Pericardial Disease

• Inflammation and increased permeability: Cytokine and inflammatory mediator release (TNF-α, IL-1, IL-6) increases vascular permeability in the visceral and parietal pericardium, leading to transudative or exudative effusion. Endothelial dysfunction allows fluid and fibrin deposition, progressing to fibrinous pericarditis (acute phase) with potential organization and fibrosis.

• Pericardial constraint and tamponade physiology: The inelastic fibrous pericardium has a fixed compliance; rapid fluid accumulation (>200 mL acutely) or loculated effusions prevent normal ventricular filling. Equalization of diastolic pressures across all cardiac chambers occurs, reducing stroke volume and cardiac output. The pulsus paradoxus (>10 mmHg systolic BP drop with inspiration) reflects exaggerated ventricular interdependence, with increased right ventricular filling compressing the left ventricle during inspiration.

• Fibrous organization and constriction: Chronic pericardial inflammation triggers fibroblast activation and excessive collagen deposition, resulting in a thickened, inelastic pericardium (>3 mm, normally 1-2 mm). Unlike tamponade's acute physiology, constriction produces a restrictive pattern with preserved ventricular function until late diastole, then abrupt cessation of filling ("square root sign" on catheterization). This represents pathological remodeling rather than acute compression.

• Molecular mechanisms of inflammation: Autoimmune pericarditis involves T-cell infiltration and autoantigen recognition (cardiac myosin, tropomyosin); viral pericarditis features direct myocardial viral invasion with molecular mimicry triggering cross-reactive antibodies. Bacterial toxins and lipopolysaccharides activate innate immunity through TLR pathways, amplifying inflammatory cascades.

Infectious causes

• Viral pericarditis (most common in developed nations): Enteroviruses (coxsackievirus B, echovirus), adenovirus, parvovirus B19, influenza, HIV; mechanisms include direct viral replication within pericardial mesothelium and immune-mediated inflammation
• Bacterial pericarditis: Staphylococcus aureus, Streptococcus pneumoniae, Gram-negative organisms; often follows cardiothoracic surgery, trauma, or hematogenous seeding in endocarditis
• Tuberculous pericarditis: Mycobacterium tuberculosis; common in endemic regions and immunocompromised hosts; creates caseating granulomas with effusion rich in lymphocytes
• Fungal pericarditis: Histoplasma, Coccidioides, Candida (immunocompromised); Aspergillus (post-transplant)

Autoimmune and idiopathic causes

• Post-myocardial infarction pericarditis (Dressler syndrome): Occurs weeks to months post-MI; autoimmune reaction against cardiac antigens exposed during necrosis; produces lymphocytic and fibrinous inflammation
• Systemic lupus erythematosus (SLE): LE cells and anti-dsDNA antibodies deposited in pericardium; presents with fibrinous pericarditis
• Rheumatoid arthritis: Rheumatoid nodules may form within pericardium; immune complex deposition drives inflammation
• Idiopathic pericarditis: Presumed viral etiology; accounts for ~80% of acute pericarditis cases in developed countries

Neoplastic causes

• Primary pericardial tumors: Mesothelioma (rare, asbestos-related), angiosarcoma, pericardial teratoma
• Secondary pericardial involvement: Metastatic carcinoma (lung, breast, melanoma, lymphoma); creates hemorrhagic or exudative effusion; may produce malignant pericardial effusion with cytologically positive fluid

Traumatic and mechanical causes

• Post-cardiac surgery syndrome: Pericarditis within 2-3 weeks post-op; inflammatory response to myocardial injury and pericardial manipulation
• Penetrating trauma: Direct pericardial laceration with hemopericardium
• Uremic pericarditis: Uremia-induced serosal inflammation in end-stage renal disease; "shaggy" fibrin deposition

Other causes

• Radiation pericarditis: Fibrotic and inflammatory response to chest radiation (Hodgkin lymphoma, breast cancer); can progress to constrictive physiology years post-treatment
• Myocardial infarction with free wall rupture: Creates hemorrhagic pericarditis and tamponade
• Aortic dissection into pericardium: Hemorrhagic pericarditis with acute tamponade
• Hypothyroidism: Myxedematous infiltration and pericardial effusion with high cholesterol content

