The Role of Cardiovascular T2*MRI and Tissue Doppler Measurement in Assesment of Cardiac Status in β-Thalassemia Major

Abstract Introduction: Early detection of myocardial dysfunction and modification of treatment may prevent from progressing into the end stage heart failure and lethal arrhythmias in beta-thalassemia major (β-TM). T2* magnetic resonance imaging (MRI), a non-invasive technic determining iron accumulation in myocardium has been widespreadly used in these patients. Cardiac T2* MRI is not capable to evaluate cardiac functions but, indicates patients with risk for developing cardiac disease. Therefore, combining T2*MRI with tissue Doppler (TD) echocardiography, another technic defining both functional and structural evaluation of myocardium, could give a better information in evaluating the actual status of myocardium. The aim of this study was to evaluate cardiac status of thalassemics by using both T2*MRI and TD measurement. Methods: The study group includedpatientswith β-TM on regular transfusion and chelation program with preserved systolic function; ejection fraction > 55% and fractional shortening > 30% determined by conventional echocardiography. None of them had other organ dysfunctions adversely effecting cardiac functions. The control group was consisted of age and sex matched healthy persons. Serum ferritin levels were measured in both groups. In addition, TD measurements (S,E,A waves, time intervals; ejection time, total systolic time, isovolumetric accelaration time, isovolumetric contraction time, isovolumetric relaxation time and myocardial performance index) were obtained from three different regions of myocardium; septum, left and right ventricular posterior walls. T2* MRI was only determined in thalassemics. The study group was divided into two different subgroups according to serum ferritin level (low ferritin < 2500 ng/ml and high ferritin > 2500 ng/ml) and T2* MRI score (iron overloaded <20 ms and unloaded >20ms). The results obtained by TD within these subgroups were compared. TD measurements in thalassemics without cardiac iron overload were separately compared with the controls. Results: The study and control groups were consisted of 33 β-TM patients (16 girls/17 boys, mean age 18,7±7,7 years) and 37 healthy individuals (18 girls/19 boys, age 19,9±8,4 years), in respectively. Gender and age were similar (p>0,05). Systolic and diastolic functions by TD were found significantly impaired in thalassemics compared to the controls (p<0,05). S-lateral wave measurement showing early myocardial systolic function was more adversely effected in thalassemics (p<0,001). The patients' mean ferritin level was found 2242,3±2174,2 ng/ml (109-9843). Twelve patients (36,4%; 12/33) had high ferritin level and the rest (63,6%; 21/33) had low. T2*MRI and TD measurements did not differ in both subgroups (p>0.05). The mean T2*MRI score was 18,7±7,7 (7,3-29,8) ms in the study group. Twenty-one patients (63,6%; 21/33) had myocardial iron overload. Serum ferritin levels were similar between iron overloaded and unloaded groups (p>0.05). Both isovolumetric acceleration time of left ventricule and myocardial performance index (MPI-septal) showing systolic and diastolic functions were found significantly impaired in iron overloaded subgroup (p<0,05). There was negative correlation between MPI-septal and T2*MRI measurements in thalassemics (r:-0,343, p=0,050, fig 1). When we compared the velocity measurements (S,E,A waves) of iron unloaded thalassemics with the controls; only S wave velocity obtained from left ventricular wall was found significantly low (p<0,05). The time intervals measured from septum were found similar with the controls (p>0,05) but, the same measurements obtained from left and right ventricular posterior walls were significantly impaired (p<0,05). Figure 1: Correlation between Cardiac T2*MRI score and MPI-septal Figure 1:. Correlation between Cardiac T2*MRI score and MPI-septal Conclusions: This study showed that thalassemics with iron overload had significantly impaired TD measurements and MPI-septal index worsened when the mycardial iron load was increased (fig 1). Patients considered as iron unloaded according to T2*MRI result had left and right ventricular dysfunction determined by TD. Normal cardiac T2*MRI does not always associated with normal cardiac function. Therefore, we conclude that combining T2*MRI with TD measurements in evaluating cardiac status in β-TM, especially in patients with normal T2*MRI score, could lead to a better management of cardiac complications. Disclosures No relevant conflicts of interest to declare.

