Myocardial Iron Loading Research Articles

Left atrial stiffness evaluation in beta-thalassemia major patients

Abstract Introduction Diastolic dysfunction is the earliest cardiac abnormality in β-thalassemia major (β-TM) patients and HFpEF is the predominant cardiac phenotype in symptomatic β-TM patients. Left atrial stiffness index (LASI) has been proved to have prognostic value in HFpEF patients. Purpose In our study we aimed to evaluate LASI in β-TM patients and assess its relation with conventional indices of diastolic function. Methods Sixty β-TM patients and twenty-nine controls were included in this cross-sectional study. Left ventricular ejection fraction (LVEF), early mitral inflow velocity to basal septal early diastolic velocity ratio (E/e'), left atrial volume index (LAVI), tricuspid valve regurgitation velocity (TVR) and left atrial deformation at reservoir phase (LASr) were calculated. T2* was used for myocardial iron load estimation. LASI was calculated as the [E/e’]/[LASr] ratio. Patients with LVEF <50% were excluded. LAVI, E/e’ and TVR were used as criteria of diastolic dysfunction. Results LASI was greater in patients compared to controls (0.30 ± 0.22 vs 0.18 ± 0.06, p = 0.003). Patients with diastolic dysfunction (n = 16) had greater LASI than patients without (n = 20) (0.49 ± 0.35 vs 0.21 ± 0.05, p = 0.001) as well as lower LASr (34.0 ± 15.6% vs 42.1 ± 6.7%, p = 0.043). Patients with indeterminate diastolic status (n = 24) had LASI = 0.26 ± 0.08 and LASr = 45.5 ± 13.6%. No correlation was found between LASI and T2* (p = 0.221). Conclusions β-TM patients with echocardiographic evidence of diastolic dysfunction have increased LASI. Myocardial iron load did not correlate with left atrial stiffness. A significant portion of β-TM patients have indeterminate diastolic function based on conventional criteria and novel indices, such as LASI or LASr, could be useful for reclassification of these particular patients.

MRI Deep Learning-Based Automatic Segmentation of Interventricular Septum for Black-Blood Myocardial T2* Measurement in Thalassemia.

The T2* value of interventricular septum is routinely reported for grading myocardial iron load in thalassemia major, and automatic segmentation of septum could shorten analysis time and reduce interobserver variability. To develop a deep learning-based method for automatic septum segmentation from black-blood MR images for the myocardial T2* measurement of thalassemia patients. Retrospective. One hundred forty-six transfusion-dependent thalassemia patients with cardiac MR examinations from two centers. Data from Center 1 (1.5 T) were assigned to the training (100 examinations) and internal testing (20 examinations) sets; data from Center 2 were assigned to the external testing set (26 examinations; 10 at 1.5 T and 16 at 3.0 T). 1.5 T and 3.0 T, multiecho gradient-echo sequence. A modified attention U-Net for septum segmentation was constructed and trained, and its performance evaluated on unseen internal and external datasets. T2* was measured by fitting the average septum signal, separately segmented by automatic and manual methods. Agreement between manual and automatic septum segmentations was assessed with the Dice coefficient, and T2* agreement was assessed using the Bland-Altman plot and the coefficient of variation (CoV). The median Dice coefficient of deep network-based septum segmentation was 0.90 [0.05] on the internal dataset, 0.82 [0.10] on the external 1.5 T dataset, and 0.86 [0.14] on the external 3.0 T dataset. T2* measurements using automatic segmentation corresponded with those from manual segmentation, with a mean difference of 0.02 (95% LoA: -0.74 to 0.79) msec, 0.43 (95% LoA: -2.1 to 3.0) msec, and 0.36 (95% LoA: -0.72 to 1.4) msec on the three datasets. The CoVs between the two methods were 3.1%, 7.0%, and 6.1% on the internal and two external datasets, respectively. The proposed septum segmentation yielded myocardial T2* measurements which were highly consistent with those obtained by manual segmentation. This automatic approach may facilitate data processing and avoid operator-dependent variability in practice. 4 TECHNICAL EFFICACY: Stage 1.

Evaluation of cardiac fibrosis and subclinical cardiac changes in children with sickle cell disease using magnetic resonance imaging, echocardiography, and serum galectin-3

BackgroundMyocardial fibrosis has recently been proposed as one of the contributing factors to the diverse pathogenicity of cardiomyopathy in sickle cell disease.ObjectiveIn this study, cardiac fibrosis and subclinical cardiac changes in children with sickle cell disease were evaluated using cardiac magnetic resonance imaging (MRI), tissue Doppler echocardiography and serum galectin-3.Materials and methodsThe study included 34 children with sickle cell disease who were compared with a similar number of healthy controls. Cardiac MRI was used to evaluate late gadolinium enhancement, native T1 mapping, extracellular volume, and T2* for estimation of iron load. Cardiac function and myocardial performance index (MPI, evaluated by tissue Doppler echocardiography) and serum galectin-3 were compared to controls.ResultsThe mean age of the included patients was 13.3 ± 3.2 years. Myocardial iron load by T2* was normal. The mean level of extracellular volume (35.41 ± 5.02%) was significantly associated with the frequency of vaso-occlusive crises (P = 0.017) and negatively correlated with hemoglobin levels (P = 0.005). Galectin-3 levels were significantly higher among cases than controls (P = 0.00), at a cutoff value on the receiver operating characteristic curve of 6.5 ng/ml, sensitivity of 82.5% and specificity of 72.8%. The extracellular volume was significantly higher in cases, with a MPI > 0.4.ConclusionDiffuse interstitial myocardial fibrosis can be detected early in children with sickle cell disease using T1 mapping and is associated with a high frequency of vaso-occlusive crisis. MPI of the left ventricle and serum galectin-3 are recommended screening tools for subclinical cardiac abnormalities.Graphical abstract

Evaluation of the efficacy of signal-averaged electrocardiogram testing in the cardiac assessment of beta-thalassemia major patients

BackgroundMore than 70% of thalassemia’s major mortality is due to the cardiac complications of this syndrome, mostly consequent to myocardial Iron overload; therefore, evaluation of such complications is of utmost importance. T2*MRI is used to assess hepatic and myocardial Iron load in thalassemia patients, which is not always available. Signal-Averaged Electrocardiography is a rather easy method of evaluating major thalassemia patients regarding their risk for sudden cardiac death.Methods and materialsIn this cross-sectional study, 48 patients with thalassemia major underwent evaluation with electrocardiography, signal-averaged electrocardiography, echocardiography, T2*MRI, and ferritin level. The association of the existence of ventricular late potentials in SAECG and other cardiac variables was evaluated. Moreover, the association between myocardial and hepatic Iron load and cardiac characteristics was assessed.Results48 patients with a mean age of 30.31 ± 7.22 years old entered the study. 27 (56.3%) of the patients had ventricular late potentials, which were associated with myocardial dry Iron weight (P = 0.011). Nonspecific ST-T changes and premature atrial and ventricular contractions were seen more frequently in patients with late potentials (P = 0.002, 0.031, and 0.031, respectively). Patients with higher myocardial and hepatic Iron loads had longer QTc in their 12-lead surface electrocardiograms.ConclusionPatients with ventricular late potentials assessed by SAECG had a higher myocardial Iron load. Higher myocardial Iron load is associated with higher cardiac complications in patients with beta-thalassemia major; therefore, SAECG can be used as a screening test for cardiac complications in beta-thalassemia major patients.

