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

Authors

John D Groarke
Kirsten K Ness
Rikeenkumar Dhaduk
Juan C Plana
Jean Bernard Durand
Russell V Luepker
Vijaya M Joshi
Matthew Ehrhardt
Daniel A Mulrooney
Stephanie B Dixon
Anju Nohria
Daniel M Green
Rebecca M Howell
Deo Kumar Srivastava
John L Jefferies
Leslie L Robison
Melissa M Hudson
Gregory T Armstrong

Publication Date

10-1-2024

Journal

JACC: CardioOncology

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, childhood cancer survivors, cardio-oncology, impaired cardiorespiratory fitness

DOI

10.1016/j.jaccao.2024.08.005

PMID

39479326

PMCID

PMC11520214

PubMedCentral® Posted Date

10-8-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes