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Journal of Cardiovascular Magnetic Resonance

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Open Access 01-12-2011 | Research

On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

Authors: DJ Pennell, JP Carpenter, M Roughton, ZI Cabantchik

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2011

Abstract

Background

Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful.

Methods

This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM).

Results

A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001).

Conclusion

These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

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Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ: Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001, 23: 2171-9.CrossRef

Carpenter JP, He T, Kirk P, Roughton M, Anderson LJ, de Noronha SV, Sheppard MN, Porter JB, Walker JM, Wood JC, Galanello R, Forni G, Catani G, Matta G, Fucharoen S, Fleming A, House MJ, Black G, Firmin DN, St Pierre TG, Pennell DJ: On T2* magnetic resonance and cardiac iron. Circulation. 2011, 123: 1519-28. 10.1161/CIRCULATIONAHA.110.007641.PubMedCentralCrossRefPubMed

Tanner MA, Galanello R, Dessi C, Westwood MA, Smith GC, Nair SV, Anderson LJ, Walker JM, Pennell DJ: Myocardial iron loading in patients with thalassemia major on deferoxamine chelation. J Cardiovasc Magn Reson. 2006, 8: 543-7. 10.1080/10976640600698155.CrossRefPubMed

Daar S, Pathare AV, Jain R, Zadjali SA, Pennell DJ: T2* cardiovascular magnetic resonance in the management of thalassemia patients in Oman. Haematologica. 2009, 94: 140-1. 10.3324/haematol.13845.PubMedCentralCrossRefPubMed

Chouliaras GL, Kattamis A, Berdoukas V, Gotsis ED, Mavrogeni S, Ladis V: Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction. Br J Haematol. 2010, 151: 397-401. 10.1111/j.1365-2141.2010.08365.x.CrossRefPubMed

Marsella M, Borgna-Pignatti C, Meloni A, Caldarelli V, Dell'Amico MC, Spasiano A, Pitrolo L, Cracolici E, Valeri G, Positano V, Lombardi M, Pepe A: Cardiac iron and cardiac disease in males and females with transfusion-dependent thalassemia major: a T2* magnetic resonance imaging study. Haematologica. 2011, 96: 515-20. 10.3324/haematol.2010.025510.PubMedCentralCrossRefPubMed

Pennell DJ, Berdoukas V, Karagiorga M, Ladis V, Piga A, Aessopos A, Gotsis ED, Tanner MA, Smith GC, Westwood MA, Wonke B, Galanello R: Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood. 2006, 107: 3738-44. 10.1182/blood-2005-07-2948.CrossRefPubMed

Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, Roughton M, Assomull R, Nair SV, Walker JM, Pennell DJ: A randomized, placebo controlled, double blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation. 2007, 115: 1876-84. 10.1161/CIRCULATIONAHA.106.648790.CrossRefPubMed

10.

Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, Pibiri M, Nair SV, Walker JM, Pennell DJ: Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson. 2008, 10: 12-10.1186/1532-429X-10-12.PubMedCentralCrossRefPubMed

11.

Pennell DJ, Porter JB, Cappellini MD, El-Beshlawy A, Chan LL, Aydinok Y, Elalfy MS, Sutcharitchan P, Li CK, Ibrahim H, Viprakasit V, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A: Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia. Blood. 2010, 115: 2364-71. 10.1182/blood-2009-04-217455.CrossRefPubMed

12.

Berdoukas V, Chouliaras G, Moraitis P, Zannikos P, Berdoussi E, Ladis V: The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study. J Cardiovasc Magn Reson. 2009, 11: 20-10.1186/1532-429X-11-20.PubMedCentralCrossRefPubMed

13.

Borgna-Pignatti C, Cappellini MD, De Stefano P, Del Vecchio GC, Forni GL, Gamberini MR, Ghilardi R, Piga A, Romeo MA, Zhao H, Cnaan A: Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood. 2006, 107: 3733-7. 10.1182/blood-2005-07-2933.CrossRefPubMed

14.

Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ: Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2008, 10: 42-10.1186/1532-429X-10-42.PubMedCentralCrossRefPubMed

15.

Telfer PT, Warburton F, Christou S, Hadjigavriel M, Sitarou M, Kolnagou A, Angastiniotis M: Improved survival in thalassemia major patients on switching from desferrioxamine to combined chelation therapy with desferrioxamine and deferiprone. Haematologica. 2009, 94: 1777-8. 10.3324/haematol.2009.009118.PubMedCentralCrossRefPubMed

16.

