Background/Objectives: Synthetic artificial intelligence (AI) is increasingly used in cardiovascular medicine to generate realistic clinical data from limited samples while preserving patient privacy. Despite its promise, concerns remain regarding the clinical reliability of synthetic datasets, which hampers their integration into routine practice. This article introduces the TIMA method (Team-Implementation Multidisciplinary Approach), designed to involve clinicians directly in every phase of synthetic data development. The objective of this work is to describe the TIMA framework and to illustrate how structured clinician-data scientist collaboration can enhance the clinical robustness and plausibility of synthetic AI outputs. Methods: The TIMA approach structures the synthetic data generation workflow around continuous interaction between clinicians and data scientists. Cardiologists define clinical constraints, verify inter-variable relationships, and assess the coherence and plausibility of generated records. The framework is illustrated through multiple cardiology use cases, including atrial fibrillation risk prediction and surgical mortality estimation in infective endocarditis, to demonstrate its adaptability across different clinical contexts. Each phase includes iterative validation steps aimed at ensuring alignment with established clinical knowledge rather than reporting quantitative performance outcomes. Results: Application of the TIMA framework supported the development of synthetic datasets that adhered more closely to clinical logic and domain-specific constraints. Clinician-data scientist collaboration enabled early detection of implausible variable interactions, improved interpretability of synthetic data patterns, and enhanced internal consistency across different cardiology-oriented scenarios. Conclusions: TIMA represents a scalable and replicable methodological model for integrating synthetic AI into cardiology by embedding clinical expertise throughout the data generation process. Its structured, multidisciplinary workflow supports the production of synthetic data that is not only statistically coherent but also clinically meaningful, thereby strengthening trust and reliability in AI-assisted cardiovascular research.

Synthetic artificial intelligence (AI) is rapidly redefining biomedical research—yet in cardiovascular medicine, its clinical relevance remains obscure, underexplored, and underestimated. Unlike traditional AI, which interprets data, synthetic AI generates entirely new, patient-like information: from realistic ECG signals to cardiac imaging and virtual cohorts that simulate disease progression. While recent publications have addressed specific synthetic AI tools in cardiology, no prior review has comprehensively synthesized their architectures, clinical applications, and implementation challenges within a single, practice-oriented framework.This State-of-the-Art Review fills that gap. We provide a clear, critical synthesis of core architectures—Generative Adversarial Networks (GANs), Variational Autoencoders (VAEs), Diffusion Models, Transformers, Autoregressive Models, Digital Twins, and Synthetic Cohort Simulators—and map their emerging cardiovascular applications. We examine technical barriers, ethical concerns, regulatory uncertainties, and integration challenges, while anchoring the discussion in real-world clinical priorities. This review is not only a scientific analysis—it is a call to engagement. For academic researchers, it offers conceptual and technical clarity. For clinicians in resource-constrained settings, it presents synthetic AI not as abstract innovation, but as a practical opportunity to enhance diagnostic precision, optimize workflows, and extend clinical insight. Traditional AI supports cardiologists by interpreting data; synthetic AI extends this paradigm by creating new, clinically coherent information that enhances decision-making without replacing physician expertise.As investment grows and methods mature, cardiologists must shape this evolution—not as passive adopters, but as active drivers. This review invites them to take the wheel.

