Residency · Residency · Internal Medicine

Acute and Chronic Pericardial Disease

Anatomy and Physiology of the Pericardium

The pericardium consists of two layers -- the visceral layer (also called the epicardium) and the parietal layer -- separated by the pericardial space, which normally contains 15 to 50 mL of serous fluid. The pericardium serves several important functions: it reduces friction during cardiac contraction, limits acute cardiac distension, provides a barrier against infection from adjacent structures, and anchors the heart within the mediastinum. A clinically critical concept is pericardial compliance. The normal pericardium is relatively stiff, meaning that rapid fluid accumulation can produce tamponade physiology at volumes as small as 150 to 200 mL, whereas chronic effusions that develop slowly may be tolerated at volumes exceeding 1 liter.

Acute Pericarditis

Etiology

The vast majority of acute pericarditis cases in developed countries are idiopathic, with a presumed viral etiology in 80 to 90 percent. Known viral culprits include Coxsackievirus B, echovirus, adenovirus, parvovirus B19, HHV-6, HIV, and SARS-CoV-2. Bacterial (purulent) pericarditis is caused by organisms such as Staphylococcus and Streptococcus, while tuberculosis is a common cause in endemic areas. Autoimmune and inflammatory conditions including SLE, rheumatoid arthritis, sarcoidosis, and post-cardiac injury syndromes (Dressler syndrome, post-pericardiotomy) can all cause pericarditis. Uremic pericarditis is seen in advanced CKD and ESRD and represents an indication for urgent dialysis. Neoplastic causes include lung cancer, breast cancer, lymphoma, and melanoma. Drug-induced pericarditis may result from hydralazine, procainamide, isoniazid, or immune checkpoint inhibitors. Post-MI pericarditis occurs in two forms: early (within 1 to 3 days, from direct inflammation) and late (Dressler syndrome, 2 to 10 weeks out, autoimmune in nature). Radiation-induced pericarditis is often delayed by months to years.

Clinical Presentation

The chest pain of acute pericarditis is typically sharp and pleuritic, worsened by lying supine and improved by sitting up and leaning forward. Radiation to the trapezius ridge is nearly pathognomonic for pericardial origin, resulting from irritation of the phrenic nerve. The pericardial friction rub is a scratchy, high-pitched sound best heard with the diaphragm of the stethoscope at the left lower sternal border in end-expiration with the patient leaning forward. It is classically triphasic (corresponding to atrial systole, ventricular systole, and early diastole) but may be mono- or biphasic. Importantly, the rub is evanescent -- its absence at any given moment does not exclude pericarditis. Patients may also have low-grade fever, malaise, and a preceding viral prodrome.

Diagnostic Criteria (At least 2 of 4 required -- ESC 2015)

The diagnosis of acute pericarditis requires at least two of four criteria: typical pericardial chest pain, a pericardial friction rub on examination, new widespread ST elevation or PR depression on ECG, and new or worsening pericardial effusion on imaging.

ECG Findings -- Four Stages

The ECG changes of pericarditis evolve through four stages. Stage 1, occurring within hours to days, shows diffuse concave-upward ST elevation with PR depression, except in lead aVR which shows ST depression and PR elevation. Stage 2 (days) features normalization of ST segments and T-wave flattening. Stage 3 (weeks) shows diffuse T-wave inversions. Stage 4 (weeks to months) shows normalization. The key distinction from STEMI is that pericarditis produces diffuse rather than territorial changes, concave ST elevation, PR depression, no reciprocal changes, and no Q waves. The Spodick sign, a downsloping TP segment visible in stage 1, is an additional helpful clue.

Laboratory Studies

Inflammatory markers are typically elevated, with CRP increased in more than 75 percent of cases. Troponin may be mildly elevated in up to 30 percent of cases, indicating myopericarditis. This distinction matters: myopericarditis refers to pericarditis with troponin elevation but preserved LV function, while perimyocarditis refers to pericarditis with both troponin elevation and LV dysfunction, which carries a worse prognosis. Baseline workup includes CBC, BMP, and TSH, with additional testing directed by clinical suspicion (ANA, RF, QuantiFERON, HIV, blood cultures).

Imaging

Echocardiography is used to assess for pericardial effusion and tamponade physiology, though it may be normal in dry pericarditis. Chest X-ray is usually normal unless a large effusion produces the classic water-bottle silhouette. Cardiac MRI is the gold standard for demonstrating pericardial inflammation via late gadolinium enhancement of the pericardium and is particularly useful for diagnosing myopericarditis.

