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

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4268-4268
Author(s):  
Alessia Pepe ◽  
Maria Marsella ◽  
Antonella Meloni ◽  
Valeria Caldarelli ◽  
Maria Chiara Dell'Amico ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cardiac Disease ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Myocardial Iron ◽  
Heart Dysfunction ◽  
Female Patients ◽  
Cardiac Iron ◽  
Significant Difference ◽  
Males And Females

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

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

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2157-2157
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Brunella Favilli ◽  
Marcello Capra ◽  
Domenico Giuseppe D'Ascola ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Paediatric Patients ◽  
Biventricular Function ◽  
Significant Difference

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

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.

Hypothyroidism and Cardiac Complications In Thalassemia Major Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2254-2254 ◽  
Author(s):  
Maria Rita Gamberini ◽  
Antonella Meloni ◽  
Giuseppe Rossi ◽  
Giuseppina Secchi ◽  
Alfonso D'Ambrosio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Iron Overload ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Volume Index ◽  
Hypothyroid Patient ◽  
Myocardial Iron ◽  
Heart Dysfunction ◽  
Hypothyroid Patients

Abstract Introduction In the non-thalassemic population hypothyroidism has been associated with an increased risk of cardiac disease while the link thyroid-heart disease has been little explored in thalassemia major (TM). This retrospective cohort study aimed to systematically evaluate in a large historical cohort of TM in the cardiovascular magnetic resonance (CMR) era whether hypothyroidism was associated with a higher risk of heart complications (heart failure, arrhythmias and pulmonary hypertension). Methods From a cohort of 957 TM patients who underwent CMR for myocardial iron overload (MIO) assessment, quantification of biventricular function and detection of myocardial fibrosis within the MIOT network (Myocardial Iron Overload in Thalassemia), we identified 115 (12%) hypothyroid patients. Each hypothyroid patient was matched by sex and age (at the time of the CMR) with two non-hypothyroid patients, creating 115 triples. A cardiac event was considered valid if diagnosed at an age older than the hypothyroidism’s onset age for the hypothyroid patient in the belonging triple. Results Hypothyroid and non-hypothyroid patients had comparable MIO, but hypothyroid patients showed significantly lower biventricular stroke volume index, ejection fraction and left ventricular cardiac index. Accordingly, the prevalence of overall heart dysfunction (LV, RV or both) was higher in hypothyroid patients (43.5% vs 33.5%, P=0.0314). Hypothyroid patients had a significant higher frequency of heart failure (19.1% vs 9.1%, P=0.003) and arrhythmias (11.3% vs 4.3%; P=0.003). Figure1 shows odds ratios (OR) estimating the relationship between hypothyroidism and cardiac involvement. Hypothyroid patients had a significant higher risk of heart dysfunction, heart failure and arrhythmias, also adjusting for the endocrine co-morbidity. Conclusions Hypothyroidism seems to increase the risk for heart failure, arrhythmias and heart dysfunction in TM patients. Our data confirm the link thyroid-heart disease also in TM patients and they stress the need to prevent hypothyroidism in this population. Disclosures: No relevant conflicts of interest to declare.

Glutathione S-Transferase Gene Polymorphism and Heart Iron Overload in Thalassemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2767-2767
Author(s):  
Raffaella Origa ◽  
Stefania Satta ◽  
M. Dolores Cipollina ◽  
Lucia Perseu ◽  
Annalisa Agus ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Thalassemia Major ◽  
Myocardial Iron ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Body Iron ◽  
Cardiac Iron ◽  
Iron Load ◽  
Allelic Distribution

