Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study

Abstract

Background: The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown.

Objectives: We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors.

Methods: We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo₂ < 80% predicted).

Results: Survivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors (P < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P < 0.001).

Conclusions: Survivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness.

Keywords: autonomic dysfunction; autonomic function; cardio-oncology; childhood cancer survivors; impaired cardiorespiratory fitness.

Graphical abstract

Figure 1

Measures of Autonomic Dysfunction in Adult Survivors of Childhood Cancer (A) Prevalence of each measure of autonomic dysfunction (AD) in survivors vs community control subjects. P value for intergroup comparison for each measure of autonomic dysfunction is <0.001. (B) Burden of autonomic dysfunction in survivors vs community control subjects, categorized by the aggregate number of each of the 4 measures present. P value for intergroup comparison for each measure of autonomic dysfunction is <0.001. HR = heart rate; SBP = systolic blood pressure.

Figure 2

Relationship of Autonomic Dysfunction With Exercise and Echocardiographic Assessments Relationship of peak oxygen consumption (A), E/e′ (B), and global longitudinal stain (C) to the aggregate number of measures of autonomic dysfunction among adult survivors of childhood cancer.

Figure 2

Relationship of Autonomic Dysfunction With Exercise and Echocardiographic Assessments Relationship of peak oxygen consumption (A), E/e′ (B), and global longitudinal stain (C) to the aggregate number of measures of autonomic dysfunction among adult survivors of childhood cancer.

Central Illustration

Autonomic Dysfunction in Childhood Cancer Survivors vs Control Subjects in SJLIFE This illustration outlines the 4 measures of autonomic dysfunction evaluated in this analysis and highlights a higher prevalence of autonomic dysfunction among survivors vs control subjects. It provides a summary of the predictors of autonomic dysfunction in survivors and outlines the association of autonomic dysfunction with peak oxygen consumption in survivors. SBP = systolic blood pressure; SJLIFE = St. Jude Lifetime Cohort Study.