Biventricular Function Parameters Research Articles

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

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).Table 1Inter-treatment (DFP-DFO vs DFP and DFP-DFP vs DFO) comparisons in terms of changes between the two MRs in patients with global heart T2* <20 ms.PDFP (n = 9)DFP-DFO (n = 10)DFO (n = 21)PMean Diff. Global Heart T2* (ms)0.195+8.8 ± 8.6+4.8 ± 3.93.7 ± 5.50.581Mean Diff. N seg. with T2* < 20 ms0.214−6.0 ± 5.6−3.2 ± 3.8−2.9 ± 3.70.838Mean Diff. LV EF (%)0.800+5.0 ± 6.4+4.3 ± 5.1+2.0 ± 6.20.330Mean Diff. RV EF (%)0.941+6.8 ± 3.7+6.7 ± 6.6+0.2 ± 8.80.058Mean Diff. Ferritin (ng/ml)0.259−113 ± 241−333 ± 516−133 ± 5750.362Among 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.

Onset of Cardiac Iron Loading in a Large and Homogeneous Cohort of Thalassemia Major Paediatric Patients

Abstract 2157 Introduction:Magnetic Resonance Imaging (MRI) by the T2* technique allows highly reproducible and non invasive quantifications of myocardial iron burden and it is the gold standard for quantifying biventricular function parameters. It is important to determine the appropriate age to start MRI screening, because its high cost. Few data are available in the literature and they are contrasting. So the aim of this study was to address this issue in our paediatric patients with thalassemia major (TM). Methods:We studied retrospectively 72 patients (47 males, 4.2–17.9 years old, mean age 13.03 ± 3.70 years), enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network. Myocardial iron overload was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results:The global heart T2* value was 29.7 ± 11.2 ms (range 6.2 – 48.0 ms). No significant correlation was found between global heart T2* value and age (see figure). The global heart T2* value did not show significant differences according to the sex (male 30.2 ± 11.0 ms versus female 28.7 ± 11.8 ms, P=0.568). Sixteen patients (22%) showed an abnormal global heart T2* value (<20 ms) and none of them was under 8 years of age. Global heart T2* value was negatively correlated with mean serum ferritin levels. Odds Ratio for high serum ferritin levels (≥ 1500 ng/ml) was 8.4 (1.01–69.37, OR 95%CI) for abnormal global heart T2* values (< 20 ms). The global heart T2* value did not show a significant difference with respect to the chelation therapy (P=0.322). No significant correlations were found between the global heart T2* values and the bi-atrial areas or the LV and RV morphological and functional parameters. Eight patients showed a left ventricular (LV) ejection fraction (EF) < 57% and none of them was under 7 years of age. Two patients showed a right ventricular (RV) EF < 52% and none of them was under 14 years of age. Conclusion:The MRI screening for both cardiac iron overload and function assessment can be started for TM patients at the age of 7 years. At this age not sedation is generally needed. If the availability of cardiac MRI is low, the serum ferritin levels could be used as a discriminating factor. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Different patterns of myocardial iron overload by multislice T2* Cardiovascular MR as markers of risk for cardiac dysfunction in thalassemia major

