Acute Pericarditis

Inflammatory Cascade and Pericardial Response

• Inciting agent (viral, bacterial, autoimmune, uremic toxins, or neoplastic infiltration) triggers innate immune response within pericardial tissue
• Upregulation of pro-inflammatory cytokines (TNF-α, IL-1, IL-6) and chemokines recruit immune cells to pericardial space
• Mast cell degranulation releases histamine and tryptase, further amplifying inflammation
• Increased vascular permeability leads to fibrinous exudation and accumulation of inflammatory fluid within pericardial sac

Visceral-Parietal Interface Inflammation

• Viral or bacterial organisms directly invade pericardial tissues or trigger molecular mimicry
• Neutrophilic infiltration predominates in early bacterial/purulent pericarditis; lymphocytic predominance in viral/autoimmune disease
• Fibrin deposition on pericardial surfaces creates characteristic friction rub on auscultation when inflamed visceral and parietal layers move against each other
• Exudative effusion accumulation increases intrapericardial pressure, potentially compromising ventricular filling if accumulation is rapid (>200 mL acutely)

Electrocardiographic Manifestations

• Transmural inflammation depolarizes myocardial tissue adjacent to pericardium, creating atrial and ventricular injury currents
• Stage 1: Diffuse ST elevation (concave upward, except aVR/V1) and PR depression due to atrial injury
• Stage 2: Gradual ST normalization with T wave flattening (hours to days)
• Stage 3: Generalized T wave inversion develops
• Stage 4: T waves normalize; may see persistent T wave inversion in some cases
• Unlike myocardial infarction, ST elevation is typically diffuse (not localized to coronary territory) and PR segment depression is highly specific

Diastolic Function Impairment

• Pericardial stiffness increases with inflammation and effusion accumulation
• Reduced ventricular compliance impairs early diastolic filling
• If effusion accumulates rapidly (>250 mL within hours), equalization of diastolic pressures across all cardiac chambers occurs (tamponade physiology)
• Kussmaul sign (paradoxical venous distension with inspiration) reflects impaired right ventricular filling from pericardial constraint

• Viral pericarditis: Enterovirus (coxsackievirus, echovirus), parvovirus B19, influenza, Epstein-Barr virus, cytomegalovirus, HIV; viral prodrome often precedes pericarditis by 1-2 weeks
• Bacterial pericarditis: Staphylococcus aureus (most common), Streptococcus pneumoniae, gram-negative organisms, Mycobacterium tuberculosis; often secondary to pneumonia, cardiac surgery, or bacteremia
• Fungal pericarditis: Histoplasma, Coccidioides, Blastomyces; typically in immunocompromised hosts
• Parasitic pericarditis: Echinococcosis, toxoplasmosis; geographically limited

Autoimmune and Inflammatory Causes

• Systemic Lupus Erythematosus (SLE): Most common autoimmune cause; anti-DNA and anti-ribosomal-P antibodies implicated
• Rheumatoid Arthritis: Can present with acute pericarditis; associated with worse prognosis
• Inflammatory Bowel Disease: Enteropathic arthropathy associated with pericarditis
• Vasculitis: ANCA-associated vasculitis, Behçet's disease, Kawasaki disease (in children)
• Familial Mediterranean Fever: MEFV gene mutations; recurrent acute pericarditis episodes
• Antiphospholipid Syndrome: Thrombotic tendency with pericardial involvement

Metabolic and Uremic Causes

• Uremic pericarditis: Associated with elevated blood urea nitrogen; typically occurs in patients with chronic kidney disease or acute renal failure
• Dialysis-associated pericarditis: Paradoxically can occur despite dialysis, associated with inadequate clearance of inflammatory mediators
• Hypothyroidism: Severe cases with high TSH can present with pericarditis

Neoplastic Causes

• Primary pericardial mesothelioma: Asbestos exposure history
• Metastatic disease: Lung cancer, breast cancer, lymphoma most common; can cause hemorrhagic or serosanguineous effusion
• Leukemia and lymphoma: Direct infiltration or secondary infection due to immunosuppression

