National networking in rare diseases and reduction of cardiac burden in thalassemia major

Abstract

Aims A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM). Methods and results Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths. Conclusion Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients. Key Question Which was the impact on cardiac outcomes in thalassemia major by a national network among thalassemia and magnetic resonance imaging centres ensuring the continuous and standardized monitoring of the cardiac iron levels? Key Finding There was a reduction of myocardial iron overload (MIO) in almost 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related heart failure. Take Home Message A national clinical and imaging networking in rare diseases was effective in improving the care and in reducing the cardiac burden in thalassemia major patients.

Random Forest Clustering Identifies Three Subgroups of β-Thalassemia with Distinct Clinical Severity

“…These could possibly represent sub-optimally chelated patients with TDT. Cluster 2 patients, however, have comparable age at diagnosis and initiation of transfusion and iron chelation (marginally delayed compared with Cluster 3), and yet have more favorable serum ferritin levels, probably reflecting a well-chelated cohort of patients with TDT [27]. They may also represent NTDT patients who eventually end up receiving regular transfusion and iron chelation therapy and have improved survival [28].…”

Fat-Corrected Pancreatic R2* Relaxometry from Multi-Echo Gradient-Recalled Echo Sequence Using Convolutional Neural Network

“…Images from 192 thalassemia major patients (92 males and 100 females, age 7-58 years, mean age 39.5 ± 16.2 years) were retrospectively studied. All patients were consecutively enrolled from years 2009 to 2020 in the core lab of the MIOT/eMIOT (Myocardial Iron Overload in Thalassemia) network, constituted by thalassemia and MRI centers where MRI exams are performed using homogeneous, standardized, and validated procedures and where patients' clinical-instrumental data are collected in a centralized, web-based database [33,34]. The study complied with the Declaration of Helsinki.…”

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

“…The introduction of the chelation therapy has led to a decrease of the iron burden, significantly prolonging the survival of the patients [ 9 ]. Moreover, the deployment of the T2* magnetic resonance imaging (MRI) technique for the noninvasive quantification of organ-specific iron overload has offered the possibility to design tailor-made chelation therapies meeting the individual patient’s needs [ 10 , 11 ], further improving the prognosis [ 12 , 13 ]. However, hepatic, cardiovascular and endocrine complications still occur [ 13 , 14 ].…”

“…Moreover, the deployment of the T2* magnetic resonance imaging (MRI) technique for the noninvasive quantification of organ-specific iron overload has offered the possibility to design tailor-made chelation therapies meeting the individual patient’s needs [ 10 , 11 ], further improving the prognosis [ 12 , 13 ]. However, hepatic, cardiovascular and endocrine complications still occur [ 13 , 14 ]. The underlying genetic defect in thalassemia is an important factor in the development of these complications because the homozygous β0 genotype state demands more red cells consumption and a greater rate of iron overloading [ 15 , 16 ].…”