Radiation induced pericarditis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-In-Chief: Mandana Chitsazan, M.D. ; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.
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, Kussmaul’s 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.
Radiation-induced pericarditis was first described in the mid-1960s.
Based on the presentation and onset of symptoms, the radiation-induced pericardial disease may be classified as:
- Acute pericarditis
- Delayed pericarditis
- Constrictive pericarditis
- Pericardial effusion
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 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:
|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|
- Constrictive pericarditis should be differentiated from restrictive cardiomyopathy:
|Type of disease||History and Physical examination||Chest X-ray and ECG||2D and Doppler echo||CT and MRI||Catheterization hemodynamics||Biopsy|
||May reveal underlying cause|
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
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.
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.
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:
- 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 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:
- 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:
Laboratory findings consistent with the diagnosis of radiation-induced acute pericarditis include elevated inflammatory markers such as neutrophil count and erythrocyte sedimentation rate (ESR).
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
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.
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.
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.
- 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.
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.
- 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.
Effective measures for the primary prevention of radiation-induced pericarditis include reducing the dose and volume of cardiac irradiation when possible.
There are no established measures for the secondary prevention of radiation-induced pericarditis.
- ↑ "Radiation-Induced CAD: Incidence, Diagnosis, and Management Outcomes - American College of Cardiology".
- ↑ 2.0 2.1 2.2 Yusuf SW, Sami S, Daher IN (2011). "Radiation-induced heart disease: a clinical update". Cardiol Res Pract. 2011: 317659. doi:10.4061/2011/317659. PMC 3051159. PMID 21403872.
- ↑ Fajardo LF (1989). "The unique physiology of endothelial cells and its implications in radiobiology". Front Radiat Ther Oncol. 23: 96–112. doi:10.1159/000416574. PMID 2697671.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Yusuf SW, Venkatesulu BP, Mahadevan LS, Krishnan S (2017). "Radiation-Induced Cardiovascular Disease: A Clinical Perspective". Front Cardiovasc Med. 4: 66. doi:10.3389/fcvm.2017.00066. PMC 5662579. PMID 29124057.
- ↑ Taunk NK, Haffty BG, Kostis JB, Goyal S (2015). "Radiation-induced heart disease: pathologic abnormalities and putative mechanisms". Front Oncol. 5: 39. doi:10.3389/fonc.2015.00039. PMC 4332338. PMID 25741474.
- ↑ Hooning MJ, Aleman BM, van Rosmalen AJ, Kuenen MA, Klijn JG, van Leeuwen FE (2006). "Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study". Int J Radiat Oncol Biol Phys. 64 (4): 1081–91. doi:10.1016/j.ijrobp.2005.10.022. PMID 16446057.
- ↑ American College of Physicians (ACP). Medical Knowledge Self-Assessment Program (MKSAP-15): Cardiovascular Medicine. "Pericardial disease." p. 64. ISBN 978-934465-28-8 
- ↑ 8.0 8.1 Rammos A, Meladinis V, Vovas G, Patsouras D (2017). "Restrictive Cardiomyopathies: The Importance of Noninvasive Cardiac Imaging Modalities in Diagnosis and Treatment-A Systematic Review". Radiol Res Pract. 2017: 2874902. doi:10.1155/2017/2874902. PMC 5705874. PMID 29270320.
- ↑ 9.0 9.1 Hong JA, Kim MS, Cho MS, Choi HI, Kang DH, Lee SE, Lee GY, Jeon ES, Cho JY, Kim KH, Yoo BS, Lee JY, Kim WJ, Kim KH, Chung WJ, Lee JH, Cho MC, Kim JJ (September 2017). "Clinical features of idiopathic restrictive cardiomyopathy: A retrospective multicenter cohort study over 2 decades". Medicine (Baltimore). 96 (36): e7886. doi:10.1097/MD.0000000000007886. PMC 6393124. PMID 28885342.
- ↑ Ramasamy V, Mayosi BM, Sturrock ED, Ntsekhe M (September 2018). "Established and novel pathophysiological mechanisms of pericardial injury and constrictive pericarditis". World J Cardiol. 10 (9): 87–96. doi:10.4330/wjc.v10.i9.87. PMC 6189073. PMID 30344956.
- ↑ Biçer M, Özdemir B, Kan İ, Yüksel A, Tok M, Şenkaya I (November 2015). "Long-term outcomes of pericardiectomy for constrictive pericarditis". J Cardiothorac Surg. 10: 177. doi:10.1186/s13019-015-0385-8. PMC 4662820. PMID 26613929.
- ↑ Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ (January 2003). "Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations". J. Clin. Invest. 111 (2): 209–16. doi:10.1172/JCI16336. PMC 151864. PMID 12531876.
