Iron and the heart
The deposition of iron in cardiac tissue is arguably the most harmful manifestation of transfusional iron overload, particularly in patients with beta-thalassemia.1 Liver iron and ferritin correlate only weakly with cardiac iron deposition,2 and it is also notable that in some patients, cardiac dysfunction secondary to iron overload occurs in patients who would otherwise be deemed low risk on the basis of their serum ferritin and liver iron concentration levels.2
While direct measurement of liver iron can be undertaken using a liver biopsy, it is unusual to take such an action on the heart due to the risk of complications. Echocardiography is widespread, accessible and inexpensive and used routinely in functional assessment and monitoring of patients with iron overload.3 However echocardiography has been shown to not correlate strongly with cardiac iron.4
Instead, MR-based techniques may be applied to better characterize and quantify the extent of iron deposition in the heart – so-called cardiac siderosis.
Cardiac Magnetic Resonance (CMR)
T2* CMR is used for the assessment of cardiac iron. The technique is now validated after demonstrating correlation with cardiac iron concentration measurement on postmortem cardiac biopsies.5
Indicative CMR T2* values for iron overload states6
|T2* > 20 ms|
Indicative of some deposition
|T2* 10 – 20 ms|
Deposition sufficient to risk cardiac decompensation
|T2* < 10 ms|
CMR can rapidly assess iron content in the heart with the potential to measure heart function. In patients with transfusion-dependent thalassemia, cardiac MRI values <20 milliseconds (ms) are indicative of declining left ventricular ejection fraction1 and associated with arrhythmias while values <10 ms are associated with overt heart failure and mortality.7,8
Considering the slow deposition of iron in the heart compared to the liver, guidelines recommend assessment not before the age of 10 years or younger if the patient is compliant,9 especially in view of recent evidence on myocardial iron overload in patients as young as 6 years of age.10
Next: Bone Marrow Examination
- Anderson L. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. European Heart Journal. 2001;22(23):2171-2179.
- Tanner MA, Galanello R, Dessi C, et al. Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson. 2008;10:12.
- Kremastinos DT, Farmakis D. Iron overload cardiomyopathy in clinical practice. Circulation. 2011;124(20):2253-2263.
- Leonardi B, Margossian R, Colan SD, et al. Relationship of magnetic resonance imaging estimation of myocardial iron to left ventricular systolic and diastolic function in thalassemia. JACC Cardiovasc Imaging. 2008;1(5):572-578.
- Carpenter JP, He T, Kirk P, et al. On T2* magnetic resonance and cardiac iron. Circulation. 2011;123(14):1519-1528.
- Wood JC. Magnetic resonance imaging measurement of iron overload. Curr Opin Hematol. 2007;14(3):183-190.
- Kirk P, Roughton M, Porter JB, et al. Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation. 2009;120(20):1961-1968.
- Carpenter JP, Roughton M, Pennell DJ, et al. International survey of T2* cardiovascular magnetic resonance in beta- thalassemia major. Haematologica. 2013;98(9):1368-1374.
- Cappellini MD, Cohen A, Porter J, et al. Guidelines for the management of transfusion dependent thalassemia (TDT). 3rd Ed. Nicosia, Cyprus: Thalassemia International Federation; 2014.
- Yang G, Liu R, Peng P, et al. How early can myocardial iron overload occur in beta thalassemia major? PLoS One. 2014;9(1):e85379.