Anderson LJ, Westwood MA, Holden S, Davis B, Prescott E, Wonke B, Porter JB, Walker JM, Pennell DJ: Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance. Br J Haematol. 2004, 127: 348-55. 10.1111/j.1365-2141.2004.05202.x.CrossRefPubMed

17.

Kremastinos DT, Tsetsos GA, Tsiapras DP, Karavolias GK, Ladis VA, Kattamis CA: Heart failure in beta thalassemia: a 5-year follow-up study. Am J Med. 2001, 111: 407-8. 10.1016/S0002-9343(01)00943-3.CrossRef

18.

Kirk P, Roughton M, Porter JB, Walker JM, Tanner MA, Patel J, Wu D, Taylor J, Westwood MA, Anderson LJ, Pennell DJ: Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation. 2009, 120: 1961-8. 10.1161/CIRCULATIONAHA.109.874487.PubMedCentralCrossRefPubMed

19.

Westwood MA, Anderson LJ, Maceira AM, Shah FT, Prescott E, Porter JB, Wonke B, Walker JM, Pennell DJ: Normalized left ventricular volumes and function in thalassemia major patients with normal myocardial iron. J Magn Reson Imaging. 2007, 25: 1147-51. 10.1002/jmri.20915.CrossRefPubMed

20.

Westwood M, Anderson LJ, Firmin DN, Gatehouse PD, Charrier CC, Wonke B, Pennell DJ: A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload. J Magn Reson Imaging. 2003, 18: 33-9. 10.1002/jmri.10332.CrossRefPubMed

21.

Maceira AM, Prasad SK, Khan M, Pennell DJ: Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2006, 8: 417-26. 10.1080/10976640600572889.CrossRefPubMed

22.

Grothues F, Smith GC, Moon JCC, Bellenger NG, Collins P, Klein H, Pennell DJ: Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol. 2002, 90: 29-34. 10.1016/S0002-9149(02)02381-0.CrossRefPubMed

23.

Maceira AM, Bellenger NG, Pennell DJ: Assessment of cardiac function. Cardiovascular magnetic resonance. Edited by: Manning WJ, Pennell DJ. 2010, Churchill Livingstone, Philadelphia, USA, 2

24.

Piga A, Gaglioti C, Fogliacco E, Tricta F: Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica. 2003, 88: 489-96.PubMed

25.

26.

Ceci A, Baiardi P, Catapano M, Felisi M, Cianciulli P, De Sanctis V, Del Vecchio GC, Magnano C, Meo A, Maggio A: Risk factors for death in patients with beta-thalassemia major: results of a case-control study. Haematologica. 2006, 91: 1420-1.PubMed

27.

28.

Maggio A, Vitrano A, Capra M, Cuccia L, Gagliardotto F, Filosa A, Magnano C, Rizzo M, Caruso V, Gerardi C, Argento C, Campisi S, Cantella F, Commendatore F, D'Ascola DG, Fidone C, Ciancio A, Galati MC, Giuffrida G, Cingari R, Giugno G, Lombardo T, Prossomariti L, Malizia R, Meo A, Roccamo G, Romeo MA, Violi P, Cianciulli P, Rigano P: Improving survival with deferiprone treatment in patients with thalassemia major: a prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies. Blood Cells Mol Dis. 2009, 42: 247-51. 10.1016/j.bcmd.2009.01.002.CrossRefPubMed

29.

Anderson LJ, Wonke B, Prescott E, Holden S, Walker JM, Pennell DJ: Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet. 2002, 360: 516-20. 10.1016/S0140-6736(02)09740-4.CrossRefPubMed

30.

Davis BA, O'Sullivan C, Jarritt PH, Porter JB: Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major. Blood. 2004, 104: 263-9. 10.1182/blood-2003-08-2841.CrossRefPubMed

31.

Bellenger NG, Burgess MI, Ray SG, Lahiri A, Coats AJ, Pennell DJ, CHRISTMAS Study Steering Committee and Investigators: Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance Are they interchangeable?. Eur Heart J. 2000, 21: 1387-96. 10.1053/euhj.2000.2011.CrossRefPubMed

32.

Velasco-Sánchez D, Aracil A, Montero R, Mas A, Jiménez L, O'Callaghan M, Tondo M, Capdevila A, Blanch J, Artuch R, Pineda M: Combined therapy with idebenone and deferiprone in patients with Friedreich's ataxia. Cerebellum. 2011, 10: 1-8. 10.1007/s12311-010-0212-7.CrossRefPubMed

33.