Abstract Heart is the target lethal organ for iron accumulation in thalassemia major. Currently, magnetic resonance imaging (MRI) is the only non-invasive method with the potential to assess myocardial iron. MRI T2* has proven to be a fast, simple, robust and clinically useful tool for the assessment of cardiac iron load. In chelated patients, myocardial iron is usually inversely related to compliance with chelation while there is no meaningful correlation with liver iron and serum ferritin concentration measured at the time of T2* assessment. However, in a subset of patients, myocardial iron overload occurs despite an history of good compliance with chelation therapy, suggesting the possible role of genetic factors. Several gene polymorhisms including apolipoprotein epsylon and HLA haplotypes have been described as protective or predisposing factors for cardiac iron dysfunction. Wu et al. (2006) analyzed polymorphisms of two endogenous antioxidant enzymes, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1). They found that the GSTM1 null (deleted) genotype was associated with a decreased signal intensity ratio on MRI, suggesting that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition. The aim of the current study was to evaluate if the GSTM1 null genotype is a predisposing factor for myocardial iron overload in thalassemia major patients on chelation treatment with desferrioxamine with low body iron load as assessed by serum ferritin levels. Allelic distribution of wild and null GSTM1 genotype was assessed in 24 patients with thalassemia major in whom the severe myocardial iron overload (T2* <10 msec) was unexpected based on low body iron load (mean of lifelong serum ferritin determinations 1360 ± 268 ng/ml), and in 26 thalassemia patients in whom the myocardial iron overload was expected based on high body iron load (mean of lifelong serum ferritin determinations 4724 ± 1530 ng/ml). Twenty-six healthy subjects were analyzed as controls. We found that the GSTM1 null genotype was more frequent in thalassemia patients with unexpected myocardial iron load (p=0.02) than in patients with expected myocardial iron load (Table 1). The presence of the GSTM1 null genotype can therefore explain in part the development of severe myocardial iron overload in thalassemia major patients who have been adequately chelated since their first years of life. Based on the inhibition of the cardiac ryanodine receptor calcium channels by members of the glutathione transferase structural family, and given the little difference in permeability among divalent cations in those channels, we hypothesized that the deletion of GSTM1 is associated with increased entry of iron into the myocites, in patients with thalassemia major. Further studies are needed to understand the mechanisms that underlie the association between GSTM1 gene polymorphisms and predisposition to myocardial iron overload. Table 1. Allelic distribution of wild and null GSTM1 genotype in beta thalassemia patients with expected and unexpected heart iron overload, and in 26 healthy controls GSTM1 wild GSTM1 wild GSTM1 null GSTM1 null n % n % χ2 test : A vs C p>0.05; A vs B p=0.02; B vs C p=0.04 A. Thalassemic patients with expected heart iron overload 17 65.4 9 34.6 B. Thalassemic patients with unexpected heart iron overload 8 33.3 16 61.5 C. Healthy controls 16 61.5 10 38.4

Gender Differences in Iron Overload and Left Ventricular Function in a Cohort of Thalassemia Major Patients: A Prospective Study of a Single Italian Center Using Cardiovascular Magnetic Resonance.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3819-3819
Author(s):  
Elisabetta Volpato ◽  
Elena Cassinerio ◽  
Maria Rosaria Fasulo ◽  
Paola Pedrotti ◽  
Stefano Pedretti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gender Differences ◽  
Cardiovascular Magnetic Resonance ◽  
Iron Overload ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Myocardial Iron ◽  
Iron Intake ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction: cardiac failure due to secondary iron overload remains the main cause of death in patients with b-Thalassemia Major (TM). Cardiovascular Magnetic Resonance Imaging (CMR) T2* technique is a new tool to assess myocardial iron concentration that allows to tailor the optimal iron chelation treatment for each patient. Aim of the study: to assess left ventricular function and myocardial iron overload in a cohort of TM patients, cared at Hereditary Anemia Center in Milan, Italy. Methods and Results: In 91 TM patients (33 males/58 females, mean age 32 ± 6 yrs) myocardial iron loading was assessed with the use of CMR T2* measurements (CMR Tools, Cardiovascular Imaging Solutions, London, UK). Left ventricular ejection fraction (LVEF) was also assessed with CMR. In the overall group hemoglobin levels were 9.0 ± 1.0 g/dl; the mean serum ferritin levels and iron intake during the six months before CMR evaluation were 1507 ± 1884 ng/ml and 0.34 ± 0.08 mg/kg/die respectively. T2* was significantly different between females and males (24 ± 11 and 32 ± 12 ms, respectively; p &lt; 0.0001), with significant differences in diabetes mellitus prevalence (17% vs 8%, p&lt;0.01) but not in age, serum ferritin, iron intake and hemoglobin levels (Table 1). Seven (7.6%) asymptomatic females showed a severe cardiac iron overload (T2* ≤ 10 ms), 9 patients (9.9%) moderate (T2* between 10.1 and 14 ms), 15 patients (16.4%) mild cardiac iron overload (T2* between 14.1 and 20 ms) and 60 patients (65.9%) had normal T2* (&gt; 20 ms). LVEF was significantly different between females and males (35% vs 57%, p&lt;0.001) with evidence of a significant relationship between iron overload severity and LVEF impairment (r=0.92). Conclusions: CMR cardiac function and T2* assessment allow to detect pre-symptomatic cardiac iron overload. Females are more at risk for severe iron overload and left ventricular impairment. The prevalence of diabetes mellitus and compliance to chelation therapy could be relevant in explaining the gender differences. Clinical parameters and T2* values in men and women with thalassemia major Men p Women SD: standard deviation Number of patients (n. of pts) 33 - 58 Age ± SD (years) 33 ± 6 ns 32 ± 6 Hemoglobin levels ± SD (g/dl) 9.0 ± 1.7 ns 9.0 ± 0.8 Ferritin levels ± SD (ng/ml) 964 ± 891 ns 1821 ± 2216 Iron intake ± SD (mg/Kg/die) 0.30 ± 0.07 ns 0.36 ± 0.09 Mean T2* value ± SD (ms) 32 ± 12 &lt;0.0001 24 ± 11 T2*&lt; 10 ms (n. of pts) 0 - 7 T2* between 10.1 and 14 ms (n. of pts) 1 - 8 T2* between 14.1 and 20 ms (n. of pts) 7 - 8 T2* &gt; 20 ms (n. of pts) 25 - 35 T2*&lt; 10 ms (n. of pts) plus LVEF≤ 57 % 0/0 (0%) - 6/7 (85.7%) T2* between 10.1 and 14 ms (n. of pts) plus LVEF≤ 57 % 1/1 (100%) - 3/8 (37.5%) T2* between 14.1 and 20 ms (n. of pts) plus LVEF≤ 57 % 3/7 (42.8%) - 1/8 (12.5%) T2* &gt; 20 ms (n. of pts) plus LVEF≤ 57 % 7/25 (28%) - 5/35 (14.3%)

