Pericarditis

Anatomy and Physiology of the Pericardium

• Bilayer membrane enveloping heart.
• Visceral layer: Inner layer. Single layer mesothelial cells, collagen, elastin. Adherent to epicardium and proximal great vessels.
• Parietal layer: Outer layer. Fibrous, acellular. Collagen and elastin fibers.
• Pericardial space: Contains small amount of serous fluid between layers. Facilitates smooth cardiac movement.
• Function: Optimizes diastolic coupling between right and left-sided cardiac chambers through transmission of intracavitary filling pressures.

Acute Pericarditis

Definition

• Inflammation of pericardial layers.
• Episode lasting <4-6 weeks.
• Incessant pericarditis: Lasts >4-6 weeks without remission.
• Recurrent pericarditis: New signs/symptoms following symptom-free interval of 4-6 weeks.
• Chronic pericarditis: Lasts >3 months.

Etiology

Category	Agents / Conditions
Viral	Enteroviruses (Coxsackievirus, echoviruses), Influenza, Herpesviruses (EBV, CMV, HHV-6), Adenovirus, Varicella, Mumps, Rubella, Parvovirus B19, Hepatitis B/C, HIV, COVID-19. Most common cause in developed nations.
Bacterial	Mycobacterium tuberculosis (most frequent worldwide/developing nations), Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Meningococcus, Mycoplasma.
Fungal/Parasitic	Aspergillus, Candida, Histoplasma, Toxoplasma, Echinococcus, Trypanosoma cruzi.
Autoimmune/Connective Tissue	Acute rheumatic fever, Systemic Lupus Erythematosus (SLE), Juvenile Idiopathic Arthritis (JIA), Scleroderma, Sjogren syndrome, Systemic vasculitides. Periodic fever syndromes (Familial Mediterranean Fever, TRAPS).
Metabolic/Endocrine	Uremia, Hypothyroidism, Gaucher disease.
Neoplastic	Lymphoma, Leukemia, Primary/Secondary metastatic tumors, Radiation therapy.
Trauma/Injury	Post-pericardiotomy syndrome, Post-myocardial infarction (Dressler syndrome), Direct penetrating trauma, Blunt thoracic injury.
Drug/Toxin	Anthracyclines, Procainamide, Hydralazine, Isoniazid, Penicillins. Venoms (scorpion fish).
Idiopathic	Accounts for 37-68% of pediatric cases. Presumed undiagnosed viral origin or immune response.

Clinical Features

• Chest Pain:
  • Central symptom.
  • Sharp, stabbing, squeezing, or throbbing. Positional exacerbation.
  • Worse in supine, during inspiration, or coughing.
  • Ameliorated on sitting upright or leaning forward.
  • Radiation to trapezius ridge common.
• Systemic Symptoms:
  • Fever, dyspnea, cough, malaise.
  • Abdominal pain occasionally present from hepatic distention in rapidly accumulating effusions.
• Pericardial Friction Rub:
  • Pathognomonic physical finding.
  • High-frequency, scratching, crunching sound.
  • Result of friction between inflamed pericardial layers.
  • Best auscultated at left lower sternal border.
  • Accentuated with patient leaning forward or kneeling.
  • Classically possesses three components: systolic, diastolic, and presystolic scratch.
  • Absence does not exclude diagnosis, especially with large effusions causing muffled sounds.

Diagnostic Criteria

Diagnosis requires presence of at least two of four criteria:

1. Pleuritic chest pain.
2. Pericardial friction rub.
3. Characteristic electrocardiogram (ECG) changes.
4. New or worsening pericardial effusion.

Investigations

Electrocardiogram (ECG)

• Widespread or localized changes. Characteristic sequential changes noted in 60% of patients.
• Sinus tachycardia frequently present. Low QRS voltage with large effusion.
• Electrical alternans: Specific but insensitive sign. Related to anterior-posterior cardiac motion within effusion.

Stage	ECG Findings
Stage 1	PR segment depression. Generalized concave ST segment elevation in lateral/inferior leads (I, II, aVF, aVL, V4-V6). Reciprocal ST depression in aVR and V1.
Stage 2	ST segment normalizes. J points on baseline. T wave amplitude begins flattening.
Stage 3	ST segment remains normal. T wave inversion in lateral/inferior leads (aVF, aVL, V4-V6).
Stage 4	Normalization of ECG. Some T wave changes may persist.

Laboratory Biomarkers

• Elevated inflammatory markers: C-reactive protein (CRP) elevated in up to 80%, erythrocyte sedimentation rate (ESR), white blood cell (WBC) count.
• Cardiac troponins: Elevated in 20-30% of patients. Indicates coexistent myocardial involvement (myopericarditis). Does not portend worse outcome unlike acute coronary syndrome.
• Fluid analysis: Classic Light’s criteria misleading for pericardial fluid. High baseline LDH and cellularity falsely classify normal pericardial fluid as exudate. Lymphocytosis common in viral etiologies.