The relation among myocardial iron load and the severity of heart failure

Abstract Heart failure (HF) symptoms are related to reduced circulatory perfusion, peripheral congestion, also impaired peripheral muscle strength & oxygen utilization due to iron deficiency. Despite many premises, the correlation between myocardial iron load and failing heart function was not proved. The purpose of this study was to assess iron itself and iron-related proteins in human failing (FH) vs non-failing (NFH) myocardium. The study group consisted of 58 explanted FHs vs the control consisted of 31 NFHs unsuitable for transplantation. HF study group presented with LV dilatation (LVDD 67±8 mm; LVSD 59±13 mm), reduced contraction (LVEF 20±7.5%), RV enlargement (RVD 42±6.5 mm), pulmonary hypertension (2.21±0.93 Wu) and elevated NTproBNP (3955.5±2250.5pg/ml). We assessed iron serum markers: ferritin (FR), transferrin/saturation (TSAT), transferrin receptor (soluble sTfR), sTFR/log FR; myocardial iron homeostasis assessment: M-Iron (Instrumental Neutron Activation Analysis, μg/g) and iron gathering proteins (by ELISA): divalent metal transporter (DMT-1); L-type calcium channel (L-CH), TfR-1/TfR-2; ferritins: heavy (FT-H), light (FT-L) chain, mitochondrial (FT-MT); ferroportin (FPN) and oxidative stress marker: 4-hydroxynonenal (4-HNE). In FH vs NFH, M-Iron was reduced (164.6±25.2 vs 182.3±23.9; p=0.0358) however, did not apply to the entire group. Therefore we divvied the FH group into two subgroups (based on M-Iron concentration in NFH controls). Average iron concertation in non-iron-deficient (NIDM) subgroup was 172.5±19.1 (n=35) and in iron-deficient (IDM) subgroup wad 127.0±16.5; (n=23, p=0.0001). Regardless M-Iron load in FH vs NFH myocardial proteins expressions were reduced: L-CH (NIDM vs IDM vs NFH: 49.2±9.2; 42.5±4.2; 67.3±23.0, p=0.0022); FT-L (16.4±7.3; 11.6±4.8; 26.3±7.5, p= <0.0001, respectively); FT-MT (41.2±7.6; 38.7±4.1; 59.3±10.4 p≤0,0001, respectively). With regard to M-Iron load, only in DMT-1 expression was changed (NIDM vs IDM vs NFH 4.8±0.7; 4.0±0.5; 5.8±0.8; p≤0.0001). 4-HNE levels in FH vs NFH were increased, regardless M-Iron load (NIDM-Iron vs IDM-Iron vs NFH; 55.7±29.2; 57.2±47.8; 9.9±8.1 p≤0.0001). Interestingly, the iron load (NIDM-Iron vs IDM-Iron) did not modify the assessed clinical parameters. With regard to commonly used systemic iron markers only sTFR/log FR proved M-Iron load difference (NIDM-Iron vs IDM-Iron 0.6±0.2; 0.7±0.3; p=0.047910) In FH, we observed, the subgroup with the reduced M-Iron load. The observed reduction of iron gathering proteins were independent on M-Iron load, except DMT-1 the main iron transportation protein into the cell. The results showed that the HF degree and concertation of iron proteins are unlikely to be affected by the M-Iron load, except DMT-1 protein. The oxidative stress was also regardless from M-Iron load, and increased in the whole FH group. Commonly used systemic iron markers except sTFR/log FR did not define M-Iron load. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Cardinal Stefan Wyszyński National Institute of Cardiology

