Cardiac autonomic dysfunction in survivors of childhood acute lymphoblastic leukemia: The St. Jude Lifetime Cohort Study

Abstract

Background: Cardiac autonomic dysfunction (CAD) is possible following treatment for childhood cancer. The aims of our analyses were to compare the prevalence of CAD between adult survivors of childhood acute lymphoblastic leukemia and controls, compare exercise response among survivors with and without CAD, and identify treatment-related risk factors for CAD.Procedure: Participants were treated for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital between 1980 and 2003 (N = 338). A comparison group matched for race/ethnicity, age, and sex was also recruited (N = 325). Resting heart rate (HR) was assessed via electrocardiogram, and heart rate recovery (HRR) and exercise capacity were evaluated with submaximal cardiopulmonary exercise testing.Results: CAD was present in 33.7% of survivors and 27.6% of controls (P = 0.09). Although mean resting HR did not differ between survivors and controls (74 ± 12 vs 72 ± 12 beats per minute (bpm), P = 0.07), survivors had lower mean HRR than controls (22 ± 9 vs 25 ± 10 bpm; P < 0.001). Survivors with CAD had lower peak exercise tolerance (25.7 ± 6.5 vs 21.2 ± 4.9 mL/kg/min, P < 0.001) than those without. Survivors treated with cyclophosphamide in combination with vincristine ≥38 mg/m 2 and/or glucocorticoids ≥10 000 mg/m 2 were 1.56 (95% CI 1.09-2.24) times more likely to have CAD than those without this treatment. Obese survivors were 1.78 (95% CI:1.31-2.40) times more likely to have CAD than nonobese survivors (P < 0.001).Conclusion: CAD was present in over one third of survivors and was associated with lower exercise capacity. Obese survivors and those exposed to cyclophosphamide with high doses of vincristine and/or corticosteroids were at greatest risk. K E Y W O R D Sacute lymphoblastic leukemia, autonomic dysfunction, cardiac, chemotherapy, obesity, survivor Abbreviations: %, percent; ±, plus-minus sign; ≤, less than or equal to; ≥, more than or equal

Cardiac Autonomic and Endothelial Function in Acute Lymphoblastic Leukaemia Patients Immediately After Chemotherapy and at the Three-Month Follow-up

“…Further, the lower 30:15 ratio and E:I ratio indicate reduced vagal modulation and higher DBP response to IHG indicates increased adrenergic drive. This corroborates findings from the study by Christoffersen et al that reported cardiac autonomic dysfunction in childhood ALL survivors [7]. Cardiac autonomic neuropathy has been constantly associated with adverse cardiovascular events.…”

“…ALL survivors have a greater preponderance of developing cardiac disease compared to healthy controls. Christoffersen et al reported that over one-third of childhood ALL survivors develop cardiac autonomic dysfunction (CAD) in the form of lower exercise capacity, which is higher compared to age, gender, race, ethnicity, drug-matched controls that predispose them to poor exercise performance, thereby enhancing the risk of cardiovascular comorbidities like the enhanced risk of arrhythmia and sudden cardiac death [7]. Kamath et al demonstrated reduced resting state heart rate variability (HRV) abnormalities among childhood ALL survivors [8].…”

Within 5‐year off‐chemotherapy: How the cardio‐respiratory response to exercise is related to energy expenditure, fatigue, and adiposity in children with acute lymphoblastic leukaemia?

“…Previous studies on the cardio‐respiratory function in survivors of ALL and its relationship with the other health factors have been limited to a small sample of ALL survivors (Warner et al, 1997), included children with different types of malignancies (Braam et al, 2016) or adult survivors of ALL who were more than 5 years post‐treatment (Christoffersen et al, 2020), or have been limited to different measures of body function (Marchese & Chiarello, 2004). To the knowledge of the research team, studies that have carried out to check changes in cardio‐respiratory functions in survivors of ALL, in particular, who are no longer than 5 years post‐treatment remain insufficient, while no previous studies examined whether these changes were related to other clinical symptoms such as decreased EE, fatigue and adiposity.…”

Modifiable Cardiometabolic Risk Factors in Survivors of Childhood Cancer

“…Self-reported obesity interacts in a near multiplicative fashion with cardiotoxic therapies to potentiate the risk of coronary artery disease, valvular disease, and arrhythmia ( Figure 2 ). 6 Independent of treatment exposure, obesity has been linked to diastolic dysfunction, 26 cardiac autonomic dysfunction, 27 and late venous thromboembolism in survivors. 28 It also serves as a central driver of morbidity by doubling the risk of hypertension and dyslipidemia 29 and increasing the risk of diabetes by 5- to 7-fold.…”