Background The multislice multiecho T2* CMR technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this study was to verify the risk of biventricular dysfunction related to different patterns of MIO in a large cohort of thalassemia major (TM) patients. Methods 1135 TM patients (538 M, mean age 30 ± 19 years) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network underwent CMR (1.5 T). For the assessment of MIO, three short-axis views of the left ventricle (LV) were acquired and the myocardium was segmented into 16-segments standardized LV model. The T2* value on each segment was calculated as well as the global T2* value. A conservative cut off of 20 ms was considered the limit of normal for the segmental and global T2* values. Biventricular function parameters were quantitatively evaluated by SSFP cine images. The lower limit of normal for the LVEF and the RVEF were established from CMR in a large cohort of well-treated TM patients without myocardial iron overload and cardiac diseases. Results Four groups of patients were identified: homogeneous MIO (all segments with T2* values <20 ms) (N=173, 15%), heterogeneous MIO (some segments with T2* values≥20 ms and other segments with T2* values < 20 ms) and global heart T2*<20 ms (N=160, 14%), heterogeneous MIO and global heart T2*≥20 ms (N=337, 30%) and no MIO (all segments with T2* values≥ 20 ms) (N=465, 41%). The LV ejection fraction (EF) was significant different among the groups (P<0.0001) (figure 1A). Odds Ratio for LV dysfunction (LV EF<57%) was 4.8 (3.1-7.3 OR 95% CI; P<0.0001) for patients with homogeneous MIO vs patients with no MIO and 1.9 (1.2-3.2 OR 95% CI; P=0.007) for patients with heterogeneous MIO and global heart T2*<20 vs patients with no MIO. The right ventricular (RV) EF was significant different among the groups (P<0.0001) (figure 1B). Odds Ratio for RV dysfunction (RV EF<55%) was 2.1 (1.4-3.2 OR 95% CI; P=0.001) for patients with homogeneous MIO vs patients with no MIO. Conclusions Biventricular dysfunction is correlated with MIO distribution decreasing from the patients with homogeneous MIO to the patients with no MIO. Homogeneous MIO and heterogeneous MIO with a global heart T2*<20 predicts a significantly higher risk to develop cardiac dysfunction suggesting an intensive chelation therapy in this group of patients.

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

AbstractAbstract 4267 Introduction:Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. In thalassaemia available three iron chelation regimes in monotherapy may achieve different changes in cardiac iron and function and liver iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with deferasirox (DFX) versus deferiprone (DFP) and desferrioxamine (DFO) in monotherapy. Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFX versus DFP and DFO in monoterapy 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 according to the protocol. We evaluated prospectively the 193 TM patients who had been received one chelator alone between the 2 MR scans. We identified 3 groups of patients: 80 treated with DFX, 39 treated with DFP and 74 treated with DFO. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Results:The dose of DFX was 26±7 mg/kg/d, DFP was 73±13 mg/kg/d and DFO was 41±6 mg/kg for 5.5 d/wk. Excellent/good levels of compliance were similar in the 3 groups (DFX 99%, DFP 95%; DFO 96%, P = 0.6). Among the patients with no significant myocardial iron overload at baseline (global heart T2* ≥ 20 ms) (DFX 54 pts, DFP 30 pts, DFO 53 pts), there were no significant differences in all 3 groups to maintain the patients without significant myocardial iron overload (DFX 98%; DFP 100%; DFO 98%; P=1.0)Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms) in all 3 groups there was a significant improvement in the global heart T2* value (DFX P=0.001, DFP P=0.015 and DFO P =0.007) and in the number of segment with a normal T2* value (DFX + 2.4 P=0.003, DFP +6.0 P=0.031 and DFO + 2.9 P=0.001); only in the DFP group there was a significant improvement in the right global systolic function (+ 6.8% P = 0.016). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group (P=0.0026), but it was not significantly different in the DFX versus the DFO group (mean difference global heart T2* 3.5 ± 4.7 ms versus 8.8 ± 8.6 ms and versus 3.7 ± 5.5 ms, respectively; P = 0.90) (see the figure). The changes in the mean serum ferritin level and in the global systolic bi-ventricular function were not significantly different among groups.In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significant among groups (mean difference liver T2*DFX 2.1 ± 4.2 ms vs DFO 1.9 ± 3.8 ms vs DFP 1.3 ± 3.3 ms; P = 0.9). Conclusions:Prospectively over 15 months in a large clinical setting of TM patients DFP monotherapy was significantly more effective than DFX in improving myocardial siderosis, no significant differences were found between DFX and DFO monotherapy. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Cardiac Iron Loading Measured by Multislice Multiecho T2* MRI and Cardiac Disease In Male and Female Patients with Thalassemia Major