Treatment of Acute Pericarditis

NSAIDs are first-line therapy, with ibuprofen 600 mg three times daily or aspirin 750 to 1000 mg three times daily being standard options. Aspirin should be used preferentially in post-MI pericarditis. Treatment is tapered over 2 to 4 weeks, guided by symptoms and CRP levels. Colchicine is now considered mandatory adjunctive therapy based on the COPE and ICAP trials, given at a dose of 0.5 mg twice daily (or 0.5 mg daily if the patient weighs less than 70 kg) for 3 months after a first episode. Colchicine reduces the recurrence rate from approximately 30 percent to 15 percent and should be started with the first episode, not reserved for recurrent disease. Corticosteroids should be avoided as first-line therapy because they are associated with increased recurrence rates. They are reserved for patients with contraindications to both NSAIDs and colchicine, those with autoimmune etiology, or uremic pericarditis. When steroids are necessary, low-dose prednisone (0.25 to 0.5 mg/kg) with a very slow taper is recommended. Activity restriction is important: patients should avoid strenuous exercise until symptoms have resolved and CRP has normalized, with a minimum of 3 months for athletes.

High-Risk Features Requiring Hospitalization

Features that should prompt hospitalization include fever above 38 degrees Celsius, subacute onset, large effusion, tamponade, failure of NSAID therapy after one week, immunosuppression, concurrent anticoagulation use, and myopericarditis with LV dysfunction. Elevated troponin alone with preserved ejection fraction (simple myopericarditis) does not mandate admission.

Recurrent Pericarditis

Recurrent pericarditis occurs in 15 to 30 percent of patients after a first episode, and the risk increases with each subsequent recurrence. It is defined as symptom recurrence after a symptom-free interval of at least 4 to 6 weeks. Incessant pericarditis, by contrast, refers to symptoms persisting beyond 4 to 6 weeks but less than 3 months without any period of remission.

Management of Recurrent Pericarditis

Treatment involves resuming NSAIDs plus colchicine, with colchicine extended to at least 6 months. Corticosteroids may be added at low doses with a very slow taper, decreasing by no more than 1 to 2.5 mg every 2 to 4 weeks. For corticosteroid-dependent recurrent pericarditis, steroid-sparing agents are introduced in a stepwise fashion. Options include azathioprine and IVIG. Anakinra, an IL-1 receptor antagonist, showed dramatic reduction in recurrence in the AIRTRIP trial and should be considered for colchicine-resistant, corticosteroid-dependent disease. Rilonacept, an IL-1 trap, became the first FDA-approved targeted therapy for recurrent pericarditis based on the RHAPSODY trial. Pericardiectomy remains a last resort for severely refractory cases.

Pericardial Effusion

Classification by Size

Pericardial effusions are classified by the echo-free space: small (less than 10 mm, posterior only), moderate (10 to 20 mm), and large (greater than 20 mm).

Etiology

The differential diagnosis mirrors that of pericarditis, with the addition of hypothyroidism, heart failure (transudative), and aortic dissection (hemorrhagic). Large chronic effusions without active inflammation may be remarkably well tolerated.

Evaluation

Echocardiography assesses size, location, fibrin strands, and signs of tamponade. Pericardiocentesis is indicated for tamponade, suspected bacterial or tuberculous pericarditis, large effusions not responding to medical therapy, and diagnostic uncertainty. Pericardial fluid analysis includes cell count, protein, LDH, glucose, cytology, cultures (bacterial, mycobacterial, fungal), and adenosine deaminase for tuberculosis.

Cardiac Tamponade

Pathophysiology

Cardiac tamponade occurs when pericardial fluid accumulation exceeds the compliance of the pericardium, leading to equalization of diastolic pressures across all four cardiac chambers. This impairs ventricular filling and decreases cardiac output. Critically, the rate of fluid accumulation matters more than the absolute volume.

Clinical Features -- Beck's Triad

The classic Beck's triad consists of hypotension, jugular venous distension, and muffled heart sounds, though all three are not always present. Pulsus paradoxus, defined as a drop in systolic blood pressure of more than 10 mmHg during inspiration, reflects exaggerated ventricular interdependence and is a key bedside clue to tamponade. It may be absent in the setting of atrial septal defect, severe aortic regurgitation, or positive-pressure ventilation. Other findings include tachycardia, tachypnea, electrical alternans on ECG (from a swinging heart), and low-voltage QRS complexes.

Echocardiographic Findings

The earliest and most sensitive echocardiographic sign is right atrial collapse in systole, while right ventricular diastolic collapse is the most specific finding. IVC plethora without respiratory variation (greater than 2.1 cm with less than 50 percent collapse) and exaggerated respiratory variation in mitral and tricuspid inflow velocities are additional supportive findings.

Management

Pericardiocentesis is the definitive treatment, typically performed using an echo-guided subxiphoid approach. Temporizing measures include an IV fluid bolus to increase preload, while diuretics and vasodilators should be avoided. A surgical pericardial window is considered for recurrent effusions or loculated collections. Positive-pressure ventilation should be avoided because it further decreases preload.

Constrictive Pericarditis

Etiology

Constrictive pericarditis results from chronic pericardial inflammation leading to fibrosis and calcification. Common causes include post-infectious (viral, tuberculosis), post-surgical, post-radiation, and idiopathic etiologies.

