Myocardial Siderosis Research Articles

Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study.

In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). Sixty-three (73%) patients had pancreatic IO (R2*>38Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18±3months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.

Correlation Between Serum Ferritin Levels and Echocardiographic Changes in Children with Beta-thalassaemia MajorA Cross-sectional Analytical Study

Introduction: Heart failure secondary to iron overload is the leading cause of mortality in patients with beta-thalassaemia major. Prevention of myocardial siderosis is a key step to reducing the rate of mortality in thalassaemia children. Aim: To study the correlation between serum ferritin levels and echocardiography parameters in children with beta-thalassaemia major. Materials and Methods: This cross-sectional analytical study was conducted in the Department of Paediatrics, RG Kar Medical College and Hospital, Kolkata, India from March, 2020 to July, 2021. A total of 85 beta-thalassaemia major children aged between 2-12 years without having any active infections or congenital heart diseases, were included in this study. Blood samples were obtained from these children for serum ferritin level assessment and echocardiography was performed to evaluate their cardiac function. Data were statistically analysed using the Chi-square test. Results: The mean age of patients was 7.24±2.76 years and the age range was 1-12 years. Mean serum ferritin levels in the study was 1938.67±992.57 and more than three-fourth of our population had serum ferritin levels more than 1000 ng/ mL. A 30% of present study population had abnormal echo findings. A significant correlation was noted between serum ferritin levels and echo parameters like Fractional Shortening (FS), Deceleration Time (DT), Early and Late Ratio (E/A ), Left Ventricular Mass (LV Mass). But negative correlation was found between serum ferritin levels and Ejection Fraction (EF). Conclusion: The present study concluded that due to the significant correlation between serum ferritin levels and echocardiographic parameters, it is beneficial to conduct echocardiography in all patients of beta thalassaemia major in their first decade to gain a better understanding of cardiac function.

Role of myocardial deformation imaging in transfusion-dependent thalassemia—Correlation with severity of myocardial siderosis

ObjectivesTo study clinical and echocardiographic parameters in Transfusion Dependent Thalassemia (TDT) patients, correlating them with T2*CMRI. To identify features of Speckle Tracking Echocardiography (STE) in those with severe TDT to prioritize patients in need of early T2*CMRI and aggressive chelation. BackgroundHemosiderosis from life-long transfusions in TDT is amplified in Low- and Middle-Income Countries (LMIC) when access to resources may be scarce, delaying timely chelation. T2* imaging is the gold standard to non-invasively estimate myocardial iron and guide therapy. In resource constraint areas, we propose use of STE to prioritize those with severe disease to obtain early T2* CMRI. MethodsTDT patients (N = 25) who underwent clinical, echocardiographic, and CMRI evaluation were included, with recruitment of age matched controls. Echocardiographic indices of ventricular function and strain were correlated with T2*. Severe disease was defined as T2* < 10 ms. Differences among patients with severe disease and controls were analyzed in addition to differences between those with normal and abnormal T2*. ResultsThere was moderate (R −0.60, p = 0.002) inverse correlation between T2* and peak systolic global longitudinal strain (GLS) and regional basal strain (R −0.62, p < 0.001) indicating these parameters were lower in patients with severe disease when compared with controls and non-severe TDT group. GLS and most indices of regional strain were lower in patients with severe disease (T2* < 10 ms) when compared with the control group (p < 0.05). The Apex- base ratio reached significance (p = 0.02) in patients with abnormal T2*(<20 ms) when compared with normal T2*(<20 ms) in TDT positive patients. ConclusionsEarly decrease in global and regional strain can serve as a useful tool to identify patients with severe TDT before reduction in ejection fraction. This study makes a case for utilizing STE as an adjunct or initial screen to T2* CMRI in LMIC to prioritize patients in need of T2*CMRI to facilitate aggressive iron chelation protocols.

Safety and Efficacy of the New Combination Iron Chelation Regimens in Patients with Transfusion-Dependent Thalassemia and Severe Iron Overload.

