Radiation induced pericarditis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Overview

The survival rate in Hodgkin lymphoma, Non-Hodgkin's lymphoma and breast carcinomas has significantly improved with use of radiation therapy. However, radiation therapy to thoracic and mediastinal cancers have also led to the development of pericarditis, coronary artery disease, cardiomyopathy, conduction abnormalities in heart and valvular heart diseases which account for significant morbidity and mortality. The incidence is higher with doses greater than 40 Gy (4000 rad).

Classification

Based on the presentation and onset of symptoms, the radiation-induced pericardial disease may be classified as:

1. Acute pericarditis
2. Delayed pericarditis
3. Pancarditis
4. Constrictive pericarditis
5. Pericardial effusion

Pathophysiology

Radiation therapy disrupts endothelial cells of the microvasculature of the pericardium and leads to repeated episodes of ischemia. The final result is the formation of fibrosis and fibrinous exudates that are ultimately replaced by fibroblasts and collagen fibers .

Radiation-induced pericarditis depends on:

• Total dose of radiation
• Amount of cardiac silhouette exposed
• Nature of the radiation source
• Duration and fractionation of therapy

In a retrospective study, 27.7% of the patients developed pericardial effusion after median time period of 5.3 months following radiotherapy for esophageal carcinoma with radiation dose ranging between 3 to 50Gy. It was concluded that high dose-volume of the irradiated pericardium and heart increased the risk of developing pericarditis.

Causes

Radiation-induced pericardial disease can occur in any cancer survivor who receive thoracic radiation therapy, including breast cancer, Hodgkin's lymphoma, esophageal cancer, and lung cancer. However, most data come from patients treated for breast cancer and Hodgkin's lymphoma, in which radiation therapy is a frequent component of management.

Differentiating Radiation-induced Pericarditis from other Diseases

• Pericarditis must be differentiated from diseases presenting with chest pain, shortness of breath and tachypnea.
  • For a full discussion of the differential diagnosis of chest pain click here
  • For an expert algorithm that aids in the diagnosis of the cause of chest pain click here
• Pericarditis must be differentiated from myocardial infarction as an important cause of chest pain.The differentiating features include:

Characteristic/Parameter	Pericarditis	Myocardial infarction
Pain description	Sharp, pleuritic, retro-sternal (under the sternum) or left precordial (left chest) pain.	Crushing, pressure-like, heavy pain. Described as "elephant on the chest".
Radiation	Pain radiates to the trapezius ridge (to the lowest portion of the scapula on the back) or no radiation.	Pain radiates to the jaw, or the left or arm, or does not radiate.
Exertion	Does not change the pain	Can increase the pain
Position	Pain is worse supine or upon inspiration (breathing in)	Not positional
Onset/duration	Sudden pain, that lasts for hours or sometimes days before a patient comes to the ER	Sudden or chronically worsening pain that can come and go in paroxysms or it can last for hours before the patient decides to come to the ER

Differentiating pericarditis from other diseases on the basis of chest pain, shortness of breath, and tachypnea

The differentials include the following:

