scholarly journals The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study

2021 ◽  
Vol 10 (23) ◽  
pp. 5561
Author(s):  
Antonella Meloni ◽  
Laura Pistoia ◽  
Maria Rita Gamberini ◽  
Paolo Ricchi ◽  
Valerio Cecinati ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Iron Chelation ◽  
Cardiac Complications ◽  
Oral Glucose ◽  
Thalassemia Intermedia ◽  
Multicenter Observational Study ◽  
Cardiac Iron ◽  
Biventricular Function

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

scholarly journals Prospective Changes of Cardiac and Hepatic Iron and Cardiac Function in Low and Intermediate-1 Risk MDS Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1911-1911
Author(s):  
Alessia Pepe ◽  
Antonella Meloni ◽  
Giancarlo Carulli ◽  
Esther Natalie Oliva ◽  
Francesco Arcioni ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Chelation Therapy ◽  
Mean Difference ◽  
Volume Index ◽  
Hepatic Iron ◽  
Cardiac Iron ◽  
Biventricular Function ◽  
Hepatic Iron Overload

Abstract Background: In patients with myelodysplastic syndrome (MDS) no longitudinal studies on myocardial and hepatic iron and on cardiac function and fibrosis are available in literature. So, the aim of our study was to assess the changes in cardiac and hepatic iron overload and the morpho-functional cardiac parameters by Magnetic Resonance Imaging (MRI) in MDS patients enrolled in the MIOMED (Myocardial Iron Overload in MyElodysplastic Diseases) study who performed the follow-up (FU) MRI at 12 months. Methods: MIOMED is an observational, MRI multicentre study in low and intermediate-1 risk MDS patients who have not received regular iron chelation therapy. Out of the 51 MDS patients enrolled, 48 underwent the baseline MRI exam and 28 performed the MRI FU. This analysis was limited to patients who performed both the MRIs. Mean age was 72.8±7.6 years and 8 patients were females. MIO was assessed using a multislice multiecho T2* approach. Hepatic T2* values were assessed in a homogeneous tissue area and converted into liver iron concentration (LIC). Biventricular function parameters were quantified by cine sequences. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) acquisitions. Results: The FU MRI was not performed for the following reasons: 4 deaths and 16 patient refusal. At baseline only one patient showed cardiac iron overload (global heart T2*=14.8 ms) but he recovered at the FU (global heart T2*=28.8 ms). He was not transfused. Out of the 27 patients without significant cardiac iron at the baseline, 26 maintained the same status at the FU while one showed cardiac iron (global heart T2*=12.3 ms). Thirteen patients (8 transfusion-dependent - TD) had hepatic iron overload (MRI LIC≥3mg/g/dw) at the baseline.For this subgroup, the baseline and the FU LIC values were, respectively, 14.9±12.0 mg/g/dw and 20.1±16.1 mg/g/dw. The increase in MRI LIC values was not significant (P=0.196). Out of the 11 patients with a baseline MRI LIC<3 mg/g/dw, two (13.3%) showed hepatic iron at the FU. Only one patient was TD but both patients had not received any chelation therapy. Serum ferritin levels were comparable at both the MRIs (923±618 vs 1168±1004 ng/ml; P=0.150). Due mainly to technical reasons, biventricular function was assesses at both baseline and FU MRIs in 22 patients. At baseline 6 patients showed a reduced left ventricular ejection fraction (LVEF) and 4 of them recovered at the FU. All patients had a baseline global heart T2*>20 ms (one with 2 segmental T2* values<20 ms). At baseline 5 patients showed a reduced right ventricular EF (RV EF) and all recovered at the FU. One patient with normal LV EF at baseline showed pathological LV EF at the and 2 patients with normal RV EF at baseline showed reduced RV EF at the FU (one patient suffered from pulmonary hypertension). At the FU we detected a significant increase in the LV end-diastolic volume index (EDVI) (mean difference: 6.5±11.3 ml/m2; P=0.015) as well as in the RV EDVI (mean difference: 7.8±9.3 ml/m2; P=0.002). The change in the LV mass index between the 2 MRIs was not significant. For 18 patients the presence of myocardial fibrosis was investigated at both baseline and FU MRIs, and this subgroup was considered. Eight patients had myocardial fibrosis at the baseline. One patient showed a subendocardial ischemic pattern and seven patients showed a non-ischemic pattern and myocardial fibrosis was detected for all of them also at the FU. At the FU one new occurrence of non-ischemic myocardial fibrosis was detected. Conclusion. The new occurrences of cardiac iron, reduced cardiac function, increased LV and RV EDVI and myocardial fibrosis and the worsening in MRI LIC values suggest the need of performing periodic MRI scans, in order to better manage these patients. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Oliva: Celgene: Consultancy, Honoraria; Novartis: Consultancy, Speakers Bureau.