The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly. Adverse events were checked at each transfusion visit. The safety of both the combinations was consistent with established monotherapies. Both treatments were able to decrease the serum ferritin and liver iron concentration over time, depending on the level of compliance with therapy. Cardiac iron measured as R2* did not significantly change in patients treated with deferasirox plus desferrioxamine. Most patients with MRI indicative of myocardial siderosis at the beginning of treatment reached normal values of cardiac iron at the last determination if treated with deferasirox plus desferrioxamine. The greatest limitation of these therapies was low patient adherence to the two drugs, which is not surprising considering that the need for an intensive chelation is generally linked to previous issues of compliance.

Contribution of Cardiac Magnetic Resonance to Hematochromatosis

Hemochromatosis is a disease characterized by the progressive accumulation of iron in the body. It can be primitive or secondary. It affects several organs including the heart, liver, pancreas and pituitary gland. The preponderant cardiac involvement is myocardial, related to the iron myocyte overload, causing a decrease in left ventricular distensibility. Echocardiography is the first-line examination, showing an abnormality of left ventricular filling and, later, cavitary dilatation with left ventricular systolic dysfunction. Cardiac MRI is the gold standard for measuring excess iron in the myocardium in the context of hemochromatosis using the T2 * technique. It plays a major role for the diagnosis of cardiac involvement and for monitoring the chelation treatment. In this study, we report three cases of patients with hemochromatosis whose cardiac localization was confirmed or eliminated using cardiac MRI. Cardiovascular magnetic resonance has been used to assess myocardial iron deposition using the relaxation parameters T2*. Heart T2* falls with increasing iron loading. One patient had a myocardial T2* below 20 ms indicating myocardial siderosis. The others patients had a T2 *&gt; 20 ms. The late enhancement was absent in all our patients. This study aims at detecting the myocardial iron overload using cardiac MRI. The treatment is based on bleeding in primary hemochromatosis while in secondary hemochromatosis, it is based on excretion of iron by chemical chelation.

The PIEZO1 gene mutation (c.2005G&gt;T) causes iron overload cardiomyopathy: a case report

Abstract Background: Cardiomyopathy has a variety of etiologies. Here, we report a case of iron overload cardiomyopathy (IOC) in combination with hereditary stomatocytosis (HST) due to a rare mutation in the PIEZO1 gene. Case summary: A 31-year-old man presented to the clinic with a new onset of fatigue and abdominal distension. He had a history of 9-year cholelithiasis, 4-year hemolytic anemia, 7-month diabetes mellitus (DM), and 6-month low sex drive. The specific features of bronze skin, liver palms, yellow eyes, DM, and cardiomyopathy raised our suspicion of hemochromatosis, which was confirmed by an elevated serum ferritin concentration and high transferrin saturation. Echocardiography and cardiovascular magnetic resonance (CMR) imaging demonstrated dilation of all cardiac cavities with a left ventricular ejection fraction of 30%. CMR T2∗ mapping showed myocardial, hepatic, and pancreatic siderosis. Next-generation sequencing identified one missense variant in the PIEZO1 gene (c.2005G&gt;T), which conferred HST and hyperferritinemia. We screened his close family members and identified his son as a heterozygous carrier of this variant, who had intermittent jaundice. Conclusion: In this case, the PIEZO1 c.2005G&gt;T mutation conferred HST and IOC, complicated with cholelithiasis, DM, and low sex drive. Bronze skin, liver cirrhosis, cardiomyopathy, and DM are red flags, while magnetic resonance imaging T2∗ mapping, blood iron metabolism markers, and gene testing are valuable in the diagnosis.

