Lack of clinically significant cardiac dysfunction during intermediate dobutamine doses in long-term childhood cancer survivors exposed to anthracyclines

Background Long-term survivors of childhood cancer treated with anthracycli nes may have subclinical cardiac dysfunction undetectable at a baseline eva luation. Dobutamine stress echocardiography has been proposed as a more sen sitive screening test but results of previous studies were influenced by se lection criteria, infusion protocols, and side effects. Methods We applied a modified dobutamine stress test (from 5 to 10 to 15 mu g/kg, infused over a 5-minute period) and evaluated the influence on stres s test results of reported risk factors for late cardiac toxicity (female s ex, younger age at treatment, higher dose of anthracycline, and longer dura tion of follow-up). Seventy-one patients (46 male, mean age 15 +/- 5 years) treated with anthracyclines (median dose 240 mg/m(2)) 1 to 16.5 years befo re and 20 controls (patients' siblings: 12 male, mean age 19 +/- 4 years) w ere studied. Results No major side effects were recorded. One patient was unable to perf orm the test because of anxiety. Limiting side effects were infrequent (3%) and occurred at a dobutamine dose of greater than or equal to 10 mu g/kg, when significant changes of hemodynamic and echocardiographic parameters we re detectable in all cases. Rest systolic and mean blood pressure and left ventricular fractional shortening were significantly lower in patients than in controls (P <.05), but no differences were found in any of the other in dexes of cardiac function between the 2 groups at rest and during each dobu tamine infusion step. A similar increase of global left ventricular functio n (percent of fractional shortening +45% vs +32%) and a decrease of end-sys tolic stress (-33% vs -29%) were documented. Left ventricular relaxation, e arly filling, and both relaxation and compliance improved. In all but one p atient with reduced global left ventricular function at baseline, time-depe ndent patterns of hemodynamic and echocardiographic responses to dobutamine were similar. Previously described risk factors for cardiac toxicity did n ot influence the time changes of the echocardiographic parameters in respon se to dobutamine. Conclusions Compared with controls, most of our asymptomatic childhood canc er survivors, studied an average of 7 years after treatment with anthracycl ines, showed normal baseline cardiac function. Our stress test was feasible and safe. Compared with modalities used in other studies, shorter infusion periods with higher dobutamine doses allowed a higher stress intensity to be reached without reducing patient compliance. At dobutamine stress test t he response was comparable in patients and controls except for one patient. Previously reported risk factors for cardiac toxicity had no significant i nfluence on stress test results.