Clinical Presentation

Patients present with symptoms of right-sided heart failure, including peripheral edema, ascites that is often out of proportion to peripheral edema, and hepatomegaly. The presentation can closely mimic restrictive cardiomyopathy and cirrhosis. The Kussmaul sign, a paradoxical rise in jugular venous pressure with inspiration reflecting impaired right ventricular filling, is a hallmark finding. The pericardial knock is an early diastolic sound that occurs earlier than an S3. On JVP tracing, prominent x and y descents are characteristic, with a steep y descent being particularly notable.

Diagnosis

Echocardiography reveals a septal bounce with respiratory shift, increased E velocity with a restrictive filling pattern, and annulus paradoxus (increased e-prime velocity despite restrictive filling), which is the key feature distinguishing constriction from restrictive cardiomyopathy. CT chest may show pericardial thickening greater than 4 mm and calcification. Cardiac MRI demonstrates pericardial thickening and late gadolinium enhancement indicating active inflammation. Cardiac catheterization shows equalization of diastolic pressures, the "square root sign" in ventricular pressure tracings, and discordance of RV and LV pressures with respiration (concordance would suggest restrictive cardiomyopathy instead).

Constrictive vs. Restrictive Cardiomyopathy

Management

Transient constrictive pericarditis, which may occur in up to 20 percent of cases, can resolve with anti-inflammatory therapy, so a trial of NSAIDs plus colchicine is reasonable before committing to surgery. Pericardiectomy is the definitive treatment for chronic constriction, though it carries significant operative mortality of 5 to 10 percent, with worse outcomes in radiation-induced constriction. Medical therapy with diuretics provides symptom management while awaiting surgery.

<image> A four-panel ECG comparison showing: (1) Stage 1 acute pericarditis with diffuse concave-upward ST elevation and PR depression with Spodick sign, (2) STEMI with territorial convex ST elevation and reciprocal changes, (3) early repolarization with ST elevation limited to precordial leads with notched J-point, and (4) electrical alternans in cardiac tamponade. Each panel should have clear labels and annotations highlighting the distinguishing features. </image>

<image> A medical illustration showing the pathophysiology of cardiac tamponade. The diagram should depict a heart surrounded by pericardial fluid with compressed cardiac chambers. Include a pressure-volume compliance curve of the pericardium showing the steep rise in intrapericardial pressure as fluid accumulates beyond the compliance reserve. Show the difference between rapid accumulation (acute tamponade at small volumes) versus slow accumulation (chronic effusion tolerating large volumes before tamponade). </image>

<image> An echocardiographic schematic comparing normal pericardium, pericardial effusion with tamponade physiology (showing RA and RV collapse), and constrictive pericarditis (showing thickened pericardium with septal bounce). Include corresponding M-mode and Doppler findings for each condition. Label key findings: RV diastolic collapse, respiratory variation in mitral inflow, septal bounce, and annulus paradoxus. </image>

<image> A treatment algorithm flowchart for pericarditis management. Starting with "First Episode of Acute Pericarditis," branching into risk assessment (low-risk outpatient vs. high-risk inpatient). The treatment pathway shows first-line therapy (NSAIDs + colchicine), with branches for recurrent pericarditis (corticosteroids, then steroid-sparing agents like anakinra and rilonacept) and refractory disease (pericardiectomy). Include CRP monitoring checkpoints and activity restriction timelines. </image>

Clinical Pearls

Trapezius ridge radiation is nearly pathognomonic for pericardial pain and distinguishes it reliably from myocardial ischemia. Colchicine should always be started from the first episode of pericarditis, as it is the single most important intervention to prevent recurrence. Corticosteroids should be avoided as first-line therapy for idiopathic or viral pericarditis because they increase recurrence rates. When steroids must be used, low doses with extremely slow tapers are essential, since rapid tapers are the most common cause of recurrence. Pulsus paradoxus greater than 10 mmHg is the key bedside clue to tamponade, but it can be absent in aortic regurgitation, ASD, and positive-pressure ventilation. Uremic pericarditis requires urgent dialysis, not NSAIDs. Constrictive pericarditis is one of the great masqueraders in medicine -- it should always be considered in patients with unexplained right heart failure, especially when ascites is out of proportion to peripheral edema. For post-MI pericarditis, aspirin (not ibuprofen or other NSAIDs, which may impair myocardial healing) plus colchicine is the appropriate regimen.

References

• Adler Y, et al. 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases. European Heart Journal. 2015.
• Imazio M, et al. COPE Trial: Colchicine for Acute Pericarditis. Circulation. 2005.
• Imazio M, et al. ICAP Trial: Colchicine for Acute Pericarditis. NEJM. 2013.
• Brucato A, et al. AIRTRIP Trial: Anakinra for Recurrent Pericarditis. NEJM. 2016.
• Klein AL, et al. RHAPSODY Trial: Rilonacept for Recurrent Pericarditis. NEJM. 2021.
• Imazio M, et al. Recurrent Pericarditis: State of the Art. European Heart Journal. 2022.
• Welch TD, et al. Constrictive Pericarditis: Diagnosis and Management. JACC. 2018.

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