Worldwide survey of T2* cardiovascular magnetic resonance in Thalassaemia

Introduction Thalassaemia major (TM) affects hundreds of thousands of patients worldwide but only a minority have access to regular blood transfusion and chelation therapy. Cardiovascular magnetic resonance (CMR) T2* measurement provides an accurate, reproducible measurement of cardiac iron which is the cause of heart failure and early death in many transfused TM patients. This technique has been adopted as part of routine management in many countries where survival is now approaching normal but little is known about the severity and effects of myocardial iron loading in different geographical regions. Purpose The aim of this study was to describe the burden of disease of myocardial siderosis (measured by T2*) in different populations throughout the world and to assess the relationship between T2* and outcome such as heart failure and cardiac death. Methods 34 worldwide centres were involved in this survey of 3376 patients from Europe, the Middle East, North America, South America, North Africa, Australia and Asia. Anonymised data on myocardial T2* values were analysed in conjunction with clinical outcomes (heart failure and death). Results Overall, 57.5% of patients had no significant iron loading (T2* >20ms), 22.6% had moderate cardiac iron (10ms50%) in South-East Asia had cardiac iron (T2* >20ms) at baseline. At the time of the first scan, 100 patients (3.3%) had confirmed heart failure, the majority of whom (77.0%) had myocardial T2* <10ms with almost all (99%) having T2* <20ms. There were 113 patients who subsequently developed heart failure. 92.0% of these had T2* <10ms and 99.1% had a T2* <20ms. There were 39 deaths. Cardiac T2* values were <10ms in 79.5%, with 92.3% <20ms. Conclusions Even in this well-treated cohort with access to transfusion, chelation and CMR, there is a large proportion of TM patients with moderate to severe cardiac iron loading. Low T2* (<10ms) is associated with cardiac failure and death. There is a huge unmet worldwide need in terms of access to specialist medical care (including transfusion and chelation therapy) together with advanced monitoring techniques (such as CMR)

The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

CARDIAC MAGNETIC RESONANCE IN TRANSFUSION DEPENDENT THALASSAEMIA: ASSESSMENT OF IRON LOAD AND RELATION TO LEFT VENTRICULAR EJECTION FRACTION

International audienceCardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0.57, p 8ms and ≤14 ms and reduced to 9.1% in patients with T2* between 14-20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for cardiac dysfunction (ROC Analysis, AUC = 0.68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible

Evaluation of liver fibrosis in patients with thalassemia: The important role of hyaluronic acid

Patients with transfusion-dependent thalassemia major often develop liver fibrosis due to liver iron overload and/or hepatitis virus C (HCV) infection. Hyaluronic acid (HA) plays a prominent role in the pathogenesis of liver fibrosis and the elevation of serum HA concentration is due to either increased synthesis by inflammatory cells and hepatic stellate cells or impaired degradation by sinusoidal endothelial cells (SECs) and thus is proposed as a non-invasive biomarker of liver fibrosis either by itself and/or included in the Hepascore formula. In this study we evaluated prospectively a screening of liver fibrosis in 201 adult patients aged 19-54 years with transfusion-dependent thalassemia major, based on HA measurements. 41/201 patients were HCV-RNA (+). HA was measured with a turbidimetric assay applied on a clinical chemistry analyzer. The Hepascore was computed from the results by using the model previously published. The main results of the study showed that: a) HA levels were increased in 110/201 (55%) thalassemia patients 85.0 +/- 10.3 ng/ml, ranged from 15.0 to 1495.0 mu g/l, compared to 20.8 +/- 7.4 mu g/l reference laboratory values, p&lt;0.001, b) HA levels were significantly higher in HCV-RNA( +) compared to HCV-RNA(-) patients, 171.6 +/- 202 vs 53.8 +/- 35.5 mu g/l, p&lt;0.0001 c) no significant correlations were found between HA levels and/or Hepascore with ferritin and liver iron content (LIC) assessed with MRI (p&gt;0.324 and p&gt;0.270, respectively). Our findings indicate that hyaluronic acid measurements contribute to the assessment of liver fibrosis in patients with thalassemia and might be helpful for further evaluation of patients with liver biopsy if this is truly needed. Furthermore, liver fibrosis in thalassemia seems to be independent from liver siderosis. (C) 2010 Elsevier Inc. All rights reserved

Cystatin C levels in patients with beta-thalassemia during deferasirox treatment

Deferasirox (Exjade (R)) is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload. This study was conducted to analyze changes in cystatin C concentration, an endogenous marker of glomerular filtration rate (GFR), in patients with thalassemia receiving daily deferasirox therapy over a period of at least 9 months. One hundred and fifty beta-thalassemia patients were treated with deferasirox at doses of 20-40 mg/kg/day for 9 consecutive months. Cystatin C concentrations were measured at regular intervals and GFR was calculated according to the cystatin C-based prediction equation. Plasma concentrations of NGAL protein and NT-proBNP were also monitored as indicators of renal function and LVEF, respectively. Serum ferritin concentration was also measured to assess iron overload. Throughout the 9 months of deferasirox treatment cystatin C concentration remained stable (p&gt;0.850). The baseline cystatin C mean values were 0.97 +/- 0.27 mg/L and reached a maximum of 1.01 +/- 0.29 mg/L at 4 months of treatment. No correlation was found between cystatin C and NGAL concentrations (p&gt;0.674). Cystatin C and NT-proBNP concentrations correlated positively with a binomial equation (p&lt;0.004), as also did cystatin C and serum ferritin (p&lt;0.001). These findings suggest that slight changes of cystatin C during deferasirox treatment may not reflect renal injury. However hemodynamic signals such as LVEF alterations and iron mobilization do appear to affect changes in cystatin C concentration. (C) 2010 Elsevier Inc. All rights reserved