Native T1 Values and Cardiac Involvement in Patients with Thalassemia Major

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Alessia Pepe ◽  
Nicola Martini ◽  
Antonio De Luca ◽  
Vincenzo Positano ◽  
Laura Pistoia ◽  
...  
Keyword(s):  
Iron Overload ◽  
T1 Mapping ◽  
Thalassemia Major ◽  
Clinical Impact ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Native T1 ◽  
Molli Sequence ◽  
History Of ◽  
Myocardial T1

Background.The T2* cardiovascular magnetic resonance (CMR) is the gold standard for the non invasive detection of myocardial iron overload (MIO). The native myocardial T1 mapping has been proposed as a complementary tool, thanks to its higher sensitivity in presence of small amounts of iron, but no data are available in literature about its clinical impact. Objective:To explore the clinical impact of T1 mapping for detecting cardiac complications in thalassemia major (TM). Methods.We considered 146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Three parallel short-axis slices of the left ventricle (LV) were acquired with the Modified Look-Locker Inversion recovery (MOLLI) sequence. The native T1 values in all 16 myocardial segments were obtained and the global value was the mean. Results.Twenty-one patients had an history of cardiac complications: 11 heart failure, 8 arrhythmias (7 supraventricular and 1 ventricular), and 2 pulmonary hyperthension. Patients with cardiac complications had significantly lower global heart T1 values (879.3±121.9 ms vs 963.2±98.5 ms; P<0.0001) (Figure) but comparable T2* values (33.32±11.66 ms vs 37.17±9.15 ms; P=0.116). Cardiac complications were more frequent in the group of patients with reduced global heart T1 value (<928 ms for males and <989 ms for females) compared to the group with normal global heart T1 value (71.4% vs 39.5%; P=0.009). Odds ratio (OR) for cardiac complications was 3.8 (95%CI=1.3-10.9) for patients with reduced global heart T1 value versus patients with normal global heart T1 value. Conclusion:We found out a significant association between decreased native global heart T1 values and a history of cardiac complications, suggesting that an early detection of myocardial iron burden by native T1 can support the clinicians in modifing chelation therapy earlier. Figure Disclosures Pepe: ApoPharma Inc.:Other: no profit support;Bayer:Other: no profit support;Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

scholarly journals Myocardial native T1 mapping and cardiac outcomes in thalassemia major

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Meloni ◽  
N Martini ◽  
A De Luca ◽  
V Positano ◽  
L Pistoia ◽  
...  
Keyword(s):  
Iron Overload ◽  
T1 Mapping ◽  
Thalassemia Major ◽  
Clinical Impact ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Private Company ◽  
Native T1 ◽  
Funding Sources ◽  
History Of

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The E-MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc. and Bayer). Background. The T2* cardiovascular magnetic resonance (CMR) is the gold standard for the non invasive detection of myocardial iron overload (MIO). The native myocardial T1 mapping has been proposed as a complementary tool, thanks to its higher sensitivity in presence of small amounts of iron, but no data are available in literature about its clinical impact. Objective To explore the clinical impact of T1 mapping for detecting cardiac complications in thalassemia major (TM). Methods. We considered 146 TM patients (87 females, 38.7 ± 11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Three parallel short-axis slices of the left ventricle (LV) were acquired with the Modified Look-Locker Inversion recovery (MOLLI) sequence. The native T1 values in all 16 myocardial segments were obtained and the global value was the mean. Results. Twenty-one patients had an history of cardiac complications: 11 heart failure,  8 arrhythmias (7 supraventricular and 1 ventricular), and 2 pulmonary hyperthension. Patients with cardiac complications had significantly lower global heart T1 values (879.3 ± 121.9 ms vs 963.2 ± 98.5 ms; P < 0.0001) (Figure) but comparable T2* values (33.32 ± 11.66 ms vs 37.17 ± 9.15 ms; P = 0.116). Cardiac complications were more frequent in the group of patients with reduced global heart T1 value (<928 ms for males and <989 ms for females) compared to the group with normal global heart T1 value (71.4% vs 39.5%; P = 0.009). Odds ratio (OR) for cardiac complications was 3.8 (95%CI = 1.3-10.9) for patients with reduced global heart T1 value versus patients with normal global heart T1 value. Conclusion We found out a significant association between decreased native global heart T1 values and a history of cardiac complications, suggesting that an early detection of myocardial iron  burden by  native T1 can support the clinicians in modifing chelation therapy earlier. Abstract Figure.

