Significant Myocardial Iron Overload Research Articles

Diagnostic Value of T1 Mapping in Detecting Iron Overload in Indian Patients with Thalassemia Major: A Comparison with T2* Mapping.

Purpose T2* is the gold standard for iron quantification in liver as well as myocardium. In this study, we evaluated the diagnostic accuracy of myocardial T1 mapping for the assessment of myocardial iron overload (MIO) as compared to the T2* mapping in patients with thalassemia major (TM). Methods Consecutive TM patients attending the thalassemia clinic were prospectively enrolled. Magnetic resonance imaging was performed on a 1.5 T scanner (Siemens Healthineers, Germany) using a gradient echo T2* as well as a T1 mapping (MOLLI) sequence done at a mid-ventricular short-axis single 8 mm slice of the left ventricle. Values were analyzed by manually drawing a region of interest in the mid-septum. T2*less than 20ms was used as the cutoff for significant MIO. Results One-hundred three patients (58 males, mean age: 17 ± 7.8 years, mean ferritin: 2009.5 µg/L) underwent cardiovascular magnetic resonance. Median T2* of myocardium was 33.45ms. Nineteen patients (18.4%) had T2*less than 20ms. T1 value was low (<850ms) in all the patients with T2* less than 20 ms. Receiver operating characteristic curve analysis revealed the best cutoff of native T1 mapping value as 850 ms which had high specificity (95.2%), sensitivity (94.2%) and negative predictive value (98.8%) for T2* less than 20ms. There was excellent agreement between T1 and T2* for diagnosis of MIO (Kappa-0.848, p <0.001). We did not find any patient who had normal T1 mapping values but had MIO on T2*. Conclusion T1 and T2* correlate well and normal T1 values may rule out presence of MIO. T1 mapping can act as additional imaging marker for MIO and may be helpful in centers with nonavailability or limited experience of T2*.

Multi-Parametric Cardiac Magnetic Resonance for Prediction of Heart Failure Death in Thalassemia Major.

We assessed the prognostic value of multiparametric cardiovascular magnetic resonance (CMR) in predicting death from heart failure (HF) in thalassemia major (TM). We considered 1398 white TM patients (30.8 ± 8.9 years, 725 women) without a history of HF at baseline CMR, which was performed within the Myocardial Iron Overload in Thalassemia (MIOT) network. Iron overload was quantified by using the T2* technique, and biventricular function was determined with cine images. Late gadolinium enhancement (LGE) images were acquired to detect replacement myocardial fibrosis. During a mean follow-up of 4.83 ± 2.05 years, 49.1% of the patients changed the chelation regimen at least once; these patients were more likely to have significant myocardial iron overload (MIO) than patients who maintained the same regimen. Twelve (1.0%) patients died from HF. Significant MIO, ventricular dysfunction, ventricular dilation, and replacement myocardial fibrosis were identified as significant univariate prognosticators. Based on the presence of the four CMR predictors of HF death, patients were divided into three subgroups. Patients having all four markers had a significantly higher risk of dying for HF than patients without markers (hazard ratio (HR) = 89.93; 95%CI = 5.62-1439.46; p = 0.001) or with one to three CMR markers (HR = 12.69; 95%CI = 1.60-100.36; p = 0.016). Our findings promote the exploitation of the multiparametric potential of CMR, including LGE, for better risk stratification for TM patients.

Left ventricular global function index is associated with myocardial iron overload and heart failure in thalassemia major patients.

The left ventricular global function index (LVGFI) is a comprehensive marker of cardiac performance, integrating LV morphology with global function. We explored the cross-sectional association of LVGFI with myocardial iron overload (MIO), LV ejection fraction (LVEF), myocardial fibrosis, and heart failure (HF) in β-thalassemia major (TM) patients. We considered 1352 adult TM patients (708 females, 32.79 ± 7.16years) enrolled in the Myocardial Iron Overload in Thalassemia Network and 112 healthy subjects (50 females, 32.09 ± 6.08years). LVGFI and LVEF were assessed by cine images and MIO by multislice multiecho T2* technique. Replacement myocardial fibrosis was detected by late gadolinium enhancement technique. LVGFI and LVEF were significantly lower in patients with significant MIO (global heart T2*<20ms) than in patients without MIO and in healthy subjects but were comparable between TM patients without MIO and healthy subjects. In TM, LVGFI was significantly associated with LVEF (R = 0.733; p < 0.0001). Global heart T2* values were significantly associated with both LVGFI and LVEF, but the correlation with LVGFI was significantly stronger (p = 0.0001). Male sex, diabetes mellitus, significant MIO, and replacement myocardial fibrosis were the strongest predictors of LVGFI. Eighty-six patients had a history of HF and showed significantly lower global heart T2* values, LVEF, and LVGFI than HF-free patients. A LVGFI ≤ 44.9% predicted the presence of HF. The LVGFI showed a diagnostic performance superior to that of LVEF (area under the curve: 0.67 vs. 0.62; p = 0.039). In TM patients the LVGFI correlates with MIO and provides incremental diagnostic value for HF detection compared with LVEF.