Acute pericarditis

• Pleuritic chest pain: Sharp, positional pain worse with deep inspiration and lying flat, relieved by sitting forward; correlates with visceral pericardial inflammation and fibrin deposition irritating adjacent pleura
• Dyspnea: Results from effusion-induced respiratory mechanics compromise and potential tamponade physiology
• Friction rub: Triphasic scratching sound (atrial systole, ventricular systole, early diastole) on auscultation reflects rough, inflamed pericardial surfaces; most specific clinical finding
• Fever: Common with viral, bacterial, or autoimmune etiologies due to systemic inflammatory response
• Laboratory elevation: ESR and CRP markedly elevated (often >100 mm/h); troponin elevation indicates concurrent myopericarditis with myocardial inflammation

Pericardial effusion (asymptomatic or symptomatic)

• Dyspnea and orthopnea: Mechanical compression of lungs and diaphragm; particularly with large effusions (>500 mL)
• Hepatomegaly: Passive hepatic congestion from elevated systemic venous pressure
• Muffled heart sounds: Acoustic dampening by fluid layer
• Electrical alternans on ECG: Voltage fluctuations reflecting swinging heart motion within fluid; pathognomonic for large pericardial effusion

Pericardial tamponade (cardiac emergency)

• Pulsus paradoxus (>10 mmHg systolic BP drop with inspiration): Hallmark finding reflecting exaggerated ventricular interdependence; mechanistically, increased RV filling during inspiration bulges interventricular septum leftward, reducing LV filling and stroke volume
• Beck's triad: Hypotension, elevated jugular venous pressure (JVP), muffled heart sounds
• Shock physiology: Decreased cardiac output with tachycardia, cool extremities, altered mental status; life-threatening emergency requiring urgent drainage
• Equilibration of diastolic pressures: Right atrial, right ventricular diastolic, pulmonary artery diastolic, and left ventricular diastolic pressures all equalize (normally RA < RV diastolic, etc.)

Constrictive pericarditis

• Progressive dyspnea and fatigue: Develops gradually over months to years; reflects chronic restriction of ventricular filling
• Peripheral edema and ascites: Disproportionate to pulmonary congestion; reflects elevated right atrial pressure
• Hepatomegaly and hepatic dysfunction: Passive congestion and cirrhosis development ("cardiac cirrhosis")
• Kussmaul sign: Paradoxical rise in JVP with inspiration (opposite to normal); pathognomonic finding indicating loss of normal ventricular compliance and early diastolic pressure rise
• "Square root sign" on cardiac catheterization: Rapid early diastolic filling followed by abrupt plateau as constricting pericardium prevents further filling; reflects restricted ventricular pressure curve
• Atrial fibrillation: Develops in ~30% due to chronic atrial stretch and fibrosis

Post-myocardial infarction pericarditis (Dressler syndrome)

• Onset 2-12 weeks post-MI (typically 2-3 weeks)
• Fibrinous pericarditis with extensive fibrin deposition and lymphocytic infiltration
• Associated with anteroseptal MI (more common)
• May include pleurisy, pneumonitis, and arthritis as manifestations of systemic autoimmunity

Clinical assessment

• History and physical examination for chest pain characteristics (pleuritic, positional), dyspnea, fever, presence of friction rub
• Assessment for tamponade physiology: pulsus paradoxus, hypotension, elevated JVP, altered mental status

Electrocardiography (ECG)

• Stage 1: Diffuse ST elevation (except aVR and V1) and PR depression (due to atrial injury currents); most specific early finding for acute pericarditis
• Stage 2: ST normalization with continued PR depression
• Stage 3: T-wave inversion (symmetric, diffuse)
• Stage 4: ECG normalization or persistent T-wave changes
• Distinction from STEMI: Diffuse (not territorial) ST elevation without reciprocal changes; PR depression; absence of pathological Q waves
• Electrical alternans: Large QRS voltage fluctuation with rhythm strip analysis reflecting heart swinging within effusion

Echocardiography (most useful diagnostic modality)