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Tissue doppler imaging in thalassemia major patients: correlation between systolic and diastolic function with serum ferritin level

Paediatrica Indonesiana ◽

10.14238/pi52.4.2012.187-93 ◽

2012 ◽

Vol 52 (4) ◽

pp. 187 ◽

Cited By ~ 1

Author(s):

Syarif Rohimi ◽

Najib Advani ◽

Sudigdo Sastroasmoro ◽

Bambang Mardiyono ◽

Sukman Tulus Putra ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Tissue Doppler Imaging ◽

Negative Correlation ◽

Serum Ferritin Level ◽

Systolic Function ◽

Ferritin Level ◽

Tissue Doppler ◽

Doppler Imaging ◽

Number Of Patients

Background Thalassemia is a major public health problem inIndonesia. Cardiac diseases remain as the main cause of death inthese patients due to iron overload. Although the T2* magneticresonance imaging has been considered as the gold standard forassessing cardiac iron overload but it has limited availability.The tissue doppler imaging (TDI) echocardiography, a fairly newand easy method that is suggested, can detect early abnormalmyocardial iron overload.Objective To assess myocardial systolic and diastolic functionof thalassemic patients using TDI and examine their correlationwith serum ferritin level.Methods A cross􀁌sectional study was conducted from January toMarch 2011 at the Harapan Kita Women and Children Hospital.We performed clinical examination, serum ferritin level, as wellas conventional and tissue doppler echocardiography on allsubjects.Results We included 34 regularly􀁌tranfused patients, of which17 were boys. The mean age of the subjects was 11.6 (SD 4.7years, range 2.6 􀁌 20 years). Mean pulse rate and blood pressurewere within normal range. Hemoglobin level at inclusion rangedfrom 5.8 to 6 g/dL. Almost all patients did not receive regularchelation therapy. Median serum ferritin level was 6275 ng/mL(range 2151 - 17,646 ng/mL). Conventional echocardiographyshowed normal systolic function, but some diastolic dysfunctionswere found including E wave abnormalites in 4 patients, A waveabnormalites in 3, and E/A ratio abnormalites found in 3. TheTDI showed decreased systolic function (Sa wave abnormality) in9 patients and diastolic dysfunctions (Ea wave abnormality in 11patients and Aa wave abnormaly in 2). No abnormality was foundin Ea/Aa and ElEa ratios. There was a weak negative correlationbetween ferritin level and Sa wave and Ea wave respectively anda moderately negative correlation between ferritin level and Ea/Aa ratio. There was no correlation between serum ferritin andAa wave or ElEa ratio.Conclusion TDI identifies a greater number of patients Mthsystolic and diastolic myocardial dysfunction than was revealedby conventional echocardiography. There was a weak negativecorrelation between serum ferritin to Sa wave and Ea wave, and amoderately negative correlation between ferritin and Ea/Aa ratio.There was no correlation between serum ferritin and Aa wave orElEa ratio. [paediatr Indones. 2012;52:187,93].

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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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Discrepancy between Serum Ferritin and Liver Iron Concentration in a Patient with Hereditary Hemochromatosis – The Value of T2* MRI

Case Reports in Oncology ◽

10.1159/000507756 ◽

2020 ◽

Vol 13 (2) ◽

pp. 712-715

Author(s):

Mustafa A. Al-Tikrity ◽

Mohamed A. Yassin

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

Hereditary Hemochromatosis ◽

Iron Concentration ◽

Hfe Gene ◽

Liver Iron Concentration ◽

C282y Mutation ◽

Liver Iron ◽

T2 Mri

Primary hemochromatosis is an inherited disorder, and the homeostatic iron regulator (HFE) gene C282Y mutation is a common cause of hemochromatosis in Europe. We are reporting a case of a 56-year-old female known to have hemochromatosis with the HFE gene C282Y mutation with a serum ferritin level of 482 μg/L who underwent heart and liver T2* MRI which showed no evidence of iron overload – neither in the heart nor in the liver. This indicates that there is a discrepancy between serum ferritin and liver iron concentration by MRI and the superiority of T2* MRI in diagnosis and follow-up of iron overload in patients with hereditary hemochromatosis.