Update in Combined Chelation Therapy with Deferoxamine and Deferiprone in Brazilian Patients with Thalassemia Major: Assessment of Three Years

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5415-5415
Author(s):  
Sandra Regina Loggetto ◽  
Mônica Veríssimo ◽  
Antônio Fabron Júnior ◽  
Giorgio Roberto Baldanzi ◽  
Nelson Hamerschlak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction: Cardiac failure is a main cause of morbidity and mortality in patients with thalassemia major (TM) who are receiving regular blood transfusion due to iron overload. So, effective and adequate iron chelation is extremely important. Deferoxamine (DFO), the most widely used iron chelator, has poor compliance. Combined therapy with Deferiprone (DFP) increases chelation efficacy, decreases iron-induced complications, improves compliance increasing survival in thalassemia. Objectives: Assessment of efficacy and safety in combined chelation with DFP and DFO in thalassemic patients with iron overload. Methods and results: We have 50 thalassemia major patients in 4 Brazilian Centers (Boldrini Hospital, Sao Paulo Hematology Center, HEMEPAR and FAMEMA) receiving combined chelation therapy with follow up to three years. DFP (75–100 mg/kg/daily) and DFO (30–60 mg/kg, 4–7 days/week) are being administered during one to three years. Median age of this group is 21,5 y/o (range 8–35), with 48% female. Median age to start regular transfusions was 12 months (range 2–140) and to begin chelation therapy was 57 months (range 17–216). All patients were screened for Hepatitis C and 26% had positive sorology and/or PCR. Statistical analysis were made with Spearman test and Fisher test. All patients, except two, did cardiac and liver MRI in the initial phase of the study, resulting in 60,5% with cardiac iron overload (T2*&lt;20ms), being severe in 31,2%. Assessment of liver iron concentration (LIC) showed 95,7% with liver iron overload (&gt;3ug/g dry weight), being severe in 17,4%. During follow up, only 43 patients (86%) was screened with MRI. From these, 67,4% had cardiac iron overload (severe in 32,5%) and 78,6% had liver iron overload (severe in 11,9%). Mean serum ferritin before and after three years were 3095,7 ±1934,5 ng/ml and 2373,9±1987,6 ng/ml, respectively. Our data showed positive correlation between serum ferritin, LIC and ALT, even in initial data and after combined chelation therapy (p&lt;0,001), but there is no correlation between cardiac T2* and LIC and between cardiac T2* and ferritin. DFP adverse events included 8% agranulocytosis, 22% neutropenia, 20% arthralgia and 38% gastric intolerance. DFO adverse events were 2,6% deafness, 2,0% cataract and 12% growth deficit. Hepatic toxicity was found in 6%, but without necessity to stop treatment. Compliance in this group was excellent in 48%, good in 22% and poor in 30%. Conclusions: This is the first multicenter study to evaluate combined chelation therapy in Brazil based on cardiac MRI and LIC. Most patients had cardiac and hepatic iron overload probably because they began iron chelation lately, due to difficult access to iron chelators in the past. Cardiac iron overload didn’t have correlation with ferritin and LIC and these data need more understanding. Age of initial regular blood transfusion, increased transfusional requirement, inadequate chelation or delayed chelation may play a role in this question. Combined therapy with DFO and DFP is effective to decrease serum ferritin and LIC. Follow up and improving compliance may decrease cardiac iron overload. Adverse events are similar to literature. Combined therapy is safety in TM patients with transfusional iron overload.

