Classification of patients with cardiac amyloidosis using machine learning models on Italian electronic clinical health records.

Amyloidosis refers to a range of medical conditions in which misshapen proteins accumulate in various organs and tissues, forming insoluble fibrils. Cardiac amyloidosis is frequently linked to the buildup of misfolded transthyretin (TTR) or immunoglobulin light chains (AL). Delayed diagnosis, due to lack of disease awareness, results in a poor prognosis, especially in patients with AL amyloidosis. Early identification is therefore a key factor to improve patient outcomes. This study investigates the use of supervised machine-learning algorithms to support clinicians in classifying amyloidosis and control subjects. The aim of this work is to foster model interpretability reporting the most important risk factors in predicting the presence of cardiac amyloidosis. We analyzed electronic health records (EHRs) of 418 participants acquired in a time window of 12 years as part of a case-control study conducted in Fondazione Toscana Gabriele Monasterio (Italy) clinical practice. This work paves the way for the creation of digital health solutions that can aid in amyloidosis screening. The effective handling, analysis, and interpretation of these solutions can have a transformative effect on modern healthcare, offering new opportunities for improved patient care.

Overcoming Underpowering in the Outcome Analysis of Repaired-Tetralogy of Fallot: A Multicenter Database from the CMR/CT Working Group of the Italian Pediatric Cardiology Society (SICPed).

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population.

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

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.

A New Web Score to Predict Health Status in Paediatric Patients with Chronic Diseases: Design and Development of the PENSAMI Study.

Paediatric chronic diseases (CD) are characterised by their ongoing duration and the fact that they are often managed throughout the lifespan, with the need to adjust lifestyle and expectations with the limitations coming from the CD. The aim of the PENSAMI study is to not only cure the disease, but to also care for the person from a clinical and psychosocial perspective. Data will be collected from 150 paediatric patients affected by heart disease, diabetes, and asthma admitted during in-hospital stay or outpatient visits, and from 200 healthy control subjects. The protocol will consist of two phases. The first one will aim at elaborating the predictive model by detecting (clinical, anthropometric at birth, environmental, lifestyle, social context, emotional state, and mental abilities) in order to develop a model predictive of the events considered: (1) re-hospitalisation; (2) severity and progression of the disease; (3) adherence to therapy; (4) HRQoL; (5) obesity and metabolic syndrome; (6) illness-stress related; (7) school drop-out; (8) school performance. The second one will address validating the previous predictive model. This model will aim to: (1) understand, prevent, and halt the progression of childhood CD; (2) develop new and improved diagnostic tools; (3) pave the way for innovative treatments and additional therapies to traditional clinical practice; and (4) create truly personalised therapeutic and preventive strategies in various sectors, such as cardiology, diabetes, and respiratory diseases.

The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study.

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.