BACKGROUND:Stereotactic body radiotherapy (SBRT) is increasingly used to treat lung metastasis (LM) in patients with soft tissue sarcoma (STS) and bone sarcoma (BS). METHODS:This retrospective study evaluated the outcomes of patients with BS and STS treated with SBRT for LM between 2010 and 2023. RESULTS:We enrolled 102 patients (51 each with STS and BS), of whom 71 were males and 31 were females (median age, 40 years; range, 11-81 years). At diagnosis, 76 and 26 patients had localized and metastatic disease, respectively, with a median of 4 recurrences (range, 1-12). Before SBRT, 75 patients received chemotherapy and 52 underwent surgery for LM, with 276 nodules treated with SBRT (median dose, 48 Gy; range, 40-52). Local control of irradiated LM was 86% at 1 year and 78% at 2 years. By 31 December 2023 (median follow-up, 4.8 years), 60 patients had died and 42 survived (20 without ongoing disease). From the first LM relapse, the median overall survival (OS) was 4.8 years and the 5-year OS was 49% (95% confidence interval, 39-60%), with no difference between STS and BS; the median OS was 2.9 years and the 5-year OS was 36% after SBRT. Chemotherapy before SBRT was a negative prognostic factor by multivariate analysis. CONCLUSIONS:Long-term follow-up shows that SBRT as part of a multimodal treatment approach has reasonable survival rates in patients with LM due to sarcoma. Compared with historical results using only surgery and chemotherapy, SBRT has improved the 5-year OS.

Background: This study aims to get an effective machine learning (ML) prediction model of new-onset postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG) and to highlight the most relevant clinical factors. Methods: Four ML algorithms were employed to analyze 394 patients undergoing CABG, and their performances were compared: Multivariate Adaptive Regression Spline, Neural Network, Random Forest, and Support Vector Machine. Each algorithm was applied to the training data set to choose the most important features and to build a predictive model. The better performance for each model was obtained by a hyperparameters search, and the Receiver Operating Characteristic Area Under the Curve metric was selected to choose the best model. The best instances of each model were fed with the test data set, and some metrics were generated to assess the performance of the models on the unseen data set. A traditional logistic regression was also performed to be compared with the machine learning models. Results: Random Forest model showed the best performance, and the top five predictive features included age, preoperative creatinine values, time of aortic cross-clamping, body surface area, and Logistic Euro-Score. Conclusions: The use of ML for clinical predictions requires an accurate evaluation of the models and their hyperparameters. Random Forest outperformed all other models in the clinical prediction of POAF following CABG.

Purpose: The purpose of this study was to assess the rate with which radiologists reported spinal epidural lipomatosis (SEL) when interpreting lumbosacral magnetic resonance imaging (MRI) examination. Materials and methods: A total of 450 lumbosacral MRI examinations obtained in 450 patients were included (199 men, 251 women; mean age, 56.7 +/- 13.5 [SD] years; age range: 18-91 years). Three senior radiologists assessed and classified independently SEL on MRI according to the Borre grading system (Grade 1 to Grade 3). Depiction of SEL on MRI reports (i. e., reporting rate) and association with patients' symptoms were verified. Results: SEL was found in 75/450 patients (prevalence = 16.7%), and classified as grade-1 (mild) in 49/75 (65.3%) patients, grade-2 (moderate) in 24/75 (32%), and grade-3 (severe) in 2/75 (2.7%). SEL was diagnosed on MRI report in 6/75 (8%) patients. SEL prevalence based on MRI reports was 1.3% (6/450), significantly lower than its actual prevalence based on MRI examinations (P < 0.0001). The reporting rate was 0% in grade-1 (0/ 19), 10.2% in grade-2 (5/49) and 50.0% in grade-3 (1/2), and variable on the radiologist subspecialty (10.0% among musculoskeletal radiologists, 11.1% among neuroradiologists, and 3.7% among generalists). SEL was considered as the only cause of symptoms in 7/75 patients (9.3%) and a concurrent cause in 9/75 (12%). Conclusion: SEL reporting rate is extremely low, leading to an important underestimation of disease prevalence. SEL diagnosis and grading should be refined to improve reports quality and subsequently patient care. (c) 2022 Published by Elsevier Masson SAS on behalf of Societe francaise de radiologie.

Spinal epidural lipomatosis (SEL) is defined as the abnormal accumulation of unencapsulated adipose tissue in the spinal epidural space. SEL can be asymptomatic or can cause a wide range of symptoms, the most common of which is neurogenic claudication. Several other neurological manifestations may also occur, above all myelopathy and radicular symptoms. The spinal level most frequently involved in patients with SEL is the lumbar one, followed by the thoracic one. Imaging plays a key role in the disease assessment. MRI is considered the most effective and sensitive modality for diagnosing and staging SEL. Anyway, also CT scan can diagnose SEL. The diagnosis may be incidental (in mild-moderate disease) or may be taken into account in cases with neurological symptoms (in moderate-severe disease). There are some recognized risk factors for SEL, the most common of which are exogenous steroid use and obesity. Recent studies have found an association between SEL and obesity, hyperlipidemia and liver fat deposition. As a matter of fact, SEL can be considered the spinal hallmark of metabolic syndrome. Risk factors control represents the initial treatment strategy in patients with SEL (e.g. weight loss, steroid therapy suspension). Surgical decompression may be required when conservative treatment fails or when the patient develops acute/severe neurological symptoms.

This study aims to establish the incidence of atrial fibrillation (AF) in breast cancer (BC) patients, focusing on staging and anti-cancer treatment. A meta-analysis was conducted to investigate the incidence of AF in BC patients and compare this incidence to other cancers. Furthermore, we evaluated the occurrence of AF as an adverse effect of biological therapies vs. non-biological therapies vs. biological therapies + non-biological therapies in BC. Finally, we compared the incidence of AF in early BC and metastatic BC. Thirty studies were included. Twenty-two studies focused on BC, encompassing 166,271 patients. In the BC group, 2.7% of patients developed AF, while in the "all cancer" group, 5.8% of patients developed AF. In addition, there was no difference between different types of therapies (p = 0.61) and between early and metastatic BC (p = 0.57). The type of anti-cancer therapy and the staging of BC does not influence AF's occurrence in this neoplastic disease.

Osteopetrosis (from the Greek "osteo": bone; "petrosis": stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same main characteristic of an abnormally increased bone density. Dense bones in radiological studies are considered the hallmark of these diseases, and the reason for the common term used: "Marble bone disease". Interestingly, a radiologist, Dr. Albers-Schonberg, described this disease for the first time in Germany in 1904. Indeed, radiology has a key role in the clinical diagnosis of osteopetrosis and is fundamental in assessing the disease severity and complications, as well as in follow-up controls and the evaluation of the response to treatment. Osteopetrosis includes a broad spectrum of genetic mutations with very different clinical symptoms, age onset, and prognosis (from mild to severe). This diversity translates into different imaging patterns related to specific mutations, and different disease severity. The main recognized types of osteopetrosis are the infantile malignant forms with autosomal recessive transmission (ARO-including the rarer X-linked recessive form); the intermediate autosomal recessive form (IAO); and the autosomal dominant ones ADO, type I, and type II, the latter being called 'Albers-Schonberg' disease. Imaging features may change among those distinct types with different patterns, severities, skeletal segment involvement, and speeds of progression. There are several classical and well-recognized radiological features related to osteopetrosis: increased bone density (all types with different degrees of severity assuming a 'Marble Bone Appearance' especially in the ARO type), different metaphyseal alterations/enlargement including the so-called 'Erlenmeyer flask deformity' (particularly of femoral bones, more frequent in ADO type 2, and less frequent in ARO and IAO), 'bone in bone' appearance (more frequent in ADO type 2, less frequent in ARO and IAO), and 'rugger-jersey spine' appearance (typical of ADO type 2). After conducting an overview of the epidemiological and clinical characteristic of the disease, this review article aims at summarizing the main radiological features found in different forms of osteopetrosis together with their inheritance pattern.