Gao X, Qian M, Campian JL, Marshall J, Zhou Z, Roberts AM, Kang YJ, Prabhu SD, Sun XF, Eaton JW: Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload. Free Radic Biol Med. 2010, 49: 401-7. 10.1016/j.freeradbiomed.2010.04.033.PubMedCentralCrossRefPubMed

34.

Lane N, Martin W: The energetics of genome complexity. Nature. 2010, 467: 929-34. 10.1038/nature09486.CrossRefPubMed

35.

Stanley WC, Recchia FA, Lopaschuk GD: Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005, 85: 1093-129. 10.1152/physrev.00006.2004.CrossRefPubMed

36.

Garnier A, Fortin D, Delomenie C, Momken I, Veksler V, Ventura-Clapier R: Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003, 551: 491-501. 10.1113/jphysiol.2003.045104.PubMedCentralCrossRefPubMed

37.

Montgomery C, Hamilton N, Ianuzzo CD: Energy status of the rapidly paced canine myocardium in congestive heart failure. J Appl Physiol. 1992, 73: 2363-7.PubMed

38.

Neubauer S, Krahe T, Schindler R, Horn M, Hillenbrand H, Entzeroth C, et al: 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure. Circulation. 1992, 86: 1810-8.CrossRefPubMed

39.

Zhang J, Merkle H, Hendrich K, Garwood M, From AH, Ugurbil K, Bache RJ: Bioenergetic abnormalities associated with severe left ventricular hypertrophy. J Clin Invest. 1993, 92: 993-1003. 10.1172/JCI116676.PubMedCentralCrossRefPubMed

40.

Feygin J, Mansoor A, Eckman P, Swingen C, Zhang J: Functional and bioenergetic modulations in the infarct border zone following autologous mesenchymal stem cell transplantation. Am J Physiol Heart Circ Physiol. 2007, 293: H1772-80. 10.1152/ajpheart.00242.2007.CrossRefPubMed

41.

Liao R, Nascimben L, Friedrich J, Gwathmey JK, Ingwall JS: Decreased energy reserve in an animal model of dilated cardiomyopathy. Relationship to contractile performance. Circ Res. 1996, 78: 893-902.CrossRefPubMed

42.

Murakami Y, Zhang Y, Cho YK, Mansoor AM, Chung JK, Chu C, Francis G, Ugurbil K, Bache RJ, From AH, Jerosch-Herold M, Wilke N, Zhang J: Myocardial oxygenation during high work states in hearts with postinfarction remodeling. Circulation. 1999, 99: 942-8.CrossRefPubMed

43.

Jung WI, Sieverding L, Breuer J, Hoess T, Widmaier S, Schmidt O, Bunse M, van Erckelens F, Apitz J, Lutz O, Dietze GJ: 31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy. Circulation. 1998, 97: 2536-42.CrossRefPubMed

44.

Link G, Saada A, Pinson A, Konijn AM, Hershko C: Mitochondrial respiratory enzymes are a major target of iron toxicity in rat heart cells. J Lab Clin Med. 1998, 131: 466-74. 10.1016/S0022-2143(98)90148-2.CrossRefPubMed

45.

Hershko C, Link G, Cabantchik ZI: Pathophysiology of Iron Overload. Ann NY Acad Sci. 2006, 850: 191-201.CrossRef

46.

Kuryshev YA, Brittenham GM, Fujioka H, Kannan P, Shieh CC, Cohen SA, Brown AM: Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes implications for the arrhythmogenesis of human siderotic heart disease. Circulation. 1999, 100: 675-83.CrossRefPubMed

47.

Gao X, Campian JL, Qian M, Sun XF, Eaton JW: Mitochondrial DNA damage in iron overload. J Biol Chem. 2009, 284: 4767-75.PubMedCentralCrossRefPubMed

48.

Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL: Mitochondrial dysfunction in cardiac disease: ischemia--reperfusion, aging, and heart failure. J Mol Cell Cardiol. 2001, 33: 1065-89. 10.1006/jmcc.2001.1378.CrossRefPubMed

49.

50.

Ingwall JS: ATP and the heart. 2002, Kluwer Academic Publishers. Norwell, Massachusetts, USA, 16-ISBN 1-4020-7093-4CrossRef

51.

