Table 1.
Recommendations, Basis of Evidence, and Future Directions/Gaps for Treatment and Prevention of CV Disease During and After Therapeutic Radiation for Cancer
| Recommendation Summaries | Evidence Basis | Future Directions/Gaps |
|---|---|---|
| General principles to mitigate CV events | ||
| Recommendation A.1: In all patients receiving therapeutic radiation to the head and neck, chest, and/or abdomen/pelvis, a comprehensive baseline evaluation to screen for and optimize treatment of underlying CV risk factors and/or CV disease is recommended | Impact of CV risk modification on future CV events is extrapolated from large cohorts in the general population as well as cancer cohorts, most notably in survivors of childhood cancer | Current ASCVD risk scores are hypothesized to underestimate risk of CV events in cancer populations, and an optimized risk score, potentially including CAC, could be useful Future research should investigate optimal treatment goals (ie, blood pressure, LDL reduction) in patients post-RT |
| Recommendation A.2: Before RT delivery, review of available CT chest imaging for the presence of coronary and aortic calcifications to improve CV risk stratification and mitigation of future atherosclerotic cardiovascular events is recommended | CAC is diagnostic of underlying arterial disease and predicts future CV events in large cohorts in the general population and in patients included in lung cancer screening trials, as well as in smaller cohorts receiving RT | Presence of coronary calcifications on CT imaging identifies patients at risk for future CV events, but formal CAC screening protocols should be further evaluated It is unknown what CAC score threshold (>0, >10, >100) should prompt treatment in patients post-RT |
| Recommendation A.3: Efforts to maximally reduce radiation doses to CV structures without compromising cancer treatment are recommended | Radiation exposure should maintain tumor efficacy while minimizing dose to be consistent with therapeutic radiation guidelines | Future research should continue to evaluate the trade-off between tumor efficacy and CV morbidity and mortality |
| Head and neck RT | ||
| Recommendation B.1: In patients with prior neck irradiation, auscultation for carotid bruits during their routine physical examination is recommended | A low-risk examination technique can identify patients at increased risk for future stroke based on a meta-analysis in the general population | The presence of a bruit increases risk for significant atherosclerosis, but its absence does not rule out disease |
| Recommendation B.2: In patients with prior neck irradiation, carotid ultrasound to screen for development of asymptomatic atherosclerotic plaque is recommended. Initial evaluation as early as 1 y post-radiation in higher risk patients (determined by radiation dose and CV risk) with follow-up every 3 to 5 y can be useful to guide preventive therapy | Carotid ultrasound is low risk to the patient and, based on cohort studies in survivors of neck RT, can be used to identify asymptomatic disease | Further studies are needed to identify the optimal screening interval for ultrasound in conjunction with history and physical examination |
| Recommendation B.3: In patients with prior neck irradiation, reviewing available CT scans for carotid calcifications to aid in identification of asymptomatic atherosclerosis is recommended | Inferred from basic science, clinical trials, and population studies, numerous studies have established calcified plaque as a marker of atherosclerosis in various vascular beds Patients often undergo surveillance CT scans post-RT, which can be used to identify asymptomatic disease at no additional risk |
Although statin therapy has been shown to reduce carotid atherosclerosis and prevent stroke, no studies have directly investigated whether carotid calcifications should prompt statin therapy |
| Recommendation B.4: In patients with prior neck irradiation, screening for signs and symptoms of dysautonomia on follow-up physical examinations (including orthostatic vital signs) is recommended | This is based on expert opinion and small cohort studies in patients treated with RT The history and physical examination provide a low-risk procedure to identify patients with dysautonomia |
Optimal screening and treatment algorithms for dysautonomia in patients post-RT have not been established |
| Thoracic RT | ||
| Recommendation C.1: In patients with CV risk factors receiving radiation to mediastinal structures, including the heart, a baseline ECG and a comprehensive TTE can be useful | This is based on expert opinion. Current guidelines are mixed in their recommendation for baseline ECG and TTE evaluation of patients undergoing thoracic RT A baseline ECG and TTE are low-risk tools that provide the potential to identify asymptomatic disease and allow for CV optimization before RT |
