Radiation-induced coronary artery disease

Radiation-induced heart disease must be considered in any patient with cardiac symptomatology who had prior mediastinal irradiation. Radiation can affect all the structures in the heart, including the pericardium, the myocardium, the valves and the conduction system. In addition to these pathologies, coronary artery disease following mediastinal radiotherapy is the most actual cardiac pathology as it may cause cardiac emergencies requiring interventional cardiological or surgical interventions. Case A 36-year-old man was admitted to the clinic with unstable angina pectoris of one month duration. The patient had no coronary artery disease risk factor. The history of the patient revealed that he had mediastinal radiotherapy due to Hodgkin's disease at 10-year of age. Coronary arteriography showed total occlusion of the left anterior descending artery and 70% stenosis of the proximal right coronary artery. Both arteries are dilated with placement of two stents. Control coronary arteriography at the end of the first year showed patency of both stents and the patient is free of symptoms. Previous radiotherapy to the mediastinum should be considered as a risk factor for the development of premature coronary artery disease. Percutaneous transluminal coronary angioplasty with stent placement or surgical revascularization are the preferred methods of treatment. Preoperative assessment of internal thoracic arteries should be considered prior to surgery. As the radiation therapy is currently the standard treatment for a number of mediastinal malignancies, routine screening of these patients and optimal cardiac prevention during radiotherapy are the only ways to minimize the incidence of radiation-induced heart disease.     

Radiation-related Coronary Artery Disease in Hodgkin's Disease

Summary: Radiation-related coronary artery disease in Hodgkin's disease. A. S. Y. Leong, I. J. Forbes and T. Ruzic, Aust. N.Z. J. Med., 1979, 9, pp. 423–425.
Coronary artery disease is a rare and only recently recognised complication of mediastinal irradiation. A 34-year-old man died suddenly eight years after mediastinal irradiation for Hodgkin's disease. Autopsy disclosed severe narrowing of all major extramural coronary arteries by atherosclerotic plaques whereas all other systemic and visceral arteries were virtually free of atheroma. Autopsy findings in the five reported cases of radiation-related coronary artery disease are reviewed.     

Unusual cardiac reaction to chemotherapy following mediastinal irradiation in a patient with Hodgkin's disease.

A 27 year old man with Hodgkin's disease experienced three separate episodes of chest pain, each occurring on the sixth day of a cycle of mustargen, oncovin, procarbazine, prednisone (MOPP) combination chermotherapy. The first episode appeared to represent a myocardial infarction, whereas the next two were less serious. Numerous studies were performed including coronary angiography, cardiac catheterization and open pericardial biopsy. It is suggested that the patient represents an example of a previously undescribed syndrome due to chemotherapy administered after cardiac irradiation.     

Ostial stenosis of the left main coronary artery after mediastinal radiotherapy. Apropos of a case

Coronary artery disease (CAD) is a well-known complication of mediastinal irradiation. We report a case of subocclusive ostial stenosis of the left main coronary artery, in a 27 years old man, who had been irradiated 14 years before for a stage 4 Hodgkin's disease. Among the 68 reported cases of CAD attributed to radiotherapy, 11 involved an ostial stenosis of either right coronary artery, or left main coronary artery or both. Thus mediastinal irradiation seems to be a definite cause of ostial coronary artery stenosis; several types of myocardial revascularization have been suggested for this kind of CAD.     

Clinical and angiographic features of coronary artery disease after chest irradiation

Coronary artery disease (CAD) developed in 15 patients at a mean of 16 years (range 3 to 29) after chest irradiation. The mean dose of radiation was 42 +/- 7 grays; irradiation was performed for Hodgkin's disease in 9 patients, lymphoma in 2, breast carcinoma in 3 and cystic hygroma in 1 patient. Mean age was 48 years (range 26 to 63) at diagnosis of CAD; 4 patients were younger than 35 years. Nine were women. Ten presented with angina, 3 with acute myocardial infarction, 1 patient with syncope and 1 with dyspnea. Twelve had no more than 2 risk factors of atherosclerosis. At coronary angiography, 8 had at least 50% diameter narrowing of the left main coronary artery and 4 had severe ostial stenosis of the right coronary artery. Eight patients also had valvular heart disease, 4 pericardial disease and 4 complete heart block. Mean left ventricular ejection fraction was 67 +/- 11% (range 53 to 80%). Nine had undergone coronary artery bypass grafting, but surgery was difficult or impossible in 3 because of severe mediastinal and pericardial fibrosis. Radiation-associated CAD is characterized by a high incidence of left main and right ostial coronary disease and often occurs in women with relatively few conventional risk factors for CAD.     

