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Dudley J Pennell - One of the best experts on this subject based on the ideXlab platform.
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randomized controlled trials of iron chelators for the treatment of cardiac Siderosis in thalassaemia major
Frontiers in Pharmacology, 2014Co-Authors: John A Baksi, Dudley J PennellAbstract:In conditions requiring repeated blood transfusion or where iron metabolism is abnormal, heart failure may result from accumulation of iron in the heart (cardiac Siderosis). Death due to heart failure from cardiac iron overload has accounted for considerable early mortality in β-thalassemia major. The ability to detect iron loading in the heart by cardiovascular magnetic resonance using T2* sequences has created an opportunity to intervene in the natural history of such conditions. However, effective and well tolerated therapy is required to remove iron from the heart. There are currently three approved commercially available iron chelators: deferoxamine, deferiprone and deferasirox. We review the high quality randomized controlled trials in this area for iron chelation therapy in the management of cardiac Siderosis.
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low prevalence of cardiac Siderosis in heavily iron loaded egyptian thalassemia major patients
Annals of Hematology, 2014Co-Authors: Amal El Beshlawy, Mona El Tagui, Mona Hamdy, Mona El Ghamrawy, Khaled Abdel Azim, Doria Salem, Fadwa Said, Ahmed Samir, Timothy G St Pierre, Dudley J PennellAbstract: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.
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on myocardial Siderosis and left ventricular dysfunction in hemochromatosis
Journal of Cardiovascular Magnetic Resonance, 2013Co-Authors: John Paul Carpenter, Agata Grasso, John B Porter, Farrukh Shah, James S Dooley, Dudley J PennellAbstract:Chronically increased intestinal iron uptake in genetic hemochromatosis (HC) may cause organ failure. Whilst iron loading from blood transfusions may cause dilated cardiomyopathy in conditions such as thalassemia, the in-vivo prevalence of myocardial Siderosis in HC is unclear, and its relation to left ventricular (LV) dysfunction is controversial. Most previous data on myocardial Siderosis in HC has come from post-mortem studies. Cardiovascular magnetic resonance (CMR) was performed at first presentation of 41 HC patients (58.9 ±14.1 years) to measure myocardial iron and left ventricular (LV) ejection fraction (EF). In 31 patients (genetically confirmed HFE-HC), the HFE genotype was C282Y/C282Y (n = 30) and C282Y/H63D (n = 1). Patients with other genotypes (n = 10) were labeled genetically unconfirmed HC. Of the genetically confirmed HFE-HC patients, 6 (19%) had myocardial Siderosis (T2* 1000 μg/L, and was the commonest cause of reduced LVEF. Heart failure due to myocardial Siderosis was only found in these HFE-HC patients, and was reversible with venesection. Myocardial iron was normal in patients with other causes of LV dysfunction.
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effects of combined deferiprone with deferoxamine on right ventricular function in thalassaemia major
Journal of Cardiovascular Magnetic Resonance, 2012Co-Authors: Francisco Alpendurada, Mark A Tanner, Gill Smith, John Paul Carpenter, Sunil V Nair, Winston Banya, Carlo Dessi, John Malcolm Walker, Dudley J PennellAbstract:Background: Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR). Methods: We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac Siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading. Results: In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac Siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01). Conclusions: In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac Siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac Siderosis.
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combined chelation therapy in thalassemia major for the treatment of severe myocardial Siderosis with left ventricular dysfunction
Journal of Cardiovascular Magnetic Resonance, 2008Co-Authors: Mark A Tanner, Mark Westwood, Gillian C Smith, Sunil V Nair, Carlo Dessi, Annalisa Agus, Martina Pibiri, Malcolm J Walker, Dudley J PennellAbstract:Background In thalassemia major (TM), severe cardiac Siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial Siderosis, but has not been prospectively examined in severe myocardial Siderosis.
Neeraj Kumar - One of the best experts on this subject based on the ideXlab platform.
