Cardiovascular magnetic resonance in cardiomyopathies

Background: Cardiomyopathy (CM) frequently leads to heart failure which is associated with a high degree of mortality, morbidity and financial burden on healthcare providers. Confidence in the recognition of risk factors or in early diagnosis allows timely intervention, before heart failure develops. The right ventricle (RV) has historically been overlooked when assessing cardiac function and response to therapy but its importance is increasingly recognised. Cardiovascular magnetic resonance (CMR) is established as the gold standard for assessing the functional consequences of cardiovascular disease, being non-invasive and with high accuracy and reproducibility. It can also provide in-vivo tissue information which may be diagnostic before functional changes are apparent. With this backdrop I tested the hypothesis that CMR can provide early disease markers in patients at risk of heart failure in 3 unrelated conditions associated with heart failure including: Emery-Dreifuss muscular dystrophy (EDMD), anthracycline induced cardiomyopathy and cardiac iron overload in transfusion dependent patients. Methods and Results: Patients with 3 different clinical substrates for the development of CM were studied. In group 1, patients with EDMD were studied by CMR and echo. There was a significant reduction in inferior wall contractility using CMR tagging (-0.062±0.02 versus -0.094±0.03 in the control group, p=0.048) and in echo derived early diastolic myocardial posterior wall velocity gradients (4±1.2 vs. 7.1±2.7 s-1, p=0.02). Bi-ventricular ejection fraction (EF) was normal and no late gadolinium enhancement (LGE) was detected. These findings demonstrated the relative insensitivity of EF in the detection of early disease and the need for careful follow up in these patients. In group 2, anthracycline mediated cardiotoxicity (AMC) was studied. The risk of heart failure rises with cumulative dose but not all individuals are susceptible. In a cohort of patients with early breast cancer an increase in early gadolinium relative enhancement (EGRE) from baseline to day 3 correlated with a reduction in LVEF after a year (R=0.34, p=0.01) suggesting a potential clinical role for EGRE in the prediction of late AMC. In group 3, patients with thalassaemia major (TM) were studied. The coefficient of variance (CV) for a new black blood T2* sequence was found to be significantly lower than the white blood sequence (1.47% vs 4.23%, p<0.001) and this was adopted for clinical use. The RV response to iron chelation therapy was examined in 3 clinical trials. Using deferiprone monotherapy RVEF increased from 69.6±5.2 to 72.2±5.3% (p=0.001) with a reduction in RV end-systolic volume (ESV) from 37.7±11.7 to 34.2±11.3 mL (p=0.009). With deferiprone/deferoxamine combination therapy the RVEF increase from 60.2±7.2 to 63.8±5.9% (p<0.001) and RVESV decreased from 60.8±24.2 to 50.6±17.3 mL (p<0.01). These improvements mirrored the LV response. However, the response to deferasirox monotherapy was different with no change in LVEF, but an increase in RVEF from 66.1±6.1 to 68.8±5.4 (p=0.001) driven by an increase in RV end diastolic volume (EDV) from 69.3±19.8 to 76.1±17.1 (p<0.001) with a reduction in RV mass from 32.8±7.8 to 24.7±5.6 (p<0.001) and LV mass (78.6±16.9 to 66.5±12.9, p