• Effusion size quantification: >3 mm diastolic separation of visceral and parietal pericardium at left ventricular apex in parasternal long-axis view
• Small: <1 cm
• Moderate: 1-2 cm
• Large: >2 cm
• Fibrin strands: Echogenic material within effusion suggesting inflammatory, infectious, or malignant process
• Hemorrhagic effusion: Echogenic/septated appearance; suggests malignancy, trauma, aortic dissection
• Tamponade signs:
• Right atrial diastolic collapse (>1/3 of RA area throughout diastole)
• Right ventricular diastolic collapse (most sensitive sign for tamponade)
• Dilated IVC without normal collapse
• Exaggerated respiratory variation of mitral and tricuspid inflow (>25% variation)
• Constriction findings: Thickened pericardium (>3 mm), dilated atria, restrictive mitral/tricuspid inflow patterns, septal bounce from interdependence
• Pericardial thickening: Fibrotic pericardium appears echogenic and restricted; calcification produces characteristic acoustic shadow

Laboratory investigation

• Complete blood count: Leukocytosis (typically 10,000-15,000/μL) in inflammatory and infectious etiologies
• Inflammatory markers: ESR and CRP markedly elevated (often >60-100 mm/h) in acute pericarditis; CRP more sensitive for viral disease
• Cardiac biomarkers: Troponin I or T elevation (10-50% of acute pericarditis cases) indicates concurrent myopericarditis with myocardial necrosis
• BNP/NT-proBNP: Elevated in tamponade and constriction due to ventricular diastolic dysfunction
• Comprehensive metabolic panel: Assess renal function, electrolytes; elevated creatinine suggests uremic pericarditis
• Viral serologies: PCR, culture, or serologic studies for enteroviruses, adenovirus, parvovirus B19 (not routinely performed)
• Autoimmune panel: ANA, anti-dsDNA, rheumatoid factor, complement levels if SLE or rheumatoid arthritis suspected

Pericardiocentesis and pericardial fluid analysis (if tamponade, large effusion >1 cm, or infectious concern)

• Fluid characteristics:
• Transudative (non-inflammatory): LDH <200 U/L, protein <30 g/L, glucose normal, no fibrin; seen in congestive heart failure, renal disease, hypothyroidism
• Exudative (inflammatory/infectious): LDH >200 U/L, protein >30 g/L, fibrin deposition, elevated cells; seen in pericarditis, malignancy, infection
• Hemorrhagic: RBC predominance; suggests malignancy, trauma, aortic dissection, anticoagulation
• Cell count and differential: Lymphocytic predominance (viral, tuberculous, autoimmune); neutrophilic predominance (bacterial, acute rheumatic fever)
• Gram stain and culture: Positive in bacterial and fungal pericarditis (~40% sensitivity); requires anaerobic and aerobic bottles
• AFB smear and culture: For tuberculous pericarditis (low sensitivity ~25%, but high specificity)
• Cytology: Malignant cells in secondary neoplastic effusions (sensitivity 60-80% for pericardial malignancy)
• PCR for viral pathogens: Increasingly available; helps identify viral etiology in resource-rich settings
• Adenosine deaminase (ADA): Elevated (>10 U/L) in tuberculous pericarditis; useful adjunct in endemic regions
• Glucose: Low (<30 mg/dL) in tuberculous pericarditis, lupus, and rheumatoid pericarditis

Histopathological examination (if tissue obtained via drainage or pericardectomy)

