PERICARDITIS

PERICARDITIS 

Definition

Pericarditis = inflammation of the pericardium, usually involving the visceral and parietal pericardial layers.

Clinically, pericardial inflammation may occur with or without pericardial effusion.

Anatomy relevant to pericarditis

The pericardium consists of:

Fibrous pericardium

• Tough outer layer
• Limits acute cardiac dilatation
• Anchors heart to diaphragm, sternum and great vessels

Serous pericardium

Parietal layer

• Lines inner surface of fibrous pericardium

Visceral layer = epicardium

• Covers cardiac surface

Between the layers is the pericardial cavity, normally containing approximately 15–50 mL of lubricating fluid.

Important clinical point

The phrenic nerves travel within the fibrous pericardium.

Therefore pericardial inflammation can cause:

• Chest pain
• Trapezius ridge pain
• Shoulder pain(due to diaphragmatic irritation)

The trapezius ridge sign is particularly suggestive of pericardial irritation because the phrenic nerve shares cervical roots with the supraclavicular nerves.

Classification

• Pericarditis + elevated troponin but preserved LV function → myopericarditis
• Myocarditis + LV systolic dysfunction → perimyocarditis

Etiology

The causes can be organized into:

Infectious

Viral

• Coxsackievirus
• Echovirus
• Enteroviruses
• Adenovirus
• Influenza
• SARS-CoV-2
• HIV

Bacterial

• Mycobacterium tuberculosis
• Staphylococcus aureus
• Streptococci
• Pneumococci
• Gram-negative organisms
• Meningococcus
• Gonococcus

Other

• Fungal
• Parasitic

Noninfectious causes

Autoimmune / inflammatory

• SLE
• Rheumatoid arthritis
• Systemic sclerosis
• Sjögren syndrome
• Vasculitis
• Adult-onset Still disease
• Sarcoidosis
• IgG4-related disease

Malignancy

• Lung cancer
• Breast cancer
• Lymphoma
• Leukemia
• Metastatic malignancy
• Primary pericardial tumors

Metabolic

• Uremia
• Hypothyroidism

Post-cardiac injury

• Post-MI pericarditis
• Post-pericardiotomy syndrome
• Post-traumatic pericarditis
• Iatrogenic injury

Drugs

Important examples:

• Hydralazine
• Procainamide
• Isoniazid
• Methyldopa
• Phenytoin
• Minoxidil
• Some immunotherapies

Radiation

• Mediastinal radiation

Trauma

• Blunt trauma
• Penetrating trauma
• Cardiac procedures

Clinical Features

Typical chest pain(~90% of patients)

Classical pericarditic pain is:

• Sharp stabbing (due to parietal irritation).
• Sudden Onset,May last hours to days,Often occurs episodically.
• Radiates to -Trapezius ridge pain,Shoulder pain(due to diaphragmatic irritation),Radiation down the left arm may occur (simulating ischemia)
• Worse with inspiration(pleuritic) and Swallowing(oesophagus in close to heart) 
• Worse with coughing
• Worse when lying supine
• Improved by sitting upright
• Improved by leaning forward

Important distinction

• Pericarditis → positional + pleuritic
• MI → pressure/heaviness, usually not relieved by leaning forward

However, patients with ACS and pericarditis can overlap clinically.

Associated symptoms

• Low-grade fever (~15%).
• Dyspnea (~33%) may result from respiratory splinting due to pain.
• Less frequent symptoms may include hiccups, dysphagia, or cough

Pericardial friction rub

Character

• High-pitched
• Scratchy
• Superficial
• Often triphasic

Three components correspond to:

1. Ventricular systole
2. Early ventricular diastole
3. Atrial systole

Best heard—Left lower sternal border with the patient:

• Sitting forward
• Holding breath in end-expiration

Important

The rub can be transient.

Absence of a rub does not exclude pericarditis.

Acute pericarditis — Diagnostic Criteria

The classic clinical diagnosis requires ≥2 of 4 major criteria:

1. Typical Pericarditic chest pain
2. Pericardial Friction Rub

3. New widespread ST-segment Elevation or PR-segment depression

4. New or worsening pericardial effusion

Therefore:

2 of 4 = clinical diagnosis of acute pericarditis

Supportive findings include:

• Elevated CRP/ESR
• Leukocytosis
• Imaging evidence of inflammation
• CMR evidence of pericardial inflammation

ECG in acute pericarditis

Classically there are 4 ECG stages.

Why PR depression occurs

Inflammation affects the atria/pericardium and produces an atrial injury current.This results in:PR depression and reciprocal:PR elevation in aVR

Pericarditis vs STEMI

Important exception

Myopericarditis can produce substantial troponin elevation.