Prognostic value of multiparametric cardiac magnetic resonance in sickle cell patients.

The aim of this multicenter study was to prospectively assess the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in sickle cell disease (SCD) patients. Among all patients with hemoglobinopathies consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network, we selected 102 SCD patients (34.38 ± 12.67years, 49 females). Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect focal myocardial fibrosis. At baseline CMR, only two patients had significant MIO (global heart T2* < 20ms). During a mean follow-up of 63.01 ± 24.95months, 11 cardiovascular events (10.8%) were registered: 3 pulmonary hypertension, 2 supraventricular arrhythmias, 1 heart failure, 1 death for heart failure, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, and 1 death after acute chest syndrome. In the multivariate analysis, the independent CMR predictors of cardiovascular events were left ventricular (LV) ejection fraction (hazard ratio-HR = 0.88; p = 0.025) and right ventricular (RV) mass index (HR = 1.09; p = 0.047). According to the receiver-operating characteristic curve analysis for adverse events, an LV ejection fraction < 58.9% and an RV mass index > 31g/m2 were optimal cut-off values. Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that CMR may be added as a screening tool for identifying SCD patients at high risk for cardiopulmonary and vascular diseases.

Link between Bone Marrow and Cardiac Iron Overload in Thalassemia Major

Introduction. T2* magnetic resonance imaging (MRI) is a well-established technique for the non-invasive quantification of organ-specific iron overload. However, to the best of our knowledge, no systematic T2* MRI studies focused on the bone marrow of thalassemia major (TM) patients are available in literature. Aims. This study aimed to investigate the link between bone marrow and cardiac iron overload in TM. Methods. We considered 274 TM patients (38.96±8.49 years, 151 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) network. Iron overload was quantified by the gradient-echo T2* technique. Bone marrow T2* values were obtained on a circular region of interest located in the visible body of the first or second lumbar vertebra. The left ventricle was segmented into a 16-segment standardized model and the T2* value on each segment was calculated as well as the global value. Results. Bone marrow T2* values showed a weak positive correlation with global heart T2* values (R=0.143; P=0.018) (Figure 1) and a weak inverse correlation with the number of segments with T2*<20 ms (R=-0.119; P=0.050). Out of the 227 patients with a pathological bone marrow T2* value (<13 ms), 28 (12.3%) had a pathological global heart T2* value (<20 ms). No patients without iron overload in the bone marrow had significant myocardial iron overload. In male patients, a bone marrow T2*<8.6 ms predicted the presence of significant MIO with a sensitivity of 92.3% and a specificity of 49.1% (P=0.001). The AUC was 0.71 (95% CI: 0.62-0.79). In female patients, the ROC curve did not reveal a bone marrow T2* threshold below which the probability of detecting significant MIO increases significantly with satisfying sensitivity and specificity (AUC=0.52; P=0.734). Conclusion. This is the first study to demonstrate a link between iron deposition in the bone marrow and in the heart. The correlation coefficient was really weak, but a normal bone marrow T2* value showed a negative predictive value of 100% for cardiac iron. Moreover, in the male population we were able to identify a bone marrow T2* value which may help to identify the patients at high risk for myocardial iron overload. The presence of a high number of patients with a pathologic bone marrow T2* but a normal global heart T2* probably reflects a delay in cardiac iron uptake, different mechanisms of iron loading and unloading, and a different accessibility of iron chelators to different pools. Since bone marrow T2* measurements can be easily obtained using the same MRI sequences acquired for liver iron quantification and may bring new insights into the pathophysiology of iron deposition, they should be incorporated in clinical practice. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cardiac Magnetic Resonance Predicts Heart Failure Mortality in Patients with Thalassemia Major

