Radiation-Induced Heart Disease


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J Emerg Med. 2002 Aug;23(2):175-8.
Radiation-induced aortoesophageal fistula: an unusual case of massive upper gastrointestinal bleeding.
Sivaraman SK, Drummond R.
Department of Emergency Medicine, McGill University, Montreal, Quebec, Canada.

Aortoesophageal fistula (AEF) is an unusual cause of massive upper gastrointestinal bleeding. Thoracic aortic aneurysm is the most common etiology of primary AEF followed by, respectively, foreign body ingestion, esophageal malignancy, and postsurgical fi stulization. Radiation-induced damage to the great vessels is well recognized and some authors in the past have suggested that AEF may be caused by radiotherapy. However, previous case reports of radiation-induced AEF involved patients who received radiot herapy for esophageal carcinoma, and precise histopathologic differentiation between AEF secondary to esophageal malignancy and that induced by radiation was difficult. We present here the unique case of a patient with a non-esophageal carcinoma who recei ved radiotherapy before the development of an AEF, thus providing further evidence for the role of radiation injury in the development of this condition. As well, we discuss current opinion regarding etiology, clinical presentation, diagnosis, and managem ent of this entity.


J Biomed Mater Res. 1998 Jul;41(1):131-41.
The aortic valve microstructure: effects of transvalvular pressure.
Sacks MS, Smith DB, Hiester ED.
Department of Biomedical Engineering, University of Miami, Coral Gables, Florida 33124-0621, USA. msacks@coeds.eng.miami.edu

We undertook this study to establish a more quantitative understanding of the microstructural response of the aortic valve cusp to pressure loading. Fresh porcine aortic valves were fixed at transvalvular pressures ranging from 0 mmHg to 90 mmHg, and smal l-angle light scattering (SALS) was used to quantify the gross fiber structure of the valve cusps. At all pressures the fiber-preferred directions coursed along the circumferential direction. Increasing transvalvular pressure induced the greatest changes in fiber alignment between 0 and 1 mmHg, with no detectable change past 4 mmHg. When the fibrosa and ventricularis layers of the cusps were re-scanned separately, the fibrosa layer revealed a higher degree of orientation while the ventricularis was more r andomly oriented. The degree of fiber orientation for both layers became more similar once the transvalvular pressure exceeded 4 mmHg, and the layers were almost indistinguishable by 60 mmHg. It is possible that, in addition to retracting the aortic cusp during systole, the ventricularis mechanically may contribute to the diastolic cuspal stiffness at high transvalvular pressures, which may help to prevent over distention of the cusp. Our results suggest a complex, highly heterogeneous structural response to transvalvular pressure on a fiber level that will have to be duplicated in future bioprosthetic heart valve designs.


Ann Thorac Surg. 1998 Apr;65(4):1014-9.
Surgical management of radiation-induced heart disease.
Veeragandham RS, Goldin MD.
Department of Cardiovascular and Thoracic Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.

BACKGROUND: With the increasing population of patients with prior mediastinal irradiation, cardiac surgeons will encounter patients with radiation-induced damage to the heart and the great vessels. Awareness of the pathology and the surgical management is essential to provide optimal care for these patients. METHODS: Eight patients with radiation-induced heart disease were encountered in the last 10 years. After a brief clinical presentation, the surgical management of radiation-induced heart disease is r eviewed. RESULTS: Radiation can affect all the structures in the heart, including the coronary arteries, the valves, and the conduction system. The pericardium is the most commonly involved, and the conduction system is the least involved. Pericardiectomy is quite effective in patients with symptomatic pericardial effusion or constriction. The coronary lesions are located predominantly in the ostial or proximal regions of the epicardial vessels. Percutaneous transluminal coronary angioplasty alone appears to have a high rate of restenosis. Surgical revascularization has good long-term results, and the internal mammary artery should be used if it is satisfactory. The aortic and mitral valves are more commonly involved than the tricuspid and pulmonary valve s. Myocardial dysfunction predominantly affects the right ventricle and requires particular attention during cardiopulmonary bypass and in the postoperative period. Restoration of sinus rhythm is essential in view of stiffness of the ventricles. Flexibili ty in the surgical approach with selective use of thoracotomy will facilitate the surgical procedure in certain patients. CONCLUSIONS: Surgeons should be well versed in all the manifestations and the management of radiation-induced heart disease.