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Evaluation of iron overload by cardiac and liver T2* in β-thalassemia: Correlation with serum ferritin, heart function and liver enzymes

Journal of Cardiovascular and Thoracic Research ◽

10.34172/jcvtr.2021.18 ◽

2021 ◽

Vol 13 (1) ◽

pp. 54-60

Author(s):

Hengameh Khadivi Heris ◽

Babak Nejati ◽

Khatereh Rezazadeh ◽

Hossein Sate ◽

Roya Dolatkhah ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Liver Enzymes ◽

Heart Function ◽

Ferritin Level ◽

Diagnostic Methods ◽

Iron Load ◽

The Relationship ◽

T2 Mri

Introduction: In this study, we aimed to assess the relationship of cardiac and hepatic T2* magnetic resonance imaging (MRI) values as a gold standard for detecting iron overload with serum ferritin level, heart function, and liver enzymes as alternative diagnostic methods. Methods: A total 58 patients with beta-thalassemia major who were all transfusion dependent were evaluated for the study. T2* MRI of heart and liver, echocardiography, serum ferritin level, and liver enzymes measurement were performed. The relationship between T2* MRI findings and other assessments were examined. Cardiac and hepatic T2* findings were categorized as normal, mild, moderate, and severe iron overload. Results: 22% and 11% of the patients were suffering from severe iron overload in heart and liver, respectively. The echocardiographic findings were not significantly different among different iron load categories in heart or liver. ALT level was significantly higher in patient with severe iron overload than those with normal iron load in heart (P=0.005). Also, AST level was significantly lower in normal iron load group than mild, moderate, and severe iron load groups in liver (P<0.05). The serum ferritin level was significantly inversely correlated with cardiac T2* values (r = -0.34, P=0.035) and hepatic T2* values (r = -0.52, P=0.001). Conclusion: Cardiac and hepatic T2* MRI indicated significant correlation with serum ferritin level.

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Transient Elastography of Liver in Hb E Beta Thalassemia: A Novel Tool to Determine Hepatic Iron Overload?

Blood ◽

10.1182/blood.v126.23.3368.3368 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3368-3368

Author(s):

Debmalya Bhattacharyya ◽

Maitreyee Bhattacharyya ◽

Saswata Chatterjee ◽

Abhijit Chowdhury ◽

Pramit Ghosh

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Liver Stiffness ◽

Beta Thalassemia ◽

Hepatic Iron ◽

Hepatic Iron Overload ◽

Number Of Patients ◽

T2 Mri

Abstract Introduction: Transient Elastography (TE) of liver is a well established tool to measure liver stiffness, mainly used for assessment of hepatic fibrosis due to chronic hepatitis. Liver biopsy is the gold standard test for measurement of liver iron concentration (LIC) whereas T2* MRI is the best available non-invasive method for the same in thalassemia. We intended to use hepatic TE as an alternative cheaper tool to assess hepatic iron overload so that it can be applied to larger number of patients. Objective: To assess degree of liver stiffness by TE in patients with HbE beta thalassemia and correlate the findings with LIC calculation by T2* MRI of liver. Materials and Method: 53 patients with HbE beta thalassemia from the thalassemia clinic of Institute of Haematology and Transfusion Medicine, Medical College, Kolkata were enrolled for the study. Patients with known liver disease were excluded. Baseline data like HbE%, mutations, transfusion requirement, growth status, serum ferritin level etc were collected. All of them underwent TE of liver in the School of Digestive and Liver Diseases, IPGMER using the FibroScan Touch 502 machine (Di Marco et al, British Journal of Haematology, Volume 148,3, 476-479, February 2010). 20 randomly selected patients were also assessed by T2*MRI of liver for hepatic iron assessment at the same time. LIC calculation was done from T2* value (J S Hankins et al, Blood, 14 May 2009, Volume 113:20). Data were analyzed by SPSS software-19, IBM. Results: The patients with HbE beta thalassemia had a mean HbE level of 53.66 (±18.45) %. Common beta mutations [mostly IVS-1-5(G-C)] usually found in this part of India, were detected. Mean and median age of the study population was 24.11±13.11 years and 20 years, respectively. Median age of 1st transfusion was 11 years. 35.84% patients were non-transfusion dependent. 39/53 patients had facial deformity and growth retardation. Mean baseline hemoglobin was 7.10±0.76 gm/ dl. Mean serum ferritin level was 3183.66±338.45 ng/ml. TE showed 30.18 % patients had severe liver stiffness (Liver stiffness measurement, LSM >15 kPa) whereas 43.34% had minimum stiffness (LSM≤7 kPa). No significant statistical correlation was found between serum ferritin and LSM. 12/20 patients showed very high calculated LIC (>15 mg/g) and lower T2* value (<1.8 ms) whereas only 10% of them showed mildly elevated calculated LIC. Rest had intermediate LIC. Discussion: There is lack of data regarding hepatic iron overload in HbE beta thalassemia and so also from this part of India. There was a trend that higher the age, higher was the LSM irrespective of the serum ferritin level though not found statistically significant (Figure 1). Serum ferritin level was also not significantly correlated with the calculated LIC in those 20 patients assessed with T2* MRI. 2 patients with mildly elevated LIC had a high ferritin level. Preliminary report indicates that with increase in LSM there was increase in calculated LIC also. Statistical analysis revealed patients with LSM≥7.2 kPa had moderate or severe hepatic iron overload and thus undermine the need for routine T2*MRI. The cut off value signifies that patients with LSM<7.2 kPa might or might not have significantly high liver iron overload, so obviously to be assessed by T2*MRI (Table 1). Therefore use of TE may be an alternative preliminary diagnostic method to gauge hepatic iron overload in HbE beta thalassemia patients. It would be of more value in countries like India where T2* MRI facility is not yet feasible in many centers catering to huge number of HbE-beta thalassemia patients. However, further exploration with larger number of patients is necessary to establish association of LIC and LSM in a more robust way. Conclusion: In resource-poor countries like India, TE may be a relatively cheap tool to be used as a marker of hepatic iron overload in future. Table 1. Finding Cut off: ROC (TE-value and LIC categories), n=20 Positive if Greater Than or Equal Toa Sensitivity 1 - Specificity 2.3 1.00 1.00 3.4 1.00 .50 4.4 .94 .50 5.7 .88 .50 6.2 .83 .50 6.5 .77 .50 7.2 .77 .00 8.2 .72 .00 8.85 .66 .00 9.45 .61 .00 10.2 .55 .00 11.85 .50 .00 13.85 .44 .00 15.75 .38 .00 18.3 .33 .00 22.9 .27 .00 27.9 .22 .00 35.9 .16 .00 44.7 .11 .00 48.0 .05 .00 49.8 .00 .00 Table 2. The smallest cutoff value is the minimum observed test value minus 1, and the largest cutoff value is the maximum observed test value plus 1. LSM more than 7.2 had a sensitivity of 77.2 % and specificity of 100%. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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Serum ferritin levels and it’s correlation with cardiac iron overload with the help of cardiac T2* magnetic resonance imaging

