Cardiac Iron Overload In Patients Research Articles

Frontal Plane QRS-T Angle as a Marker of Cardiac Iron Overload in Patients with Beta Thalassemia Major.

Cardiomyopathy due to myocardial iron deposition is the leading cause of death in transfusion- dependent beta-thalassemia major (β-TM) patients. Although cardiac T2* magnetic resonance imaging (MRI) can be used for the early detection of cardiac iron level before the onset of symptoms associated with iron overload, this expensive method is not widely available in many hospitals. Frontal QRS-T angle is a novel marker of myocardial repolarization and is associated with adverse cardiac outcomes. We aimed to investigate the relationship between cardiac iron load and f(QRS-T) angle in patients with β-TM. The study included 95 β-TM patients. Cardiac T2* values under 20 were considered to indicate cardiac iron overload. The patients were divided into two groups according to the presence or absence of cardiac involvement. Laboratory and electrocardiography parameters, including frontal plane QRS-T angle, were compared between the two groups. Cardiac involvement was detected in 33 (34%) patients. Multivariate analysis showed that frontal QRS-T angle independently predicted cardiac involvement (p < 0.001). An f(QRS-T) angle of ≥ 24.5° had a sensitivity of 78.8% and a specificity of 79% in detecting the presence of cardiac involvement. In addition, a negative correlation was found between cardiac T2* MRI value and f(QRS-T) angle. A widening f(QRS-T) angle could be considered a surrogate marker of MRI T2* to detect cardiac iron overload. Therefore, calculating the f(QRS-T) angle in thalassemia patients is an inexpensive and simple method for detecting the presence of cardiac involvement, especially when cardiac T2* values cannot be determined or monitored.

Hepatic and cardiac iron overload quantified by magnetic resonance imaging in patients on hemodialysis: A systematic review and meta-analysis.

Few studies have reported hepatic and cardiac iron overload in patients with end-stage renal disease (ESRD), and the current evidence regarding the prevalence is still scarce. This review aims to estimate the prevalence of hepatic and/or cardiac iron overload quantified by magnetic resonance imaging (MRI) in patients with ESRD who receive hemodialysis (HD), peritoneal dialysis (PD), or have undergone a kidney transplant. A systematic review with meta-analysis was conducted and reported in line with PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. MEDLINE and Embase bibliographic databases were searched using a comprehensive list of controlled vocabulary and keywords to identify relevant studies. All studies reporting the prevalence of hepatic and/or cardiac iron overload quantified by MRI in ESRD patients were considered. The Newcastle-Ottawa scale was used to assess the methodological quality of included studies. To investigate the heterogeneity between studies, random-effect meta-analyses for proportions were used. The review comprised seven studies that included 339 patients. Using meta-analysis, the pooled prevalence of severe and mild to moderate hepatic iron overload quantified by MRI was 0.23 [95% CI: 0.08-0.43] and 0.52 [95% CI: 0.47-0.57], respectively. Only three studies included cardiac iron quantification, and none reported iron overload. This review has revealed a high prevalence of severe hepatic iron overload in patients with ESRD treated by HD. Further studies with a larger sample size are needed to determine the impact of iron overload on vital organs in patients with ESRD and guide future research in this understudied field. Proper use of iron chelation and continuous monitoring will help in the early detection of unsolicited complications; however, the low renal clearance of most iron chelators limits the options for treating iron excess in patients with ESRD.

Global longitudinal strain for detection of cardiac iron overload in patients with thalassemia: a meta-analysis of observational studies with individual-level participant data

BackgroundAlthough cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO).MethodsWe searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist.ResultsA total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76–2.4], p = 0.001, I2 = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91–3.5], p = 0.001, I2 = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6–0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO.ConclusionsAccording to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients.Graphical

The prevalence of cardiac and hepatic iron overload in patients with kidney failure: A protocol for systematic review and meta-analysis.

IntroductionFew studies have reported cardiac and hepatic iron overload in patients with kidney failure or end‐stage renal disease and the current evidence regarding the prevalence is still scarce. To the best of the authors' knowledge and following an exhaustive search; no systematic review/meta‐analysis has estimated the aggregated prevalence of cardiac and hepatic iron overload in this patient population.AimThis review aims to estimate the prevalence of hepatic and/or cardiac iron overload in patients with kidney failure who are receiving hemodialysis, peritoneal dialysis, or underwent kidney transplants.MethodsA systematic review with meta‐analysis will be conducted and reported in line with PRISMA guidelines. MEDLINE and Embase bibliographic databases will be searched using a comprehensive list of controlled vocabularies and keywords to identify relevant studies. All studies reporting the prevalence of hepatic and/or cardiac iron overload prevalence in patients with kidney failure will be considered. Risk of bias assessment for included studies will be conducted based on the study design. StataBE v17 and MetaXL v5.3 will be utilized to perform the meta‐analysis.DiscussionThe findings of this systematic review and analysis are expected to give information on the prevalence of iron overload among patients with kidney failure, which will optimize interventions and guide future research in this understudied field.

Assessment of plasma level of matrix metalloproteinase-9 in patients with sickle cell disease and its relationship to myocardial iron overload: a case–control study

Background Cardiac iron overload is secondary to chronic blood transfusion in patients with sickle cell disease (SCD). Iron overload cardiomyopathy is a restrictive cardiomyopathy associated with systolic and diastolic dysfunction. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling. Many studies offer strong evidence for the role of MMP-9 in left ventricular (LV) remodeling.Objective The authors aimed to detect the plasma levels of MMP-9 in patients with SCD and its relationship to myocardial iron overload.Materials and methods A case–control study was carried out on 75 patients with SCD and 75 age-matched and sex-matched healthy controls. Assessment of cardiac iron overload in patients by MRI T2* was performed. Plasma MMP-9 levels were measured for patients and controls using enzyme-linked immunosorbent assay.Results Patients with SCD had significantly higher levels of MMP-9 than controls. There was a highly significant relationship between plasma levels of MMP-9 and each of cardiac T2* and serum ferritin. Patients with vaso-occlusive crises (VOC) greater than 5/year had significantly higher levels of MMP-9 than those with VOC less than or equal to 5 /year.Conclusion MMP-9 seems to be a useful marker in patients with SCD. Patients with cardiac T2* less than 20 ms, serum ferritin greater than 1000 ng/ml, and recurrent VOC greater than 5/year had significantly higher MMP-9 serum levels than others.

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.

Evaluation of electrocardiographic markers of cardiac arrhythmic events and their correlation with cardiac iron overload in patients with β-thalassemia major.

Iron overload is associated with an increased risk of atrial and ventricular arrhythmias. Data regarding the relationship between electrocardiographic parameters of atrial depolarisation and ventricular repolarisation with cardiac T2* MRI are scarce. Therefore, we aimed to investigate these electrocardiographic parameters and their relationship with cardiac T2* value in patients with β-thalassemia major. In this prospective study, 52 patients with β-thalassemia major and 52 age- and gender-matched healthy patients were included. Electrocardiographic measurements of QT, T peak to end interval, and P wave intervals were performed by one cardiologist who was blind to patients' data. All patients underwent MRI for cardiac T2* evaluation. Cardiac T2* scores less than 20 ms were considered as iron overload. P wave dispersion, QTc interval, and the dispersions of QT and QTc were significantly prolonged in β-thalassemia major patients compared to controls. Interestingly, we found prolonged P waves, QT and T peak to end dispersions, T peak to end intervals, and increased T peak to end/QT ratios in patients with T2* greater than 20 ms. No significant correlation was observed between electrocardiographic parameters and cardiac T2* values and plasma ferritin levels. In conclusion, our study demonstrated that atrial depolarisation and ventricular repolarisation parameters are affected in β-thalassemia major patients and that these parameters are not correlated with cardiac iron load.

Early detection of ventricular dysfunction by tissue Doppler echocardiography related to cardiac iron overload in patients with thalassemia.

