Study of Renal Iron Overload by T2* MRI in a Large Cohort of Thalassemia Major Patients

Abstract Abstract 5177 Background. Renal dysfunction has been reported in adult subjects with thalassemia major (TM) since 1975. One of the main cause is the iron overload consequent to regular transfusions. Multiecho T2* MRI is a well-established technique for cardiac and hepatic iron overload assessment, but there very few report concerning the kidneys. The aims of this study were to describe the T2* values of the kidneys in patients with TM, to investigate the correlation between renal and myocardial or hepatic siderosis and biventricular cardiac function. Methods. 119 TM patients (58 men, 30. 7 ± 8. 2 years) enrolled in the Myocardial Iron Overload (MIOT) networks underwent MRI. For the measurement of iron overload, multiecho T2* sequences were used. The left ventricle was segmented into a 16-segments standardized model and the T2* value on each segment was calculated as well as the global value. In the liver, the T2* value was assessed in a single region of interest (ROI) in a homogeneous area of the parenchyma. For each kidney, T2* values were calculated in three different ROIs and were averaged to obtain a representative value for the kidney. The mean T2* value over the kidneys was also calculated. Cine images were obtained to quantify biventricular morphological and functional parameters in a standard way. Results. T2* values in the right kidney were significant lower than in the left kidney (40. 3±11. 9 ms vs 44. 1±12. 7 ms, P<0. 0001). The mean T2* value over the kidneys was 42. 2±11. 9 ms and 40 patients (33. 6%) had a pathological value (T2*<36 ms, lower limit of normal evaluated on 20 healthy subjects). The mean T2* value did not show a significant difference amongst men ad women (43. 2±11. 7 ms versus 41. 3±12. 1 ms, P=0. 378). The mean T2* values increased with age in a significant manner (r=0. 321, P<0. 0001). There was a significant negative correlation between serum ferritin levels and mean renal T2* values (r=-0. 446, P<0. 0001). Significant positive correlations of the mean T2* values were demonstrated for liver (r=0. 511, P<0. 0001) and global heart (r=0. 262, P=0. 004) T2* values (Figure 1). No correlation was found between renal iron overload and bi-ventricular function parameters. Conclusions. Systemic T2* differences between left and right kidneys were found, with significant lower values in the right one. Mean T2* value increased with age. We confirmed that kidney iron deposition was not very common in TM, but it was correlated with iron deposition in liver and heart. Disclosures: No relevant conflicts of interest to declare.

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Frequency, Pattern, and Associations of Renal Iron Accumulation in Sickle Beta-Thalassemia

Blood ◽

10.1182/blood-2021-144592 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3086-3086

Author(s):

Alessia Pepe ◽

Luigi Barbuto ◽

Laura Pistoia ◽

Vincenzo Positano ◽

Francesco Massei ◽

...

Keyword(s):

Iron Overload ◽

Board Of Directors ◽

Thalassemia Major ◽

Iron Deposition ◽

Beta Thalassemia ◽

Advisory Committees ◽

Frequency Pattern ◽

Iron Load ◽

Significant Difference ◽

Chronic Hemolysis

Abstract Background: Chronically transfused homozygous sickle cell disease (HbSS) patients were shown to have higher kidney iron deposition than thalassemia major patients, not associated to total body iron and mainly caused by chronic hemolysis. Kidney iron deposition has not been explored in sickle beta-thalassemia (Sβ-thal), resulting from the inheritance of both sickle cell and beta-thalssemia genes. Aim: This multi center study aimed to study frequency, pattern, and associations of renal iron accumulation in sickle beta-thalassemia. Methods: Thirty-three Sβ-thal patients (36.49±14.72 years; 13 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) network were considered. Moreover, 20 healthy subjects, 14 HbSS patients and 71 thalassemia major (TM) patients were included as comparison groups. Hepatic, cardiac, pancreatic, and renal iron overload was quantified by the gradient-echo T2* technique. In each kidney T2* was measured in anterior, posterolateral, and posteromedial parenchymal regions and the global T2* value was calculated as the average of the two kidneys T2* values. Results. Global renal T2* were significantly higher in healthy subjects versus both Sβ-thal patients (49.68±10.09 ms vs 43.19±8.07 ms; P=0.013) and HbSS patients (49.68±10.09 ms vs 26.21±17.07 ms; P<0.0001). Sβ-thal patients showed comparable age, sex, frequency of regular transfusion, hematochemical parameters, and hepatic, cardiac and pancreatic iron load than HbSS patients, but they had a significant lower frequency of renal iron overload (global renal T2*<31 ms) (9.1% vs 57.1%; P=0.001). Regularly transfused patients (16 Sβ-thal and 10 HbSS) were compared with TM patients, homogeneous for age and sex, but TM started regular transfusions significantly earlier and they were more frequently chelated. No significant difference was detected in terms of hepatic and cardiac iron levels, but TM patients had significantly lower pancreas T2* values than both the other two groups and significantly higher global renal T2* values than HbSS patients (42.87±9.43 ms vs 24.39±15.74 ms; P=0.001). In Sβ-thal patients no significant difference was detected between T2* values in left and right kidneys, and global renal T2* values were not associated to age, gender, splenectomy, and they were comparable between regularly transfused and non transfused patients. No correlation was detected between renal T2* values and serum ferritin levels or iron load in the other organs. Global renal T2* values were not associated with serum creatinine levels but showed a significant inverse correlation with serum lactate dehydrogenase (Figure 1). Conclusion. Renal iron deposition is not common in Sβ-thal patients, with a prevalence significantly lower compared to that of HbSS patients, but with a similar underlying mechanism due to the chronic hemolysis. Figure 1 Figure 1. Disclosures Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees.

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Correlation between serum ferritin level, cardiac and hepatic T2-star MRI in patients with β-thalassemia major in Al-Diwaniya thalassemia center

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1392 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Alaa Mutter Jabur Al-Shibany ◽

AalanHadi AL-Zamili

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Iron Level ◽

The Mean ◽

T2 Mri

Patients with transfusion dependent thalassemia major is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) is the preferred method to measure iron level in the liver andthe heart. The goal of our study was to see if there is an association exists between serum ferritin level and T2* MRI results in patients with beta thalassemia major.This study was done in Al-Diwaniya Thalassemia center,Maternity and children teaching hospital,Iraq. During the period from 1st of January to 31st of October. Fifty eight patients with a diagnosis of beta thalassemia major were enrolled in the study. They were older than five years old,transfusion dependent and on chelation therapy. Hepatic and Myocardial T2*MRI and the mean serum ferritin levels were measured during the study period for all patients.There is a significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.018 ). also a significant correlation was observed between serum ferritin and hepatic T2*MRI (p=0.02). Neither cardiac T2* MRI nor hepatic T2* MRI show any correlation with the mean age.our study also showa positive correlation between the patients withcardiac T2* MRI and the development of diabetes mellitus in contrast to hepatic T2* MRI in which there is no any correlation. Hypothyroidism was observedno correlation with either cardiac or hepatic T2* MRI.Our results showed a positiveassociation between hepatic, cardiac T2*MRI and serum ferritin levels.

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

Blood ◽

10.1182/blood.v118.21.2157.2157 ◽

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.

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Assessment of the Relationship Between Iron Overload Based on Cardiac T2* MRI and Fragmented QRS in Beta-Thalassemia Major Patients

Shiraz E-Medical Journal ◽

10.5812/semj.96612 ◽

2020 ◽

Vol 21 (8) ◽

Author(s):

Yazdan Ghandi ◽

Danial Habibi ◽

Aziz Eghbali

Keyword(s):

Iron Overload ◽

Chelation Therapy ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Cardiac Iron ◽

Fragmented Qrs ◽

Beta Thalassemia Major ◽

Cardiac Iron Overload ◽

The Mean ◽

T2 Mri

Background: Cardiac involvement in beta-thalassemia major patients is an important cause of mortality. Therefore, in these patients, timely diagnosis of cardiac disorder is essential. Objectives: The present study aimed at determining the association between cardiac iron overload and fragmented QRS (fQRS). Methods: This cross-sectional study was conducted on 40 β-TM patients, aged 5 - 40 years. The presence of fQRS was evaluated in 12-lead surface electrocardiograms. Cardiac T2* MRI was performed to determine the iron overload. The patients were divided into four groups of chelation therapy. Results: The mean age of patients was reported to be 22.50 ± 6.75 years. The groups showed no significant difference regarding gender, age, or left ventricular ejection fraction. The presence of fQRS was detected in 10 patients (25%), while T2* value was lower than 20 ms in 10 patients (25%). The mean age of patients with and without fQRS was 26.23 ± 2.71 and 19.40 ± 2.61 years, respectively (P = 0.001). The univariate analysis indicated that fQRS had a significant relationship with cardiac iron overload (OR = 5; 95% CI: 1.04 - 23.99; P < 0.044). The multiple logistic regression analysis represented a significant association between iron overload and fQRS (OR = 5.556; 95% CI: 1.027 - 30.049). The sensitivity and specificity of the fQRS against MRI were equal to 50% and 83.3% respectively. Conclusions: The absence of fQRS on ECGs could be a good predictor of the lack of cardiac iron overload in β-TM patients. The results showed that fQRS might indicate the no need for close monitoring for cardiac overload with cardiac MRI and aggressive chelation therapy.

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Dosimetric comparison of constant dose rate volumetric modulated arc therapy (CDR-VMAT) and intensity-modulated radiation therapy (IMRT) for gallbladder cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396920001132 ◽

2020 ◽

pp. 1-6

Author(s):

Varsha R. Gedam ◽

Anirudh Pradhan

Keyword(s):

Gallbladder Cancer ◽

Left Kidney ◽

Volumetric Modulated Arc Therapy ◽

Intensity Modulated Radiation Therapy ◽

Treatment Delivery ◽

Significant Difference ◽

Arc Therapy ◽

Constant Dose ◽

The Mean ◽

The Right

Abstract Aim: To study the feasibility of constant dose rate volumetric modulated arc therapy (CDR-VMAT) in radiotherapy for gallbladder cancer by comparing dosimetric parameter suggested by International Commission on Radiation Units and Measurements-83 (ICRU-83) with step and shoot intensity-modulated radiation therapy (SS IMRT). Methods: For this study, we selected 21 post-operative gallbladder cancer patients, which were treated with the IMRT technique from 2016 to 2019. For each patient, we generated SS IMRT plan and CDR-VMAT plan and were dosimetrically compared by parameters suggested by ICRU-83 for PTV. Homogeneity Index (HI) and Conformity Index (CI) were also calculated. For evaluation of Organ at Risk (OAR), we compared the mean doses, volume doses to the right kidney, left kidney, both kidneys combined, liver and max dose to the spinal cord. Monitor units (MUs) and treatment delivery time were also compared. Results: On comparing, we found that CDR-VMAT plans were highly conformed as CI and PCI (CI define by Paddick) were found more (0·98 ± 0·01 vs. 0·97 ± 0·03 and 0·86 ± 0·05 vs. 0·85 ± 0·05) than IMRT plans but not statistically significant. Better dose HI was found for IMRT plans with statistical significant difference (p < 0·001). The tumour coverage was found similar 98·24% and 97·83% for SS IMRT and CDR-VMAT, respectively. For D2%, the maximum dose to PTV was significantly lower in IMRT (p = 0·001). D50% and mean dose to PTV were also comparable to IMRT with no statistically significant difference. The OAR parameters were comparable in both the techniques. The mean doses and volume doses V10, V20 and V30 to the right kidney, left kidney and liver were also comparable with no significant difference (p > 0·05) was noted among them. However, the maximum dose to the spinal cord was significantly less in CDR-VMAT (21·1 Gy vs. 25·1Gy) than SS IMRT with p = 0·006. More MUs were associated with the CDR-VMAT technique, but shorter treatment delivery time than the IMRT technique. Conclusions: On dosimetric comparison of two treatment techniques, we conclude that CDR-VMAT can be a valid option in radiotherapy as it achieved highly conformed dose distribution, comparable tumour coverage and OAR sparing as IMRT technique for gallbladder cancer.