Radiation-related atrioventricular block

Twelve years after mediastinal irradiation for Hodgkin's disease, a 38-years old man developed an infra-hisian atrioventricular block with syncopes. The rarity of this complication of radiotherapy is emphasized. A review of the literature yielded only 6 cases of atrioventricular block associated with cobalt therapy; a pathological examination was performed in two of these patients and an electrophysiological study in two others.     

Acute myocardial infarction with normal coronary arteries in a patient with Hodgkin's disease: a late complication of irradiation and chemotherapy

We describe the case of a 31-year-old man who experienced an acute myocardial infarction 16 years after undergoing radiation and vinca alkaloid therapy for Hodgkin's disease. Even though coronary artery disease is a well-established complication after mediastinal radiation therapy, this adult patient had normal coronary angiographic results, with no traditional risk factors for coronary artery disease, and no hematologic or other abnormality associated with hypercoagulability.     

Atrioventricular block, a complication of radiotherapy of the mediastinum

Cardiac complications of mediastinal irradiation usually concern the pericardium, the ventricular myocardium and the coronary arteries. We report the case of a 42-year old woman who experienced a syncopal atrioventricular (AV) block 12 years after irradiation of a mediastinal Hodgkin's lymphoma. Electrophysiological recordings showed infranodal conduction disturbances. A review of the literature yielded only 12 cases of syncopal radiation-induced AV block. This case highlights the risk of syncopal AV blocks occurring a long time after mediastinal irradiation and leading to severe damage of the His bundle and its branches. The presence, as in our patient, of an associated right ventricular outflow tract stenosis confirms the importance and severity of radiation-induced cardiac lesions.     

Evaluation of late cardiotoxicity with pulsed Doppler echocardiography in patients treated for Hodgkin's disease

Summary. The impact of valvular, myocardial and pericardial abnormalities on cardiac haemodynamics in patients treated for Hodgkin's disease with COPP/ABVD with and without mediastinal irradiation was determined in 49 patients 2–10 years after induction therapy. Diagnostic procedures to evaluate cardiac function consisted of history, physical examination, exercise bicycle stress test, M-mode two-dimensional and pulsed Doppler echocardiography. No patient reported symptoms related to cardiomyopathy, and only one of the 49 had evidence of coronary heart disease. Pericardial thickening was seen on echocardiograms in 19/49 patients (38.8%), valvular thickening in 21/49 (42·9%), and reduced fractional shortening in 9/49 (18·4%). The Doppler-derived mean E and A (±SD) of transmitral flow were 0·75 ± 0·14 m/s and 0·56 ± 0·09 m/s, respectively, in patients receiving chemotherapy and 0·81 ± 0.19 m/s and 0·63 ± 0·20 m/s in those with additional mediastinal irradiation. There was no statistically significant difference between mean E and A in transmitral flow in patients treated for Hodgkin's disease and control subjects. Furthermore, the transtricuspid and hepatic vein flow velocities did not differ significantly. Although the present study demonstrates high frequencies of pericardial and valvular thickening in patients treated for Hodgkin's disease with the COPP/ABVD regimen with or without mediastinal irradiation, it showed no impact on cardiac flow velocities. The abnormalities might thus be of minor clinical relevance in these patients.     

Vascular complications of thorium dioxide.

Vascular complications occurring late after exposure to thorium dioxide (thorotrast) are described in two patients. One patient had both cerebral andmyocardial infarcts and died at age 25 years. Necropsy disclosed both adventitial and intimal fibrosis of the left carotid artery and greater than 75 per cent cross-sectional area luminal narrowing of both the left main and left anterior descending coronary arteries. The other patient, a 33 year old man, had no cerebral symptoms in life but total obstruction of the right carotid artery secondary to a thorotrastoma was found at necropsy. Vascular complications due to thorotrast appear to represent consequences of chronic alpha irradiation.     