AbstractAbstract 4268 Introduction.Heart disease remains the main cause of mortality in thalassemia major patients. Female patients with thalassemia major have a proved lower prevalence of cardiac complications than males and survive longer. It has been suggested that females have a better compliance than males, and therefore accumulate less iron in crucial organs like the heart (Borgna-Pignatti C et al, Haematologica 2004). The aim of our study was to verify if the decreased prevalence of cardiac disease in females could be attributed to lesser iron accumulation in their hearts as measured by multislice multiecho T2* Magnetic Resonance Imaging (MRI) technique. Methods.We performed a retrospective review of the MRI results and of clinical data about the thalassemia major patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project. The MIOT is a network where MRI is performed using standardized and validated procedures and the MRI and thalassemia centers are linked by a web-based network, configured to collect patients' clinical and diagnostic data (Meloni A et al, Int J Med Inform 2009). Myocardial iron concentrations were measured by T2* multislice multiecho technique (Pepe A et al, JMRI 2006).Biventricular function parameters were quantitatively evaluated by cine images. Results.Seven hundred and seventy six thalassemia patients (370 males) were present in the MIOT database having undergone at least one MRI exam. The prevalence of cardiac disease (heart dysfunction and/or arrhythmias requiring medications) was significantly higher in males than in females (males 28% vs females 17%; P<0.0001). The analysis of different chelation treatments did not demonstrate a significant difference between patients with and without cardiac disease (P=0.59), nor between sexes (P=0.46). In addition, there was no difference in the reported compliance to chelation therapy between males and females (P=0.52). Global heart T2* values were significantly lower in both males and females with heart dysfunction (males: 20 ± 15 ms; females: 18 ± 12 ms), compared to those without dysfunction (males: 29 ± 11 ms; females: 27 ± 13 ms) (P<0.0001), but no difference was observed according to sex (Figure 1A). Global heart T2* values were not significantly lower in patients with arrhythmias compared to those without arrhythmias, nor was there a significant difference between sexes (Figure 1B). Conclusions.The confirmed higher prevalence of cardiac disease in males with thalassemia major was not correlated to a worse compliance to chelation therapy or to an higher cardiac iron burden. Increased survival of female thalassemia major patients seems to not be attributed to lower cardiac iron overload. It can be hypothesized that females tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Prospective Comparison on Cardiac Iron and Liver Iron by MR In Thalassemia Major Patients Treated with Combination Deferipron–Desferrioxamine Versus Deferipron and Desferrioxamine In Monoterapy

AbstractAbstract 5164 Introduction:Using T2* MR a randomised placebo controlled study from Sardinia demonstrated combination therapy with deferiprone and desferrioxamine (DFP+DFO) significantly more effective than DFO in improving myocardial iron. One non-randomised study from Sardinia and one observational study from Greece seem to confirm for DFP+DFO therapy the most rapid clearance of cardiac iron. No data are available in literature about prospective comparisons on cardiac iron and function and liver iron in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. The aim of this multi-centre study was to assess prospectively in a large clinical setting the efficacy of the DFP+DFO versus DFP and DFO in 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 43 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. Biventricular function parameters were quantitatively evaluated by cine images. Results:The doses of the combination treatment were DFP 66±23 mg/kg/d for 6±1 d/w and DFO 41±7 mg/kg/d for 4±1 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 91% versus DFP 97% versus DFO 92%; P =0.76).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 90% versus DFP 100% versus DFO 100%; P = 0.053).Among the patients with myocardial iron overload at baseline (global heart T2*<20 ms), in all groups there was a significant improvement in the global heart T2* value (DFP+DFO P=0.0001, DFP P=0.001 and DFO P=0.003), in the number of segment with a normal T2* value (DFP+DFO P=0.0001, DFP P=0.031, DFO P=0.0001) and in the right global systolic function (DFP+DFO P =0.002, DFP P=0.031, DFO P=0.045). The improvement in the global heart T2* was significantly different among groups (mean difference global heart T2* DFP+DFO 6.6±6.5 ms, DFP 10.7±7.2, DFO 3.6±5.4; P=0.009). The improvement in the global heart T2* was significantly higher in the DFP+DFO versus the DFO group (P=0.017), but it was not significantly different in the DFP+DFO versus the DFP group (P = 0.36) (see the figure). The changes in the global systolic bi-ventricular function were not significantly different among groups. [Display omitted] 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 2.9±4.7 ms, DFP 2.3±5.8, DFO 2.9±4.9; P=0.91). Conclusions:Prospectively in a large clinical setting over 15 months in TM patients combined therapy DFP+DFO confirmed superior reduction in myocardial iron in comparison to DFO, but no significant differences were found versus DFP monotherapy. Disclosures:No relevant conflicts of interest to declare.

Cardiac Iron Overload and Heart Function by CMR In Different Phenotypic Groups of Thalassemia Major Patients

AbstractAbstract 4264 Introduction.β-thalassemia major is a genetic disorder characterized by the absence (β°) or reduced output (β+) of the β chains of haemoglobin. This disorder displays a great deal of phenotypic heterogeneity, not fully investigated in terms of cause-effect (Refaldi C et al, Blood Transf 2005; Thein SL, Haematologica 2005). The aim of our study was to detect if different phenotypes could be related to different levels of cardiac impairments, evaluated by cardiovascular magnetic resonance (CMR). Methods.We performed a retrospective review of the CMR results and of clinical data about 328 TM patients (age 29 ± 9 years, 52% females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project (Meloni A et al, Int J Med Inform). In the MIOT network all CMR and thalassemia centers are linked by a web-based network, configured to collect patients' anamnestic, clinical, and diagnostic data. Myocardial iron overload was assessed by using a multislice multiecho T2* approach (Pepe A et al, Eur J Haem 2006). Three short axis views (basal, medium, and apical) of the left ventricle (LV) were acquired and analyzed using a custom-written, previous validated software (HIPPO MIOT®). The myocardium was automatically segmented into a 16-segments standardized LV model and the T2* value on each segment was calculated as well as the global T2* value. Cine sequences were obtained to quantify biventricular morphological and functional parameters. Results.Three groups of patients were identified: heterozygous (N=172), homozygous β+ (N=58), homozygous β° (N=98). No significant differences for sex and age were found among the groups. The homozygous β+ group showed higher global heart T2* values than the heterozygous and homozygous β° group (32 ± 11 ms vs 26 ± 13 ms vs 23 ± 13 ms, P=0.001) (see figure). The homozygous β+ group showed lower left LV mass index than the heterozygous group (54 ± 10 g/m2 vs 60 ± 14 g/m2, P=0.045). The homozygous β+ group showed higher LV ejection fraction (EF) values than the heterozygous group (64 ± 5 % vs 60 ± 7 %, P<0.0001) and higher right ventricular EF values than the heterozygous and homozygous β° group (64 ± 5 % vs 59 ± 8 % vs 60 ± 7 %, P<0.0001). Conclusions.The homozygous β+ TM patients showed less myocardial iron overload and a concordant better global systolic heart function and cardiac remodelling. These data support the knowledge of the different phenotypes in the clinical and instrumental management of the TM patients suggesting stricter monitoring by CMR in homozygous β° TM patients. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

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

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. From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. The global heart T2* value was significantly higher in the deferiprone (34 ± 11 ms) than in the deferasirox (21 ± 12 ms) and the desferrioxamine groups (27 ± 11 ms) (P = 0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P = 0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P = 0.004). The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine.

Comparison of Deferasirox, Deferiprone, and Desferrioxamine Effectiveness on Myocardial Iron Concentrations and Biventricular Function by Quantitative MR in Beta-Thalassemia Major

Despite dramatic gains in life expectancy in the desferrioxamine era for thalassemia major patients, the leading cause of death for this young adult's population remains iron-induced heart failure. For this reason, strategies to reduce heart disease by improving chelation regimens have the highest priority in this phase. These strategies include development of novel oral iron chelators to improve compliance. Oral deferipron was proved more effective than subcutaneous desferrioxamine in removing cardiac iron. The novel oral one-daily chelator deferasirox has been recently commercially available but its long-term efficacy on myocardial iron concentrations and cardiac function is unknown. Aim of this study was to compare in thalassemia major patients the effectiveness of deferasirox, deferipron, and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function by quantitative magnetic-resonance imaging (MRI).Among the 550 thalassemic subjects enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network between September 2006 and September 2007, we selected patients receiving one chelator alone for longer than one year. MIOT is an Italian network of six MR sites where the cardiac and liver iron status is assessed by validated and homogeneous standard procedures. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferipron and 89 treated with desferrioxamine. The three groups were matched for gender, Hb pre-transfusion levels, age of starting chelation, and good compliance to the treatment. The deferasirox group was significantly younger (26±7 years) than the deferipron (32±9 years) and desferioxamine group (33±8 years) (P=0.0001) and showed significantly higher mean serum ferritin levels (2516±2106 ng/ml) than the deferipron (1493±1651 ng/ml) and the desferrioxamine group (987±915 ng/ml) (P=0.0001). Myocardial iron concentrations and distribution were measured by MRI T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine-dynamic MRI images. Liver iron concentrations were measured by MR T2* multiecho technique. Written informed consent was obtained from all subjects.The global heart T2* value was significantly higher in the deferipron group (34±11 ms) versus the deferasirox (21±12 ms) and the desferrioxamine group (27±11 ms) (P=0.0001), as showed in Figure A. The T2* in the mid ventricular septum was significantly higher in the deferipron (36 ± 12 ms) versus the deferasirox (20 ± 12 ms) and the desferrioxamine group (28 ± 13 ms) (P = 0.0001). The number of segments with normal T2* value was significantly higher in the deferipron and the desferrioxamine group versus the deferasirox group (14 ± 2 versus 11 ± 6 versus 7 ± 7 segments; P = 0.0001). Among the biventricular function parameters, we found higher left ventricular ejection fractions in the deferipron and the desferrioxamine group versus the deferasirox group (64 ± 7 versus 62 ± 6 versus 58 ± 7 %; P = 0.005), as showed in Figure B. Liver T2* values were significantly higher in the desferrioxamine group versus the deferipron and the deferasirox group (10 ± 9 versus 6 ± 6 versus 5 ± 5 segments; P = 0.002).In conclusion, Oral deferipron seems to be more effective than oral deferasirox and subcutaneous desferrioxamine in removal of myocardial iron with concordant positive effect on left global systolic function. [Display omitted]

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

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. [Display omitted]

Normal limits of gated blood pool SPECT count-based regional cardiac function parameters

Computations of left and right ventricular (LV and RV) gated blood pool SPECT (GBPS) ejection fraction (EF) have been well validated against other imaging modalities. As GBPS images depict the entire extent of both blood pools, it is possible to compute not only global but also regional biventricular function parameters, which have the prospect of being clinically useful for planning cardiac resynchronization therapy. This investigation sought to establish LV and RV count-based GBPS regional functional normal limits and to quantify their reproducibility. Count-versus-time curves were fit to third-order Fourier series for each of 17 LV and RV sub-volumes to compute global and regional EF, timing, phase and dyssynchrony parameters. Algorithms were applied to data for 40 normal controls (NLs) and 15 patients with CHF. To assess reproducibility, data were reprocessed a second time, blinded to initial calculations. There were no statistically significant differences between any initial and reprocessed LV or RV parameters for NLs or patients with CHF. Percent of subjects categorized as abnormal were the same for initial and reprocessed parameters (McNemar's differences = 0-7%, P > 0.05 for each parameter). Most parameters were significantly different for patients with CHF versus NLs. Normal limits for the new technique agreed well with the literature for other imaging methods, and RV normal limits closely paralleled LV limits. GBPS global and regional LV and RV normal limits are reproducible, and application of these normal limits to patients with CHF results in reproducible detection of functional abnormalities.

