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

Authors

• John D. Groarke, Brigham and Women's Hospital
• Kirsten K. Ness, St. Jude Children's Research Hospital
• Rikeenkumar Dhaduk, St. Jude Children's Research Hospital
• Juan C. Plana, Baylor College of Medicine
• Jean Bernard Durand, University of Texas Health Science Center at Houston
• Russell V. Luepker, University of Minnesota Twin Cities
• Vijaya M. Joshi, University of Tennessee Health Science Center
• Matthew Ehrhardt, St. Jude Children's Research Hospital
• Daniel A. Mulrooney, St. Jude Children's Research Hospital
• Stephanie B. Dixon, St. Jude Children's Research Hospital
• Anju Nohria, Brigham and Women's Hospital
• Daniel M. Green, St. Jude Children's Research Hospital
• Rebecca M. Howell, University of Texas Health Science Center at Houston
• Deo Kumar Srivastava, St. Jude Children's Research Hospital
• John L. Jefferies, University of Tennessee Health Science Center
• Leslie L. Robison, St. Jude Children's Research Hospital
• Melissa M. Hudson, St. Jude Children's Research Hospital
• Gregory T. Armstrong, St. Jude Children's Research Hospital

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.

Publication Title

Jacc Cardiooncology

Recommended Citation

Groarke, J., Ness, K., Dhaduk, R., Plana, J., Durand, J., Luepker, R., Joshi, V., Ehrhardt, M., Mulrooney, D., Dixon, S., Nohria, A., Green, D., Howell, R., Srivastava, D., Jefferies, J., Robison, L., Hudson, M., & Armstrong, G. (2024). Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study. Jacc Cardiooncology, 6 (5), 775-787. https://doi.org/10.1016/j.jaccao.2024.08.005