Journal of Cardiac Failure
Volume 16, Issue 11 , Pages 888-900 , November 2010

Iron-Overload Cardiomyopathy: Pathophysiology, Diagnosis, and Treatment

  • Colm J. Murphy, MD, FRCPC
    • ,
  • Gavin Y. Oudit, MD, PhD, FRCPC

      Affiliations

    • Corresponding Author InformationReprint requests: Gavin Y. Oudit, MD, PhD, FRCP(C), Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada. Tel: (780) 407-8569; Fax: 780-407-6452.

Received 7 April 2010 ,Revised 11 May 2010 ,Accepted 11 May 2010.

References 

  1. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341:1986–1995
  2. Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell. 2004;117:285–287
  3. Weatherall DJ, Clegg JB. Thalassemia—a global public health problem. Nat Med. 1996;2:847–849
  4. Olivieri NF. The beta-thalassemias. N Engl J Med. 1999;341:99–109
  5. Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79:704–712
  6. Pietrangelo A. Hereditary hemochromatosis—a new look at an old disease. N Engl J Med. 2004;350:2383–2397
  7. Templeton DM, Liu Y. Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta. 2003;1619:113–124
  8. Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood. 2003;102:2670–2677
  9. Oudit GY, Trivieri MG, Khaper N, Liu PP, Backx PH. Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. J Mol Med. 2006;84:349–364
  10. Rochette J, Pointon JJ, Fisher CA, Perera G, Arambepola M, Arichchi DS, et al. Multicentric origin of hemochromatosis gene (HFE) mutations. Am J Hum Genet. 1999;64:1056–1062
  11. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 2004;36:77–82
  12. Chen FE, Ooi C, Ha SY, Cheung BM, Todd D, Liang R, et al. Genetic and clinical features of hemoglobin H disease in Chinese patients. N Engl J Med. 2000;343:544–550
  13. Olivieri NF. Progression of iron overload in sickle cell disease. Semin Hematol. 2001;38(1 Suppl. 1):57–62
  14. Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004;103:4023–4027
  15. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:1021–1030
  16. Hellstrom-Lindberg E. Management of anemia associated with myelodysplastic syndrome. Semin Hematol. 2005;42(2 Suppl. 1):S10–S13
  17. Dreyfus F. The deleterious effects of iron overload in patients with myelodysplastic syndromes. Blood Rev. 2008;22(Suppl 2):S29–S34
  18. Angelucci E, Di Tucci AA. Iron overload, cardiac iron loading and function in myelodysplastic syndrome. Leuk Res. 2009;33:743–744
  19. Kletzmayr J, Horl WH. Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant. 2002;17(Suppl 2):25–29
  20. Sood MM, Oudit GY, Mohammadi H, Huang H, Lok CE. Effects of parenteral iron on inflammation and the myocardium in hemodialysis patients. Hemodial Int. 2008;12:362–368
  21. Engle MA, Erlandson M, Smith CH. Late cardiac complications of chronic, severe, refractory anemia with hemochromatosis. Circulation. 1964;30:698–705
  22. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994;331:574–578
  23. Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med. 1994;331:567–573
  24. Zurlo MG, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, et al. Survival and causes of death in thalassaemia major. Lancet. 1989;2:27–30
  25. Li CK, Luk CW, Ling SC, Chik KW, Yuen HL, Shing MM, et al. Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: retrospective study. Hong Kong Med J. 2002;8:255–260
  26. Modell B, Khan M, Darlison M. Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet. 2000;355:2051–2052
  27. 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;111:349–354
  28. Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G. Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985;313:1256–1262
  29. Cecchetti G, Binda A, Piperno A, Nador F, Fargion S, Fiorelli G. Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation. Eur Heart J. 1991;12:224–230
  30. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology. 1996;110:1107–1119