Therefore:Elevated troponin does NOT automatically mean ACS.

Spodick’s sign

Spodick sign = downsloping TP segment, particularly in:

• Lead II
• Lateral precordial leads

It supports acute pericarditis.

But it is not diagnostic by itself.

PR depression vs atrial infarction

Diffuse PR depression strongly favors pericarditis.

The combination:Diffuse ST elevation + diffuse PR depression + ST depression only in aVR/V1 is highly characteristic.

Differential diagnosis of ST elevation

Acute MI

• Regional ST elevation
• Reciprocal changes
• Q waves
• Troponin elevation
• Regional wall-motion abnormality

Early repolarization

• Stable over time
• No inflammatory symptoms
• Usually no PR depression
• Often prominent in young people

Myocarditis / myopericarditis

• Troponin elevation
• LV dysfunction possible
• Arrhythmias possible

Takotsubo syndrome

• Characteristic wall-motion abnormalities
• Troponin often modest relative to LV dysfunction

Pulmonary embolism

• Usually not diffuse ST elevation
• RV strain pattern may occur

Workup

Initial

1. History
2. Examination
3. ECG
4. Troponin
5. CBC
6. CRP/ESR
7. Renal function
8. Electrolytes
9. Chest X-ray
10. Echocardiography

Additional according to context

• ANA/autoimmune panel
• TB evaluation
• HIV
• Blood cultures
• CT
• CMR
• Pericardial fluid analysis
• Cytology
• Pericardial biopsy

Laboratory investigations

CBC

May show:

• Leukocytosis(WBC >13,000-14,000 may suggest a specific underlying etiology (rather than idiopathic pericarditis). (Braunwald 12e)
• Anemia depending on underlying cause

CRP

CRP measured >12 hours after symptom onset may have a sensitivity closer to 95%.

Useful for:

• Supporting diagnosis
• Assessing inflammatory activity
• Monitoring treatment response
• Guiding duration of anti-inflammatory therapy

ESR

May be elevated.

CRP is generally more useful for monitoring.

Troponin

Troponin should be measured when pericarditis is suspected.Why?

Because myocardial involvement can coexist.

Terminology(based on which component predominate)

• Pericarditis + elevated cardiac biomarkers without new LV dysfunction→ myopericarditis
• Predominant myocarditis with associated pericardial involvement→ perimyocarditis

Troponin elevation is disproportionately low, as compared to MI.

Echocardiography

Echo is important because it detects:

• Pericardial effusion
• Tamponade
• LV/RV function
• Regional wall-motion abnormalities
• Hemodynamic consequences

Important

A normal echocardiogram does NOT exclude acute pericarditis.

Many cases have little or no effusion.

Pericardial effusion

The effusion may be:

• Serous
• Serosanguineous
• Hemorrhagic
• Purulent
• Chylous

Echo grading

A commonly used simplified classification:

Measurement is generally performed at end-diastole.

CT

CT is useful for:

• Pericardial thickening
• Calcification
• Loculated effusions
• Malignancy
• TB
• Mediastinal disease
• Constrictive pericarditis

Cardiac MRI

CMR is particularly useful when the diagnosis is uncertain or when myocardial involvement is suspected.

Findings include:

• Pericardial thickening
• Pericardial edema
• Pericardial late gadolinium enhancement(This reflects the neovascularization of the pericardium)
• Increased T2 signal
• Myocardial edema
• Myocardial LGE in myocarditis

Indications for pericardiocentesis may include:

1. Suspected bacterial, tuberculous, or neoplastic pericarditis 
2. Cardiac Tamponade.
3. Symptomatic moderate-large effusion plus the failure of anti-inflammatory therapy. 

Pericardial fluid analysis

If drainage is performed, fluid can be analyzed for:

• Cell count/differential
• Protein
• LDH
• Glucose
• Gram stain
• Bacterial culture
• AFB smear
• Mycobacterial culture
• NAAT
• ADA
• Cytology
• Triglycerides/chylomicrons when chylous effusion suspected

When to investigate the cause aggressively

Most uncomplicated presumed viral/idiopathic cases do not require an exhaustive etiologic workup.

Search for a specific cause when there are:

• Fever >38°C
• Subacute onset
• Large effusion
• Cardiac tamponade
• Failure to respond to treatment
• Recurrent disease
• Immunosuppression
• Trauma
• Malignancy suspicion
• TB risk
• Systemic autoimmune features
• Significant myocardial involvement

High-risk features in acute pericarditis

These identify patients requiring closer evaluation/hospitalization.

