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Ann Thorac Surg 1998;65:1014-1019
© 1998 The Society of Thoracic Surgeons

Surgical Management of Radiation-Induced Heart Disease

^a Department of Cardiovascular and Thoracic Surgery, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois, USA

Accepted for publication October 29, 1997.

Address reprint requests to Dr Goldin, Department of Cardiovascular and Thoracic Surgery, Rush-Presbyterian-St. Luke’s Medical Center, 1750 W Harrison Ave (714 Jelke S), Chicago, IL 60612

	Abstract

Top Abstract Introduction Clinical summary Spectrum of disease Screening techniques Conclusions References

 
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 reviewed.

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 valves. 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. Flexibility 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.

	Introduction

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With the widespread use of mediastinal irradiation to control or cure many neoplasms, the population of patients surviving for a substantial period is steadily increasing. Contrary to the previous belief [1], there is strong evidence of radiation-induced damage to the heart and great vessels in these patients [2–4]. The spectrum of involvement includes the three layers of the heart as well as the coronary vessels, the valvular and subvalvular apparatus, and the conduction system. Cardiac surgeons must be well versed not only in the pathology and the management of radiation-induced heart disease, but also in the difficulties associated with the approach to the heart in such patients. Although there is some literature on this topic, there is a need to comprehensively address all of the surgical complications and their management. Here, after a brief clinical summary, we review the problems and their management in this group of patients.

	Clinical summary

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We have encountered 8 patients with radiation-induced heart disease in the last 10 years. The mode of presentation, the nature of the lesions, and the management of the lesions are summarized in Table 1. This does not include all the patients with radiation-induced heart disease seen in our institution and hence does not indicate the true incidence of the problem. There were 6 men and 2 women between the ages of 22 and 67 years at initial presentation. Lymphoma was the most common primary diagnosis (50% of patients). Patients received a mean radiation dose of 4,250 cGy to the mediastinum and after a mean of 13.6 years, were seen with new-onset cardiac symptoms.

Four of the patients had six valvular lesions. Patient 4 had mitral and tricuspid regurgitation 10 years after radiation therapy and excision of a malignant thymoma. Repair of both valves was accomplished through a right thoracotomy, which avoided entry through the irradiated skin and sternum. Patient 5 had three-vessel bypass 15 years after radiation treatment for breast cancer. Seven years later, she was seen with aortic and mitral regurgitation and constrictive pericarditis. She underwent double-valve replacement and pericardiectomy. Patient 6 had combined mitral valve replacement and CABG.

Twenty years after mediastinal irradiation for Hodgkin’s disease, patient 8 was seen with bilateral femoral embolization secondary to mural thrombi from a diffusely hypokinetic left ventricle and was managed with thrombolysis and subsequent warfarin therapy. He died 3 years later of biventricular failure. The follow-up data are shown in Table 1.

	Spectrum of disease

Top Abstract Introduction Clinical summary Spectrum of disease Screening techniques Conclusions References

 
Irradiation can affect all of the structures in the heart. The spectrum of disease, the mean dose of radiation, and the time of presentation compiled from large series are shown in Table 2. The pericardium is the most often involved and the conduction system, the least frequently involved. The overall incidence of clinically detectable radiation-induced heart disease is about 5% to 30% depending on the method of diagnosis. Three groups of patients treated with mediastinal irradiation are commonly affected: patients with Hodgkin’s disease; those with non-Hodgkin’s disease; and patients with carcinoma (breast, lung, esophagus, seminoma). The important factors influencing the risk of subsequent damage to the heart include total radiation dose to the mediastinum, use of radiation-blocking modalities, young age at radiation, and longevity of the patient. Most of the patients received total doses of more than 3,500 cGy delivered at 1,000 to 1,100 cGy per week [2, 3].

Most cases of acute pericarditis occur within the first year after radiation therapy. The clinical features include fever, pleuritic chest pain, pericardial friction rub, and some enlargement of the cardiac silhouette on the chest radiograph. All patients respond to bed rest, nonsteroid medications, and mild diuretics [5].

Symptomatic pericardial effusion presents relatively early, within 15 months after irradiation, whereas the mean time of presentation for constrictive pericarditis is 48 months. Patients with prior pericardial effusion can have development of constriction in later years [2, 3]. The effusion is serofibrinous with a protein content of 4 to 6 g and may be difficult to differentiate from pericardial metastasis from the primary disease [5]. Radiation-induced pericardial disease should be a differential diagnosis in all such patients, and those with no evidence of metastatic disease should be managed aggressively.

