenter, double-blind trial, eligible adults with acute pericarditis were randomly assigned to receive colchicine or a placebo alongside conventional anti-inflammatory therapy (aspirin or ibuprofen). Colchicine was given at 0.5 mg twice daily for patients over 70 kg and once daily for those 70 kg or less. The primary outcome was the occurrence of incessant or recurrent pericarditis.
Of the 240 enrolled patients, 120 were assigned to each group. The primary outcome occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group, achieving a relative risk reduction of 0.56 (95% CI: 0.30 to 0.72; P<0.001).
Colchicine also decreased symptom persistence at 72 hours (19.2% vs. 40.0%, P=0.001), the number of recurrences per patient (0.21 vs. 0.52, P=0.001), and hospitalization rates (5.0% vs. 14.2%, P=0.02). The remission rate at one week was higher in the colchicine group (85.0% vs. 58.3%, P<0.001). Adverse effects and drug discontinuation rates were similar in both groups, with no serious adverse events reported.
Recurrent pericarditis
The Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial: A prospective, randomized, open-label study investigated the safety and efficacy of colchicine as an adjunct to conventional treatment for the first episode of recurrent pericarditis. Eighty-four patients were assigned to receive either aspirin alone or aspirin combined with colchicine (1.0-2.0 mg on the first day, then 0.5-1.0 mg daily for six months). For those for whom aspirin was contraindicated, prednisone (1.0-1.5 mg/kg daily) was used for one month.
Over 1,682 patient-months (mean follow-up of 20 months), colchicine significantly reduced the recurrence rate (24.0% vs. 50.6% at 18 months; P = 0.02) and symptom persistence at 72 hours (10% vs. 31%; P = 0.03). Prior corticosteroid use was linked to higher recurrence (odds ratio = 2.89; P = 0.04). No serious adverse effects were noted.
Multiple recurrent pericarditis
The Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial: A multicenter, double-blind trial conducted at four hospitals in northern Italy enrolled adult patients with multiple recurrences of pericarditis (two or more episodes). Patients were randomly assigned in a 1:1 ratio to receive either a placebo or colchicine (0.5 mg twice daily for those over 70 kg, or once daily for those 70 kg or less), along with standard anti-inflammatory treatment (aspirin, ibuprofen, or indometacin). Randomization was performed using a central automated system, and both patients and investigators were blinded to the treatment allocation.
Out of 240 enrolled patients, 120 were in each group. In the colchicine group, 26 patients (21.6%) had recurrent pericarditis compared to 51 patients (42.5%) in the placebo group, resulting in a relative risk of 0.49 (95% CI 0.24–0.65; p=0.0009), with a number needed to treat of 5. Adverse effects, primarily gastrointestinal intolerance (nine patients in each group) and hepatotoxicity (three in colchicine vs. one in placebo), occurred at similar rates, and no serious adverse events were reported.
Post-cardiotomy syndrome
The COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): A multicenter, randomized, double-blind, placebo-controlled trial included 360 patients (mean age 65.7 years; 66% male), randomly assigned to receive either a placebo or colchicine. The colchicine regimen started with 1.0 mg twice daily on the first day, followed by 0.5 mg twice daily for one month for patients weighing 70 kg or more, with lower doses for lighter patients.
The primary endpoint was the incidence of post-pericardiotomy syndrome (PPS) at 12 months, while secondary endpoints included disease-related hospitalization and other cardiac complications. Results showed that colchicine significantly reduced PPS incidence compared to placebo (8.9% vs. 21.1%; P = 0.002). It also lowered rates of secondary endpoints (0.6% vs. 5.0%; P = 0.024). Side effects were similar between groups (8.9% for colchicine vs. 5.0% for placebo; P = 0.212).
Immunosupressive in patients with recurrent or refractory pericarditis
Corticosteroid:
Systemic corticosteroids, such as prednisone, are mainly used as second- or third-line treatments. Retrospective studies have linked their use to longer disease courses and higher recurrence rates. The COPE trial found that a history of corticosteroid use increases the risk of recurrence by 4.3 times.
Low-dose, weight-based corticosteroid treatment therapy (e.g., prednisone 0.2 to 0.5 mg/kg) was associated with lower rates of recurrence or treatment failure, hospitalizations, and adverse effects compared with high-dose corticosteroids (e.g., prednisone 1.0 mg/kg/day).
There is evidence suggesting that probably due to inadequate clearance of viral particles in the pericardial space.
The tapering should be done very slowly, and every decrease in dose should be performed only in asymptomatic patients with CRP levels <3.0 mg/l
IL-1 receptor antagonist
Anakinra, an IL-1 receptor antagonist, has proven beneficial in recurrent pericarditis in a randomized clinical trial (below).
