Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major

Regular monitoring of left ventricular ejection fraction (LVEF) for thalassemia major is widely practiced, but its informativeness for iron chelation treatment is unclear. Eighty-one patients with thalassemia major but no history of cardiac disease underwent quantitative annual LVEF monitoring by radionuclide ventriculography for a median of 6.0 years (interquartile range, 2-12 years). Intraobserver and interobserver reproducibility for LVEF determination were both less than 3%. LVEF values before and after transfusion did not differ, and exercise stress testing did not reliably expose underlying cardiomyopathy. An absolute LVEF of less than 45% or a decrease of more than 10 percentage units was significantly associated with subsequent development of symptomatic cardiac disease (P <.001) and death (P =.001), with a median interval between the first abnormal LVEF findings and the development of symptomatic heart disease of 3.5 years, allowing time for intervention. In 34 patients in whom LVEF was less than 45% or decreased by more than 10 percentage units, intensified chelation therapy was recommended (21 with subcutaneous and 13 with intravenous deferoxamine). All 27 patients who complied with intensification survived, whereas the 7 who did not comply died (P <.0001). The Kaplan-Meier estimate of survival beyond 40 years of age for all 81 patients is 83%. Sequential quantitative monitoring of LVEF is valuable for assessing cardiac risk and for identifying patients with thalassemia major who require intensified chelation therapy.