A Decade Follow-up of a Thalassemia Major (TM) Cohort Monitored by Cardiac Magnetic Resonance Imaging (CMR): Significant Reduction In Patients with Cardiac Iron and In Total Mortality

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1011-1011 ◽  
Author(s):  
Alison S Thomas ◽  
Maciej Garbowski ◽  
Ai Leen Ang ◽  
Farrukh T Shah ◽  
J. Malcolm Walker ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Chelation Therapy ◽  
Thalassemia Major ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Advisory Committees ◽  
Cardiac Iron

Abstract Abstract 1011 Background. CMR was introduced in London to assess myocardial iron loading in 1999 and some of these patients now have 10 years of follow-up, most with contemporary CMR determinations. The impact of long-term monitoring of myocardial iron loading in thalassemia major (TM) on the proportion of patients with increased myocardial iron (cT2* <20ms) and on patterns of mortality has not been previously described in a longitudinal cohort over this duration. Patients and Methods. All patients regularly attending two London thalassemia centres, who received their first CMR Jan 1999 - Dec 2000 were analyzed as a cohort. Patients underwent initial CMR at the Royal Brompton Hospital and received CMR follow up (FU) either there or at the Heart Hospital (UCLH). 132 patients were identified as having received a CMR in 1999–2000. A minimum 7 years CMR FU was required for inclusion in the long-term CMR analysis. 109 patients had at least 7 years of CMR follow up (range 7.0–10.6 years, median 9.2). The median age at 1st CMR was 27.9 years (range 7.7 – 49.5 years). At baseline, patients were receiving chelation with deferoxamine (DFO) monotherapy (70%), deferiprone (DFP) monotherapy (21%), or a combination of these agents (9%). At latest FU, patients were receiving DFO (32%), deferasirox (DFX) (28%), DFP (22%), or combined DFP and DFO therapy (18%). Results: Improvement in cardiac iron: In 1999–2000, 60% of TM patients had cT2* values ≤20ms and 17% had cT2* values <10ms. By contrast, at long term FU, only 23% now have cT2* ≤20ms, 7% have cT2* values <10ms (p<0.001). Changes to chelation therapy: 31% of patients stayed on the same chelator; 33% had 1 chelator switch, 26% 2 switches and 11% 3 or more switches. 18 switches in chelation therapy were due to side-effects (12 DFP, 5 DFX, 1 DFO). There were 9 breaks in chelation therapy during pregnancy in 8 different women. The proportions of patients with T2* < 20ms fell significantly for those who remained on DFO or DFP monotherapies throughout, or who changed chelation modalities on only one (p=0.002) or two (p=0.02) occasions. Patients who received had 3 or more switches did not show a improvement in this respect. The latter group was also the only subset that showed significant deterioration in myocardial iron (p<0.001). Mortality rates: the overall mortality rate for the initial cohort was 1.65 per 1000 patient years (95% CI 0.71 – 3.24); median age at death 35.6 years (range 27.3–48.4). This is a substantial improvement in the mortality index compared with the UK thalassemia registry data, of 4.3 per 1000 patient years during the period 2000–2003 (Modell et al, JCMR, 2008). The incidence rate ratio is 0.387 (95% CI 0.11–0.961), p<0.05, with patients in our cohort 61% less likely to die than those in the 2000–2003 cohort. Causes of death: there were 8 deaths during the FU period: 3 with complications of hepatitis C (all with cT2* > 20ms), 3 with sepsis (2 with cT2* <10ms and impaired ejection fraction, 1 with cT2* of 18ms), 1 with breast cancer, 1 with sudden unexplained death (cT2* > 20ms). Thus in only 2 patients could excessive cardiac iron loading be considered a causal/contributory factor. There was no significant difference in the baseline cT2* between those who died and those currently still alive (p= 0.2), meaning that death as a drop-out cause does not explain iron loading trends over FU. Chelators at death: DFO (4), DFP (2), DFX (1), combination (1). Conclusions: Over a decade we have seen an almost 3 fold fall in the proportion of patients with myocardial iron overload. Mortality has become substantially lower and cardiac iron overload is no longer the leading cause of mortality. In addition to CMR, this decade has seen the advent of two new oral iron chelators and many patients switched chelation regimen, sometimes several times, during the follow up period. Whilst the contribution of the individual components of this practice to the improved outcome cannot be concluded without randomized studies, it is clear that this modern management of TM is associated with reduced TM mortality. Disclosures: Off Label Use: Deferiprone is off label in the USA but licensed in Europe. Shah:Novartis: Honoraria, Speakers Bureau; Apotex/ Swedish Orphan: Honoraria. Pennell:Siemens: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Apotex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cardiovascular Imaging Solutions: Director of CVIS, Equity Ownership. Porter:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