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T2* MRI in Hypertransfused Children with Thalassemia Intermedia: Serum Ferritin Does Not Reflect the Reality

Blood ◽

10.1182/blood.v118.21.5304.5304 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5304-5304

Author(s):

Surekha Tony ◽

Shahina Daar ◽

Shoaib Al Zadjali ◽

Murtadha K. Al-Khabori ◽

Mohammed El Shinawy ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Conflicts Of Interest ◽

Iron Deposition ◽

Hepatic Iron ◽

Thalassemia Intermedia ◽

Hepatic Iron Overload ◽

T2 Mri ◽

Beta Gene ◽

Group 1

Abstract Abstract 5304 Background: Non-transfused patients with thalassemia intermedia (TI) accumulate iron in their body due to increased gastrointestinal absorption of iron and release of iron from the macrophages. Earlier studies have revealed that serum ferritin does not reflect the severity of iron overload in non-transfused TI patients. The current study aims at evaluating the iron overload status in a group of young hypertransfused TI children. Materials and Methods: Eleven patients (mean age 13.18±4.094 years) with TI on regular follow-up at the Pediatric Thalassemia Day Care Centre, Sultan Qaboos University Hospital, Oman were included in the study after approval by the Medical Research and Ethics Committee. All patients had beta gene mutational analysis. They were diagnosed as intermedia because of their definitive TI mutation, late age at presentation (>5 years) and transfusion independence (mean baseline Hb 6.9 g/dl). Patients were treated conventionally with hypertransfusion, and chelation, as guided by their serum ferritin levels. Serum ferritin (2 monthly) was analyzed using the Beckman Coulter Access 2 Immunoassay System. Based on serum ferritin levels, patients were classified into 2 groups, group 1(six patients) and 2 (five patients) with serum ferritin levels below and above 1000 ng/ml respectively. All patients underwent cardiac T2* MRI assessment. Based on local reference values for T2*MRI, quantification of cardiac iron deposition was categorized as normal, mild, moderate and severe iron overload at values > 20 ms, 14–20 ms, 10–14 ms and < 10 ms respectively. Simultaneous liver iron T2* values were categorized into normal, mild, moderate and severe iron overload at values > 9.1 ms, 7.1–9.0 ms, 3.1– 7.0 ms and <3.0 ms respectively. Results: Patients in group 1 and 2 had mean serum ferritin levels of 817.300±244.690 ng/ml and 1983.80±662.862 ng/ml respectively (p = 0.003). Despite this very high variation in serum ferritin values, T2* MRI showed comparable hepatic iron overload status in both the groups with mean hepatic T2* value of 2.51±0.46 ms and 3.4±1.63 ms in group 1 and group 2 respectively. The difference in hepatic T2* between the 2 groups is −0.88 (95% confidence interval −2.44 to 0.68) which is statistically insignificant (p =0.23, t-test). None of the studied patients had myocardial iron deposition (overall mean 36.86±7.8 ms). Other confounders like initial ages at presentation, pre-transfusion hemoglobin levels, durations of transfusion and chelation therapies were statistically insignificant for the 2 groups. No specific pattern of beta gene sequence was noted in either group. Conclusions: We conclude in our patients with TI on hypertransfusion, serum ferritin does not reflect their moderate to severe hepatic iron overload status. Inspite of steady serum ferritin trends, evaluation of iron overload by T2* MRI and optimal chelation is strongly recommended in hypertransfused TI patients. Disclosures: No relevant conflicts of interest to declare.

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Multicenter Validation of the Magnetic Resonance T2* Technique for Quantification of Pancreatic Iron

Blood ◽

10.1182/blood-2018-99-110161 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3637-3637

Author(s):

Alessia Pepe ◽

Laura Pistoia ◽

Daniele De Marchi ◽

Stefano Pulini ◽

Elena Facchini ◽

...

Keyword(s):

Iron Overload ◽

Healthy Subjects ◽

The Other ◽

Absolute Difference ◽

Angular Coefficient ◽

Gradient Echo ◽

Mean Absolute Difference ◽

Significant Difference ◽

The Mean ◽

T2 Mri

Abstract Introduction. The gradient echo multiecho T2* MRI technique is the most robust method for the non invasive, sensitive, and fast quantification of organ-specific iron overload. A crucial aspect is the transferability of the T2* technique among different MRI scanners, in order to expand the availability of high-quality monitoring of iron accumulation to a large population. The intra- and inter-operator reproducibility, inter-study reproducibility, and inter-scanner reproducibility of the T2* MRI method for measuring iron concentrations in the heart and liver have already been demonstrated. However, the transferability of the MRI multislice multiecho T2* technique for pancreatic iron overload assessment has not been evaluated. Thus, the aim of our study was to assess the transferability of this approach among ten MRI sites. Methods. All subjects underwent MRI using conventional clinical 1.5T scanners of three main vendors. Fifty healthy subjects, five for each site, including the reference centre, were scanned. Five patients with thalassemia were scanned locally at each site and were rescanned at the reference site in Pisa within 1 month. T2* image analysis was performed using custom-written, previously validated software (HIPPO MIOT®). T2* values over pancreatic head, body and tail were calculated and the global pancreatic T2* value was obtained as the mean. The lowest threshold of normal T2* value was 26 ms6. Results. On healthy subjects the global pancreas T2* values ranged from 28.93 to 48.89 ms (mean 37.88 ms, SD 5.08 ms). No significant difference was detected among the sites (P=0.334). Table 1 shows the global pancreas T2* values measured at the different MRI sites. The global pancreas T2* values ranged from 2.08 to 38.39 ms. There was not a significant difference between the T2* values measured in the MRI sites and the correspondent values observed in Pisa (12.02±10.20 ms vs 11.98±10.47 ms; P=0.808). All patients categorized as having pancreatic iron overload in the MRI sites, fell in the same category after the MRI executed in Pisa. There was a strong correlation between the global pancreas T2* values calculated from images obtained in Pisa and at the other MRI sites (R=0.978, P<0.0001). Figure 1 shows the global pancreas T2* values calculated from images obtained at the 9 MRI sites as a function of global pancreas T2* calculated from images obtained in Pisa. The line of best fit had a slope of 0.965 ± 0.021 and an intercept of 0.459 ± 0.328 ms. The R-squared value for the fit was 0.981. Neither constant bias (intercept did not significantly differs from zero) nor proportional bias (angular coefficient did not significantly differ from 1) affected the measurements. CoVs for all MRI sites are provided in Table 2; they ranged from 4.22 to 9.77%. The CoV for all the T2* values independently from the sites was 8.55%. The ICC considering all the T2* values, independently from the sites, was 0.995. The ICC for each MRI site is provided in Table 2 and it was always excellent. The comparison between Pisa and the other MRI sites by Bland-Altman analysis showed a mean absolute difference of -0.04 ± 1.47 ms for the global pancreas T2* values (Figure 2). No bias was present and no greater differences for higher T2* values were detected. The mean absolute difference in patients with pancreatic iron (N=39) was -0.15 ± 1.38 ms. Conclusion. The gradient-echo T2* MRI technique is an accurate and reproducible means for the calculation of pancreatic iron and may be transferred between MRI scanners in different centers from different manufacturers. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

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Quantitative T2*MRI for Bone Marrow Iron Overload Assessment in Thalassemia Major and Intemedia Patients

Blood ◽

10.1182/blood.v124.21.4042.4042 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4042-4042

Author(s):

Antonella Meloni ◽

Roberta Renni ◽

Nicola Romano ◽

Carla Cirotto ◽

Francesco Gagliardotto ◽

...

