Global longitudinal strain by cardiac magnetic resonance is associated with cardiac iron and complications in beta-thalassemia major patients.

BACKGROUND: The aim of this cross-sectional study was to investigate the association of left ventricular (LV) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in patients with ß-thalassemia major (ß-TM). METHOD: We considered 266 ß-TM patients (134 females, 37.08 ±â€¯11.60 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project and 80 healthy controls (50 females, mean age 39.77 ±â€¯11.29 years). The CMR protocol included cine images for the assessment of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) using feature tracking (FT) and for the quantification of LV function parameters, the T2* technique for the assessment of myocardial iron overload, and late gadolinium enhancement (LGE) technique. RESULTS: In comparison to the healthy control group, ß-TM patients showed impaired GLS, GCS, and GRS values. Among ß-TM patients, sex was identified as the sole independent determinant of all LV strain parameters. All LV strain parameters displayed a significant correlation with LV end-diastolic volume index, end-systolic volume index, mass index, and ejection fraction, and with the number of segments exhibiting LGE. Only GLS exhibited a significant correlation with global heart T2* values and the number of segments with T2* < 20 ms. Patients with cardiac complications exhibited significantly impaired GLS compared to those without cardiac complications. CONCLUSION: In patients with ß-TM, GLS, GCS, and GRS were impaired in comparison with control subjects. Among LV strain parameters, only GLS demonstrated a significant association with cardiac iron levels and complications.

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.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (ß-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

Myocardial tissue characterization by segmental T2 mapping in thalassaemia major: detecting inflammation beyond iron.

AIMS: We measured myocardial T2 values by a segmental approach in thalassaemia major (TM) patients, comparing such values against T2* values for the detection of myocardial iron overload (MIO), evaluating their potential in detecting subclinical inflammation, and correlating with clinical status. METHODS AND RESULTS: One-hundred and sixty-six patients (102 females, 38.29 ± 11.49years) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent magnetic resonance imaging for the assessment of hepatic, pancreatic, and cardiac iron overload (T2* technique), of biventricular function (cine images), and of replacement myocardial fibrosis [late gadolinium enhancement (LGE)]. T2 and T2* values were quantified in all 16 myocardial segments, and the global value was the mean of all segments. Global heart T2 values were significantly higher in TM than in a cohort of 80 healthy subjects. T2 and T2* values were significantly correlated. Out of the 25 patients with a decreased global heart T2* value, 11 (44.0%) had reduced T2 values. No patient with a normal T2* value had a decreased T2 value.Eleven (6.6%) patients had a decreased global heart T2 value, 74 (44.6%) a normal global heart T2 value, and 81 (48.8%) an increased global heart T2 value. Biventricular function was comparable amongst the three groups, whilst LGE was significantly more frequent in patients with reduced vs. increased global heart T2 value. Compared with the other two groups, patients with reduced T2 values had significantly higher hepatic and pancreatic iron deposition. CONCLUSION: In TM, T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment but detects subclinical myocardial inflammation.

Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major.

OBJECTIVES: This multicenter study assessed the extent of pancreatic fatty replacement and its correlation with demographics, iron overload, glucose metabolism, and cardiac complications in a cohort of well-treated patients with thalassemia major (TM). METHODS: We considered 308 TM patients (median age: 39.79 years; 182 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Magnetic resonance imaging was used to quantify iron overload (IO) and pancreatic fat fraction (FF) by T2* technique, cardiac function by cine images, and to detect replacement myocardial fibrosis by late gadolinium enhancement technique. The glucose metabolism was assessed by the oral glucose tolerance test. RESULTS: Pancreatic FF was associated with age, body mass index, and history of hepatitis C virus infection. Patients with normal glucose metabolism showed a significantly lower pancreatic FF than patients with impaired fasting glucose (p = 0.030), impaired glucose tolerance (p < 0.0001), and diabetes (p < 0.0001). A normal pancreatic FF (< 6.6%) showed a negative predictive value of 100% for abnormal glucose metabolism. A pancreatic FF > 15.33% predicted the presence of abnormal glucose metabolism. Pancreas FF was inversely correlated with global pancreas and heart T2* values. A normal pancreatic FF showed a negative predictive value of 100% for cardiac iron. Pancreatic FF was significantly higher in patients with myocardial fibrosis (p = 0.002). All patients with cardiac complications had fatty replacement, and they showed a significantly higher pancreatic FF than complications-free patients (p = 0.002). CONCLUSION: Pancreatic FF is a risk marker not only for alterations of glucose metabolism, but also for cardiac iron and complications, further supporting the close link between pancreatic and cardiac disease. KEY POINTS: • In thalassemia major, pancreatic fatty replacement by MRI is a frequent clinical entity, predicted by a pancreas T2* < 20.81 ms and associated with a higher risk of alterations in glucose metabolism. • In thalassemia major, pancreatic fatty replacement is a strong risk marker for cardiac iron, replacement fibrosis, and complications, highlighting a deep connection between pancreatic and cardiac impairment.

Link between Genotype and Multi-Organ Iron and Complications in Children with Transfusion-Dependent Thalassemia.

We evaluated the impact of the genotype on hepatic, pancreatic and myocardial iron content, and on hepatic, cardiac and endocrine complications in children with transfusion-dependent ß-thalassemia (ß-TDT). We considered 68 ß-TDT patients (11.98 ± 3.67 years, 51.5% females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network. Iron overload was quantified by T2* technique and biventricular function by cine images. Replacement myocardial fibrosis was evaluated by late gadolinium enhancement technique. Three groups of patients were identified: homozygous ß+ (N = 19), compound heterozygous ß0ß+ (N = 24), and homozygous ß0 (N = 25). The homozygous ß0 group showed significantly lower global heart and pancreas T2* values than the homozygous ß+ group. Compared to patients with homozygous ß+ genotype, ß0ß+ as well as ß0ß0 patients were more likely to have pancreatic iron overload (odds ratio = 6.53 and 10.08, respectively). No difference was detected in biventricular function parameters and frequency of replacement fibrosis. No patient had cirrhosis/fibrosis, diabetes or heart failure, and the frequency of endocrinopathies was comparable among the groups. In pediatric ß-TDT patients, there is an association between genotype and cardiac and pancreatic iron overload. The knowledge of patients' genotype can be valuable in predicting some patients' phenotypic features and in helping the clinical management of ß-TDT patients.

Pain Coping Strategies in Pediatric Patients with Acute Leukemias in the First Month of Therapy: Effects of Treatments and Implications on Procedural Analgesia.

Children with leukemia experience difficulties adapting to medical procedures and to the chemotherapy's adverse effects. Study's objectives were to identify which coping strategies could be associated with the treatments' factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. A total of 125 patients (mean = 6.79 years; standard deviation = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the Pediatric Pain Coping Inventory. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2 = 0.25) showed that, weighing the age factor (F = 3.47; df = 3; p = 0.02), the number of episodes of fever (F = 4.78; df = 1; p = 0.03), nausea (F = 4.71; df = 1; p = 0.03) and mucositis (F = 5.81; df = 1; p = 0.02) influenced the use of distraction. Cognitive self-instructions (R2 = 0.22) were influenced by the number of hospitalizations (F = 5.14; df = 1; p = 0.03) and mucositis (F = 8.48; df = 3; p = 0.004) and by child's age (F = 3.76; df = 3; p = 0.01). Children who sought parental support more frequently (F = 9.7; df = 2; p = 0.0001) and who tended not to succumb to a catastrophic attitude (F = 13.33; df = 2; p = 0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social support.

Pain coping strategies in paediatric patients newly diagnosed with leukaemia compared with healthy peers.

