Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.

Through cardiac looping during embryonic development, paths of flow through the mature heart have direction changes and asymmetries whose topology and functional significance remain relatively unexplored. Here we show, using magnetic resonance velocity mapping, the asymmetric redirection of streaming blood in atrial and ventricular cavities of the adult human heart, with sinuous, chirally asymmetric paths of flow through the whole. On the basis of mapped flow fields and drawings that illustrate spatial relations between flow paths, we propose that asymmetries and curvatures of the looped heart have potential fluidic and dynamic advantages. Patterns of atrial filling seem to be asymmetric in a manner that allows the momentum of inflowing streams to be redirected towards atrio-ventricular valves, and the change in direction at ventricular level is such that recoil away from ejected blood is in a direction that can enhance rather than inhibit ventriculo-atrial coupling. Chiral asymmetry might help to minimize dissipative interaction between entering, recirculating and outflowing streams. These factors might combine to allow a reciprocating, sling-like, 'morphodynamic' mode of action to come into effect when heart rate and output increase during exercise.

Background Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance (CMR) relaxation parameter R2* (assessed clinically via its reciprocal T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans is limited. Methods and Results Twelve human hearts were studied from transfusion dependent patients following either death (heart failure n=7, stroke n=1) or transplantation for end-stage heart failure (n=4). After CMR R2* measurement, tissue iron concentration was measured in multiple samples of each heart using inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean (±SD) global myocardial iron causing severe heart failure in 10 patients was 5.98 ±2.42mg/g dw (range 3.19–9.50), but in 1 outlier case of heart failure was 25.9mg/g dw. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R2=0.910, p<0.001) leading to [Fe]=45.0•(T2*)−1.22 for the clinical calibration equation with [Fe] in mg/g dw and T2* in ms. Mid-ventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron. Conclusions These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for CMR R2* against myocardial iron concentration. The iron values are of considerable interest with regard to the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in-vivo by CMR of the mid septum.