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

Gender Differences in the Development of CMR Abnormalities and Cardiac Complications: A Multicentric Prospective Study in a Large Cohort of Thalassemia Major Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 849-849 ◽  
Author(s):  
Alessia Pepe ◽  
Silvia Maffei ◽  
Laura Pistoia ◽  
Angela Ciancio ◽  
Giovanni Palazzi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Ventricular Dysfunction ◽  
Thalassemia Major ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Cardiac Iron ◽  
Cardiac Evaluation

Abstract Introduction. We aimed to prospectively assess if the male gender was associated with an higher risk of progressive cardiac iron accumulation, development of biventricular dysfunction and myocardial fibrosis assessed by CMR, and development of cardiac complications including heart failure (HF), arrhythmias and pulmonary hypertension (PH). Methods. We considered 1711 TM patients (899 females, 31.09±9.08 years), consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis. Results. Although having a similar risk of accumulating iron, males showed a significant higher risk of developing cardiac dysfunction, heart failure, arrhythmias and cardiac complications globally considered (Table 1). Figure 1 shows the Kaplan-Meier curves for the outcomes for which the male sex was a significant prognosticator. Until 20-30 years of follow-up the two lines (male and female sex) were almost overlapping while after they clearly diverged. So, patients were divided in two groups based on the follow-up duration. A significant gender-specific difference in the frequency of ventricular dysfunction and cardiac complications appeared for patients followed for at least 20 years. So, two subgroups of patients were identified: patients followed for less than 20 years and patients followed for more than 20 years. In the first subgroup males and females had a comparable risk of developing cardiac iron overload, ventricular dysfunction and cardiac complications. Conversely, if a follow-up longer than 20 years was considered, males exhibited a significant higher risk of having ventricular dysfunction, heart failure, arrhythmias, and cardiac complications. Conclusion. Females seem to tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress. According to the International Guidelines, TM patients should perform a complete cardiac evaluation every year. Our study suggested that in females older than 20 years the follow-up may be performed every 24 months, thus reducing health care costs. Table 1 Table 1. Figure 1 Figure 1. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.. De Franceschi:F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Funding.

P601Heart disease and pancreatic iron in thalassemia major

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Meloni ◽  
L Pistoia ◽  
G Restaino ◽  
S Renne ◽  
N Giunta ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Iron Overload ◽  
Myocardial Fibrosis ◽  
Strong Predictor ◽  
Pancreatic Head ◽  
Thalassemia Major ◽  
Cardiac Complications ◽  
Myocardial Iron ◽  
Cardiac Iron

Abstract Background Some preliminary data have postulated a correlation between pancreatic iron overload and heart iron and function in thalassemia major (TM) patients. Purpose In the present multicenter study we explored systematically the link between pancreatic iron and heart disease in a large cohort of TM patients. Methods We considered 880 TM patients (467 M, mean age 37.83±10.05 years) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. Myocardial iron overload (MIO) was quantified using a T2* segmental approach. Biventricular function parameters were assessed by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis. Results A significant correlation between pancreatic and cardiac iron was reconfirmed in this more numerous population and a normal pancreas T2* showed negative predictive value of 100% for cardiac iron. LGE sequences were acquired in 273 TM patients and 84 (30.77%) of them showed macroscopic myocardial fibrosis. Global pancreas T2* values were significantly lower in patients with fibrosis (7.38±6.19 ms vs 11.91±9.79 ms; P<0.0001). Sixty-four patients had at least one cardiac complication (arrhythmias, heart failure, pulmonary hyperthension, vascular disease). Patients with cardiac complications showed a significant lower global pancreas T2* (7.83±5.61 ms vs 12.76±10.34 ms; P=0.024). Specifically, global pancreas T2* values were significantly lower in patients with heart failure as well as in patients with arrhythmias and all patients with one of these two diseases had a pathologic global pancreas T2* value (see Figure). Conclusion Pancreatic iron is a strong predictor not only for cardiac iron, but also for cardiac complications supporting a more profound link between pancreatic iron and heart disease in TM.

