The pericardium is a fibroelastic sac with the following layers (from outermost to innermost) ^[1]:

• Lubrication: Pericardial fluid reduces friction between the beating heart and surrounding structures
• Mechanical constraint: Limits acute cardiac distension (prevents overdilation of chambers)
• Barrier: Protects the heart from infection spreading from adjacent structures (lungs, mediastinum)
• Ventricular interdependence: The fixed pericardial space means that when one ventricle fills more, the other fills less — this principle underlies pulsus paradoxus in tamponade
• Anchoring: Fixes the heart in the mediastinum

• By definition, no identifiable cause is found
• Most are presumed viral — but we don't routinely test for viruses because it doesn't change management
• In clinical practice, "idiopathic" and "viral" pericarditis are treated synonymously

• Pathophysiology: Direct pericardial invasion, lymphatic obstruction (preventing drainage of pericardial fluid), or haematogenous metastasis
• Often causes haemorrhagic or exudative effusion
• May present with large effusion and tamponade as first manifestation of malignancy

• SLE: Pericarditis is one of the most common cardiac manifestations (occurs in 20–40% of SLE patients during their disease course ^[2])
  • SLE cardiac features: pericarditis, cardiomyopathy, pulmonary hypertension, Libman-Sacks endocarditis ^[6]
  • Pathophysiology: Immune complex deposition in pericardium → complement activation → inflammation
• RA: Up to 30% have echocardiographic pericardial effusion but only < 10% have clinical pericarditis. Management is related to disease activity — usually treated by steroids/NSAIDs ^[8]
• Systemic sclerosis, Sjögren's syndrome ^[1]
• Vasculitis: EGPA (Eosinophilic Granulomatosis with Polyangiitis), GPA (Granulomatosis with Polyangiitis), Polyarteritis nodosa ^[1]
• Mixed Connective Tissue Disease (MCTD): Cardiac involvement in ~20% including pericarditis, conduction abnormality, cor pulmonale ^[8]

• Uraemic pericarditis ^[1][7][9]:
  • Occurs in advanced CKD / ESRD (typically GFR < 15 mL/min or on dialysis)
  • Pathophysiology: Accumulation of uraemic toxins → direct chemical irritation of pericardial mesothelial cells → "sterile" inflammation → fibrinous pericarditis
  • Characteristically does not show the typical ECG changes of acute pericarditis (no diffuse ST elevation) because the inflammation is more "chemical" than inflammatory
  • Management: intensification of dialysis is the primary treatment ^[9]
• Hypothyroidism (Myxoedema) ^[1]:
  • Causes pericardial effusion due to accumulation of mucopolysaccharides (myxoedematous fluid)
  • Usually slowly accumulating → rarely causes tamponade
  • Resolves with thyroid hormone replacement

• Doxorubicin, Procainamide, Hydralazine, Isoniazid, Cyclosporin A ^[1]
• Procainamide and hydralazine can cause a drug-induced lupus-like syndrome → serositis including pericarditis ^[8]
• Immune checkpoint inhibitors (e.g. nivolumab, pembrolizumab) — increasingly recognized in 2024–2026 as a cause of immune-related pericarditis/myocarditis

• Pericardial perforation: Post-pericardiotomy, Penetrating injury, Chest trauma ^[1]
• Cardiac injury: Pacemaker insertion, PCI, Radiofrequency ablation ^[1][7]
• Post-pericardiotomy syndrome: Occurs days to weeks after cardiac surgery; mechanism is autoimmune (similar to Dressler's syndrome)

This is an extremely high-yield distinction:

• Why does Dressler's syndrome occur? Myocardial necrosis releases intracellular antigens (e.g. cardiac myosin) that are normally hidden from the immune system → the immune system mounts an autoimmune response against these "neo-antigens" → pericardial inflammation

Why does pericardial effusion cause tamponade only sometimes?