Iron-induced Heart Failure (HF) still remains the main cause of mortality in patients with thalassemia major (TM), although the introduction of the T2* Cardiovascular Magnetic Resonance (CMR) for the non-invasive assessment of Myocardial Iron Overload (MIO) led to a significant increase in survival rate. However, the pathophysiology of heart failure in TM can be multifactorial. Thanks to its multiparametric potential, CMR represents a unique tool for characterization of myocardial involvement. It is the gold standard for the quantification of biventricular size and function by cine images and for the detection of replacement fibrosis by late gadolinium enhancement (LGE) technique. The aim of this multicenter study was to evaluate the prognostic value of multiparametric CMR in predicting death for HF. We considered 1398 white TM patients who performed a baseline CMR exam within the Myocardial Iron Overload in Thalassemia (MIOT) network. As per inclusion criteria, no patient had a history of HF. Mean age was 30.8±8.9 years and 725 (51.9%) patients were females. During a mean follow-up of 4.83±2.05 years, 49.1% of the patients changed at least once the chelation regimen (i.e.: either switched to a different type of chelator or underwent dose/frequency modification); these patients were more likely to have a global heart T2* value<20ms than patients who maintained the same regimen (33.2% vs 19.7%; P<0.0001) Twelve (1.0%) patients died from heart failure. Table 1 shows the results, presented as hazard ratio (HR) with 95% confidence intervals (CI), of the univariate Cox Regression analysis, performed to test the association between the considered prognostic variables and the outcome. No association was detected between age or gender and HF mortality. Significant MIO (global heart T2*<20 ms), ventricular dysfunction, ventricular dilation, and replacement myocardial fibrosis were identified as significant univariate prognosticators. Due to the low number of deaths for HF, it was not possible to perform a multivariate model. However, based on the presence of the four CMR predictors of HF death, patients were divided into three subgroups: four markers (7 patients; one HF death-14.3%), one to four markers (617 patients, 9 HF deaths-1.5%), and none of the four markers (488 patients; one HF death-0.2%). Patients having all four markers had a significantly higher risk of dying for HF than patients without markers (HR=89.93; 95%CI=5.62-1439.46; P=0.001) or with one to three CMR markers (HR=12.69; 95%CI=1.60-100.36; P=0.016). In our homogeneous white and well-treated Italian/Mediterranean population, we detected a low incidence of deaths for HF, since the T2* report guided the patient-specific adjustment of the chelation regimen. As expected, MIO was a significant predictor of HF death but also other CMR parameters, namely ventricular dilatation, ventricular dysfunction, and replacement myocardial fibrosis emerged as unfavorable prognosis determinant. Importantly, when the four CMR indices were evaluated in combination, they fine-tuned the prognostic stratification of TM patients. Hence, the findings of the present study promote the exploitation of the full potential of CMR, including LGE, for a better risk stratification of TM patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Left Ventricular Function and Iron Loading Status in a Tertiary Center Hemochromatosis Cohort-A Cardiac Magnetic Resonance Study.

Haemochromatosis (HCH), a common genetic disorder with variable penetrance, results in progressive but understudied iron overload. We prospectively evaluated organ iron loading and cardiac function in a tertiary center HCH cohort. 42 HCH patients (47 ± 14 years) and 36 controls underwent laboratory workup and cardiac magnetic resonance (CMR), including T1 and T2* mapping. Myocardial T2* (myoT2*), myocardial T1 (myoT1) and liver T2* (livT2*) were lower in patients compared to controls (33 ± 4 ms vs. 36 ± 3 ms [p = 0.004], 964 ± 33 ms vs. 979 ± 25 ms [p = 0.028] and 21 ± 10 ms vs. 30 ± 5 ms [p &lt; 0.001], respectively). MyoT2* did not reach the threshold of clinically significant iron overload (&lt;20 ms), in any of the patients. In 22 (52.4%) patients, at least one of the tissue parameters was reduced. Reduced myocardial T2* and/or T1 were found in 10 (23.8%) patients, including 4 pts with normal livT2*. LivT2* was reduced in 18 (42.9%) patients. MyoT1 and livT2* inversely correlated with ferritin (rs = -0.351 [p = 0.028] and rs = -0.602 [p &lt; 0.001], respectively). LivT2* by a dedicated sequence and livT2* by cardiac T2* mapping showed good agreement (ICC = 0.876 p &lt; 0.001). In contemporary hemochromatosis, significant myocardial iron overload is rare. Low myocardial T2* and/or T1 values may warrant closer follow-up for accelerated myocardial iron overload even in patients without overt liver overload. Cardiac T2* mapping sequence allows for liver screening at the time of CMR.

Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major.

