Cardiac and Liver Magnetic Resonance Characterization of Thalassemia Intermedia Patients: A Comparative Multicenter Study Versus Thalassemia Major Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5421-5421
Author(s):  
Alessia Pepe ◽  
Brunella Favilli ◽  
Anna Ramazzotti ◽  
Vincenzo Positano ◽  
Caterina Borgna-Pignatti ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Thalassemia Major ◽  
Ventricular Septum ◽  
Myocardial Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron ◽  
Biventricular Function ◽  
Liver Iron Overload

Abstract Little is known about cardiac involvement in Thalassemia Intermedia (TI) using magnetic resonance imaging (MRI). Thus, we investigated myocardial and liver iron overload, myocardial fibrosis, biventricular function parameters and their inter-relationship in 60 TI using MRI. Then, we compared the data of 35 selected TI with age < 39 years with that of 60 Thalassemia Major (TM) patients matched for age. Myocardial Iron Overload (MIO) was assessed using a multislice multiecho T2* approach. Biventricular function parameters were measured quantitatively by cine images. Myocardial fibrosis was evaluated by late gadolinium-enhanced. MIO was present in the 22% of TI patients, more frequently (92%) with an heterogeneous distribution. TI patients with myocardial fibrosis (32%) showed significantly reduced left ventricular ejection fraction (LVEF) (P=0.01). No significant correlation was found between myocardial fibrosis and MIO. Figure shows a TI patient with no myocardial iron overload (all 16 segments and the mid-ventricular septum with T2* values > 20 ms) (A) and late enhancement (white arrows) in the antero-septal junction, in the infero-septal junction and in the mid-ventricular septum (B). In TI patients MIO was significantly lower respect to TM patients; conversely volumes, cardiac indexes, LVEF, bi-atrial areas, and liver iron overload were significantly higher. Myocardial fibrosis was comparable between the 2 groups. TI patients showed lower myocardial iron burden and more pronounced high cardiac output findings with myocardial fibrosis significantly associated to impaired heart function. These data seem to suggest using MRI also for TI patients and could place the basis to reconsider the current cardiological and haematological management in this population. Figure Figure

Prospective Survey on Heart and Liver Iron and Heart Function in Thalassemia Major Patients Treated with Sequential deferiprone–desferrioxamine Versus Deferiprone and Desferrioxamine in Monotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5298-5298
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giuseppe Rossi ◽  
Anna Spasiano ◽  
Domenico Giuseppe D'Ascola ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Heart Function ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
The Other ◽  
Hepatic Iron ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Biventricular Function

Abstract Abstract 5298 Introduction: Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluate quantitatively the changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients under different chelation regimens. This study aimed to prospectively assess the efficacy of the sequential deferiprone–deferrioxamine (DFP-DFO) versus deferiprone (DFP) and deferrioxamine (DFO) in monotherapy in a large cohort of TM patients by quantitative MR. Methods: Among the first 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 392 patients performed a MR follow up study at 18±3 months. We evaluated prospectively the 35 patients treated with DFP-DFO versus the 39 patients treated with DFP and the 74 patients treated with DFO between the 2 MR scans. Iron concentrations were measured by T2* multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results: Excellent/good levels of compliance were similar in the DFP-DFO (97.1%) versus DFP (94.9%) and DFO (95.9%) groups. No significant differences were found in the frequency of side effects in DFP-DFO (15.6%) versus DFP group (9.4%). The percentage of patients who maintained a normal global heart T2* value (≥20 ms) was comparable between DFP-DFO (96%) versus DFP (100%) and DFO (98.1%) groups. Among the patients with myocardial iron overload (MIO) at baseline (global heart T2*<20 ms), in all three groups there was a significant improvement in the global heart T2* value (DFO-DFP: P=0.004, DFP: P=0.015 and DFO: ms P=0.007) and a significant reduction in the number of pathological segments (DFO-DFP: P=0.026, DFP: P=0.012 and DFO: P=0.002). In DFO-DFP and DFP groups there was a significant increment in the left ventricular (LV) ejection fraction (EF) (P=0.035 and P=0.045, respectively) as well as in the right ventricular (RV) EF (P=0.017 and P=0.001, respectively). The improvement in the global heart T2* and in biventricular function were not significantly different in DFO-DFP compared to the other groups (Table 1). Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in DFO group there was a significant improvement in the liver T2* value (2.0±3.5 ms P=0.010). Liver T2*changes were not significantly different in DFO-DFP versus the other groups. Conclusions: Prospectively we did not find significant differences on cardiac and hepatic iron or in cardiac function in TM patients treated with sequential DFP–DFO therapy versus the TM patients treated with DFO or DFP in monotherapy. Disclosures: Pepe: Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy. Lai:Novartis: Honoraria, Research Funding.

Regional Myocardial Contractility In Thalassemia Major By Magnetic Resonance Tagging

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4708-4708
Author(s):  
Antonella Meloni ◽  
Chiara Tudisca ◽  
Emanuele Grassedonio ◽  
Giancarlo Izzi ◽  
Maddalena Lendini ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Iron Overload ◽  
Myocardial Contractility ◽  
Healthy Subjects ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Biventricular Function

Introduction Magnetic resonance (MR) tagging analyzed by dedicated tracking algorithms allows very precise measurements of myocardial motion and characterization of regional myocardial function. No extensive data are available in literature. Our aim was to quantitatively assess for the regional myocardial contractility in thalassemia major (TM) patients and to correlate it with heart iron overload and global biventricular function. Methods Seventy-four TM patients (46 F; 31.8 ± 8.5 yrs) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network underwent MR (1.5T). Three short-axis (basal, medial and apical) tagged MR images were analyzed off-line using harmonic phase (HARP) methods (Diagnosoft software) and the circumferential shortening (Ecc) was evaluated for all the 16 myocardial segments. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. The same axes were acquired by a T2* GRE multiecho technique to assess myocardial iron overload (MIO). Biventricular function parameters were quantitatively evaluated by cine images. Results Segmental ECC values ranged from -9.66 ± 4.17 % (basal anteroseptal segment) to 13.36 ± 4.57 % (mid-anterior segment). No significant circumferential variability was detected. Compared with previous studied healthy subjects, TM patients showed strain values significantly lower in all the circumferential regions at each level (mean difference from 4 % to 13 %; P<0.001 for all the comparisons). Segmental Ecc values were not significantly correlated with the correspondent T2* values and no correlation was detected considering the global values, averaged over all segmental values. Three groups identified on the basis of cardiac iron distribution: no MIO, heterogenous MIO and homogeneous MIO. The global ECC was comparable among the three groups (-11.56 ± 1.60 % vs -11.70 ± 2.43 % vs -11.14 ± 1.95 %; P=0.602). Global ECC values were not significantly correlated with age and were comparable between the sexes. Circumferential shortening was not associated to left ventricular (LV) volumes and ejection fraction (with a P>0.5 in all the comparisons). Conclusions TM patients showed a significantly lower cardiac contractility compared with healthy subjects, but this altered contractility was not related to cardiac iron, volumes and function. Disclosures: No relevant conflicts of interest to declare.

Magnetic Resonance T2* Technique for Segmental and Global Quantification of Myocardial Iron : Multi-Centre Validation in the MIOT (Myocardial Iron Overload in Thalassemia) Network

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5420-5420
Author(s):  
Vincenzo Positano ◽  
Anna Ramazzotti ◽  
Alessia Pepe ◽  
Cristina Salvatori ◽  
Paolo Marcheschi ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Iron Overload ◽  
Healthy Subjects ◽  
Iron Status ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Mri Examination ◽  
Number Of Patients ◽  
Liver Iron Overload ◽  
The Mean

Abstract Iron induced cardiomiopathy is the main cause of mortality in thalassemic population. Thus, the improvement of chelation regimens, to reduce cardiac disease, has the highest priority. Efficient evaluation of cardiac iron status and careful epidemiologic assessment of thalassemic patients play an important role in this matter. T2* magnetic resonance imaging (MRI) is a unique technique to quantify myocardial iron overload and useful to tailor the chelation therapy. Effective and reproducible assessment of myocardial iron loading using the multislice multiecho T2* approach for segmental and global myocardial iron distribution, has been demonstrated at the MRI centre in Pisa [1,2]. Aim of this work is to build within the MIOT (Myocardial Iron Overload in Thalassemia) project a reliable network of haematological and paediatric centers specializing in thalassemia care and MRI centers able to perform feasible and reproducible heart and liver iron overload assessments for a consistent number of thalassemia patients in a standardized and robust manner. First, the transferability of the multislice multiecho T2* technique was assessed. Heart multislice multiecho T2* and liver multiecho T2* sequences were installed on 1.5 T MRI scanners (GE Healthcare) at six different sites in Italy. Five healthy subjects at each site (n=30) were scanned to verify the homogeneity of normal ranges (T2* lover limit of normal 20ms). Then, five thalassemia major (TM) patients were scanned at the reference site and were rescanned locally (n=25) within one month. T2* images were analysed using a previously validated software (HIPPO MIOT®). T2* values of healthy subjects showed inter-sites homogeneity. On TM patients, for global heart T2* values the correlation coefficient was 0.97, Coefficients of Variation (CoVs) ranged from 0.04 to 0.12 and Intraclass Coefficients (ICCs) ranged from 0.94 to 0.99. The mean CoV and ICC for segmental T2* distribution were 0.198 and 88, respectively. After the assessment of MRI technique reproducibility, patients enrolling started in September 2006. Since the project’s beginning, 695 thalassemia patients have been involved in the network. Six hundred and thirteen patients (88%) successfully underwent MRI examination. Each MRI center had a specific absorption capacity that seemed to remain constant over time, but the network was capable of sustaining an increasing number of patients due to continuous enrolment of new centers. The mean distance from the patients’ home locations to the MRI centers where the patients underwent the exams, which is considered an indicator of patient comfort, significantly decreased during the network’s evolution. In Figure, the average distances from the thalassemia centers which sent the patients for MRI examination are plotted versus time. With the activation of delocalized MRI centers, average distances tend to be comparable. In conclusion, the multislice multiecho T2* technique is transferable among scanners with good reproducibility. The MIOT network seems to be a robust and scalable system in which T2* MRI-based cardiac and liver iron overload assessment is available, accessible and reachable for a significant and increasing number of thalassemia patients in Italy, reducing the mean distance from the patients’ locations to the MRI sites. A solid, wide and homogeneous database will constitute an important scientific resource, shortening the time scale for diagnostic, prognostic and therapeutical evidence-based research on the management of thalassemia disease. Figure Figure

A MRI Prospective Survey on Heart and Liver Iron and Cardiac Function in Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine in Monotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3631-3631
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Liana Cuccia ◽  
Monica Fortini ◽  
Vincenzo Caruso ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Biventricular Function

