Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease.

PURPOSE: a) To assess the age-related incidence of morbid cardiac events including cardiac death (CD), nonfatal myocardial infarction (MI), and angina pectoris (AP) in all patients treated for Hodgkin's disease at a single institution; b) to examine the prevalence of cardiac risk factors and presence of coronary artery disease (CAD) in affected patients. METHODS AND MATERIALS: 475 patients were treated for Hodgkin's disease in our institution between 1954 and 1989. The status of 97% of the cohort was established either by patient visit and examination in 1992-1993, personal telephone contact, or documentation of death. The 326 of these patients who had mantle irradiation (RT) and survived 3 years formed the study population. Patients who experienced AP, MI, or CD secondary to CAD were assessed for the presence of specific cardiac risk factors. Cardiac catheterization and necropsy data were reviewed to determine the presence and degree of coronary artery stenosis.
RESULTS: Eighteen of 326 patients (5.5%) have had a morbid cardiac event directly related to CAD. Seven patients had CD. Seven patients experienced nonfatal MI, and four patients had AP. The mean interval from RT to morbid cardiac event was 13.1 years (range: 4.4-27.0), and the mean age at the time of the event was 39.4 years (range: 24-65). Four of these patients had morbid cardiac events between ages 24-29 years. Based on US statistics of CD secondary to MI, the relative risk of CD for the treated group was 2.8 (3.1 for males and 1.8 for females). Remarkably, no difference was found in the risk of experiencing a morbid cardiac endpoint in patients stratified by either decile of age at which RT was given, or by duration of follow-up. Only one patient experiencing an event (AP) had received an anthracycline. The mean RT dose to the central cardiac volume for the affected patients was 44.3 Gy (range: 35-60.4). Autopsy or catheterization data were available on 15 patients and revealed 90-100% stenosis of at least one major vessel in 11 patients (73%), and no single artery was more commonly stenosed. Specifically, the left anterior descending and right coronary arteries were each greater than or equal to 60% stenosed in 10 out of 15 patients (67%), and either the left main or circumflex arteries were greater than or equal to 50% stenosed in 5 out of 15 patients (33%); triple vessel disease was present in seven patients. Risk factor data were available on all patients experiencing morbid cardiac events: 72% smoked, 72% were male, 78% had hypercholesterolemia, 61% were obese, 28% had a positive family history, 33% had hypertension, and 6% (one) had diabetes. The average number of risk factors per patient was 2.9; seven patients had at least four risk factors, and all patients had at least one risk factor. This frequency of risk factors is elevated when compared to the US population.
CONCLUSIONS: In our institution, 5.5% of patients treated for Hodgkin's disease experienced a morbid cardiac event following RT to the central cardiac volume. The doses given were greater than commonly used today. Some patients experienced events at a young age, and the likelihood of experiencing CD was increased compared to the general population. This observation is consistent with RT as an additional risk factor in the induction of morbid cardiac events. Appropriate cardiac shielding and radiation doses, careful follow-up, which includes monitoring of cardiac function, and a preventative program of sensible dietary habits, exercise, and nonsmoking may be beneficial in reducing cardiac morbidity in long-term survivors of Hodgkin's disease.