- ↑ 13.0 13.1 Carmel RJ, Kaplan HS (1976). "Mantle irradiation in Hodgkin's disease. An analysis of technique, tumor eradication, and complications". Cancer. 37 (6): 2813–25. doi:10.1002/1097-0142(197606)37:6<2813::aid-cncr2820370637>3.0.co;2-s. PMID 949701.
- ↑ Maisch B, Ristić AD (2003). "Practical aspects of the management of pericardial disease". Heart. 89 (9): 1096–103. PMC 1767862. PMID 12923044.
- ↑ Maisch B, Seferović PM, Ristić AD, Erbel R, Rienmüller R, Adler Y; et al. (2004). "Guidelines on the diagnosis and management of pericardial diseases executive summary; The Task force on the diagnosis and management of pericardial diseases of the European society of cardiology". Eur Heart J. 25 (7): 587–610. doi:10.1016/j.ehj.2004.02.002. PMID 15120056.
- ↑ Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M; et al. (2009). "Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort". BMJ. 339: b4606. doi:10.1136/bmj.b4606. PMID 19996459.
- ↑ Wei X, Liu HH, Tucker SL, Wang S, Mohan R, Cox JD; et al. (2008). "Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy". Int J Radiat Oncol Biol Phys. 70 (3): 707–14. doi:10.1016/j.ijrobp.2007.10.056. PMID 18191334.
- ↑ Cosset JM, Henry-Amar M, Pellae-Cosset B, Carde P, Girinski T, Tubiana M; et al. (1991). "Pericarditis and myocardial infarctions after Hodgkin's disease therapy". Int J Radiat Oncol Biol Phys. 21 (2): 447–9. doi:10.1016/0360-3016(91)90794-5. PMID 1905691.
- ↑ "Radiation Associated Cardiac Disease - American College of Cardiology".
- ↑ Gaya AM, Ashford RF (2005). "Cardiac complications of radiation therapy". Clin Oncol (R Coll Radiol). 17 (3): 153–9. doi:10.1016/j.clon.2004.09.016. PMID 15900998.
- ↑ 21.0 21.1 Morton DL, Glancy DL, Joseph WL, Adkins PC (1973). "Management of patients with radiation-induced pericarditis with effusion: a note on the development of aortic regurgitation in two of them". Chest. 64 (3): 291–7. doi:10.1378/chest.64.3.291. PMID 4127171.
- ↑ Applefeld MM, Cole JF, Pollock SH, Sutton FJ, Slawson RG, Singleton RT; et al. (1981). "The late appearance of chronic pericardial disease in patients treated by radiotherapy for Hodgkin's disease". Ann Intern Med. 94 (3): 338–41. doi:10.7326/0003-4819-94-3-338. PMID 7224379.
- ↑ Chesler E, Mitha AS, Matisonn RE (1976). "The ECG of constrictive pericarditis--pattern resembling right ventricular hypertrophy". Am Heart J. 91 (4): 420–4. doi:10.1016/s0002-8703(76)80321-3. PMID 1258748.
- ↑ 24.0 24.1 24.2 24.3 Nielsen KM, Offersen BV, Nielsen HM, Vaage-Nilsen M, Yusuf SW (2017). "Short and long term radiation induced cardiovascular disease in patients with cancer". Clin Cardiol. 40 (4): 255–261. doi:10.1002/clc.22634. PMC 6589645 Check
|pmc=value (help). PMID 28139844.
- ↑ 25.0 25.1 Yusuf SW, Hassan SA, Mouhayar E, Negi SI, Banchs J, O'Gara PT (2016). "Pericardial disease: a clinical review". Expert Rev Cardiovasc Ther. 14 (4): 525–39. doi:10.1586/14779072.2016.1134317. PMID 26691443.
- ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID 10.1016/j.jacc.2013.01.090 DOI: 10.1016/j.jacc.2013.01.090 Check
- ↑ Darby SC, Cutter DJ, Boerma M, Constine LS, Fajardo LF, Kodama K; et al. (2010). "Radiation-related heart disease: current knowledge and future prospects". Int J Radiat Oncol Biol Phys. 76 (3): 656–65. doi:10.1016/j.ijrobp.2009.09.064. PMC 3910096. PMID 20159360.
- ↑ Bertog SC, Thambidorai SK, Parakh K, Schoenhagen P, Ozduran V, Houghtaling PL; et al. (2004). "Constrictive pericarditis: etiology and cause-specific survival after pericardiectomy". J Am Coll Cardiol. 43 (8): 1445–52. doi:10.1016/j.jacc.2003.11.048. PMID 15093882.
- ↑ Maraldo MV, Ng AK (2016). "Minimizing Cardiac Risks With Contemporary Radiation Therapy for Hodgkin Lymphoma". J Clin Oncol. 34 (3): 208–10. doi:10.1200/JCO.2015.64.6588. PMID 26628476.
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