Right ventricular mechanics among beta-thalassemia major patients

Abstract Introduction Right ventricular function among β-thalassemia (β-TM) patients is affected by both pulmonary circulation pressure and primary iron deposition on right ventricular myocardium. Purpose In our study we aimed to detect the presence of impaired right ventricular function and right ventricle to pulmonary circulation (RV-PC) coupling by applying novel echocardiographic techniques among these patients. Methods 47 β-TM patients (mean age 39.02±8.76 years, 48.9% male sex) and 24, age and sex matched, healthy controls were examined by transthoracic echocardiography. Conventional echocardiographic parameters were estimated (LVEF, E/e' ratio, left atrial volume index (LAVI), right ventricular systolic pressure (RVSP), S' wave of tricuspid annulus), alongside with deformation indices (left atrial strain at reservoir phase (LASr), right ventricular free wall (RVfw) and 4 chamber (RV4c) strain), as well as RV-PC coupling expressed as S'/RVSP, RVfw/RVSP and RV4c/RVSP. T2* was calculated by cardiac magnetic resonance imaging in β-TM patient group. Results E/e' ratio, LVEF, LAVI, RVSP, LASr, RVfw, RV4c, S'/RVSP, RVfw/RVSP and RV4c/RVSP differed significantly between patients and controls (Table 1). T2* did not correlate with either right ventricular deformation indices or RV-PC coupling indices. A correlation was found regarding LASr with both S'/RVSP (r=0.383, p=0.008) and RV4c/RVSP (r=−0.388, p=0.007) but not with RVfw/PVSP (Table 2). Conclusions Right ventricular deformation indices were found to be impaired in β-TM patients compared to controls, but they do not seem to be associated with myocardial iron load (T2* index). RV-PC coupling was also found to be impaired among patients and a correlation was found between RV-PC indices and left atrial strain. The latter suggests that the presence of atrial cardiomyopathy in β-TM patients could be associated with the impaired RV-PC coupling. Funding Acknowledgement Type of funding sources: None.

Left atrial deformation indices in β-thalassemia major patients.

The presence of atrial cardiomyopathy in β-thalassemia major (β-TM) patients complicates their clinical condition. The diagnosis is challenging even with cardiac magnetic resonance (CMR) imaging. Novel echocardiographic techniques are applied to increase the diagnostic yield. Fifty-six β-TM patients and thirty age and sex-matched controls were included in the present cross-sectional study. Heart rate, PR duration, and P axis were measured by electrocardiography, left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD), ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), left atrial volume index (LAVI), left atrial strain at reservoir (LASr), conduit (LAScd) and contraction (LASct) phases respectively, left ventricular global longitudinal strain (GLS) by echocardiography, and T2* calculation in patient group by CMR. PR duration, LVEF, LAVI, E/e', GLS, and left atrial deformation parameters differed between patients and controls (p <0.05). In patient group, left atrial strain was correlated with PR duration, LAVI, E/e', GLS, and T2* (p <0.05). T2* was correlated only with left atrial deformation indices (p <0.05). Patients with a history of atrial fibrillation were older, had lower heart rate, prolonged PR, increased E/e' and LAVI, and impaired left atrial strain (p <0.05). LASct differed relative to the presence of atrial fibrillation and myocardial iron overload. Atrial strain could be of clinical use in the early detection of atrial cardiomyopathy. An impaired LASct could identify β-TM patients with undetected episodes of atrial fibrillation. Finally, left atrial strain may be helpful in myocardial iron load estimation.

Native cardiac magnetic resonance T1 mapping and cardiac mechanics as assessed by speckle tracking echocardiography in patients with beta-thalassaemia major.

BackgroundWe hypothesize that cardiac magnetic resonance (CMR) native T1 is associated with myocardial deformation in thalassaemia patients. The present study aimed to compare CMR native T1 values to conventional T2* values in patients with beta-thalassaemia and to explore relationships between these CMR parameters of myocardial iron overload and left ventricular (LV) and left atrial (LA) myocardial deformation.MethodsThirty-four (16 males) patients aged 35.5 ± 9.2 years were studied. Myocardial T2* and T1 mapping were performed to assess the cardiac iron overload, while two-dimensional speckle-tracking echocardiography was performed in determine LV and LA myocardial deformation.ResultsT2* was 36.4 ± 8.7 ms with 3 patients having myocardial iron load (T2*<20 ms). The native T1 was 947.1 ± 84.8 ms, which was significantly lower than the reported normal values in the literature. There was a significant correlation between T1 and T2* values (r = 0.68, p < 0.001). There were no significant correlations between T1 and T2* values and conventional and tissue Doppler parameters of left ventricular systolic and diastolic function. On the other hand, T1, but not T2*, values were found to correlate negatively with maximum LA area indexed by body surface area (r = -0.34, p = 0.047) and positively with LA strain rate at atrial contraction (r = 0.36, p = 0.04). There were no associations between either of these CMR parameters with indices of ventricular deformation.ConclusionsIn patients with beta-thalassaemia major, native T1 values are decreased, associated with T2* values, and correlated with maximum LA area and LA strain rate at atrial contraction.

