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Cardiovascular Status in Long-Term Survivors of Hodgkin's Disease Treated With Chest Radiotherapy

From the Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY; Department of Radiation Oncology, Massachusetts General Hospital; Department of Radiation Oncology, Brigham and Women's Hospital; Department of Cardiology, Department of Oncology and the Department of Radiology, The Children's Hospital; The Dana-Farber Cancer Institute; Harvard University School of Medicine, Boston, MA; Department of Biostatistics, Medical University of South Carolina, Charleston, SC; Department of Pediatrics, University of Miami School of Medicine, the Holtz Children’s Hospital of the University of Miami/Jackson Memorial Medical Center, and the Sylvester Comprehensive Center, Miami, FL

Address reprint requests to Steven E. Lipshultz, MD, Department of Pediatrics, University of Miami School of Medicine, PO Box 016820, Miami, FL 33101; e-mail: slipshultz{at}med.miami.edu

PURPOSE: Cardiovascular status was assessed in 48 Hodgkin's disease (HD) survivors at a median of 14.3 years (range, 5.9 to 27.5 years) after diagnosis because they may be at increased risk for cardiovascular abnormalities.

PATIENTS AND METHODS: Patients completed the Short-Form 36 quality-of-life instrument and were screened by echocardiography, exercise stress testing, and resting and 24-hour ECG.

RESULTS: All patients received mediastinal irradiation (median, 40.0 Gy; range, 27.0 to 51.7 Gy) at a median age of 16.5 years (range, 6.4 to 25.0 years). Four patients received an anthracycline. Although every patient described their health as good or better, and none had symptomatic heart disease at screening, all but one had cardiac abnormalities on screening. Restrictive cardiomyopathy was suggested by reduced average left ventricular (LV) dimension (P < .001) and mass (P < .001), without increased LV wall thickness. Significant valvular defects were present in 42%; 75% had conduction defects. One survivor developed complete heart block shortly after the study visit. Autonomic dysfunction was suggested by a monotonous heart rate in 57%, persistent tachycardia in 31%, and blunted hemodynamic responses to exercise in 27%. Peak oxygen uptake (VO₂max) during exercise, a predictor of mortality in heart failure, was significantly reduced (< 20 mL/kg/m²) in 30% of survivors. VO₂max was correlated with increasing fatigue, increasing shortness of breath (both, r = –0.35; P = .02), and decreasing physical component score on the SF-36 (r = 0.554; P = .00017).

CONCLUSION: A variety of unsuspected, clinically significant cardiovascular abnormalities are common in long-term survivors of HD who are treated at a young age with mediastinal irradiation. We recommend serial, comprehensive cardiac screening of HD survivors who fit this profile.

Supported by the United States Food and Drug Administration, National Institutes of Health (grant Nos. RRO2172, CA79060, CA68484, HL53392, HL04161, HL07937, HL59837, and HL70930), and Wilmot Cancer Research Fellowship of the James P. Wilmot Foundation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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