On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure
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RESEARCH
Open Access
On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure DJ Pennell1,2*, JP Carpenter1,2, M Roughton3 and ZI Cabantchik4
Abstract Background: Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in betathalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods: This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM). Results: A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001). Conclusion: These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.
Background Major advances have been made in the last 10 years in the understanding and treatment of cardiac siderosis in beta-thalassaemia major (TM) patients. Those advances are attributable primarily to the development of a method for the quantification of myocardial iron based on magnetic resonance T2* imaging and its worldwide adoption,[1,2] which has permitted the recognition of the high prevalence of cardiac siderosis in patients chronically treated with deferoxamine, [1,3,4]the establishment of the association of cardiac siderosis with impaired left ventricular ejection fraction (LVEF) [1,5-7] the identification of iron-chelation regimes which are * Correspondence: [email protected] 1 Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London UK Full list of author information is available at the end of the article
effective in removal of iron from the heart [8-12] and the reduction in cardiac mortality in populations[13-15]. Studies reporting on the use of iron chelators in treating transfusional iron overload have raised interesting questions with regard to cardiac efficacy relating to changes in the mean LVEF of the TM cohorts under
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