Cardiac T2* MRI is used as a gold standard for cardiac iron quantification in patients with transfusion-dependent thalassemia (TDT). We hypothesized that left ventricular (LV) diastolic dysfunction would reflect the severity of iron overload and can serve as an early detection of cardiac iron deposits. A study was conducted on all patients with TDT. Hemoglobin, serum ferritin and non-transferrin bound iron, together with a complete echocardiography and cardiac T2* MRI, were performed on all patients. Seventy-seven patients with TDT were enrolled (median age 14years). In the patient group with a mean serum ferritin of > 2500ng/mL during the past 12 months, there were more patients with severe cardiac iron deposits than in the group with a mean serum ferritin of ≤ 2500ng/mL. Diastolic dysfunction was absent in all patients with a serum ferritin of < 1000ng/mL. All patients with cardiac T2* ≤ 20ms had grade III LV diastolic dysfunction. However, twenty-one percent of patients with cardiac T2* >20ms had LV diastolic dysfunction. The differences observed in pulmonary vein atrial reversal duration and mitral A-wave (PVAR-MVA) duration ≥ - 1ms and an E/E' ratio ≥ 11 were proven to be the associated factors with the cardiac T2* ≤ 20ms. Increased PVAR-MVA duration and increased E/E'ratio reliably reflected a severe iron overload, according to a cardiac T2* in patients with TDT. LV diastolic dysfunction can occur prior to severe cardiac iron deposition. Tissue Doppler echocardiography has the potential for the early detection of cardiac involvement in patients with TDT .

A study of echocardiographic changes in patients of thalassemia major

Background: Thalassemia major is a chronic hematological disorder. Regular blood transfusion is the only modality of long-term survival for these patients. This leads to iron overload, the heart being the most severely affected organ. The gold standard for detecting myocardial iron deposition is cardiac MRI. However, very few patients can afford this investigation. Hence, authors carried out this study to find out whether early iron overload can be detected by echocardiography which is a simple and less expensive tool. The objective of this study was to document echocardiographic changes of cardiac iron overload in patients of thalassemia major even before appearance of symptoms.Methods: A comparative cohort study conducted from January 2018 to October 2018 in the Department of Paediatrics of SSG Hospital, and Government Medical College, Vadodara. The case group consisted of 35 patients of Thalassemia major. 35 age and sex matched normal children were selected as controls. Relevant blood investigations were performed in cases. 2-Dimensional M-Mode Echocardiography was performed in both patients and controls. Thalassemia major patients were compared to normal healthy children for various parameters in echocardiography indicating the systolic and diastolic function. Proportion and percentage were calculated for descriptive analysis. Independent t-Test was applied between two groups to find out significance level.Results: For all parameters except End systolic volume and fractional shortening, p values were less than 0.05 which is significant. 85% (30/35) had increase in interventricular septal dimensions (IVSD), 97%(34/35) had increase in posterior wall dimensions (PWD),  82%(29/35) had  increased left ventricular internal diameter diastole(LVIDD), 88%(31/35) had increased left ventricular internal diameter systole (LVIDS), 80%(28/35) had increased E/A RATIO .Ejection fraction was affected in 77%(27/35).This shows that patients of thalassemia major have significant cardiac dysfunction; possibly because of cardiac iron overload.Conclusions: Echocardiography is an effective tool for screening cardiac iron overload in patients of thalassemia major and should be done periodically in all patients.

The Correlation of Cardiac and Hepatic Hemosiderosis as Measured by T2*MRI Technique with Ferritin Levels and Hemochromatosis Gene Mutations in Iranian Patients with Beta Thalassemia Major.

Organ-specific hemosiderosis and iron overload complications are more serious and more frequent in some patients with beta thalassemia major (BTM) compared with others. We investigated whether coinheritance of HFE H63D or C282Y gene mutations in patients with BTM contributes to the phenotypic variation of iron overload complications and assessed the correlation of cardiac and hepatic hemosiderosis with plasma ferritin levels. We studied 60 patients with BTM with a mean age of 17.5±9.1 years from the Northwest of Iran. HFE gene mutations were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Cardiac and hepatic hemosiderosis was assessed using T2*magnetic resonance imaging (MRI). Ferritin levels were measured using the enzyme immunoassay method. Ferritin levels showed a strong inverse correlation with hepatic T2*MRI values (r = -0.631, p = 0.001) but a poor correlation with cardiac T2*MRI values (r = -0.297, p = 0.044). The correlation between cardiac T2*MRI values and hepatic T2*MRI values was poor and insignificant (r = 0.287, p = 0.058). Genotype and allele distribution of HFE H63D and C282Y mutation did not differ significantly between patients with and without hepatic or cardiac hemosiderosis (p > 0.050). However, carriers of HFE 63D allele had significantly higher ferritin levels compared with non-carriers (1 903±993 vs. 992±683, p < 0.001). Cardiac T2*MRI values showed a poor correlation with hepatic T2*MRI values and ferritin levels. Accurate assessment of cardiac iron overload in patients with BTM can only be done using the T2*MRI technique. Additionally, HFE H63D is a significant determinant factor for elevated ferritin levels in BTM patients.