Myocardial extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) is a surrogate marker of diffuse fibrosis. We evaluated the association between ECV and demographics, CMR findings, and cardiac involvement in patients with thalassemia major (TM). A total of 108 β-TM patients (62 females, 40.16 ± 8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, and 16 healthy subjects (6 females, 37.12 ± 16.13 years) underwent CMR. The protocol included assessment of T2*, native T1, and T2 values in all 16 myocardial segments for myocardial iron overload (MIO) quantification, cine images for left ventricular (LV) function quantification, post-contrast T1 mapping for ECV calculation, and late gadolinium enhancement (LGE) technique for replacement myocardial fibrosis detection. Global ECV values were significantly higher in females than in males. Global ECV values were significantly higher in patients with significant MIO (global heart T2* < 20 ms) than in patients without significant MIO, and both groups exhibited higher global ECV values than healthy subjects. No association was detected between native T1 and ECV values, while patients with reduced global heart T2 values showed significantly higher global ECV values than patients with normal and increased global heart T2. Global ECV values were not correlated with LV function/size and were comparable between patients with and without LGE. Compared to patients without heart failure, patients with a history of heart failure (N = 10) showed significantly higher global heart ECV values. In TM, increased myocardial ECV, potentially reflecting diffuse interstitial fibrosis, is associated with MIO and heart failure. • CMR-derived myocardial extracellular volume is increased in thalassemia major patients, irrespective of the presence of late gadolinium enhancement. • In thalassemia major, myocardial iron overload contributes to the increase in myocardial ECV, which potentially reflects diffuse interstitial fibrosis and is significantly associated with a history of heart failure.

Significance of Cardiac Magnetic Resonance Feature Tracking of the Right Ventricle in Predicting Subclinical Dysfunction in Patients with Thalassemia Major.

In patients with thalassemia major (TM), cardiac magnetic resonance feature-tracking (CMR-FT) has been shown to be an effective method for diagnosing subclinical left ventricular (LV) dysfunction. This study aimed to determine whether CMR-FT could detect abnormal RV dysfunction in patients with a normal right ventricular ejection fraction (RVEF). We performed a retrospective analysis of TM patients admitted to Dubai’s Rashid Hospital between July 2019 and March 2021. The inclusion criteria were TM patients with SSFP cine with T2* (T2*-weighted imaging), while exclusion criteria included any other cardiovascular disease. When there was no myocardial iron overload (MIO) (T2* ≥ 20 ms) and when there was significant MIO (T2* < 20 ms), the CMR-FT was used to correlate with EF. Among the 89 participants, there were 46 men (51.7%) and 43 women (48.3%), with a mean age of 26.14 ± 7.4 years (range from 10 to 48 years). Forty-six patients (51.69%) did not have MIO, while 43 individuals did (48.31%). Thirty-nine patients (32.6%) were diagnosed with severe MIO, while seventeen (19.1%) were diagnosed with mild to moderate MIO. A significant correlation existed between RVEF and T2* values (r = 0.274, p = 0.014) and between left ventricular ejection fraction (LVEF) and T2* values (r = 0.256, p = 0.022). Using a multiple logistic regression model with predictors such as right ventricular longitudinal strain (RVGLS), LV ejection fraction (LV EF), and hemoglobin, abnormal myocardial iron overload can be predicted. This model demonstrates an AUC of 78.3%, a sensitivity of 72%, and a specificity of 76%. In the group with preserved RVEF > 53%, the left ventricular radial strain (LVGRS) (p = 0.001), right ventricular radial strain (RVGRS) (p = 0.000), and right ventricular basal circumferential strain (RVGCS-basal) (p = 0.000) CMR-FT strain values are significantly lower than those of the control group (p > 0.05). There was no significant correlation between the LVGLS and T2*. RVGLS was ranked among the most accurate predictors of abnormal myocardial iron overload. The LVGRS, RVGRS, and RVGCS-basal CMR-FT strain values were the best predictors of subclinical RV dysfunction in the group with preserved RVEF. The most accurate way to diagnose MIO is still T2*, but FT-strain can help us figure out how MIO affects the myocardium from a pathophysiological point of view.

Setting for "Normal" Serum Ferritin Levels in Patients with Transfusion-Dependent Thalassemia: Our Current Strategy.

This cross-sectional study aimed to establish the association between serum ferritin levels and organ iron overload (IO) and overall morbidity in transfusion-dependent thalassemia (TDT) patients. One hundred and three TDT patients (40.03 ± 9.15 years; 57.3% females) with serum ferritin < 2500 ng/mL were included. IO was assessed by T2* magnetic resonance imaging. Three groups were identified based on mean serum ferritin levels: <500 ng/mL (group 0; N = 32), 500–1000 ng/mL (group 1; N = 43), and 1000–2500 ng/mL (group 2; N = 28). All demographic and biochemical parameters were comparable among the three groups, with the exception of the triglycerides being significantly lower in group 0 than in group 2. No difference was found in the frequency of hepatic, endocrine, and cardiac complications. Hepatic IO was significantly less frequent in group 0 versus both groups 1 and 2. No patient with a serum ferritin level < 500 ng/mL had significant myocardial IO and alterations in the main hematological parameters. No difference in the distribution of the different chelation regimens was found. Serum ferritin < 500 ng/mL appears to be achievable and safe for several TDT patients. This target is associated with the absence of significant cardiac iron and significantly lower hepatic IO and triglycerides that are well-demonstrated markers for cardiac and liver complications.

