Radiation-Induced Cardiovascular Disease: Review of an Underrecognized Pathology

Abstract

Radiation therapy demonstrates a clear survival benefit in the treatment of several malignancies. However, cancer survivors can develop a wide array of cardiotoxic complications related to radiation. This pathology is often underrecognized by clinicians and there is little known on how to manage this population. Radiation causes fibrosis of all components of the heart and significantly increases the risk of coronary artery disease, cardiomyopathy, valvulopathy, arrhythmias, and pericardial disease. Physicians should treat other cardiovascular risk factors aggressively in this population and guidelines suggest obtaining regular imaging once symptomatology is established. Patients with radiation-induced cardiovascular disease tend to do worse than their traditional counterparts for the same interventions. However, there is a trend toward fewer complications and lower mortality with catheter-based rather than surgical approaches, likely because radiation makes these patients poor surgical candidates. When appropriate, these patients should be referred for percutaneous management of valvulopathy and coronary disease.

Keywords: cancer survivors; cardiomyopathies; cardiotoxicity; cardiovascular diseases; coronary artery disease; fibrosis; heart disease risk factors.

Figure 1. Mechanism of radiation‐induced coronary artery disease.

A, Normal blood vessel with circulating red cells and white cells with a normal, thin intima. B, Acute changes after radiation with inflammatory cytokines and white cells entering the vessel through endothelial disruption and injury. C, Chronic changes after radiation where large quantities of collagen have been produced leading to vessel stenosis and intimal fibrosis. Modified with permission from Cuomo et al ©2018, BMJ Publishing Group Ltd.

Figure 2. Echocardiographic findings of radiation‐induced heart disease.

A, 3‐chamber view showing a heavily calcified and stenotic aortic valve (arrow) in a patient with radiation‐induced cardiotoxicity. B, Classic findings of aortomitral continuity calcifications caused by radiation (arrow) and pericardial thickening and calcifications (arrowhead)

Figure 3. Immunohistochemistry staining of aortic valves after TAVR with staining for collagen, and calcium.

Hodgkin’s lymphoma patients who have received high‐dose radiation at a young age have a different pathology for aortic stenosis where their valves are more fibrotic with collagen deposits, as opposed to calcified. Left‐sided breast cancer is believed to lead to more heart disease than right‐sided breast cancer because radiation to the left breast is in more direct line with the heart. However, this study found similar composition of calcium and collagen in both entities. This is perhaps explained by that radiation to the breast is angulated toward the apex of the heart as opposed to the base, where the valves are found. Modified with permission from van Rijswijk et al ©2020, Elsevier. TAVR indicates transcatheter aortic valve replacement.

Figure 4. Screening guidelines of radiation‐induced cardiovascular disease.

CMR indicates cardiac magnetic resonance; CT, computed tomography; and TTE, transthoracic echocardiogram. Modified with permission from Lancelloti et al ©2013, Elsevier.

Figure 5. Summary of the findings of radiation‐induced cardiovascular disease.

AR indicates aortic regurgitation; AS, aortic stenosis; CABG, coronary artery bypass graft; CAD, coronary artery disease; CMR, cardiac magnetic resonance; CT, computed tomography; DLP, dyslipidemia; DM2, diabetes type 2; HTN, hypertension; LIMA, left internal mammary artery; PCI, percutaneous coronary intervention; RBBB, right bundle branch block; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement; and TTE, transthoracic echocardiogram.