Autonomic Dysfunction in Survivors of Hodgkin Lymphoma Treated With Thoracic Irradiation | Journal Scan

Study Questions:

What is the prevalence and significance of elevated resting heart rate (HR) and abnormal heart rate recovery (HRR) in Hodgkin lymphoma (HL) survivors treated with radiation therapy (RT) and referred for exercise treadmill testing (ETT)?


This was a retrospective review of survivors of HL undergoing ETT at the study institution between 2003 and 2013. For every RT patient, two controls were matched by age, sex, and Morise clinical risk score (which allows for the assessment of the pretest probability of coronary artery disease). All patients underwent ETT according to the standard Bruce protocol. Elevated resting HR and abnormal HRR at 1 minute were primary endpoints. All-cause mortality was also assessed.


In adjusted analyses, RT was associated with elevated HR and abnormal HRR with odds ratios of 3.96 (95% confidence interval [CI], 2.52-6.23) and 5.32 (95% CI, 2.94-9.65), respectively. Among RT patients, exercise duration was significantly reduced among those with an elevated resting HR and those with abnormal HRR. When RT patients were divided into tertiles based on interval from RT to ETT, frequency of elevated resting HR and abnormal HRR increased with time from RT. The prevalence of abnormal HRR was significantly higher in the high radiation dose group (median dose >38 Gy) than in the low radiation dose group. In age-adjusted analyses, abnormal HRR was associated with increased all-cause mortality (adjusted hazard ratio, 4.60; 95% CI, 1.62-13.02).


Compared to age- and risk-matched controls, HL survivors who had been treated with thoracic radiation therapy had higher odds of elevated resting HR and abnormal HRR.


This is an important study that adds to our understanding of the cardiovascular morbidity and mortality seen in HL survivors treated with thoracic RT. As the authors discuss, it is known that HL survivors treated with RT are at risk of ischemic heart disease and valvular disease. This analysis is the first that demonstrates the risk for autonomic dysfunction in this vulnerable population. The data from this retrospective analysis also suggest that autonomic dysfunction may be associated with adverse outcomes, including increased all-cause mortality and impaired exercise tolerance. Certainly, future studies should clarify the consequences of autonomic dysfunction in this population and evaluate the benefits of medical therapies that regulate adrenergic tone.

Clinical Topics: Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure

Keywords: Coronary Artery Disease, Coronary Disease, Exercise Test, Exercise Tolerance, Heart Rate, Hodgkin Disease, Myocardial Ischemia, Retrospective Studies, Survivors, Radiation, Heart Failure

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