Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major.

Background The multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. Methods We considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. Results We identified 4 groups of patients: 138 with homogeneous MIO (all segments with T2* < 20 ms), 97 with heterogene…

Preferential patterns of myocardial iron overload by multislice multiecho T2* CMR in thalassemia major patients.

T*(2) multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty-three thalassemia major patients underwent cardiac MR. Three short-axis views of the left ventricle were acquired and analyzed using a 16-segment standardized model. The T*(2) value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (glob…

Feasibility, reproducibility, and reliability for the T*2 iron evaluation at 3 T in comparison with 1.5 T

This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T * 2 Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T * 2 values at 3 and 1.5 T. Thirty-eight transfusion-dependent patients and 20 healthy subjects were studied. Cardiac segmental and global T * 2 values were calculated after developing a correction map to compensate the artifactual T * 2 variations. The hepatic T * 2 value was determined over a region of interest. The intraoperator and interoperator reproducibility for T * 2 measurements at 3 T was good. A linear relationship was found between patients' R (1000/T * …

Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron

Purpose To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for global and segmental measurement of iron overload in thalassemia patients. Materials and Methods Multiecho T2* sequences were installed on six MRI scanners. Five healthy subjects (n = 30) were scanned at each site; five thalassemia major (TM) patients were scanned at the reference site and were rescanned locally (n = 25) within 1 month. T2* images were analyzed using previously validated software. Results T2* values of healthy subjects showed intersite homogeneity. On TM patients, for global heart T2* values the correlation coefficient was 0.97, coefficients of variation (CoV…

Myocardial fibrosis by delayed enhancement cardiovascular magnetic resonance and HCV infection in thalassemia major patients.

Abstract Abstract 4265 Introduction. Delayed enhancement (DE) cardiac magnetic resonance (CMR) technique with intravenous administration of gadolinium (Gd) chelates contrast agents is the only validated non-invasive approach for detecting myocardial fibrosis (Mahrholdt H et al, Eur Heart J 2005). This technique has been confirmed safe in patients with hemoglobinopathies (Meloni A et al, Haematologica 2009). In thalassemia major (TM), myocardial fibrosis has been detected using the DE technique and a positive correlation with anti-HCV antibodies has been described (Pepe A et al, Heart 2009). However, HCV-induced cardiomyopathy is still controversial (Matsumori A et al. J Card Fail 2006). The…

Cardiac and hepatic iron and ejection fraction in thalassemia major: Multicentre prospective comparison of combined Deferiprone and Deferoxamine therapy against Deferiprone or Deferoxamine Monotherapy

Background: Due to the limited data available in literature, the aim of this multi-centre study was to prospectively compare in thalassemia major (TM) patients the efficacy of combined deferiprone (DFP) and deferoxamine (DFO) regimen versus either DFP and DFO in monotherapy by cardiovascular magnetic resonance (CMR) over a follow up of 18 months. Methods: Among the first 1135 TM patients in the MIOT (Myocardial Iron Overload in Thalassemia) network, we evaluated those who had received either combined regimen (DFO + DFP, N=51) or DFP (N=39) and DFO (N=74) monotherapies between the two CMR scans. Iron overload was measured by T2* multiecho technique. Biventricular function parameters were qua…

Non-compact myocardium assessment by cardiac magnetic resonance: dependence on image analysis method

To compare image analysis methods for the assessment of left ventricle non-compaction from cardiac magnetic resonance (CMR) imaging. CMR images were analyzed in 20 patients and 10 normal subjects. A reference model of the MR signal was introduced and validated based on image data. Non-compact (NC) myocardium size and distribution were assessed by tracing a single, continuous contour delimiting trabeculated region (Jacquier) or by one-by-one selection of trabeculae (Grothoff). The global non-compact/compact (NC/C) ratio, the NC mass, and the segmental NC/C ratio were assessed. Results were compared with the reference model. A significant difference between Grothoff and Jacquier approaches in…

Improved T2* assessment in liver iron overload by magnetic resonance imaging.

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A softwar…

Evaluation of the efficacy of oral deferiprone in beta-thalassemia major by multislice multiecho T2*.