scholarly journals Association between Native Myocardial T1 Mapping and Cardiac Function and Macroscopic Fibrosis in Thalassemia Major

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Alessia Pepe ◽  
Nicola Martini ◽  
Antonio De Luca ◽  
Vincenzo Positano ◽  
Laura Pistoia ◽  
...  
Keyword(s):  
Iron Overload ◽  
Myocardial Fibrosis ◽  
T1 Mapping ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Lv Function ◽  
Myocardial Iron ◽  
Native T1 ◽  
Molli Sequence ◽  
Lv Volume

Background.Cardiovascular magnetic resonance (CMR) is the only available technique for the non-invasive quantification of MIO. The native T1 mapping has recently been proposed as an alternative to the universally adopted T2* technique, due to the higher sensitivity for detection of changes associated with mild or early iron overload. Objective.To study the association between T1 values and left ventricular (LV) function in thalassemia major (TM) and to evaluate for the first time if T1 measurements quantifying MIO are influenced by macroscopic myocardial fibrosis. Methods.146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent CMR. Native T1 values were obtained by Modified Look-Locker Inversion recovery (MOLLI) sequence in all 16 myocardial segments and the global value was the mean. LV function parameters were quantified by cine images. Late gadolinium enhancement (LGE) technique was used to detect macroscopic myocardial fibrosis. Results.No correlation was detected between global heart T1 values and LV volume indexes, LV mass index, or LV ejection fraction. Foourteen (9.6%) patients had an abnormal LV motion (13 hypokinesia and 1 dyskinesia) and they showed significantly lower global heart T1 values than patients without LV motion abnormalities (883.8±139.7 ms vs 959.0±91.3 ms; P=0.049). LGE images were acquired in 88 patients (60.3%) and macroscopic myocardial fibrosis was detected in 36 patients (40.9%). The 72.2% of patients had two or more foci of fibrosis. Patients with macroscopic myocardial fibrosis had significantly lower global heart T1 values (921.3±100.3 ms vs 974.5±72.7 ms; P=0.027) (Figure 1A). Data about the LGE was present for 1408 segments (88 patients x 16 segments) and 105 (7.5%) were positive. Segments with LGE had significantly lower T1 values than segments LGE-negative (905.6±110.6 ms vs 956.9±103.8 ms; P<0.0001) (Figure 1B). Conclusion.No correlation between T1 values and LV function parameters was detected, probably because the majority of the patients had normal or mild abnormal LV parameters. TM patients with macroscopic myocardial fibrosis showed significantly lower T1 values suggesting that T1 measurements for quantifying MIO are not influenced by macroscopic myocardial fibrosis and an association between myocardial iron and macroscopic fibrosis, previously detected only in pediatric TM patients. Figure Disclosures Pepe: Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria;Bayer:Other: no profit support;ApoPharma Inc.:Other: no profit support.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

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

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5165-5165
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Antonella Meloni ◽  
Dell'Amico Maria Chiara ◽  
D'Ascola Domenico Giuseppe ◽  
...  
Keyword(s):  
Iron Overload ◽  
Conflicts Of Interest ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Mean Difference ◽  
Quantitative Mri ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Multi Centre Study

Abstract Abstract 5165 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 deferiprone–deferoxamine (DFP-DFO) versus deferasirox (DFX). 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 DFP-DFO vs DFX 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 44 patients treated with DFX 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 DFX was 26±6 mg/kg/d. Excellent/good levels of compliance were similar in the 2 groups (DFP-DFO 96% vs DFX 100%; P = 0.36). At baseline the 2 groups were homogeneous for cardiac and liver iron. Among the patients with no significant myocardial iron overload at baseline (global heart T2* 3 20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 95% vs DFX 96%; P = 1.0). Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms), only in the DFX group there was a significant improvement in the global heart T2* value (11 ± 5 ms at baseline versus 16 ± 8 at 18 ± 3 months, P = 0.0001) and in the number of segment with a normal T2* value (P = 0.003). The improvement in the global heart T2* was not significantly difference in the DFP-DFO versus the DFX group (mean difference global heart T2* 2.2 ± 4.1 ms versus 4.6 ± 4.8 P = 0.2). The changes in the mean serum ferritin level were not significantly different between groups. In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significant between groups (mean difference liver T2* 0.9 ± 2.1 ms vs 2.4 ± 5.2; P = 0.3). Conclusions: Prospectively in the clinical setting over 15 months we did not find significant differences on cardiac and liver iron by quantitative MRI in TM patients treated with sequential DFP–DFO versus the TM patients treated with DFX. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Changes in CMR parameters and prediction of cardiac complications in thalassemia major: fibrosis tells us more than iron