The surgical management of 27 patients was reviewed by Morton and associates [5]. Pericardiocentesis was unsuccessful in preventing six deaths caused by cardiac tamponade. This led to the recommendation that pericardiectomy be performed in all patients with major symptomatic effusion, constriction, or both. The procedure is much easier when done during the effusion phase. Pericardiectomy can be accomplished through a left anterior thoracotomy or a median sternotomy if it is being done concomitantly with another procedure. The pericardium is removed from one phrenic nerve to the other and from the diaphragm to the base of the aorta and pulmonary trunk, with special care taken to avoid injury to the phrenic nerves. In all patients, the central venous pressure returned to normal, and long-term relief was excellent. Constrictive pericarditis developed 7 years after CABG in 1 patient in our series (patient 5), and she underwent pericardiectomy during aortic and mitral valve replacement. This late-onset pericardial fibrosis requiring repeat surgical intervention and in some cases causing vein graft compression prompted some authors to advocate routine pericardiectomy during the first procedure [6]. As many of these patients may have development of coronary or valvular disease requiring redo sternotomy at a later date, placement of an artificial pericardial membrane may be justified to facilitate reentry.

Myocardium and endocardium
Patients receiving mediastinal irradiation can manifest myocardial fibrosis either as a result of direct injury or as a secondary phenomenon related to radiation-induced coronary artery disease. The most conspicuous change is diffuse interstitial fibrosis seen chiefly in the right ventricle, presumably because of the commonly used anterior radiation fields. The impact of right ventricular fibrosis in the management of postoperative cardiac surgical patients is dealt with in the following section. The endocardium was thickened, again mainly in the right ventricle, in 12 of 16 patients in an autopsy series [4]. The thickening is from fibrous proliferation with some increase in elastic fibers. This makes the ventricular muscle less compliant and necessitates higher filling pressures to maintain stroke volume.

Coronary artery disease
Coronary artery disease in patients with prior mediastinal irradiation must be assessed carefully, as these lesions mimic atherosclerotic disease. Despite some negative reports [7], this relationship was established in several young patients in whom myocardial infarction developed after chest irradiation [2, 8]. The distribution of the lesions correlates with the radiation dosimetry. The proximal epicardial vessels and the coronary ostia are the most commonly involved sites [9]. The mechanism is either a combination of fibrointimal hyperplasia from intimal injury and secondary lipid deposition or synergy with dietary factors causing premature atherosclerosis [10].

Clinically, patients commonly present with angina or myocardial infarction (see Table 2). Two interesting but rare presentations are sudden death syndrome and coronary spasm. Sudden death after prior mediastinal irradiation is well described and is thought to be secondary to either diffuse fibrointimal hyperplasia of all coronary vessels [2] or ostial left main stenosis [11]. The other rare presentation is coronary spasm with normal coronary arteries. An interesting case was that of a 44-year-old patient who was seen with recurrent inferior wall ischemia despite normal coronary arteries after receiving 4,500 cGy 41 months earlier [12]. Coronary spasm was suspected, and the patient was successfully treated with nifedipine.

The management of radiation-induced coronary artery disease is similar to that of atherosclerotic disease with some important differences. For proximal lesions in one or two coronary vessels, PTCA has been successful [13, 14], but the rate of restenosis appears high without stent placement [15]. One patient in our series (patient 7) had PTCA for a proximal right coronary artery lesion and needed repeat angioplasty with stent placement within 2 months. Another (patient 2) had PTCA with stenting for a lesion in the middle of the right coronary artery and was doing well at 3 years. One must be aware that complications during PTCA that require emergency CABG can be technically difficult because of extensive mediastinal fibrosis. Left main disease, ostial lesions, and multivessel coronary artery disease require CABG. Several studies [6, 9, 16] have reported good long-term results with surgical intervention. As most radiation fields include the course of the mammary arteries, their suitability must be carefully assessed. One or both internal mammary arteries have been used as conduits successfully [6, 17, 18]. However, several reports [6, 19] have described fibrotic and unusable internal mammary vessels. One of our patients (patient 1) had an internal mammary–left anterior descending coronary artery anastomosis and was doing well at 4 years, whereas in another patient, the internal mammary artery was not usable. Hence, the suitability of this artery should be assessed during both cardiac catheterization and operation and should be used whenever possible.