Drug-Induced Pericarditis

• Minoxidil, hydralazine, procainamide, isoniazid: Classic drug-induced causes
• Chemotherapy agents: 5-Fluorouracil, doxorubicin, tyrosine kinase inhibitors; dose-dependent cardiotoxicity
• Immunotherapy: Checkpoint inhibitors (anti-PD-1, anti-CTLA-4) with immune-related adverse events

Post-Cardiac Intervention and Post-Myocardial Infarction

• Dressler's Syndrome: Autoimmune pericarditis occurring weeks to months after cardiac surgery or myocardial infarction; antithymocyte antibodies and immune complexes implicated
• Early Post-MI Pericarditis: Within days of transmural MI due to myocardial necrosis with pericardial inflammation
• Post-cardiac surgery pericarditis: Following cardiac surgery, pericardiotomy, or device placement

Traumatic Causes

• Blunt trauma: Motor vehicle accidents, falls
• Penetrating trauma: Stab wounds, iatrogenic injury during procedures
• Radiation therapy: Delayed pericarditis months to years after thoracic radiation

• Presumed viral etiology in majority despite negative serologies and cultures

Cardinal Symptom: Pleuritic Chest Pain

• Sharp, substernal or left-sided pain that worsens with lying supine and improves with sitting forward
• Radiation to left shoulder, trapezius ridge (pathognomonic)
• Exacerbated by inspiration, cough, and swallowing (pleuritic features distinguish from acute myocardial infarction)
• Typically acute onset over hours, may be preceded by viral prodrome (fever, upper respiratory symptoms)
• Severity ranges from mild discomfort to severe pain requiring narcotic analgesia

Associated Constitutional Symptoms

• Fever: Present in majority of acute cases; higher temperatures suggest infectious (especially bacterial) etiology
• Malaise and fatigue: Often severe, impairing daily function
• Dyspnea: Due to reduced cardiac compliance, pericardial effusion, or anxiety
• Palpitations: Secondary to tachycardia from fever and inflammation, or arrhythmias (often atrial fibrillation)

Physical Examination Findings

• Pericardial friction rub: Pathognomonic finding present in 33-50% of cases; best heard at left lower sternal border with patient leaning forward in full expiration; described as squeaky, leathery, or scratching sound; may be transient, disappearing within hours to days as effusion accumulates
• Fever: Usually low-grade (38-38.5°C) unless bacterial infection
• Tachycardia: Proportionate to fever degree; disproportionate tachycardia suggests tamponade or significant effusion
• Tachypnea: From pleuritic pain or compromised cardiac function
• Elevated jugular venous pressure (JVP): Indicates elevated intrapericardial pressure; prominent in constrictive physiology
• Pulsus paradoxus: >10 mmHg drop in systolic BP during inspiration; suggests tamponade physiology (also seen in constrictive pericarditis, restrictive cardiomyopathy, severe COPD)
• Muffled heart sounds: Due to pericardial effusion dampening sound transmission
• Signs of tamponade: Beck's triad (hypotension, elevated JVP, muffled heart sounds) indicates life-threatening emergency

Clinical Variation by Etiology

• Tuberculous pericarditis: Insidious onset over weeks; often presents with tamponade or constriction; night sweats, weight loss common
• Purulent bacterial pericarditis: Acute presentation with sepsis; high fever, hemodynamic instability, altered mental status
• Post-MI pericarditis: Chest pain recurrence 3-7 days after MI with distinctive pericardial rub and renewed ST elevation
• Dressler's syndrome: Delayed presentation (weeks to months) with constitutional symptoms and sometimes pleural effusion or pulmonary infiltrates

Clinical Diagnosis Criteria

• ESC 2015 Criteria require two of the following four features:

