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Cardiovascular disease and cancer are the top two causes of global mortality, accounting for 46% of deaths worldwide. To complicate matters further, cancer treatment has led to a significant increase in the global incidence of cardiovascular disease. A mainstay of cancer treatment is radiation therapy (RT). Its success with and without systemic therapy as an effective modality in Hodgkin’s and non-Hodgkin’s lymphomas, breast cancer, and lung cancer, for example, has led to improved survival rates. There were an estimated 16.9 million American cancer survivors in 2019 and this number is expected to grow to 26 million by 2040. This increase in survivorship will continue to lead to an increase in manifestations of various cardiovascular toxicities.
Compared with nonirradiated patients, patients who have received mediastinal radiation have a 2% higher absolute risk of cardiac toxicity and death at 5 years and 23% increased absolute risk after 20 years. Cardiovascular disease associated with RT presents via a spectrum of disorders. This is thought to reflect the differing radiosensitivities of involved cells and tissues. Coronary artery atherosclerosis, valvular disease, pericardial disease, cardiomyopathy, and autonomic dysfunction represent the main clinical manifestations of radiation-induced cardiovascular disease (RICD).
Late cardiac toxicity has been notably described in pediatric patients receiving mediastinal radiation for lymphomas. Given that these patients have curable cancers and live for decades after initial treatment with radiation with or without chemotherapy, they have a greater potential for the development of RICD. Although not as prevalent, cardiovascular toxicity has also been described in women with breast cancer receiving adjuvant RT. As cure rates are high, women live long enough for cardiac toxicity to be exhibited.
Advances in modern chest radiotherapy techniques have led to the development of newer considerations in radiation oncology. Beyond the initial radiation course with or without systemic therapy, the implementation of reirradiation as well as stereotactic body RT have led to unique clinical situations requiring careful thought. Although the clinical manifestations of cardiotoxicity may remain similar, the nuances provided by possible cardiac cell regeneration and hypofractionation serve to make an already complex situation even more challenging in terms of safely delivering therapies.
In this chapter, we will review the clinical manifestations of cardiovascular toxicity and the mechanistic changes associated with such toxicities. We will then review preventative methods including published dose constraints for the major cardiovascular organs and discuss management options and considerations.
Radiation-induced cardiovascular toxicity has become an important issue as outcomes have improved with advances in thoracic RT. Risk factors for the development of toxicity include younger age at time of RT (<50), higher cumulative dose of RT (>30 Gy), volume of heart irradiated, higher dose per fraction (>2 Gy/day), anterior or left chest irradiation, presence of tumor in the mediastinum, concurrent cardiotoxic systemic therapy, and preexisting cardiovascular disease as well as cardiovascular risk factors.
Cardiotoxicity manifests itself in a number of ways. The tissues affected include the pericardium, coronary arteries, the myocardium, the valves, the cardiac electrical conduction system, and the great vessels of the chest. Whereas acute effects can manifest themselves during RT or weeks to months after RT, long-term effects are demonstrated years to decades later. Table 29.1 shows the various toxicities and associated early and late effects. Although pericarditis is the most common manifestation of RICD, ischemic heart disease is the most common cause of cardiac death in patients who have undergone RT. The risk of RICD relates to both the dose and duration of RT.
Early | Late |
---|---|
PericarditisAcute exudative pericarditis, rare—occurs during RT—reaction to necrosis/inflammation of tumor adjacent to the heartDelayed acute pericarditis—within weeks—manifests as asymptomatic pericardial effusion or symptomatic pericarditis. Cardiac tamponade, rare. Spontaneous clearance of effusion can take up to 2 years | PericarditisDelayed chronic pericarditis—weeks to years after RT—extensive fibrous thickening, adhesions, chronic constriction, and chronic pericardial effusion—observed in up to 20% of patients within 2 yearsConstrictive pericarditis seen in 4%–20% of patients and is dose-dependent and related to presence of pericardial effusion in delayed acute phase |
CardiomyopathyAcute myocarditis—radiation-induced inflammation with transient repolarization abnormalities and mild myocardial dysfunction | CardiomyopathyDiffuse myocardial fibrosis (after >30 Gy) with systolic/diastolic dysfunction, conduction abnormalities, and autonomic dysfunctionRestrictive cardiomyopathy—advanced myocardial damage due to fibrosis with severe diastolic dysfunction and heart failure signs and symptoms |
Valvular DiseaseNo immediate effects | Valvular DiseaseValve apparatus and leaflet thickening, fibrosis, shortening, and calcification on mostly left-sided valvesValve regurgitation > valve stenosisStenosis more commonly affects aortic valveValve disease increases significantly after 20 years |
Conduction System DiseaseNo immediate effects | Conduction System DiseaseRight bundle branch block most commonProlongation of the corrected QT intervalAtrioventricular nodal bradycardia, heart block, sick sinus syndrome |
Coronary Artery DiseaseNo immediate effects—perfusion defects can be seen in ∼50% of patients 6 months after RT, sometimes a/w wall-motion abnormalities and chest pain | Coronary Artery DiseaseAccelerated CAD appearing at younger agePatients <50 tend to develop CAD in first 10 years, patients >50 have longer latencyCoronary ostia and proximal segments typically involvedCAD doubles risk of death via myocardial infarction |
Carotid Artery DiseaseNo immediate effects | Carotid Artery DiseaseRT–induced lesions more extensive, involve longer segments, and atypical areas of carotid segments |
Vascular DiseaseNo immediate effects | Vascular DiseaseAtherosclerotic calcifications of ascending aorta and aortic arch |
The clinical presentation of RICD is similar to that of cardiac disease unrelated to RT, which makes it difficult to differentiate the two. It is important to assess the risk factors and the timeframe for development in diagnosing radiation-induced cardiotoxicity.
Syndrome | Clinical Presentation |
---|---|
Acute pericarditis | Chest pain, fever, pericardial rub |
Chronic pericarditis | Dyspnea, hypotension, thready pulse |
Cardiomyopathy | Dyspnea, fatigue, weakness, edema, pulmonary edema |
Valvular disease | Dyspnea, symptoms of valvular regurgitation/stenosis |
Coronary artery disease | Chest pain/tightness/heaviness, dyspnea, fatigue |
Conduction abnormalities | Palpitations, dizziness, dyspnea, chest discomfort |
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