Radiation-associated valvular disease

The prevalence of radiation-associated cardiac disease is increasing due to prolonged survival following mediastinal irradiation. Side effects of radiation include pericarditis, accelerated coronary artery disease, myocardial fibrosis and valvular injury. We evaluated the cases of three young patients with evidence of significant valvular disease following mediastinal irradiation. One patient underwent the first reported successful aortic and mitral valve replacement for radiation-associated valvular disease (RAVD) as well as concurrent coronary artery revascularization. A review of the literature revealed 35 reported cases of RAVD, with only one successful case of valve replacement that was limited to the aortic valve. Asymptomatic RAVD is diagnosed 11.5 years after mediastinal irradiation compared with 16.5 years for symptomatic patients, emphasizing that long-term follow-up is important for patients receiving mediastinal irradiation. This study defines a continuum of valvular disease following radiation that begins with mild asymptomatic valvular thickening and progresses to severe valvular fibrosis with hemodynamic compromise requiring surgical intervention.     

Ostium stenosis of both coronary arteries and latent hypothyroidism as sequelae of radiotherapy in Hodgkin disease

Premature arteriosclerosis following irradiation is a known experimental and clinical phenomenon. Although the heart was once considered a relatively radioresistant organ, now all components, including the coronary arteries, are recognised as possible targets of radiation injury. We present a 40-year-old women who received extensive neck and thoracic radiation for treatment of Hodgkin's disease. Ten years later she developed severe coronary artery disease with ostium stenosis of the left and right coronary arteries, as well as subclinical hypothyroidism.     

Coronary aneurysms in a case of Ehlers-Danlos syndrome

An asymptomatic 48 year old man had transient T-wave inversion in the anterolateral leads after nonpenetrating chest trauma. Both the patient and his 6 year old son showed the typical skin hyperelasticity and joint hyperextensibility of the Ehlers-Danlos syndrome, suggesting autosomal dominant inheritance. The coexisting cardiac abnormalities of the patient included multiple coronary aneurysms, mitral valve prolapse with slight regurgitation, fusiform dilatation of the ascending aorta with moderate insufficiency and left anterior hemiblock. A routine noninvasive cardiovascular evaluation should be performed in all patients with Ehlers-Danlos syndrome in order to exclude valvular heart disease and dilatation of the aortic root or of other vessels, including the coronary arteries.     

Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin

Among 41 evaluable patients whose first treatment for advanced Hodgkin's disease had consisted of alternating cycles of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to low-dose mediastinal irradiation, 19 underwent retrospective cardiac evaluation by routine posteroanterior and lateral chest x-ray, 12-lead ECG, M-mode echocardiogram, and ECG-gated left ventricular blood pool scan at rest and during exercise. Fifteen patients had unequivocally normal left ventricular function by all these parameters. Two patients had minimally reduced left ventricular ejection fraction (LVEF) at rest with a normal increment with exercise. In two other patients with high normal resting LVEF and subnormal increment with exercise, the elevated resting values implied initial measurement in a nonbasal state. A twentieth patient (the oldest; one of two with active Hodgkin's disease at the time of evaluation and the stimulus for this study) had markedly reduced LVEF as determined by radionuclide cardiac angiography and had developed clinical congestive heart failure shortly before evaluation. Despite this patient, the study indicates that treatment with MOPP/ABVD and low-dose mediastinal irradiation entails low risk for cardiac complications.     

Esophageal localization revealing Hodgkin's disease

The authors report the case of a 28 year old man with Stage III E Hodgkin's disease presenting with massive upper oesophageal involvement with cervical and mediastinal lymphadenopathy. The diagnosis was confirmed by lymph node and endoscopic biopsies (mixed cellularity). A complete remission was obtained by chemotherapy (ABVD) followed by extended radiotherapy. Then other cases have been previously reported. Upper oesophageal involvement with mediastinal lymphadenopathy often occurring in young patients raises the differential diagnosis of a carcinoma. The efficacy of chemotherapy of first intention is underlined.     

Isolated primary oesophageal involvement by lymphoma: a rare cause of dysphagia: two case histories and a review of other published data.

Primary oesophageal involvement by lymphoma in two patients, one with Hodgkin's disease and one with non-Hodgkin's lymphoma is reported. In both, there were no manifestations of the disease outside the oesophagus, which is exceptionally rare. In the patient with non-Hodgkin's lymphoma, the oesophageal tumour was the first manifestation of lymphoma. Shortly after admission he developed a tracheo-oesophageal fistula from which he died before treatment could be started. In the patient with Hodgkin's disease, isolated oesophageal lymphoma was the first relapse after a 13 year interval free of disease. As he had previously received mediastinal irradiation he was treated with combination chemotherapy that resulted in long term survival (> five years). Several other long term survivors have been described but only after radiotherapy or surgery. These findings suggest that systemic chemotherapy may be equally successful in treating isolated primary oesophageal lymphoma, thus offering an alternative for those patients in whom local treatment is contraindicated.     