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Pepe ◽  
P Giuliano ◽  
L Pistoia ◽  
N Giunta ◽  
S Renne ◽  
...  
Keyword(s):  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Cox Regression ◽  
Thalassemia Major ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Private Company ◽  
Risk Class ◽  
Cox Regression Analysis

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project received “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.). Background Cardiovascular magnetic Resonance (CMR) has dramatically changed the clinical practice and improved the prognosis in thalassemia major (TM). Aim This is the first study evaluating the predictive value of changes in CMR parameters (myocardial iron, function, and fibrosis) for cardiac complications in TM. Methods We followed prospectively 709 TM patients (374 females; 29.77 ± 8.53 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who performed a baseline and a 1st follow up CMR scan after 18 months.  Myocardial iron overload (MIO) was measured by multislice multiecho T2* technique and atrial dimensions and biventricular function by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Risk classes were defined based on  the 4 patterns of MIO from worst to normal. For patients with baseline MIO (at least one segmental T2*&lt;20 ms), improvement was defined as a transition to a better risk class, stabilization as no change in risk class, and worsening as a transition to a worse risk class. For patients without baseline MIO, the worsening was the transition to a worse risk class. The percentage change was used for continuous variables. For biventricular ejection fractions, improvement was a %change &gt; 10%, stabilization a %change between -10% and 10%, and worsening a %change&lt;-10%. For biventricular volumes, LV mass index, and atrial areas, improvement was a % change&lt;-10%, stabilization a % change between -10% and 10%, and worsening a % change &gt; 10%. Myocardial fibrosis was considered absent if not detected in any of the two CMRs and present if detected in at least one examination. Results During a mean follow-up of 89.4 ± 33.3 months, cardiac events were recorded in 50 (7.1%) patients: 24 (48%) episodes of heart failure, 24 (48%) arrhythmias (23 supraventricular and 1 hypokinetic), and 2 (4.0%) pulmonary hypertension.  Mean time from the 1st follow up CMR to the development of a cardiac complication was 75.31 ± 35.35 months. In the univariate Cox regression analysis, cardiac iron cleareance and myocardial fibrosis were identified as univariate prognosticators (Table 1). In the multivariate analysis only myocardial fibrosis remained an independent predictor factor. Conclusion The presence of myocardial fibrosis at the baseline CMR or developed within 18 months emerges as the strongest long-term predictor for cardiac complications in TM. Our data demonstrate the importance in using the contrast medium for CMR scans in thalassemia patients.

scholarly journals Detection of Myocardial Iron Overload with Magnetic Resonance By Native T1 and T2* Mapping Using a Segmental Approach

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2346-2346
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Nicola Martini ◽  
Daniele De Marchi ◽  
Andrea Barison ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Iron Overload ◽  
T1 Mapping ◽  
T2 Mapping ◽  
Basal Medium ◽  
Motion Artifacts ◽  
Myocardial Iron ◽  
Native T1 ◽  
T1 And T2 ◽  
Segmental Approach

