Pancreatic iron loading predicts cardiac iron loading in thalassemia major

Abstract

Diabetes mellitus and cardiomyopathy are common in chronically transfused thalassemia major patients, occurring in the second and third decades of life. We postulated that pancreatic iron deposition would precede cardiac iron loading, representing an environment favorable for extrahepatic iron deposition. To test this hypothesis, we examined pancreatic and cardiac iron in 131 thalassemia major patients over a 4-year period. Cardiac iron (R2* > 50 Hz) was detected in 37.7% of patients and pancreatic iron (R2* > 28 Hz) in 80.4% of patients. Pancreatic and cardiac R2* were correlated (r 2 ‫؍‬ 0.52), with significant pancreatic iron occurring nearly a decade earlier than cardiac iron. A pancreatic R2* less than 100 Hz was a powerful negative predictor of cardiac iron, and pancreatic R2* more than 100 Hz had a positive predictive value of more than 60%. In serial analysis, changes in cardiac iron were correlated with changes in pancreatic iron (r 2 ‫؍‬ 0.33, IntroductionIron overload is common in chronically transfused thalassemia major (TM) patients. Liver iron is a surrogate for total body iron burden 1 and has been used for years to monitor chelation therapy in thalassemia patients. 2 Liver iron quantification by magnetic resonance imaging (MRI) is well validated and becoming increasingly routine at major thalassemia centers. 3 It is also now possible to directly image preclinical iron deposition in heart tissue and endocrine glands. 4,5 Extrahepatic tissues have different kinetics of iron uptake and clearance than the liver 6,7 because they selectively, or near selectively, load circulating non-transferrin-bound iron (NTBI). 8 As a result, cardiac iron accumulation exhibits threshold behavior with respect to liver iron concentration 9 and is quite sensitive to the duration of iron chelation therapy. 10 In contrast, the liver is the dominant storage depot for transferrin-mediated iron uptake and fluctuates proportionally to global iron balance. 11 As a result, cross-sectional correlations between heart and liver iron loading are poor 5,12 and longitudinal relationships exhibit complicated, highly nonlinear behaviors. 7 More importantly, dangerous heart iron accumulation and cardiac dysfunction can occur despite apparently superb control of liver iron during prospective longitudinal evaluation. 7,13 These observations demonstrate that iron chelation therapy sufficient for neutral or negative liver iron balance may be inadequate to protect the heart in some patients.Because the heart and pancreas predominantly load NTBI, iron burdens in these organs should be more closely correlated to one another than between the heart and the liver. 8 Recent work by Au et al 4 and by our laboratory 14 supports this hypothesis. Because glucose intolerance/diabetes are common comorbidities with cardiac dysfunction, 11,15 we postulated that pancreatic iron uptake might predict cardiac iron deposition in a clinically useful manner. To test this hypothesis, we compared pancreatic, hepatic, and cardiac iron loading in 131 patients with...

Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age

“…In our experience, cardiac iron is not observed when pancreatic iron is normal, and a pancreatic R Ã 2 >27 Hz predicts future cardiac iron loading [10]. Except in DBA and CDA, there was no significant change in the median pancreatic R Ã 2 in the other disease groups between the first and subsequent studies, indicating that the pancreas did not load iron in those patients, or cleared it, possibly related to the efficacy of the chelation.…”

Impact of Iron Assessment by MRI

“…For inaccessible organs such as the pituitary and pancreas glands, absolute iron concentrations may never be derived; however, the R2 and R2* values associated with glandular dysfunction and destruction are under investigation. [25][26][27][28] Although most 1.5 Tesla magnets are intrinsically able to perform iron estimation measurements, specialized software and local expertise/training are required for accurate assessment. As a result, some centers have chosen to purchase commercial software or outsource their image analysis to fee-for-service vendors rather than commit the resources to obtain the measurements themselves.…”

Exercise performance in thalassemia major: Correlation with cardiac iron burden

“…Pancreatic iron levels were severely elevated at 395 Hz (> 27 Hz is abnormal), consistent with significant extrahepatic iron deposition [20]. Cardiac iron overload (cardiac R2* > 50 Hz) was common (59%) with a mean cardiac R2* of 97.3 Hz.…”