• The pericardium has a pressure-volume curve with an initial flat portion (compliant) and then a steep exponential rise ^[2]
• Acute ↑volume → no time for pericardium to stretch → rapid ↑pressure ^[2]
• Chronic ↑volume → gradual ↑compliance → slow ↑pressure → can accumulate up to 2L of fluid without tamponade ^[2]
• This explains why a post-traumatic haemopericardium of only 150–200 mL can cause tamponade (acute), while a malignant effusion of 1–2L may only cause mild symptoms (chronic)

Why does sitting up and leaning forward relieve pericardial pain?

• This is due to ↓pressure on the parietal pericardium in this position ^[2] — gravity pulls the heart anteriorly and slightly away from the posterior parietal pericardium, reducing friction and irritation of pain-sensitive nerve endings

Why is the pain pleuritic (worse with inspiration)?

• During inspiration, the diaphragm descends → lung expands → the inflamed pericardium is stretched and moves against the adjacent inflamed pleura → increased friction → increased pain
• The phrenic nerve (which innervates the parietal pericardium) is also stretched during deep inspiration

• Pericarditis occurs as part of pancarditis (affects all three layers: endocardium, myocardium, pericardium) ^[10]
• Characteristically, rheumatic heart disease is the only disease that affects all three layers of the heart ^[10]
• Usually children 5–15 years old, preceded by GAS pharyngitis 2–3 weeks before

• Pericarditis associated with pericardial effusion is a recognized complication ^[11]
• Part of the spectrum of pancarditis (pericarditis, myocarditis, endocarditis) in acute KD

• 20–40% of SLE patients experience clinically detectable pericarditis during the course of the disease ^[2]
• SLE cardiac features: pericarditis, cardiomyopathy, pulmonary hypertension, Libman-Sacks endocarditis ^[6]

• Uraemic pericarditis: Occurs in underdialysed or predialysis patients with advanced CKD
• Management: Intensification of dialysis (not NSAIDs) — because the cause is uraemic toxin accumulation, not a prostaglandin-driven process ^[9]

• Early (2–4 days): inflammatory pericarditis overlying transmural infarction
• Late (weeks–months): Dressler's syndrome — autoimmune ^[1][7]
• Management: aspirin (avoid NSAIDs/steroids → ↑risk of ventricular aneurysm) ^[7]

Pericarditis is listed alongside pneumothorax, PE, acute pancreatitis, and AMI as a differential diagnosis of aortic dissection ^[15][16] — this tells you they occupy the same diagnostic "space" in acute chest pain presentations.

The CXR is part of the baseline workup for any patient with chest pain, but its findings in pericarditis vary depending on whether effusion is present.

Why is the heart "globular" in effusion? The pericardial sac is a roughly flask-shaped structure. When fluid accumulates uniformly, it expands the sac symmetrically in all directions, producing a rounded/globular silhouette rather than the normal asymmetric cardiac shadow with distinct chamber borders.

Echocardiography is essential in all patients with suspected pericarditis. It is the most important imaging tool because it can:

1. Detect and quantify pericardial effusion
2. Assess for tamponade physiology
3. Evaluate LV function (to differentiate myopericarditis from perimyocarditis)
4. Detect pericardial thickening (constrictive pericarditis)
5. Guide pericardiocentesis

Cardiac MRI is the most comprehensive non-invasive imaging modality for pericardial disease. It provides anatomical AND functional information.

CT is particularly useful for constrictive pericarditis — CT/MRI done if echo non-diagnostic, to show calcification and thickened pericardium ^[2].

Reserved for cases where constrictive pericarditis is suspected and non-invasive imaging is inconclusive.

Cardiac catheterization: characteristic sharp y descent in RA pressure with rapid termination ^[2]

Constrictive vs Restrictive — Catheterization Differentiation

Functional resemblance to constrictive pericarditis. Differentiating the two is mandatory because of the potential for successful surgical treatment of constriction ^[22].