Abstract Introduction. T2* measurement of myocardial iron overload (MIO) is presently the gold standard for monitoring and tailoring the chelation in thalassemia patients. Native T1 mapping has been proposed also for the MIO quantification because it is known that iron can reduce native T1 values. No data are available in literature comparing T1 and T2* mapping using a segmental approach including the whole left ventricle. The goal of our study was to assess the relationship between T1 and T2* values using a segmental approach. Methods. 29 patients with hemoglopinopathies (18 females, 45.39±13.49 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered. Native T1 and T2* images were acquired, respectively, with the Modified Look-Locker Inversion recovery (MOLLI) and with the multi-echo gradient-echo techniques. Three parallel short-axis views (basal, medium and apical) of the left ventricle (LV) were acquired with ECG-gating. The myocardial T1 and T2* distribution was mapped into a 16-segment LV model, according to the AHA/ACC model. The lower limit of normal for each segment was established as mean±2 standard deviations on data acquired on 14 healthy volunteers. In 25 patients also post-contrastografic images were acquired. Results. T1 images showed more pronounced motion artifacts and lower contrast-to-noise-ratio, determining the exclusion of 18/464 segments. No segments were excluded by T2* mapping. So, globally, 446 segmental T1 and T2* values were considered. The mean of all segmental T2* and T1 values were, respectively, 37.83±11.30 ms and 982.72±118.24 ms. Normal T2* and T1 values were found in 374 segments (83.9%) while 29 (6.5%) segments had pathologic T2* and T1 values. For 33 segments (7.4%) (13 patients) a pathologic T1 value was detected in presence of a normal T2* value. For 10 segments (2.2%) a pathologic T2* value was detected in presence of a normal T1 value. Out of the 9 patients with pathologic T2* values in presence of normal T1, in 7 patients post-contrastografic images were acquired; in all segments with pathologic T2* value macroscopic fibrosis by late gadolinium enhancement technique and/or microscopic fibrosis by T1 mapping were found. The relation between segmental T1 and T2* values is shown in the figure. For patients with pathologic segmental T2* values there was a linear relationship between T1 and T2* values (R=0.735, P<0.0001) while the whole data was fitted with a quadratic curve. Conclusion. T2* and T1 mapping showed a good correlation in identifying iron by a segmental approach. However, we found a scatter between results. In 9 patients T1 mapping was not able to detect iron probably due to the presence of macroscopic and/or microscopic fibrosis that it is known to increase the native T1 . Conversely, in 13 patients T1 mapping seems to be more sensitive than T2* (sensitive to different iron chemistry or error measurements?). Further studies on larger population and correlation with clinical outcome are need. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

4326Reduction of cardiac outcomes in thalassemia major thanks to a ten-year national Italian networking

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Meloni ◽  
L Pistoia ◽  
N Giunta ◽  
N Schicchi ◽  
P Giuliano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Cause Of Death ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Cardiac Outcomes ◽  
Number Of Patients

Abstract Introduction The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients. Purpose We describe the impact of this ten-year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM). Methods 1746 TM patients (911 F; age 31.17±9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results 1392 TM patients performed an end-of-study CMR. At the last CMR significantly higher global heart T2* values (35.44±10.69 ms vs 29.16±12.02 ms; P<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all T2*<20 ms). At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were found (Figure 1). In patients with global heart T2*<20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2±8.5%, P<0.0001) as well as in right ventricular EF (difference: 1.2±8.9%, P=0.002) were detected. Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P<0.0001). The complete history of cardiac complications-CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4%, significantly lower (P=0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P<0.0001). Forty-six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death. Conclusion Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.

scholarly journals Genotypic Groups As Risk Factor for Cardiac MR Abnormalities and Complications in Thalassemia Major

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1057-1057
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Stefano Salvadori ◽  
Silvia Macchi ◽  
Angelantonio Vitucci ◽  
...  
Keyword(s):  
Iron Overload ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Beta Thalassemia ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Genotype Group ◽  
Compound Heterozygotes

Abstract Introduction. Beta thalassemia major (β-TM) displays a great deal of genotypic heterogeneity, not fully investigated in terms of cause-effect. This prospective and multicentre study aimed to detect if different genotypic groups could predict the development of cardiovascular magnetic resonance (CMR) abnormalities and cardiac complications (CC). Methods. We considered 708 β-TM patients (373 females, 30.05±9.47 years), consecutively enrolled in Myocardial Iron Overload in Thalassemia (MIOT) network. Data were collected from birth to the first CMR imaging scan. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis. Results. On the basis of the type of gene mutation, three groups of patients were identified: homozygotes β+ (N=158), compound heterozygotes β+ / β° (N=298) and homozygotes β° (N=252). Table 1 shows the effect of genotype group on the development of different cardiac outcomes. Compared to the milder genotype group homozygotes β+, the other two groups showed a significantly higher risk of myocardial iron overload (MIO) and left ventricular dysfunction. We recorded 90 (13.0 %) cardiac events: 46 heart failures (HF), 38 arrhythmias (33 supraventricular, 3 ventricular and 2 hypoinetic) and 6 pulmonary hypertensions (PH). No prospective association was detected between genotype group and HF and PH. The homozygous β° group showed a significantly higher risk of arrhythmias than the homozygous β+ group and at the limit of significance than the compound heterozygotes. Globally, homozygotes β° showed a significantly higher risk of CC than homozygotes β+. Conclusion. Different genotypic groups predict the development of MIO, left ventricular dysfunction, arrhythmias and CC in β-TM patients. These data support the knowledge of the different genotypic groups in the clinical management of β-TM patients. Table Table. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