Objectives: Oral deferiprone (L1) appears to be promising in the treatment of beta-thalassemia major (TM) patients. T2* magnetic resonance imaging (MRI) with a single measurement in the mid-ventricular septum was validated as a quantitative evaluation of myocardial iron overload. Previous studies suggested a marked heterogeneity of iron distribution in the myocardium. We set up a multislice multiecho T2* MRI for the detection of this heterogeneity. The aim of our study was to investigate differences between the L1 vs. the subcutaneous desferrioxamine (DF)-treated patients using this new approach.Methods: Thirty-six beta-TM patients (age 29 +/- 8 yr) underwent MRI. Eighteen patients received…

Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalasse…

Myocardial fibrosis by delayed enhancement cardiovascular magnetic resonance and HCV infection in thalassemia major patients

ss Open Acce Oral presentation Myocardial fibrosis by delayed enhancement cardiovascular magnetic resonance and HCV infection in thalassemia major patients Alessia Pepe1, Antonella Meloni1, Zelia Borsellino2, Maria Chiara Dell'Amico1, Vincenzo Positano1, Caterina Borgna-Pignatti3, Aurelio Maggio4, Gennaro Restaino5, Francesco Gagliardotto2, Paolo Cianciulli6, Luciano Prossomariti7, Aldo Filosa7, Michele Centra8, Domenico D'Ascola9, Antonella Quarta10, Angelo Peluso11, Antonello Pietrangelo12, Eliana Cracolici13, Massimo Lombardi*1 and Marcello Capra2

Multislice multiecho T2* cardiac magnetic resonance for the detection of heterogeneous myocardial iron distribution in thalassaemia patients

The present study investigated myocardial T2* heterogeneity in thalassaemia major (TM) patients by cardiac magnetic resonance (CMR), to determine whether is related to inhomogeneous iron overload distribution. A total of 230 TM patients consecutively referred to our laboratory were studied retrospectively. Three short-axis views (basal, medium and apical) of the left ventricle (LV) were obtained by multislice multiecho T2* CMR. T2* segmental distribution was mapped on a 16-segment LV model. The level of heterogeneity of the T2* segmental distribution, evaluated by the coefficient of variation (CoV), was compared with that of a surrogate data set, to determine whether the inhomogeneous segme…

Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload.

Purpose To evaluate the effectiveness of the single ROI approach for the detection of hepatic iron burden in thalassemia major (TM) patients in respect to a whole liver measurement. Materials and Methods Five transverse hepatic slices were acquired by a T2* gradient-echo sequence in 101 TM patients and 20 healthy subjects. The T2* value was calculated in a single region of interest (ROI) defined in the medium-hepatic slice. Moreover, the T2* value was extracted on each of the eight ROIs defined in the functionally independent segments. The mean hepatic T2* value was calculated. Results For patients, the mean T2* values over segments VII and VIII were significantly lower. This pattern was su…

40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload.

Purpose To assess the tissue iron concentration of the left ventricle (LV) using a multislice, multiecho T2* MR technique and a segmental analysis. Materials and Methods T2* multiecho MRI was performed in 53 thalassemia major patients. Three short-axis views of the LV were obtained and analyzed with custom-written software. The myocardium was automatically segmented into 12 segments. The T2* value on each segment as well as the global T2* value were calculated. Cine dynamic images were also obtained to evaluate biventricular function parameters by quantitative analysis. Results For the T2* global value, the coefficient of variation (CoV) for intra-/interobserver and interstudy reproducibili…

The prognostic role of CMR using global planimetric criteria in patients with excessive left ventricular trabeculation.

Objectives: Although cardiovascular magnetic resonance (CMR) is widely used in the assessment of left ventricular non-compaction (LVNC), there are no universally accepted diagnostic criteria and limited data regarding their prognostic value. We assessed the long-term prognostic role of the planimetric global Grothoff’s criteria and of the CMR findings in predicting adverse cardiovascular events (CE). Methods: We prospectively enrolled 78 patients (46.7 ± 18.7 years, 33.3% females) with documented positive Jenni’s echocardiographic criteria for LVNC. Cine images were used to quantify function parameters and to assess for the presence of all four quantitative Grothoff’s criteria (global Groth…

Nitrate-induced coronary vasodilation by stress-magnetic resonance imaging: A novel noninvasive test of coronary vasomotion

Purpose To evaluate the feasibility of assessing coronary vasodilation following exogenous nitrates, using magnetic resonance angiography (MRA). The assessment of coronary response to exogenous nitrovasodilators may have a diagnostic and prognostic impact in patients with coronary artery disease. To date, stress imaging of coronary artery vasomotion has been confined to the catheterization laboratory. MRA is emerging as a noninvasive tool for coronary artery imaging. Materials and Methods Coronary MRA was performed in 20 healthy volunteers (12 males, age = 33 ± 8). We used spiral spoiled gradient echo (SSGE) sequences for imaging of coronary artery lumen. After the baseline short-axis view …

