Prevalence and distribution of iron overload in patients with transfusion‐dependent anemias differs across geographic regions: results from the CORDELIA study

Abstract

Objectives: The randomized comparison of deferasirox to deferoxamine for myocardial iron removal in patients with transfusion-dependent anemias (CORDELIA) gave the opportunity to assess relative prevalence and body distribution of iron overload in screened patients. Methods: Patients aged ≥10 yr with transfusion-dependent anemias from 11 countries were screened. Data were summarized descriptively, overall and across regions. Results: Among 925 patients (99.1% with b-thalassemia major; 98.5% receiving prior chelation; mean age 19.2 yr), 36.7% had myocardial iron overload (myocardial T2* ≤20 ms), 12.1% had low left ventricular ejection fraction. Liver iron concentration (LIC) (mean 25.8 mg Fe/ g dw) and serum ferritin (median 3702 ng/mL) were high. Fewer patients in the Middle East (ME; 28.5%) had myocardial T2* ≤20 ms vs. patients in the West (45.9%) and Far East (FE, 40.9%). Patients in the West had highest myocardial iron burden, but lowest LIC (26.9% with LIC <7 mg Fe/g dw) and serum ferritin. Among patients with normal myocardial iron, a higher proportion of patients from the ME and FE had LIC ≥15 than <7 mg Fe/g dw (ME, 56.7% vs. 17.2%; FE, 78.6% vs. 7.8%, respectively), a trend which was less evident in the West (44.6% vs. 33.9%, respectively). Transfusion and chelation practices differed between regions. Conclusions: Evidence of substantial myocardial and liver iron burden across regions revealed a need for optimization of effective, convenient iron chelation regimens. Significant regional variation exists in myocardial and liver iron loading that are not well explained; improved understanding of factors contributing to differences in body iron distribution may be of clinical benefit.

Serum ferritin in the diagnosis of cardiac and liver iron overload in thalassaemia patients real‐world practice: a multicentre study

“…In our study the comparable cut‐off values were 2071, 1710 and 835 μg/l, respectively, higher than those reported by Vitrano et al (). These results may be due to geographical differences, similar to the higher threshold for development of CIO in the Far East population described earlier (Aydinok et al , ), although not to the same extent because the mechanism of CIO is more directly related to non‐transferrin‐bound iron levels.…”

Long‐term improvement in cardiac magnetic resonance in β‐thalassemia major patients treated with deferasirox extends to patients with abnormal baseline cardiac function

“…A portion of our patients which experienced significant increase of LVEF at the follow up had no cardiac iron overload, as expressed by a T2* value persistently >20 msec. This finding concurs with data from a wide MRI screening for prevalence and distribution of iron overload, assessing around 1000 TM patients, and reporting 8% of subjects with cardiac T2* >20 msec had pathological LVEF …”

“…Mortality from cardiac disease, however, started showing a decline in the past decade owing to advances in non‐invasive monitoring with cardiac magnetic resonance (CMR) T2* imaging and the availability of iron chelators which can effectively remove excess iron from the heart . Nevertheless, about half of patients with TM in the West continue to have cardiac iron overload which is associated with increased likelihood of heart failure and mortality …”

A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major

“…Monotherapy or combination therapies with iron chelators may not be sufficient to remove iron deposits in the tissue especially in the heart and vessels. Iron deposits are able to raise the oxidative stress and initiate inflammation within cardiomyocytes which can eventually lead to heart failure, cardiomyopathy, and arrhythmia . Studies have provided evidence for role of L‐type calcium channels in iron uptaking by cardiomyocytes .…”