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Late cardiovascular complications after AHSCT include cardiomyopathy, valvular dysfunction, arrhythmia, ischemic heart disease, and subsequent congestive heart failure (CHF)⁷. In a retrospective cohort study of 1244 AHSCT recipients, the cumulative incidence of CHF was 4.8% at 5 years, 6.8% at 10 years, and 9.1% at 15 years [20]. Significant risk factors for the development of CHF were female sex, diagnosis of lymphoma, and age at transplant. Furthermore, AHSCT survivors had a 4.5‐fold excess risk of developing CHF compared to a demographically matched healthy population, with the absolute increase in risk being greatest in patients less than 35 years of age [20]. Notably, the risk of CHF was substantially higher in patients with hypertension or a cumulative pretransplant anthracycline exposure of ≥250 mg/m². In patients with AL amyloidosis receiving high‐dose melphalan conditioning prior to AHSCT, the decision to administer a melphalan dose <200 mg/m², pretransplant left ventricular ejection fraction of <60%, and involvement of amyloid in three or more organs were significantly associated with cardiac dysfunction at 4 months posttransplant [21].

A case‐control study on 249 patients surviving 1+ year after transplant identified pre‐and posttransplant risk factors for coronary artery disease (CAD) and cerebrovascular disease²². Around 65% of patients in this study were AHSCT survivors. Two independent risk factors for development of late cardiovascular disease were identified: ≥2 traditional risk factors including obesity, hyperlipidemia, hypertension, and diabetes posttransplant (5‐fold increased risk) and conditioning with cyclophosphamide (2.5‐fold increase in risk). Furthermore, pretransplant chest irradiation was associated with an almost 10‐fold increased risk of CAD [22]. Notably, neck or cranial irradiation was not associated with an increased risk of cerebrovascular disease. The incidence of cardiovascular risk factors such as hyperlipidemia and diabetes are greater in transplant survivors compared to healthy controls [23]. Exposure to TBI can also lead to an increased incidence of hypertension and diabetes in transplant survivors, leading to downstream cardiovascular complications [24].

The risk of late deaths due to cardiac complications in AHSCT survivors is higher in females (SMR 4.4 compared to a demographically matched healthy population) [8]. Guidelines for monitoring patients for late cardiac and cardiovascular complications have been previously published [17,18]. Briefly, AHSCT survivors should undergo routine clinical assessment for cardiovascular risk factors at one year and at least yearly thereafter in a survivorship clinic to identify and intervene on modifiable risk‐factors such as hypertension, hyperlipidemia, smoking, obesity, and diabetes. In patients with a high risk of atherosclerotic cardiovascular disease (≥10% at 10 years), treatment of hypertension should be initiated at a threshold of 130/80 mmHg, with the treatment threshold for remaining patients being 140/90 mmHg [25]. A meta‐analysis of 17 randomized controlled trials testing neurohormonal therapies (β‐blockers, mineralocorticoid receptor antagonists, or angiotensin converting enzyme inhibitors/angiotensin receptor blockers) against placebo in adult patients receiving chemotherapy showed a statistically significant but clinically modest increase in left ventricular ejection fraction (LVEF) with neurohormonal therapies [26]. Notably, there was substantial heterogeneity between studies and the clinical significance of a modest LVEF increase is unclear. Hence, with limited evidence on the efficacy of neurohormonal therapies for prevention of chemotherapy‐induced cardiotoxicity, these drugs should be administered to AHSCT survivors only for other compelling indications (e.g. angiotensin converting enzyme inhibitors in diabetes and beta‐blockers in well compensated CHF). Longitudinal monitoring of global longitudinal strain, in addition to ejection fraction, can help identify early or subclinical cardiotoxicity from chemotherapy [27]. In patients with LDL‐C (Low Density Lipoprotein‐Cholesterol) more than 190 mg/dl (4.91 mmol/l) or at a high risk of atherosclerotic cardiovascular disease, high‐intensity statin therapy should be initiated [28]. The HbA1c goal for patients with diabetes mellitus should be individualized, based on age, and comorbidities and co‐management with an endocrinologist should be considered. Identification of novel risk factors for CAD like clonal hematopoiesis of indeterminate potential (CHIP) [29] can help identify high‐risk patients who would benefit from targeted screening and early intervention.