Prognostic Role of Multiparametric Cardiac Magnetic Resonance in Neo Transfusion-Dependent Thalassemia.

BACKGROUND: We prospectively evaluated the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in non-transfusion-dependent ß-thalassemia (ß-NTDT) patients who started regular transfusions in late childhood/adulthood (neo ß-TDT). METHODS: We considered 180 patients (38.25 ± 11.24 years; 106 females). CMR was used to quantify cardiac iron overload, biventricular function, and atrial dimensions, and to detect left ventricular (LV) replacement fibrosis. RESULTS: During a mean follow-up of 76.87 ± 41.60 months, 18 (10.0%) cardiovascular events were recorded: 2 heart failures, 13 arrhythmias (10 supraventricular), and 3 cases of pulmonary hypertension. Right ventricular (RV) end-diastolic volume index (EDVI), RV mass index (MI), LV replacement fibrosis, and right atrial (RA) area index emerged as significant univariate prognosticators of cardiovascular complications. The low number of events prevented us from performing a multivariable analysis including all univariable predictors simultaneously. Firstly, a multivariable analysis including the two RV size parameters (mass and volume) was carried out, and only the RV MI was proven to independently predict cardiovascular diseases. Then, a multivariable analysis, including RV MI, RA atrial area, and LV replacement fibrosis, was conducted. In this model, RV MI and LV replacement fibrosis emerged as independent predictors of cardiovascular outcomes (RV MI: hazard ratio (HR) = 1.18; LV replacement fibrosis: HR = 6.26). CONCLUSIONS: Our results highlight the importance of CMR in cardiovascular risk stratification.

It's a long way to the top! Congenital venous anomalies and left isomerism limiting atrial fibrillation transcatheter ablation.

BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia in adults and it is associated with a high burden of mortality and morbidity worldwide. Catheter ablation is increasingly used to improve symptoms and prognosis in selected patients. Lower limb venous access with subsequent transseptal approach to the left atrium is the standard procedure for atrial fibrillation catheter ablation. CASE PRESENTATION: We report an unusual case of complex venous anomaly with a left-sided inferior vena cava with hemiazygos continuation to a persistent left superior vena cava draining in an enlarged coronary sinus in a patient with persistent atrial fibrillation scheduled for transcatheter ablation. DISCUSSION: Lower limb venous anomalies may limit a standard transseptal approach to the left atrium thus precluding an effective catheter ablation procedure for atrial fibrillation. Alternative interventions, such as unconventional percutaneous access, thoracoscopic approach and "ablate and pace" procedures, may be necessary in patients with symptomatic atrial fibrillation and complex venous anomalies.

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.

Preoperative Tumor Texture Analysis on MRI for High-Risk Disease Prediction in Endometrial Cancer: A Hypothesis-Generating Study.

OBJECTIVE: To develop and validate magnetic resonance (MR) imaging-based radiomics models for high-risk endometrial cancer (EC) prediction preoperatively, to be able to estimate deep myometrial invasion (DMI) and lymphovascular space invasion (LVSI), and to discriminate between low-risk and other categories of risk as proposed by ESGO/ESTRO/ESP (European Society of Gynaecological Oncology-European Society for Radiotherapy & Oncology and European Society of Pathology) guidelines. METHODS: This retrospective study included 96 women with EC who underwent 1.5-T MR imaging before surgical staging between April 2009 and May 2019 in two referral centers divided into training (T = 73) and validation cohorts (V = 23). Radiomics features were extracted using the MODDICOM library with manual delineation of whole-tumor volume on MR images (axial T2-weighted). Diagnostic performances of radiomic models were evaluated by area under the receiver operating characteristic (ROC) curve in training (AUCT) and validation (AUCV) cohorts by using a subset of the most relevant texture features tested individually in univariate analysis using Wilcoxon-Mann-Whitney. RESULTS: A total of 228 radiomics features were extracted and ultimately limited to 38 for DMI, 29 for LVSI, and 15 for risk-classes prediction for logistic radiomic modeling. Whole-tumor radiomic models yielded an AUCT/AUCV of 0.85/0.68 in DMI estimation, 0.92/0.81 in LVSI prediction, and 0.84/0.76 for differentiating low-risk vs other risk classes (intermediate/high-intermediate/high). CONCLUSION: MRI-based radiomics has great potential in developing advanced prognostication in EC.

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.

Prospective cardiac magnetic resonance imaging survey in myelodysplastic syndrome patients: insights from an Italian network.