Thorac Cardiovasc Surg. 1997 Feb;45(1):27-31.
Coronary artery and aortic valve disease as a long-term sequel of mediastinal and thoracic irradiation.
Kleikamp G, Schnepper U, Korfer R.
Department of Thoracic- and Cardiovascular Surgery, Nordrhein-Westfalen Heart Center, Bad Oeynhausen, Germany.

Mediastinal and thoracic irradiation has been identified as a risk factor for the development of among other things, coronary artery disease (CAD) and valvular disease. We screened all patients for a history of mediastinal or thoracic radiotherapy. Betwee n 01.07.1989 and 31.12.1995 we identified 33/16,364 patients with such a history. In 19 cases (0.12%) the cardiac disease was considered radiation-induced, nine patients were female, ten were male. Mean age was 51.7 years (range 38-73). All 19 patients di splayed proximal coronary artery stenoses. Mean age in the CAD group was significantly lower (48.5, range 38-63) than in the valvular group (mean age 64.0, range 55-73). The mean interval since radiotherapy in the valvular group was significantly longer ( 22.25 years, range 13-32) than the one in the CAD group (12.2 years, range 7-24). All patients were treated surgically and made an uneventful recovery. Some form of mediastinal fibrosis or pericardial adhesions was present in all patients. We conclude fro m these findings that radiation-induced cardiac disease is infrequently encountered in patients from a large surgical center. However, especially the radiation-induced coronary artery disease displays a specific pattern of stenosis location.


Hum Pathol. 1996 Aug;27(8):766-73. Related Articles, Links
Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases.
Veinot JP, Edwards WD.
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.

During the 20 years between 1973 and 1992, 27 patients were identified in whom cardiac tissue was available (15 surgical, 10 autopsy, and 2 both) that exhibited radiation-related injury. Specimens were assessed for damage to the pericardium, valves, myoca rdium, and coronary arteries. Patients ranged in age from 22 to 76 years (mean, 49 years), and 19 were men. Among 20 cases with available pericardium, 14 (70%) had radiation-related disease including six with an effusion, three with constriction, two with both, and three with neither. In 17 cases with available valves, 12 (71%) showed radiation injury involving 25 valves (nine mitral, eight aortic, five tricuspid, and three pulmonary), although clinically significant dysfunction was diagnosed in only eigh t. For the 16 patients from whom myocardium was available, 10 (63%) exhibited radiation-related fibrosis, which was moderate or severe in only the seven who received more than 3,000 rad (cGy). Among the 13 cases with available coronary arteries, only two had unequivocal radiation-induced obstructions (26- and 44-year-old men with Hodgkin's disease). In conclusion, radiation injury to the heart includes not only constrictive pericarditis and myocardial fibrosis, but also appreciable valvular and coronary a rtery lesions. As patients with malignancies survive longer, the surgical relief of radiation-induced heart disease may become more prevalent.


Anadolu Kardiyol Derg. 2001 Dec;1(4):276-82, AXVI.
Radiation and the heart
Kirac FS.
Pamukkale Universitesi Tip Fakultesi, Nukleer Tip Anabilim Dali, Denizli.

The use of radiotherapy in the management of malignant tumors causes low or high radiation exposure doses to normal tissues and undesired side effects may occur in early and late period following irradiation. All mediastinal structures, lungs and heart ca n exposure to total therapeutic dose during radiation therapy for thoracal or mediastinal malignancies such as Hodgkin disease and breast cancer. While early deaths following irradiation are caused by primary malignancies among these patients, long-term m ortalities are resulted from radiation-induced morphological and functional organ abnormalities. Cardiac changes are the most frequently seen. Significant cardiac anatomical changes occur particularly in pericardium, myocardium, valves and result in sever e cardiac dysfunctions after 10 to 20 years following administration of radiation into mediastinal or thoracal areas. The precision of the development of radiation-induced cardiovascular complications has increased due to achieving the complete cure of pr imary tumor and to the extended survival time of irradiated cases by using advanced radiotherapy and adjuvant chemotherapy modalities. Early detection of radiation-induced morphological changes leading to cardiac dysfunction offers the possibility for ear ly intervention such as administration of cardiovascular drugs and/or cardiac surgery in order to reduce or delay severe irreversible late complications.