Diseases	Diagnostic tests			Physical Examination			Symptoms							Past medical history	Other Findings
	CT scan and MRI	EKG	Chest X-ray	Tachypnea	Tachycardia	Fever	Chest Pain	Hemoptysis	Dyspnea on Exertion	Wheezing	Chest Tenderness	Nasalopharyngeal Ulceration	Carotid Bruit
Percarditis	On contrast enhanced CT scan: Enhancement of the pericardium (due to inflammation) Pericardial effusion Pericardial calcification On gadolinium-enhanced fat-saturated T1-weighted MRI: Pericardial enhancement (due to inflammation) Pericardial effusion	ST elevation PR depression	Large collection of fluid inside the pericardial sac (pericardial effusion) Calcification of pericardial sac	✔	✔	✔ (Low grade)	✔ (Relieved by sitting up and leaning forward)	-	✔	-	-	-	-	Infections: Viral (Coxsackie virus, Herpes virus, Mumps virus, HIV) Bacteria (Mycobacterium tuberculosis-common in developing countries) Fungal (Histoplasmosis) Idiopathic in a large number of cases Autoimmune Uremia Malignancy Previous myocardial infarction	May be clinically classified into: Acute (< 6 weeks) Sub-acute (6 weeks - 6 months) Chronic (> 6 months)
Pulmonary embolism	On CT angiography: Intra-luminal filling defect On MRI: Narrowing of involved vessel No contrast seen distal to obstruction Polo-mint sign (partial filling defect surrounded by contrast)	S1Q3T3 pattern representing acute right heart strain	Fleischner sign (enlarged pulmonary artery), Hampton hump, Westermark's sign	✔	✔	✔ (Low grade)	✔	✔ (In case of massive PE)	✔	-	-	-	-	Hypercoagulating conditions (Factor V Leiden, thrombophilia, deep vein thrombosis, immobilization, malignancy, pregnancy)	May be associated with metabolic alkalosis and syncope
Congestive heart failure	On CT scan: Mediastinal lymphadenopathy Hazy mediastinal fat On MRI: Abnormality of cardiac chambers (hypertrophy, dilation) Delayed enhancement MRI may help characterize the myocardial tissue (fibrosis) Late enhancement of contrast in conditions such as myocarditis, sarcoidosis, amyloidosis, Anderson-Fabry's disease, Chagas disease)	Goldberg's criteria may aid in diagnosis of left ventricular dysfunction: (High specificity) SV1 or SV2 + RV5 or RV6 ≥3.5 mV Total QRS amplitude in each of the limb leads ≤0.8 mV R/S ratio <1 in lead V4	Cardiomegaly	✔	✔	✔	-	-	✔	-	-	-	-	Previous myocardial infarction Hypertension (systemic and pulmonary) Cardiac arrythmias Viral infections (myocarditis) Congenital heart defects	Right heart failure associated with: Hepatomegaly Positive hepato-jugular reflex Increased jugular venous pressure Peripheral edema Left heart failure associated with: Pulmonary edema Eventual right heart failure
Pneumonia	On CT scan: (not generally indicated) Consolidation (alveolar/lobar pneumonia) Peribronchial nodules (bronchopneumonia) Ground-glass opacity (GGO) Abscess Pleural effusion On MRI: Not indicated	Prolonged PR interval Transient T wave inversions	Consolidation (alveolar/lobar pneumonia) Peribronchial nodules (bronchopneumonia) Ground-glass opacity (GGO)	✔	✔	✔	✔	-	✔	✔	-	-	-	Ill-contact Travelling Smoking Diabetic Recent hospitalization Chronic obstructive pulmonary disease	Requires sputum stain and culture for diagnosis Empiric management usually started before culture results
Vasculitis	On CT scan: (Takayasu arteritis) Vessel wall thickening Luminal narrowing of pulmonary artery Masses or nodules (ANCA-associated granulomatous vasculitis) On MRI: Homogeneous, circumferential vessel wall swelling	Right or left bundle-branch block (Churg-Strauss syndrome) Atrial fibrillation (Churg-Strauss syndrome) Non-specific ST segment and T wave changes	Nodules Cavitation	✔	✔	✔	✔	✔	✔	-	✔	✔	✔	Takayasu arteritis usually found in persons aged 4-60 years with a mean of 30 Giant-cell arteritis usually occurrs in persons aged > 60 years Churg-Strauss syndrome may present with asthma, sinusitis, transient pulmonary infiltrates and neuropathy alongwith cardiac involvement Granulomatous vasculitides may present with nephritis and upper airway (nasopharyngeal) destruction
Chronic obstructive pulmonary disease (COPD)	On CT scan: Chronic bronchitis may show bronchial wall thickening, scarring with bronchovascular irregularity, fibrosis Emphysema may show alveolar septal destruction and airspace enlargement (Centrilobular- upper lobe, panlobular- lower lobe) Giant bubbles On MRI: Increased diameter of pulmonary arteries Peripheral pulmonary vasculature attentuation Loss of retrosternal airspace due to right ventricular enlargement Hyperpolarized Helium MRI may show progressively poor ventilation and destruction of lung	Multifocal atrial tachycardia (atleast 3 distinct P wave morphologies)	Enlarged lung shadows (emphysema) Flattening of diaphragm (emphysema)	✔	✔	-	-	-	✔	✔	-	-	-	Smoking Alpha-1 antitrypsin deficiency Increased sputum production (chronic bronchitis) Cough	Alpha 1 antitrypsin deficiency may be associated with hepatomegaly