OBJECTIVE: Children with leukaemia experience special difficulties adapting to stressful medical procedures and to the adverse effects of chemotherapy, though they can implement their coping strategies. The aims of the study were to assess whether the coping-with-pain strategies could be influenced by a child's personal and illness factors and to render possible comparisons between children with leukaemia and healthy peers. Another aim was to compare parents' and children's reports on coping strategies. METHODS: A total of 125 patients (average age = 6.79 years; SD = 3.40) with acute leukaemia (lymphocytic leukaemia 90.4% and myeloid leukaemia 9.6%) and age-matched healthy children with their parents were enrolled in the study. A socio-demographic questionnaire and the Waldon-Varni Pediatric Pain Coping Inventory, parent and self-report versions, were administered 1 month after diagnosis. Data regarding the therapy's side effects were recorded. RESULTS: The comparison between proxy-reports of the two groups of parents found significant differences in terms of social support, self-cognitive instructions and catastrophising strategies. Children aged 6-10 years relied more heavily on distraction than children of other ages, using more problem-solving and self-cognitive instructions. The results indicated moderate parent-child agreement. CONCLUSION: Health professionals could help paediatric leukaemic patients in adopting more efficiently pain coping strategies applicable for different ages.

Essential Thrombocythemia in Children and Adolescents.

This paper reviews the features of pediatric essential thrombocythemia (ET). ET is a rare disease in children, challenging pediatric and adult hematologists alike. The current WHO classification acknowledges classical Philadelphia-negative MPNs and defines diagnostic criteria, mainly encompassing adult cases. The presence of one of three driver mutations (JAK2V617F, CALR, and MPL mutations) represent the proof of clonality typical of ET. Pediatric ET cases are thus usually confronted by adult approaches. These can fit only some patients, because only 25-40% of cases present one of the driver mutations. The diagnosis of hereditary, familial thrombocytosis and the exclusion of reactive/secondary thrombocytosis must be part of the diagnostic process in children and can clarify most of the negative cases. Still, many children present a clinical, histological picture of ET, with a molecular triple wild-type status. Moreover, prognosis seems more benign, at least within the first few decades of follow-up. Thrombotic events are rare, and only minor hemorrhages are ordinarily observed. As per the management, the need to control symptoms must be balanced with the collateral effects of lifelong drug therapy. We conclude that these differences concert a compelling case for a very careful therapeutic approach and advocate for the importance of further cooperative studies.

Oncological Children and Well-Being: Occupational Performance and HRQOL Change after Fine Motor Skills Stimulation Activities.

Cancer children experience long periods of hospitalization, which are associated with limited performance in several developmental domains and participation restrictions in age appropriate occupations. Fine motor abilities represent building blocks in performing daily life skills and have been found to be closely connected with later academic success. Moreover, medical and psychological sequelae for cancer inpatients may result in diminished daily activities functioning, poor perceived health related quality of life (HRQOL), and increase the likelihood of long-term impairments. This study examines the variations in the occupational performance of children hospitalized for acute lymphoblastic leukemia (ALL) after their participation to a stimulation program designed to enhance fine motor skills. Parents reported significant gains in children's motor functioning, a slight improvement in overall occupational performance related to an increase in the area of productivity and self-care, and a better quality of life perception following the stimulation activities. Feasibility of the stimulation program in a health care setting are discussed evaluating its benefits for cancer children and their families.

CD56, HLA-DR, and CD45 recognize a subtype of childhood AML harboring CBFA2T3-GLIS2 fusion transcript.

The presence of CBFA2T3-GLIS2 fusion gene has been identified in childhood Acute Myeloid Leukemia (AML). In view of the genomic studies indicating a distinct gene expression profile, we evaluated the role of immunophenotyping in characterizing a rare subtype of AML-CBFA2T3-GLIS2 rearranged. Immunophenotypic data were obtained by studying a cohort of 20 pediatric CBFA2T3-GLIS2-AML and 77 AML patients not carrying the fusion transcript. Enrolled cases were included in the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP) AML trials and immunophenotypes were compared using different statistical approaches. By multiple computational procedures, we identified two main core antigens responsible for the identification of the CBFA2T3-GLIS2-AML. CD56 showed the highest performance in single marker evaluation (AUC = 0.89) and granted the most accurate prediction when used in combination with HLA-DR (AUC = 0.97) displaying a 93% sensitivity and 99% specificity. We also observed a weak-to-negative CD45 expression, being exceptional in AML. We here provide evidence that the combination of HLA-DR negativity and intense bright CD56 expression detects a rare and aggressive pediatric AML genetic lesion improving the diagnosis performance.