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acquired progressive ataxia and palatal tremor importance of mri evidence of hemosiderin deposition and vascular malformations
Parkinsonism & Related Disorders, 2011Co-Authors: Neeraj Kumar, Margherita Milone, Scott D Z Eggers, Mark B KeeganAbstract:Abstract Oculopalatal tremor is frequently accompanied by progressive ataxia. In symptomatic oculopalatal tremor the ataxia frequently is delayed in onset. Progressive ataxia is a defining clinical feature of superficial Siderosis. We report 5 cases with palatal tremor and ataxia. Four cases had evidence of intraparenchymal hemosiderin deposition on T2-gradient-echo imaging. Three cases had a brainstem vascular malformation. In two cases the hemosiderin deposition was likely due to prior trauma. The significance of these associations and possible similarities between ataxia related to superficial Siderosis and ataxia and intraparenchymal hemosiderin is discussed.
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a unifying hypothesis for a patient with superficial Siderosis low pressure headache intraspinal cyst back pain and prominent vascularity case report
Journal of Neurosurgery, 2010Co-Authors: Neeraj Kumar, Gary M Miller, David G Piepgras, Bahram MokriAbstract:A source of bleeding is often not evident during the evaluation of patients with superficial Siderosis of the CNS despite extensive imaging. An intraspinal fluid-filled collection of variable dimensions is frequently observed on spine MR imaging in patients with idiopathic superficial Siderosis. A similar finding has also been reported in patients with idiopathic intracranial hypotension. The authors report on a patient with superficial Siderosis and a longitudinally extensive intraspinal fluid-filled collection secondary to a dural tear. The patient had a history of low-pressure headaches. His spine MR imaging and spine CT suggested the possibility of an underlying vascular malformation, but none was found on angiography. Repair of the dural tear resulted in resolution of the intraspinal fluid collection and CSF abnormalities. The significance of the association between superficial Siderosis and idiopathic intracranial hypotension, and potential therapeutic and pathophysiological implications, are the su...
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a unifying hypothesis for a patient with superficial Siderosis low pressure headache intraspinal cyst back pain and prominent vascularity
Journal of Neurosurgery, 2010Co-Authors: Neeraj Kumar, Gary M Miller, David G Piepgras, Bahram MokriAbstract:A source of bleeding is often not evident during the evaluation of patients with superficial Siderosis of the CNS despite extensive imaging. An intraspinal fluid-filled collection of variable dimensions is frequently observed on spine MR imaging in patients with idiopathic superficial Siderosis. A similar finding has also been reported in patients with idiopathic intracranial hypotension. The authors report on a patient with superficial Siderosis and a longitudinally extensive intraspinal fluid-filled collection secondary to a dural tear. The patient had a history of low-pressure headaches. His spine MR imaging and spine CT suggested the possibility of an underlying vascular malformation, but none was found on angiography. Repair of the dural tear resulted in resolution of the intraspinal fluid collection and CSF abnormalities. The significance of the association between superficial Siderosis and idiopathic intracranial hypotension, and potential therapeutic and pathophysiological implications, are the subject of this report.
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superficial Siderosis associations and therapeutic implications
JAMA Neurology, 2007Co-Authors: Neeraj KumarAbstract:Superficial Siderosis of the central nervous system results from hemosiderin deposition in the subpial layers of the brain and spinal cord. A clinical history of subarachnoid hemorrhage is often absent. Patients present with slowly progressive gait ataxia and sensorineural hearing impairment. A history of prior intradural surgery or trauma is common. With widespread use of magnetic resonance imaging, presymptomatic cases are being diagnosed and it is difficult to be certain about the true incidence of this disorder. Despite extensive investigations, the cause of bleeding is often not apparent. An intraspinal fluid–filled collection is a common accompaniment and may be the likely bleeding source. An early diagnosis and prompt intervention directed at removal of the bleeding source may prevent progression. This review discusses the role of multimodality imaging in evaluation of superficial Siderosis and the therapeutic implications of identified associations.