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

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

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4267-4267
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Antonella Meloni ◽  
Maria Chiara Dell'Amico ◽  
Anna Spasiano ◽  
...  
Keyword(s):  
Iron Overload ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Mean Difference ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Multi Centre Study ◽  
Cardiac Iron ◽  
And Function

Abstract Abstract 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. Disclosures: No relevant conflicts of interest to declare.

Diabetes Mellitus and Cardiac Complications in Thalassemia Major Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2150-2150
Author(s):  
Maria Rita Gamberini ◽  
Antonella Meloni ◽  
Vincenzo Caruso ◽  
Marcello Capra ◽  
Paolo Cianciulli ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Thalassemia Major ◽  
Cardiac Complication ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Heart Dysfunction ◽  
Co Morbidity

Abstract Abstract 2150 Introduction. In thalassemia major (TM) patients myocardial iron overload and chronic anemia are the recognized leading causes of cardiomyopathy, but a role can also be played by other factors such as endocrine abnormalities. The aim of this retrospective study was to evaluate if diabetes mellitus (DM) was associated with an higher prevalence and risk of cardiac dysfunction and of heart complications, regardless to the presence of myocardial iron overload. Methods. From a cohort of 957 TM patients who underwent MRI within the MIOT network (Myocardial Iron Overload in Thalassemia), among the patients (N = 358) with no cardiac iron (all cardiac segments with a T2* ≥ 20 ms) we identified 29 patients with DM and 329 patients without DM. The normal values of ejection fraction (EF) normalized by sex and age, obtained in a cohort of 142 TM patients without cardiac disease and iron overload, were used to define left ventricular (LV) and right ventricular (RV) heart dysfunction (EF < mean – 2 standard deviation). Heart failure (HF) was diagnosed by Magnetic Resonance Imaging (MRI) in presence of a LV and/or RV EF lower than 4 standard deviations from the normalized mean value and by a positive history (clinical symptoms, confirmation by physical examination and treatment). Myocardial fibrosis was evaluated by delayed enhancement MRI technique. Results. The prevalence of overall heart dysfunction (LV, RV or both) was higher in patients with DM (44.8%) versus patients without DM (28.3%), with a P-value very close to the statistically significance (P=0.061). In more details, patients with DM presented significantly more biventricular dysfunction (20.7% vs 7.6%, P=0.016). The prevalence of myocardial fibrosis was significantly higher in the DM patients vs the no DM patients (37.5% vs 19.2 %; P=0.033). Cardiac complications occurred with a significantly higher frequency in patients with DM (55.2% vs 15.5%, P<0.0001). Taking into account each cardiac complication separately, a significant difference between the groups was found in the occurrence of heart failure (27.6% vs 9.4%, P<0.003) and hyperkinetic arrhythmias (34.5% vs 5.2%,P<0.0001), both supraventricular (27.6% vs 4%, P<0.0001) and ventricular (6.9% vs 0.6%, P=0.034). Table 1 shows odds ratios (OR) estimating the relationship between diabetes and cardiac involvement. Among cardiac dysfunctions, only the biventricular forms were significantly positively associated with the diabetes. However, the correction for age caused the loss of the significance. The association between DM and myocardial fibrosis became not significant after the correction for age and endocrine co-morbidity. Patients with DM were significantly more likely to have cardiac complications and the results were not affected by the adjustment for age and/or endocrine co-morbidity. Considering separately each cardiac complication, a significant association was found for HF and hyperkinetic arrhythmias. The association between DM and HF resulted not significant after the correction for age. For the hyperkinetic arrhythmias, the OR remained significant after the correction for age and/or endocrine co-morbidity. Conclusion. In TM patients without myocardial iron DM was significantly associated with the presence of cardiac complications globally considered and hyperkinetic arrhythmias. Disclosures: No relevant conflicts of interest to declare.

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