Biologic Considerations
 
Ionizing radiation may interact with individual cells via direct ionization of DNA or other critical molecules, or indirectly by ionizing water molecules to form free radicals, which themselves are freely diffusible and can damage chromosomal DNA or critical membrane sites.
In general, the radiation dose necessary to destroy the function of a differentiated cell, such as a smooth muscle cell or endothelial cell, is far greater than the dose of radiation necessary to prevent cell division. Most lethally irradiated cells die during the mitotic process. It is unclear what, if any, the relative contribution of apoptosis is to postirradiation cell death seen in the arterial wall.
 
In radiotherapy of parenchymal organs, injury to capillaries and arterioles of normal parenchyma accounts for the majority of delayed effects of radiation. Experimental studies of large arteries (greater than 100 µm in diameter) have revealed that these vessels are less sensitive to radiation than smaller caliber vessels. Rarely, arterial perforation may occur. Large veins appear to be even more resistant to radiation than corresponding size arteries. 

The risk of late coronary artery disease (CAD) as a consequence of radiation therapy has been best assessed in studies of patients irradiated for thoracic neoplasms. A retrospective analysis of Hodgkin's disease patients who received mediastinal radiation as part of their treatment reported a relative risk of myocardial infarction of 2.56 . Another retrospective study reported a relative hazard of death of 3.2 in patients who received high-dose radiation involving the heart for treatment of carcinoma of the left breast. Factors that were thought to be important in this increased mortality were the irradiated volume, radiation energy, fractionation (number and size of individual treatments), and total dose. Finally, a review of 2,232 Hodgkin's disease patients receiving mantel radiation reported the overall relative risk for cardiac death was 3.1 (confidence interval, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n = 385 patients) did not increase risk; above 30 Gy (n = 1,830), relative risk was 3.5 (confidence interval, 2.7 to 4.3). Interestingly, the relative risk decreased as the age at the time of treatment increased. The latency for these events in the population was as long as 5 years. The risk of secondary neoplasms because of radiation of a small volume of tissue appears to be exceedingly low.
 
Late Effects
The administration of significant doses of therapeutic radiation has been associated with a vasculopathy, which affects vessels in the radiated region. In parenchymal organ radiation, the principal effect of radiation injury to blood vessels is at the level of the capillaries and arterioles. The effects on large arteries, such as the epicardial coronary arteries, analyzed in retrospective studies of patients who have received radiation for thoracic neoplasms, appear to be dose-related and inversely related to the age of the patient at the time of irradiation. The earliest evidence of coronary disease appears 5 years after radiation. These data are derived from studies of patients who have received fractionated doses of radiation and have had the entire heart in the radiated field. The long-term effects of single-dose (as opposed to fractionated dose) radiation of the magnitude suggested by the animal trials are not known. It is clear, however, that the risk of late complication, such as myocardial infarction or pericarditis, is related to the volume of radiated tissue. The late risk of radiation to the arterial wall is thus minimized when the volume of treated tissue is small, as with treatment by endovascular sources.
 
Radiation Injury
The heart was thought to be resistant to radiation injury in the first half of the twentieth century. High-dose radiation was delivered without proper cardiac shielding. Many reports of radiation-induced cardiac abnormalities changed the perception of safety of radiation to the heart. Radiation, when used in the treatment of mediastinal tumors, primarily Hodgkin's and non–Hodgkin's lymphoma, and spinal irradiation can cause cardiac abnormality in as many as 40% of patients. This awareness and the availability of better radiation techniques in the last decade have led to careful use of high-dose radiation to the chest with proper cardiac shielding. More than 30 Gy to the chest is usually not used. Therefore, the long-term effects of modern radiation may be less severe than before. However, due to better long-term survival of patients who received radiation in the past and delayed manifestation of cardiac effects, we are likely to continue to encounter these problems. The injuries due to radiation involve various cardiac structures and can cause acute or delayed manifestations.
 
Pericardium
Acute pericarditis due to radiation is rare (approximately 2% of total population undergoing chest radiation). Over the years, approximately one-half of the patients develop echocardiographically demonstrable abnormalities, and approximately 5% develop clinically significant pericardial disease.
 
Myocardium
Radiation causes progressive fibrin deposition and capillary destruction, leading to fibrosis in the myocardium . This leads to mild left ventricular dysfunction not requiring specific treatment. Coronary artery disease should  be ruled out when significant systolic dysfunction of the left ventricle is identified. Restrictive cardiomyopathy has also been described from radiation treatment
 
Valves
Valvular thickening is present in many patients after radiation treatment, but significant valvular disease is an infrequent sequela. The mean time from radiation to clinically recognizable valvular disease is approximately 10 years, and the symptoms develop approximately 5 years after that. Aortic and mitral replacement from radiation-induced sclerosis with significant aortic stenosis or mitral regurgitation has been reported. Pulmonary and tricuspid valve disease is even less common
 
Conduction System
Nodal and infranodal conduction abnormalities occur with radiation injury. Although right bundle branch block is most common, complete heart block has been reported. Management of these abnormalities is similar to that from other causes.
 
Coronary Arteries
External radiation injury involves the proximal portion of coronary arteries. Left and right coronary ostia and proximal left anterior descending and left circumflex are involved in most cases. The lesions have an increased number of plasma cells with paucity of lipids. Large, bizarre fibroblasts are also present. Coronary disease commonly presents approximately 5 years after radiation but can present as late as 29 years. Predisposing factors other than the total dose of radiation are not clearly identified. Patients can present with any ischemic complication, such as angina, MI, arrhythmia, or heart failure. Children treated with chest radiation have a higher risk of MI. For significant left main stenosis, coronary artery bypass grafting with left internal mammary artery conduit is recommended, although surgery can be technically difficult due to excessive scarring. For other focal lesions, percutaneous transluminal coronary angioplasty can be useful. Intracoronary radiation is now used to treat recurring in-stent restenosis. The long-term effects of this type of therapy remain unknown.