Vincenzo Positano

Cardiac computed tomography (CCT) has emerged as a central imaging modality in the workflow for left atrial appendage occlusion (LAAO), as accurate anatomical assessment is vital for successful intervention. CCT provides superior three-dimensional (3D) anatomical detail and isotropic spatial resolution compared to traditional trans-esophageal echocardiography, enabling precise pre-procedural planning, device sizing, and identification of optimal fluoroscopic projections. Furthermore, CCT serves as a highly accurate, non-invasive tool for detecting post-procedural complications such as peri-device leaks and device-related thrombosis. Beyond conventional imaging, CCT-derived datasets now facilitate advanced computational applications, including patient-specific 3D printing, computational fluid dynamics, and finite element modeling, to predict device-tissue interactions and post-implant hemodynamics. Additionally, artificial intelligence is increasingly integrated to automate segmentation and enhance risk stratification. This review provides a comprehensive overview of the expanding role of CCT in LAAO, highlighting its contribution to procedural optimization and the transition toward personalized, engineering-driven cardiac interventions.

Summary: This multicentre cross‐sectional study evaluated whether pancreatic iron loading could serve as a reliable biomarker for the identification of endocrine disorders in transfusion‐dependent thalassaemia (TDT) patients. A total of 994 adult TDT patients (53.7% female; 39.2 ± 8.3 years) from the Extension‐Myocardial Iron Overload in Thalassemia network underwent R2* magnetic resonance imaging to quantify hepatic, pancreatic and cardiac iron. Endocrine disorders (diabetes, hypogonadism, hypothyroidism, hypoparathyroidism and growth hormone deficiency) were diagnosed using standardized clinical criteria. Overall, 60.4% of patients had at least one endocrine disorder. Pancreatic R2* was significantly higher in patients with endocrine disorders compared to those without. Multivariable regression analysis identified age, splenectomy, pancreatic R2* and cardiac R2* as independent predictors of endocrine dysfunction, with a significant interaction between pancreatic and cardiac iron. A pancreatic R2* > 80.86 Hz was the best cut‐off for predicting endocrine disorders. Pancreatic R2* remained a significant predictor of endocrine disorders even after excluding diabetic patients. Pancreatic iron increased with endocrine severity, being the highest in patients with multiple endocrinopathies, intermediate in those with a single disorder and the lowest in those without endocrine involvement. Pancreatic iron appears to act as a ‘sentinel’ marker for extra‐hepatic toxicity, supporting its integration into routine risk stratification.

Objectives: This multicenter cross-sectional study investigated the relationship between age and organ-specific iron burden and characterized multi-organ iron phenotypes across different age groups in adults with non-transfusion-dependent thalassemia (NTDT). Methods: We retrospectively evaluated 96 adults with NTDT enrolled in the multicenter Italian Extension-Myocardial Iron Overload in Thalassemia network. Hepatic, pancreatic, and cardiac iron burden were assessed by quantitative magnetic resonance imaging (MRI). Results: The median age was 41.64 (36.08–53.92) years. Hepatic iron overload (IO) was present in 59.4% of patients and pancreatic IO in 29.2%, whereas no patient exhibited myocardial IO. Age was not associated with liver iron concentration (LIC) or cardiac R2*. A weak positive correlation was observed between age and pancreatic R2* (R = 0.215, p = 0.035), although this association was no longer significant after the exclusion of one extreme value. LIC and pancreatic R2* were not correlated. Across age groups (<40, 40–59, and ≥60 years), the prevalence of pancreatic IO increased (22.9%, 28.6%, and 50.0%, respectively), whereas hepatic IO remained stable. Isolated hepatic IO was the most common phenotype overall, while combined hepatic and pancreatic IO was more frequent among patients aged ≥60 years. Conclusions: In adults with NTDT, age was not associated with greater hepatic or cardiac iron burden, whereas older patients showed a higher prevalence of pancreatic iron accumulation and combined hepatic–pancreatic iron involvement. These findings highlight the organ-specific heterogeneity of iron distribution in NTDT and support the role of multi-organ MRI assessment beyond LIC evaluation, particularly in older patients.

