Stefania Renne

The prevalence of diabetes and heart failure rises sharply with age, and their coexistence amplifies cardiovascular and renal risk. Elderly patients display unique clinical and biological profiles characterised by frailty, multimorbidity, and pharmacodynamic variability that challenge conventional treatment strategies. Sodium–glucose co-transporter-2 inhibitors (SGLT2i) have emerged as a cornerstone of cardio–renal–metabolic protection, with the most consistent cardiovascular benefit being the reduction in heart failure hospitalisation, whereas effects on cardiovascular death and major adverse cardiovascular events vary according to baseline cardiovascular risk, heart failure phenotype, diabetic status, and trial design. However, real-world use among the elderly remains limited due to concerns about tolerability, polypharmacy, and cost. This review analyses the pharmacological rationale and evidence base for SGLT2i therapy in older adults, highlighting mechanisms beyond glucose control, quantitative data from pivotal trials, and practical issues for geriatric implementation.

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.

Objectives: We compared changes in hepatic and cardiac iron levels, left ventricular (LV) and right ventricular (RV) dimensions and function, and bi-atrial areas, all assessed through magnetic resonance imaging (MRI), between patients with non-transfusion-dependent thalassemia (NTDT) and those with neo-transfusion-dependent thalassemia (neo-TDT) over an 18-month follow-up period. Methods: We included 32 NTDT patients (42.78 ± 12.62 years, 53.1% females) and 58 neo-TDT (>4 transfusions per year) patients (44.08 ± 14.13 years, 46.6% females), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Iron overload was quantified by T2* technique, biventricular function and atrial areas by cine images. Macroscopic myocardial fibrosis was detected by the late gadolinium enhancement technique. Results: Changes in cardiac and hepatic iron levels, in biventricular ejection fractions, in LV mass index, and bi-atrial areas were comparable between the two groups. A trend of worsening biventricular dimensions was observed in the NTDT group, while the neo-TDT group showed an improvement (decrease) in biventricular size (LV stroke volume index: p = 0.036; LV cardiac index: p = 0.031; RV end-diastolic volume index: p = 0.034; RV stroke volume index: p = 0.033). The inter-group comparison showed significant differences in the changes of biventricular end-diastolic volume indexes (LV: p = 0.011 and RV: p = 0.034) and stroke volume indexes (LV: p = 0.036 and RV: p = 0.033) and in the cardiac index (p < 0.0001). At both MRI scans, the frequency of replacement myocardial fibrosis was comparable between the two groups. Conclusions: Our 18-month longitudinal data revealed distinct patterns of cardiac remodeling in NTDT and neo-TDT patients. The progressive ventricular dilation observed in NTDT patients highlights the need for careful MRI monitoring and potential interventions to address the long-term cardiac consequences of anemia.

Background/Objectives: We aimed to establish biatrial and biventricular reference ranges using cardiac magnetic resonance (CMR) parameters in SCD patients without heart damage. Methods: This study compared CMR parameters, quantified by cine SSFP sequences, in 48 adult SCD patients without apparent cardiac involvement (defined by the absence of known risk factors, normal electrocardiogram, and no macroscopic myocardial fibrosis or significant cardiac iron on T2* CMR) to matched cohorts of 96 healthy controls and 96 thalassemia major (TM) patients without cardiac damage. Nine paediatric SCD patients were also analysed and compared to age- and gender-matched groups of nine TM patients and nine healthy subjects. Results: In all groups, studied males displayed higher biventricular volumes and mass indexes than females. Male SCD patients showed significantly higher left ventricular (LV) end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), LV stroke volume index (SVI), cardiac index, LV and right ventricular (RV) mass index, and atrial areas than healthy subjects. Females with SCD exhibited increased LV EDVI, LV SVI, RV mass index, and left atrial area index compared to healthy controls. SCD and TM patients showed comparable biatrial areas and biventricular volumes and function. When compared to TM, SCD males exhibited a larger mass index, while SCD females showed an increased RV mass index. CMR parameters were similar across all paediatric groups. Conclusions: By establishing the biatrial and biventricular reference ranges through CMR for adult male and female SCD patients, we aimed to prevent possible misdiagnosis of cardiomyopathy in this population by taking into account cardiac adaptation due to anaemia.

Objectives: This multicenter, retrospective, population-based, matched-cohort study compared clinical characteristics and magnetic resonance imaging (MRI) findings, including hepatic, pancreatic, and cardiac iron levels and cardiac function, between 135 adult regularly transfused thalassemia intermedia (TI) patients (44.73 ± 12.16 years, 77 females) and 135 age- and sex-matched thalassemia major (TM) patients (43.35 ± 9.83 years, 77 females), enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Methods: The MRI protocol included the quantification of hepatic, pancreatic, and cardiac iron levels (R2* technique), the assessment of biventricular function parameters (cine images), and the detection of replacement myocardial fibrosis (late gadolinium enhancement technique). Results: Age, sex, frequency of splenectomy and chelation, and serum ferritin levels were not significantly different (p > 0.05) between the two groups, but TI patients started regular transfusions significantly later (p < 0.0001) and showed significantly lower pre-transfusion hemoglobin levels (p = 0.005). No difference was found in hepatic iron levels (p = 0.853). TI patients exhibited significantly lower pancreatic R2* values (p < 0.0001), also correcting for the duration of regular transfusions, and significantly lower cardiac R2* values (p < 0.0001). In the receiver operating characteristic analysis, pancreatic iron was the strongest discriminator between the two diseases. Left and right ventricular end-diastolic volume indexes were significantly higher in TI than in TM patients (p = 0.003 and p = 0.046, respectively), but the correction for the duration of regular transfusions removed the disease-specific differences (p > 0.05). Left ventricular (LV) mass index was significantly higher in TI (p = 0.049), while no difference (p > 0.05) was found in biventricular ejection fractions and replacement myocardial fibrosis. Conclusions: TI patients showed lower pancreatic and cardiac iron burden and more pronounced LV hypertrophy. These differences could not be explained by the different duration of the transfusional regimen.

Cardiac involvement in sickle beta thalassemia (Sβ-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. One-hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sβ-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sβ-thal and SCA patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCA-specific bi-atrial and biventricular reference values.

Background: We prospectively evaluated the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in non-transfusion-dependent β-thalassemia (β-NTDT) patients who started regular transfusions in late childhood/adulthood (neo β-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.

We employed an unsupervised clustering method that integrated demographic, clinical, and cardiac magnetic resonance (CMR) data to identify distinct phenogroups (PGs) of patients with beta-thalassemia intermedia (β-TI). We considered 138 β-TI patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who underwent MR for the quantification of hepatic and cardiac iron overload (T2* technique), the assessment of biventricular size and function and atrial dimensions (cine images), and the detection of replacement myocardial fibrosis (late gadolinium enhancement technique). Three mutually exclusive phenogroups were identified based on unsupervised hierarchical clustering of principal components: PG1, women; PG2, patients with replacement myocardial fibrosis, increased biventricular volumes and masses, and lower left ventricular ejection fraction; and PG3, men without replacement myocardial fibrosis, but with increased biventricular volumes and masses and lower left ventricular ejection fraction. The hematochemical parameters and the hepatic and cardiac iron levels did not contribute to the PG definition. PG2 exhibited a significantly higher risk of future cardiovascular events (heart failure, arrhythmias, and pulmonary hypertension) than PG1 (hazard ratio-HR = 10.5; p = 0.027) and PG3 (HR = 9.0; p = 0.038). Clustering emerged as a useful tool for risk stratification in TI, enabling the identification of three phenogroups with distinct clinical and prognostic characteristics.

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.

Background. The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. Methods. The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. Results. The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March–June 2020, and a reduction in the gap between the two years in the period July–September. A new drop (41.4%) was recorded in the period October–December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. Conclusions. The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.