Epidemiology and Demographics

Pericardial changes are the most common cardiac complications of radiation therapy. Incidence of radiation induced pericarditis has significantly decreased with the use of lower doses and newer radiotherapy techniques . In a study, incidence decreased from 20% to 2.5% with the changes in methods of RT administration

In as study among pediatric population with various cancers, radiation therapy with ≥15 GY increased the risk of developing pericarditis by two to six times

Risk Factors

Screening

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

There are no established criteria for radiation induced pericarditis.

History and Symptoms

• Acute pericarditis: Acute pericarditis is a rare complication of radiation therapy. It presents with nonspecific pericarditis symptoms such as chest pain and fever shortly after radiation therapy.

• Delayed pericarditis: Delayed pericarditis occurs from months to years after exposure to radiation . It usually presents with:
  • Chest pain
  • Dyspnea
  • Orthopnea
• Pericardial effusion: Protein-rich exudate may accumulate in the pericardial sac leading to pericardial effusion. Rapid accumulation may result in the development of cardiac tamponade presenting with clinical signs and symptoms of tamponade.

• Constrictive pericarditis: Constrictive pericarditis is a late complication of radiation therapy. Patients typically present with signs and symptoms of heart failure, similar to other causes of constrictive pericarditis.

Physical Examination

Physical examination of patients with radiation-induced pericarditis depends on the presentation. In acute pericarditis, the physical examination may show fever and pericardial rub. In patients presenting with tamponade physical examination may show:

• Hypotension
• Tachycardia
• Jugular venous distention with a prominent Y descent
• Kussmaul's sign, and distant heart sounds

In constrictive pericarditis, signs of congestive heart failure may be present, including:

• Hepatomegaly
• Ascites
• Ankle edema

Laboratory Findings

Laboratory findings consistent with the diagnosis of radiation-induced acute pericarditis include elevated inflammatory markers such as neutrophil count and erythrocyte sedimentation rate (ESR).

Electrocardiogram

In acute pericarditis, non-specific ST and T wave changes or ST segment elevation in all leads may be noted.

Acute pericarditis

In patients presenting with constrictive pericarditis, electrocardiographic changes are similar to other causes of constrictive pericarditis. Electrocardiographic signs of constrictive chronic pericarditis is usually inconsistent and non specific

• Left atrial enlargement
• Frequent atrial arrhythmias
• Right axis deflection
• Possible reduction in voltages
• Diffuse negative T-waves
• Typical (normal QRS axis, low voltage, and generalized T wave flattening or inversion)
• Right ventricular hypertrophy
• Right axis deviation

X-ray

Echocardiography or Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Pericardiocentesis

• Radiation induced pericardial effusion can be confused with malignant pericarditis and hypothyroidism (secondary to mediastinal irradiation) induced pericarditis.
• Pericardiocentesis can be used to differentiate them with fluid analysis for malignant cells and thyroid function tests.
• For more information on pericardiocentesis, click here.

Treatment

Medical Therapy

Surgery

• Pericarditis with large effusion can be drained either percutaneously or surgically
• Those with recurrent pericardial effusion can be treated with pericardiotomy(pericardial window) or by surgical stripping.
• Pericardiectomy is recommended for patients who develop constrictive pericarditis. However, the perioperative mortality rate is higher in postradiation constrictive pericarditis compared to that of idiopathic constrictive pericarditis.

Primary Prevention

Secondary Prevention

References

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