Prevention of Cardiomyopathy in Transfusion-Dependent Homozygous Thalassaemia Today and the Role of Cardiac Magnetic Resonance Imaging

Transfusion and iron chelation therapy revolutionised survival and reduced morbidity in patients with transfusion-dependent beta thalassaemia major. Despite these improvements, cardiac disease remained the most common cause of death in those patients. Recently the ability to determine the degree of cardiac iron overload, through cardiac magnetic resonance imaging (CMR) has allowed more logical approaches to iron removal, particularly from the heart. The availability of two oral chelators, deferiprone and deferasirox has reduced the need for the injectable chelator deferrioxamine and an additional benefit has been that deferiprone has been shown to be more cardioprotective than deferrioxamine. This review on the prevention of cardiac disease makes recommendations on the chelation regime that would be desirable for patients according to their cardiac iron status as determined by CMR determined by CMR. It also discusses approaches to chelation management should CMR not be available

Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload

<p>Abstract</p> <p>Background</p> <p>Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs.</p> <p>Methods</p> <p>In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment.</p> <p>Results</p> <p>From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p = 0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p = 0.001). This was associated with a 27% increase in T2* (p < 0.001) and 3.1% increase in LVEF (p < 0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p = 0.38), or RVEF (70.0 to 69.9%, p = 0.93) whereas the T2* increased by 13% (p < 0.001), but with no change in LVEF (0.32%; p = 0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p = 0.014) and 1.16% for RVEF (p = 0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p < 0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p = 0.012).</p> <p>Conclusion</p> <p>In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.</p

Thalassemia intermedia today: should patients regularly receive transfusions?

BACKGROUND: beta-Thalassemia is an inherited hemoglobin disorder characterized by reduced synthesis of beta-globin chain. The severity of clinical course distinguishes this heterogeneous disease in two main subtypes: thalassemia major (TM) and thalassemia intermedia (TI). TI has a later clinical onset with a milder anemia that does not require transfusions at least during the first few years of life. The clinical picture of TI patients who have not received transfusions or have occasionally received transfusions is dominated by the consequences of chronic hemolytic anemia, tissue hypoxia, and their compensatory reactions, such as bone deformities and fractures, extramedullary hemopoiesis, spleen and liver enlargement, hypercoagulability, and pulmonary hypertension. These complications, especially the latter two, are getting more frequent and severe over the years. Nowadays, although TI patients have almost no changes in the course of the disease, well-treated TM patients with regular transfusion-chelation therapy showed suppression of the anemia-related disorders in parallel to prolongation of life. The new oral iron chelators and the magnetic resonance imaging application for early detection of heart iron load are promising for further improvement on survival. CONCLUSIONS: Considering the current cost-benefit balance of regular treatment in TM as well as the frequency and severity of complications in TI, it seems that the majority of TI patients will be benefited if this kind of treatment is applied targeting prevention and not palliation of the anemia-induced complications

Comparison of echocardiographic (US) volumetry with cardiac magnetic resonance (CMR) imaging in transfusion dependent thalassemia major (TM)

Abstract Background Despite advances in survival in patients with thalassemia major (TM) the most common cause of death is cardiac disease. Regular cardiac follow-up is imperative in order to identify and reverse pathology. Cardiac Magnetic Resonance (CMR) and Echocardiography (US) are applied in parallel to TM patients for cardiac evaluation and ongoing monitoring. A comparison between mutual features would be useful in order to assess the accuracy and reliability of the two methods, with a particular focus on routine US application. TM's special attributes offer an excellent opportunity for cardiac imaging research that has universal general purpose applications. Methods 135 TM patients underwent US (Teichholz's M-mode formula – rapidly accessible means of measuring volumes and ejection fraction) and CMR volumetry. Paired-samples t-test, Passing & Badlock regression and Bland & Altman plot were used while comparing the common parameters between the CMR and the US. Results We found that the US volumes were underestimated, especially the end-diastolic volume (p Conclusion In cases where cardiac wall movement abnormalities are absent, the US Teichholz's M-mode formula for volume measurements, though less sophisticated in comparison to the high resolution CMR technique, offers an adequate ejection fraction estimation for routine use, especially when monitoring gross alterations in cardiac function over time, and is easy to perform.</p

Histological features from an autopsy from a 29 yr old male thalassaemia patient who died of congestive cardiac failure

<p><b>Copyright information:</b></p><p>Taken from "The heart in transfusion dependent homozygous thalassaemia today – prediction, prevention and management"</p><p></p><p>European Journal of Haematology 2008;80(2):93-106.</p><p>Published online Jan 2008</p><p>PMCID:PMC2253710.</p><p>© 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard</p> Histology shows individual myocyte hypertrophy with multiple deposits of brown granular material within the cytoplasm of the myocytes. These granules stain positive with Prussian blue, confirming heavy myocardial iron deposition

A 30 yr old female thalassaemia patient 2-D four chamber view with the presence of an apical thrombus

<p><b>Copyright information:</b></p><p>Taken from "The heart in transfusion dependent homozygous thalassaemia today – prediction, prevention and management"</p><p></p><p>European Journal of Haematology 2008;80(2):93-106.</p><p>Published online Jan 2008</p><p>PMCID:PMC2253710.</p><p>© 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard</p

Acute brucellosis: presentation, diagnosis, and treatment of 144 cases

Objectives: Brucellosis, whether in an endemic region or not, remains a diagnostic puzzle due to occasional misleading unusual presentations and non-specific symptoms. Presented herein is our 14-year experience with acute brucellosis at Sparta General Hospital, Lakonia, Greece. Methods: A case series of 144 patients admitted to the internal medicine, pediatrics, and urology departments, through evaluation of history, occupational data, serological. tests, cultures of blood and other body fluids, and imaging studies. Patients were treated with a 21-day course of intramuscular streptomycin and a prolonged two-month course of doxycycline with a six-month follow-up. Results: Infected patients had a relevant occupational history in fewer than 20% of cases. Clinical manifestations included non-specific symptoms (fever, malaise, sweats, arthralgias, lower back pain, headache), findings such as splenomegaly (51%), osteoarticular involvement (42%), cervical lymphadenitis (31%), hepatomegaly (25%), genitourinary involvement (13% of men), chotecystitis (2%), breast abscess (0.7%), and acute abdomen (0.7%). Ninety-five percent of the patients had a serotogical titer &gt;= 1/160 with culture-proven brucellosis. Overall, 82% of blood cultures and 100% of other body fluid cultures (synovial, bite) were positive. Ninety-seven percent of the patients were cured. Relapse in the follow-up period was observed in four patients who had not complied with treatment. Conclusions: Brucellosis is an infection with multiple presentations, and whether in an endemic region or not, a thorough history of exposure and clinical. suspicion are required since thresholds in serological evaluation may lead to misdiagnosis and withholding of adequate treatment. (c) 2006 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved