Magnetic resonance imaging assessment of the changes of cardiac and hepatic iron load in thalassemia patients before and after hematopoietic stem cell transplantation.

To investigate the value of T2* technique on 3.0 T magnetic resonance imaging (MRI) in evaluating the changes of cardiac and hepatic iron load before and after hematopoietic stem cell transplantation (HSCT) in patients with thalassemia (TM), the 141 TM patients were divided into 6 group for subgroup analysis: 6, 12, 18, 24 and > 24 months group, according to the postoperative interval. The T2* values of heart and liver (H-T2*, L-T2*) were quantified in TM patients before and after HSCT using 3.0 T MRI T2* technology, and the corresponding serum ferritin (SF) was collected at the same time, and the changes of the three before and after HSCT were compared. The overall H-T2* (P = 0.001) and L-T2* (P = 0.041) of patients after HSCT were higher than those before HSCT (mean relative changes = 19.63%, 7.19%). The H-T2* (P < 0.001) and L-T2* (P < 0.001) > 24 months after HSCT were significantly higher than those before HSCT (mean relative changes = 69.19%, 93.73%). The SF of 6 months (P < 0.001), 12 months (P = 0.008), 18 months (P = 0.002) and > 24 months (P = 0.001) were significantly higher than those before HSCT (mean relative changes = 57.93%, 73.84%, 128.51%, 85.47%). There was no significant improvement in cardiac and liver iron content in TM patients within 24 months after HSCT, while the reduction of cardiac and liver iron content in patients is obvious when > 24 months after HSCT.

Quantitative T2* MRI for bone marrow iron overload: normal reference values and assessment in thalassemia major patients.

PURPOSE: We evaluated the feasibility and reproducibility of bone marrow T2* values and established the lower limit of normal in a cohort of healthy subjects. We investigated the clinical correlates of bone marrow T2* values in patients with thalassemia major (TM). MATERIAL AND METHODS: Thirty healthy subjects and 274 consecutive TM patients (38.96 ± 8.49 years, 151 females) underwent MRI at 1.5T. An axial slice in the upper abdomen was acquired by a T2* gradient-echo multiecho sequence and the T2* value was calculated in a circular region of interest defined in the visible body of the first or second lumbar vertebra. In patients, also liver and heart T2* values were assessed. RESULTS: In healthy subjects bone marrow T2* values were independent of age and gender. The lower limit of normal for bone marrow T2* was 13 ms. In both healthy subjects and 30 randomly selected patients, the coefficient of variation for inter-operator-reproducibility was < 10%. TM patients exhibited significantly lower bone marrow T2* values than healthy subjects (7.47 ± 5.18 ms vs. 17.08 ± 1.89 ms; p < 0.0001). A pathological bone marrow T2* was detected in 82.8% of TM patients. In TM, the female sex was associated with reduced bone marrow T2* values. Bone marrow T2* values were inversely correlated with mean serum ferritin levels (R = -0.431; P < 0.0001) and hepatic iron load (R = - 0.215; P < 0.0001). A serum ferritin level > 536 ng/ml predicted the presence of a pathological bone marrow T2*. A positive correlation was found between bone marrow and heart T2* values (R = 0.143; P = 0.018). A normal bone marrow T2* showed a negative predictive value of 100% for cardiac iron. CONCLUSION: Bone marrow T2* measurements can be easily obtained using the same sequences acquired for liver iron quantification and may bring new insights into the pathophysiology of iron deposition; hence, they should be incorporated into clinical practice.

Dual gradient echo in-phase and out of phase sequences in assessment of hepatic iron overload in patients with beta-thalassemia, would be better?