• Acute pericarditis: Fibrinous inflammation with acute inflammatory cell infiltrate (neutrophils, monocytes); fibrin deposition on serosal surface; vascular dilatation and edema; preservation of pericardial architecture
• Viral pericarditis: Lymphocytic infiltration (CD8+ T cells predominate) with minimal fibrin; myocardial inflammation may be present (myopericarditis); no specific viral inclusions visible on H&E (unless herpesviruses with Cowdry bodies)
• Tuberculous pericarditis: Caseating granulomas with central caseous necrosis surrounded by epithelioid histiocytes, multinucleated Langhans giant cells, and lymphocytic collar; pericardial thickening with fibrosis; AFB stain reveals acid-fast bacilli (variable staining)
• Bacterial pericarditis: Acute suppurative inflammation with neutrophilic exudate, fibrin, and bacterial organisms on Gram stain; abscess formation possible; tissue necrosis and hemorrhage
• Constrictive pericarditis: Dense fibrous tissue with collagen deposition, minimal inflammation (chronic phase); thickened pericardium (>3 mm); may show calcification; fibroblast and myofibroblast proliferation; loss of normal pericardial elasticity
• Malignant effusion/mesothelioma: Malignant cells in fluid cytology; mesothelioma shows biphasic pattern (epithelioid and sarcomatoid components), asbestos bodies, positive immunostain for calretinin/WT-1
• Post-MI pericarditis: Fibrinous inflammation with granulation tissue at MI border; can show early organization of fibrin

Imaging modalities

• Chest X-ray: "Water bottle heart" appearance with globular cardiac silhouette if large effusion present; Kerley B lines if concurrent pulmonary edema; pericardial calcification in constrictive physiology (eggshell pattern)
• Cardiac CT: Excellent for

Immediate stabilisation (tamponade is the emergency)

• Urgent drainage: echo-guided pericardiocentesis is the first move in hemodynamically significant tamponade; surgical drainage (subxiphoid window or thoracotomy) is preferred for hemopericardium from trauma, free-wall rupture, or type A dissection, where needle drainage only decompresses the tamponade and permits further bleeding.
• Bridging measures: cautious IV volume expansion supports a preload-dependent ventricle. Avoid diuretics, nitrates, and other vasodilators — dropping preload in a fixed-volume pericardium collapses cardiac output. Positive-pressure ventilation is hazardous for the same reason.

First-line therapy for acute pericarditis (ESC 2015 Guidelines on Pericardial Diseases, the reference standard used in US practice; there is no dedicated ACC/AHA pericardial disease guideline)

• NSAID or high-dose aspirin: ibuprofen 600 mg every 8 hours, or aspirin 750–1000 mg every 8 hours, continued until symptom resolution and CRP normalisation, then tapered; aspirin is preferred when pericarditis follows MI.
• Colchicine: should be added to NSAID/aspirin in all patients without a contraindication (ESC 2015, Class I). Conventional dosing is 0.5 mg (US formulation 0.6 mg) once daily if <70 kg and twice daily if ≥70 kg, for 3 months in acute disease and 6 months in recurrent disease. Colchicine impairs microtubule-dependent neutrophil chemotaxis and inflammasome activity and roughly halves recurrence (CORP/ICAP trials).
• Exercise restriction until symptoms and inflammatory markers resolve.

Escalation

• Low-dose corticosteroids: prednisone 0.2–0.5 mg/kg/day with slow taper (ESC 2015), reserved for NSAID/colchicine failure, contraindication, or an autoimmune/uremic cause; the higher doses used historically are associated with steroid dependence and recurrence.
• IL-1 blockade: anakinra or rilonacept for corticosteroid-dependent, colchicine-resistant recurrent pericarditis.
• Etiology-specific therapy: intensified dialysis for uremic pericarditis; urgent drainage plus IV antimicrobials for purulent pericarditis, with intrapericardial thrombolysis or subxiphoid pericardiotomy for loculated pus (ESC 2015); RIPE antitubercular therapy for tuberculous disease.

Definitive/surgical

• Pericardiectomy: the only cure for chronic constrictive pericarditis; also considered for refractory recurrent disease.
• Pericardial window or intrapericardial sclerosis: for recurrent malignant effusions.

Contraindicated/avoid

• Non-aspirin NSAIDs and steroids early after MI: impair infarct healing and raise free-wall rupture risk.
• Anticoagulation: relative contraindication with significant effusion (hemopericardium risk).
• Colchicine with strong CYP3A4/P-glycoprotein inhibitors (e.g., clarithromycin) and in severe renal or hepatic impairment.