Evaluation of right and left ventricular function using speckle-tracking echocardiography in thalassemic patients.

Background:Beta-thalassemia major is the most common chronic hemolytic anemia among children and adolescents across the world. Several studies have demonstrated that thalassemic patients who have preserved left ventricle systolic function could still have subtle systolic dysfunction. Among patients with beta-thalassemia, early detection of transfusion-induced myocardial iron loading and its intervention with aggressive chelation therapy may delay or reverse heart failure. Two-dimensional speckle-tracking echocardiography (2D-STE) is a novel tool that may detect early myocardial dysfunction in these patients.Objective:The aim of this study was to investigate whether longitudinal strain based on speckle tracking can detect subtle right or left ventricular dysfunction.Patients and Methods:Fifty thalassemic patients with preserved left ventricular ejection fraction (>55%), mean age of 14.75 ± 4.73 years, and thirty age-matched healthy control subjects have been included in the study. Conventional echo Doppler, tissue Doppler echocardiography, and 2D-STE were performed in all patients and control subjects.Results:The right ventricular and left ventricular longitudinal strains were significantly lower in patients than in controls (21.67 ± 5.59 vs. 25.32 ± 2.29, P = 0.001 for right ventricular and 21.29 ± 3.49 vs. 24.90 ± 0.97, P = 0.001 for left ventricular).Conclusions:The 2D-STE can detect early ventricular (left and right) systolic dysfunction in thalassemic patients in the presence of normal systolic function by conventional methods. It may be suggested that the assessment of global longitudinal strain (GLS) can be used as a useful and less expensive tool for screening myocardial iron overload, especially in countries with a limited magnetic resonance imaging (MRI) availability for logistic and economic reasons. Hence, we can refer positive cases with GLS to a higher center to do MRI and start intensive iron chelation treatment.

A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β-thalassemia patients.

This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent β-thalassemia (TDT), through a placebo-controlled, crossover study. Amlodipine (5mg, daily) or placebo were prescribed to all patients (n=19) for 6months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83±2.67ms Myocardial MRI T2* value rose to 11.44±4.14ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29±4.01ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.

Left ventricular systolic dyssynchrony index and endothelial dysfunction parameters as subclinical predictors of cardiovascular involvement in patients with beta‐thalassemia major

Cardiovascular iron load is the leading cause of morbidity and mortality in beta-thalassemia major (β-TM). However, many patients remain asymptomatic until the late stage. In this cross-sectional study, we investigated the role of three-dimensional (3D) echocardiography and endothelial dysfunction parameters in asymptomatic β-TM patients, and the relationship between these parameters and cardiac magnetic resonance imaging (MRI) T2* value. A total of 51 asymptomatic β-TM patients receiving regular blood transfusions were divided into two groups based on cardiac MRI-T2* values (MRI-T2*<20ms and ≥20ms), which MRI-T2*<20ms determines myocardial iron load and evaluated by two-dimensional (2D) and 3D-echocardiography including endothelial dysfunction parameters. The relationships between ferritin levels, 2D and 3D-echocardiography measurements, endothelial dysfunction parameters, and cardiac MRI-T2* values were investigated. All left ventricle ejection fraction (LVEF) obtained by 2D-echocardiography were normal (≥50%). LVEF-3D (53.25±2.33 vs. 58.81+1.02), SDI12 (6.53±0.56 vs. 2.85+0.48), and SDI16 (7.65±0.75 vs. 3.26+0.49) were significantly different and negatively correlated between groups with MRI-T2*<20ms and ≥20ms, respectively. Flow-mediated dilatation (FMD) (6.08%±0.34% vs. 14.46%±1.12), aortic strain (7.79%±2.19% vs. 12.76%±4.19), ferritin levels were significantly different and negatively correlated between groups with MRI-T2*<20ms and ≥20ms, respectively. Higher ferritin, SDI12/16 were significant independent predictors of MR-T2*<20ms. SDI16>5.5, SDI12>4.3 predicted MRI-T2*<20ms with a sensitivity of 92%, specificity of 81% (AUC 0.85, P<.001), and sensitivity of 92%, specificity of 78% (AUC 0.83, P<.001), respectively. SDI12/16 calculated by 3D-echocardiography may be a promising predictors of cardiovascular iron load and, decreased LVEF-3D, FMD, and aortic strain might be good indicators of subclinical cardiovascular involvement of β-TM.