PURPOSE: To evaluate the diagnostic accuracy of the dual gradient-echo (GRE) in- and out-of-phase sequences as a quantitative tool for hepatic iron overload in comparison with MRI R2* relaxometry in paediatric patients with beta-thalassemia. METHOD: Sixty-three patients with beta-thalassemia major (transfusion-dependent) or beta-thalassemia intermedia (transfusion- and non-transfusion-dependent) were referred from the paediatric department (haematology unit) to the radiology department at a university hospital. The paediatrician conducted a clinical examination for the studied group, assessed their laboratory data, conducted R2* relaxometry and dual gradient echo sequences to calculate R2* and relative signal intensity index at the axial mid-section of the liver, and studied their correlation. A 1.5 Tesla MR scanner was used (Achieva; Philips Medical Systems, the Netherlands). Data were fed to the computer and analysed using the IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). The Kolmogorov-Smirnov test was used to verify the normality of distribution. The significance of the results was determined at the 5% level. The Chi-square, Fisher's exact correction, Pearson coefficient, and Bland-Altman tests were used. RESULTS: Dual gradient-echo in- and out-of-phase sequences using visual assessment accurately assessed 93.65% of our patient group with hepatic iron overload. A significant correlation was found between the relative signal intensity index and hepatic MRI R2* relaxometry (p < 0.001, r = 0.861). CONCLUSIONS: Dual gradient-echo in and out-of-phase sequences are good imaging tools for hepatic iron detection and quantification. These sequences showed good correlation with R2* relaxometry (r = 0.861, p < 0.001).

Assessment of ventricular dysfunction in Egyptian children with Beta-thalassemia major.

OBJECTIVE/BACKGROUND: The purpose of this study was to evaluate serum cardiac troponin I and serum N-terminal (NT) pro-brain natriuretic peptide (pro-BNP) levels and the utility of tissue Doppler imaging in assessing cardiovascular changes following left ventricular (LV) dysfunction in children with beta-thalassemia major (ß-TM). In children with ß-TM who depend on regular blood transfusion, cardiac iron toxicity is a common serious complication. The most common cause of death among these patients is congestive heart failure. METHODS: This is a cross-sectional study which included 50 patients with ß-TM and 50 healthy controls. Tissue Doppler imaging was performed and levels of serum ferritin, cardiac troponin I, and NT pro-BNP were estimated for all included patients. RESULTS: Serum NT pro-BNP and cardiac troponin (cTnI) showed a significant increase in patients with ß-TM (p < .001). In patients with ß-TM, LV dimensions (LV end systolic diameter) and (LV end diastolic diameter) were large (p < .01); LV mass (p < .01), E wave, and E/A ratio (p < .01) were high (p < .05); and deceleration time was short (p < .05). Besides, transmitral ratio (E/Em) (p < .05) and tricuspid valve velocity were higher (p < .05), and early diastolic velocity (Em) (p < .05) and systolic wave velocity (Sm) were lower in patients with ß-TM (p < .05). A significant positive correlation was detected between the pro-BNP and E wave (r = 0.558, p < .001), E/A ratio (r = 0.403, p < .001), E/Em ratio (r = 0.576, p < .001), and ferritin (r = 0.545, p < .001). CONCLUSION: Pulsed wave tissue Doppler imaging and NT pro-BNP had a significant role in the estimation of ventricular dysfunction in children with ß-TM.

Assessment of Bone Density by DXA in Poorly Controlled Children With ß-Thalassemia: Correction for Hepatic Iron Overload by Manual Analysis.

INTRODUCTION: Beta thalassemia major (BTM) is characterized by anemia and iron overload, especially with inadequate chelation therapy. Dual energy x-ray absorptiometry software (DXA) may misanalyse bone measurements due to iron deposition in organs such as the liver. Our objective was to study difference between the posterior-anterior spine measurements of bone mineral content (BMC), area (BA) and density (BMD) in poorly chelated beta thalassemia patients with and without inclusion of the liver in the DXA analysis. METHODS: We studied hemoglobin and serum ferritin concentrations in 208 patients with BTM (children n = 177, young adults n = 31). Posteroanterior spine measurements BMC, BA and areal BMD were performed using a GE iDXA. Using the tissue point typing feature (EnCore software, version 16), analysis was carried out including and excluding (manually) the iron overloaded liver. Machine generated Z-scores of L1-L4 BMD were used for analysis. RESULTS: The mean age of the study group was 12.9 ± 5.4 yr. Mean hemoglobin and serum ferritin concentrations were 8.0 ± 1.7 g/dl and 2256.9 ± 1978.0 ng/ml, respectively. The mean BMC, BA, and aBMD at the lumbar spine were 23.2 ± 11.4 g, 29.9 ± 8.5 cm2 and 0.736 ± 0.173 g/cm2 respectively with inclusion of liver that is standard machine analysis. After the liver was excluded from the analysis, the mean BMC, BA, and aBMD were 23.9 ± 11.6 g, 30.0 ± 8.6 cm2 and 0.757 ±0.173 g/cm2, respectively and the BMC and aBMD were significantly greater (p < 0.05). Mean BMD Z-score was -1.5 ± 1.2, which significantly (p < 0.05) improved to -1.3 ± 1.2 after exclusion of the liver from the analysis. CONCLUSION: In poorly chelated patients with thalassemia, inclusion of the iron-overloaded liver in the tissue analysis may exaggerate the deficit in bone parameters. Iron overloaded tissues need to be manually excluded during analysis of the PA spine.

