CARDIAC-FUNCTION, PERFUSION, AND MORBIDITY IN IRRADIATED LONG-TERM SURVIVORS OF HODGKINS-DISEASE

Purpose: The incidence of cardiotoxicity and clinical cardiac events f ollowing mantle irradiation (RT) in patients with Hodgkin's disease us ing modern techniques is controversial. The use of quantitative, progn ostically validated noninvasive tests to assess systolic and diastolic cardiac function and regional myocardial blood flow may reveal precli nical abnormalities associated with subsequent clinical events of myoc ardial infarction, cardiac death, or angina. The goals of this study a re to determine, through noninvasive measures, the presence and time c ourse of alterations in cardiac systolic and diastolic function and of relative myocardial blood how in long-term survivors of Hodgkin's dis ease, and assess their correlation with subsequent clinical cardiac en d points. Methods and Materials: Equilibrium radionuclide angiocardiog raphy (ERNA) was used to assess left ventricular (LV) systolic and dia stolic function by measuring LV ejection fraction (LVEF) and peak fill ing rate (PFR), respectively, in patients without known ischemic heart disease who received RT. Electrocardiography was performed to assess electrical cardiac function under conditions of rest and either exerci se or dipyridamole vasodilator stress. Quantitative rest/stress myocar dial perfusion imaging with thallium-201 and/or Tc-99m sestamibi was u sed to assess myocardial perfusion. Patients at least 1.0 year after R T were eligible if they were <50 years old at RT, had no known cardiac disease, and remained free of clinical recurrence of Hodgkin's diseas e. Fifty patients, ages 10.2-46.1 years (mean 26.0 +/- 8.6) at RT, wer e tested 1.1 to 29.1 years (mean 9.1 +/- 7.5) after RT. Seventeen of t hese patients were tested two times separated by 1.1 to 8.1 years. The mean central cardiac RT dose was 35.1 +/- 7.8 Gy (range 18.5-47.5) in daily 1.5-2.0 Gy fractions. Twelve patients were concomitantly irradi ated to the left ventricle, usually through partial transmission left lung shields (mean 17.0 +/- 2.2 Gy, range 14.3-21.3). Results: No pati ents had signs or symptoms of cardiac disease at the time of evaluatio n. The mean LVEF at the time of initial testing was 59.6 +/- 6.2% (n = 50; range 42-73%; normal greater than or equal to 50%), and the mean peak filling rate (PFR) was 3.46 +/- 0.88 end diastolic volumes per se cond (EDV/s) (range 1.5-5.4 EDV/s; normal greater than or equal to 2.5 4 EDV/s). The 12 patients also treated to the left ventricle had a nor mal mean ejection fraction that was lower (56.6 +/- 5.0%) than that of the other 38 patients (LVEF = 60.6 +/- 6.3%, p = 0.051) when initiall y evaluated. Average PFR was similar in the two groups. For the 15 pat ients who had repeat tests, changes in LVEF were generally modest in i ndividual patients, and there was no change in the group mean. For all patients, no significant association was found between cardiac functi on indices and age at RT, dose, or interval from RT to testing. Myocar dial perfusion scintigraphy demonstrated mild ischemia in one or more segments in two patients, and borderline normal perfusion in three pat ients. Rest and stress ECG testing demonstrated mild repolarization ab normalities in three, and one patient was abnormal at rest and had non diagnostic changes with stress. Conclusions: Patients irradiated to th e heart incidental to the treatment of Hodgkin's disease using modern techniques have generally normal measures of left ventricular function and myocardial perfusion. Modest differences in the normal left ventr icular ejection fraction observed may be attributable to the cardiac v olume irradiated. Some patients may manifest improved cardiac function as time from RT elapses, while a significant deterioration of ejectio n fraction was not observed and reduction in diastolic peak filling ra te is uncommon. The previously reported increased risk of cardiac deat h may relate to use of older techniques of RT employing higher doses a nd lack of cardiac shielding, and uncontrolled patient selection with additional behaviors and cardiac risk factors. (C) 1997 Elsevier Scien ce Inc.