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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2973-2978.
Prepublished online as a Blood First Edition Paper on July 23, 2008; DOI 10.1182/blood-2008-04-148767.
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Submitted April 10, 2008
Accepted July 3, 2008
Longitudinal analysis of heart and liver iron in thalassemia major
Leila J Noetzli, Susan M Carson, Anne S Nord, Thomas D Coates, and John C Wood*
Department of Pediatrics, Division of Cardiology, Childrens Hospital Los Angeles, Los Angeles, CA, United States
Department of Pediatrics, Division of Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles, CA, United States
Department of Radiology, Childrens Hospital Los Angeles, Los Angeles, CA, United States
* Corresponding author; email: jwood{at}chla.usc.edu.
High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated MRI techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared to one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time-lag correlated with initial HIC (r =0.47, p<0.003) and initial cardiac R2* (r = 0.57, p< 0.0002), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.
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