Assessment of mandibular characteristics in patients affected with ß-thalassaemia major: A retrospective case-control study.

OBJECTIVE: Thalassemia is the most common hereditary blood disorder across the world. This study aimed to identify some mandibular features of thalassaemic patients and compare them with unaffected counterparts. MATERIAL AND METHODS: This retrospective case-control study was carried out on lateral cephalograms of 60 subjects (26 males, 34 females) with class II malocclusion and age range of 11 to 15 years. The control group consisted of 60 non-thalassaemic subjects with class II malocclusion and similar chronological age, gender and vertical facial dimension. Based on the Jarabak index, the case and control subjects were classified into hyperdivergent, normodivergent and hypodivergent growth patterns. Four linear (ramus height, ramus width, mandibular depth, and antegonial notch depth) and 3 angular (symphyseal angle, gonial angle, and mandibular arc angle) cephalometric parameters were measured to represent mandibular morphology. The data were analysed using Chi-square test and Student's t-test. RESULTS: No significant difference was found in linear measurements between thalassaemic patients and controls. The symphysis angle was significantly greater and the mandibular arc angle was significantly smaller in the total thalassaemic sample than the control individuals (P<0.001 and P=0.004, respectively). The difference in symphysis angle was significant in both hyperdivergent and normodivergent subjects (P=0.004 and P=0.002, respectively), whereas the difference in mandibular arc angle was only significant in the normodivergent subgroup P=0.001). CONCLUSIONS: The smaller mandibular arc angle in the thalassaemic sample suggests a more superior than posterior growth direction of condyles compared with healthy individuals. The difference in symphyseal angle represents inherent differences in chin morphology between thalassaemic subjects and controls.

Assessment of cardiac and liver iron overload by magnetic resonance imaging in patients with thalassemia major: short-term follow-up.

OBJECTIVE: This study was performed to assess cardiac and hepatic iron overload in young patients with thalassemia. METHODS: We reviewed the medical records of patients with thalassemia at a pediatric hematology clinic who had recently undergone cardiac and hepatic magnetic resonance imaging. RESULTS: Eleven patients underwent cardiac and hepatic T2* imaging at a mean age of 13.9 ± 4.48 (range, 9-21) years. Three patients had cardiac iron overload and all patients had hepatic iron overload according to the magnetic resonance imaging scan. Ten patients underwent control imaging approximately 1 year later. The mean serum ferritin level at the initial imaging examination was 1820.87 ± 1275.22 (range, 634.04-4221.03) ng/mL. There was a strong negative correlation between the ferritin level and cardiac T2* time and between the blood hemoglobin level and hepatic T2* time. Among the 10 patients who underwent control imaging, the average hemoglobin and ferritin levels significantly decreased from the initial to control imaging examinations, but there was no significant increase in the cardiac and hepatic T2*times. CONCLUSIONS: Cardiac and hepatic T2* imaging is a feasible method of assessing cardiac and hepatic iron overload even before complications and clinical signs of iron overload appear.

Estimation of pancreatic R2* for iron overload assessment in the presence of fat: a comparison of different approaches.

OBJECTIVES: To propose a method for estimating pancreatic relaxation rate, R2*, from conventional multi-echo MRI, based on the nonlinear fitting of the acquired magnitude signal decay to MR signal models that take into account both the signal oscillations induced by fat and the different R2* values of pancreatic parenchyma and fat. MATERIALS AND METHODS: Single-peak fat (SPF) and multi-peak fat (MPF) models were introduced. Single-R2* and dual-R2* assumptions were considered as well. Analyses were conducted on simulated data and 20 thalassemia major patients. RESULTS: Simulations revealed the ability of the MPF model to correctly estimate the R2* value in a large range of fat fractions and R2* values. From the comparison between the results obtained with a single R2* value for water and fat and the dual-R2* approach, the latter is more accurate in both water R2* and fat fraction estimation. In patient's data analysis, a strong concordance was found between SPF and MPF estimated data with measurements done with manual signal correction and from fat-saturated images. The MPF method showed better reproducibility. CONCLUSION: The MPF dual-R2* approach improves reproducibility and reduces image analysis time in the assessment of pancreatic R2* value in patients with iron overload.