The effect of measurement area size on the reliability of myocardial iron load measurement in cardiac magnetic resonance imaging examinations of thalassemia patients

Background/aimThe aim of this study was to evaluate the intraobserver and interobserver reliability of cardiac T2* MRI measurements in different region of interest (ROI) sizes.Materials and methodsCardiac T2* MRIs of 24 thalassemia major patients were evaluated. Two different ROI sizes were used for measurement. In the first measurement, an ROI approximately 5 mm in diameter was used in the interventricular septal myocardium. In the other method, the whole ventricular septal myocardium was used as the measurement. The intraobserver and interobserver variabilities were assessed with the intraclass correlation coefficient (ICC). ResultsThe measurement of the first observer, the ICC of the small-sized ROI (ssROI), was 0.869, and the measurement for the second observer, the ICC of the ssROI, was 0.659. The ICC of the whole-septal ROI (wsROI) was 0.991 for the first observer and 0.980 for the second observer. Interobserver variability, for the mean measurement, was 0.442 for the ICC of ssROI and 0.883 for the ICC of wsROI. ConclusionFor the evaluation of myocardial iron load with T2* MRI we suggest making measurements with ROI, including all of the interventricular septum, as a consequence of high intraobserver and interobserver consistency.

A Study of the Spectrum of Ocular Manifestations in Patients with Thalassemia

Background: Thalassemia is a globally prevalent genetic disorder. Patients with thalassemia are prone to develop systemic and ocular adverse effects such as myocardial iron loading, heart failure, decreased visual acuity, color vision abnormalities, contrast sensitivity changes, ocular surface disease, lens opacities, etc. Fundus abnormalities such as retinal pigment epithelium degeneration, arteriovenous (AV) tortuosity, etc. may be seen. Patients with the long-standing disease are at risk of developing ocular adverse effects that demand baseline ophthalmic evaluation and regular monitoring. Context: Need for a regular ophthalmic checkup in patients with thalassemia. Aim: To determine the prevalence of ocular manifestations in patients with thalassemia. Settings and Design: A cross-sectional study was conducted by recruiting patients with thalassemia after obtaining ethical approval from the institute and informed consent from the parents. Materials and Methods: Fifty patients with thalassemia underwent a detailed ophthalmic evaluation, and the findings were recorded. The Statistical Package AQ6 for the Social Sciences software was used for statistical analysis. Results: Ocular involvement was seen in 37 patients (74%). We observed that 20% of the patients had decreased visual acuity, 38% of the patients had mild dry eye disease, and 14% of the patients had AV tortuosity. Conclusion: Ocular changes in patients with thalassemia occur over a long period. Adverse effects such as ocular surface diseases, lens opacities, increased cup disc ratio, retinal pigment epithelium degeneration, etc. may progress and cause visual impairment at a later stage. It is important to create awareness in these patients to prevent long-term side effects and maintain optimum visual health.