MRI monitoring of myocardial iron overload: use of cardiac MRI combined with hepatic MRI in a cohort of multi-transfused patients with thalassaemia.

We report the results of combining cardiac and hepatic MRI in the same examination to monitor 48 multi-transfused patients presenting iron overload secondary to their transfusions. This cardiac MRI technique uses acquisition sequences and calculation software that are readily available for 1.5 T systems, and it has been validated to screen for patients at risk of cardiac complications who present myocardial iron overload (T2*<20milliseconds). A total of 176 combined MRI examinations were performed between May 2006 and January 2012 in 48 patients who had received transfusions due to thalassaemia. This monocentric retrospective study brings together all of the imaging examinations carried out. There was a positive correlation between the cardiac T2* values and left ventricular ejection fraction, which were measured in the same examination. At the first assessment 23/48 patients had a T2*<20ms. These patients showed a significant improvement in cardiac T2* over time while their iron chelation therapy was being intensified. This study validates the application of the cardiac MRI technique used to monitor cardiac iron overload in patients who have undergone multiple transfusions.

Assessment of the relationship between fragmented QRS and cardiac iron overload in patients with beta-thalassemia major.

Objective:Beta-thalassemia major (TM) is a genetic hemoglobin disorder causing chronic hemolytic anemia. Since cardiac insufficiency and arrhythmias are the primary causes of mortality in such patients, monitoring of cardiac iron load is important in management of the disorder. The purpose of this study was to investigate the importance of fragmented QRS (fQRS) and its relation to the cardiac T2* value for the evaluation of cardiac iron load in TM patients.Methods:This retrospective study included 103 TM patients. The patients’ T2* values, measured by cardiac MRI and 12-lead surface ECGs, were interpreted. The cardiac T2* values under 20 were considered as cardiac iron overload. The relationship between the cardiac T2* value and fQRS in ECG was investigated.Results:The median age of the patients was 22.6±6.6 years. All patients were on regular blood transfusions and iron chelators. The patients had no risk factors for coronary artery disease. In 50 (48%) patients fQRS was detected, and in 37 (74%) of these the T2* values were low. 86% of patients with cardiac involvement (37) had fQRS, but 22% of patients with non-involvement (13) had fQRS (p<0.001).Conclusion:Since cardiac involvement is the primary cause of mortality in TM patients, the early diagnosis of cardiac dysfunction is of vital importance. The search for fQRS in the ECGs of these patients, particularly when cardiac T2* values cannot be determined and followed, is a non-expensive and easy-to-attain method for therapy management.

The Effect of HFE Polymorphisms on Cardiac Iron Overload in Patients with Beta-Thalassemia Major

Objective: We aimed to investigate the effect of human hemochromatosis protein (HFE) polymorphisms on cardiac iron overload in patients with beta-thalassemia major. Methods: Our study included 33 patients diagnosed with beta-thalassemia major who were treated with regular transfusions and chelation therapy. M-mode, tissue Doppler, and pulsed wave Doppler echocardiography were performed on all patients. T2* magnetic resonance imaging (MRI) scans were also performed. The HFE polymorphisms (H63D, C282Y, S65C, Q283P, E168Q, E168X, W169X, P160delC, Q127H, H63H, V59M, and V53M) were studied using polymerase chain reaction. Results: The H63D polymorphism was detected in six patients with beta-thalassemia major. Five patients were heterozygous for the H63D polymorphism, while one was homozygous. There were no other polymorphisms. There was no relationship between the HFE polymorphisms and either the serum ferritin levels or the T2-weighted MRI values (P > .05). Moreover, conventional echo and tissue Doppler echo findings were not correlated with the HFE polymorphisms. Pulmonary vein atrial reversal flow velocity, which is a manifestation of diastolic dysfunction measured with pulse wave echo, was higher in the patients with HFE polymorphisms (P = .036). Conclusions: The HFE polymorphisms had no effect on cardiac iron overload. However, pulmonary vein atrial reversal flow velocity measurements can provide important information for detecting diastolic dysfunction during cardiac follow-up of patients with HFE polymorphisms. Studies with more patients are needed to provide more information regarding this matter.