  31. Muhlestein JB. Cardiac abnormalities in hemochromatosis. In:  Barton JC,  Edwards CQ editor. Hemochromatosis: genetics, pathophysiology, diagnosis, and treatment. Cambridge: Cambridge University Press; 2000;p. 297–310
  32. Palka P, Macdonald G, Lange A, Burstow DJ. The role of Doppler left ventricular filling indexes and Doppler tissue echocardiography in the assessment of cardiac involvement in hereditary hemochromatosis. J Am Soc Echocardiogr. 2002;15:884–890
  33. Kremastinos DT, Tsiapras DP, Tsetsos GA, Rentoukas EI, Vretou HP, Toutouzas PK. Left ventricular diastolic Doppler characteristics in beta-thalassemia major. Circulation. 1993;88:1127–1135
  34. Liu P, Olivieri N. Iron overload cardiomyopathies: new insights into an old disease. Cardiovasc Drugs Ther. 1994;8:101–110
  35. Walker JM. The heart in thalassaemia. Eur Heart J. 2002;23:102–105
  36. Sachdev V, Machado RF, Shizukuda Y, Rao YN, Sidenko S, Ernst I, et al. Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease. J Am Coll Cardiol. 2007;49:472–479
  37. Kremastinos DT, Tiniakos G, Theodorakis GN, Katritsis DG, Toutouzas PK. Myocarditis in beta-thalassemia major. A cause of heart failure. Circulation. 1995;91:66–71
  38. Kremastinos DT, Flevari P, Spyropoulou M, Vrettou H, Tsiapras D, Stavropoulos-Giokas CG. Association of heart failure in homozygous beta-thalassemia with the major histocompatibility complex. Circulation. 1999;100:2074–2078
  39. Walter PB, Fung EB, Killilea DW, Jiang Q, Hudes M, Madden J, et al. Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol. 2006;135:254–263
  40. Economou-Petersen E, Aessopos A, Kladi A, Flevari P, Karabatsos F, Fragodimitri C, et al. Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia. Blood. 1998;92:3455–3459
  41. Valenti L, Conte D, Piperno A, Dongiovanni P, Fracanzani AL, Fraquelli M, et al. The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis. J Med Genet. 2004;41:946–950
  42. Shizukuda Y, Bolan CD, Tripodi DJ, Yau YY, Nguyen TT, Botello G, et al. Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis. Am J Cardiol. 2006;98:954–959
  43. Shizukuda Y, Bolan CD, Nguyen TT, Botello G, Tripodi DJ, Yau YY, et al. Oxidative stress in asymptomatic subjects with hereditary hemochromatosis. Am J Hematol. 2007;82:249–250
  44. Miranda CJ, Makui H, Soares RJ, Bilodeau M, Mui J, Vali H, et al. Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin. Blood. 2003;102:2574–2580
  45. Buja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med. 1971;51:209–221
  46. Laurita KR, Chuck ET, Yang T, Dong WQ, Kuryshev YA, Brittenham GM, et al. Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy. J Lab Clin Med. 2003;142:83–89
  47. Turoczi T, Jun L, Cordis G, Morris JE, Maulik N, Stevens RG, et al. HFE mutation and dietary iron content interact to increase ischemia/reperfusion injury of the heart in mice. Circ Res. 2003;92:1240–1246
  48. Arena R, Shizukuda Y, Bolan CD, Tripodi DJ, Yau YY, Smith KP, et al. Heart rate recovery is lower following supine exercise in asymptomatic hereditary hemochromatosis subjects compared with healthy controls. J Cardiopulm Rehabil Prev. 2007;27:157–160
  49. Young IS, Trouton TG, Torney JJ, McMaster D, Callender ME, Trimble ER. Antioxidant status and lipid peroxidation in hereditary haemochromatosis. Free Radic Biol Med. 1994;16:393–397
  50. Livrea MA, Tesoriere L, Pintaudi AM, Calabrese A, Maggio A, Freisleben HJ, et al. Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants. Blood. 1996;88:3608–3614
  51. Lim PS, Chan EC, Lu TC, Yu YL, Kuo SY, Wang TH, et al. Lipophilic antioxidants and iron status in ESRD patients on hemodialysis. Nephron. 2000;86:428–435
  52. Tsushima RG, Wickenden AD, Bouchard RA, Oudit GY, Liu PP, Backx PH. Modulation of iron uptake in heart by L-type Ca2+ channel modifiers: possible implications in iron overload. Circ Res. 1999;84:1302–1309