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

BACKGROUND: Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. METHODS: In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. RESULTS: The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. CONCLUSIONS: In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Non-invasive MRI biomarkers for the early assessment of iron overload in a humanized mouse model of ß-thalassemia.

ß-thalassemia (ßT) is a genetic blood disorder causing profound and life threatening anemia. Current clinical management of ßT is a lifelong dependence on regular blood transfusions, a consequence of which is systemic iron overload leading to acute heart failure. Recent developments in gene and chelation therapy give hope of better prognosis for patients, but successful translation to clinical practice is hindered by the lack of thorough preclinical testing using representative animal models and clinically relevant quantitative biomarkers. Here we demonstrate a quantitative and non-invasive preclinical Magnetic Resonance Imaging (MRI) platform for the assessment of ßT in the γß0/γßA humanized mouse model of ßT. Changes in the quantitative MRI relaxation times as well as severe splenomegaly were observed in the heart, liver and spleen in ßT. These data showed high sensitivity to iron overload and a strong relationship between quantitative MRI relaxation times and hepatic iron content. Importantly these changes preceded the onset of iron overload cardiomyopathy, providing an early biomarker of disease progression. This work demonstrates that multiparametric MRI is a powerful tool for the assessment of preclinical ßT, providing sensitive and quantitative monitoring of tissue iron sequestration and cardiac dysfunction- parameters essential for the preclinical development of new therapeutics.

Doppler assessment of renal hemodynamic alterations in homozygous sickle cell disease and sickle Beta-thalassemia.

We evaluated the renal vascular indices in children and adolescents with sickle cell disease (SCD) using Doppler ultrasonography. We also assessed the renal hemodynamics alterations in patients with homozygous SCD and sickle beta-thalassemia (sickle ß-thalassemia). We studied 75 patients (age range = 3-20 years; M = 9.95 ± 4.15) with SCD: 42 patients suffering from homozygous SCD and 33 patients diagnosed with sickle ß-thalassemia. Thirty, age- and sex-matched, normal subjects were also included as a control group. Both patients and control groups had Doppler assessment of pulsatility (PI) and resistivity (RI) indices of main renal, segmental, interlobar, and arcuate arteries. Both PIs and RIs were significantly higher in SCD patients, compared with the control group. Among patients, PIs and RIs in the main renal, segmental, interlobar, and arcuate arteries were significantly higher in patients with homozygous SCD as compared with those with sickle ß-thalassemia (p values <0.01, <0.001, <0.001, and <0.001 for PIs and <0.001, <0.001, <0.001, and <0.01 for RIs, respectively). We concluded that renal vascular resistance is raised in children and adolescents with SCD. This is more pronounced in patients with homozygous SCD as compared with those with sickle ß-thalassemia.

Assessment of left ventricular and atrial diastolic function using two-dimensional (2D) strain imaging in patients with ß-thalassemia major.