Reversal of underlying cause, e.g. uraemia ^[2] — this is the first and most important principle. Anti-inflammatory therapy treats the symptoms, but if the underlying cause is not addressed, the pericarditis will persist or recur.

Strenuous physical activity may trigger recurrence of symptoms and thus activity should be avoided until symptom resolution and normalization of biomarkers ^[1]

Avoid strenuous activity ^[2]

Why? Exercise increases heart rate and myocardial motion → increased friction between inflamed pericardial surfaces → worsens pain and inflammation → delays healing and increases recurrence risk. The ESC 2015/2024 guidelines recommend:

• Non-athletes: Restrict strenuous activity until symptoms resolve AND CRP normalizes
• Athletes: Complete restriction from competitive sport for at least 3 months (or 6 months if myopericarditis with elevated troponin or LV dysfunction)

Symptomatic active pericarditis / myocarditis is listed as a contraindication for resumption of activity / exercise in the early mobilisation guidelines ^[23].

Whenever NSAIDs are prescribed, always co-prescribe a proton pump inhibitor (PPI) — gastroprotective agents should be prescribed as adjuncts ^[1]. Why? NSAIDs inhibit COX-1 → ↓prostaglandin synthesis → ↓gastric mucosal protection → increased risk of peptic ulcer and GI bleeding.

NSAIDs ("non-steroidal anti-inflammatory drugs") work by inhibiting cyclooxygenase (COX) enzymes → ↓prostaglandin and thromboxane synthesis → ↓inflammation, pain, and fever. They are the cornerstone of pericarditis treatment because pericardial inflammation is driven largely by prostaglandin-mediated pathways.

NSAIDs choices include aspirin, ibuprofen and indomethacin ^[1]

How to taper: The principle is guided by CRP normalization. Do NOT taper NSAIDs until CRP has normalized — premature tapering is the most common cause of recurrence. The approach is:

1. Full-dose NSAIDs until symptoms resolve AND CRP normalizes
2. Then taper every 1–2 weeks
3. Only taper one drug at a time (taper NSAIDs first, then colchicine)

Contraindications to NSAIDs:

• Active peptic ulcer disease / GI bleeding
• Severe renal impairment (NSAIDs → afferent arteriole vasoconstriction → ↓GFR)
• Known NSAID allergy / aspirin-exacerbated respiratory disease
• Pregnancy (3rd trimester — risk of premature closure of ductus arteriosus)
• Concurrent anticoagulation with high bleeding risk

Colchicine (from the autumn crocus plant, Colchicum autumnale) is an anti-inflammatory agent that works by a completely different mechanism from NSAIDs:

Mechanism: Binds to tubulin → inhibits microtubule polymerization → disrupts:

• Neutrophil chemotaxis and adhesion (they can't migrate to the inflamed pericardium)
• Inflammasome (NLRP3) activation → ↓IL-1β release
• Mitotic spindle formation (at high doses, but not relevant at therapeutic doses)

The landmark COPE and ICAP trials demonstrated that adding colchicine to NSAIDs significantly reduces recurrence rates (from ~30% to ~15%) and speeds symptom resolution.

Colchicine is indicated for patients with acute idiopathic or viral pericarditis. Effective for systemic inflammatory diseases and post-cardiac injury syndrome. NOT effective for bacterial pericarditis and malignancy-related pericarditis ^[1]

This is one of the most commonly tested management scenarios because of the important contraindications.

Need to differentiate post-cardiac injury syndrome (Dressler's syndrome) from peri-infarct pericarditis ^[23]. High dose aspirin with colchicine or NSAID with colchicine for post-cardiac injury syndrome (but not peri-infarct pericarditis) ^[23].