ROLE OF CARDIOVASCULAR MAGNETIC RESONANCE IMAGING IN ASSESSMENT OF MYOCARDIAL IRON OVERLOAD IN THALASSEMIA PATIENTS

Background: Thalassemia major anemia patients require repeated blood transfusions, which improves their survival and quality of life, however it leads to iron overload and cellular damage. Serum ferritin and liver biopsy were used classically to measure iron overload and to monitor patient response to chelation therapy. Magnetic resonance imaging (MRI T2*) has proven to be a non-invasive, effective technique in detecting and quantifying myocardial and hepatic iron overload and in adjustment of iron chelation therapy.Aim of Work: To assess myocardial siderosis among our patients using MRI T2* technique and to correlate it with hepatic iron load and left ventricular ejection fraction (LVEF).Patients and methods: Our study included 42 cases of regularly transfused patients. Hepatic and myocardial iron overload were measured by multi-breath-hold MRI T2* technique and a cine view sequence was used to assess left ventricular function (EF).Results: Myocardial and hepatic iron overload were inter-correlated to each other and correlated to left ventricular function (LVEF). There was insignificant correlation between cardiac and hepatic T2* value results (k = 0.014, P > 0.05). However, there was a progressive and significant decline in left ventricular ejection fraction (r = 0·61, P < 0·001) in patients with low cardiac T2* values (T2* < 20 ms).Conclusion: MRI T2* technique is a precise, reproducible, and non-invasive technique for measuring tissue iron concentration and sparing the patients from an invasive biopsy technique. It also benefits in early detection of cardiac dysfunction and provides a follow up tool helping in chelation therapy adjustment.

The Importance of Cardiac T2* Magnetic Resonance Imaging for Monitoring Cardiac Siderosis in Thalassemia Major Patients.

Objective: Cardiac T2* magnetic resonance imaging (MRI) has recently attracted considerable attention as a non-invasive method for detecting iron overload in various organs in thalassemia major patients. This study aimed to identify the prevalence of cardiac siderosis in thalassemia major patients and evaluate cardiac T2* MRI for monitoring cardiac siderosis before and after patients receive iron chelation therapy and its relation to serum ferritin, left ventricular ejection fraction, and liver iron concentration. The information gathered would be used for the direct monitoring, detection, and treatment of complications early on. Methods: A total of 119 thalassemia major patients were recruited in the present study. The cardiac T2* MRI was compared to serum ferritin levels, liver iron concentration (LIC), and left ventricular ejection fraction. All patients were classified into four groups based on their cardiac siderosis as having normal, marginal, mild to moderate, or severe cardiac iron overload. At the follow-up at years one, three, and five, the cardiac T2* MRI, LIC, serum ferritin, and left ventricular ejection fraction (LVEF) were determined. Results: The prevalence of cardiac siderosis with cardiac T2* MRI ≤ 25 ms was 17.6% (n = 21). There was no correlation between cardiac T2* MRI and serum ferritin, liver iron concentration, and LVEF (p = 0.39, 0.54, and 0.09, respectively). During one year to five years’ follow-up periods, cardiac T2* MRI (ms) in patients with severe cardiac siderosis had significantly improved from 8.5 ± 1.49 at baseline to 33.9 ± 1.9 at five years (p < 0.0001). Patients with severe, mild-moderate, marginal, and no cardiac siderosis had median LIC (mg/g dw) of 23.9 ± 6.5, 21.6 ± 13.3, 25.3 ± 7.7, and 19.9 ± 5.5 at baseline, respectively. Conclusions: This study supports the use of cardiac T2* MRI to monitor cardiac iron overload in patients who have had multiple blood transfusions. Early diagnosis and treatment of patients at risk of cardiac siderosis is a reasonable method of reducing the substantial cardiac mortality burden associated with myocardial siderosis. Cardiac T2* MRI is the best test that can identify at-risk patients who can be managed with optimization of their chelation therapy.

Deferoxamine as a Treatment for Cardiac Siderosis Induced Cardiomyopathy Post Liver Transplantation