Role of CMR feature-tracking derived left ventricular strain in predicting myocardial iron overload and assessing myocardial contractile dysfunction in patients with thalassemia major.

Myocardial iron overload (MIO) in thalassemia major (TM) may cause subclinical left ventricular (LV) dysfunction which manifests with abnormal strain parameters before a decrease in ejection fraction (EF). Early detection of MIO using cardiovascular magnetic resonance (CMR)-T2* is vital. Our aim was to assess if CMR feature-tracking (FT) strain correlates with T2*, and whether it can identify early contractile dysfunction in patients with MIO but normal EF. One hundred and four consecutive TM patients with LVEF > 55% on echocardiography were prospectively enrolled. Those fulfilling the inclusion criteria underwent CMR, with T2* being the gold standard for detecting MIO. Group 1 included patients without significant MIO (T2* > 20 ms) and group 2 with significant MIO (T2* < 20 ms). Eighty-six patients (mean age, 17.32 years, 59 males) underwent CMR. There were 68 (79.1%) patients in group 1 and 18 (20.9%) in group 2. Fourteen patients (16.3%) had mild-moderate MIO, and four (4.6%) had severe MIO. Patients in group 2 had significantly lower global radial strain (GRS). Global longitudinal strain (GLS) and global circumferential strain (GCS) did not correlate with T2*. T1 mapping values were significantly lower in patients with T2* < 10 ms than those with T2* of 10-20 ms; however, FT-strain values were not significantly different between these two groups. CMR-derived GRS, but not GLS and GCS, correlated with CMR T2*. GRS is significantly decreased in TM patients with MIO and normal EF when compared with those without. FT-strain may be a useful adjunct to CMR T2* and maybe an early marker of myocardial dysfunction in TM. • A global radial strain of < 29.3 derived from cardiac MRI could predict significant myocardial iron overload in patients with thalassemia, with a sensitivity of 76.5% and specificity of 66.7%. • Patients with any myocardial iron overload have significantly lower GRS, compared to those without, suggesting the ability of CMR strain to identify subtle myocardial contractile disturbances. • T1 and T2 mapping values are significantly lower in those with severe myocardial iron than those with mild-moderate iron, suggesting a potential role of T1 and T2 mapping in grading myocardial iron.

359 Pregnancy outcomes in a contemporary cohort of thalassemia patients

Historically, women with transfusion dependent thalassemia (TDT) were considered very high risk for adverse pregnancy outcomes including death, primarily due to iron induced cardiomyopathy. However, recent advances in chelation therapy, better transfusion protocols and enhanced cardiac monitoring have resulted in markedly improved pregnancy outcomes in women with TDT. The purpose of this study is to evaluate risks of pregnancy in women with TDT in a contemporary cohort. A retrospective chart review was conducted of pregnancies in transfusion dependent women with different beta thalassemia genotypes treated at the Weill Cornell Thalassemia Center from 2005-2020. 15 women with TDT had a total of 25 pregnancies with 20 liveborns. 48% of pregnancies were achieved via ART with 4 multiple gestations but only one live set of twins (1 multifetal reduction, 1 2nd trimester loss of quadruplets, 1 2nd trimester loss of triplets due to maternal death). Pregnancy loss rate was 24% and women with TDT had high rates of hypertension in pregnancy (21%), gestational diabetes (52.4%) and post-partum hemorrhage (23.5%). Ongoing pregnancies had favorable fetal outcomes with mean GA of 38 weeks and mean birthweight of 3129g. Cesarean section rates were high (10/19 deliveries). 40% of women had diagnosis of cardiac disease before conception or during pregnancy (see Table 1). There was 1 major complication in the second pregnancy in a woman with a triplet pregnancy, known cardiomyopathy, and severe myocardial iron overload resulting in maternal death from cardiogenic shock at 18 weeks. Women with TDT who are considering pregnancy should have a thorough assessment preconception and select patients, without evidence of significant myocardial iron overload or cardiomyopathy, may safely pursue pregnancy. While many women with TDT will require ART for conception, multiple gestations should be discouraged due to poor outcomes. A multidisciplinary approach to care in pregnancy is paramount in this high-risk population with majority of patients achieving favorable pregnancy outcomes.

Left and Right Atrial Function and Remodeling in Beta-Thalassaemia Major.