  53. Hahalis G, Manolis AS, Apostolopoulos D, Alexopoulos D, Vagenakis AG, Zoumbos NC. Right ventricular cardiomyopathy in beta-thalassaemia major. Eur Heart J. 2002;23:147–156
  54. Oudit GY, Sun H, Trivieri MG, Koch SE, Dawood F, Ackerley C, et al. L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy. Nat Med. 2003;9:1187–1194
  55. Oudit GY, Trivieri MG, Khaper N, Husain T, Wilson GJ, Liu P, et al. Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model. Circulation. 2004;109:1877–1885
  56. Rosenqvist M, Hultcrantz R. Prevalence of a haemochromatosis among men with clinically significant bradyarrhythmias. Eur Heart J. 1989;10:473–478
  57. Kuryshev YA, Brittenham GM, Fujioka H, Kannan P, Shieh CC, Cohen SA, et al. Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease. Circulation. 1999;100:675–683
  58. Wu VC, Huang JW, Wu MS, Chin CY, Chiang FT, Liu YB, et al. The effect of iron stores on corrected QT dispersion in patients undergoing peritoneal dialysis. Am J Kidney Dis. 2004;44:720–728
  59. Cooper JM, Schapira AH. Friedreich's Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy. Biofactors. 2003;18:163–171
  60. Pepe A, Positano V, Capra M, Maggio A, Pinto CL, Spasiano A, et al. Myocardial scarring by delayed enhancement cardiovascular magnetic resonance in thalassaemia major. Heart. 2009;95:1688–1693
  61. Gerry JL, Baird MG, Fortuin NJ. Evaluation of left ventricular function in patients with sickle cell anemia. Am J Med. 1976;60:968–972
  62. Lester LA, Sodt PC, Hutcheon N, Arcilla RA. Cardiac abnormalities in children with sickle cell anemia. Chest. 1990;98:1169–1174
  63. Lewis BS, Lewis N, Dagan I, Rachmilewitz EA, Gotsman MS, Sapoznikov D. Studies of left-ventricular function in anemia due to beta-thalassemia. Isr J Med Sci. 1982;18:928–934
  64. Lau KC, Li AM, Hui PW, Yeung CY. Left ventricular function in beta thalassaemia major. Arch Dis Child. 1989;64:1046–1051
  65. Westwood MA, Shah F, Anderson LJ, Strange JW, Tanner MA, Maceira AM, et al. Myocardial tissue characterization and the role of chronic anemia in sickle cell cardiomyopathy. J Magn Reson Imaging. 2007;26:564–568
  66. Alpert BS, Gilman PA, Strong WB, Ellison MF, Miller MD, McFarlane J, et al. Hemodynamic and ECG responses to exercise in children with sickle cell anemia. Am J Dis Child. 1981;135:362–366
  67. Varat MA, Adolph RJ, Fowler NO. Cardiovascular effects of anemia. Am Heart J. 1972;83:415–426
  68. Almeida AG, Araujo F, Rego F, David C, Lopes MG, Ducla-Soares J. Abnormal myocardial flow reserve in sickle cell disease: a myocardial contrast echocardiography study. Echocardiography. 2008;25:591–599
  69. Assanasen C, Quinton RA, Buchanan GR. Acute myocardial infarction in sickle cell anemia. J Pediatr Hematol Oncol. 2003;25:978–981
  70. Tuomainen TP, Punnonen K, Nyyssonen K, Salonen JT. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation. 1998;97:1461–1466
  71. Roest M, van der Schouw YT, de Valk B, Marx JJ, Tempelman MJ, de Groot PG, et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation. 1999;100:1268–1273
  72. Zheng H, Cable R, Spencer B, Votto N, Katz SD. Iron stores and vascular function in voluntary blood donors. Arterioscler Thromb Vasc Biol. 2005;25:1577–1583
  73. Gaenzer H, Marschang P, Sturm W, Neumayr G, Vogel W, Patsch J, et al. Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol. 2002;40:2189–2194
  74. Cheung YF, Chan GC, Ha SY. Arterial stiffness and endothelial function in patients with beta-thalassemia major. Circulation. 2002;106:2561–2566
  75. Lemogoum D, Van Bortel L, Najem B, Dzudie A, Teutcha C, Madu E, et al. Arterial stiffness and wave reflections in patients with sickle cell disease. Hypertension. 2004;44:924–929
  76. Day SM, Duquaine D, Mundada LV, Menon RG, Khan BV, Rajagopalan S, et al. Chronic iron administration increases vascular oxidative stress and accelerates arterial thrombosis. Circulation. 2003;107:2601–2606
