Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure.</p> <p>Methods</p> <p>We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR), and following this, late gadolinium enhancement (LGE) was used to determine the presence of macroscopic myocardial fibrosis.</p> <p>Results</p> <p>The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms). Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* < 20 ms at the time of scan.</p> <p>Conclusion</p> <p>This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.</p

Value of black blood T2* cardiovascular magnetic resonance

Purpose To assess whether black blood T2* cardiovascular magnetic resonance is superior to conventional white blood imaging of cardiac iron in patients with thalassaemia major (TM). Materials and methods We performed both conventional white blood and black blood T2* CMR sequences in 100 TM patients to determine intra and inter-observer variability and presence of artefacts. In 23 patients, 2 separate studies of both techniques were performed to assess interstudy reproducibility. Results Cardiac T2* values ranged from 4.5 to 43.8 ms. The mean T2* values were not different between black blood and white blood acquisitions (20.5 vs 21.6 ms, p = 0.26). Compared with the conventional white blood diastolic acquisition, the coefficient of variance of the black blood CMR technique was superior for intra-observer reproducibility (1.47% vs 4.23%, p < 0.001), inter-observer reproducibility (2.54% vs 4.50%, p < 0.001) and inter-study reproducibility (4.07% vs 8.42%, p = 0.001). Assessment of artefacts showed a superior score for black blood vs white blood scans (4.57 vs 4.25; p < 0.001). Conclusions Black blood T2* CMR has superior reproducibility and reduced imaging artefacts for the assessment of cardiac iron, in comparison with the conventional white blood technique, which make it the preferred technique for clinical practice

Effects of combined deferiprone with deferoxamine on right ventricular function in thalassaemia major

BACKGROUND: Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR). METHODS: We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading. RESULTS: In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01). CONCLUSIONS: In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis

Electrocardiographic (ECG) criteria for determining left ventricular mass in young healthy men; data from the LARGE Heart study

Background: Doubts remain over the use of the ECG in identifying those with increased left ventricular (LV) mass. This is especially so in young individuals, despite their high prevalence of ECG criteria for LV hypertrophy. We performed a study using cardiovascular magnetic resonance (CMR), which provides an in vivo non-invasive gold standard method of measuring LV mass, allowing accurate assessment of electrocardiography as a tool for defining LV hypertrophy in the young.Methods and results: Standard 12-lead ECGs were obtained from 101 Caucasian male army recruits aged (mean +/- SEM) 19.7 +/- 0.2 years. LV mass was measured using CMR. LV mass indexed to body surface area demonstrated no significant correlation with the Cornell Amplitude criteria or Cornell Product for LV hypertrophy. Moderate correlations were seen with the Sokolow-Lyon Amplitude (0.28) and Sokolow-Lyon Product (0.284). Defining LV hypertrophy as a body surface area indexed left ventricular mass of 93 g/m(2), calculated sensitivities [and specificities] were as follows; 38.7% [74.3%] for the Sokolow-Lyon criteria, 43.4% [61.4%] for the Sokolow-Lyon Product, 19.4% [91.4%] for Cornell Amplitude, and 22.6% [85.7%] for Cornell Product. These values are substantially less than those reported for older age groups.Conclusion: ECG criteria for LV hypertrophy may have little value in determining LV mass or the presence of LV hypertrophy in young fit males