Major risk factors

• Fever >38°C
• Subacute onset
• Large pericardial effusion(>20 mm end-diastolic depth).
• Cardiac tamponade
• Failure to respond to NSAIDs after about 1 week

Minor risk factors

• Myopericarditis
• Immunosuppression
• Trauma
• Oral anticoagulant therapy

High-risk patients should generally be admitted and evaluated for secondary causes.

Treatment of acute idiopathic/viral pericarditis

NSAID/aspirin + colchicine

plus:

Gastroprotection when appropriate to prevent ulceration ( proton pump inhibitor B.D).

Aspirin

• Particularly preferred when pericarditis occurs after MI,Risk of acute kidney injury,Coronary artery stents.
• Dosing:Aspirin 750–1000 mg PO every 8 hours
• Duration commonly:1–2 weeks, followed by taper over 3-4 weeks

Ibuprofen—600–800 mg PO every 8 hours

Typically for:1–2 weeks then taper.

Advantages:

• Effective
• Shorter half-life
• Generally preferred over some longer-acting NSAIDs

NSAID contraindications/cautions

Use caution or avoid with:

• Severe renal dysfunction
• Active peptic ulcer disease
• GI bleeding
• Significant heart failure
• Severe uncontrolled hypertension
• NSAID allergy
• Certain anticoagulated patients

Colchicine

Colchicine inhibits:

• Microtubule polymerization
• Neutrophil chemotaxis
• Inflammasome-mediated inflammation

It has an important role in suppressing the inflammatory cascade responsible for recurrence.

It reduces:

• Symptom persistence
• Recurrence
• Treatment failure

Typical acute pericarditis regimen:0.5 mg once daily if <70 kg

or 0.5 mg twice daily if ≥70 kg

Duration:3 months for a first episode

For recurrent pericarditis:≥6 months

Dose adjustment is required in:

• Renal impairment(GFR <30 ml/min)
• Hepatic impairment
• Drug interactions(Myotoxicity risk inceases with statins.)

contraindications

• Renal failure (GFR <30 ml/min),relative contraindication.
• Severe hepatic failure.
• Preexisting cytopenia(s).

side effects

• GI side effects (especially diarrhea; also nausea, emesis, anorexia, abdominal pain).
• Gastrointestinal symptoms may represent the first sign of toxicity. If ignored, toxicity may progress. Progressive gastrointestinal toxicity may lead to hemorrhagic gastroenteritis, ileus, and bowel perforation.
• Myotoxicity (muscle pain, weakness, elevated CK, myotonia, rhabdomyolysis).
• Cytopenia(s) including neutropenia, thrombocytopenia, aplastic anemia, pancytopenia.
• B12 deficiency 
• Sensory motor neuropathy (more likely in chronic therapy).
• Dermatological (alopecia, rash, purpura, maculopapular rash).
• Hepatotoxicity.

Important drug interactions with colchicine

Colchicine is metabolized through:

• CYP3A4
• P-glycoprotein

Toxicity increases with strong inhibitors such as:

• Clarithromycin
• Certain azole antifungals
• Cyclosporine
• Some calcium-channel blockers

Corticosteroids

Not first-line in uncomplicated idiopathic acute pericarditis.

Why?Steroids may:

• Increase recurrence
• Promote dependence
• Mask underlying infection
• Complicate TB pericarditis

Use when there is a specific indication or contraindication to NSAIDs/colchicine.

Examples:

• Patients with underlying connective tissue disease.
• NSAID/Aspirin contraindication
• Pregnancy in selected situations
• Refractory disease-Pericarditis is unresponsive to a reasonable duration of therapy with maximal doses of aspirin/NSAID and colchicine (especially with persistently elevated CRP).
• Constrictive/effusive pericarditis on echocardiography or CMRI

Typical low-to-moderate dose:Prednisone 0.2–0.5 mg/kg/day

followed by a very slow taper.

Steroid taper

The most important principle: Do not taper corticosteroids rapidly in recurrent pericarditis.

A practical approach:

• Reduce only when asymptomatic
• CRP normalized
• Maintain each dose for sufficient time
• Smaller reductions at low doses

The lowest-dose range can be particularly difficult.

Aspirin/NSAID treatment endpoint

• Treatment should generally continue until:Symptoms resolve,CRP normalizes.
• Then taper NSAID/aspirin.

Activity restriction

Patients with acute pericarditis should restrict strenuous physical activity until:

• Symptoms resolved
• Inflammatory markers normalized

Athletes require more stringent restriction and evaluation.

If myocarditis is present, exercise restriction is generally longer and more stringent.