  77. Hahalis G, Alexopoulos D, Kremastinos DT, Zoumbos NC. Heart failure in beta-thalassemia syndromes: a decade of progress. Am J Med. 2005;118:957–967
  78. Yunker LM, Parboosingh JS, Conradson HE, Faris P, Bridge PJ, Buithieu J, et al. The effect of iron status on vascular health. Vasc Med. 2006;11:85–91
  79. van der AD, Rovers MM, Grobbee DE, Marx JJ, Waalen J, Ellervik C, et al. Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects. Circ Cardiovasc Genet. 2008;1:43–50
  80. Moser KM, Shea JG. The relationship between pulmonary infarction, cor pulmonale and the sickle states. Am J Med. 1957;22:561–579
  81. Oppenheimer EH, Esterly JR. Pulmonary changes in sickle cell disease. Am Rev Respir Dis. 1971;103:858–859
  82. Collins FS, Orringer EP. Pulmonary hypertension and cor pulmonale in the sickle hemoglobinopathies. Am J Med. 1982;73:814–821
  83. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. 2005;294:81–90
  84. Schechter AN, Gladwin MT. Hemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med. 2003;348:1483–1485
  85. Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350:886–895
  86. Machado RF, Anthi A, Steinberg MH, Bonds D, Sachdev V, Kato GJ, et al. N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease. JAMA. 2006;296:310–318
  87. Hamdy AM, Zein El-Abdin MY, Abdel-Hafez MA. Right ventricular function in patients with beta thalassemia: relation to serum ferritin level. Echocardiography. 2007;24:795–801
  88. Alpendurada F, Carpenter JP, Deac M, Kirk P, Walker JM, Porter JB, et al. Relation of myocardial T2∗ to right ventricular function in thalassaemia major. Eur Heart J. 2010 Apr 22;[Epub ahead of print]
  89. Schafer AI, Cheron RG, Dluhy R, Cooper B, Gleason RE, Soeldner JS, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med. 1981;304:319–324
  90. Arnold JM, Howlett JG, Ducharme A, Ezekowitz JA, Gardner MJ, Giannetti N, et al. Canadian Cardiovascular Society Consensus Conference guidelines on heart failure—2008 update: best practices for the transition of care of heart failure patients, and the recognition, investigation and treatment of cardiomyopathies. Can J Cardiol. 2008;24:21–40
  91. Alizad A, Seward JB. Echocardiographic features of genetic diseases: part 2. Storage disease. J Am Soc Echocardiogr. 2000;13:164–170
  92. Kremastinos DT, Tsiapras DP, Kostopoulou AG, Hamodraka ES, Chaidaroglou AS, Kapsali ED. NT-proBNP levels and diastolic dysfunction in beta-thalassaemia major patients. Eur J Heart Fail. 2007;9:531–536
  93. Isma'eel H, Chafic AH, Rassi FE, Inati A, Koussa S, Daher R, et al. Relation between iron-overload indices, cardiac echo-Doppler, and biochemical markers in thalassemia intermedia. Am J Cardiol. 2008;102:363–367
  94. Caldas MC, Meira ZA, Barbosa MM. Evaluation of 107 patients with sickle cell anemia through tissue Doppler and myocardial performance index. J Am Soc Echocardiogr. 2008;21:1163–1167
  95. Click RL, Olson LJ, Edwards WD, Miller FA, Khandheria BK, Seward JB, et al. Echocardiography and systemic diseases. J Am Soc Echocardiogr. 1994;7:201–216
  96. Palka P, Lange A, Atherton J, Stafford WJ, Burstow DJ. Biventricular diastolic behaviour in patients with hypertrophic and hereditary hemochromatosis cardiomyopathies. Eur J Echocardiogr. 2004;5:356–366
  97. Shizukuda Y, Bolan CD, Tripodi DJ, Sachdev V, Nguyen TT, Botello G, et al. Does oxidative stress modulate left ventricular diastolic function in asymptomatic subjects with hereditary hemochromatosis?. Echocardiography. 2009;26:1153–1158
  98. Spirito P, Lupi G, Melevendi C, Vecchio C. Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. Circulation. 1990;82:88–94
  99. Lattanzi F, Bellotti P, Picano E, Chiarella F, Mazzarisi A, Melevendi C, et al. Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload. Circulation. 1993;87:748–754