We prospectively evaluated changes in cardiac and hepatic iron overload (IO) and in morpho-functional cardiac parameters and myocardial fibrosis by magnetic resonance imaging (MRI) in patients with low-risk and intermediate-1-risk myelodysplastic syndromes (MDS). Fifty patients enrolled in the Myocardial Iron Overload in MyElodysplastic Diseases (MIOMED) study were followed for 12 months. IO was quantified by the T2* technique and biventricular function parameters by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Twenty-eight patients (71.89±8.46 years; 8 females) performed baseline and follow-up MRIs. Thirteen patients had baseline hepatic IO, with a higher frequency among transfusion-dependent patients. Out of the 15 patients with a baseline MRI liver iron concentration <3 mg/g/dw, two (non-chelated) developed hepatic IO. Thirteen (46.4%) patients had an abnormal T2* value in at least one myocardial segment. One patient without hepatic IO and non-transfused had baseline global T2* <20 ms. Among the 15 patients with no baseline myocardial IO (MIO), 2 worsened. There was a significant increase in both left and right ventricular end-diastolic volume indexes. Thirty-six percent of patients showed myocardial fibrosis correlating with aging. Two new occurrences were detected at the follow-up. In conclusion, by a more sensitive segmental approach, MIO is quite frequent in MDS patients and it can be present also in non-transfused patients and in absence of detectable hepatic iron. The incidence of cardiac and hepatic IO and of myocardial fibrosis and the increase in biventricular volumes after a 12-month interval suggest performing periodic MRI scans to better manage MDS patients.

Cardiac involvement by CMR in different genotypic groups of thalassemia major patients.

Beta thalassemia major (ß-TM) displays a great deal of phenotypic heterogeneity, not fully investigated in terms of cause-effect. We aimed to detect if different genotypic groups could be related to different levels of cardiac impairment, evaluated by cardiovascular magnetic resonance (CMR). We considered 671 ß-TM patients (age 30.1 years, 52.9% females) consecutively enrolled in the Myocardial Iron Overload (MIO) in Thalassemia network. MIO was assessed by T2* technique. Biventricular function was quantified by cine images. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Three groups of patients were identified: heterozygotes ß+/ß° (N = 279), homozygotes ß + (N = 154), homozygotes ß° (N = 238). Transfusional needs resulted significantly lower in homozygous ß + TM patients when compared to the other groups. The homozygous ß + group versus the heterozygous and homozygous ß° groups showed higher global heart T2* values (P < 0.0001) and a lower number of patients with a global heart T2* value<20 ms (P < 0.001). The homozygotes ß + showed a lower number of patients with a pathological left ventricular ejection fraction (LVEF) than the other two groups (P < 0.05). The ß+/ß + TM patients showed less MIO and a concordant better systolic heart function. These data support the knowledge of different genotypic groups in the management of ß-TM patients.

Multicenter validation of the magnetic resonance T2* technique for quantification of pancreatic iron.

OBJECTIVES: To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for pancreatic iron overload assessment. METHODS: Multiecho T2* sequences were installed on ten 1.5-T MRI scanners of the three main vendors. Five healthy subjects (n = 50) were scanned at each site. Five patients with thalassemia (n = 45) were scanned locally at each site and were rescanned at the reference site within 1 month. T2* images were analyzed using a previously validated software and the global pancreatic T2* value was calculated as the mean of T2* values over the head, body, and tail. RESULTS: T2* values of healthy subjects were above 26 ms and showed inter-site homogeneity. The T2* values measured in the MRI sites were comparable to the correspondent values observed in the reference site (12.02 ± 10.20 ms vs 11.98 ± 10.47 ms; p = 0.808), and the correlation coefficient was 0.978 (p < 0.0001). Coefficients of variation (CoVs) ranged from 4.22 to 9.77%, and the CoV for all the T2* values independently from the sites was 8.55%. The intraclass correlation coefficient (ICC) for each MRI site was always excellent and the global ICC was 0.995, independently from the sites. The mean absolute difference in patients with pancreatic iron (n = 39) was -0.15 ± 1.38 ms. CONCLUSION: The gradient-echo T2* MRI technique is an accurate and reproducible means for the quantification of pancreatic iron and may be transferred among MRI scanners by different vendors in several centers. KEY POINTS: • The gradient-echo T2* MRI technique is an accurate and reproducible means for the quantification of pancreatic iron. • The gradient-echo T2* MRI technique for the quantification of pancreatic iron may be transferred among MRI scanners by different vendors in several centers. • Pancreatic iron might serve as an early predictor of cardiac siderosis and is the strongest overall predictor of glucose dysregulation.