Numerous long-term follow-up studies have shown the significant CV impact of RT, but a baseline ECG or echocardiogram to detect pre-existing disease has not been studied. Although identifying asymptomatic disease may help with risk stratification, there are no data to suggest that it should prevent a patient from receiving RT |
| RecommendationC.2: In patients with prior chest irradiation, review of available CT scans for coronary or aortic calcifications to guide therapy for asymptomatic atherosclerosis is recommended.The absence of coronary artery calcifications, particularly from a non-gated CT scan, cannot fully exclude the presence of CAD | Large cohort studies in the general population and small cohort studies in the cancer population have established the impact of CAC on future cardiac events Evaluating existing CT scans, which correlate with quantitative CAC scores, provides a tool to improve CV stratification and to help guide initiation of preventive therapy |
Although CAC on CT imaging identifies patients with underlying CAD, it is important to note that non–ECG-gated CT scans have a 9% false-negative rate and may not detect CAC in some patients with underlying CAD It is not known what threshold of qualitative CAC should prompt aspirin and/or statin use The impact of aspirin and statin therapy on identified atherosclerosis post-RT is not known |
| Recommendation C.3: In patients with prior chest irradiation without documented atherosclerosis on prior evaluations, further screening for CAD with CAC, coronary CT angiography, or functional stress testing during follow-up evaluations is recommended. Screening at 5-y intervals, depending on the patient’s overall CV risk, can be useful | Functional stress testing, CAC, and CT angiography can identify asymptomatic patients with underlying CAD based on large cohort studies in the general population and small cohort studies in patients post-RT | Optimal screening protocols have not been established. CTCA and CAC have the advantage of identifying nonobstructive CAD to help target preventive therapy, but there have not been comparison trials in patients post-thoracic RT. Further studies are needed to understand the relative prevalence of noncalcified and calcified plaque in patients post-RT by using historical and modern techniques |
| Recommendation C.4: In patients with prior chest irradiation who are at increased risk for cardiomyopathy, screening TTEor cardiac MRI after completion of cancer therapy are recommended | Prospective cohort studies have shown a high rate of cardiomyopathy and heart failure post-RT necessitating screening protocols | The optimal screening interval has not been established with historical or current radiation techniques and should be further evaluated with future studies |
| Recommendation C.5: The timing of the first echocardiogram post–chest RT can be guided by the individual patient risk, with echocardiography as early as 6-12 months after RT in high-risk patients. In all patients in whom the heart is in the radiation field, an echocardiogram within 5 y post-RT is recommended. Additional screening TTE and measurement of NT-proBNP levels every 5 y can be useful | The recommended timing of screening is based on the incidence of heart failure post-RT in cohort studies Recent cohort studies have suggested that cardiac biomarkers may also be an effective screening tool |
Additional research in the timing and measurement of biomarkers or cardiac imaging post-RT is needed |
| Recommendation C.6: In patients with prior RT with the heart in the radiation field, evaluation for subclinical valvular heart disease with TTE 5 y post-RT and then every 5 y thereafter is recommended | The recommended timing of screening is based on the incidence of valvular disease post-RT in cohort studies | The optimal screening interval has not been established with historical or current radiation techniques and should be further evaluated in future studies |
| Recommendation C.7: In patients with prior RT with the heart in the radiation field, evaluation for pericardial disease with TTE 5 y post-RT and then every 5 y thereafter is recommended | The recommended timing of screening is based on incidence of pericardial disease post-RT in cohort studies | The optimal screening interval has not been established with historical or current radiation techniques and should be further evaluated in future studies |
| Recommendation C.8: In patients who have received radiation involving the subclavian artery, bilateral BP on annual examination to screen for subclavian stenosis is recommended | A comprehensive physical examination with bilateral BP measurement allows for minimal-risk screening of patients for subclavian artery disease that can occur post- thoracic RT | No studies have evaluated screening protocols for subclavian disease post-thoracic RT |
| Recommendation C.9: In patients who have received radiation involving the subclavian artery and/or LIMA, evaluation with CT angiography or a comparable study before CABG is recommended | Case studies have shown that undiagnosed subclavian artery stenosis or LIMA atrophy can have significant consequences on surgical outcomes post-CABG | A complete angiographic assessment is recommended before planned bypass surgery to reduce risk of graft failure after surgery, but an optimal screening protocol has not been established |