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unusual neuroimaging in superficial Siderosis
Neurology, 2005Co-Authors: J A Wilden, H R Murali, Paul E Lindell, Neeraj Kumar, Dudley H. DavisAbstract:Superficial CNS Siderosis from bleeding into the subarachnoid space causes sensorineural hearing loss and cerebellar ataxia.1 Spinal origins of superficial Siderosis are rare but can include nerve root pathology.2 A 42-year-old man presented with an 8-year history of gait difficulty, dysarthria, and hearing loss. Past history was remarkable for a motor vehicle accident at age 10. Abnormalities on neurologic examination included decreased hearing, dysarthria, positive Babinski, and a wide-based …
Bahram Mokri - One of the best experts on this subject based on the ideXlab platform.
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a unifying hypothesis for a patient with superficial Siderosis low pressure headache intraspinal cyst back pain and prominent vascularity case report
Journal of Neurosurgery, 2010Co-Authors: Neeraj Kumar, Gary M Miller, David G Piepgras, Bahram MokriAbstract:A source of bleeding is often not evident during the evaluation of patients with superficial Siderosis of the CNS despite extensive imaging. An intraspinal fluid-filled collection of variable dimensions is frequently observed on spine MR imaging in patients with idiopathic superficial Siderosis. A similar finding has also been reported in patients with idiopathic intracranial hypotension. The authors report on a patient with superficial Siderosis and a longitudinally extensive intraspinal fluid-filled collection secondary to a dural tear. The patient had a history of low-pressure headaches. His spine MR imaging and spine CT suggested the possibility of an underlying vascular malformation, but none was found on angiography. Repair of the dural tear resulted in resolution of the intraspinal fluid collection and CSF abnormalities. The significance of the association between superficial Siderosis and idiopathic intracranial hypotension, and potential therapeutic and pathophysiological implications, are the su...
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a unifying hypothesis for a patient with superficial Siderosis low pressure headache intraspinal cyst back pain and prominent vascularity
Journal of Neurosurgery, 2010Co-Authors: Neeraj Kumar, Gary M Miller, David G Piepgras, Bahram MokriAbstract:A source of bleeding is often not evident during the evaluation of patients with superficial Siderosis of the CNS despite extensive imaging. An intraspinal fluid-filled collection of variable dimensions is frequently observed on spine MR imaging in patients with idiopathic superficial Siderosis. A similar finding has also been reported in patients with idiopathic intracranial hypotension. The authors report on a patient with superficial Siderosis and a longitudinally extensive intraspinal fluid-filled collection secondary to a dural tear. The patient had a history of low-pressure headaches. His spine MR imaging and spine CT suggested the possibility of an underlying vascular malformation, but none was found on angiography. Repair of the dural tear resulted in resolution of the intraspinal fluid collection and CSF abnormalities. The significance of the association between superficial Siderosis and idiopathic intracranial hypotension, and potential therapeutic and pathophysiological implications, are the subject of this report.
Mark Westwood - One of the best experts on this subject based on the ideXlab platform.
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combined chelation therapy in thalassemia major for the treatment of severe myocardial Siderosis with left ventricular dysfunction
Journal of Cardiovascular Magnetic Resonance, 2008Co-Authors: Mark A Tanner, Mark Westwood, Sunil V Nair, Carlo Dessi, Annalisa Agus, Martina Pibiri, Malcolm J Walker, Renzo Galanello, Gillian Smith, Dudley J PennellAbstract:In thalassemia major (TM), severe cardiac Siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial Siderosis, but has not been prospectively examined in severe myocardial Siderosis. T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial Siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up. At baseline, deferoxamine was prescribed at 38 ± 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 ± 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 ± 0.98 ms to 7.9 ± 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 ± 10.9% to 65.6 ± 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) μg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 ± 2.9 ms to 10.8 ± 7.3 ms; p = 0.006). In patients with severe myocardial Siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans. This trial is registered as NCT00103753
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combined chelation therapy in thalassemia major for the treatment of severe myocardial Siderosis with left ventricular dysfunction
Journal of Cardiovascular Magnetic Resonance, 2008Co-Authors: Mark A Tanner, Mark Westwood, Gillian C Smith, Sunil V Nair, Carlo Dessi, Annalisa Agus, Martina Pibiri, Malcolm J Walker, Dudley J PennellAbstract:Background In thalassemia major (TM), severe cardiac Siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial Siderosis, but has not been prospectively examined in severe myocardial Siderosis.