Neubauer S: The failing heart-an engine out of fuel. N Engl J Med. 2007, 356: 1140-51. 10.1056/NEJMra063052.CrossRefPubMed

52.

Neubauer S, Horn M, Cramer M, Harre K, Newell JB, Peters W, Pabst T, Ertl G, Hahn D, Ingwall JS, Kochsiek K: Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation. 1997, 96: 2190-6.CrossRefPubMed

53.

Eaton JW, Qian M: Molecular bases of cellular iron toxicity. Free Radic Biol Med. 2002, 32: 833-40. 10.1016/S0891-5849(02)00772-4.CrossRefPubMed

54.

Kadiiska MB, Burkitt MJ, Xiang QH, Mason RP: Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation. J Clin Invest. 1995, 96: 1653-7. 10.1172/JCI118205.PubMedCentralCrossRefPubMed

55.

Fry M, Green DE: Cardiolipin requirement by cytochrome oxidase and the catalytic role of phospholipid. Biochem Biophys Res Commun. 1980, 93: 1238-46. 10.1016/0006-291X(80)90622-1.CrossRefPubMed

56.

Goormaghtigh E, Brasseur R, Ruysschaert JM: Adriamycin inactivates cytochrome c oxidase by exclusion of the enzyme from its cardiolipin essential environment. Biochem Biophys Res Commun. 1982, 104: 314-20. 10.1016/0006-291X(82)91976-3.CrossRefPubMed

57.

Houglum K, Filip M, Witztum JL, Chojkier M: Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J Clin Invest. 1990, 86: 1991-8. 10.1172/JCI114934.PubMedCentralCrossRefPubMed

58.

Stadtman ER: Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med. 1990, 9: 315-25. 10.1016/0891-5849(90)90006-5.CrossRefPubMed

59.

Pitkanen S, Robinson BH: Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. J Clin Invest. 1996, 98: 345-51. 10.1172/JCI118798.PubMedCentralCrossRefPubMed

60.

Zhou R, Yazdi AS, Menu P, Tschopp J: A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011, 469: 221-5. 10.1038/nature09663.CrossRefPubMed

61.

Gustafsson AB, Gottlieb RA: Heart mitochondria: gates of life and death. Cardiovasc Res. 2008, 77: 334-43.CrossRefPubMed

62.

Lyon AR, Joudrey PJ, Jin D, Nass RD, Aon MA, O'Rourke B, Akar FG: Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart. J Mol Cell Cardiol. 2010, 49: 565-75. 10.1016/j.yjmcc.2010.07.002.PubMedCentralCrossRefPubMed

63.

Wood JC, Glynos T, Thompson A, Giardina P, Harmatz P, Kang BP, Paley C, Coates TD: Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial. Haematologica. 2011, 96: 1055-8. 10.3324/haematol.2010.032862.PubMedCentralCrossRefPubMed

64.

Kakhlon O, Manning H, Breuer W, Melamed-Book N, Lu C, Cortopassi G, Munnich A, Cabantchik ZI: Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation. Blood. 2008, 112: 5219-27. 10.1182/blood-2008-06-161919.CrossRefPubMed

65.

Galanello R: Deferiprone in the treatment of transfusion-dependent thalassemia: a review and perspective. Ther Clin Risk Manag. 2007, 3: 795-805.PubMedCentralPubMed

66.

Waldmeier F, Bruin GJ, Glaenzel U, Hazell K, Sechaud R, Warrington S, Porter JB: Pharmacokinetics, metabolism, and disposition of deferasirox in beta-thalassemic patients with transfusion-dependent iron overload who are at pharmacokinetic steady state. Drug Metab Dispos. 2010, 38: 808-16. 10.1124/dmd.109.030833.CrossRefPubMed

67.

Porter JB: Deferoxamine pharmacokinetics. Semin Hematol. 2001, 38 (Suppl 1): 63-8.CrossRefPubMed

68.

Shalev O, Repka T, Goldfarb A, Grinberg L, Abrahamov A, Olivieri NF, Rachmilewitz EA, Hebbel RP: Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo. Blood. 1995, 86: 2008-13.PubMed

69.

De Franceschi L, Shalev O, Piga A, Collell M, Olivieri O, Corrocher R, Hebbel RP, Brugnara C: Deferiprone therapy in homozygous human beta-thalassemia removes erythrocyte membrane free iron and reduces KCl cotransport activity. J Lab Clin Med. 1999, 133: 64-9. 10.1053/lc.1999.v133.a94241.CrossRefPubMed

70.