Echocardiography

• Primary imaging modality. Normal in up to 40% of acute pericarditis cases.
• Identifies effusion size. Classifications based on echo-free space at end-diastole: trivial (systole only), small (<10 mm), moderate (10-20 mm), large (21-25 mm), very large (>25 mm).
• Excludes complications: Identifies concurrent ventricular dysfunction (myopericarditis), signs of tamponade, or constrictive physiology.

Cardiac Magnetic Resonance (CMR) and Chest X-Ray (CXR)

• CMR: Essential for evaluating ambiguous echocardiography or suspected myocardial involvement.
  • Late Gadolinium Enhancement (LGE): Quantifies inflammation/fibrosis. Sensitivity ~94%.
  • T2-STIR sequences: Detects myocardial/pericardial edema. Classifies acute inflammation.
  • Staging:
    • Positive LGE + increased T2 = acute phase.
    • Positive LGE + normal T2 = subacute phase.
    • Negative LGE + elevated T2 = healed/burned-out phase.
• CXR: Evaluates for alternative etiologies (TB, neoplasia, pneumonia). Enlarged cardiac silhouette (“water bottle” or Erlenmeyer flask shape) seen in significant effusion. Normal cardiac silhouette does not exclude tamponade if fluid accumulated rapidly.

Management

Medical Therapy

Medication Class	Guidelines / Details
NSAIDs + Colchicine	First-line therapy. Colchicine disrupts tubulin, inhibits neutrophil chemotaxis/mobility. Proven efficacy preventing recurrences.
Corticosteroids	E.g., Prednisone 0.2-0.5 mg/kg/day. Associated with increased risk of disease recurrence, prolonged tapering, and corticosteroid-dependence. Reserved for incomplete response, failure of first-line agents, or known autoimmune etiologies.
IL-1 Receptor Antagonists	Anakinra, Rilonacept. Highly effective in refractory, colchicine-resistant, or corticosteroid-dependent recurrent pericarditis.

Procedural and Lifestyle Management

• Pericardiocentesis: Indicated for cardiac tamponade, moderate-to-large symptomatic effusions refractory to medical therapy, or suspicion of purulent/neoplastic etiology.
• Activity Restriction: Prohibit competitive sports during acute phase. Resumption permitted only after complete resolution of active disease, normalization of echocardiogram, and normalized inflammatory markers.

Specific Subtypes

Viral Pericarditis

• Self-limited disease. Mnemonic: Enteroviruses, Influenza, Herpesviruses, Adenovirus.
• Treatment: Symptomatic management. NSAIDs + Colchicine. Corticosteroids generally contraindicated.

Bacterial (Purulent) Pericarditis

• Severe, life-threatening. Fulminant course leading to tamponade.
• Organisms: Staphylococcus aureus (most common, ~50%), H. influenzae, S. pneumoniae.
• Presentation: High fever, tachycardia out of proportion, hypotension, toxemia.
• Management: Urgent pericardiocentesis/surgical drainage mandatory. Fibrinolysis (streptokinase) may prevent organization. Broad-spectrum IV antibiotics (penicillinase-resistant penicillin + 3rd-generation cephalosporin + Vancomycin for MRSA risk) for 3-4 weeks. High risk of subsequent constrictive pericarditis.

Tuberculous Pericarditis

• Most common cause in developing nations. Subacute/insidious onset (fever, night sweats, weight loss).
• Diagnosis: Serosanguinous/hemorrhagic fluid. Lymphocytic predominance. Elevated Adenosine Deaminase (ADA) level (30-60 U/L). Acid-fast bacilli on auramine-rhodamine stain.
• Treatment: Multi-drug regimen. Rifampin, Isoniazid, Pyrazinamide, Ethambutol for 2 months. Followed by 4 months Isoniazid + Rifampin. High risk of constrictive pericarditis development.

Post-Cardiac Injury Syndrome (PCIS)

• Encompasses Post-pericardiotomy syndrome (PPS), Post-myocardial infarction (Dressler syndrome), post-traumatic pericarditis.
• Pathophysiology: Autoimmune trigger from damaged pericardial/pleural tissues and exposed endogenous antigens.
• Diagnosis: COPPS criteria (needs 2 of 5): Fever, pericardial/pleuritic pain, friction rub, pericardial effusion, pleural effusion with elevated CRP.
• Treatment: NSAIDs + Colchicine for 4-6 weeks.

Constrictive Pericarditis

Definition and Pathophysiology

• Characterized by fibrosis, calcification, and thickening of pericardium.
• Pericardium becomes stiff, loses compliance. Restricts cardiac chamber expansion, severely impairing diastolic filling.
• Decreased stroke volume and cardiac output.
• Ventricular Interdependence: Hallmark pathophysiology. Fixed total cardiac volume. Respirophasic changes in intrathoracic pressure fail to transmit to intracardiac chambers.
  • Inspiration: Negative intrathoracic pressure not transmitted to left atrium. Pulmonary vein-to-LA gradient drops. Decreased left heart venous return and stroke volume. Interventricular septum deviates leftward, augmenting right heart venous return and stroke volume.
  • Expiration: Septum deviates rightward. Left heart venous return recovers, right heart return decreases.