If recent MI: aspirin (avoid NSAID/steroid: ↑risk of aneurysm) ^[7]

Why are NSAIDs dangerous early post-MI? NSAIDs inhibit COX-2 → ↓prostaglandin production → prostaglandins are involved in the healing/scarring process of infarcted myocardium. Without prostaglandins, the infarcted area thins and weakens → ↑risk of:

• Ventricular free wall rupture (fatal)
• Ventricular aneurysm formation
• Ventricular septal defect

This risk is highest in the first 7–10 days when the necrotic myocardium is being replaced by granulation tissue (the "weakest" phase of healing). Aspirin at analgesic doses is safer because it preferentially inhibits COX-1 (platelet aggregation) with less effect on COX-2-mediated healing at the doses used.

Tx: usually dialysis, pericardiocentesis ± pericardiectomy if large size ± tamponade ^[9]

Uraemia: features of uraemia, e.g. pericarditis, neuropathy, ↓mental status is listed as an indication for haemodialysis ^[24].

Patients become symptomatic of uraemia — presents as anorexia, nausea, vomiting, pericarditis, peripheral neuropathy ^[25].

The approach varies by disease but follows the principle of treating the underlying autoimmune condition:

SLE pericarditis ^[8]:

• Asymptomatic: conservative treatment
• Symptomatic: HCQ, short course NSAIDs or low to medium dose steroids
• Colchicine may be used if unresponsive
• Percutaneous drainage with echocardiographic guidance if cardiac tamponade

RA pericarditis ^[8]: Related to disease activity → usually treated by steroids/NSAIDs

Scleroderma pericarditis ^[8]: NSAIDs + avoid steroids for pericarditis (high-dose steroids risk precipitating scleroderma renal crisis)

MCTD pericarditis ^[8]: Classically very responsive to steroid

Inflammation of the pericardium leads to increased permeability of pericardial capillaries → exudation of fluid (plasma, protein, fibrin, cells) into the pericardial space. The amount and rate of accumulation depend on the etiology and severity.

Range from asymptomatic to cardiac tamponade — determined by rate of accumulation ^[7]

• Dull, constant ache on left side of chest ^[2]
• Compression symptoms: dysphagia, SOB, hoarseness, hiccups (phrenic nerve stimulation) ^[2][7]
• P/E: muffled heart sound, Ewart sign (dullness over left angle of scapula: compressive atelectasis) ^[2][7]

Why hoarseness? The recurrent laryngeal nerve runs between the aorta/pulmonary artery and the oesophagus. A large pericardial effusion can compress this nerve → left vocal cord paralysis → hoarseness.

Why hiccups? The phrenic nerve (C3–C5) runs along the lateral border of the pericardium. Distension of the pericardial sac stretches and irritates the phrenic nerve → involuntary diaphragmatic contractions (hiccups).

• Small effusions are very common with any cause of pericarditis and are often clinically insignificant
• Post-MI pericardial effusion: common, occurs in ~1/3 of acute STEMI, often minimal. Usually asymptomatic and detected incidentally ^[2]
• The critical determinant is rate of accumulation, not volume — this is what determines whether tamponade develops

Common causes: neoplastic, pericarditis (infective or non-infective), uraemia, iatrogenic (e.g. cardiac instrumentation), traumatic, acute pericarditis treated with anticoagulants, idiopathic ^[23]

This is an important point — acute pericarditis treated with anticoagulants can precipitate tamponade. Why? Anticoagulants promote haemorrhagic conversion of the pericardial effusion → rapid accumulation of blood → tamponade. This is clinically relevant when pericarditis is initially misdiagnosed as ACS and the patient is started on heparin/anticoagulation.

Tamponade can also occur from free wall rupture, myocarditis, pericarditis, or iatrogenic causes as an acute mechanical complication from MI ^[26].

AMI complications include: heart failure, arrhythmias, VSD (anterior MI), mitral regurgitation complicating papillary muscle dysfunction (inferior MI), pericarditis ^[5]. Tamponade in this context usually results from free wall rupture.