1. 1.Characteristic pleuritic chest pain
2. 2.Pericardial friction rub
3. 3.Suggestive electrocardiographic changes
4. 4.New or worsening pericardial effusion on imaging

• Any single criterion plus objective evidence of pericardial inflammation (elevated biomarkers, imaging findings) supports diagnosis

Electrocardiography (ECG)

• Stage 1 (Days 1-3): Diffuse ST elevation (concave upward, most widespread in leads representing atrial wall—I, II, aVL, aVF, V3-V6); PR segment depression (highly specific, present in 80-90% of acute pericarditis, absent in myocardial infarction); atrial injury pattern
• Stage 2 (Days 3-7): Gradual return to baseline with T wave flattening; ST segments normalize
• Stage 3 (Week 2): Widespread T wave inversion develops; more diffuse than in MI
• Stage 4: T waves normalize (may take weeks to months; persistent T wave inversion in some cases)
• Key distinguishing features from acute MI: ST elevation is diffuse (not localized to coronary territory), PR depression present, and reciprocal ST depression absent
• RP ratio (ST elevation to T wave amplitude ratio in V6): Ratio >0.24 favors pericarditis over acute MI

Laboratory Tests

• Acute phase reactants:
• C-reactive protein (CRP): Elevated in majority; prognostically important (higher levels associated with complications)
• Erythrocyte sedimentation rate (ESR): Often elevated; less specific
• Complete blood count: Leukocytosis common (WBC 10,000-15,000/μL) unless viral etiology
• Cardiac biomarkers:
• Troponin I/T: Elevated in 20-50% of acute pericarditis due to myopericarditis (associated with worse outcomes)
• Myoglobin: May be elevated; less specific
• BNP/NT-proBNP: Elevated if significant effusion or diastolic dysfunction
• Infectious workup (perform when bacterial or specific infection suspected):
• Blood cultures: Before antibiotics in suspected bacterial pericarditis
• Viral serology and PCR: Enterovirus, parvovirus B19, EBV, CMV, influenza
• Tuberculin skin test and chest imaging: For TB suspicion
• HIV serology: Patients at risk or immunocompromised
• Autoimmune/inflammatory markers:
• Antinuclear antibody (ANA): Screen for SLE
• Anti-dsDNA, anti-Smith antibodies: If SLE suspected
• Rheumatoid factor and anti-CCP: If rheumatoid arthritis suspected
• Inflammatory markers: Consider vasculitis serologies (c/p-ANCA) if indicated
• Metabolic panel:
• Blood urea nitrogen and creatinine: Essential to evaluate for uremic pericarditis
• Thyroid-stimulating hormone: If hypothyroidism suspected

• Pericardial effusion assessment: Size in millimeters at end-diastole (small <10 mm, moderate 10-20 mm, large >20 mm); location (circumferential vs. loculated)
• Effusion characteristics: Echo-free (simple serous), echogenic material (fibrinous or hemorrhagic), septations
• Tamponade physiology findings:
• Right atrial collapse (>1/3 of atrial area during systole)
• Right ventricular collapse (>1/3 of RV area during diastole)
• Respiratory variation >25% (mitral inflow velocity increase during inspiration, tricuspid inflow decrease during expiration)
• Dilated inferior vena cava (>2 cm) with minimal respiratory variation
• Other findings: Pericardial thickening (suggests chronic or organized inflammation), epicardial fat stripe separation
• Doppler abnormalities: Mitral inflow velocity variation, tricuspid inflow velocity variation reflecting constrictive/restrictive physiology

• Tissue characterization: T1 and T2 mapping quantifies pericardial inflammation
• Late gadolinium enhancement: Depicts areas of pericardial inflammation and necrosis
• Superior to echocardiography: For thin pericardial effusions, loculated effusions, adhesions
• Role: Particularly useful when diagnosis unclear despite clinical presentation and ECG findings; guides prognosis (higher inflammation burden associated with recurrence)