BACKGROUND: ß-thalassemia major is a unique disease characterized by early severe diastolic dysfunction, due to iron myocardial deposition alone, while left ventricular systolic dysfunction and failure seem to be multifactorial in aitiology. OBJECTIVES: The purpose of this study was to investigate left ventricular diastolic dysfunction using a new echo index as speckle tracking in comparison with the conventional methods. MATERIAL AND METHODS: Eighty-eight consecutive patients (38 male, 50 female) aged 36 ± 8.2 yr with ß-thalassemia major and preserved LV ejection fraction (LVEF>55%) were studied. Patients were divided into two groups according to the E mitral/E mitral annulus ratio (E/E'): group A patients with E/E' ratio ≤8 and group B patients with E/E' >8. Cutoff value of eight was used to separate patients with normal and abnormal diastolic function. All subjects were studied thoroughly by tissue Doppler echocardiography as also by 2D left ventricular and atrial strain imaging 2-4 d following blood transfusion. Blood samples were also taken for plasma BNP measurements at the same time. RESULTS: Left atrial volumes(LAV max, LAV min) as also left atrial index were significantly higher in patients with diastolic dysfunction compared with patients without diastolic dysfunction(LAV max: 57.6 ± 19.4 vs. 71.3 ± 22.9, P < 0.01,LAV min: 20.2 ± 11.4 vs. 33.9 ± 18, P < 0.01, LAVI: 37.66 ± 12.18 vs. 47.13 ± 14.77, P < 0.01). Radial 2D strain (RS) and peak atrial 2D strain (AS) were significantly reduced in patients with suspected diastolic dysfunction compared with patients without diastolic dysfunction (RS: 43.48 ± 13.92 vs. 35.58 ± 11.32, P < 0.05; AS: 36.36 ± 8.45 vs. 29.85 ± 9.25, P < 0.01). Using ROC analysis, peak atrial 2D strain at a cutoff of 41.1 cm/s was highly accurate (AUC: 0.66, P < 0.05 in ruling out diastolic dysfunction (E/E'<8) with a sensitivity of 90% and a specificity of 81%. CONCLUSIONS: B-thalassemic major patients with preserved left ventricular systolic function had impaired left atrial function at the longitudinal axis and left ventricular function at the radial axis. The new echo markers have better prognostic value than the traditional echo indexes in detecting latent diastolic dysfunction in ß-thalassemia major, earlier than E/E' ratio.

Usefulness of pulsed wave tissue doppler imaging in assessment of left ventricular functions in children with beta-thalassemia major.

OBJECTIVE: To evaluate the changes in the LV systolic and diastolic function in children with beta-thalassemia major (ß-TM) using pulsed wave tissue doppler (TD) echocardiography. METHODS: Clinical, conventional echo doppler and pulsed wave tissue doppler imaging parameters were compared in 40 beta-thalassemia major patients (mean age, 6.52 ± 3.5 y) and 25 age and sex matched normal subjects (mean age, 6.5 ± 2.7 y). RESULTS: There were no significant statistical differences between mean fractional shortening (FS) and ejection fraction (EF) of left ventricle (LV) of the patients and control group. Children with beta-thalassemia had significantly lower E' wave velocities measured at the left ventricular septal annulus (8.1 ± 3.3 vs. 13 ± 2.5, P < 0.001), lateral margin of the mitral annulus (9.1 ± 5.4 vs. 13.3 ± 2.5, P < 0.001) and lateral margin of the tricuspid annulus (9.3 ± 3.9 vs. 13.3 ± 2.5, P < 0.001) when compared to the control group. Furthermore children with beta-thalassemia had significantly lower E'/A' wave ratio at the left ventricular septal annulus (0.76 ± 0.34 vs. 1.36 ± 0.23), lateral margin of the mitral annulus (0.83 ± 0.17 vs. 1.28 ± 0.22), and lateral margin of the tricuspid annulus ((0.90 ± 0.27 vs. 1.26 ± 0.23, (P < 0.05) when compared to the control group. CONCLUSIONS: This study showed that patients with beta-thalassemia major and normal conventional echo doppler parameters had statistically significant changes detected by pulsed wave tissue doppler imaging.

Ultrasonographic assessment of the prevalence of cholelithiasis and biliary sludge in beta-thalassemia patients in Iran.

BACKGROUND: Thalassemia is a hereditary disease related to hemoglobin synthesis. The aim of this study was to determine the prevalence of gallbladder sludge and stones in beta-thalassemic children. MATERIAL/METHODS: One hundred fifty-three beta-thalassemia patients on a long-term transfusion/chelation program were selected by a cluster randomized method and were evaluated ultrasonographically for the presence of sludge and biliary lithiasis. Relationships between the prevalence of gallbladder sludge and stones with age, sex, age at the start and the frequency of transfusion, mean pretransfusion Hb and ferritin levels, age at start of deferoxamine injection, splenectomy, and degree of splenomegaly were evaluated statistically. RESULTS: Gallstones and biliary sludge were detected in 12.4% and 13.1% of the patients, respectively. There was a significant increase in the prevalence of gallstones with increasing age, transfusion periods of <21 days, severe splenomegaly, splenectomy, and deferoxamine injection started after 5 years of age. Such a relationship was not detected for hemoglobin and ferritin levels. Multiple logistic regression analysis revealed that the frequency of transfusions and age at the start of deferoxamine injections were the only positive factors that predicted the subsequent development of gallstones. CONCLUSIONS: Longer survival of beta-thalassemic patients leads to a higher prevalence gallbladder sludge and stones. Therefore a proper follow-up of patients with abdominal ultrasonography and improving the transfusion/chelation program should be mandatory.