Cardiac tamponade is a clinical diagnosis, i.e. it is diagnosed when a pericardial effusion is associated with haemodynamic compromise ^[23].

Signs and symptoms: Tachypnoea, tachycardia, small pulse volume, pulsus paradoxus. Raised JVP with prominent x descent, Kussmaul's sign. Absent apex impulse, faint heart sound, hypotension, clear chest ^[23].

Management: (1) Expand intravascular volume — D5 or NS or plasma, full rate if in shock. (2) Positive pressure mechanical ventilation should be avoided, if possible, because the positive thoracic pressures can further impair cardiac filling. (3) Pericardiocentesis with echo guidance — apical or subcostal approach, risk of damaging epicardial coronary artery or cardiac perforation. (4) Open drainage under LA/GA ^[23].

Do not misdiagnose as CHF: AVOID vasodilators / diuretics (↓preload) and positive airway pressure (↓cardiac filling) ^[7]

The mechanism is thought to be autoimmune in most cases:

1. The initial episode (usually viral) damages pericardial mesothelial cells → release of intracellular antigens
2. The immune system develops antibodies against these pericardial "neo-antigens"
3. Once the acute treatment is stopped, the autoimmune response reactivates → recurrence
4. This explains why colchicine (which dampens the NLRP3 inflammasome and reduces IL-1β) is so effective at preventing recurrence

• Recurrent episodes are often equally or more severe than the first
• Significantly impairs quality of life (repeated hospitalizations, activity restriction, medication side effects)
• May eventually progress to incessant or constrictive pericarditis

1. Chronic or recurrent pericardial inflammation → fibrin deposition
2. Fibrin organizes into dense fibrous tissue (fibrosis)
3. Calcium deposits within the fibrotic pericardium (calcification)
4. The result: a rigid, inelastic shell encasing the heart

Rigid casing outside heart → abrupt arrest of ventricular filling during diastole ^[2]

Diastolic dysfunction results in: LV → ↓SV + CO + S/S of LV failure. RV → S/S of RV failure ^[2]

Why does this cause biventricular failure? The rigid shell limits filling of both ventricles equally. The LV cannot fill properly → ↓stroke volume → ↓cardiac output → forward failure symptoms (fatigue, hypotension). The RV cannot fill properly → blood backs up into the systemic venous system → backward failure symptoms (↑JVP, hepatomegaly, ascites, peripheral oedema).

• Cardiac cirrhosis (congestive hepatopathy): Chronic elevation of RA pressure → chronic hepatic venous congestion → centrilobular necrosis → progressive fibrosis → cirrhosis. Constrictive pericarditis (along with MS/TR) is a cause of cardiac cirrhosis ^[13]
• Protein-losing enteropathy: Elevated systemic venous pressure → increased intestinal capillary hydrostatic pressure → loss of protein into the gut lumen → hypoalbuminaemia → worsening oedema and ascites
• Atrial fibrillation: Chronic atrial stretching and fibrosis from elevated atrial pressures
• Renal impairment: ↓CO → ↓renal perfusion → pre-renal AKI; chronic venous congestion → congestive nephropathy

Anti-inflammatory agent in early disease, pericardiectomy in late disease ^[2]

The visceral pericardium (epicardium) is directly adherent to the myocardial surface. Inflammatory mediators do not respect anatomical boundaries — they diffuse from the inflamed epicardium into the superficial myocardium (subepicardium). Many viral agents (Coxsackie, Echovirus) also have tropism for both pericardial and myocardial cells.

ECG changes in pericardial diseases: widespread upwardly concave ST elevation with PR depression (reciprocal changes in aVR possible), T wave flattened later followed by inversion, low voltage ^[27]

ECG changes in myocarditis: sinus tachycardia, non-specific ST/T changes, prolonged QRS/QTc, bundle branch block, progressive AV block, PVC/NSVT, can be associated with pericarditis ^[27]