Emergencies

• Cardiac tamponade: fluid accumulating faster than the fibrous pericardium can stretch equalises diastolic pressures and abolishes filling. Signalled by hypotension with distended neck veins and muffled sounds (Beck triad), pulsus paradoxus, and echocardiographic right atrial/right ventricular diastolic collapse. Requires immediate drainage.
• Purulent pericarditis: bacterial seeding produces a neutrophilic, loculated exudate; signalled by high fever, toxic appearance, and low-glucose exudative fluid. Mortality is high without drainage plus antibiotics.
• Free-wall rupture with hemopericardium: sudden pulseless electrical activity days after transmural MI — the classic electromechanical dissociation stem.

Disease complications

• Recurrent pericarditis: incomplete resolution of IL-1–driven inflammation; recurrence is common after a first idiopathic episode and is the principal reason colchicine is added up front. Signalled by return of pleuritic pain with re-elevated CRP.
• Constrictive pericarditis: organisation of fibrinous exudate into dense collagen, sometimes calcified. Suspect with right-sided failure out of proportion to pulmonary congestion, Kussmaul sign, pericardial knock, and calcification on lateral chest film. Tuberculous, purulent, radiation, and post-surgical pericarditis carry the highest risk; idiopathic viral disease rarely constricts.
• Effusive-constrictive physiology: elevated right atrial pressure persists after drainage — the visceral pericardium is the constricting layer.
• Myopericarditis: troponin elevation with preserved or mildly reduced ejection fraction; carries arrhythmia risk and mandates exercise restriction.
• Atrial fibrillation and cardiac cirrhosis: from chronic atrial stretch and hepatic venous congestion in long-standing constriction.

Treatment complications

• NSAIDs: GI ulceration, renal hypoperfusion, and impaired post-MI infarct healing.
• Colchicine: diarrhoea is dose-limiting; myopathy and myelosuppression occur with renal impairment or CYP3A4/P-glycoprotein inhibitors.
• Corticosteroids: steroid dependence with paradoxically higher recurrence rates.
• Pericardiocentesis: right ventricular or coronary laceration, pneumothorax, arrhythmia, and pericardial decompression syndrome (acute pulmonary oedema after rapid drainage).
• Pericardiectomy: perioperative low cardiac output, particularly when myocardial atrophy has occurred.

• Bread-and-butter pericardium: the gross buzzword for fibrinous pericarditis — shaggy fibrin strands that pull apart like buttered bread. Its bedside correlate is the triphasic friction rub, the most specific physical finding.
• Diffuse ST elevation with PR depression, no reciprocal changes, no Q waves = acute pericarditis, not STEMI. The distractor is a territorial pattern with reciprocal depression. Remember separately that a new LBBB is not a stand-alone STEMI criterion — apply Sgarbossa criteria.
• Electrical alternans + tachycardia + low voltage points to a large effusion; the single best next step is transthoracic echocardiography, and if tamponade physiology is present, pericardiocentesis. Do not order CT first in an unstable patient.
• Pulsus paradoxus = tamponade; Kussmaul sign = constriction. This is the association examiners test most. Kussmaul sign (JVP rising with inspiration) is characteristically absent in pure tamponade because the pericardium cannot accommodate the augmented venous return at all.
• Constriction versus restrictive cardiomyopathy: constriction gives pericardial knock, respirophasic septal shift (interventricular interdependence), thickened/calcified pericardium, and discordant ventricular pressures; restriction gives a loud S3-type filling sound, high BNP, and concordant pressures. Amyloidosis is the restrictive distractor.
• After MI: early peri-infarction pericarditis (days) versus Dressler syndrome (weeks, autoimmune, responds to aspirin). Give aspirin, not ibuprofen or steroids — non-aspirin NSAIDs and corticosteroids impair infarct healing.
• Colchicine should be added to first-line NSAID/aspirin therapy in all patients without a contraindication (ESC 2015, Class I) because it substantially reduces recurrence; corticosteroids up front are the wrong answer and predispose to steroid-dependent recurrent disease. Contraindications include severe renal or hepatic impairment and concurrent strong CYP3A4/P-glycoprotein inhibitors.
• Tuberculous pericarditis is the leading cause of constriction worldwide: lymphocyte-rich exudate, low glucose, high adenosine deaminase, caseating granulomas. Uremic pericarditis is treated with intensified dialysis, not NSAIDs.