Radiation-related heart disease: current knowledge and future prospects

Abstract

The heart has traditionally been considered a radio-resistant organ that would be unaffected by cardiac doses below about 30 Gray. During the last few years, however, evidence that radiation-related heart disease can occur following lower doses has emerged from several sources. These include studies of breast cancer patients, who received mean cardiac doses of 3–17 Gray when given radiotherapy following surgery, and studies of survivors of the atomic bombings of Japan who received doses of up to 4 Gray.

At doses above 30 Gray, radiation-related heart disease may occur within a year or two of exposure and risk increases with higher radiotherapy dose, younger age at irradiation, and the presence of conventional risk factors. At lower doses the typical latent period is much longer and is often more than a decade. However, the nature and magnitude of the risk following lower doses is not well characterized, and it is not yet clear whether there is a threshold dose below which there is no risk.

The evidence regarding radiation-related heart disease comes from several different disciplines. The present review brings together information from pathology, radiobiology, cardiology, radiation oncology and epidemiology. It summarises current knowledge, identifies gaps in that knowledge, and outlines some potential strategies for filling them. Further knowledge about the nature and magnitude of radiation-related heart disease would have immediate application in radiation oncology. It would also provide a basis for radiation protection policies for use in diagnostic radiology and occupational exposure.

Fig. 1

Perpendicular sections of human pericardium. The left panel illustrates the normal parietal pericardium with a thin, uniform fibrous layer that faces the heart (upper section) and an outer layer of adipose tissue (lower section). The right panel is a typical example of irradiated pericardium at 17 months after receiving 67 Gy. The adipose tissue has been replaced by dense fibrous tissue that actually extends well below the limits of this micrograph. Hematoxylin-eosin stain. (From Kajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Keynote lecture. 5th Nordic Conference on Radiation Oncology. Bergen. Norway. Acta Oncologica 2005;44:13–22. with permission.)

Fig. 2

Fatal diffuse myocardial fibrosis several years after irradiation for Hodgkin’s disease. Whereas normally there should be very little collagen among the dark red myocytes, this heart muscle is criss-crossed by multiple bands of blue collagen. Gomori trichrome stain.

Fig. 3

Left anterior descending coronary artery in a 16-year-old boy 1 year after receiving 40 Gy mantle radiotherapy for Hodgkin’s disease. Myointimal proliferation has considerably narrowed the lumen. Fatal cases like this in a patient who had no cardiac risk factors other than radiation illustrate that the morphology of arterial disease due to radiation is essentially no different from that of age-related atherosclerosis. Hematoxylin-eosin stain. (From Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Keynote lecture. 5th Nordic Conference on Radiation Oncology, Bergen. Norway. Acta Oncologica 2005;44:13–22; with permission.)

Fig. 4

An outline of how microvascular and macrovascular radiation-related cardiac injury could theoretically combine to cause myocardial ischemia after RT.

Fig. 5

Left-sided vs. right-sided breast cancer. Mortality ratios by radiotherapy status, cause, and years since diagnosis in 300,000 women with breast cancer and registered in the Surveillance Epidemiology and End Results (SEER) cancer registries, 1973 to 2001 (From Darby SC, McGale P, Taylor CW, et al. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: Prospective study of about 300,000 women in US SEER cancel registries. Lancet Oncol 2005;6:557–565: with permission.)

Fig. 6

Representative axial images pre-RT (left panel) and post-RT (right panel) cardiac SPECT scans. The deep borders of the tangential RT beams are shown as solid lines. A new perfusion defect in the anterior left ventricle after radiation is seen.