How to prevent and manage radiation-induced coronary artery disease

Abstract

Radiation-induced coronary heart disease (RICHD) is the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin's lymphoma and other prevalent mediastinal malignancies. The risk of RICHD increases with radiation dose. Exposed patients may present decades after treatment with manifestations ranging from asymptomatic myocardial perfusion defects to ostial, triple-vessel disease and sudden cardiac death. RICHD is insidious, with a long latency and a tendency to remain silent late into the disease course. Vessel involvement is often diffuse and is preferentially proximal. The pathophysiology is similar to that of accelerated atherosclerosis, characterised by the formation of inflammatory plaque with high collagen and fibrin content. The presence of conventional risk factors potentiates RICHD, and aggressive risk factor management should ideally be initiated prior to radiation therapy. Stress echocardiography is more sensitive and specific than myocardial perfusion imaging in the detection of RICHD, and CT coronary angiography shows promise in risk stratification. Coronary artery bypass grafting is associated with higher risks of graft failure, perioperative complications and all-cause mortality in patients with RICHD. In most cases, the use of drug-eluting stents is preferable to surgical intervention, bare metal stenting or balloon-angioplasty alone.

Keywords: cardiac catheterization and angiography; cardiac risk factors and prevention; coronary artery disease; percutaneous coronary intervention.

Figure 1

(A) and (B) Angiographic images of the stenotic left circumflex artery (arrow). (C) and (D) Images of intravascular ultrasound with and without virtual histology.

Figure 2

Mechanism of radiation-induced coronary injury. The intima of the healthy vessel is thin, and its collagenous component is well organized, as in frame (A). In the hours after radiation exposure, the endothelium becomes effaced, permitting chemotaxis of macrophages into the intima, where they begin to secrete profibrotic chemokines such as TGF-beta (B). This results in the terminal differentiation of SMCs into myofibroblasts, which enter the intima, where they generate large quantities of type IV collagen (C). The result is a state of chronic fibrosis and progressive stenosis (D), occurring over the months and years after. SMC, smooth muscle cell; TGF, transforming growth factor.

Figure 3

Proposed algorithm for monitoring in patients who have undergone mediastinal radiotherapy. BNP, Brain natriuretic peptide; CHD, coronary heart disease; RT, radiotherapy; transthoracic echocardiogram,TTE, transthoracic echocardiogram.