Am J Cardiol. 1996 Jul 1;78(1):114-5.
Radiation-induced cardiovascular dysfunction.
Mittal S, Berko B, Bavaria J, Herrmann HC.
Cardiovascular Division, Princeton Medical Center, New Jersey, USA.

Coronary artery disease and valvular dysfunction are long-term complications of mediastinal irradiation. We describe 3 patients who underwent successful combined coronary artery bypass grafting and valve replacement for symptoms related to radiation-induc ed coronary artery and valvular disease.


J Heart Valve Dis. 1995 May;4(3):288-90.
Surgery for radiation-induced valvular disease.
Jahangiri M, Edmondson SJ, Rees GM.
Department of Cardiothoracic Surgery, St. Bartholomew's Hospital, London, United Kingdom.

The effects of radiation on the heart have been well described including acute and chronic pericarditis, myocardial fibrosis, accelerated arteriosclerosis of the coronary arteries. However, valvular dysfunction secondary to mediastinal irradiation has rec eived less attention. We report two cases who developed valvular dysfunction associated with coronary artery disease possibly caused by mediastinal irradiation and a review of the literature regarding surgery for radiation induced valvular disease. Both p atients underwent aortic valve replacement and coronary artery bypass graft surgery. With increasingly prolonged survival following mediastinal irradiation, we believe that long term follow up in patients who receive mediastinal irradiation is indicated.


G Ital Cardiol. 1994 Jul;24(7):817-23.
Radiation-induced constrictive pericarditis. Associated cardiac lesions, therapy and follow-up
Orzan F, Brusca A.
Istituto di Medicina e Chirurgia Cardiovascolare, Universita di Torino.

OBJECTIVES. To evaluate the diagnostic and therapeutic problems that occur in managing patients with radiation-induced constrictive pericarditis. BACKGROUND. Radiation therapy of the chest and mediastinum can damage all cardiac structures, the pericardium being the most frequently involved one. It is little appreciated, however, that radiation-induced constrictive pericarditis can be associated with significant involvement of coronary arteries, myocardium and valves. METHODS. Retrospective evaluation of c linical, hemodynamic, surgical and postoperative data in 8 patients, (7 women, 1 man, aged 26-67 years, mean 44), who had received 30-50 Gy to the chest because of Hodgkin's disease, lymphoma, or breast cancer 7-23 years before the diagnosis of constricti ve pericarditis. RESULTS. Six patients had symptoms related to the pericardial disease, one had angina and syncope, one was in congestive heart failure. Hemodynamic signs of constriction were obvious in 6, and were revealed by volume load in 2. All patien ts had mitral regurgitation, 5 had also tricuspid insufficiency and 5 had aortic regurgitation. The degree of the valvular regurgitation was > or = 3+ in four instances. Critical coronary arterial stenoses were discovered in 3 cases. The coronary ostia we re involved in 5 cases (2 critical, 3 non critical). A diagnosis of restrictive cardiomyopathy was arrived at in 4 instances, always after pericardiectomy. Seven patients were operated on: there were 6 pericardiectomies, associated with either valvular su rgery or myocardial revascularization or both in 3. One patient underwent myocardial revascularization only. The remaining patient is being treated medically. One patient died at surgery, two died 16 and 72 months thereafter. The remaining 5 have mild sym ptoms 11-60 months (mean 29) after the discharge from the hospital. CONCLUSIONS. Radiation-induced pericardial constriction is frequently associated with coronary artery disease, mostly silent, with valvular insufficiency, and with myocardial disease. Tho rough cardiac evaluation in such patients is mandatory. Surgical treatment frequently uncovers an underlying restrictive myopathy that presents a serious diagnostic and therapeutic challenge.