Background/Objectives: We measured hepatic T2*, T1, and T2 values in N = 81 transfusion-dependent thalassemia (TDT) patients to assess and compare their reproducibility, evaluate their correlations with demographics and clinical parameters, and explore their association with disease-related complications. Methods: All TDT patients (52 females, 38.13 ± 10.79 years), were enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network. The magnetic resonance imaging protocol (1.5 T) included: multi-echo gradient echo sequences for T2* relaxometry, modified look-locker inversion recovery (MOLLI) sequences for T1 mapping, and multi-echo fast-spin-echo (MEFSE) sequences for T2 mapping. Results: All three relaxation times demonstrated good intra- and inter-observer reproducibility and were significantly correlated with each other. Of the 59 patients with reduced T2*, 45 (76.3%) also had reduced T1, and 42 (71.2%) had reduced T2 values. Among 22 patients with normal T2*, 3 (13.6%) exhibited reduced T1. No patients showed increased T1, and only one had elevated T2. Liver relaxation times were not associated with gender or splenectomy status. All relaxation times inversely correlated with serum ferritin levels, while T2 and T2* inversely correlated with mean alanine aminotransferase levels. Cirrhosis and glucose metabolism alterations were associated with lower relaxation times. All three relaxation times effectively discriminated between the absence and presence of cirrhosis [areas under the curve (AUCs) with 95% confidence intervals (CIs): 0.85 (0.75–0.92) for T2*, 0.78 (0.68–0.87) for T1, and 0.92 (0.84–0.97) for T2]. T2* showed comparable accuracy to T1 and T2, while a significant difference was observed between T1 and T2 values. All liver relaxation times demonstrated similar diagnostic performance in identifying glucose metabolism alterations [AUCs with 95% CIs: 0.67 (0.55–0.77) for T2*, 0.69 (0.57–0.79) for T1, and 0.67 (0.56–0.77) for T2]. Conclusions: In TDT, a comprehensive assessment of hepatic relaxation times may enhance clinical monitoring and management of iron overload and its related complications.

Background: This retrospective cross-sectional study evaluated the association of the global wall thickness index (GTI), derived from cardiovascular magnetic resonance (CMR), with demographic, clinical, and imaging findings, as well as heart failure history in transfusion-dependent thalassemia (TDT) patients. Methods: We analyzed 1154 TDT patients (52.9% female, 37.46 ± 10.67 years) from the Extension-Myocardial Iron Overload in Thalassemia project and 167 healthy controls (54.5% female, 36.33 ± 15.78 years). The CMR protocol included the T2* technique for the assessment of iron overload, cine imaging for the assessment of left ventricular (LV) function and size, and late gadolinium enhancement (LGE) imaging for the detection of replacement myocardial fibrosis (in the subset of 366 patients who underwent contrast administration). GTI (in mm/m²) was calculated from LV mass and end-diastolic volume. Results: GTI discriminated TDT patients from controls better than the LV end-diastolic volume index. Among TDT patients, GTI was higher in males, in those with diabetes, and in those with severe myocardial iron overload (cardiac T2* < 10 ms), but was unrelated to age, hemoglobin and ferritin levels, splenectomy, hepatic and pancreatic T2* values, LV ejection fraction, and fibrosis. GTI showed a diagnostic performance comparable to global heart T2* and superior to LV ejection fraction in identifying patients with prior heart failure. Conclusions: GTI is elevated in TDT patients compared with healthy controls. Male sex and severe myocardial iron overload are key determinants of GTI in TDT. Increased GTI is linked to a history of heart failure, supporting its role as a complementary tool to conventional CMR indices.