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randomized controlled trial of deferiprone or deferoxamine in beta thalassemia major patients with asymptomatic myocardial Siderosis
Blood, 2006Co-Authors: Dudley J Pennell, Vasili Berdoukas, Vasili Ladis, Athanassios Aessopos, Efstathios D Gotsis, Mark A Tanner, Gill Smith, M Karagiorga, Antonio Piga, Mark WestwoodAbstract:Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial Siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial Siderosis (myocardial T2*) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% ± 5.3% and 93% ± 9.7% ( P = .81), respectively. The improvement in myocardial T2* was significantly greater for deferiprone than deferoxamine (27% vs 13%; P = .023). Left ventricular ejection fraction increased significantly more in the deferiprone-treated group (3.1% vs 0.3% absolute units; P = .003). The changes in liver iron level (-0.93 mg/g dry weight vs -1.54 mg/g dry weight; P = .40) and serum ferritin level (-181 μg/L vs -466 μg/L; P = .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial Siderosis in beta-thalassemia major.
Mark A Tanner - One of the best experts on this subject based on the ideXlab platform.
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effects of combined deferiprone with deferoxamine on right ventricular function in thalassaemia major
Journal of Cardiovascular Magnetic Resonance, 2012Co-Authors: Francisco Alpendurada, Mark A Tanner, Gill Smith, John Paul Carpenter, Sunil V Nair, Winston Banya, Carlo Dessi, John Malcolm Walker, Dudley J PennellAbstract:Background: Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR). Methods: We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac Siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading. Results: In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac Siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01). Conclusions: In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac Siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac Siderosis.
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combined chelation therapy in thalassemia major for the treatment of severe myocardial Siderosis with left ventricular dysfunction
Journal of Cardiovascular Magnetic Resonance, 2008Co-Authors: Mark A Tanner, Mark Westwood, Gillian C Smith, Sunil V Nair, Carlo Dessi, Annalisa Agus, Martina Pibiri, Malcolm J Walker, Dudley J PennellAbstract:Background In thalassemia major (TM), severe cardiac Siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial Siderosis, but has not been prospectively examined in severe myocardial Siderosis.
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combined chelation therapy in thalassemia major for the treatment of severe myocardial Siderosis with left ventricular dysfunction
Journal of Cardiovascular Magnetic Resonance, 2008Co-Authors: Mark A Tanner, Mark Westwood, Sunil V Nair, Carlo Dessi, Annalisa Agus, Martina Pibiri, Malcolm J Walker, Renzo Galanello, Gillian Smith, Dudley J PennellAbstract:In thalassemia major (TM), severe cardiac Siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial Siderosis, but has not been prospectively examined in severe myocardial Siderosis. T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial Siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up. At baseline, deferoxamine was prescribed at 38 ± 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 ± 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 ± 0.98 ms to 7.9 ± 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 ± 10.9% to 65.6 ± 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) μg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 ± 2.9 ms to 10.8 ± 7.3 ms; p = 0.006). In patients with severe myocardial Siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans. This trial is registered as NCT00103753
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randomized controlled trial of deferiprone or deferoxamine in beta thalassemia major patients with asymptomatic myocardial Siderosis
Blood, 2006Co-Authors: Dudley J Pennell, Vasili Berdoukas, Vasili Ladis, Athanassios Aessopos, Efstathios D Gotsis, Mark A Tanner, Gill Smith, M Karagiorga, Antonio Piga, Mark WestwoodAbstract:Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial Siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial Siderosis (myocardial T2*) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% ± 5.3% and 93% ± 9.7% ( P = .81), respectively. The improvement in myocardial T2* was significantly greater for deferiprone than deferoxamine (27% vs 13%; P = .023). Left ventricular ejection fraction increased significantly more in the deferiprone-treated group (3.1% vs 0.3% absolute units; P = .003). The changes in liver iron level (-0.93 mg/g dry weight vs -1.54 mg/g dry weight; P = .40) and serum ferritin level (-181 μg/L vs -466 μg/L; P = .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial Siderosis in beta-thalassemia major.