J Formos Med Assoc. 1991 Apr;90(4):398-402.
Heart diseases following radiotherapy.
Chen MF, Yang CY, Wu CC, Chen WJ, Liau CS, Hou SW, Lee YT.
Department of Internal Medicine (Cardiology), National Taiwan University Hospital, Taipei, R.O.C.

Three women had cardiac complaints 10-17 years after a radical mastectomy and radiotherapy for cancer of the left breast. Their ages were 42, 43 and 57 years, respectively. The first patient had a precocious coronary artery disease (CAD). She had segmenta l stenosis in the middle and distal portions of the left main coronary artery and pericardial fibrosis. Symptoms and signs of severe pericardial constriction became the problem after bypass surgery. She died 1 year later due to cardiorespiratory failure. The second case had sick sinus syndrome presenting a prolonged pause for 12 seconds alternating with tachy- and bradyarrhythmias, a complete atrio-ventricular block in association with pericardial effusion plus aortic and mitral valvular regurgitation. Th e condition improved after the implantation of a permanent pacemaker. To date, this is a very rare complication of radiation induced panconduction disturbance. The third patient had significant stenosis in the proximal portion of the left anterior descend ing coronary artery and myocardial fibrosis was proven by an endocardial biopsy. She had an uneventful course after medical treatment.


Am J Med. 1981 Mar;70(3):519-30.
Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart.
Brosius FC 3rd, Waller BF, Roberts WC.

Certain clinical and necropsy findings are described in 16 young (aged 15 to 33 years) patients who received greater than 3,500 rads to the heart five to 144 months before death. All 16 had some radiation-induced damage to the heart: 15 had thickened peri cardia (five of whom had evidence of cardiac tamponade); eight had increased interstitial myocardial fibrosis, particularly in the right ventricle; 12 had fibrous thickening of the mural endocardium and 13 of the valvular endocardium. Except for valvular thickening, the changes were more frequent in the right side of the heart than in the left, presumably because of higher radiation doses to the anterior surface of the heart. In six of the 16 study patients and in one of 10 control subjects, one or more m ajor epicardial coronary arteries were narrowed from 76 to 100 percent in cross-sectional area by atherosclerotic plaque; one patient had a healed myocardial infarct at necropsy and one died suddenly. In 10 patients and in the 10 control subjects, the fou r major epicardial coronary arteries were examined quantitatively: 6 percent of the 469 five millimeter segments of coronary artery from the patients were narrowed from 76 to 100 percent (controls = 0.2 percent, p = 0.06) and 22 percent were narrowed from 51 to 75 percent (controls = 12 percent). The proximal portion of the arteries in the patients had significantly more narrowing than the distal portions. The arterial plaques in the patients were largely composed of fibrous tissue; the media were frequen tly replaced by fibrous tissue, and the adventitia were often densely thickened by fibrous tissue. In five patients, there was focal thickening (with or without luminal narrowing) of the intramural coronary arteries. Thus, radiation to the heart may produ ce a wide spectrum of functional and anatomic changes but particularly damage to the pericardia and the underlying epicardial coronary arteries.


Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1205-11.
Radiation injury to the heart.
Stewart JR, Fajardo LF, Gillette SM, Constine LS.
Division of Radiation Oncology, University of Utah Medical Center, Salt Lake City, USA.

For the RTOG Consensus Conference on Late Effects of Cancer Treatment we summarize the clinical manifestations of cardiac complications appearing months to years following incidental irradiation of the heart during treatment of thoracic neoplasms. The mos t common effects present as pericardial disease, however, it is becoming more clear that precocious or accelerated coronary artery disease is an important late effect, especially in patients treated with radiation before the age of 21 years. To the extent it is known, the pathophysiology of the various syndromes is described and the extensive literature on dose, volume, and fractionation factors is reviewed. Based upon our current understanding of late cardiac effects, a clinical grading system has been d eveloped and is published elsewhere in this issue.


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