Low prevalence of cardiac siderosis in heavily iron loaded Egyptian thalassemia major patients

Abstract

Myocardial siderosis in thalassemia major remains the leading cause of death in developing countries. Once heart failure develops, the outlook is usually poor with precipitous deterioration and death. Cardiovascular magnetic resonance (CMR) can measure cardiac iron deposition directly using the magnetic relaxation time T2*. This allows earlier diagnosis and treatment and helps to reduce mortality from this cardiac affection. This study aims to determine the prevalence of cardiac siderosis in Egyptian patients who are heavily iron loaded and its relation to liver iron concentration, serum ferritin, and left ventricular ejection fraction. Eighty-nine β-thalassemia patients receiving chelation therapy (mean age of 20.8 ± 6.4 years) were recruited in this study. Tissue iron levels were determined by CMR with cardiac T2* and liver R2*. The mean ± standard deviation (range) of cardiac T2* was 28.5 ± 11.7 ms (4.3 to 53.8 ms), the left ventricular ejection fraction (LVEF) was 67.7 ± 4.7 % (55 to 78 %), and the liver iron concentration (LIC) was 26.1 ± 13.4 mg Fe/g dry weight (dw) (1.5 to 56 mg Fe/g dw). The mean serum ferritin was 4,510 ± 2,847 ng/ml (533 to 22,360 ng/ml), and in 83.2 %, the serum ferritin was >2,500 ng/ml. The prevalence of myocardial siderosis (T2* of <20 ms) was 24.7 % (mean age 20.9 ± 7.5 years), with mean T2* of 12.7 ± 4.4 ms, mean LVEF of 68.6 ±5.8 %, mean LIC of 30.9 ± 13 mg Fe/g dw, and median serum ferritin of 4,996 ng/ml. There was no correlation between T2* and age, LVEF, LIC, and serum ferritin (P = 0.65, P = 0.085, P = 0.99, and P = 0.63, respectively). Severe cardiac siderosis (T2* of <10 ms) was present in 7.9 %, with a mean age of 18.4 ± 4.4 years. Although these patients had a mean T2* of 7.8 ± 1.7 ms, the LVEF was 65.1 ± 6.2 %, and only one patient had heart failure (T2* of 4.3 ms and LVEF of 55 %). LIC and serum ferritin results were 29.8 ± 17.0 mg/g and 7,200 ± 6,950 ng/ml, respectively. In this group of severe cardiac siderosis, T2* was also not correlated to age (P = 0.5), LVEF (P = 0.14), LIC (P = 0.97), or serum ferritin (P = 0.82). There was a low prevalence of myocardial siderosis in the Egyptian thalassemia patients in spite of very high serum ferritin and high LIC. T2* is the best test that can identify at-risk patients who can be managed with optimization of their chelation therapy. The possibility of a genetic component for the resistance to cardiac iron loading in our population should be considered.

Peripheral expression of hepcidin gene in Egyptian β-thalassemia major

“…Iron overload is the main cause of morbidity and mortality among β-thalassemia major patients (El Beshlawy et al, 2014). Hepcidin, a key regulator of body iron homeostasis, is synthesized mainly from hepatocytes in the liver, it is also produced from various organs and tissues, in addition to monocytes and lymphocytes (Pinto et al, 2010).…”

“…Evaluation of cardiac siderosis using cardio-vascular magnetic resonance (CMR) relaxation time T*, T* was measured in milliseconds (ms), and liver iron concentration (LIC) measurements was measured using SDPA R2-MRI (FerriScan®) (El Beshlawy et al, 2014). Aspartate and alanine aminotransferases (AST and ALT) were measured using Integra-400 (Roche), HCV antibodies were tested using enzyme immunoassay (EIA) (COBAS-Amplicore), and estimation of serum ferritin level which was done using micro particle enzyme immunoassay (MEIA) (Abbott AxSYM System).…”

Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease

“…Yet it is clear from recent studies that the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with thalassaemia major (Voskaridou et al, 2004;Fung et al, 2007;Porter & Garbowski, 2013). Serum ferritin is a simple, widely available laboratory test that has been used to monitor iron overload in chronically transfused patients in different settings, including those with limited resources (Brittenham et al, 1993;Adamkiewicz et al, 2009;Kwiatkowski et al, 2012a;Porter & Garbowski, 2013;Ware & Kwiatkowski, 2013;El Beshlawy et al, 2014). Liver biopsy has been commonly used to monitor transfusional iron overload.…”

Cardiac Hemosiderosis in Transfusion DependentThalassemia: A Mini-Review

“…39,40 In another study, T2* was not correlated with LVEF. 26 Furthermore, LVEF was of no predictive value for either estimation of heart iron content or occurrence of clinical symptoms such as arrhythmia. 7 Conclusively, LVEF may not be a true representative of cardiac iron in TDT.…”

“…16,[26][27][28] Different indicators have been suggested as predicting factors for the rate of iron deposits within cardiomyocytes in TDT. In following sections, some of the commonly used indicators have been reviewed.…”