Galanello R, Campus S: Deferiprone chelation therapy for thalassemia major. Acta Haematol. 2009, 122: 155-64. 10.1159/000243800.CrossRefPubMed

71.

Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A: Continued improvement in myocardial T2* over 2 years of deferasirox therapy in beta-thalassemia major patients with cardiac iron overload. Haematologica. 2011, 96: 48-54. 10.3324/haematol.2010.031468.PubMedCentralCrossRefPubMed

72.

Pennell D, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A: Continued improvement and normalization of myocardial T2* in patients with β thalassemia major treated with Deferasirox (Exjade^®) for up to 3 years. Blood. 2010, 116: abstract 4276-

73.

Wood JC, Kang BP, Thompson A, Giardina P, Harmatz P, Glynos T, Paley C, Coates TD: The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood. 2010, 116: 537-43. 10.1182/blood-2009-11-250308.CrossRefPubMed

74.

Wood JC, Glynos T, Thompson A, Giardina P, Harmatz P, Kang BP, Paley C, Coates TD: Follow-up report on the 2-year cardiac data from a deferasirox monotherapy trial. Am J Hematol. 2010, 85: 818-9. 10.1002/ajh.21830.CrossRefPubMed

75.

Hileti D, Panayiotidis P, Hoffbrand AV: Iron chelators induce apoptosis in proliferating cells. Br J Haematol. 1995, 89: 181-7.CrossRefPubMed

76.

Kim BS, Yoon KH, Oh HM, Choi EY, Kim SW, Han WC, Kim EA, Choi SC, Kim TH, Yun KJ, Kim EC, Lyou JH, Nah YH, Chung HT, Cha YN, Jun CD: Involvement of p38 MAP kinase during iron chelator-mediated apoptotic cell death. Cell Immunol. 2002, 220: 96-106. 10.1016/S0008-8749(03)00031-5.CrossRefPubMed

77.

Choi SC, Kim BS, Song MY, Choi EY, Oh HM, Lyou JH, Han WC, Moon HB, Kim TH, Oh JM, Chung HT, Jun CD: Downregulation of p38 kinase pathway by cAMP response element-binding protein protects HL-60 cells from iron chelator-induced apoptosis. Free Radic Biol Med. 2003, 35: 1171-84. 10.1016/S0891-5849(03)00503-3.CrossRefPubMed

78.

Arvapalli RK, Paturi S, Laurino JP, Katta A, Kakarla SK, Gadde MK, Wu M, Rice KM, Walker EM, Wehner P, Blough ER: Deferasirox decreases age-associated iron accumulation in the aging F344XBN rat heart and liver. Cardiovasc Toxicol. 2010, 10: 108-16. 10.1007/s12012-010-9068-9.CrossRefPubMed

79.

Kakhlon O, Breuer W, Munnich A, Cabantchik ZI: Ion redistribution as a therapeutic strategy for treating diseases of localized iron accumulation. Can Physiol Pharmacol. 2010, 88: 187-96. 10.1139/Y09-128.CrossRef

80.

Sohn YS, Mitterstiller AM, Breuer W, Weiss G, Cabantchik ZI: Rescuing iron-overloaded macrophages by conservative relocation of the accumulated metal. Br J Pharmacol. 2011, 164: 406-18.PubMedCentralCrossRefPubMed

81.

Gaboriau F, Leray AM, Ropert M, Gouffier L, Cannie I, Troadec MB, Loréal O, Brissot P, Lescoat G: Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG. Biometals. 2010, 23: 231-45. 10.1007/s10534-009-9281-9.CrossRefPubMed

82.

Voskaridou E, Christoulas D, Terpos E: Successful chelation therapy with the combination of deferasirox and deferiprone in a patient with thalassaemia major and persisting severe iron overload after single-agent chelation therapies. Br J Haematol. 2011, 154: 654-6. 10.1111/j.1365-2141.2011.08626.x.CrossRefPubMed

Title: On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure
Authors: DJ Pennell
JP Carpenter
M Roughton
ZI Cabantchik
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Cardiovascular Magnetic Resonance / Issue 1/2011
Electronic ISSN: 1532-429X
DOI: https://doi.org/10.1186/1532-429X-13-45

Keynote webinar | Spotlight on medication adherence

Springer Medicine

On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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