MRI multicentre prospective survey in thalassaemia major patients treated with deferasirox versus deferiprone and desferrioxamine.

We prospectively assessed the efficacy of deferasirox versus deferiprone or desferrioxamine as monotherapy in thalassaemia major (TM) patients by magnetic resonance imaging (MRI). We selected the patients enrolled in the Myocardial Iron Overload in Thalassaemia network who received only one chelator between two MRIs (deferasirox = 235, deferiprone = 142, desferrioxamine = 162). Iron overload was measured by T2* technique and biventricular function by cine images. Among the patients with baseline myocardial iron, in all three groups there was a significant improvement in global heart T2* values. The deferiprone and desferrioxamine groups showed a significant improvement in left ventricular ejection fraction (LVEF). Only the deferiprone group showed a significant improvement in right ventricular ejection fraction (RVEF). The improvement in global heart T2* was significantly lower in the deferasirox versus the deferiprone group. The improvement in the LVEF was significantly higher in the deferiprone and desferrioxamine groups than in the deferasirox group and the improvement in the RVEF was significantly higher in the deferiprone than in deferasirox group. Among the patients with baseline hepatic iron, the changes in hepatic iron were comparable in deferasirox versus the other groups. Deferasirox monotherapy was less effective than deferiprone in improving myocardial siderosis and biventricular function and less effective than desferrioxamine in improving the LVEF.

Myocardial fibrosis by late gadolinium enhancement cardiac magnetic resonance and hepatitis C virus infection in thalassemia major patients.

AIMS: Our aim was to evaluate the correlation between myocardial fibrosis detected using the late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) technique and chronic hepatitis C (CHC) in a large, retrospective, multicentre cohort of thalassemia major patients. METHODS: LGE images were acquired in 434 thalassemia major patients (233 men, 31 ±â€Š9 years) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) study. Hepatitis C virus (HCV)-RNA tests were sensitive to detect more than 50  copies/ml. RESULTS: No patient manifested moderate/severe adverse events associated with the use of Gadobutrol. Myocardial fibrosis was detected in 90 (21%) patients. Among the 312 patients tested for HCV-RNA, there was a significant correlation between the presence of myocardial fibrosis and CHC (P = 0.011). Among the 62 patients with myocardial fibrosis tested for HCV-RNA, we found a significantly higher prevalence of diabetes mellitus in CHC patients versus the no-CHC patients (P = 0.049). CONCLUSION: Our findings support the use of the LGE CMR approach well tolerated in the thalassemia major patients with CHC. HCV infection can be involved in the pathogenesis of myocardial fibrosis through both myocarditis directly and the pancreas and liver damage with the development of diabetes indirectly. These patients could therefore benefit from cardioactive drugs and therapeutic interventions directed towards the eradication of virus.

Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy.

AIMS: [Formula: see text] multislice multiecho cardiac magnetic resonance (CMR) allows quantification of the segmental distribution of myocardial iron overload (MIO). We evaluated whether a preferential pattern MIO was preserved between two CMR scans in regularly chelated thalassaemia major (TM) patients. METHODS AND RESULTS: We evaluated prospectively 259 TM patients enrolled in the MIO in Thalassaemia (MIOT) network with a CMR follow-up (FU) study at 18 ± 3 months and significant MIO at baseline. The [Formula: see text] in the 16 segments and the global value were calculated. Four main circumferential regions (anterior, septal, inferior and lateral) were defined. We identified two groups: severe (n = 80, global [Formula: see text] <10 ms) and mild-moderate MIO (n = 179, global [Formula: see text] = 10-26 ms). Based on the CMR reports, 56.4% of patients changed the chelation regimen. For each group, there was a significant improvement in the global heart as well as in regional [Formula: see text] values (P < 0.0001). At the baseline, the mean [Formula: see text] value over the anterior region was significantly lower than the values over the other regions, and the mean [Formula: see text] over the inferior region was significantly lower than the values over the septal and the lateral regions. The same pattern was present at the FU, with a little difference for patients with mild-moderate MIO. CONCLUSION: A preferential pattern of iron store in anterior and inferior regions was present at both CMRs, with an increment of [Formula: see text] values at FU due to a baseline CMR-guided chelation therapy. The anterior region seems the region in which the iron accumulates first and is removed later.

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.

Italian registry of cardiac magnetic resonance.

OBJECTIVES: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). MATERIALS AND METHODS: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1-92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. RESULTS: Exams were performed with 1.5T scanners in 96% of cases followed by 3T (3%) and 1T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. CONCLUSIONS: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile.

