title: Abnormal exercise response in long-term survivors of hodgkin lymphoma treated with thoracic irradiation: evidence of cardiac autonomic dysfunction and impact on outcomes.
abstract: BACKGROUND
  Hodgkin lymphoma (HL) survivors treated with thoracic radiation therapy (RT) have impaired exercise tolerance and increased cardiovascular mortality.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the prevalence of autonomic dysfunction and its implications on exercise capacity and mortality in long-term survivors of HL.
  
  
  METHODS
  Exercise parameters in 263 HL survivors referred for exercise treadmill testing at a median interval of 19 years after RT were compared with 526 age-, sex-, and cardiovascular risk score-matched control subjects. Within the RT cohort, the presence of autonomic dysfunction, defined by an elevated resting heart rate (HR) (≥80 beats/min) and abnormal heart rate recovery (HRR) at 1 min (≤12 beats/min if active cool-down, or ≤18 beats/min if passive recovery), was correlated with exercise capacity and all-cause mortality over a median follow-up of 3 years.
  
  
  RESULTS
  RT was associated with elevated resting HR and abnormal HRR after adjusting for age, sex, cardiovascular risk factors, medications, and indication for exercise treadmill testing: odds ratio: 3.96 (95% confidence interval [CI]: 2.52 to 6.23) and odds ratio: 5.32 (95% CI: 2.94 to 9.65), respectively. Prevalence of autonomic dysfunction increased with radiation dose and time from RT. Both elevated resting HR and abnormal HRR were associated with reduced exercise capacity in RT patients. Abnormal HRR was also associated with increased all-cause mortality (age-adjusted hazard ratio: 4.60 [95% CI: 1.62 to 13.02]).
  
  
  CONCLUSIONS
  Thoracic RT is associated with autonomic dysfunction, as measured by elevated resting HR and abnormal HRR. These abnormalities are associated with impaired exercise tolerance, and abnormal HRR predicts increased all-cause mortality in RT patients.
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Noninvasive Cardiovascular Imaging Program, Department of Medicine (Cardiovascular Division) and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts; Cardio-Oncology Program, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors: John D
authors: JD
authors: Groarke
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Varsha K
authors: VK
authors: Tanguturi
authors: Noninvasive Cardiovascular Imaging Program, Department of Medicine (Cardiovascular Division) and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Jon
authors: J
authors: Hainer
authors: Noninvasive Cardiovascular Imaging Program, Department of Medicine (Cardiovascular Division) and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Josh
authors: J
authors: Klein
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Cardio-Oncology Program, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors: Javid J
authors: JJ
authors: Moslehi
authors: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors: Andrea
authors: A
authors: Ng
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Noninvasive Cardiovascular Imaging Program, Department of Medicine (Cardiovascular Division) and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Daniel E
authors: DE
authors: Forman
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Noninvasive Cardiovascular Imaging Program, Department of Medicine (Cardiovascular Division) and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Marcelo F
authors: MF
authors: Di Carli
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Cardio-Oncology Program, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: anohria@partners.org.
authors: Anju
authors: A
authors: Nohria
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology* / Q000528:radiation effects; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000401:mortality / Q000503:physiopathology* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
keywords: Hodgkin lymphoma; abnormal heart rate recovery; cardiac autonomic dysfunction; elevated resting heart rate; prognosis; radiation therapy