Assessment of LV diastolic function in patients with beta-thalassemia major with special reference to E/Eann ratio.

OBJECTIVE: The present study was undertaken to evaluate left ventricular function in patients with beta-thalassemia major with special reference to pulsed wave tissue Doppler imaging. METHODS: The present study compared 30 diagnosed cases of beta-thalassemia major (mean age: 9.43+/-2.78 y) with 30 age-sex-matched healthy controls (mean age: 8.3+/-2.83 y) for left ventricular function assessment using following parameters: ejection fraction, mitral valve E/A ratio and E deceleration time (Edec), isovolumic relaxation time, and E/Eann ratio. Serum ferritin levels were also measured. RESULTS: There was significant increase in E/Eann (9.46+/-1.5 vs. 6.16+/-2.4, P<0.0001) and significant prolongation of Edec (177.66+/-40.73 vs. 138.5, P<0.001) and isovolumic relaxation time (40.2+/-14.89 vs. 36.67+/-5.12, P<0.05) in cases as compared with controls. However, there was no significant difference in ejection fraction value (65.55+/-8.98 vs. 63.87+/-16.35) and E/A ratio (2.0386+/-0.73 vs. 2.119+/-0.92). Serum ferritin levels although increased significantly in cases (8370.85+/-2660.35), no correlation could be established between increased serum ferritin and progressive diastolic dysfunction (r=0.148, P=0.258). CONCLUSIONS: Diastolic dysfunction precedes systolic dysfunction in patients with beta-thalassemia major as assessed by Edec and E/Eann ratio.

Longitudinal assessment of cardiac status by echocardiographic evaluation of left ventricular diastolic function in thalassaemic children.

Cardiac disease is the primary cause of death in patients affected by thalassaemia major. In most cases diastolic dysfunction precedes the onset of systolic impairment at a time when appropriate therapy can prevent progression of cardiac damage. We have assessed the pattern of left ventricular filling by Doppler echocardiography in six transfusion-dependent thalassaemic patients. They were re-evaluated 5 y after the first observation, after additional blood transfusions and consequent iron load. We registered a significantly impaired relaxation pattern in all of them. A state of cardiac anoxia has been hypothesized.

[The cardiac changes in thalassemia major: their assessment by Doppler echocardiography]. / Alterazioni cardiache nella talassemia major: valutazione con ecocardiografia Doppler.

Dilated cardiomyopathy with impaired left ventricular function is the most common cause of death in patients (pts) with Thalassemia Major (TM) undergoing multiple transfusions. To assess the cardiac status in a young population with TM, 25 pts (mean age 15.8 +/- 5.7 years) and 25 controls (sex and age matched), underwent clinical, echocardiographic and Doppler evaluation. Thirteen pts who received a correct chelation therapy had serum Ferritin (F) below, and nine pts up to 1300 ng/ml. Three out of 9 pts with F > 1300 ng/ml were symptomatic for heart failure, and echocardiography showed a dilated cardiomyopathy. All pts with F < 1300 ng/ml had a normal systolic function. Mean left ventricular (LV) diastolic dimension and LV mass index were significantly increased in pts with TM versus controls (respectively: 37.2 +/- 7.9 mm vs 30.5 +/- 4.3 mm--p < 0.001; 78.6 +/- 16.7 g vs 65.2 +/- 19.4 g--p < 0.05). Moreover, LV end-diastolic dimension was significantly increased in patients with TM having normal systolic function versus controls (36.1 +/- 7.5 mm vs 30.5 +/- 4.3 mm). No difference was found between patients with TM and controls for wall thickness nor for Doppler diastolic indexes obtained from analysis of transmitral flow. Our study suggests that a correct chelation therapy may protect pts with TM from early development of a dilated cardiomyopathy. The first echocardiographic abnormality in pts still asymptomatic and with normal systolic function seems to be an increased end diastolic LV dimension. In our experience, left ventricular filling is not altered in asymptomatic patients.