Iron in the human hearts: distribution and association with R2* values by CMR

Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy

[Formula: see text] multislice multiecho cardiac magnetic resonance (CMR) allows quantification of the segmental distribution of myocardial iron overload (MIO). We evaluated whether a preferential pattern MIO was preserved between two CMR scans in regularly chelated thalassaemia major (TM) patients.We evaluated prospectively 259 TM patients enrolled in the MIO in Thalassaemia (MIOT) network with a CMR follow-up (FU) study at 18 ± 3 months and significant MIO at baseline. The [Formula: see text] in the 16 segments and the global value were calculated. Four main circumferential regions (anterior, septal, inferior and lateral) were defined. We identified two groups: severe (n = 80, global [For…

Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts.

A segmental, multislice, multi-echo T2* MRI approach could be useful in heart iron-overloaded patients to account for heterogeneous iron distribution, demonstrated by histological studies. However, segmental T2* assessment in heart can be affected by the presence of geometrical and susceptibility artefacts, which can act on different segments in different ways. The aim of this study was to assess T2* value distribution in the left ventricle and to develop a correction procedure to compensate for artefactual variations in segmental analysis. MRI was performed in four groups of 22 subjects each: healthy subjects (I), controls (II) (thalassemia intermedia patients without iron overload), thala…

The Prognostic Role of Hypertrabeculation By Cardiac Magnetic Resonance in Thalassemia Intermedia Patients

Abstract Background. Differentiation of left ventricle non-compaction (LVNC) from hypertrabeculated LV due to a negative heart remodeling in thalassemia intermedia (TI) can depends on the selected CMR criterion. The recently proposed Piga's criterion (NC/C ratio threshold of &gt;2.5, Am J Haem 2012) seems to have a low specificity to identify the true LVNC in TI. Anyway, the Piga's criterion could well detect easy a negative heart remodeling in TI patients. Purpose: To assess prospectively whether the Piga's criterion has a prognostic role for adverse cardiovascular outcomes in TI patients. Methods. We studied prospectively by CMR 168 TI patients (81 males, mean age 38.32 ±11.61 years) cons…

Influence of myocardial fibrosis and blood oxygenation on heart T2* values in thalassemia patients

Purpose To determine whether T2* measurements quantifying myocardial iron overload in thalassemia patients are influenced by myocardial fibrosis and blood oxygenation. Materials and Methods Multislice multiecho T2* was performed in 94 thalassemia patients in order to quantify myocardial iron overload. The left ventricle was automatically segmented into a 16-segment standardized heart model, and the T2* value on each segment as well as the global T2* were calculated. Delayed enhanced cardiovascular magnetic resonance (DE-CMR) images were obtained to detect myocardial fibrosis. The blood oxygenation was assessed by the noninvasive measurement of partial pressure of oxygen (pO2). Results Myoca…

Myocardial scarring by delayed enhancement cardiovascular magnetic resonance in thalassaemia major

Background: Cardiovascular magnetic resonance (CMR) by delayed enhancement (DE) enables visualisation of myocardial scarring, but no dedicated studies are available in thalassaemia major. Objective: To investigate the prevalence, extent, clinical and instrumental correlates of myocardial fibrosis or necrosis by DE CMR in patients with thalassaemia major. Patients: 115 Patients with thalassaemia major consecutively examined at an MRI laboratory. Methods: DE images were acquired to quantify myocardial scarring. Myocardial iron overload was determined by multislice multiecho T2*. Cine images were obtained to evaluate biventricular function. Results: DE areas were present in 28/115 patients (24…

The planimetric Grothoff's criteria by cardiac magnetic resonance can improve the specificity of left ventricular non-compaction diagnosis in thalassemia intermedia

We differentiated the left ventricle non-compaction (LVNC) from hypertrabeculated myocardium due to a negative remodeling in thalassemia intermedia (TI) patients applying linear and planimetric criteria and comparing the cardiovascular magnetic resonance (CMR) findings. CMR images were analyzed in 181 TI patients enrolled in the Myocardial Iron Overload in Thalassemia Network and 27 patients with proved LVNC diagnosis. The CMR diagnostic criteria applied in TI patients were: a modified linear CMR Petersen’s criterion based on a more restrictive ratio of diastolic NC/C &gt; 2.5 at segmental level and the combination of planimetric Grothoff’s criteria (percentage of trabeculated LV myocardial…