Abstract Background: No prospective data are available about the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy. Our study aimed to prospectively assess the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy in a large cohort of thalassemia major (TM) patients by quantitative Magnetic Resonance (MR). Methods: Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans. We identified three groups of patients: 235 treated with DFX, 142 with DFP and 162 with DFO. Iron overload was measured by T2* multiecho technique. Liver T2* values were converted into liver iron concentration (LIC) values. Biventricular function parameters were quantitatively evaluated by cine images. Results: Excellent/good levels of compliance were similar in the DFX (98.7%) vs DFP (96.3%) and DFO (97.5%) groups. Among the patients with myocardial iron overload at baseline, in all three groups there was a significant improvement in the global heart T2* value (DFX: +4.58±5.91ms P<0.0001, DFP: 8.53±6.97ms P<0.0001 and DFO: +3.93±5.21 ms P<0.0001) and a reduction in the number of pathological segments (DFX: -4.49±4.55 P<0.0001, DFP: -8.08±5.5.84 ms P=0.001 and DFO: -3.65±3.81 ms P<0.0001). In DFP and in DFO groups there was a significant improvement in left ventricular ejection function (LVEF) (+4.86±6.99% P=0.044 and +3.87±7.48% P=0.004, respectively). Only in the DFP group there was a significant improvement in right ventricular ejection function (RVEF) (6.69±4.61% P=0.001). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group , but it was not significantly different in the DFX versus the DFO group (Figure 1). The improvement in the LVEF was significantly higher in both DFP and DFO groups than in the DFX group while the improvement in the RVEF was significantly higher in the DFP than in DFX group (Figure 2). Among the patients with hepatic iron at baseline (LIC≥3mg/g dw) the changes were not significantly different in DFX versus the other groups. Conclusions: Prospectively in a large clinical setting of TM patients, DFX monotherapy was significantly less effective than DFP in improving myocardial siderosis and biventricular function and it was significantly less effective than DFO in improving the LVEF. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

Prevalence, Clinical and Instrumental Correlates of Myocardial Fibrosis and Necrosis by Delayed Contrast Enhancement Cardiovascular Magnetic Resonace in Thalassemia Major Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5424-5424
Author(s):  
Alessia Pepe ◽  
Brunella Favilli ◽  
Vincenzo Positano ◽  
Marcello Capra ◽  
Aurelio Maggio ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Thalassemia Major ◽  
Cardiac Complications ◽  
Apical Region ◽  
Myocardial Iron ◽  
Ecg Changes ◽  
Myocardial Scarring ◽  
Biventricular Function

Abstract Cardiovascular Magnetic Resonance (CMR) by delayed enhancement (DE) has proven to visualize myocardial scarring, but no dedicated studies are available in thalassemia major. Aim of our study was to investigate the prevalence, extent, clinical and instrumental correlates of myocardial fibrosis or necrosis by DE CMR in thalassemia major patients. CMR-DE was performed in 115 thalassemia major patients. Myocardial iron overload was determined by multislice multiecho T2*. Cine images were obtained to evaluate biventricular function. All patients gave written informed consent to the protocol. The project was approved by the institutional ethics committee. DE areas were present in 28 patients (24%). Extent of DE was 3.9±2.4 %. In 26 patients the location of fibrosis was not specific and patchy distribution was prevalent. Two patients showed transmural DE following coronary distribution. The DE group was significantly older (P=0.004). DE correlated with cardiac risk factors (P=0.01), history of cardiac complications (P=0.001), anti-HCV antibodies (P = 0.04) and ECG-changes (P=0.002). We did not find significant relation of DE with heart T2* values and biventricular function. Figure shows a thalassemia major patient with no myocardial iron overload (all 16 segments T2* values &gt; 20 ms) (A) and transmural DE (black arrows) following coronary distribution in the apical region (B,C). In conclusion, in thalassemia major patients the significant presence of myocardial fibrosis/necrosis seems to be a time dependent process correlating with cardiovascular risk factors and cardiac complications. HCV infection could be a causal agent in the pathogenesis of myocardial scarring. ECG-changes showed a good accuracy in predicting myocardial scarring. Figure Figure

scholarly journals Multiparametric cardiac magnetic resonance assessmenti in sickle-beta-thalassemia

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Pepe ◽  
A Meloni ◽  
G Peritore ◽  
M Zerbini ◽  
N Vallone ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Sickle Cell ◽  
Healthy Subjects ◽  
Beta Thalassemia ◽  
Myocardial Iron ◽  
Private Company ◽  
Funding Sources ◽  
Biventricular Function

