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The three main LTFU categories of cardiovascular (CV) complications are heart failure (anthracycline but occasionally high‐dose cyclophosphamide‐related and augmented by radiation); radiation‐induced structural abnormalities in valves, coronary arteries or the conduction system; and development of metabolic syndrome (MS) components (dyslipidemia, hypertension, glucose intolerance). MS increase the risk for type 2 diabetes and atherosclerotic CV disease (CVD, myocardial infarction, vascular disease and stroke) [44–46].

Risk for CV toxicities is cumulative and includes genetics, pre‐HCT exposures plus side effects of cGVHD therapies (glucocorticoids, CNIs) since most patients take >2 years to discontinue all IST after an initial diagnosis of cGVHD; 10% require IST >5 years. Relative to siblings, allogeneic HCT survivors were 3–4 times more likely to report diabetes mellitus and twice as likely to report hypertension [47]. They were significantly more likely to develop hypertension than autologous recipients. TBI exposure was associated with an increased risk of diabetes mellitus (OR= 3.42, 95% CI: 1.55–7.52). Compared with a well‐matched general population, pediatric HCT survivors (>70% allogeneic recipients) had significantly higher rates of cardiomyopathy, stroke, dyslipidemia and diabetes [48], in an analysis that adjusted for sex, race, age, BMI, current smoking, daily fruit/vegetable intake, and recreational physical activity time. An analysis of potential risk reduction for serious CV outcomes (ischemic heart disease, cardiomyopathy, stroke) found that controlling dyslipidemia was most helpful, followed by control of hypertension, diabetes and smoking. Obesity was a risk factor for post‐HCT hypertension, dyslipidemia, and diabetes. Lower fruit/vegetable intake was associated with greater risk of dyslipidemia and diabetes, and lower physical activity level was associated with greater risk of hypertension and diabetes. Healthier survivor lifestyle characteristics attenuated the risk for all CV conditions assessed.

Pediatric survivorship recommendations usually begin by conducting an annual history and physical (dyspnea, chest pain, palpitations, exertional intolerance, edema), calculating anthracycline and radiation exposures, and requesting 2D‐echocardiography every 1–5 years depending on age plus exposures [12]. Variables used for COG’s risk algorithm require doxorubicin‐equivalent dose conversions, recognizing that total cumulative lifetime doses of anthracycline need to be multiplied by 4.0 (mitoxantrone), 5.0 (idarubicin), or by only 0.5 (daunorubicin) or 0.67 (epirubicin), due to potency differences. The Childhood Cancer Survivorship Study Cardiovascular Risk Calculator [49] uses information about exposures (anthracycline, alkylator, platinums, and radiation) but also demographics (gender, current age, age at HCT, use of medications to treat diabetes, dyslipidemia or hypertension) to predict incidence of heart failure, ischemic heart disease and stroke among survivors. Based on CCSG findings prevention of obesity and avoidance of smoking is important. Because improved survival and other benefits are observed in solid organ transplantation when dyslipidemia, hypertension and diabetes are addressed [13,50–53]. It is also reasonable to use medications to lower blood pressure and use statins to target lower LDL‐C after HCT when therapeutic lifestyle modifications are ineffective or not feasible. The lowest dose possible is used to minimize the potential for adverse drug interactions. Pleiotropic effects of statins may extend to improvement in renal function, hypertension, BMD, reduced incidence of AVN, and even improved control of GVHD [54–61].