Introduction Iron overload cardiomyopathy (CM) occurring after liver transplantation in the absence of preexisting myocardial dysfunction or severe hepatic iron overload (ie hemochromatosis) has been described post-mortem. Cardiac siderosis without primary iron overload syndromes was found to be positively correlated to both higher pretransplant transferrin saturation (TSAT) and transfusion of red blood cells. We report an unusual case of a patient with alcohol-induced cirrhosis and heterozygous C282Y mutation who developed a dilated CM post-liver transplant with confirmed cardiac siderosis treated with IV deferoxamine leading to improvement in cardiac function. Case Report A 47-year-old woman with alcohol-induced cirrhosis underwent liver transplantation with a normal pre-operative cardiac evaluation including a transthoracic echocardiogram (TTE) with left ventricular ejection fraction (LVEF) 55-60%. Pre-operative iron studies showed an iron saturation of 91% with ferritin of 156. Her post-op course was uncomplicated, receiving minimal blood products (4 units of packed red blood cells). Two months later she was hospitalized for dyspnea and large pleural effusions. TTE showed depressed LVEF 17%. A cardiac MRI demonstrated a severely dilated LV indexed to BSA (1.5) with severe myocardial siderosis indicated by decreased T2* of 9-14 ms as well as significant mid-wall myocardial fibrosis. Right heart catheterization demonstrated a normal right atrial pressure, wedge pressure 18 mmHg, mean pulmonary pressure 26 mmHg and Fick cardiac index of 2.02 L/min/m2 for which milrinone was initiated. Endomyocardial biopsy confirmed intramyocardial iron deposition and native liver biopsy had grade 2-3 iron deposition. Etiology of her CM post-transplant was attributed to HFE gene heterozygosity in the setting of cirrhosis with post-transplant iron sensitivity (hepcidin depletion). She was initiated on IV chelation therapy with deferoxamine with follow up CMRI showing improved cardiac siderosis indicated by T2* of 13-17 ms with RV function 41% from 20% and LV function 25% from 17%. She was weaned off milrinone and continued on weekly deferoxamine chelation sessions. Summary This case highlights an unusual cause of cardiac siderosis related cardiomyopathy post-liver transplantation treated with IV iron chelation therapy leading to partial LV/RV recovery.

Role of Cardiovascular Magnetic Resonance Imaging in Assessment of Myocardial Iron Overload in Thalassemic Patients

Background: Thalassemia major anemia patients require repeated blood transfusions, which improves their survival and quality of life, however it leads to iron overload and cellular damage. Serum ferritin and liver biopsy were used classically to measure iron overload and to monitor patient response to chelation therapy. Magnetic resonance imaging (MRI T2*) has proven to be a non-invasive, effective technique in detecting and quantifying iron in the heart and liver and in adjustment of iron chelation therapy. Objective: To assess myocardial siderosis among our patients using MRI T2* technique and correlate it with hepatic iron load and left ventricular ejection fraction (LVEF). Patients and methods: Our study included 42 cases of monthly transfused patients. Hepatic and myocardial iron overload were measured by multi-breath-hold MRI T2* technique and a cine view sequence was used to assess left ventricular function (EF). Results: Myocardial and hepatic iron overload were inter-correlated to each other and correlated to left ventricular function (LVEF). There was insignificant correlation between cardiac and hepatic T2* value results (k = 0.014, P > 0.05). However, there was a progressive and significant decline in left ventricular ejection fraction (r = 0·61, P < 0·001) in patients with low cardiac T2* values (T2* < 20 ms). Conclusion: MRI T2* technique is a precise, reproducible, and non-invasive technique for measuring tissue iron concentration and sparing the patients from an invasive biopsy technique. It also benefits in early detection of cardiac dysfunction and provides a follow up tool helping in chelation therapy adjustment.

Reduction of cardiac iron overload by optimising iron chelation therapy in transfusion dependent thalassaemia using cardiac T2* MRI: a quality improvement project from Pakistan

ObjectivesCardiac T2* MRI (T2*CMR), for accurate estimation of myocardial siderosis, was introduced as part of a QI collaborative to optimise chelation therapy in order to improve cardiac morbidity in transfusion...

No child with a transfusion-dependent haemoglobinopathy left unchelated: are we there yet?