Myocardial iron is strongly associated with reproductive function in beta-thalassemic women under chelation therapy

Objective: To evaluate gynaecological features of a group of transfusion dependent beta-thalassemic women and to analyze their reproductive function with the morpho-functional features of genital female tract. Materials and Methods: Cross-sectional study in a University Hospital and Tertiary Care Center. Fifty-nine transfusion-dependent beta-thalassemic women in reproductive age, were divided into two groups: to group A were assigned women with spontaneous menarche (n=44), while to group B were allocated patients with inducted menarche. Data on demographic characteristics, iron overload in liver and heart (evaluated with T2* RMN method), chelation therapy, and reproductive function were collected. Difference in demographic characteristics, chelation therapy, iron status, and reproductive function between groups were assessed, together with correlation analysis of iron overload. Results: Patients in group B had a worse reproductive function and a higher myocardial iron overload, than patients in group A. Moreover multivariate logistic regression showed a significant correlation between uterine biometry, FSH, E2, parity and hearth iron T2*HSIV, but not with liver iron. Conclusion: The present data shows that myocardial iron loading could be putative of prolonged and severe iron overload in the female genital tract, impairing fertility and reproductive function in patients affected with beta-thalassemia major under chelation therapy.

Effects of Luspatercept on Iron Overload and Impact on Responders to Luspatercept: Results from the BELIEVE Trial

Effects of Luspatercept on Iron Overload and Impact on Responders to Luspatercept: Results from the BELIEVE Trial

The Effect of Iron Replacement Therapy on Electrocardiographic Consequences in Pediatric Patients

Background Sudden cardiac death is an important problem, because the patients have no opportunity to receive medical service. Recently some electrocardiogram (ECG) parameters are used for predicting arrhythmias, including P wave duration for predicting atrial arrhythmias and corrected QT and T wave peak to end interval (Tp-e), for predicting ventricular arrhythmias. Iron deficiency is the most prevalent nutrient disorder worldwide in which iron loads in different tissues including myocardium are decreased. We aimed to investigate the relationship between iron deficiency and arrhythmogenic ECG parameters. Then we compared electrocardiographic parameters of iron deficient patients before and after iron replacement therapy. Materials and Methods In the first phase of study, ECG and blood samples were taken from 9-18 years old healthy adolescents for CBC and ferritin tests. They were divided into three groups according to serum ferritin: group 1 (ferritin below 15), group 2 (ferritin 15-30), and group 3 (ferritin above 30) ng/ml. In phase two, group 1 were given standard iron replacement therapy. We compared ECG parameters in three groups and then in group 1 before and after treatment. Results The number of individuals in three groups was 120 (group 1= 25, group 2= 26 and group 3= 69). The results showed that all parameters were significantly higher in group one and the lowest in group three. Also, there was a significant decrease in these parameters after treatment in group one (P<0.05). Conclusion Based on the results, Iron deficiency through decreased myocardial iron load can prolong ECG parameters and elevate risk of arrhythmia. Also, iron replacement therapy can reduce this risk.

Can myocardial remodeling be a useful surrogate predictor of myocardial iron load? A 3D echocardiographic multicentric study.

The relationship between myocardial iron load and eccentric myocardial remodeling remains an under-investigated area; it was thought that remodeling is rather linked to fibrosis. This study aims to determine whether or not measures of remodeling can be used as predictors of myocardial iron. For this purpose, 60 patients with thalassemia were studied with 3D echocardiography and myocardial relaxometry (T2*) by Cardiac MRI. 3D derived sphericity index was significantly higher in patients with myocardial iron load. It was correlated with T2* with a 100% sensitivity and specificity (cut-off value of 0.34) to discriminate between patients with and without myocardial iron overload.

