Novel concepts in radiation-induced cardiovascular disease

Abstract

Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future. Thus, there is a pressing need for enhanced understanding of the disease mechanisms, and improved detection methods and treatment strategies. Newly characterized mechanisms responsible for the establishment of chronic fibrosis, such as oxidative stress, inflammation and epigenetic modifications, are discussed and linked to potential treatments currently under study. Novel imaging modalities may serve as powerful screening tools in RICVD, and recent research and expert opinion advocating their use is introduced. Data arguing for the aggressive use of percutaneous interventions, such as transcutaneous valve replacement and drug-eluting stents, are examined and considered in the context of prior therapeutic approaches. RICVD and its treatment options are the subject of a rich and dynamic body of research, and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardio-oncology.

Keywords: Radiotherapy; Radiation; Cardiovascular; Atherosclerosis; Cardiomyopathy; Pericarditis; Valvular; Hodgkin; Breast cancer; Radiation fibrosis

Core tip: Radiation-induced cardiovascular disease is a common complication of mediastinal radiotherapy and often occurs years or decades after treatment. It most commonly manifests as chronic pericarditis, cardiomyopathy, and valvular or coronary heart disease. Its pathophysiology is chiefly that of radiation fibrosis, fueled by chronic states of inflammation and oxidative stress. Conventional risk factors impose additive risk to these patients and must be addressed as early as possible. Development of more sensitive imaging modalities is enabling detection at earlier stages of the disease and creating opportunities for novel treatment strategies. Percutaneous interventions have an increasing role in the treatment of symptomatic vascular and valvular disease.