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A., ApoPharma Inc.). Background. Sickle β-thalassemia (Sβ-thal) is a hereditary hemoglobinopathy resulting from the combined heterozygosity for sickle cell and β-thalassemia genes. Cardiac involvement in Sβ-thal patients has been poorly investigated. Aim. We aimed to evaluate myocardial iron overload and cardiac function by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. Methods. One hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell disease (SCD) patients. Biatrial and biventricular function CMR parameters of Sβ-thal patients were compared with those of 111 healthy volunteers, matched by gender and age. Myocardial iron overload (MIO) was assessed by T2* technique. Cine images were acquired to quantify biventricular function. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Results. In Sβ-thal and SCD patients morphological and functional MR parameters were not significantly different, except for left atrial area and SVI (p = 0.023 and p = 0.048, respectively) that were significantly higher in SCD patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters except for LVEF that was significantly lower (Fig.1). Conclusions. The CMR analysis confirmed that Sβ-thal and SCD patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCD-specific bi-atrial and biventricular reference values.

A T2* MRI Prospective Survey on Heart and Liver Iron In Thalassemia Major Patients Treated with Sequential Deferiprone–Desferrioxamine versus Deferiprone and Desferrioxamine In Monotherapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4259-4259
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Antonella Meloni ◽  
Maria Chiara Dell'Amico ◽  
Luciano Prossomariti ◽  
...  
Keyword(s):  
Iron Overload ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Mean Difference ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Multi Centre Study ◽  
Quantitative Mr ◽  
Liver Iron Overload

Abstract Abstract 4259 Introduction: Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. No data are available in literature about possible different changes in cardiac and liver iron in TM patients treated with sequential deferipron–deferoxamine (DFP-DFO) versus deferipron (DFP) and deferoxamine (DFO) in monotherapy. Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluate quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFP-DFO versus DFP and DFO in monotherapy in a cohort of TM patients by quantitative MR. Methods: Among the first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively the 25 patients treated with DFP-DFO versus the 30 patients treated with DFP and the 66 patients treated with DFO between the 2 MR scans. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Results: The doses of the sequential treatment were DFP 70±14 mg/kg/d for 4 d/w and DFO 42±8 mg/kg/d for 3 d/w, the dose of DFP was 73±16 mg/kg/d, DFO was 41±7 mg/kg/d for 5.5 d/w. Excellent/good levels of compliance were similar in the 3 groups (DFP-DFO 96% versus DFP 97% versus DFO 92%; P = 0.67). Among the patients with no significant myocardial iron overload at baseline (global heart T2* ≥ 20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 95% versus DFP 100% versus DFO 100%; P = 0.23). Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms), only DFP and DFO showed a significant improvement in the global heart T2* value (P = 0.001 and P = 0.003, respectively) and in the number of segment with a normal T2* value (P = 0.031 and P = 0.0001, respectively). The improvement in the global heart T2* was significantly different among groups (mean difference global heart T2* DFP-DFO 2.2 ± 4.1 ms, DFP 10.7 ± 7.2, DFO 3.6 ± 5.4; P = 0.007). The improvement in the global heart T2* was significantly lower in the DFP-DFO versus DFP group (P =0.014), but it was not significantly different in the DFP-DFO versus the DFO group (P = 0.63) (see the figure). In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significantly different among groups (mean difference liver T2* DFP-DFO 0.9 ± 2.1 ms, DFP 2.3 ± 5.8, DFO 2.9 ± 4.9; P = 0.58). Conclusions: prospectively in a clinical setting over 15 months we did not find significant differences on cardiac and liver iron in TM patients treated with sequential DFP–DFO versus the TM patients treated with DFO. Conversely, DFP monotherapy was significantly more effective than DFP-DFO in improving myocardial siderosis. Disclosures: No relevant conflicts of interest to declare.

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