  100. Suarez WA, Snyder SA, Berman BB, Brittenham GM, Patel CR. Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography. J Am Soc Echocardiogr. 1998;11:948–956
  101. Hahalis G, Manolis AS, Gerasimidou I, Alexopoulos D, Sitafidis G, Kourakli A, et al. Right ventricular diastolic function in beta-thalassemia major: echocardiographic and clinical correlates. Am Heart J. 2001;141:428–434
  102. Vogel M, Anderson LJ, Holden S, Deanfield JE, Pennell DJ, Walker JM. Tissue Doppler echocardiography in patients with thalassaemia detects early myocardial dysfunction related to myocardial iron overload. Eur Heart J. 2003;24:113–119
  103. Gharzuddine WS, Kazma HK, Nuwayhid IA, Bitar FF, Koussa SF, Moukarbel GV, et al. Doppler characterization of left ventricular diastolic function in beta-thalassaemia major. Evidence for an early stage of impaired relaxation. Eur J Echocardiogr. 2002;3:47–51
  104. Bosi G, Crepaz R, Gamberini MR, Fortini M, Scarcia S, Bonsante E, et al. Left ventricular remodelling, and systolic and diastolic function in young adults with beta thalassaemia major: a Doppler echocardiographic assessment and correlation with haematological data. Heart. 2003;89:762–766
  105. Akpinar O, Acarturk E, Kanadasi M, Unsal C, Baslamisli F. Tissue Doppler imaging and NT-proBNP levels show the early impairment of ventricular function in patients with beta-thalassaemia major. Acta Cardiol. 2007;62:225–231
  106. Silvilairat S, Sittiwangkul R, Pongprot Y, Charoenkwan P, Phornphutkul C. Tissue Doppler echocardiography reliably reflects severity of iron overload in pediatric patients with beta thalassemia. Eur J Echocardiogr. 2008;9:368–372
  107. de Gregorio C, Piraino B, Morabito G, Salpietro CD, Coglitore S. On the use of conventional and tissue Doppler echocardiography in patients with beta-thalassemia major and myocardial iron- overload: preliminary data by a single centre study. Int J Cardiol. 2009 Jun 27;[Epub ahead of print]
  108. Cheung YF, Liang XC, Chi-Fung Chan G, Wong SJ, Ha SY. Myocardial Deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study. Echocardiography. 2010;27:253–259
  109. Hou JW, Wu MH, Lin KH, Lue HC. Prognostic significance of left ventricular diastolic indexes in beta-thalassemia major. Arch Pediatr Adolesc Med. 1994;148:862–866
  110. Westwood MA, Wonke B, Maceira AM, Prescott E, Walker JM, Porter JB, et al. Left ventricular diastolic function compared with T2∗ cardiovascular magnetic resonance for early detection of myocardial iron overload in thalassemia major. J Magn Reson Imaging. 2005;22:229–233
  111. Seliem MA, Al-Saad HI, Bou-Holaigah IH, Khan MN, Palileo MR. Left ventricular diastolic dysfunction in congenital chronic anaemias during childhood as determined by comprehensive echocardiographic imaging including acoustic quantification. Eur J Echocardiogr. 2002;3:103–110
  112. Kremastinos DT. Heart failure in beta-thalassemia. Congest Heart Fail. 2001;7:312–314
  113. Hamdy AM. Use of strain and tissue velocity imaging for early detection of regional myocardial dysfunction in patients with beta thalassemia. Eur J Echocardiogr. 2007;8:102–109
  114. Abraham TP, Dimaano VL, Liang HY. Role of tissue Doppler and strain echocardiography in current clinical practice. Circulation. 2007;116:2597–2609
  115. Dabestani A, Child JS, Henze E, Perloff JK, Schon H, Figueroa WG, et al. Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy. Am J Cardiol. 1984;54:153–159
  116. Yu CM, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler imaging a new prognosticator for cardiovascular diseases. J Am Coll Cardiol. 2007;49:1903–1914
  117. Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, et al. Cardiovascular T2-star (T2∗) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001;22:2171–2179