Haemoglobinopathies such as thalassaemias and sickle cell disease pose substantial clinical and public health challenges across the world. 1 Shah FT Sayani F Trompeter S Drasar E Piga A Challenges of blood transfusions in β-thalassemia. Blood Rev. 2019; 37100588 Crossref PubMed Scopus (33) Google Scholar The Global Burden of Disease Study 2017 2 GBD 2017 Disease and Injury Incidence and Prevalence CollaboratorsGlobal, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1789-1858 Summary Full Text Full Text PDF PubMed Scopus (3032) Google Scholar estimates a prevalence of 411 000 and incidence of 106 300 new cases per year globally of clinically significant thalassaemias. Because most patients with β-thalassaemia major require regular blood transfusions for the treatment of severe anaemia, often starting within the first 2 years of life, most of these patients have transfusion-associated iron overload with its long-term sequelae. Allogeneic haematopoietic stem-cell transplantation is the only potentially curative therapeutic option; however, this treatment is limited by accessibility issues and its associated morbidity and mortality. Therefore, iron chelation therapy to mitigate the effects of transfusion-associated iron overload has been a standard of care in the treatment of transfusion-dependent haemoglobinopathies. 1 Shah FT Sayani F Trompeter S Drasar E Piga A Challenges of blood transfusions in β-thalassemia. Blood Rev. 2019; 37100588 Crossref PubMed Scopus (33) Google Scholar , 3 Di Maggio R Maggio A The new era of chelation treatments: effectiveness and safety of 10 different regimens for controlling iron overloading in thalassaemia major. Br J Haematol. 2017; 178: 676-688 Crossref PubMed Scopus (16) Google Scholar Iron chelation therapy has been shown to improve outcomes, and the oral iron chelators deferiprone and deferasirox seem to be more effective and lead to greater compliance than the parenteral deferoxamine. 4 Pennell DJ Berdoukas V Karagiorga M et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood. 2006; 107: 3738-3744 Crossref PubMed Scopus (388) Google Scholar , 5 Pennell DJ Porter JB Piga A et al. A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA). Blood. 2014; 123: 1447-1454 Crossref PubMed Scopus (82) Google Scholar , 6 Ladis V Chouliaras G Berdoukas V et al. Survival in a large cohort of Greek patients with transfusion-dependent beta thalassaemia and mortality ratios compared to the general population. Eur J Haematol. 2011; 86: 332-338 Crossref PubMed Scopus (43) Google Scholar Although data for patients as young as 2 years are available for deferasirox, there are few high-quality randomised studies in paediatric patients receiving deferiprone. Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trialIn paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group. Full-Text PDF

Arrhythmias and Sudden Cardiac Death in Beta-Thalassemia Major Patients: Noninvasive Diagnostic Tools and Early Markers.

Beta-thalassemias are a group of inherited, autosomal recessive diseases, characterized by reduced or absent synthesis of beta-globin chains of the hemoglobin tetramer, resulting in variable phenotypes, ranging from clinically asymptomatic individuals to severe anemia. Three main forms have been described: heterozygotes, homozygotes β+, and homozygotes β°. Beta-thalassemia major (β-TM), the most serious form, is characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Cardiac complications represent a leading cause of mortality in β-TM patients, although an important and progressive increase of life expectancy has been demonstrated after the introduction of chelating therapies. Iron overload is the primary factor of cardiac damage resulting in thalassemic cardiomyopathy, in which diastolic dysfunction usually happens before systolic impairment and overt heart failure (HF). Although iron-induced cardiomyopathy is slowly progressive and it usually takes several decades for clinical and laboratory features of cardiac dysfunction to manifest, arrhythmias or sudden death may be present without signs of cardiac disease and only if myocardial siderosis is present. Careful analysis of electrocardiograms and other diagnostic tools may help in early identification of high-risk β-TM patients for arrhythmias and sudden cardiac death.

Evaluation of Myocardial Siderosis in Children With Beta Thalassemia at Hematology Unit of Zagazig University Hospital

Evaluation of Myocardial Siderosis in Children With Beta Thalassemia at Hematology Unit of Zagazig University Hospital

PB2389 UNDERDOSING DEFERIPRONE IN TM: MYTH OR REALITY?