Another randomized controlled trial is ongoing to evaluate anakinra's efficacy for treating acute pericarditis [NCT03224585]. However, data supporting IL-1 blockade in acute pericarditis is limited and primarily consists of a single case series [full text]
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The Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence (AIRTRIP) trial: A double-blind, placebo-controlled, randomized withdrawal trial was conducted among 21 patients at three Italian referral centers between June and November 2014, with follow-up ending in October 2015. Participants had recurrent pericarditis (three or more episodes), elevated C-reactive protein, colchicine resistance, and corticosteroid dependence.
Patients received anakinra at 2 mg/kg per day (up to 100 mg) for two months. Those who responded were randomized to continue with anakinra (n = 11) or switch to placebo (n = 10) for six months or until recurrence. Follow-up lasted 12 months, with a median duration of 14 months.
Recurrent pericarditis occurred in 9 of 10 patients (90%) on placebo and 2 of 11 patients (18.2%) on anakinra, showing a significant difference in incidence rates (-1.95%, 95% CI, -3.3% to -0.6%). Median time to recurrence was 72 days for the placebo group and not reached for anakinra (P < .001).
During treatment, 95.2% of anakinra patients experienced transient local skin reactions, including one case of herpes zoster and three cases of elevated transaminase levels. No patients discontinued treatment, and no adverse events were reported during placebo treatment.
Lifestyle modifications
Exercise-induced tachycardia and shear stress may worsen inflammation, and increased blood flow to the pericardium can contribute to oxidative stress.
U.S. and European guidelines advise that athletes should return to competitive sports only after symptoms have resolved and tests are normal, with a minimum restriction of three months.
Patients with myocardial involvement should avoid physical activity for at least six months.
Summary of treatment
Acute pericarditis
Aspirin 750-1,000 mg every 8 h for 1-2 weeks
Ibuprofen 600 mg every 8 h for 1-2 weeks
Colchicine 0.5-1.2 mg in one or divided doses for 3 months
Recurrent pericarditis
Aspirin 750-1,000 mg every 8 h for weeks to months
Ibuprofen 600-800 mg every 8 h for weeks to months
Indomethacin 25-50 mg every 8 h for weeks to months
Colchicine 0.5-1.2 mg in one or divided dose at least 6 months
Prednisolone 0.2-0.5 mg/kg/day for months
Anakinra 1-2 mg/kg/day up to 100 mg/day for months
Rilonacept 320 mg once, then 160 mg weekly for months
Azathioprine 1 mg/kg/day up to 2-3 mg/kg/day for months
Methotrexate 10-15 mg weekly for months
IVIGs 400-500 mg/kg/day for 5 days
Tamponade
Pericardiocentesis
Pericardial window
Constrictive pericarditis
If there is active inflammation, then anti-inflammatory therapy is the first line of treatment; pericardiectomy is recommended for refractory cases.
If there is no active inflammation, then pericardiectomy is the preferred approach.
References
Bonow, Robert O.; Mann, Douglas L. ; Zipes, Douglas P.; Libby, Peter. Braunwald's Heart Disease E-Book. Elsevier Health Sciences. Kindle Edition.
Chiabrando JG, Bonaventura A, Vecchié A, Wohlford GF, Mauro AG, Jordan JH, et al. Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2020 Jan 7;75(1):76–92.
Imazio M. Pericarditis Associated with Myocardial Involvement (Myopericarditis/Perimyocarditis). In: Imazio M, editor. Myopericardial Diseases: Diagnosis and Management [Internet]. Cham: Springer International Publishing; 2016. p. 105–12.
Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, et al. Colchicine in Addition to Conventional Therapy for Acute Pericarditis. Circulation. 2005 Sep 27;112(13):2012–6.
Imazio Massimo, Brucato Antonio, Cemin Roberto, Ferrua Stefania, Maggiolini Stefano, Beqaraj Federico, et al. A Randomized Trial of Colchicine for Acute Pericarditis. New England Journal of Medicine. 369(16):1522–8.
Imazio M, Bobbio M, Cecchi E, Demarie D, Pomari F, Moratti M, Ghisio A, Belli R, Trinchero R. Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial. Arch Intern Med. 2005 Sep 26;165(17):1987-91.
Imazio M, Belli R, Brucato A, Cemin R, Ferrua S, Beqaraj F, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. The Lancet. 2014 Jun 28;383(9936):2232–7.
Brucato A, Imazio M, Gattorno M, et al. Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA. 2016;316(18):1906–1912.
Kougkas N, Fanouriakis A, Papalopoulos I, Bertsias G, Avgoustidis N, Repa A, Sidiropoulos P. Canakinumab for recurrent rheumatic disease associated-pericarditis: a case series with long-term follow-up. Rheumatology (Oxford). 2018 Aug 1;57(8):1494-1495.