Keyword(s):

Bone Marrow ◽

Iron Overload ◽

Serum Ferritin ◽

Conflicts Of Interest ◽

Iron Concentration ◽

Lumbar Vertebra ◽

Thalassemia Major ◽

Liver Iron ◽

Transfusion Requirements ◽

T2 Mri

Abstract Introduction. Multiecho T2* MRI is a well-established technique for cardiac and hepatic iron overload assessment, but there are limited data on its potential to quantify iron in other organs. The aims of this study were to describe for the first time the T2* values of the bone marrow in patients with thalassemia major (TM) and intermedia (TI) and to investigate the correlation between bone marrow T2* and iron deposition in myocardium and liver. Methods. 283 TM patients (32.25±8.28 years, 144 females) and 46 TI patients (38.30±8.73 years, 17 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network underwent MRI. For the measurement of iron overload, multiecho T2* sequences were used. Bone marrow T2* values were obtained on a circular regions of interest (ROI) located in the visible body of the first or second lumbar vertebra. The left ventricle was segmented into a 16-segments standardized model and the T2* value on each segment was calculated as well as the global value. In the liver the T2* value was assessed in a single ROI defined in a homogeneous area of the parenchyma]and it was converted into liver iron concentration (LIC). Results. Bone marrow T2* values were significantly lower in TM than in TI patients (7.65±6.29 vs 13.22±6.01 ms; P<0.0001). Bone marrow T2* values were significantly lower in females than in males in both the diseases (Figure 1), but they increased with age in a significant manner only in TM (R=0.343, P<0.0001). In TM bone marrow T2* values were weakly associated with global heart T2* values (R=0.143; P=0.016) and negatively correlated with LIC values (R=-0.439; P<0.0001) and mean serum ferritin levels (R=-0.582; P<0.0001). In TI no association was present between bone marrow and global heart T2* value, but bone marrow T2* values were negatively correlated with LIC values (R=-0.273; P=0.046) and mean serum ferritin levels (R=-0.569; P<0.0001). One hundred and sixty-six TM patients (58.7%) were splenectomised and splenectomised TM patients showed significant higher bone marrow T2* values than non-splenectomised patients (9.78±6.78 ms vs 4.61±3.85 ms, P<0.0001). The difference remained significant also correcting for the age, significantly higher in splenectomised patients. Fourty TI patients (87.0%) were splenectomised and bone marrow T2* were comparable between splenectomised and non-splenectomised TI patients (13.46±6.26 ms vs 11.61±4.05 ms, P=0.493). Conclusions. In both TM and TI groups, males showed significantly higher T2* values. This difference may be due to the fact that the male sex is associated with severely low bone mass , which can influence the T2* values. Bone marrow T2* values were associated with heart T2* values only in TM, maybe because in TI cardiac iron overload was not common. In both TM and TI a positive correlation was found between hepatic and bone marrow siderosis. Splenectomised TM patients showed higher bone marrow T2* values, probably due to the fact that splenectomy is generally performed in patients with hypersplenism to reduce transfusion requirements. Conversely, bone marrow T2* values were comparable in splenectomised and non-splenectomised TI patients. In fact, the current indications for splenectomy in TI include growth retardation, leukopenia, thrombocytopenia, increased transfusion demand, symptomatic splenomegaly. Moreover the transfusion iron intake is significantly lower in TI. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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POS0586 RHEUMATOID ARTHRITIS IS AN INFLAMMATORY DISEASE WITH A HIGH CARDIOVASCULAR RISK

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4080 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 526.1-526

Author(s):