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

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

Abstract Little is known about cardiac involvement in Thalassemia Intermedia (TI) using magnetic resonance imaging (MRI). Thus, we investigated myocardial and liver iron overload, myocardial fibrosis, biventricular function parameters and their inter-relationship in 60 TI using MRI. Then, we compared the data of 35 selected TI with age &lt; 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 &gt; 20 ms) (A) and late enhancement (white arrows) in the antero-septal junction, in the infero-septal junction and in the mid-ventricular septum (B). In TI patients MIO was significantly lower respect to TM patients; conversely volumes, cardiac indexes, LVEF, bi-atrial areas, and liver iron overload were significantly higher. Myocardial fibrosis was comparable between the 2 groups. TI patients showed lower myocardial iron burden and more pronounced high cardiac output findings with myocardial fibrosis significantly associated to impaired heart function. These data seem to suggest using MRI also for TI patients and could place the basis to reconsider the current cardiological and haematological management in this population. Figure Figure

MRI Prospective Survey on Cardiac and Hepatic Iron in Thalassemia Intermedia Patients Treated with Desferrioxamine, Deferiprone and Deferasirox

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4041-4041
Author(s):  
Antonella Meloni ◽  
Aurelio Maggio ◽  
Anna Pietrapertosa ◽  
Pier Paolo Bitti ◽  
Sabrina Armari ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Hepatic Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Number Of Patients ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri

Abstract Background. Few studies have evaluated the efficacy of iron chelation therapy in thalassemia intermedia (TI) patients. Our study aimed to prospectively assess by quantitative Magnetic Resonance imaging (MRI) the efficacy of the three available chelators in monotherapy in transfusion dependent (TD) TI patients. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 103 TI patients TD with an MRI follow-up (FU) study at 18±3 months who had been received one chelator alone between the two MRI scans. Iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Three groups of patients were identified: 27 patients (13 females, mean age 40.12±10.31 years) treated with desferioxamine (DFO – mean dosage 37.52±8.69 mg/kg/die), 23 patients (14 females, mean age 34.73±10.67 years) treated with deferiprone (DFP– dosage 71.70±14.46mg/kg/die) and 14 patients (9 females, mean age 36.63±10.92 years) treated with deferasirox (DFX – mean dosage 27.75±5.04 mg/kg/die). Excellent/good levels of compliance were similar in the DFO (92.6%), DFP (100%) and DFX (100%) groups (P=0.345). The mean starting age of regular transfusion was 14.73±15.89 years. At baseline in DFO group two patients (7.4%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. At baseline in DFP group two patients (8.7%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. All the 5 patients (35.7%) under DFX therapy with pathological global heart T2* at the baseline remained at the same status at the FU. The percentage of patients who maintained a normal global heart T2* value was comparable for DFO (100%), DFP (100%) and DFX (88.9%) groups (P=0.164). Among the 46 patients with hepatic iron at baseline (MRI LIC ≥3 mg/g/dw), the reduction in the MRI LIC values was significant only in the DFO group (DFO: -3.39±6.38 mg/g/dw P=0.041; DFP: -2.25±6.01 mg/g/dw P=0.136 and DFX: -0.36±5.56 mg/g/dw P=0.875). The decrease in MRI LIC values was comparable among the groups (P=0.336). The number of patients with a MRI LIC<3 mg/g/dw went up from 10 (37%) to 11 (40.7%) in the DFO group, from 6 (26.1%) to 8 (34.8%) in the DFP group and from 2 (14.3%) to 8 (57.1%) in the DFX group. The percentage of patients who maintained a normal MRI LIC value was comparable for DFO (90%) vs DFP (50%) and DFX (100%) groups (P=0.191). Conclusion: Prospectively in transfusion-dependent TI patients at the dosages used in the clinical practice, DFO and DFP showed 100% efficacy in maintaining a normal global heart T2* value while DFX had 100% efficacy in maintaining a normal LIC value. Further prospective studies involving more patients with iron at the baseline are needed to establish which is the most effective drug in reducing iron levels. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