Etiology

• Idiopathic: Most common (~50% of cases).
• Iatrogenic: Prior cardiac surgery (~30%), Radiation therapy for malignancies (~10%).
• Infectious: Tuberculosis (historically common, major cause in developing world), Purulent bacterial infections.
• Autoimmune: SLE, Rheumatoid arthritis, vasculitis.
• Metabolic: Uremia.

Clinical Manifestations

• Subacute or chronic disease course. “Transient constriction” occurs in ~20% of patients and resolves with anti-inflammatory therapy.
• Right-sided heart failure symptoms: Peripheral edema, hepatomegaly, ascites, pulsatile liver, cachexia.
• Left-sided heart failure symptoms: Dyspnea, fatigue, exercise intolerance.
• Physical Examination:
  • Elevated Jugular Venous Pressure (JVP). Prominent ‘x’ and ‘y’ descents. Steep y-descent reflects rapid early diastolic filling.
  • Kussmaul’s Sign: Paradoxical inspiratory filling/distension of neck veins.
  • Pulsus Paradoxus: >10 mmHg fall in systolic blood pressure during inspiration.
  • Pericardial Knock: Early third heart sound. Caused by abrupt cessation of rapid ventricular filling.
  • Quiet precordium, normal sized heart. Tachycardia.

Investigations

Echocardiography

• Initial imaging modality of choice. Must perform with respirometer capabilities.
• Respirophasic Interventricular Septal Shift: Septal bounce towards LV during inspiration. Reflects ventricular interdependence.
• Inferior Vena Cava (IVC): Dilated with minimal (<50%) respiratory collapse.
• Annulus Reversus: Tissue Doppler shows septal (medial) mitral annular e’ velocity > lateral e’ velocity. Medial e’ > 8 cm/s indicates constriction.
• Hepatic Vein Doppler: End-diastolic flow reversal during expiration. Ratio of reversal flow velocity to forward flow velocity >0.8.

Cardiac Magnetic Resonance (CMR) and CT

• CT Scan: Highly sensitive for identifying pericardial calcifications (present in up to 50% of cases). Detects abnormal pericardial thickness (>4 mm).
• CMR: Preferred second-line modality. Superb spatial resolution.
  • Identifies septal motion, wall tethering, conical ventricular deformity.
  • Late Gadolinium Enhancement (LGE) assesses ongoing pericardial inflammation/fibrosis (guides potential medical management for transient constriction).

Cardiac Catheterization

• Gold standard hemodynamic confirmation. Necessary when noninvasive imaging is inconclusive.
• Equalization of diastolic pressures: Right atrial mean, RV end-diastolic, PA diastolic, and Pulmonary Capillary Wedge Pressure (PCWP) are identical or within 5 mmHg.
• Square root sign / Dip-and-plateau sign: Present in ventricular pressure tracing. Reflects rapid early filling followed by abrupt halt.
• RV End-Diastolic Pressure > 1/3 of RV Systolic Pressure.
• Right-to-left ventricle systolic area ratio > 1.1 during inspiration.

Differentiating Restrictive Cardiomyopathy vs. Constrictive Pericarditis

Feature	Restrictive Cardiomyopathy	Constrictive Pericarditis
Physical Exam	Kussmaul sign may be present, prominent Point of Maximal Impulse (PMI).	Kussmaul sign present, absent PMI. Pericardial knock.
ECG	Low-voltage QRS unusual.	Low-voltage QRS common.
Echocardiography	Marked atrial dilation. Reduced longitudinal strain. Septal e’ <6 cm/s. Hepatic vein flow reversal on inspiration.	May be enlarged. Respirophasic septal shift. Septal e’ >8 cm/s (Annulus reversus). Hepatic vein flow reversal on expiration.
MRI / CT	Normal pericardium.	Thickened (>4 mm) or calcified pericardium.
Cardiac Catheterization	LVEDP exceeds RVEDP by >4 mmHg. RVSP >50 mmHg. No respirophasic changes in wedge-LV gradient.	RVEDP = LVEDP. RVSP <50 mmHg. Dip-and-plateau (square root) sign.

Management

Medical Therapy

• Limited efficacy in chronic cases. Diuretics utilized for symptomatic relief of venous congestion (edema, ascites).
• For suspected transient constriction (evidence of active inflammation on CMR via LGE/T2-STIR): Trial of anti-inflammatory therapy (Colchicine + NSAIDs/Steroids) for 3 months. Inflammation may resolve spontaneously or respond to therapy.

Surgical Therapy

• Radical Pericardiectomy: Definitive and only effective treatment for chronic constrictive pericarditis.
• Approaches: Median sternotomy (preferred, maximizes access for cardiopulmonary bypass), bilateral thoracotomy, clamshell incision.
• Goal: Complete or wide anterior resection. Frees ventricles, normalizes hemodynamics.
• Comorbidities: Tricuspid regurgitation is common. Tricuspid valve surgery indicated in ~12% of procedures if moderate-severe regurgitation persists.
• Prognosis: Early surgical intervention indicated if calcification is present. Etiology dictates long-term survival (Idiopathic best prognosis; post-radiation worst prognosis). Resolves symptoms in 89% of pediatric patients with low early mortality.