A MRI Prospective Survey on Cardiac and Hepatic Iron and Cardiac Function in Thalassemia Major Patients Treated with Sequential deferiprone–desferrioxamine versus Deferasirox

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1087-1087
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giuseppe Rossi ◽  
Domenico Giuseppe D'Ascola ◽  
Marcello Capra ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Right Ventricular ◽  
Systolic Function ◽  
Thalassemia Major ◽  
Ventricular Ejection ◽  
Hepatic Iron ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Cardiac Iron

Abstract Abstract 1087 Introduction: No data are available in literature about possible different changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients treated with sequential deferipron–desferrioxamine (DFP-DFO) versus deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue.Our aim was to prospectively assess the efficacy of the DFP-DFO vs DFX 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 35 patients treated with DFP-DFO versus 80 patients treated with DFX between the 2 MR scans. Cardiac iron was evaluated by T2* multiecho multislice technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron was measured by T2* multiecho technique. Results: Excellent/good levels of compliance were similar in the two groups (DFP-DFO 97.1% vs DFX 98.8%; P=0.544). Among the patients with no significant myocardial iron overload (MIO) at baseline (global heart T2*≥20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 96% vs DFX 98%; P=0.536). Among the patients with MIO at baseline, in both groups there was a significant improvement in the global heart T2* value (DFP-DFO: 4.8±3.9 ms P=0.004 and DFX: 3.5±4.7 P=0.001) and a significant reduction in the number of pathological segments (DFP-DFO: −3.2±3.8 P=0.026 and DFX: −2.4±3.8 P=0.003). Only in sequential group there was a significant increment in the left and right ventricular ejection fractions (4.3±5.1% P=0.035 and 6.7±6.6% P=0.017, respectively). The improvement in the global heart T2* was not significantly different between groups. The improvement in the left as well in the right ventricular ejection fractions was significantly different between groups (P=0.009 and P=0.015, respectively) (Figure 1). Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in the DFX group there was a significant improvement in the liver T2* value (2.6±5.3 ms P=0.001). The changes in liver T2* were significantly higher in DFX group than in DFP-DFO (0.5±2.0 ms) group (P=0.030) (Figure 2). Conclusions: In TM patients prospectively no significant differences on cardiac iron were found between sequential DFP–DFO treatment versus DFX in monoterapy, although the DFP-DFO treatment was significantly more effective in improving biventricular global systolic function. Conversely, DFX was significantly more effective in reducing hepatic siderosis. 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. Borgna-Pignatti:Apotex: Honoraria; 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.