MRI-measured myocardial iron load in patients with severe diabetic heart failure

To investigate whether a correlation exists between abnormal myocardial iron status and cardiac lipid deposition as well as other biomarkers in patients with diabetic heart failure (DHF). Seventeen volunteers (Group 1), 26 patients with non-severe DHF (Group 2), and 25 patients with severe DHF (Group 3) were recruited for this study. Myocardial middle-section T2* mapping and septal 1H magnetic resonance spectroscopy (1H-MRS) were performed using a 3 T magnetic resonance imaging (MRI) machine to assess the iron status and lipid deposition individually. Fasting venous blood was used to examine serum biomarkers. Cardiac T2* (ms) of the three groups were 22.8±2.1, 21.7±1.8, and 18.6±1.3, respectively. The value of Group 3 was significantly lower than that of the other two groups (p<0.001). Myocardial triglyceride (%) levels differed among the three groups (Group 1, 0.53±0.13; Group 2, 1.11±0.29; Group 3, 1.47±0.12; p<0.001). Cardiac T2* was inversely correlated with both cardiac triglycerides and left ventricular ejection fraction (LVEF) in overall participants (Groups 1-3) or Group 3 (each p<0.001). Abnormal myocardial iron status was found in patients with severe diabetic heart failure. Myocardial lipotoxicity may be responsible for this process.

Management of cardiac hemochromatosis.

Iron-overload syndromes may be hereditary or acquired. Patients may be asymptomatic early in the disease. Once heart failure develops, there is rapid deterioration. Cardiac hemochromatosis is characterized by a dilated cardiomyopathy with dilated ventricles, reduced ejection fraction, and reduced fractional shortening. Deposition of iron may occur in the entire cardiac conduction system, especially the atrioventricular node. Cardiac hemochromatosis should be considered in any patient with unexplained heart failure. Screening for systemic iron overload with serum ferritin and transferin saturation should be performed. If these tests are consistent with iron overload, further noninvasive and histologic confirmation is indicated to confirm organ involvement with iron overload. Cardiac magnetic resonance imaging is superior to other diagnostic tests since it can quantitatively assess myocardial iron load. Therapeutic phlebotomy is the therapy of choice in nonanemic patients with cardiac hemochromatosis. Therapeutic phlebotomy should be started in men with serum ferritin levels of 300 μg/l or more and in women with serum ferritin levels of 200 μg/l or more. Therapeutic phlebotomy consists of removing 1 unit of blood (450 to 500 ml) weekly until the serum ferritin level is 10 to 20 μg/l and maintenance of the serum ferritin level at 50 μg/l or lower thereafter by periodic removal of blood. Phlebotomy is not a treatment option in patients with anemia (secondary iron-overload disorders) nor in patients with severe congestive heart failure. In these patients, the treatment of choice is iron chelation therapy.

Assessment of left ventricular functions and myocardial iron load with tissue Doppler and speckle tracking echocardiography and T2* MRI in patients with β-thalassemia major.

The purpose of this study is to determine early myocardial dysfunction in β-thalassemia major (BTM) patients. Where the myocardial dysfunction cannot be detected by conventional echocardiography, it could be detected by tissue Doppler imaging (TDI) or speckle tracking echocardiography (STE). In this study, we analyzed 60 individuals, 30 of whom were BTM patients and the other 30 of whom were the control group. T2* magnetic resonance imaging (MRI) was used to measure cardiac iron deposition. The myocardial functions were evaluated by conventional echocardiography, TDI and STE. When basal lateral left ventricular and basal septal wall TDI values were compared between the patient group and control group, only isovolumic contraction time values were significantly longer in the patients. The global circumferential strain was significantly lower in the patients. When evaluated as segmental, longitudinal strain values of basal inferoseptum and circumferential strain values of anteroseptum, anterior, and inferolateral segments were significantly lower in the patients. In the patients, global longitudinal and circumferential strains in the group who had pathological T2* values were significantly lower than the group who did not. In addition, circumferential strain values in anteroseptum, anterolateral, inferior, and inferoseptum segments were significantly lower in the patients with T2* values<20ms than those with T2* values≥20ms. Although T2* MRI is the most sensitive test detecting myocardial iron load, TDI and STE can be used for screening myocardial dysfunction. The abnormal strain values, especially circumferential, may be detected as the first finding of abnormal iron load and related to T2* values.