This study aimed to assess left (LA) and right atrial (RA) function in patients with beta-thalassaemia major. Thirty-eight patients (19 males) aged 34.5 ± 10.7years and 43 (18 males) controls aged 30.3 ± 12.6years (p = 0.12) were studied. The maximum RA and LA areas were measured using two-dimensional planimetry, while atrial and ventricular strain and strain rates were quantified using speckle-tracking echocardiography. Compared with controls, patients had significantly reduced LA and RA peak positive strain and total strain, and LA strain rate during ventricular systole and at atrial contraction (all p < 0.05). The LA and RA strain parameters were significantly associated (all p < 0.05). The maximum LA (10.2 ± 1.6cm2/m2 vs. 8.6 ± 1.3cm2/m2, p < 0.001) and RA (9.2 ± 1.2cm2/m2 vs. 7.5 ± 1.3cm2/m2, p < 0.001) areas were significantly greater in patients than controls. The LV and RV strain and early strain rates were similar between patients and controls (all p > 0.05). Four patients with significant myocardial iron overload had larger LA area (p < 0.001) than those without. Functional and structural remodeling of both the right and left atria occurs in patients with beta-thalassaemia major, even in the absence of ventricular diastolic dysfunction.

Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study.

Cardiovascular magnetic resonance (CMR) plays a key role in the management of thalassemia major patients, but few data are available in pediatric population. This study aims at a retrospective multiparametric CMR assessment of myocardial iron overload, function, and fibrosis in a cohort of pediatric thalassemia major patients. We studied 107 pediatric thalassemia major patients (61 boys, median age 14.4 years). Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. All scans were performed without sedation. The 21.4% of the patients showed a significant myocardial iron overload correlated with lower compliance to chelation therapy (P<0.013). Serum ferritin ≥2000 ng/mL and liver iron concentration ≥14 mg/g/dw were detected as the best threshold for predicting cardiac iron overload (P=0.001 and P<0.0001, respectively). A homogeneous pattern of myocardial iron overload was associated with a negative cardiac remodeling and significant higher liver iron concentration (P<0.0001). Myocardial fibrosis by late gadolinium enhancement was detected in 15.8% of the patients (youngest children 13 years old). It was correlated with significant lower heart T2* values (P=0.022) and negative cardiac remodeling indexes. A pathological magnetic resonance imaging liver iron concentration was found in the 77.6% of the patients. Cardiac damage detectable by a multiparametric CMR approach can occur early in thalassemia major patients. So, the first T2* CMR assessment should be performed as early as feasible without sedation to tailor the chelation treatment. Conversely, late gadolinium enhancement CMR should be postponed in the teenager age.

Myocardial Iron overload In Thalassemia Major. how Early To Check?

Introduction It is still controversy in thalassemia major (TM) if Cardiovascular Magnetic Resonance (CMR) T2* screening should be initiated before the 10 years. To answer this question, we studied retrospectively the prevalence of cardiac iron and function and myocardial fibrosis by CMR in a consistent cohort of TM patients younger than 10 years. Methods From the 2171 patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we retrospectively selected the 35 TM patients aged less than 10 years who had undergone at least one MRI scan. Myocardial iron overload (MIO) was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated in a standard way by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Results Patients’ age ranged from 4.2 to 9.7 years. All MRI scans were performed without sedation. Nine patients (25.7%) showed no myocardial iron overload (MIO),22 patients (62.9%) showed an heterogeneous MIO with a T2* global value ≥ 20 ms; 2 patients (5.7%) showed an heterogeneous MIO and a T2* global value &lt; 20 ms and 2 patients (5.7%) had a homogeneous MIO. No patients showed myocardial fibrosis. Table 1 reports the data of the 4 patients (3 males and 1 female) with significant myocardial iron overload (global heart T2* &lt; 20 ms). The youngest was 6 years old, all showed no heart dysfunction and in all the iron transfused was less than 35 g. Conclusion The first cardiac T2* assessment should be performed as early as possible without sedation and it is mandatory whenever poor compliance is suspected or if chelation has been started late. The use of the contrast medium to detect myocardial fibrosis can be postponed until after 10 years of age. A more sensitive segmental approach to detected heart iron should be considered. Therapy can be modified on the basis of the MRI results and serious organ damage can be prevented. Disclosures: No relevant conflicts of interest to declare.

Early Identification of Cardiovascular Involvement in Patients With β-Thalassemia Major