• Pericardial effusion signs: Cardiomegaly with globular silhouette ("water bottle" heart) when moderate-to-large effusion present
• Pulmonary findings: Infiltrates (suggesting pneumonia or malignancy), pleural effusion (Dressler's syndrome, autoimmune causes)
• Mediastinal widening: Suggests superior vena cava involvement or malignancy
• Normal CXR: Does not exclude diagnosis

• When to perform:
• Suspected purulent/bacterial pericarditis (obtain fluid for culture/sensitivities)
• Large effusion with hemodynamic compromise (tamponade)
• Refractory symptoms despite optimal medical therapy
• Suspicion of malignancy, TB, or other specific etiology
• Technique: Echocardiographically-guided percutaneous pericardiocentesis under fluoroscopic or ultrasound guidance; reduces complication risk
• Pericardial fluid analysis:
• Cell count and differential: WBC differential helps determine etiology (lymphocytic in viral/TB, neutrophilic in bacterial, RBCs in malignancy/trauma)
• Protein and LDH: Exudate vs. transudate classification (exudate if protein >3.0 g/dL, LDH >200 IU/L)
• Gram stain and bacterial culture: Gold standard for bacterial identification
• AFB smear and TB culture: For TB diagnosis (culture may take weeks)
• Fungal culture and stains: If fungal infection suspected
• Cytology: Malignant cells identification (sensitivity

Immediate priorities

• Exclude tamponade first: hypotension, pulsus paradoxus, or elevated JVP mandates urgent echocardiography; hemodynamically significant effusion is treated with echo-guided pericardiocentesis, not with anti-inflammatories.
• Triage for admission (ESC 2015 Pericardial Diseases guideline high-risk features): fever >38°C, subacute onset, large effusion or tamponade, immunosuppression, trauma, oral anticoagulant use, troponin elevation (myopericarditis), or failure of NSAID therapy after a week.
• Treat the cause when it is not idiopathic/viral: purulent pericarditis requires IV antibiotics plus surgical drainage; tuberculous pericarditis requires four-drug antituberculous therapy; uremic pericarditis responds to intensified dialysis, not to NSAIDs.

First-line therapy (ESC 2015)

• NSAID or high-dose aspirin: ibuprofen 600–800 mg every 8 hours, or aspirin 750–1000 mg every 8 hours; both suppress prostaglandin-mediated pericardial inflammation. Add a proton pump inhibitor for gastroprotection. Taper once symptoms resolve and CRP normalizes.
• Colchicine, added to the NSAID in every patient without contraindication: 0.5 mg twice daily (once daily if <70 kg) for 3 months in a first episode, 6 months for recurrence. It impairs microtubule assembly and neutrophil/inflammasome activation, and roughly halves recurrence (ICAP, CORP trials).
• Exercise restriction until symptoms resolve and CRP normalizes; longer (about 3 months) in competitive athletes.

Escalation

• Corticosteroids (low-to-moderate dose prednisone) only for NSAID/colchicine failure, contraindication, or a steroid-responsive cause (autoimmune, uremic). Steroids favor viral persistence and increase recurrence and steroid dependence — a common exam trap.
• IL-1 blockade (anakinra; rilonacept is FDA-approved for recurrent pericarditis) or azathioprine/IVIG for corticosteroid-dependent recurrent disease.
• Pericardiectomy: last resort for refractory recurrent pericarditis and definitive treatment for constrictive pericarditis.

Avoid

• Non-aspirin NSAIDs and steroids early after MI — they impair infarct healing and predispose to wall thinning; use aspirin for post-MI/Dressler pericarditis.
• Anticoagulation where avoidable (hemorrhagic effusion risk), colchicine in pregnancy, and NSAIDs after 20 weeks' gestation (ductal constriction, oligohydramnios).