Systemic Fusariosis: A Rare Complication in Children with Acute Lymphoblastic Leukemia.

Fusarium species are ubiquitous pathogens causing opportunistic infections in immunocompromised patients. Clinical presentation depends on a host's immunity and can be localized or disseminated. Since there are few reports of disseminated fusariosis in children, we described an unusual case of Fusarium solani infection in a 9-year-old child with acute lymphoblastic leukemia (ALL). This patient presented a deep wound in the elbow at diagnosis. During the induction phase of chemotherapy, he developed multiple skin lesions and severe pneumonia; Fusarium solani was cultured from the skin lesions. He was treated with a high dose of liposomal amphotericin B, followed by voriconazole. Starting from this peculiar case, we collected all patients with acute leukemia affected by Fusarium infection, treated in the pediatric Onco-Hematology Division of Padua University Hospital during the last 20 years. We identified another six cases: all these patients were affected by acute myeloid leukemia (AML) and five of them presented a relapsed/refractory disease. Two out of seven patients died because of infection; five patients recovered from infection, but three out of seven died because of leukemia. Skin lesions in immunocompromised patients should rise the suspicion of disseminated fusariosis. Furthermore, considering the emergence of filamentous fungi in immunocompromised patients, we all should be aware of Fusarium infection, reminding us that the diagnosis is important to cure the infection.

The Close Link of Pancreatic Iron With Glucose Metabolism and With Cardiac Complications in Thalassemia Major: A Large, Multicenter Observational Study.

OBJECTIVE: We systematically explored the link of pancreatic iron with glucose metabolism and with cardiac complications in a cohort of 1,079 patients with thalassemia major (TM) enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. RESEARCH DESIGN AND METHODS: MRI was used to quantify iron overload (T2* technique) and cardiac function (cine images) and to detect macroscopic myocardial fibrosis (late gadolinium enhancement technique). Glucose metabolism was assessed by the oral glucose tolerance test (OGTT). RESULTS: Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with impaired fasting glucose, impaired glucose tolerance, and diabetes. A pancreas T2* <13.07 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for disturbances of glucose metabolism and for cardiac iron. Patients with myocardial fibrosis showed significantly lower pancreas T2* values. Patients with cardiac complications had significantly lower pancreas T2* values. No patient with arrhythmias/heart failure had a normal global pancreas T2*. CONCLUSIONS: Pancreatic iron is a powerful predictor not only for glucose metabolism but also for cardiac iron and complications, supporting the close link between pancreatic iron and heart disease and the need to intensify iron chelation therapy to prevent both alterations of glucose metabolism and cardiac iron accumulation.

Pediatric Patients Treated for Leukemia Back to School: A Mixed-Method Analysis of Narratives about Daily Life and Illness Experience.

In the last few years, more children and adolescents healed from leukemia go back to their daily life, even if they can show some psycho-social difficulties. The study adopted semi-structured interviews and a mixed-method approach to examine the narratives of 75 children and adolescents about their return to school post 2-years treatment for leukemia. The aims are to collect their illness experiences, to understand how they feel about school and daily routines and to identify the best socio-demographic and illness predictors of a good re-adaptation to school and daily life. The results show that by increasing age and when the pediatric patient have received a hematopoietic stem cell transplantation, at the stop-therapy time, her/his perception about relationships at school and academic performance decrease, especially if his/her feelings about the disease and follow-up visits are negative.

Health Locus of Control in Parents of Children with Leukemia and Associations with Their Life Perceptions and Depression Symptomatology.

