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

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

Multiparametric cardiac magnetic resonance in patients with thalassemia intermedia: new insights from the E-MIOT network.

PURPOSE: In a relatively large cohort of thalassemia intermedia (TI) patients, we systematically investigated myocardial iron overload (MIO), function, and replacement fibrosis using cardiac magnetic resonance (CMR), we assessed the clinical determinants of global heart T2* values, and we explored the association between multiparametric CMR findings and cardiac complications. MATERIALS AND METHODS: We considered 254 beta-TI patients (43.14 ± 13.69 years, 138 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. MIO was quantified by T2* technique and biventricular function and atrial areas by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. RESULTS: Compared to never/sporadically transfused patients, regularly transfused (RT)-TI patients exhibited significantly lower global heart T2* values, biventricular end-diastolic volume indexes, left ventricular mass index, and cardiac index. In RT-TI patients, age and serum ferritin levels were the strongest predictors of global heart T2* values. Independently from the transfusional state, cardiac T2* values were not associated with biventricular function. Of the 103 (40.6%) patients in whom the contrast medium was administrated, 27 (26.2%) had replacement myocardial fibrosis. Age, sex distribution, cardiac iron, and biventricular function parameters were comparable between patients without and without replacement myocardial fibrosis. Twenty-five (9.8%) patients had a history of cardiac complications (heart failure and arrhythmias). Increased age and replacement myocardial fibrosis emerged as significant risk markers for cardiac complications. CONCLUSIONS: In TI, regular transfusions are associated with less pronounced cardiac remodeling but increase the risk of MIO. Replacement myocardial fibrosis is a frequent finding associated with cardiac complications.

Left and right atrioventricular coupling index in patients with beta-thalassemia major.

The aim of this cross-sectional study was to investigate the relationship of left atrioventricular coupling index (LACI) and right atrioventricular coupling index (RACI) with demographics, clinical data, cardiovascular magnetic resonance findings, and cardiac complications (heart failure, arrhythmias, and pulmonary hypertension) in a cohort of patients with beta-thalassemia major (ß-TM). We evaluated 292 ß-TM patients (151 females, 36.72 ± 11.76 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. Moreover, we assessed 32 sex- and age-matched healthy controls (12 females, mean age 40.78 ± 14.35 years). LACI was determined by calculating the ratio of the left atrium end-diastolic volume to the left ventricle end-diastolic volume, while RACI was defined by calculating the ratio of the right atrium end-diastolic volume to the right ventricle end-diastolic volume. Compared to healthy control, ß-TM demonstrated increased LACI (22.99 ± 13.58% vs. 16.05 ± 5.28%; p < 0.0001) and RACI (27.84 ± 10.30% vs. 17.06 ± 5.03%; p < 0.0001). Aging, diabetes, splenectomy, and the presence of late gadolinium enhancement (LGE) showed a significant positive association with both LACI and RACI. In stepwise regression analysis, the presence of LGE was found to be an independent predictor of both impaired LACI and RACI (ß coefficient = 0.244, p < 0.0001 and ß coefficient = 0.218, p = 0.003; respectively). LACI and RACI were not correlated with myocardial iron overload. Patients with cardiac complications had significantly higher LACI and RACI than patients without cardiac complications. In patients with ß-TM, LACI and RACI were significantly associated with the presence of LV LGE. In addition, patients with cardiac complications had impaired LACI and RACI.

Bone status and HCV infection in thalassemia major patients.

PURPOSE: Hepatitis C virus (HCV) infection increases the risk for osteoporosis but this relationship has not been investigated among multi-transfused patients with thalassemia major (TM). We cross-sectionally explored the association of HCV infection with bone mineral density (BMD), vitamin D, and bone turnover biomarkers in TM. METHODS: We considered 130 TM patients (41.89 ± 5.49 years, 67 females) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) Network. BMD measurements taken at the lumbar spine, femoral neck and total hip were expressed as Z-scores, with a BMD Z-score ≤ -2.0 indicating low bone mass. RESULTS: Z-scores were not associated with gender, iron overload indices, vitamin D levels, and biochemical bone turnover markers, but decreased with aging and in presence of hypogonadism and were directly correlated with body mass index (BMI). The prevalence of low bone mass was 70.7 %. Three groups of patients were identified: 78 who never contracted the infection (group 0), 72 who cleared HCV (group 1), and 29 with chronic HCV infection (CHC) (group 2). All Z-scores progressively decreased according to HCV status from group 0 to group 2. Osteocalcin levels were significantly lower in groups 2 and 1 than in group 0. CHC patients were more likely to have low bone mass compared to HCV naive patients, after adjusting for age, BMI, hypogonadism, and pancreatic iron. CONCLUSION: In TM, CHC appears as one additive risk factor for low bone mass and osteocalcin may play a role in this association.

Pancreatic T2* Magnetic Resonance Imaging for Prediction of Cardiac Arrhythmias in Transfusion-Dependent Thalassemia.

We assessed the value of pancreatic T2* magnetic resonance imaging (MRI) for predicting cardiac events from a large prospective database of transfusion-dependent thalassemia (TDT) patients. We considered 813 TDT patients (36.47 ± 10.71 years, 54.6% females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. MRI was used to measure hepatic, pancreatic, and cardiac iron overload (IO), to assess biventricular function and atrial dimensions, and to detect replacement myocardial fibrosis. The mean follow-up was 50.51 ± 19.75 months. Cardiac complications were recorded in 21 (2.6%) patients: one with heart failure (HF) and 20 with arrhythmias. The single patient who developed HF had, at the baseline MRI, a reduced pancreas T2*. Out of the 20 recorded arrhythmias, 17 were supraventricular. Pancreatic T2* values were a significant predictor of future arrhythmia-related events (hazard ratio = 0.89; p = 0.015). Pancreas T2* remained significantly associated with future arrhythmias after adjusting for any other univariate predictor (age and male sex, diabetes, history of previous arrhythmias, or left atrial area index). According to the receiver-operating characteristic curve analysis for arrhythmias, a pancreas T2* < 6.73 ms was the optimal cut-off value. In TDT, pancreatic iron levels had significant prognostic power for arrhythmias. Regular monitoring and the development of targeted interventions to manage pancreatic IO may help improve patient outcomes.

Gender Differences in Knowledge and Perception of Cardiovascular Disease among Italian Thalassemia Major Patients.

We evaluated gender differences in knowledge and perception of cardiovascular disease (CVD) among Italian thalassemia major (TM) patients. An anonymous questionnaire was completed by 139 ß-TM patients (87 (62.7%) females, 40.90 ± 8.03 years). Compared to females, males showed a significantly higher frequency of CVDs, and they less frequently selected tumors in general as the greatest health problem for people of the same age and gender (48.1% vs. 66.7%; p = 0.031) and as the greatest danger to their future health (26.9% vs. 43.7%; p = 0.048). CVDs were designated as the greatest danger to their future health by a significantly higher percentage of males than females (53.8% vs. 36.8%; p = 0.048). Both males and females showed a good knowledge of cardiovascular risk factors and preventive measures for CVDs. No gender differences were detected in the subjective well-being and the perceived cardiovascular risk. The perceived risk was not influenced by age, presence of cardiovascular risk factors, or disease, but no patient with a low perceived CVD risk had myocardial iron overload. Our findings highlight the need to implement future educational programs aimed at increasing the awareness of CVD as the greatest health issue, especially among the female TM population, and at informing TM patients of the different actors, besides iron, that play a role in the development of cardiovascular complications.