Background:Data from clinical practice show that some patients with thalassemia major (TM) received underdoses of deferiprone (DFP).Aims:This retrospective real‐life study aimed to investigate the reasons of the underdosing of DFP and to assess if the underdosing could result in an inadequate response.Methods:Among the 1746 TM patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network between 2006 and 2015, we selected the 171 consecutively patients (100 M and 71 F) patients who were treated with DFP dosages&lt;75 mg/Kg/day. Mean age at starting underdosed therapy was 30.95 ± 8.78 years. Heart and liver iron overload were measured by T2∗ Magnetic resonance imaging (MRI) technique.Results:Fifty‐four patients were treated with DFP in monotherapy (60.31 ± 12.82 mg/kg/die for 6.96 ± 0.19 days/week), 87 with combined DFP + deferoxamine (DFO) therapy (52.28 ± 21.29 mg/kg/die for 6.00 ± 1.43 days/week), and 30 with sequential DFO/DFP therapy (60.53 ± 9.75 mg/kg/die for 4.07 ± 0.69 days/week).Table 1 shows the motivations of underdosage, divided by chelation regimens. The most frequent motivation was the weight‐driven adjustment of the dosage, followed by the presence of low ferritin levels and side effects (gastric disturbances = 14/33 pts, increase of transaminases 6/33 pts and neutropenia 5/33).Sixty‐eight patients maintained the same chelation regimen (24 monotherapy, 27 combined and 17 sequential) during the execution of two consecutive MRI scans, performed in a time span of 18 months. At the first MRI 17 patients showed myocardial iron overload (MIO‐global heart T2∗ value&lt;20 ms). In this subgroup there was a significant increase of global heart T2∗ values (12.39 ± 3.77 ms vs 20.43 ± 10.71 ms; P = 0.002) and six (35.3%) patients reached a global heart T2∗ &gt; 20 ms at the second MRI. None of the 51 patients with a normal global heart T2∗ value at the first MRI showed MIO at the second MRI. In the 39 patients with hepatic iron overload (MRI liver iron concentration‐LIC≥3 mg/g dw) at the first MRI, there was not a significant decrease in LIC values, although 7 (17.9%) patients reached a normal value at the second MRI. Out of the 21 patients with a normal LIC value at the first MRI, 5 (17.2%) showed hepatic iron at the second MRI.Summary/Conclusion:In the real world the weight‐driven adjustment of the dosage, low ferritin levels and sides effects were the main causes of the DFP underdosage in TM. DFP dosages&lt;75 mg/Kg/day can be effective in improving myocardial siderosis but do not allow an improvement in terms of hepatic iron.image

Cardiac and hepatic siderosis in myelodysplastic syndrome, thalassemia and diverse causes of transfusion-dependent anemia: the TIMES study.

The significant morbidity and mortality associated with iron overload can be reduced by effective iron chelation. Magnetic resonance imaging (MRI) provides accurate and reproducible iron load assessment. The aim of this epidemiological study was to assess the prevalence and severity of cardiac and hepatic siderosis by MRI and to evaluate the impact of MRI on clinical management in patients with transfusion-dependent anemia and non-transfusion-dependent thalassemia (NTDT). We enrolled 243 patients with myelodysplastic syndromes (MDS), thalassemia major (TM), NTDT or other chronic anemia. Overall, 10% and 48% had cardiac and hepatic siderosis, respectively. Mean liver iron concentration (LIC) was above target range in all groups; mean myocardial T2∗ was normal. Hepatic siderosis was more prevalent than myocardial siderosis in patients with MDS, occurring in 54.4% and 4.4% of patients, respectively. As also observed in patients with NTDT or other anemia, hepatic siderosis was present in a large proportion of MDS patients who were chelation naïve (57.7%), as well as in patients receiving iron chelation therapy (ICT) (52.4%), despite a lower transfusion load compared with TM. Correlation between LIC and serum ferritin was observed across diseases; however, not all patients requiring ICT could be identified with serum ferritin alone, as serum ferritin underestimated LIC in 4.4% and overestimated LIC in 7.5% of patients. Exploratory analyses showed serum ferritin thresholds for liver siderosis detected by MRI at approximately 300 ng/mL higher in MDS than in TM. Most patients reported low-medium adherence to ICT; MRI assessment led to change in ICT in 46% of evaluable patients, including 52% of MDS patients. Accurate organ iron monitoring by MRI facilitated appropriate initiation of chelation, dose optimization and clinical decision making. Trial registration: ClinicalTrials.gov: NCT01736540.

Clinical utility of endocrine markers predicting myocardial siderosis in transfusion dependent thalassemia major.