A series of 14 patients who had coronary revascularization by a single surgeon resulted in several important observations [6]. Standard operative technique (moderate hypothermia and cold blood cardioplegia) was used with good results in all patients. A substantial number of these patients had moderate to severe right ventricular fibrosis with elevated right atrial pressures and failure of the right ventricle to empty on cardiopulmonary bypass. Hence, particular attention should be given to optimize right ventricular protection. Also, restoration of normal sinus rhythm with its atrial kick on completion of cardiopulmonary bypass is optimal in view of the stiffness of the ventricles. Postoperatively, higher filling pressures are needed for these less compliant ventricles, and patients may have pulmonary insufficiency requiring ventilatory support. The risk of sternal wound infection is low with only one case reported [20].

Valvular dysfunction
Radiation-associated valvular disease has been well described. The exact clinical incidence is not known. However, in one postmortem series [4], the incidence was high, with 80% of the patients showing evidence of valvular damage 4.5 years after irradiation. The affected valves have diffuse cusp or leaflet fibrosis. Left-sided valves seem to be more frequently involved: the mitral valve in 43% of patients; the aortic valve in 37%; the tricuspid valve in 13%; and the pulmonary valve in 7% [3]. The reason for the preponderance of left-sided lesions and the rarity of pulmonary valve involvement despite its anterior position is not known. This may be related to the higher pressures across the left-sided valves [4]. Both regurgitation and stenosis are common in the aortic area, but regurgitant lesions are the only ones described in the mitral area. The treatment is based on standard indications. In our series, six valvular lesions were identified in 4 patients: mitral regurgitation in 3, aortic stenosis and regurgitation in 1 each, and tricuspid regurgitation in 1. One patient (patient 4) had mitral and tricuspid valve repair and was doing well 1 year later. Two patients had valve replacements (patients 5 and 6), and the other received an apicoaortic conduit for aortic stenosis (patient 7). Several previous reports [18, 20, 21] showed a high mortality rate of 50% and 65% after valve procedures. This is not reflected in our series; its absence may be due to advances in the intraoperative and postoperative care of these patients.

Conduction system
The conduction system is the least commonly involved of all the cardiac structures, and its true incidence is not known. The most common manifestation is complete atrioventricular block. In these patients, atrioventricular sequential pacing is important in view of right ventricular stiffness and dysfunction [22], and several cases of ventricular pacing that required change to dual-chamber pacing resulting in substantial clinical improvement have been reported [23].

	Screening techniques

Top Abstract Introduction Clinical summary Spectrum of disease Screening techniques Conclusions References

 
As radiation-induced heart disease occurs in a substantial number of patients with prior mediastinal irradiation, screening of asymptomatic patients should be considered. The extent to which these patients benefit from systematic screening with electrocardiography, stress test, echocardiography, or cardiac catheterization is controversial. In a series [24] of 25 patients with Hodgkin’s disease evaluated 37 to 144 months after thoracic mantle irradiation, only 1 patient had normal findings. This led to the recommendation that electrocardiography and stress testing be done at 5-year intervals as a relatively cost-effective screening mechanism for patients with prior mediastinal irradiation [24, 25].

	Conclusions

Top Abstract Introduction Clinical summary Spectrum of disease Screening techniques Conclusions References

 
Radiation-induced heart disease must be considered in any patient who has had mediastinal irradiation of more than 3,500 cGy and is seen with cardiac symptomatology. Newer radiation techniques with cardiac shielding may decrease the incidence, but physicians will continue to encounter patients with this problem. Pericardial disease is the most common manifestation, and anterior pericardiectomy is advisable when a patient is seen with symptomatic pericardial effusion. Concomitant pericardiectomy should be considered in a patient undergoing operation for radiation-induced coronary or valvular disease to avoid later complications. Percutaneous transluminal coronary angioplasty has a high restenosis rate, and stent implantation may improve the long-term patency. Long-term results with coronary revascularization have been excellent, and the internal mammary artery should be used if it appears to be of satisfactory quality at cardiac catheterization and during the operation. Valvular disease commonly affects the left-sided valves, whereas myocardial damage and fibrosis affect chiefly the right ventricle. Particular attention should be given to right ventricular protection during cardiopulmonary bypass, and right ventricular dysfunction should be anticipated in the perioperative period. The mortality after surgical intervention for radiation-induced valvular lesions is not prohibitive provided adequate care is taken in regard to myocardial protection. Restoration of sinus rhythm is essential, and atrioventricular sequential pacing is the modality of choice if permanent pacing is indicated. Physicians should strongly suspect a diagnosis of radiation-induced heart disease in patients with prior mediastinal irradiation and must be cognizant of the extent of the disease.

	References

Top Abstract Introduction Clinical summary Spectrum of disease Screening techniques Conclusions References

 

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