| Abdominal and pelvic RT | ||
| Recommendation D.1: In patients with prior abdominal or pelvic irradiation, screening for symptoms of claudication, assessment of pedal pulses, and auscultation of aortic or renal artery bruits are recommended | A comprehensive physical examination can identify patients with underlying peripheral vascular disease to aid in management | No studies have evaluated screening protocols for peripheral arterial disease post-abdominal and pelvic RT. The prevalence of PAD post-abdominal and pelvic RT is not known |
| Recommendation D.2: In patients with prior abdominal or pelvic irradiation, reviewing available CT scans for aortic and iliofemoral calcifications to identify atherosclerosis can be useful | Aortic calcifications increase a patient’s mortality risk based on the Framingham Risk Study and in a lung cancer cohort receiving RT and can help risk-stratify patients. It is expert opinion that evaluating for calcifications post-RT can potentially help clinicians target preventive therapy | Screening for significant peripheral vascular disease post-abdominal and pelvic RT has not been adequately investigated |
| Recommendation D.3: In patients with prior abdominal or pelvic irradiation with worsening renal function and/or systemic hypertension, evaluation for radiation nephropathy and/or renal artery stenosis can be useful. | Based on case series, renal artery stenosis and radiation nephropathy are known complications of RT and may lead to hypertension. Identification of underlying renal artery stenosis and/or radiation nephropathy may help in disease and risk factor management | The incidence and prevalence of hypertension, renal artery stenosis, and radiation nephropathy in patients post-abdominal and pelvic RT are not established |
| CV disease prevention after RT | ||
| Recommendation E.1: In patients who have received RT, regular screening for and aggressive treatment of CV risk factors and CV disease are recommended. The interval of screening visits should be guided by the patient’s risk (patient and treatment factors). Screening at least annually can be useful | Modifiable CV risk factors significantly increase risk of future CV events post-RT, with the strongest evidence in cohorts of adult survivors of childhood RT In accordance with prevention guidelines and numerous studies in the general population, treatment of CV risk factors is indicated |
Screening intervals for CV risk factors post-RT remain to be clarified |
| CV management after RT | ||
| Recommendation F.1: In patients with prior chest RT, careful consideration before surgical versus percutaneous treatment for valvular or CAD is recommended due to their increased surgical risk. The percutaneous approach is often advantageous, especially in patients with higher radiation doses to the mediastinum or prior cardiac surgery | Small cohort studies have shown that survivors of thoracic RT are at increased risk for complications from chest surgery, and they may benefit from a percutaneous approach if technically feasible | Additional research is needed to determine the multidisciplinary strategy that is most successful for management of obstructive CAD and/or valvular disease post-RT |
| Recommendation F.2: In patients with prior chest RT and heart failure with preserved ejection fraction, consideration of both restrictive cardiomyopathy and constrictive pericarditis is recommended | This is based on expert opinion. The presentations of restrictive cardiomyopathy and constrictive pericarditis are similar, but management of the 2 conditions is vastly different. Distinguishing between the 2 is of major clinical importance | Diagnostic protocols vary between institutions and are not standardized |
| Recommendation F.3: In patients with prior chest RT and confirmed constrictive pericarditis who have failed initial medical management, pericardiectomy can be considered. Surgery is considered high risk, although timing surgery before progression to advanced disease can improve morbidity | This is based on expert opinion. Case series of patients with constriction have shown a high mortality with pericardiectomy but patients likely do better if they undergo surgery earlier in the disease process | Timing and best practices for pericardiectomy in patients with constriction post-thoracic RT needs further research |
ASCVD = atherosclerotic CV disease; BP = blood pressure; CABG = coronary artery bypass graft; CAC = coronary artery calcium; CAD = coronary artery disease; CT = computed tomography; CV = cardiovascular; ECG = electrocardiogram; LDL = low-density lipoprotein; LIMA = left internal mammary artery; MRI = magnetic resonance imaging; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PAD = peripheral arterial disease; RT = radiation therapy; TTE = transthoracic echocardiogram.