Background: This multicenter cross-sectional study aimed to assess the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications and to identify factors associated with their occurrence in adult patients with neo-transfusion-dependent thalassemia (neo-TDT). Methods: A total of 140 adult neo-TDT patients (defined as receiving >4 transfusions/year; mean age 44.3 ± 12.1 years; 56.4% female) were retrospectively enrolled from the Extension–Myocardial Iron Overload in Thalassemia (E-MIOT) network. Iron overload (IO) was assessed by magnetic resonance imaging and complications were classified according to established clinical criteria. Logistic regression analyses were performed to investigate associations of complications with age, sex, splenectomy status, chelation therapy, hemoglobin < 9 g/dL, ferritin ≥ 1000 ng/mL, and hepatic, pancreatic, and cardiac IO. Results: Complications affecting fewer than 5% of patients—including leg ulcers, cirrhosis, thrombosis, heart failure, and hypoparathyroidism—were excluded from statistical analysis. Bone metabolism disorders were the most prevalent complications (68.6%), followed by impaired glucose metabolism (15.7%). The prevalence of other complications was: extramedullary hematopoiesis (EMH) 19.3%, pulmonary hypertension (PH) 7.1%, arrhythmias 12.1%, hypogonadism 11.4%, and hypothyroidism 15.0%. Male sex was independently associated with EMH (odds-ratio [OR] = 2.67; p = 0.027). Hepatic IO was the only significant predictor of PH (OR = 4.12; p = 0.047). Arrhythmias were strongly associated with older age (OR = 22.67; p < 0.0001), while both older age (OR = 4.42; p = 0.004) and pancreatic IO (OR = 7.40; p = 0.012) were independently associated with impaired glucose metabolism. No significant associations were identified for hypogonadism, hypothyroidism, or bone metabolism disorders. Conclusion: This study offers updated insights into the burden of complications in neo-TDT patients and highlights specific risk factors that may inform comprehensive, multidisciplinary surveillance strategies.

Background: Myocardial contraction fraction (MCF) is a promising volumetric index of myocardial function. Purpose: To evaluate the association of MRI‐derived MCF with demographic characteristics, clinical data, MRI findings, and the history of heart failure in patients with transfusion‐dependent thalassemia (TDT). Study Type: Retrospective. Subjects: 1154 TDT patients (52.9% female, 37.46 ± 10.67 years) enrolled in the Extension–Myocardial Iron Overload in Thalassemia project and 167 healthy subjects (54.5% female, 36.33 ± 15.78 years). Field Strength/Sequence: 1.5 T/cine imaging for assessment of left ventricular (LV) function parameters, gradient‐echo T2* technique for myocardial iron overload (MIO) assessment, late gadolinium enhancement (LGE) imaging for detection of replacement myocardial fibrosis. Assessment: MCF was calculated as LV stroke volume divided by LV myocardial volume. Statistical Tests: Independent‐samples t ‐test, Wilcoxon signed‐rank test, and chi‐squared test for comparison between groups; analysis of covariance; Pearson's or Spearman's correlations; univariable and stepwise multivariable linear regression analyses; receiver operating characteristic curve analysis for assessment of diagnostic efficiency and DeLong's test for area under the curves (AUCs) comparison. Statistical significance was defined as p < 0.05. Results: Healthy subjects and TDT patients showed comparable MCF values (99.5% ± 15.0% vs. 102.7% ± 29.7%, p = 0.820). In TDT, MCF was significantly lower in males compared to females (98.4% ± 27.1% vs. 106.6% ± 31.3%) and in patients with diabetes (96.8% ± 29.7% vs. 103.7% ± 29.1%). MCF significantly decreased with age ( R = −0.066). MCF was significantly correlated with global heart T2* values ( R = 0.075), and patients with MIO (T2* < 20 ms) had a significantly lower MCF compared to those without (96.3% ± 22.0% vs. 103.3% ± 30.2%). MCF had a significant inverse correlation with the number of LGE‐positive segments ( R = −0.314). MCF demonstrated a diagnostic performance comparable to that of global heart T2* values in distinguishing between TDT patients with and without a history of heart failure (AUC 0.63 vs. 0.58, p = 0.401 for the difference). The LV ejection fraction did not significantly differentiate patients based on heart failure history (AUC = 0.55, p = 0.223). Data Conclusion: In patients with TDT, MCF was significantly correlated with MIO and LGE extent. Additionally, patients with a history of heart failure had significantly impaired MCF. Evidence Level: 4. Technical Efficacy: Stage 2.