Atrial fibrillation (AF) is the most common arrhythmia, increasing with age and comorbidities. Obstructive sleep apnea (OSA) is a chronic sleep disorder more common in older men. It has been shown that OSA is linked to AF. Nonetheless, the prevalence of OSA in patients with AF remains unknown because OSA is significantly underdiagnosed. This review, including 54,271 patients, carried out a meta-analysis to investigate the association between OSA and AF. We also performed a meta-regression to explore cofactors influencing this correlation. A strong link was found between these two disorders. The incidence of AF is 88% higher in patients with OSA. Age and hypertension independently strengthened this association, indicating that OSA treatment could help reduce AF recurrence. Further research is needed to confirm these findings. Atrial Fibrillation (AF) is the most common arrhythmia, increasing with age and comorbidities. Obstructive sleep apnea (OSA) is a regulatory respiratory disorder of partial or complete collapse of the upper airways during sleep leading to recurrent pauses in breathing. OSA is more common in older men. Evidence exists that OSA is linked to AF. Nonetheless, the prevalence of OSA in patients with AF remains unknown because OSA is underdiagnosed. In order to investigate the incidence of AF in OSA patients, we carried out a meta-analysis including 20 scientific studies with a total of 54,271 subjects. AF was present in 4801 patients of whom 2203 (45.9%) had OSA and 2598 (54.1%) did not. Of a total of 21,074 patients with OSA, 2203 (10.5%) had AF and 18,871 (89.5%) did not. The incidence of AF was 88% higher in patients with OSA. We performed a meta-regression to explore interacting factors potentially influencing the occurrence of AF in OSA. Older age and hypertension independently strengthened this association. The clinical significance of our results is that patients with OSA should be referred early to the cardiologist. Further research is needed for the definition of the mechanisms of association between AF and OSA.

Background: Ischemic stroke after coronary artery bypass (CABG) has been often linked to aortic manipulation during surgery. Objectives: The objective of the study was to estimate the rate of postoperative ischemic stroke within 30 days from CABG by surgical risk factors alone or in combination. Methods: The multinomial propensity score for multiple treatments was used to create six models with a total of 16,255 consecutive patients undergoing isolated CABG. For each model, a different classification variable was used to stratify patients. Results: Balance achieved in all models was substantial, enabling unbiased estimation of the treatment estimand. Both off-pump techniques with (0.009; 95% CI 0.006-0.011) or without proximal anastomoses (0.005; 0.005-0.003), and surgery performed on the beating heart using cardiopulmonary bypass with (0.009; 0.006-0.011) or without proximal anastomoses (0.024; 0.021-0.029) showed a mean stroke estimate significantly lower than the other techniques. Off-pump surgery and on-pump surgery without an aortic cross-clamp yielded nearly equal incidences of stroke (0.012; 0.008-0.015 and 0.018; 0.012-0.023, respectively). Using an aortic cross-clamp significantly increased the stroke estimate (0.075; 0.061-0.088), whereas using a side-biting clamp did not (0.039; 0.033-0.044). The number of aortic touches (0.029; 0.026-0.031) and the number of proximal anastomoses (0.044; 0.035-0.047) did not significantly increase the incidence of stroke. Conclusions: Aortic cross-clamping was found to be the primary cause of post-CABG ischemic stroke. Instead, additional aortic manipulation from a side-biting clamp, on-pump surgery, multiple aortic touches, number of proximal anastomoses, and aortic cannulation were found not to increase the estimate of stroke significantly. Further research on this topic is warranted.

Background: Synovial sarcoma is a relatively chemosensitive type of soft tissue sarcoma and it often metastasizes to the lung. We investigated the role of adjuvant chemotherapy in patients with high-grade synovial sarcoma at their first lung metastasectomy (LMTS). Methods: Forty-six HGSS patients had their first LMTS at our institute (Rizzoli Orthopedic Hospital, Bologna, Italy) between 2000 and 2020. We divided them into two groups: (1) those undergoing adjuvant chemotherapy (n = 24) and (2) those not receiving adjuvant chemotherapy (n = 22). The primary outcome was a median survival at 32.5 (IQR 18.0–82.7) median follow-up. The disease-free interval was calculated at time zero (DFI0, interval between the diagnosis of the primary tumor and the first CT-diagnosed lung metastasis) and at any further lung relapse (DFI1–3). T0 was defined as the time at first LMTS and T1–T3 referred to the time of further metastasectomy. Results: Freedom from SS-specific mortality at 60 months was significantly higher in patients without chemotherapy (50.0% (33.0–76.0%) vs. 20.8% (9.55%–45.4%), p = 0.01). Chemotherapy was associated with a higher risk of SS-specific mortality at multivariable Cox regression (HR 2.8, p = 0.02). Furthermore, DFI0 ≤ 6 months, female sex, age > 40 years, and primary tumor > 10 cm increased the risk of death by about four, six, >three, and >five times, respectively. Conclusions. Adjuvant chemotherapy did not show any advantage in terms of freedom from SS-specific mortality in HGSS patients. Further larger studies are necessary to confirm our findings.

