Cardiac iron across different transfusion-dependent diseases

Abstract

Iron overload occurs in patients who require regular blood transfusions to correct genetic and acquired anaemias, such as beta-thalassaemia major, sickle cell disease, and myelodysplastic syndromes. Although iron overload causes damage in many organs, accumulation of cardiac iron is a leading cause of death in transfused patients with beta-thalassaemia major. The symptoms of cardiac iron overload will occur long after the first cardiac iron accumulation, at a point when treatment is more complex than primary prevention would have been. Direct measurement of cardiac iron using T2* magnetic resonance imaging, rather than indirect methods such as measuring serum ferritin levels or liver iron concentration have contributed to earlier recognition of myocardial iron loading and prevention of cardiac toxicity. Cardiac siderosis occurs in all transfusional anaemias, but the relative risk depends upon the underlying disease state, transfusional load, and chelation history. All three available iron chelators can be used to remove cardiac iron, but each has unique physical properties that influence their cardiac efficacy. More prospective trials are needed to assess the effects of single-agent or combination iron chelation therapy on the levels of cardiac iron and cardiac function. Ultimately, iron chelation therapies should be tailored to meet individual patient needs and lifestyle demands.

Fig. 1

Scheme showing iron entry, storage, and toxicity in the heart, each represented as separate processes. Reproduced with permission from Wood JC, et al. Ann NY Acad Sci 2005;1054:387–95. © 2005 New York Academy of Sciences.

Figure 2

Relationships between myocardial T2* values and parameters of ventricular function: (A) left ventricular ejection fraction, (B) left ventricular mass index, (C) left ventricular end-systolic volume index. The broken lines represent the normal reference ranges for myocardial T2* and parameters of cardiac function. Below a myocardial T2* of 20 ms, there is a progressive and significant decline in left ventricular ejection fraction and an increase in the left ventricular end-systolic volume index and left ventricular mass index. Reproduced with permission from Anderson LJ, et al. Eur Heart J 2001;22:2271–9. By permission of Oxford University Press. © 2001 by the European Society of Cardiology.

Figure 3

Relationship between left ventricular ejection fraction and myocardial T2* in patients with thalassaemia and rare anaemias. Dotted line represents reference range for ejection fraction. Wood JC, et al. Unpublished data.

Figure 4

Relationship between left ventricular ejection fraction and myocardial T2* in patients with thalassaemia and sickle cell disease. Dotted lines represent reference range for ejection fraction. Shading round points indicates a need for cardiac medications. Two patients had ventricular tachycardia, indicated by the letters VT. Reproduced with permission from Wood JC, et al. Blood 2004;103:1934–6. © 2004 the American Society of Hematology.