Complications of the disease

• Cardiac tamponade — emergency: rapid exudate accumulation raises intrapericardial pressure above chamber diastolic pressures, equalizing them and abolishing filling. Signals: Beck triad, pulsus paradoxus >10 mmHg, sinus tachycardia, low-voltage QRS with electrical alternans, and echocardiographic RA systolic/RV diastolic collapse. Treat with pericardiocentesis; give volume, never diurese.
• Purulent pericarditis — emergency: bacterial seeding produces neutrophilic pus that loculates rapidly; high fever, sepsis physiology, and echogenic septated effusion. Requires drainage plus IV antibiotics.
• Recurrent pericarditis: incomplete resolution of the initial immune response (often autoinflammatory); recurrence follows a first episode in a substantial minority, and is markedly reduced by colchicine. Signaled by return of pleuritic pain with re-elevated CRP.
• Myopericarditis: contiguous myocardial involvement raising troponin; watch for new regional or global LV dysfunction and ventricular arrhythmia. Troponin elevation predicts neither constriction nor worse long-term outcome, but does mandate exercise restriction.
• Constrictive pericarditis: chronic fibrosis and calcification encase the heart, causing dissociation of intrathoracic and intracardiac pressures. Signals: Kussmaul sign, pericardial knock, ventricular interdependence with septal bounce, square-root/dip-and-plateau pressure tracing, pericardial calcification on lateral chest film. Risk is very low after idiopathic/viral disease but high after tuberculous, purulent, or post-surgical pericarditis.
• Effusive-constrictive physiology: persistently elevated right atrial pressure after fluid removal.
• Atrial fibrillation: atrial epicardial inflammation as an arrhythmogenic substrate.

Complications of treatment

• NSAIDs/aspirin: peptic ulceration and GI bleeding, sodium retention, and AKI from loss of prostaglandin-mediated afferent arteriolar dilation.
• Colchicine: diarrhea (dose-limiting), myopathy/rhabdomyolysis and cytopenias, amplified by renal impairment and by CYP3A4/P-glycoprotein inhibitors (clarithromycin, verapamil, cyclosporine).
• Corticosteroids: steroid dependence and higher recurrence rates, hyperglycemia, osteoporosis, infection.
• Pericardiocentesis: RV laceration with hemopericardium, pneumothorax, coronary injury, arrhythmia — emergencies — minimized by echo guidance.

• The pain script: sharp, pleuritic, worse supine and relieved by sitting forward, radiating to the trapezius ridge — trapezius radiation is essentially unique to pericardial irritation (shared phrenic nerve innervation) and is the fastest discriminator from acute coronary syndrome.
• The ECG script: diffuse concave ST elevation with PR depression, PR elevation in aVR, and no reciprocal depression. PR depression reflects an atrial injury current and is the single most specific finding. A regional ST pattern with reciprocal depression means STEMI — take that patient to the cath lab, not to ibuprofen.
• The single best next step in a hypotensive patient with distant heart sounds and elevated JVP is bedside echocardiography; if the patient is in extremis, proceed directly to pericardiocentesis. Do not give diuretics or nitrates — preload is what is keeping the ventricles filled.
• The association examiners love: colchicine added to an NSAID as first-line therapy for the first episode (ESC 2015), not just for recurrence — it substantially reduces recurrence (ICAP).
• **Post-MI pericarditis and *Dressler syndrome*: use aspirin**; other NSAIDs and corticosteroids impair infarct healing and risk wall thinning/rupture.
• Uremic pericarditis: the answer is urgent/intensified dialysis, not anti-inflammatories — and it is one of the classic indications to initiate dialysis.
• Corticosteroids are the classic distractor: they relieve symptoms fast but promote steroid dependence and recurrence, so they are reserved for NSAID/colchicine failure or specific etiologies.
• Tamponade versus constriction: pulsus paradoxus points to tamponade; Kussmaul sign and a pericardial knock with pericardial calcification point to constriction. Electrical alternans with low voltage is the tamponade buzzword; definitive therapy for constriction is pericardiectomy.
• Watch for troponin elevation — it signals myopericarditis, mandates exercise restriction, and is not evidence of coronary occlusion.