In childhood cancer, parents have an important role in the promotion of their children's wellbeing and in their adoption of a locus of control style towards their children's health. The current study aimed at identifying types of locus of control in parents of children with leukemia and the possible association with depressive symptomatology and current life perception. One hundred and four parents were recruited at the Hematology-Oncology Clinic of the Department of Woman's and Child's Health, University of Padua, one month after a leukemia diagnosis. Participants were Caucasian with a mean age of 37.28 years (SD = 5.89), mostly mothers (87.5%) and with a mean of 12.16 years of education (SD = 3.82). After signing the informed consent, they filled in the Ladder of Life, the Brief Symptom Inventory-18 and the Parental Health Locus of Control (PHLOC) questionnaires. Paired-samples t-test (t = -14.42; df = 103; p = 0.0001) showed that parents of children with leukemia were more inclined to have an external locus of control than an internal one. The hierarchical regression analysis model (R2 = 0.34; F = 4.32; p = 0.0001) identified health professional influence (ß = -0.28; p = 0.004), current life perception (ß = -0.3; p = 0.013) and future life perception (ß = -0.26; p = 0.012) as significant predictors of parental depression. Current life perception was best predicted (R2 = 0.25; F = 3.96; p = 0.01) by the parental influence locus of control style (ß = 0.25; p = 0.03). Improving trust in the medical staff care and strengthening the internal locus of control in parents could be a preventive program to cope with parental depression symptomatology.

Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis.

BACKGROUND: Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS: We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS: At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).

Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality.

BACKGROUND: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce. OBJECTIVE: Our aim was to describe the natural history of XLA. METHODS: A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients' laboratory, clinical, and imaging data were recorded on an annual base. RESULTS: Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease. CONCLUSIONS: This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients' clinical management and increase awareness among physicians.

CMR for myocardial iron overload quantification: calibration curve from the MIOT Network.

OBJECTIVES: R2* cardiac magnetic resonance (CMR) allows the non-invasive measurement of myocardial iron. We calibrated cardiac R2* values against myocardial tissue-measured iron concentration by using a segmental approach and we assessed the iron distribution. METHODS: Five hearts of thalassemia patients were donated after death/transplantation to the CoreLab of the Myocardial Iron Overload in Thalassemia Network. A multislice multiecho R2* approach was adopted. After CMR, used as guidance, the heart was cut in three short-axis slices and each slice was cut into different equiangular segments according to AHA segmentation and differentiated into endocardial and epicardial layers. Tissue iron concentration was measured by atomic absorption spectrometer technique. RESULTS: Fifty-five samples were used since only for two hearts all the 16 samples were analyzed. Mean iron concentration was 4.71 ± 4.67 mg/g dw. Segmental iron levels ranged from 0.24 to 13.78 mg/g dw. The coefficient of variability of iron for myocardial segments ranged from 8.08 to 24.54% (mean 13.49 ± 6.93%). Iron concentration was significantly higher in the epicardial than in the endocardial layer (5.99 ± 6.01 vs 4.84 ± 4.87 mg/g dw; p = 0.042). Four different circumferential regions (anterior, septal, inferior, and lateral) were defined. A circumferential heterogeneity was noted, with more iron in the anterior region, followed by the inferior region. The direct nonlinear fitting of R2* and [Fe] data led to the calibration curve: [Fe] = 0.0022 ∙ (R2*-ROI)1.462 (R-square = 0.956). CONCLUSIONS: Our data further validate R2* CMR using a segmental approach as a sensitive and early technique for quantifying iron distribution in the current clinical practice. KEY POINTS: • Calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration was provided. • A circumferential heterogeneity in cardiac iron distribution was detected: more iron was observed in the anterior region, followed by the inferior region. This finding corroborates the use of a segmental T2* CMR approach in the clinical practice to detect a heterogeneous iron distribution. • The comparison between the cardiac T2* values obtained with the region-based and the pixel-wise approaches showed a significant correlation and no significant difference but, in presence of significant iron load, the region-based approach resulted in significantly higher T2* values.