The aim of the present study was to evaluate left ventricular myocardial deformation and carotid arterial stiffness using 2-dimensional strain and echo-tracking in patients with asymptomatic β-thalassemia major (β-TM) without significant myocardial iron overload to determine whether early subclinical cardiovascular abnormalities would be detectable. We enrolled 32 patients with β-TM (23 women, mean age 35 ± 8years) and 33 healthy volunteers (20 women, mean age 35 ± 6years). All subjects underwent echocardiography with 2-dimensional strain analysis (XStrain) and ultrasonography of the carotid arteries with measurement of the stiffness parameters (ProSound Alpha 10). Cardiac magnetic resonance imaging using a T2* algorithm (37.7 ± 5.6ms) for the assessment of myocardial iron overload was performed in each patient. The clinical and standard echocardiographic parameters were comparable between the patients and healthy subjects. The global left ventricular longitudinal strain was significantly impaired in the patients compared with the controls (-17.9 ± 3.5% vs-24.3 ± 3.4%, p= 0.002), although the radial and circumferential strain values were similar between the 2 groups (p= NS for both). The carotid intima-media thickness was comparable between the patients and healthy subjects (0.67 ± 0.20mm vs 0.66 ± 0.15mm, p= NS). In contrast, the arterial stiffness was significantly increased in the patients compared with the controls (stiffness index 6.16 ± 1.31 vs 4.65 ± 0.82, p <0.001; arterial compliance 1.10 ± 0.26vs 1.28 ± 0.30cm(2)/mm Hg, p= 0.027; elastic modulus 74.1 ± 19.5vs 59.1 ± 12.1mm Hg, p= 0.001). In conclusion, cardiovascular abnormalities, although often subclinical, occur at an early stage of β-TM and also in the absence of significant iron overload. Thus, 2-dimensional strain and echo-tracking might be more accurate than standard echocardiography and vascular parameters in the early identification of cardiovascular involvement.

A MRI Prospective Survey on Cardiac and Hepatic Iron and Cardiac Function in Thalassemia Major Patients Treated with Sequential deferiprone–desferrioxamine versus Deferasirox

Abstract 1087 Introduction:No data are available in literature about possible different changes in cardiac and hepatic iron and in cardiac function in thalassemia major (TM) patients treated with sequential deferipron–desferrioxamine (DFP-DFO) versus deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue.Our aim was to prospectively assess the efficacy of the DFP-DFO vs DFX in a large cohort of TM patients by quantitative MR. Methods:Among the first 1135 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 392 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively 35 patients treated with DFP-DFO versus 80 patients treated with DFX between the 2 MR scans. Cardiac iron was evaluated by T2* multiecho multislice technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron was measured by T2* multiecho technique. Results:Excellent/good levels of compliance were similar in the two groups (DFP-DFO 97.1% vs DFX 98.8%; P=0.544).Among the patients with no significant myocardial iron overload (MIO) at baseline (global heart T2*≥20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 96% vs DFX 98%; P=0.536).Among the patients with MIO at baseline, in both groups there was a significant improvement in the global heart T2* value (DFP-DFO: 4.8±3.9 ms P=0.004 and DFX: 3.5±4.7 P=0.001) and a significant reduction in the number of pathological segments (DFP-DFO: −3.2±3.8 P=0.026 and DFX: −2.4±3.8 P=0.003). Only in sequential group there was a significant increment in the left and right ventricular ejection fractions (4.3±5.1% P=0.035 and 6.7±6.6% P=0.017, respectively). The improvement in the global heart T2* was not significantly different between groups. The improvement in the left as well in the right ventricular ejection fractions was significantly different between groups (P=0.009 and P=0.015, respectively) (Figure 1). [Display omitted] Among the patients with hepatic iron at baseline (T2*<9.2 ms), only in the DFX group there was a significant improvement in the liver T2* value (2.6±5.3 ms P=0.001). The changes in liver T2* were significantly higher in DFX group than in DFP-DFO (0.5±2.0 ms) group (P=0.030) (Figure 2). [Display omitted] Conclusions:In TM patients prospectively no significant differences on cardiac iron were found between sequential DFP–DFO treatment versus DFX in monoterapy, although the DFP-DFO treatment was significantly more effective in improving biventricular global systolic function. Conversely, DFX was significantly more effective in reducing hepatic siderosis. Disclosures:Pepe:Novartis: Speakers Bureau; Apotex: Speakers Bureau; Chiesi: Speakers Bureau. Off Label Use: Association of two chelators commercially available in order to obtain a higher efficacy. Borgna-Pignatti:Apotex: Honoraria; Novartis: Honoraria, Research Funding.

A T2* MRI prospective survey on heart iron in thalassemia major patients treated with deferasirox versus deferiprone and desferrioxamine in monotherapy

Excellent/good levels of compliance were similar in the 3 groups (DFX 99%, DFP 95%; DFO 96%, P =0 .6). There were no significant differences in all 3 groups to maintain the patients without significant myocardial iron overload (global heart T2*≥20 ms) (DFX 98%; DFP 100%; DFO 98%; P=1.0). The percentage of patients that maintained a normal LVEF (>57%) was significantly lower in DFX (77%) versus DFP (100%) (P=0.018), it was no significantly different in DFX and DFO group (82%) (P=0.59). Among the patients with myocardial iron overload at baseline in all 3 groups, there was a significant improvement in the global heart T2* value and in the number of segment with a normal T2* value; only in the DFP group there was a significant improvement in the right global systolic function (+ 6.8% P =0.016). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group (P=0.0026), but it was not significantly different in the DFX versus the DFO group (mean difference global heart T2* 3.5±4.7 ms versus 8.8±8.6 ms and versus 3.7±5.5 ms, respectively; P=0.90) (Figure 1). The changes in the global systolic biventricular function were not significantly different among groups. Conclusions