Iron Overload Is Highly Prevalent in All Disease Severity States in Pyruvate Kinase Deficiency (PKD)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2430-2430
Author(s):  
Eduard J van Beers ◽  
Wilma Barcellini ◽  
Stefan W. Eber ◽  
Janet L Kwiatkowski ◽  
Jennifer A Rothman ◽  
...  
Keyword(s):  
Iron Overload ◽  
Board Of Directors ◽  
Disease Severity ◽  
Research Funding ◽  
Chelation Therapy ◽  
Iron Status ◽  
Compound Heterozygous ◽  
Advisory Committees ◽  
Cardiac Iron ◽  
Significant Difference

Abstract Background: PKD causes a defect in glycolysis resulting in a hereditary non-spherocytic hemolytic anemia. The prevalence of iron overload is not well described for PKD. Aim: We aim to describe the demographic features and prevalence of iron overload in transfusion dependent and transfusion independent patients with PKD. Methods: Between March 2014 and April 2016, 203 patients enrolled on the PKD Natural History Study at 29 IRB approved sites. All patients were confirmed to have two compound heterozygous or homozygous mutations in the PKLR gene. Children < 1 year of age (n=9) were excluded from this analysis, because elevated ferritin levels are less reliably related to iron overload. Patients were designated with iron overload at the time of enrollment if the plasma ferritin was >1000 ng/mL or the patient was on chelation therapy at any time during the prior 12 months. Patients were designated with having had iron overload if a MRI ever showed liver iron content (LIC) >3 mg/g dry weight or if they had ever received chelation therapy. Tests of association were performed using Fisher's exact test (categorical) and Wilcoxon rank sum test (continuous). Linear associations between variables were measured by Pearson correlation coefficient. P-values <0.05 were considered statistically significant. Results: Of the 194 patients, 111 (57%) were adults ≥18 years and 83 (43%) were children. The median age of enrollment was 20.6 y (range: 1.3-69.9). Splenectomy had been performed in 65% (126/194). Screening ferritin levels were available for 72% (140/194) and LIC for 32% (62/194). At enrollment, 48% (70/147) had iron overload as defined by ferritin and/or current chelation. Using the LIC criterion, iron overload had been present at some point in 86% (95/110) of patients. Ferritin positively correlated with LIC (n=45); r=0.62, p<0.0001. However, of 29 patients with an LIC measurement and a mean ferritin <1000 ng/mL, 15 (52%) had a LIC >3 mg/g DW. Baseline characteristics in patients with and without iron overload are shown in the Table. Notably, even in patients that were never regularly transfused and had a hemoglobin (Hb) >8.7 g/dl, the prevalence of iron overload was 26% (8/31). The frequency of iron overload was significantly higher in patients who had a prior splenectomy (p<0.0001), even after controlling for transfusion history (p<0.0001). Age was associated with iron overload (p=0.046); although, the age range of patients with iron overload was broad (1.3-69.9 years). The frequency of iron overload was significantly higher in those with a lower baselineHb(p=0.004) and higher bilirubin (p=0.03). Data on cardiac iron status was available for 66 patients.Only 2 had cardiac iron overload (defined as T2*<20ms); they were age 5 (T2* 17.8ms, LIC 5 mg/g) and 22 years (T2* 19.7ms, LIC 14 mg/g) at the time of the MRI. Of the 194 patients, 52 (27%) were from the Pennsylvania Amish community. These patients were managed differently than the non-Amish, in that only 2% of the Amish patients were on iron chelation therapy in the 12 months prior to enrollment compared with 43% among the non-Amish cohort. In addition, the Amish had a significant higher prevalence of splenectomy (96% vs 52%, p<0.0001) and proportion who had been historically transfused (79% vs 32%, p<0.0001). Despite these differences, the Amish patients had a lower prevalence of iron overload (34% vs. 51%). There was no significant difference inHbor enrollment age between the Amish and non-Amish cohorts. Conclusion: Iron overload is a common, serious complication in PKD, regardless of age, disease severity, or transfusion status. Although ferritin correlates with LIC for the PKD population overall, at the individual patient level, ferritin is not a good predictor of LIC and a ferritin <1000 ng/ml does not exclude hepatic iron overload. Therefore, we recommend that all patients with PKD starting at age 1 year should be screened annually for iron overload using ferritin and, at least once, using MRI. Disclosures Barcellini: Agios: Consultancy. Neufeld:Novartis: Consultancy. Morton:Agios Pharmaceuticals: Research Funding. Yaish:Octapharma: Other: Study investigator. Kuo:Agios Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Apotex: Other: unrestricted educational grant; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Thompson:bluebird bio: Consultancy, Research Funding; Eli Lily: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mast: Research Funding; Baxalta (now part of Shire): Research Funding; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Amgen: Research Funding. Grace:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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