Endocrinopathy due to iron overload is the most common morbidity whereas myocardial siderosis causing toxic cardiomyopathy is the leading cause of mortality among patients with transfusion dependent thalassemia major (TDTM). If detected early, this can be treated with aggressive chelation. T2* cardiac magnetic resonance imaging (CMR) guided chelation protocols are now the gold standard but have limited availability in low and middle-income countries. We hypothesized that markers of endocrine dysfunction would correlate with T2* CMR and can be used to predict the severity of myocardial siderosis and guide chelation therapy. We undertook a multicenter retrospective study of 280 patients with TDTM to assess the prevalence of endocrinopathies and the predictive value of a number of individual and composite markers of endocrinopathy with T2* CMR. The prevalence of hypogonadism, stunting, hypoparathyroidism, and hypothyroidism was 82%, 69%, 40%, and 30%, respectively. The sensitivity of hypogonadism and stunting predicting severe myocardial siderosis was 90% and 80%, respectively. We conclude that clinical markers of endocrine dysfunction, especially hypogonadism (positive likelihood ratio [LR+]=1.4, 95% confidence interval [CI]=1.0-1.9; positive predictive value [PPV]=77%, 95% CI=70-82; negative predictive value [NPV]=57%, 95% CI=34-77] and stunting (LR+=1.3, 95% CI=1.1-1.6; PPV=64%, 95% CI=60-69; NPV=55%, 95% CI=45-64) in TDTM can predict severe myocardial siderosis and can potentially guide chelation therapy, especially where access to T2* CMR is limited.

REFRACTORY HEART FAILURE SECONDARY TO IRON OVERLOAD CARDIOMYOPATHY AND PROGNOSTIC IMPLICATIONS OF CARDIAC MAGNETIC RESONANCE IMAGING

Myocardial siderosis is reported in up to 3% of cardiac magnetic resonance imaging (CMR) studies in patients with transfusion dependent sickle cell disease (SCD). Advanced imaging modalities can guide early initiation of iron chelation therapy and may prevent adverse outcomes, including iron

Abstract 21067: Improvements in Regional Myocardial Function on 2D STE With Optimized Chelation in Patients With Thalassemia Major (TM)

Intro: Thalassemia Major (TM) is characterized by recurrent blood transfusions leading to myocardial siderosis and complications including arrhythmias and heart failure. These can be reversible with adequate chelation. We explored the effect of improved chelation and subsequent cardiac T2* MRI (CMR) values on regional myocardial function assessed by 2D STE in setting of normal LVEF. Methods: Data was derived from TM patients recruited for the AMIT study (efficacy of amlodipine with chelation in reducing myocardial iron). All patients underwent echocardiographic imaging at baseline, 6 and 12 months. LSsys was extracted from basal, mid, and apical segments of the LV medial and lateral wall by 2D STE technique. A linear regression model was run to determine the effect of improved T2* in the setting of improved chelation on regional LSsys strain parameters. Results: Nineteen TM patients (11 males), median age 16 (8-21) yrs. All participants were transfused every 2-3 weeks. (median pre-transfusional Hb of 9.3 (8.3-10.8) mg/dL). T2* based chelation regimen was initiated at baseline and compliance to this regimen was gauged at regular clinical visits. 25 data points were available from interval 2D STE imaging for analysis. Medial basal LSsys (-17.3% ± 2.2) and lateral basal LSsys (-16.7% ± 4.4) strains were significantly lower than mean apical LSsys strains (-24.9% ± 4.0) (p &lt;0.01). With optimized improved chelation, we determined up to a 6.3% improvement was seen in LSsys basal septal and 6.7% improvement in LSsys apical septal for each 1 ms improvement in T2* (p values &lt; 0.05). Conclusion: 2D STE can help identify regional myocardial dysfunction prior to development of overt cardiac dysfunction. In patients with transfusion dependent TM, compliance to an optimized chelation regimen can help improve regional myocardial function prior to progression to systolic dysfunction and clinically symptomatic sideroblastic complications.

Recent Advances in Cardiovascular Magnetic Resonance: Techniques and Applications.

Cardiovascular magnetic resonance imaging has become the gold standard for evaluating myocardial function, volumes, and scarring. Additionally, cardiovascular magnetic resonance imaging is unique in its comprehensive tissue characterization, including assessment of myocardial edema, myocardial siderosis, myocardial perfusion, and diffuse myocardial fibrosis. Cardiovascular magnetic resonance imaging has become an indispensable tool in the evaluation of congenital heart disease, heart failure, cardiac masses, pericardial disease, and coronary artery disease. This review will highlight some recent novel cardiovascular magnetic resonance imaging techniques, concepts, and applications.