Radiation Vasculopathy of the Coronary Arteries: State-of-the Art Review

Radiation-associated coronary artery disease (RACAD) is a distinct form of coronary artery disease with several specific biological and clinical aspects as well as key knowledge gaps. RACAD is prevalent in patients with cardiac exposure to radiotherapy. As radiotherapy is integral to the effective treatment of many thoracic malignancies, improved long-term survivorship is coupled with increased risk for RACAD. Ionizing radiation induces free radical generation and activation of proinflammatory cascades, leading to endothelial dysfunction and accelerated atherosclerosis. Risks for RACAD are determined both by radiotherapy, including the radiation dose and the proximity of coronary arteries to the radiotherapy field, and by patient-specific factors, such as younger age, higher baseline cardiovascular risk, and concurrent cardiotoxic systemic therapies. Importantly, radiotherapy delivery is highly individualized on the basis of tumor location and treatment strategy, resulting in heterogeneous coronary exposure to radiation and patient-to-patient variability. Clinical presentation may occur early, within 1 to 2 years, especially in patients with higher cardiac radiation doses (eg, lung or esophageal cancer), or after a latency period of 5 to 20 years with lower cardiac dose radiation exposure (eg, left-sided breast cancer). Patients generally present with symptoms similar to conventional coronary artery disease. However, RACAD symptoms may be underrecognized in cancer survivors due to overlapping treatment-related fatigue, pulmonary disease, or competing oncologic symptoms. Diagnosis and management generally follow standard coronary artery disease guidelines while incorporating cancer-specific considerations, such as planned oncologic surgeries, bleeding risk, postradiotherapy complications such as atretic internal mammary arteries, and cardiotoxic effects of systemic cancer therapies. Primary prevention of RACAD is critical, emphasizing advances in precision radiotherapy, including delivery techniques with improved coronary dosimetry, and cardiac shielding. Key knowledge gaps include understanding long-term outcomes with contemporary 3-dimensional conformal radiotherapy techniques, validated cancer-specific risk prediction models on the basis of coronary dosimetry, optimal surveillance protocols, targeted molecular pharmacotherapies, and risk analysis of percutaneous versus surgical management of RACAD. Prospective studies are needed to develop cancer- and dosimetry-specific risk calculators, validating cardioprotective interventions, and improving multidisciplinary cardio-oncology collaboration to optimize early detection of RACAD and timely intervention in the growing population of cancer survivors.