Biventricular Reference Values by Body Surface Area, Age, and Gender in a Large Cohort of Well-Treated Thalassemia Major Patients Without Heart Damage Using a Multiparametric CMR Approach.

BACKGROUND: Cardiac MRI plays a critical role in the management of thalassemic patients. No accurate biventricular reference values are available. PURPOSE: To establish the ranges for normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) and LV mass normalized to body surface area (BSA), age, and gender in a large cohort of well-treated beta-thalassemia major (ß-TM) patients without heart damage using a multiparametric MRI. STUDY TYPE: Retrospective/cohort study. POPULATION: In all, 251 ß-TM patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2 * ≥20 msec, and 246 healthy subjects. FIELD STRENGTH/SEQUENCE: 1.5T/cine steady-state free precession (SSFP), gradient-echo T2 *, late gadolinium enhancement (LGE) images. ASSESSMENT: Biventricular end-diastolic volume, end-systolic volume, stroke volume, and LV mass were normalized to BSA (EDVI, ESVI, SVI). STATISTICAL TESTS: Comparisons between the two groups was performed with two-samples t-test or Wilcoxon's signed rank test. For more than two groups, one-way analysis of variance (ANOVA) or a Kruskal-Wallis test were applied. RESULTS: Compared to controls, males with ß-TM showed significantlt higher LVEDVI in all the age groups, while for the other volumes the difference was significant only within one or more age groups. In females the volumes were comparable between ß-TM patients and healthy subjects in all the age groups. In the male ß-TM population we found a significant effect of age on LVEDVI (P = 0.017), LVESVI (P = 0.001), RVESVI (P = 0.029), and RVEF (P = 0.031), while for females none of the biventricular parameters were significantly different among the age groups (LVEDVI: P = 0.614; LVESVI: P = 0.449; LVSVI: P = 0.186; LV mass index: P = 0.071; LVEF: P = 0.059; RVEDVI: P = 0.374; RVESVI: P = 0.180; RVSVI: P = 0.206; RVEF: P = 0.057). In ß-TM patients all biventricular volume indexes as well as the LV mass index were significantly larger in males than in females (P < 0.0001 in all cases). The LV and the RV EF were comparable between the sexes (P = 0.568 and P = 0.268, respectively). DATA CONCLUSION: Appropriate "normal" reference ranges normalized to BSA, sex, and age are recommended to avoid misdiagnosis of cardiomyopathy in ß-TM patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Changing patterns of thalassaemia in Italy: a WebThal perspective.

BACKGROUND: Migration has impacted the spread of thalassaemia which is gradually becoming a global health problem. Italy, with an approximate estimation of 7,000 patients, does not have an accurate national record for haemoglobinopathies. This cross-sectional evaluation includes data for approximately 50% of beta-thalassaemia patients in Italy to provide an overview of the burden of thalassaemia syndromes. MATERIALS AND METHODS: The analysis included data on epidemiology, transfusions and clinical parameters from 3,986 thalassaemia patients treated at 36 centres in Italy who were alive on 31st December 2017. The study used WebThal, a computerised clinical record that is completely free-of-charge and that does not have any mandatory fields to be filled. RESULTS: For patients with thalassaemia major, 68% were aged ≥35 years and 11% were aged ≤18 years. Patients with thalassaemia intermedia were slightly older. Transfusion data, reported in a subgroup of 1,162 patients, showed 9% had pre-transfusion haemoglobin <9 g/dL, 63% had levels between ≥9 and <10 g/dL, and 28% had levels ≥10 g/dL. These 1,162 patients underwent 22,272 transfusion days during 2017, with a mean of 19 transfusion days/year/patient (range 1-54 days). Severity of iron overload was reported in 756 patients; many had moderate or mild liver iron load (74% had liver iron <7.5 mg/g dry weight). In the same cohort, 85% of patients had no signs of cardiac iron load (MRT2* >20 ms), and only 3% showed signs of high-risk heart condition (T2* <10 ms). Most patients had normal alanine amino transferase levels due to treatment with the new anti-hepatitis C virus (HCV) drugs. DISCUSSION: This study provides an overview of the current health status of patients with thalassaemia in Italy. Moreover, these data support the need for a national comprehensive thalassaemia registry.

Relationship between uric acid levels and cardiometabolic findings in a large cohort of ß-thalassemia major patients.

