Radiation induced pericarditis

# 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. Radiation-induced pericarditis was first described in the mid-1960s. The radiation-induced pericardial disease may be classified as acute pericarditis, delayed pericarditis, pancarditis, constrictive pericarditis, and pericardial effusion. Radiation therapy leads to disruption of endothelium and subsequent episodes of ischemia. The resulting fibrosis and fibrinous exudates replace collagen fibers. 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. Radiation-induced pericarditis depends on the total dose of radiation, the dose per fraction, the amount of cardiac silhouette exposed, and the nature of the radiation source. The incidence is higher with doses greater than 40 Gy (4000 rad). Echocardiography is the most commonly used screening modality for the detection and follow-up of radiation-induced cardiac disease. Acute pericarditis usually develops a few weeks after radiation exposure. Nearly 20% of patients with acute pericarditis develop chronic or constrictive pericarditis in the next 5-10 years following radiation therapy. The risk is increased when pericardial effusion was present previously. Chronic pericarditis can also occur in patients without a history of 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 occurs from months to years after exposure to radiation. It usually presents with chest pain, dyspnea, and orthopnea. The physical examination may show fever and pericardial rub. Laboratory findings include elevated inflammatory markers such as neutrophil count and erythrocyte sedimentation rate (ESR). On ECG, non-specific ST and T wave changes or ST-segment elevation in all leads may be noted. The majority of acute pericarditis cases are self-limited and respond well to nonsteroidal anti-inflammatory drugs and colchicine. In acute or chronic pericarditis, protein-rich exudate may accumulate in the pericardial sac leading to pericardial effusion. Findings on a chest x-ray or chest CT suggestive of chronic pericarditis include pericardial effusion and pericardial thickening. If the effusion is large enough, it may lead to tamponade. In patients presenting with tamponade, the physical examination may show hypotension, tachycardia, and jugular venous distention with a prominent Y descent, Kussmauls sign, and distant heart sound. Radiation-induced pericardial effusion can be confused with malignant pericarditis and hypothyroidism-induced pericarditis. 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. 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. Cardiac MRI may be helpful in the diagnosis of constrictive pericarditis. It is useful to confirm the pericardial thickening. Cardiac catheterization may be also helpful in the diagnosis of constrictive pericarditis associated with radiation therapy. Pericardiectomy is recommended for patients who develop constrictive pericarditis. However, the perioperative mortality rate is higher in radiation-induced constrictive pericarditis compared to that of idiopathic constrictive pericarditis. Effective measures for the primary prevention of radiation-induced pericarditis include reducing the dose and volume of cardiac irradiation when possible.

# Historical Perspective
Radiation-induced pericarditis was first described in the mid-1960s.

# Classification
Based on the presentation and onset of symptoms, the radiation-induced pericardial disease may be classified as:
- Acute pericarditis
- Delayed pericarditis
- Pancarditis
- Constrictive pericarditis
- 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 .

# 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
- 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:
- Constrictive pericarditis should be differentiated from restrictive cardiomyopathy:

# 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 a 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
Radiation-induced pericarditis depends on:
- Total dose of radiation
- The dose per fraction
- Amount of cardiac silhouette exposed
- Nature of the radiation source
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.

# Screening
Echocardiography is the most commonly used screening modality for the detection and follow-up of radiation-induced cardiac disease. It is typically done every two years in asymptomatic individuals and more frequently when symptoms are present.

# Natural History, Complications, and Prognosis
Acute pericarditis usually develops a few weeks after radiation exposure. Nearly 20% of patients with acute pericarditis develop chronic or constrictive pericarditis in the next 5-10 years following radiation therapy.The risk is increased when pericardial effusion was present previously. Chronic pericarditis can also occur in patients without a history of acute pericarditis.

# 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
- 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 friction rub. In patients presenting with tamponade, the 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.
In patients presenting with constrictive pericarditis, electrocardiographic changes are similar to other causes of constrictive pericarditis. Electrocardiographic signs of constrictive 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
A chest x-ray may be helpful in the diagnosis of radiation-induced pericarditis. Findings on an x-ray suggestive of chronic pericarditis include pericardial effusion and pericardial thickening.

## Echocardiography or Ultrasound
Echocardiography is the gold standard for definitive diagnosis of acute or chronic pericarditis with pericardial effusion and helps to rule out a cardiac tamponade.

## CT scan
A chest CT scan may be helpful in the diagnosis of radiation-induced pericarditis. Findings on a CT scan suggestive of chronic pericarditis include pericardial effusion and pericardial thickening.

## MRI
Cardiac MRI may be helpful in the diagnosis of radiation-induced pericarditis. It is useful to confirm the pericardial thickening in chronic and constrictive pericarditis. It is also helpful to assess for concomitant myocardial involvement.

## Other Imaging Findings
There are no other imaging findings associated with radiation-induced pericarditis.

## Other Diagnostic Studies
Cardiac catheterization may be helpful in the diagnosis of constrictive pericarditis associated with radiation therapy.
For more information on cardiac catheterization findings in constrictive pericarditis, click here.

## Pericardiocentesis
- Radiation induced pericardial effusion can be confused with malignant pericarditis and hypothyroidism-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
The majority of radiation-induced acute pericarditis cases are self-limited and respond well to nonsteroidal anti-inflammatory drugs and colchicine. Steroids are associated with a higher chance of relapse and therefore are only used in cases who fail to respond to nonsteroidal anti-inflammatory agents.

## 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 radiation-induced constrictive pericarditis compared to that of idiopathic constrictive pericarditis.

## Primary Prevention
Effective measures for the primary prevention of radiation-induced pericarditis include reducing the dose and volume of cardiac irradiation when possible.

## Secondary Prevention
There are no established measures for the secondary prevention of radiation-induced pericarditis.