Amlodipine Reduces Cardiac Iron Overload in Patients with Thalassemia Major: A Pilot Trial

BackgroundIron chelation therapy in patients with thalassemia major may not prevent iron overload in all organs, especially those in which iron enters cells through specific calcium channels. We designed a controlled pilot study to assess the potential of the calcium channel blocker amlodipine in strengthening the efficacy of iron chelation. MethodsFifteen patients with thalassemia major undergoing chelation therapy were randomized to receive amlodipine added to standard treatment in a 1:2 allocation for 12 months. T2* values for assessment of iron overload in the liver and heart using magnetic resonance imaging were obtained at baseline and at 6 and 12 months. ResultsIn the amlodipine-treated group, heart T2* increased significantly in comparison to baseline at 6 and 12 months (21.7 ± 7.2 ms to 28.2 ± 7.9 ms and 28.3 ± 8.0 ms, with P = .007 and .03, respectively), while no differences were observed in the control group (25.1 ± 8.8 ms to 24.7 ± 7.8 ms and 26.2 ± 11.4 ms; P = .99 and 0.95, respectively); significant differences between groups were observed at 6 months (28.2 ± 7.9 ms vs 24.7 ± 7.8 ms in the control group, P = .03). A significant reduction in ferritin levels also was observed in the treated group at 12 months. ConclusionsThe use of amlodipine in conjunction with standard chelation therapy may suggest a new strategy in preventing and treating iron overload in patients with thalassemia major, especially in organs where iron absorption depends on active uptake by calcium channels like the heart.

Are cardiac R2* values dependent on the image analysis approach employed?

Background CMR R2* is the gold standard for monitoring cardiac iron overload in patients with hemoglobinopathies. The R2* value is obtained by fitting the signal at different echo times (TEs) to an appropriate decay model. Patients with heavy cardiac iron burden (R2*>100 Hz) exhibit rapid signal, leading to a plateau in the later images. Two approaches have been used to address this. The first one (truncation model) consists in discarding the late “plateau” points and fitting the remaining ones with a single exponential model. The second approach is to fit the signal to an exponential decay plus a constant offset (Exp-C). We aimed to determine whether systematic differences were present between R2* values obtained with these two approaches. Methods Single-center cohorts were used to compare black blood and bright sequences separately and a multi-center cohort of mixed bright and black blood studies was used to compare robustness and generalizability of the comparison. The R2* value within a region of interest (ROI) drawn in mid-ventricular septum was assessed using each of the two methods in turn. Truncated exponential estimates were calculated with CMRTools that uses a region-based approach (R2*CMRTools). Exp-C estimates were calculated using a rapid pseudo-pixelwise (PPW) implementation written in MATLAB. The mean and the median (R2*PPW-mean and R2*PPW-median) from the R2* distribution were obtained. To distinguish whether differences in measured R2* values resulted from the underlying fitting model or from the use of a PPW rather than a region-based approach, we performed Exp-C fits to a single ROI (R2*PPW-ROI_based). Results Table 1 shows the results for the two methods. No differences could be distinguished based upon whether a white or black blood sequence was examined. The two fitting algorithms gave similar R2* values, with R-squared values exceeding 0.997 and CoV of 3-4%. Results using the PPW method yielded a small systematic bias that became apparent in patients with severe iron deposition. This disparity disappeared when Exp+C fitting was used on a single ROI suggesting that the use of pixelwise mapping was responsible for 3% bias. In the multicenter cohort the strong agreement between R2* values obtained with the two approaches was reconfirmed. Conclusions Cardiac R2* values are independent of the signal model used for its calculation over clinically relevant ranges; pixelwise fitting generate insignificantly greater R2* estimates at high iron concentrations. The overall variability between the techniques is exceeding small allowing clinicians to compare results with confidence.