AIM: to evaluate the relationship between uric acid (UA), hepatic and cardiac iron overload (T2*-MRI), ferritin, endocrinological diseases and cardiac complications in a large thalassemia major (TM) cohort. METHODS: A total of 369 TM patients (187 men; 33 ± 6 years) were retrospectively studied, from the myocardial iron overload in thalassemia (MIOT) electronic databank. RESULTS: Multiple regression model identified male sex (p < 0.001), BMI (p < 0.001) and T2* (p ≤ 0.001) as UA independent correlates. Moreover, UA and derivatives of reactive oxygen species (an oxidative index; r = -0.3; p ≤ 0.05) are inversely correlated. Conversely, the multivariate logistic analysis identified low UA (NANHES-III criteria) as one independent predictor for low global heart T2* (p < 0.5) together with liver iron concentrations (>3 mg/g/dw), heart failure, endocrinopathies, ferritin (>2000 ng/l), alanine transaminase (>40 UI/l) and/or aspartate transaminase (>35 UI/l) and/or glutamyl transferase (>64 UI/l). DISCUSSION: UA appears directly associated to T2* and inversely with derivatives of reactive oxygen species, and as such reduced according to increased oxidative stress and cardiac iron overload in TM patients.

Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major.

BACKGROUND: The multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. METHODS: We considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. RESULTS: We identified 4 groups of patients: 138 with homogeneous MIO (all segments with T2* < 20 ms), 97 with heterogeneous MIO (some segments with T2* < 20 ms, others with T2* ≥ 20 ms) and significant global heart iron (global heart T2* < 20 ms), 238 with heterogeneous MIO and no significant global heart iron, and 339 with no MIO (all segments with T2* ≥ 20 ms). Compared to patients with no MIO, patients with homogeneous MIO were more likely to have cardiac complications (odds ratio-OR = 2.67), heart failure (OR = 2.54), LV dysfunction (OR = 5.59), and RV dysfunction (OR = 2.26); patients with heterogeneous MIO and significant global heart iron were more likely to have heart failure (OR = 2.38) and LV dysfunction (OR = 2.39). CONCLUSIONS: Cardiac complications, heart failure and dysfunction were correlated with MIO distribution with an increasing risk from the TM patients with no MIO to those with homogeneous MIO. Using a segmental approach, early iron deposit or homogeneous MIO patterns can be characterized to better tailor chelation therapy.

Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study.

The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non-DM patients we found a significantly higher frequency of cardiac complications (46.5% vs. 16.9%, P < 0.0001), heart failure (HF) (30.2% vs. 11.7%, P < 0.0001), hyperkinetic arrhythmias (18.6% vs. 5.5%, P < 0.0001) and myocardial fibrosis assessed by late gadolinium enhancement (29.9% vs. 18.4%, P = 0.008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2.84, P < 0.0001], HF (OR 2.32, P = 0.003), hyperkinetic arrhythmias (OR 2.21, P = 0.023) and myocardial fibrosis (OR 1.91, P = 0.021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co-morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.

Feasibility, reproducibility, and reliability for the T*2 iron evaluation at 3 T in comparison with 1.5 T.

This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T*(2) Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T*(2) values at 3 and 1.5 T. Thirty-eight transfusion-dependent patients and 20 healthy subjects were studied. Cardiac segmental and global T*(2) values were calculated after developing a correction map to compensate the artifactual T*(2) variations. The hepatic T*(2) value was determined over a region of interest. The intraoperator and interoperator reproducibility for T*(2) measurements at 3 T was good. A linear relationship was found between patients' R *2 (1000/T*(2) ) values at 3 and 1.5 T. Segmental correction factors were significantly higher at 3 T. A conversion formula returning T*(2) values at 1.5 T from values at 3 T was proposed. A good diagnostic reliability for T*(2) assessment at 3 T was demonstrated. Lower limits of normal for 3 T T*(2) values were 23.3 ms, 21.1 ms, and 11.7 ms, for the global heart, mid-ventricular septum, and liver, respectively. In conclusion, T*(2) quantification of iron burden in the mid-ventricular septum, global heart, and no heavy-moderate livers resulted to be feasible, reproducible, and reliable at 3 T. Segmental heart T*(2) analysis at 3 T may be challenging due to significantly higher susceptibility artifacts.