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

To assess the tissue iron concentration of the left ventricle (LV) using a multislice, multiecho T2* MR technique and a segmental analysis. 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. For the T2* global value, the coefficient of variation (CoV) for intra-/interobserver and interstudy reproducibility was 3.9% (r = 0.98), 5.5% (r = 0.98), and 4.7% (r = 0.99) respectively. Three groups were identified based on analysis of myocardial T2*: homogeneous (21%), heterogeneous (38%), and no myocardial iron overload (41%). The mean serum ferritin, liver iron concentration, and urinary iron excretion were significantly different among the groups. We did not find significant differences among groups in biventricular function. There was a correlation between the global T2* value and the T2* value in the mid-ventricular septum (r = 0.95, P < 0.0001). Multislice multiecho T2* MRI provides a noninvasive, fast, reproducible means of assessing myocardial iron distribution. The single measurement of mid-septal T2* correlated well with the global T2* value.

Evaluation of the efficacy of oral deferiprone in β‐thalassemia major by multislice multiecho T2*

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. Thirty-six beta-TM patients (age 29 +/- 8 yr) underwent MRI. Eighteen patients received long-term L1, and 18 other patients matched for age and sex received DF. T2* multiecho sequences on three short axis views of the left ventricle were obtained and analyzed by custom-made software. In each slice, the myocardium was automatically segmented into four segments. Cine-dynamic images were also obtained to evaluate biventricular function. For multislice T2* technique, the coefficient of variation for intra- and inter-observer, and inter-study reproducibility was 3.9%, 4.7%, and 5.5%, respectively. The global heart T2* value was significantly higher in the L1 vs. DF group (35 +/- 7 vs. 27 +/- 2 ms; P = 0.02). The number of segments with normal T2* value (>20 ms) was significantly higher in the L1 vs. the DF group (11 +/- 1 vs. 8 +/- 5 segments; P = 0.03). We did not detect significant differences in biventricular function parameters. This new approach confirms that L1 could be more effective than DF in removal of myocardial iron.

Is there a relation between duration of cyclosporine usage and right and left ventricular function in renal transplant patients?: Tissue Doppler Echocardiography study

Background Our aim was to investigate the effect of cyclosporine (CsA), which is commonly used in renal transplant patients and causes myocardial fibrosis and elevated arterial tension, on cardiac function. Methods Sixty-six renal transplant patients (RTPs) and 25 healthy controls were included in the study. Renal transplantation patients were divided according to time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months) and group 3 (>72 months). Systolic peak velocity (Sm, mitral; St, tricuspid) and mitral early (e)/late (a) (Me/a) and tricuspid e/a (Te/a) waves of the right and the left ventricles were measured by pulse-wave (PW) Doppler used for tissue Doppler imaging of both ventricles as well as the ventricle free wall near to the lateral tricuspid and the posterior mitral leaflets. The measurements included conventional diastolic early (E) and late (A) waves and deceleration time (DT) of the E wave, isovolumetric relaxation time (IVRT) of both ventricles, as well as left ventricular systolic ejection fraction (EF). Results There were no statistically significant differences between the groups with regard to demographic, clinical, and most biochemical characteristics. Left ventricular EF was normal in all groups; there were no statistically significant differences. IVRT and DT of left ventricle and right ventricle DT values were similar among RTPs. On the other hand, values were found to be increased in RTP groups compared with the control group. E/A ratio, Me/a Te/a of both ventricles were similar among RTPs. However, these values were found to be decreased in RTP groups compared with the control group. Conclusions Although left ventricular systolic functions were normal in all groups, there were statistically significant impairments of biventricular diastolic function parameters among renal transplant recipients compared with the control group.