L. Nacef ◽

H. Riahi ◽

Y. Mabrouk ◽

H. Ferjani ◽

K. Maatallah ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Cardiovascular Risk ◽

Carotid Artery ◽

Internal Carotid ◽

Subclinical Atherosclerosis ◽

External Carotid ◽

Significant Difference ◽

The Mean ◽

The Right

Background:Hypertension, diabetes, and dyslipidemia are traditional risk factors of cardiac events. Carotid ultrasonography is an available way to detect subclinical atherosclerosis.Objectives:This study aimed to compare the intima-media thickness in RA patients based on their personal cardiovascular (CV) history of hypertension (hypertension), diabetes, and dyslipidemia.Methods:The present study is a prospective study conducted on Tunisian RA patients in the rheumatology department of Mohamed Kassab University Hospital (March and December 2020). The characteristics of the patients and those of the disease were collected.The high-resolution B-mode carotid US measured the IMT, according to American Society of Echocardiography guidelines. The carotid bulb below its bifurcation and the internal and external carotid arteries were evaluated bilaterally with grayscale, spectral, and color Doppler ultrasonography using proprietary software for carotid artery measurements. IMT was measured using the two inner layers of the common carotid artery, and an increased IMT was defined as ≥0.9 mm. A Framingham score was calculated to predict the cardiovascular risk at 10-year.Results:Forty-seven patients were collected, 78.7% of whom were women. The mean age was 52.5 ±11.06 [32-76]. The rheumatoid factor (RF) was positive in 57.8% of cases, and anti-citrullinated peptide antibodies (ACPA) were positive in 62.2% of cases. RA was erosive in 81.6% of cases. Hypertension (hypertension) was present in 14.9% of patients, diabetes in 12.8% of patients, and dyslipidemia in 12.8% of patients. Nine patients were active smokers. The mean IMT in the left common carotid (LCC) was 0.069 ±0.015, in the left internal carotid (LIC) was 0.069 ±0.015, in the left external carotid (LEC) was 0.060 ±0.023. The mean IMT was 0.068 ±0.01 in the right common carotid (RCC), 0.062 ±0.02 in the right internal carotid (RIC), and 0.060 ±0.016 in the right external carotid (REC). The IMT was significantly higher in the left common carotid (LCC) in patients with hypertension (p=0.025). There was no significant difference in the other ultrasound sites (LIC, LEC, RCC, RIC, and REC) according to the presence or absence of hypertension. The IMT was also significantly increased in patients with diabetes at LCC (p=0.017) and RIC (p=0.025). There was no significant difference in the IMT at different ultrasound sites between patients with and without dyslipidemia.Conclusion:Hypertension was significantly associated with the increase in IMT at the LCC level in RA patients. Diabetes had an impact on IMT in LCC and RIC. However, dyslipidemia did not affect the IMT at the different ultrasound sites.References:[1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and Experimental Rheumatology 2018; 36: Clinical E.xperimental.[2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid arthritis. SCANDINAVIAN CARDIOVASCULAR JOURNAL, 2017.[3]Martin I. Wah-Suarez and al, Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control study. Int J Rheum Dis. 2018;1–7.[4]Gobbic C and al. Marcadores subclínicos de aterosclerosis y factores de riesgo cardiovascular en artritis temprana. Subclinical markers of atherosclerosis and cardiovascular risk factors in early arthritis marcadores subclínicos de aterosclerose e fatores de risco cardiovascular na artrite precoce.Disclosure of Interests:None declared

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Assessment of Iron Overload in a Cohort of Sri Lankan Patients with Transfusion Dependent Beta Thalassaemia and its Correlation with Pathogenic Variants in HBB, HFE, SLC40A1, and TFR2 Genes

10.21203/rs.3.rs-541471/v1 ◽

2021 ◽

Author(s):

Ruwangi Dissanayake ◽

Nayana Samarasinghe ◽

Samantha Waidyanatha ◽

Sajeewani Pathirana ◽

Vajira HW Dissanayake ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Sri Lankan ◽

Pathogenic Variants ◽

Increased Risk ◽

The Mean ◽

One Year ◽

Next Generation Sequencing Ngs ◽

T2 Mri ◽

Generation Sequencing

Abstract Background. Iron overload (IO) is a complication in transfusion dependent beta thalassaemmia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and Methods. Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for one year in all. Those who were ≥ 8 years of age underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.Results. The mean age (SD) of this cohort was 9.5 (±4.6) years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The mean serum ferritin was 3405 (±2670.5) ng/dl. Hepatic IO was seen in 38 (95%) patients and cardiac IO was seen in 17 (42.5%) patients. All patients with cardiac IO were asymptomatic and had normal echocardiogrammes. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.32 (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. 9 (17.3%) and 3 (5.8%) patients were heterozygotes for pathogenic variants of HFE and SLC40A1 genes respectively. There were no pathogenic variants for the TfR2 gene. The heterozygotes of the pathogenic variants of the HFE and SLC40A1 genes were not at increased risk of IO.Conclusions. Cardiac T2* MRI helps to detect cardiac IO prior to the onset of symptoms when the echocardiogramme is normal. It is important to perform hepatic and cardiac MRI T2* to detect IO in patients with TDT.

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