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20212881 ◽

2021 ◽

Vol 8 (8) ◽

pp. 1374

Author(s):

Shailaja V. Mane ◽

Sharad Agarkhedkar ◽

Dyaneshwar Upase ◽

Tushar Kalekar ◽

P. Sindhura

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Iron Overload ◽

Serum Ferritin ◽

Ferritin Level ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Resonance Imaging ◽

Mortality And Morbidity ◽

T2 Mri

Background: Frequent blood transfusions in thalassemia major is associated with iron overload in these patients. To reduce the mortality and morbidity, proper usage of iron chelators is necessary to treat iron overload. Cardiac magnetic resonance imaging (MRI) guides in quantification of iron overload in heart. The purpose of this study is to see the correlation between serum ferritin level and T2* MRI in patients with beta thalassemia major.Methods: Period of the study is September 2018 to September 2020. Total 25 patients diagnosed with β-thalassemia major above 5 years of age were enrolled in the study. They were on regular transfusions. Cardiac T2* MRI was done in these patients and correlated with serum ferritin levels.Results: There was no significant correlation observed between cardiac T2* MRI and serum ferritin values (p=0.66, r=-0.094).Conclusions: Our results showed no significant correlation between serum ferritin and cardiac T2* MRI values. Ferritin alone cannot be used as index of myocardial iron overload in thalassemia major.

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Noninvasive assessment of iron overload by magnetic resonance imaging

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2020-19-3-158-163 ◽

2020 ◽

Vol 19 (3) ◽

pp. 158-163

Author(s):

E. E. Nazarova ◽

D. A. Kupriyanov ◽

G. A. Novichkova ◽

G. V. Tereshchenko

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Ferritin Level ◽

Iron Concentration ◽

The Body ◽

Iron Accumulation ◽

Resonance Imaging

The assessment of iron accumulation in the body is important for the diagnosis of iron overload syndrome or planning and monitoring of the chelation therapy. Excessive iron accumulation in the organs leads to their toxic damage and dysfunction. Until recently iron estimation was performed either directly by liver iron concentration and/or indirectly by measuring of serum ferritin level. However, noninvasive iron assessment by Magnetic resonance imaging (MRI) is more accurate method unlike liver biopsy or serum ferritin level test. In this article, we demonstrate the outlines of non-invasive diagnostics of iron accumulation by MRI and its specifications.

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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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