Can radicality of surgery be safely modulated on the basis of MRI and PET/CT imaging in locally advanced cervical cancer patients administered preoperative treatment?

BACKGROUND: The goal of this study was to prospectively analyze the diagnostic performances of magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT) in predicting pathologically assessed residual disease in a large, single-institution series of locally advanced cervical cancer (LACC) patients triaged to neoadjuvant treatments followed by radical surgery. METHODS: Between April 2007 and March 2010, 96 patients with histologically documented cervical cancer (any histology) and FIGO stage IB2-IVA were enrolled. MRI and PET/CT were recommended to be performed within 4-6 weeks from the end of treatment, and histology was the reference standard. Sensitivity, specificity, and accuracy were compared using the McNemar test. RESULTS: For residual disease in the cervix, sensitivity was higher for MRI than for PET/CT (86.1% vs 63.1%; P = .002), while specificity was significantly higher for PET/CT compared with MRI (P = .002). There was no difference in accuracy values between the 2 imaging modalities. For MRI analysis of lymph node groups, sensitivity, specificity, and accuracy were 35.7%, 95.9%, and 88.0%, respectively. Conversely, sensitivity, specificity, and accuracy for PET/CT were 28.6%, 97.8%, and 88.7%, respectively. Absence of follicular structures replaced by prevalent sclerosis and/or sinus histiocytosis was the most frequently documented morphological pattern in false-positive cases. CONCLUSION: Neither MRI nor PET/CT accurately detected residual disease in LACC patients triaged to radical surgery after neoadjuvant treatment, disallowing the option of avoiding or modulating completion surgery.

Regional and global pancreatic T*2 MRI for iron overload assessment in a large cohort of healthy subjects: normal values and correlation with age and gender.

Multiecho gradient-echo T*2 magnetic resonance imaging is a well-established technique for iron overload assessment but there are few reports concerning the pancreas. The aim of this work was to assess the feasibility and reproducibility of the magnetic resonance imaging for measuring pancreatic regional and global T*2 values, to establish the lower limit of normal in a large cohort of healthy subjects and to correlate the measured values with age and gender. One hundred and twenty healthy subjects (61 males, 51±17 years) underwent magnetic resonance imaging (1.5T) using a multiecho gradient-echo T*2 sequence. T*2 measurements were performed in pancreatic head, body, and tail. The global value was calculated as the mean. Measurement of pancreatic T*2 values was feasible in all subjects. For the T*2 global value the coefficient of variation for intraoperator and interoperator reproducibility were 7.7% and 13%, respectively. The global T*2 values ranged from 24 to 52 ms with the lower limit of normal of 26 ms. There were no significant differences among the regional pancreatic T*2 values. No significant correlation was found between T*2 and patient age or gender. In conclusion, pancreatic T*2 measurements appear to be feasible, reproducible, nontime-consuming and reliable. Gender- and age-related differences concerning pancreatic T*2 were not found.

Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload.

PURPOSE: To evaluate the effectiveness of the single ROI approach for the detection of hepatic iron burden in thalassemia major (TM) patients in respect to a whole liver measurement. MATERIALS AND METHODS: Five transverse hepatic slices were acquired by a T2* gradient-echo sequence in 101 TM patients and 20 healthy subjects. The T2* value was calculated in a single region of interest (ROI) defined in the medium-hepatic slice. Moreover, the T2* value was extracted on each of the eight ROIs defined in the functionally independent segments. The mean hepatic T2* value was calculated. RESULTS: For patients, the mean T2* values over segments VII and VIII were significantly lower. This pattern was substantially preserved in the two groups identified considering the T2* normal cutoff. All segmental T2* values were correlated with the single ROI T2* value. After the application of a correction map based on T2* fluctuations in the healthy subjects, no significant differences were found in the segmental T2* values. CONCLUSION: Hepatic T2* variations are low and due to artifacts and measurement variability. The single ROI approach can be adopted in the clinical arena, taking care to avoid the susceptibility artifacts, occurring mainly in segments VII and VIII.

Endometrial cancer arising in both horns of didelphys uterus in a Down's syndrome woman.

BACKGROUND: There are only few reports of endometrial cancer arising in patients with uterine malformations. Down's syndrome is characterized by a reduced risk of solid tumors, and there are no reports about its correlation with uterine malformations. CASE: An endometrial adenocarcinoma arising in both horns of a didelphys uterus of a Down's syndrome woman. CONCLUSION: Uterine malformations and genetical disorders may cause a delayed diagnosis of gynecological cancers. Gynecological examination in asymptomatic patients and differential diagnosis in abnormal uterine bleeding patients should be considered.