Occurrence of Neoplastic Diseases in a Large Cohort of Thalassemic Patients in Greece

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3264-3264
Author(s):  
Alexandra Kouraklis ◽  
Antonia Chatziliami ◽  
Antonis Kattamis ◽  
Efthimia Vlachaki ◽  
Evangelos Briasoulis ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Cell Lymphoma ◽  
Iron Chelation ◽  
Beta Thalassemia ◽  
Thalassemia Intermedia ◽  
Neoplastic Diseases ◽  
Median Serum ◽  
Neoplastic Disorders

Abstract Abstract 3264 Life expectancy of thalassemic patients, appropriately transfused and adequately iron-chelated, has been substantially extended the last decades. However, these patients are subjected to particular risks which might favor the development of neoplasia, such as transfusional iron overload, high prevalence of viral diseases, particularly HCV infection, and transfusion-associated alteration of their immune status. The occurrence of neoplastic diseases has not been extensively investigated in this patient population. We sought to investigate the occurrence of neoplastic diseases during a 16.5 year-period, in a large cohort of 1972 thalassemic patients (homozygous beta-thalassemia N=1448, thalassemia intermedia N=352 and sickle-cell/beta thalassemia N=172), followed-up in 6 large Greek Thalassemic Units. All documented cases of neoplastic diseases, diagnosed during the period between 1.1.1996 and 30.6.2012 were collected and analyzed. The frequency of each type of neoplasia was then correlated with specific factors, potentially influencing the occurrence of these disorders, and particularly age at first transfusion, frequency of transfusions, previous splenectomy, smoking, use of hydroxyurea, previous autoimmune disorders, presence of HBV, HCV and HIV infection, adequacy of iron chelation and the degree of hepatic siderosis. Totally 38 cases of neoplastic disorders were documented among the 1972 patients. These were Hepatocellular carcinoma (10 cases), non-Hodgkin's Lymphoma (6 cases in total: Marginal-zone lymphoma N=2, Mantle-cell lymphoma N=1, Diffuse large B-cell lymphoma N=1, Burkitt's lymphoma N=1, T-cell lymphoblastic lymphoma N=1), Thyroid carcinoma (3 cases in total: papillary N=2, follicular N=1), Hodgkin's lymphoma (3 cases in total, classical N=2, LPHD N=1), Renal cell cancer (N=3), Colon cancer (N=3), Breast cancer (N=2), Cholangiocarcinoma (N=2), Pre-B Acute Lymphoblastic Leukemia (N=2), Testicular cancer (2 cases in total, seminoma N=1, teratoma N=1), melanoma (N=1), and Renal oncocytoma (N=1). Twenty-eight cases were diagnosed among patients with homozygous beta-thalassemia, 6 among patients with thalassemia intermedia and 4 among patients with sickle-cell/beta thalassemia. Median age at diagnosis of the neoplastic disease was 39 years (age range 21 to 63 years). Twenty-nine cases (76.3%) were diagnosed among previously splenectomized patients, although splenectomy had been performed in 41% of the total cohort of patients. All patients were HIV-negative, 3/31 (9.7%) were HBsAg-positive, whereas 22/37 (59.5%) had HCV infection. Patients were then classified according to the level of liver siderosis and the effectiveness of their iron chelation treatment, estimated by their annual median serum ferritin levels. Eleven patients were found to be adequately chelated (median serum ferritin 310 ng/ml), 16 were moderately-effectively chelated (median serum ferritin 1240 ng/ml) and 11 were inadequately chelated (median serum ferritin 2552 ng/ml). There was no difference in patient's age or in the type of neoplastic disorders occurred in each of the 3 categories, however 3/11 poorly chelated patients were long term survivors, versus 8/16 moderately chelated and 9/11 adequately chelated patients. In conclusion, the prolongation of overall survival of thalassemic patients results in increasing occurrence of neoplastic diseases among this patient population. Splenectomized and HCV-infected patients appear to represent higher-risk groups, whereas the role of iron overload appears not to influence the occurrence of neoplastic diseases but may have an impact on the long-term outcome and clearly deserves further investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Relation of Pancreatic Iron Overload Detected By MRI with Disorders of Glucose Metabolism and Results of Liver, Cardiac and Pitutiary MRI Among Transfusion Dependent Thalassemia (TDT) Patients in Turkey

