Cardiac risk after mediastinal irradiation for Hodgkin's disease

Abstract

Purpose: To evaluate the risk of cardiac lesions after conventionally fractionated irradiation (Rt) of the mediastine with or without chemotherapy (Ct) in patients with Hodgkin's disease (HD) and to relate them to known cardiovascular risk factors.

Patients and methods: Between 1964 and 1992, 352 (total group) patients with HD were treated with curative intention using Rt with or without Ct including the mediastine and had a follow-up of at least 1 year. More than 96% of the patients had a complete follow-up. One hundred forty-four patients (64% of the living patients, heart study group) have regular follow-up in our department and had a special heart examination including rest and exercise ECG, echocardiography and myocardial perfusion scintigraphy (112 patients). Doses per fraction in the anterior heart region were between 1.3 and 2.1 Gy. Total doses were between 30.0 and 42.0 Gy in 93% of cases. The mean length of follow-up was 11.2 years (range 1.0–31.5 years). Other cardiovascular risk factors evaluated were body mass index, blood pressure, smoking history, diabetes mellitus, hypercholesterolemia and history of coronary artery disease before Rt.

Results: In the total group, the risk of fatal cardiac ischemic events and/or of sudden unexpected death was significantly higher than expected with a relative risk of 4.2 for myocardial infarction and 6.7 for myocardial infarction or sudden death. In female patients and in patients without other cardiovascular risk factors, the risk of fatal or non-fatal ischemic cardiac events was not significantly different from the expected value. In the subgroup with no cardiovascular risk factors and treatment without Ct, there was no ischemic or other major cardiac event. Echocardiography showed valvular thickenings in a large amount of the patients (the cumulative risk after 30-year follow-up was above 60%) but mostly without hemodynamic disturbance. In patients without hypertension and without coronary artery disease, findings of perfusion scintigraphy and echocardiographic evaluation of systolic and diastolic function were normal. Treatment with Ct was not a significant risk factor for cardiac events but the number of patients whose treatment included adriamycin and with a follow-up exceeding 10 years is to low for a definitive evaluation.

Conclusions: In patients without the usual cardiovascular risk factors (smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus) the risk of serious cardiac lesions after conventionally fractionated irradiation of the mediastinum with an intermediate total dose between 30 and 40 Gy is low. Also the cardiac risk of the combination of this irradiation with Ct including adriamycin with a total dose between 200 and 300 mg/m² seems low but further long-term observation is necessary.

Introduction

In patients with HD, several published studies show a significant association between mediastinal Rt and an increased risk of coronary artery disease 4, 10, 12, 26, 27, 29as well as with some other cardiac lesions (e.g. pericardial effusion and fibrosis, valvular lesions, atrophy and fibrosis of the myocardium) 2, 8, 9, 11, 13, 21, 40, 42, 43, 47. However, in an important part of these studies, patients treated with older treatment techniques are included. Long-term data analyzing the cardiac risk after modern treatment techniques and a possible association with other known risk factors are relatively sparse. Therefore, we analyzed the incidence of cardiac lesions in our own patients, treated since 1964. A preliminary report of our analysis was published in 1994 [18]. A special interest of the following analysis was also the question of a progression of the valvular lesions and what routine tests should be recommended for the follow-up.