  118. Anderson LJ, Westwood MA, Holden S, Davis B, Prescott E, Wonke B, et al. Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2∗ cardiovascular magnetic resonance. Br J Haematol. 2004;127:348–355
  119. Leonardi B, Margossian R, Colan SD, Powell AJ. Relationship of magnetic resonance imaging estimation of myocardial iron to left ventricular systolic and diastolic function in thalassemia. JACC Cardiovasc Imaging. 2008;1:572–578
  120. Noetzli LJ, Carson SM, Nord AS, Coates TD, Wood JC. Longitudinal analysis of heart and liver iron in thalassemia major. Blood. 2008;112:2973–2978
  121. Kirk P, Roughton M, Porter JB, Walker JM, Tanner MA, Patel J, et al. Cardiac T2∗ magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation. 2009;120:1961–1968
  122. Mavrogeni SI, Markussis V, Kaklamanis L, Tsiapras D, Paraskevaidis I, Karavolias G, et al. A comparison of magnetic resonance imaging and cardiac biopsy in the evaluation of heart iron overload in patients with beta-thalassemia major. Eur J Haematol. 2005;75:241–247
  123. 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
  124. Garot J, Bluemke DA, Osman NF, Rochitte CE, McVeigh ER, Zerhouni EA, et al. Fast determination of regional myocardial strain fields from tagged cardiac images using harmonic phase MRI. Circulation. 2000;101:981–988
  125. Notomi Y, Setser RM, Shiota T, Martin-Miklovic MG, Weaver JA, Popovic ZB, et al. Assessment of left ventricular torsional deformation by Doppler tissue imaging: validation study with tagged magnetic resonance imaging. Circulation. 2005;111:1141–1147
  126. Olson LJ, Edwards WD, Holmes DR, Miller FA, Nordstrom LA, Baldus WP. Endomyocardial biopsy in hemochromatosis: clinicopathologic correlates in six cases. J Am Coll Cardiol. 1989;13:116–120
  127. Olson LJ, Edwards WD, McCall JT, Ilstrup DM, Gersh BJ. Cardiac iron deposition in idiopathic hemochromatosis: histologic and analytic assessment of 14 hearts from autopsy. J Am Coll Cardiol. 1987;10:1239–1243
  128. Pennell DJ, Porter JB, Cappellini MD, El-Beshlawy A, Chan LL, Aydinok Y, et al. Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia. Blood. 2010;115:2364–2371
  129. Pennell DJ, Berdoukas V, Karagiorga M, Ladis V, Piga A, Aessopos A, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood. 2006;107:3738–3744
  130. Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, et al. 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;115:1876–1884
  131. 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;360:516–520
  132. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2005;112:e154–e235
  133. Arnold JM, Liu P, Demers C, Dorian P, Giannetti N, Haddad H, et al. Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: diagnosis and management. Can J Cardiol. 2006;22:23–45
  134. Olivieri NF, Liu PP, Sher GD, Daly PA, Greig PD, McCusker PJ, et al. Brief report: combined liver and heart transplantation for end-stage iron-induced organ failure in an adult with homozygous beta-thalassemia. N Engl J Med. 1994;330:1125–1127
  135. Wahl S, Quirolo KC. Current issues in blood transfusion for sickle cell disease. Curr Opin Pediatr. 2009;21:15–21
  136. Murphy SW. Diastolic dysfunction. Curr Treat Options Cardiovasc Med. 2004;6:61–68
  137. Ouzounian M, Lee DS, Liu PP. Diastolic heart failure: mechanisms and controversies. Nat Clin Pract Cardiovasc Med. 2008;5:375–386
  138. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med. 1999;341:1447–1457
  139. Mason RP, Marche P, Hintze TH. Novel vascular biology of third-generation L-type calcium channel antagonists: ancillary actions of amlodipine. Arterioscler Thromb Vasc Biol. 2003;23:2155–2163

 See page 896 for disclosure information.

PII: S1071-9164(10)00215-0

doi: 10.1016/j.cardfail.2010.05.009

Journal of Cardiac Failure
Volume 16, Issue 11 , Pages 888-900 , November 2010

Article Tools

* Image Usage & Resolution