Radiation-related chronic heart disease

Three cases of radiation-related chronic heart disease are reported. All three patients had been treated for Hodgkin's disease with a mantle technique six to ten years earlier. Ten years after radiation treatment, a 34-year-old woman had dyspnea during exercise. Her heart was enlarged, and an ECG showed a RBBB. An echocardiogram showed pericardial effusion. Right-sided catheterization revealed an infundibular stenosis. A 31-year-old man had chest pain nine years after radiation. An ECG showed complete RBBB and an exercise stress test signs of ischemia; a coronary angiogram showed three proximal stenoses; and an echocardiogram revealed pericardial effusion. A 12-year-old boy had angina pectoris six years after radiation; one year later, he suffered an acute posterior infarction. Two weeks later he died suddenly. An autopsy showed a severe fibrotic and calcified narrowing of the proximal part of the left main coronary artery. Regardless of the patient's age, radiation-related cardiac complications must be kept in mind. Echocardiograms and, in cases of chest pain, exercise stress tests should be a part of routine postradiation follow-up.     

Asymptomatic cardiac disease following mediastinal irradiation

OBJECTIVES: This study was designed to evaluate the potential benefit of screening previously irradiated patients with echocardiography. BACKGROUND: Mediastinal irradiation is known to cause cardiac disease. However, the prevalence of asymptomatic cardiac disease and the potential for intervention before symptom development are unknown. METHODS: We recruited 294 asymptomatic patients (mean age 42 +/- 9 years, 49% men, mean mantle irradiation dose 43 +/- 0.3 Gy) treated with at least 35 Gy to the mediastinum for Hodgkin's disease. After providing written consent, each patient underwent electrocardiography and transthoracic echocardiography.Valvular disease was common and increased with time following irradiation. Patients who had received irradiation more than 20 years before evaluation had significantly more mild or greater aortic regurgitation (60% vs. 4%, p < 0.0001), moderate or greater tricuspid regurgitation (4% vs. 0%, p = 0.06), and aortic stenosis (16% vs. 0%, p = 0.0008) than those who had received irradiation within 10 years. The number needed to screen to detect one candidate for endocarditis prophylaxis was 13 (95% confidence interval [CI] 7 to 44) for patients treated within 10 years and 1.6 (95% CI 1.3 to 1.9) for those treated at least 20 years ago. Compared with the Framingham Heart Study population, mildly reduced left ventricular fractional shortening (<30%) was more common (36% vs. 3%), and age- and gender-adjusted left ventricular mass was lower (90 +/- 27 g/m vs. 117 g/m) in irradiated patients. CONCLUSIONS: There is a high prevalence of asymptomatic heart disease in general, and aortic valvular disease in particular, following mediastinal irradiation. Screening echocardiography should be considered for patients with a history of mediastinal irradiation.     

Symptomatic coronary artery spasm following radiotherapy for Hodgkin's disease

Four years after mediastinal radiation for Hodgkin's lymphoma, a 32-year-old man developed angina at rest and with varying levels of physical activity. At coronary arteriography, 40 percent to 50 percent stenoses were seen in the left coronary artery; ergonovine induced severe coronary spasm. Treatment with diltiazem eliminated all anginal attacks.     

Cardiac disease late after chest radiotherapy for Hodgkin's disease: a case report.

This report presents a case of occult constrictive pericarditis and mitral valve insufficiency following chest radiotherapy. A 44-year-old man had received radiotherapy for the treatment of Hodgkin's disease 8 years ago. At age 40 years, effusive pericarditis occurred and he was treated with intrapericardial drainage. Biopsy revealed a fibrotic and thickened pericardium. He developed congestive heart failure 3 years later. The patient was found to have occult constrictive pericarditis and mitral valve insufficiency. He underwent mitral valve replacement, tricuspid annul plasty, and pericardiectomy. Although there is the benefit of cure for the Hodgkin's disease, the prognosis after treatment is affected by radiotherapy-induced heart disease. After radiotherapy of the chest and mediastinum, long-term cardiological follow-up is recommended in order to detecting patients with radiation-induced heart disease, such as the present case.