Correlation study between MR quantitative cardiac iron accumulated and serum ferritin, liver iron concentration in patients with .BETA.-thalassemia major

Objective Using MRI-T2 * method to quantify the cardiac iron overload in patients with β-thalassemia major and to evaluate the correlation between cardiac T2 * values and serum ferritin (SF),liver iron concentration(LIC).Methods Fifty-eight over 10 years old transfusion-dependent patients with β-thalassemia major were underwent MRI heart measurement to obtain T2 * values.Spearman rank correlation was used to analyze the relationship between cardiac T2*,SF,and LIC.Patients were divided into two groups based on standard setting (SF ＞2500 μg/L or LIC ＞ 15 mg/g of dry tissue).Differences of cardiac T2 * values between two groups were evaluated by Wilcoxon rank sum test with cardiac T2 * ＜ 20 ms as diagnosis standard.The sensibilities and specificities of prediction for cardiac iron deposition with the index of SF ＞ 2500 μg/L or LIC ＞ 15 mg/g dry tissue were calculated,and receiver operating characteristic (ROC) curve analysis was performed.Results The range (median) of cardiac T2 * values,SF and LIC in 58 patients were 4.7-51.1 ms (14.0 ms),1345-23 640 μg/L (5741 μg/L),9.0-＞43.0 mg/g dry tissue (41.4 mg/g),respectively.There was no linear correlation between cardiac T2 * values and SF (r =-0.240,P =0.070).Cardiac T2 * values and LIC was weakly correlated (r =-0.420,P =0.002).The range (median) of cardiac T2 * values was 6.1-47.6 ms (23.7 ms) in 7 patients of SF ≤ 2500 μg/L group.The range (median) of cardiac T2 * values was 4.7-51.1 ms(13.5 ms) in 51 patients of SF ＞2500 μg/L group.There was no statistically significant difference between two groups (Z =-0.489,P =0.625).The range (median) of cardiac T2 * values was 24.4-51.1 ms (44.8 ms) in 5 patients of the LIC ≤15 mg/g dry tissue group.The range (median) of cardiac T2 * values was 4.7-45.5 ms (13.2 ms) in 53 patients of HIC ＞ 15 mg/g dry tissue group.There was significant difference between T2 * values of the two groups(Z =-2.895,P =0.004).To predict cardiac iron deposition,the sensibilities and specificities were 90.9％ (30/33) and 16.0％ (4/25) for the index of SF ＞2500 μg/L,100.0％ (33/33) and 20.0％(5/25) for LIC ＞ 15 mg/g dry tissue respectively.The areas under the ROC curve were 0.652 with the index of SF and 0.775 with the index of LIC.Conclusions MRI-T2 * method can directly quantify the cardiac iron overload in patients with β-thalassemia major.There is no linear correlation between cardiac T2 * values and SF.Cardiac T2 * values and LIC is weakly correlated.Using SF or LIC as an indirect index to predict cardiac iron deposition is not reliable in clinical. Key words: Thalassemia;  Iron metabolism disorders;  Magnetic resonance imaging;  Heart

Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P<0·001). The prevalence of CD was 32·9% in patients with T2*≤8 ms, 12·5% in patients with T2*>8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14-20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2*≤8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.

Observational study of iron overload as assessed by magnetic resonance imaging in an adult population of transfusion‐dependent patients with β thalassaemia: significant association between low cardiac T2* &lt; 10 ms and cardiac events