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2350-2350
Author(s):  
Zeynep Karakas ◽  
Cihangir Sevimli ◽  
Nurdan Gul ◽  
Rana Comert ◽  
Memduh Dursun
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Iron Overload ◽  
Pearson Correlation ◽  
Fasting Blood Glucose ◽  
The Body ◽  
C Peptide ◽  
Cardiac Iron ◽  
Iron Load ◽  
Glucose Dysregulation

Abstract The relationship between pancreatic iron overload and glucose dysregulation has not been well defined and need further investigation. Pancreas iron load measurements are also necessary to understand how hepatic, pancreatic, and cardiac iron burden prospectively modulate the evolution of diabetes in transfusion dependent thalassemia (TDT). Aim: This study aims to evaluate the presence of pancreatic iron overload among TDT patients in Turkey based on the MRI R2* and T2* results as well as to determine its association to Fasting blood glucose (FBG), insulin, fructosamine, Homa-IR, C-peptide, ferritin, liver, cardiac and hypophysis MRI R2* results. Material and Methods: This study was conducted at the Thalassemia Center in Istanbul University, Istanbul Medical Faculty. Forty-one TDT patients included the study with a mean age of 29.9±9,9 (median 29) years old, ranging from 11 to 45 years old. Pancreatic, liver, cardiac and hypophsis MRI's were conducted using 1.5 Tesla Philips MRI machine in the Department of Radiology. Pancreatic MRI R2* results < 30 Hz were considered normal, 30-100 Hz as mild, and > 100 Hz as moderate to severe pancreatic siderosis. Pancreatic MRI T2 results >26 ms were is normal, < 10 ms is severe iron overload as presented at literature. Correlations between pancreatic MRI R2* results and FBG, insulin, fructosamine, Homa-IR, C-peptide, ferritin, cardiac and hypophysis MRI R2* were evaluated using the Pearson correlation, Man Whitney U test. Results: Laboratory findings of glucose metabolism and MRI's of liver, pancreas, hypophsis and cardiac iron are shown at Table 1. There were no significant relationship between fasting blood glucose, insülin, C-peptid level, fructosamine, Homa-IR, ferritin and Pancreas T2* and R2* results (p>0.05). There was significant correlation between liver and pancreas MRI T2* and R2* results. (p<0.01). There was no significant correlation between hypophysis global R2, cardiac R2*, Pancreas T2* and, Pancreas R2* measurements (p>0.05). Fourteen patients were found to have normal pancreatic MRI R2* (34,1%) while 19 patients have normal pancreatic MRI T2 (46.3%). It is reported that T2 is irrelevant to age and sex, and R2 can be related to age-related fatty degeneration. There was significant pancreatic iron burden in 31.7% of patients (R2*>100 Hz), of whom only 1 patient was under 18 years of age.There were 22 (53.6%) patients with T2* <26 ms and had iron overload, 13 (31.7%) had T2 <10 ms and had significant iron overload. Almost three-quarters of patients (n:13, 31.7%) had moderate to severe pancreatic iron load on both T2* and R2* measurements. Thirteen patients with significant pancreatic iron overload had 3 severe hypophysis, 1 moderate, 2 severe cardiac siderosis. and had no serious liver iron burden. This shows that the treatment of chelation first led to liver, then heart and pituitary, respectively, and finally pancreatic iron burden and demonstrates the importance of pancreas MR in assessing the body iron load. Discussion:The lack of correlation between pancreatic and cardiac MRI R2* are in contrast to another demonstrating that pancreatic iron load are good predictors of cardiac iron load. This is due to the fact that our patients are followed up with cardiac MR and taken to the intensive chelation programs of the patients who detect iron in the heart. Previous studies also report that while pancreatic R2* may be sensitive for glucose dysregulation, most patients may still have no symptoms and normal blood glucose, indicating the presence of a preclinical iron burden. Pancreatic MRI R2* can detect pancreatic iron accumulation at a much earlier stage. Lack of excessive iron load in liver of our patient can be explain low glucose metabolism disorder despite high pancreatic iron overload. 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.

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