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

Abstract

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 KaplanMeier 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

Management of the Thalassemias

“…A retrospective analysis in deferoxamine-treated patients found that during a period of 15 years, maintenance of serum ferritins of 2500 mg/L was associated with estimates of improved cardiac-disease-free survival (Olivieri et al 1994). These findings were confirmed in subsequent studies, with lower ferritin concentration reported to predict even longer survivals (Telfer et al 2000;Borgna-Pignatti et al 2004a;Davis et al 2004). These findings should not be interpreted to suggest, in the day-to-day management of individual patients, that serum ferritin is an accurate assessment of body iron burden, although in clinical practice serum ferritin continues to be measured, usually at 6-mo intervals.…”

Concepts and goals in the management of transfusional iron overload

“…Iron-chelation therapy benefits thalassemia major patients both by reducing the iron-loading burden, and improving established iron-induced dysfunction within the heart [6,7]. The accumulation of iron in the heart is not inevitable provided that liver iron levels are controlled at all times, however once iron has accumulated in the heart, it is removed much more slowly by chelation therapy than liver iron [7], which can lead to a lack of correlation of liver and heart iron in previously chelated patients.…”

Impact of Iron Assessment by MRI

“…Second, some patients died because cardiac symptoms and imaging evidence of ventricular dysfunction are late and ominous findings. 4 Whereas some patients could be "rescued" by continuous IV deferoxamine therapy, the process took several years and patients who refused to comply with long-term, intensive therapy (20%) died. 5 A third reason for continued cardiac mortality was that some older patients developed cardiac symptoms despite apparently adequate control of hepatic iron stores, suggesting insidious occult cardiac iron accumulation.…”