Purulent pericarditis

Usually caused by bacteria.

Risk factors:

• Pneumonia
• Bacteremia
• Recent thoracic surgery
• Immunosuppression
• Trauma
• Infective endocarditis

Clinical clues:

• High fever
• Toxic appearance
• Neutrophilic leukocytosis
• Rapidly progressive effusion
• Tamponade

Management

Urgent drainage + IV antibiotics

Often surgical drainage is required because pus can become loculated.

Tuberculous pericarditis

Extremely important in India.

TB can produce:

• Acute pericarditis
• Pericardial effusion
• Tamponade
• Constrictive pericarditis

Symptoms may be:

• Fever
• Weight loss
• Night sweats
• Dyspnea
• Chest discomfort

TB pericardial fluid

Usually:

• Exudative
• Lymphocyte predominant
• High protein

Investigations may include:

• AFB smear
• Mycobacterial culture
• NAAT
• ADA
• Cytology
• Biopsy

Important

A negative AFB smear does not exclude TB pericarditis.

Pericardial biopsy can be important when diagnosis remains uncertain.

TB pericarditis treatment

• Standard anti-TB therapy according to susceptibility and national guidelines.
• In HIV-negative patients with TB pericarditis, adjunctive corticosteroids may reduce complications in selected patients, particularly mortality and constriction risk, although benefits vary with clinical context.

Malignant pericardial effusion

Common malignancies:

• Lung cancer
• Breast cancer
• Hematologic malignancies

Can present with:

• Large recurrent effusion
• Tamponade
• Weight loss
• Dyspnea

Diagnostic test

Pericardial fluid cytology

may establish diagnosis.

However, negative cytology does not completely exclude malignancy.

Uremic pericarditis

Occurs in:

• Severe untreated uremia
• Advanced renal failure
• Sometimes inadequate dialysis

Important distinction

Uremic pericarditis

vs

dialysis-associated pericarditis

Treatment:

Intensify dialysis

NSAIDs/colchicine are not necessarily the main treatment because the underlying driver is uremia and renal dysfunction.

If tamponade occurs:urgent drainage.

Post-MI pericarditis

Two forms are important.

1. Early Post-Myocardial Infarction Pericarditis

• Occurs shortly after(within four days ) a transmural MI.
• Mechanism:Necrotic myocardium → inflammatory response
• Treatment-Aspirin 500 mg q8-12 hours for 5-7 days usually.

2. Dressler syndrome

Usually occurs:weeks after MI and is an immune-mediated post-cardiac injury syndrome.

Can produce:

• Fever
• Pleuritic chest pain
• Pericarditis
• Pericardial effusion
• Pleural effusion

Post-pericardiotomy syndrome

Occurs after:CABG,Valve surgery,Other cardiac surgery.

Features:

• Fever
• Pleuritic chest pain
• Pericardial effusion
• Pleural effusion

Mechanism is largely immune-mediated.

Treatment often involves:

• Aspirin/NSAID
• Colchicine

Pericarditis complications

Acute

• Pericardial effusion
• Tamponade
• Myopericarditis
• Arrhythmias

Long-term

• Recurrent pericarditis
• Constrictive pericarditis
• Chronic effusion
• Effusive-constrictive disease

Recurrent pericarditis — major risk factors

Risk increases with:

• Inadequate initial treatment
• Early steroid use
• Rapid steroid taper
• Persistent inflammatory markers
• Autoimmune disease
• Previous recurrence

Hemorrhagic pericardial effusion

Consider:

• Malignancy
• TB
• Trauma
• Aortic dissection
• MI rupture
• Anticoagulation
• Iatrogenic injury

Hemopericardium + shock = emergency.

Chylopericardium

Rare.

Usually caused by:

• Thoracic duct injury
• Surgery
• Trauma
• Malignancy

Fluid:

• Milky
• High triglycerides
• Chylomicrons present

Neoplastic pericardial disease

May cause:

• Recurrent effusion
• Tamponade
• Constrictive physiology

Management may include:

• Pericardiocentesis
• Extended drainage
• Intrapericardial therapy in selected cases
• Surgical window
• Treatment of underlying malignancy

Pericardial window

A surgical connection between the pericardial space and:

• Pleural cavity

or another drainage space.

Used particularly for:

• Recurrent effusion
• Malignant effusion
• Loculated effusion
• Effusions not adequately managed by repeated pericardiocentesis

Pericardiectomy

Definitive treatment for:

Chronic symptomatic constrictive pericarditis

The diseased pericardium is surgically removed.

It is a major operation with significant perioperative risk.