A T2* MRI prospective survey on heart iron in thalassemia major patients treated with sequential deferiprone-desferrioxamine versus deferipron and desferrioxamine in monotherapy

Purpose Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. No data are available in literature about possible different changes in cardiac iron in TM patients treated with sequential deferiprondeferoxamine (DFP-DFO) versus deferipron (DFP) and deferoxamine (DFO) in monotherapy. Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluate quantitatively this issue. Our aim was to prospectively assess in the clinical practice the efficacy of the DFP-DFO versus DFP and DFO in monotherapy in a cohort of TM patients by quantitative MR. Methods Among the first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively the 25 patients treated with DFP-DFO versus the 30 patients treated with DFP and the 66 patients treated with DFO between the 2 MR scans. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Results Excellent/good levels of compliance were similar in the 3 groups (DFP-DFO 96% versus DFP 97% versus DFO 92%; P=0.67). Among the patients with no significant myocardial iron overload (MIO) at baseline (global heart T2* ≥ 20 ms), there were no significant differences between groups to maintain the patients without MIO (DFP-DFO 95% versus DFP 100% versus DFO 100%; P=0.23). Among the patients with MIO at baseline (global heart T2* < 20 ms), only DFP and DFO showed a significant improvement in the global heart T2* value (P=0.001 and P=0.003, respectively) and in the number of segment with a normal T2* value (P=0.031 and P=0.0001, respectively). The improvement in the global heart T2* was significantly different among groups (mean difference global heart T2* DFP-DFO 2.2 ± 4.1 ms, DFP 10.7 ± 7.2, DFO 3.6 ± 5.4; P=0.007).

A T2* MRI prospective survey on heart iron in thalassemia major patients treated with sequential deferipron-desferrioxamine versus deferasirox

Abstract 5165 Introduction: Most deaths in thalassemia major (TM) result from cardiac complications due to iron overload. No data are available in literature about possible different changes in cardiac and liver iron in TM patients treated with sequential deferiprone–deferoxamine (DFP-DFO) versus deferasirox (DFX). Magnetic Resonance (MR) is the unique non invasive suitable technique to evaluated quantitatively this issue. The aim of this multi-centre study was to assess prospectively in the clinical practice the efficacy of the DFP-DFO vs DFX in a cohort of TM patients by quantitative MR. Methods: Among the first 739 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, 253 patients performed a MR follow up study at 18 ± 3 months according to the protocol. We evaluated prospectively the 25 patients treated with DFP-DFO versus the 44 patients treated with DFX between the 2 MR scans. Myocardial and liver iron concentrations were measured by T2* multislice multiecho technique. Results: The doses of the sequential treatment were DFP 70±14 mg/kg/d for 4 d/w and DFO 42±8 mg/kg/d for 3 d/w, the dose of DFX was 26±6 mg/kg/d. Excellent/good levels of compliance were similar in the 2 groups (DFP-DFO 96% vs DFX 100%; P = 0.36). At baseline the 2 groups were homogeneous for cardiac and liver iron. Among the patients with no significant myocardial iron overload at baseline (global heart T2* 3 20 ms), there were no significant differences between groups to maintain the patients without myocardial iron overload (DFP-DFO 95% vs DFX 96%; P = 1.0). Among the patients with myocardial iron overload at baseline (global heart T2* < 20 ms), only in the DFX group there was a significant improvement in the global heart T2* value (11 ± 5 ms at baseline versus 16 ± 8 at 18 ± 3 months, P = 0.0001) and in the number of segment with a normal T2* value ( P = 0.003). The improvement in the global heart T2* was not significantly difference in the DFP-DFO versus the DFX group (mean difference global heart T2* 2.2 ± 4.1 ms versus 4.6 ± 4.8 P = 0.2). The changes in the mean serum ferritin level were not significantly different between groups. In patients with liver iron overload at baseline (liver T2* < 5.1 ms), the change in the liver T2* was not significant between groups (mean difference liver T2* 0.9 ± 2.1 ms vs 2.4 ± 5.2; P = 0.3). Conclusions: Prospectively in the clinical setting over 15 months we did not find significant differences on cardiac and liver iron by quantitative MRI in TM patients treated with sequential DFP–DFO versus the TM patients treated with DFX. Disclosures: No relevant conflicts of interest to declare.