Thalassaemia major patients usually die from cardiac haemosiderosis. Improved strategies are required to modify this risk. To assess the significance of cardiac iron overload in patients with beta thalassaemia. Observational study of cardiac iron overload as assessed by magnetic resonance imaging (MRI) cardiac T2* relaxometry in 30 adult patients with transfusion-dependent beta thalassaemia. 11/30 patients (37%) had cardiac T2* < 10 ms, 8/30 (27%) in range 10-20 ms and 11/30 (37%) > 20 ms. There was significant inverse correlation between T2* values and values for serum ferritin (SF) and liver iron concentration (LIC) and positive correlation with left ventricular ejection fraction (LVEF). Median LVEF values were 49% in patients with T2* < 10 ms and 58% in patients with T2* > 10 ms (P = 0.02). Very low T2* values <10 ms were strongly associated with the occurrence of cardiac events (congestive heart failure, arrhythmia, cardiac death): occurring in 5/11 patients with T2* < l0 ms and in 0/19 in patients with T2* > 10 ms (P = 0.003 Fisher's exact test; P = 0.002 log rank Kaplan-Meier time to event analysis). There was no significant association between T2* < 10 ms or cardiac events and traditional measures of iron overload, such as SF levels >2500 mg/L and LIC (evaluated at thresholds of >7 or >15 mg/g dry weight). Very low cardiac T2* values <10 ms are common in adults with beta thalassaemia and are significantly associated with risk of cardiac events. This permits the use of individually targeted chelation strategies which are more effective in removing cardiac iron.

Magnetic Resonance T2* Measurement of Myocardial Iron Deposition in Sickle Cell Disease: Risk Factors and Relationship with Cardiac Function.

Abstract 4604 BACKGROUNDChildren with thalassemia major (TM) and sickle cell disease (SCD) receiving chronic blood transfusion are at risk of developing cardiac iron overload. Magnetic resonance imaging (MRI) has emerged as a non invasive tool for the direct measurement of myocardial iron deposition in these patients. Previous studies have shown that patients with TM develop significant myocardial iron deposition that correlates with transfusion burden and cardiac function. However, the prevalence of myocardial iron overload, the risk factors and its relationship with cardiac function in patients with SCD are not well known. OBJECTIVETo review the patterns of cardiac iron overload using cardiac MRI in our cohort of children with SCD. METHODSCardiac MRI studies performed in children with SCD at a steady state from January 2009 to June 2009 at our institution were reviewed. We abstracted demographic and laboratory data and reviewed their transfusion history. These patients were receiving chronic blood transfusion every 3-4 weeks. All patients had been on chelation therapy desferrioxamine and/or deferasirox. In each patient, MR (1.5T Avanto™, Siemens) T2* measurements were performed in the interventricular septum, as well as in the paravertebral muscles as an internal control. Cardiac T2* value of 25-46 was considered normal as previously published. RESULTSA total of 20 patients with Hb SS (50 % male), with a mean age of 14 years were studied. The mean duration of blood transfusion was 9.5 ± 5.3 years. Seventeen patients (85%) were on chronic transfusion for stroke or abnormal TCD and three (15%) for other reasons such as recurrent pain crises and priapism. Overall, the mean cardiac T2* was 31.2 ± 6.6 ms in our patients. Mean T2* values in the myocardium were significantly lower than T2* values measured in the paravertebral muscles in the same patients (31.2 ± 6.6 versus 48.2 ± 5.1, p<0.05). Two patients (10%) had low cardiac T2* (17 and 22) indicating significant myocardial iron deposition. In addition, borderline low T2* values (26 each) were noted in two additional patients (10%) suggesting high myocardial iron deposition. There was a weak but not significant correlation between cardiac T2* and left ventricular end-diastolic volume (r=0.17), left ventricular ejection fraction (r=0.21) and right ventricular end-diastolic volume (r=0.37). Also, there was no statistically significant correlation between myocardial T2* and transfusional burden (r= -0.26), duration of transfusion (r= -0.35), serum ferritin (r= -0.4) and liver iron concentration by biopsy (r= -0.33) and liver T2* (r=0.04). CONCLUSIONOur study shows that patients with SCD develop significant cardiac iron overload (low cardiac T2*) than previously reported. However, there was no significant correlation between cardiac T2* and parameters of ventricular function even in patients with high myocardial iron content. The lack of correlation between cardiac T2* and serum ferritin, liver iron content and transfusion burden in our cohort concurs with previous studies. Thus the risk factors for cardiac iron accumulation and its correlation with cardiac function in this patient population remain unclear. Further prospective studies are needed to understand the pathogenesis and the consequences of cardiac iron overload in patients with SCD. Disclosures:No relevant conflicts of interest to declare.