Introduction: Osteopetrosis is an uncommon skeletal disorder characterized by generalized sclerosis of bones due to defective osteoclast function. A wide variation in clinical severity of the disease has been observed. Radiographic features and genetic testing are commonly used to diagnose the condition. Case Presentation: In the present study, we present a case of an extremely rare, atypical and genetically- undetermined form of Osteopetrosis. Conclusion: This patient had some clinical and radiological features of craniometaphyseal dysplasia along with atypical radiological signs of osteopetrosis.

Background: We identified prognostic factors in a 30-year series of STS treated at a single Institution, using an advanced statistical approach. Methods: From June 1988 to July 2019, 164 patients were referred to Rizzoli Orthopedic Hospital, Bologna, Italy) for STS lung metastasectomy (LMTS). The endpoints were lung metastasis recurrence (LMR) and lung metastasisspecific mortality (LMSM). The analysis included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias. Results: The 10- and 15- year LMR cumulative incidence were 0.77 (0.76-0.78) whereas 10- and 15- year freedom from LMSM were 0.60 [0.51-0.70] and 0.56 [0.47-0.67], respectively. The malignant peripheral nerve sheath tumor (MPNST) histotype (SHR 4.12 [2.05-8.27]), a disease-free interval (DFI) up to 68 months (HR from 2 [1.7-2.2] to 1.5 [1.1-1.9]) and a LM size >4 mm (3.1 [2.1-4.4]) predicted LMR. Myxofibrosarcoma (HR 2.52[1.64-3.86]), synovial sarcoma (2.53[1.22-5.23]), adjuvant chemotherapy (2.01 [1.11-3.61]), DFI between 2 months and 20 months (HR from 1.5 [1.1-2.3] to 1.3 [1.1-1.7] and primary tumor size a primary tumor size comprised between 3.6 cm and 10 cm predicted LMSM. A sharp increase in LMSM was observed with a tumor size from >20 cm. Conclusions: Our analysis corrected by potential confounders allowed us to identify specific histotypes and DFI intervals as predictors of both LMR and LMSM. Tumor size adjuvant chemotherapy adversely affected LM-related survival. Our findings need to be confirmed by larger randomized studies.

Background: Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Introduction: Aliterature review was performed to evaluate the outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). Methods: After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. Results: The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease-free interval was from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. Local control showed a high percentage for both procedures. Conclusion: SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.

Obesity correlates with better outcomes in many neoplastic conditions. The aim of this study was to assess its role in the prognosis and morbidity of patients submitted to resection of lung oligometastases from colorectal cancer. Seventy-six patients undergoing a first pulmonary metastasectomy were retrospectively included in the study. Seventeen (22.3%) were obese (body mass index (BMI) >30 kg/m2). Assessed outcomes were overall survival, time to recurrence, and incidence of post-operative complications. Median follow-up was 33 months (IQR 16–53). At follow-up, 37 patients (48.6%) died, whereas 39 (51.4%) were alive. A significant difference was found in the 3-year overall survival (obese 80% vs. non-obese 56.8%, p = 0.035). Competing risk analysis shows that the cumulative incidence of recurrence was not different between the two groups. Multivariate analysis reveals that the number of metastases (p = 0.028), post-operative pneumonia (p = 0.042), and DFS (p = 0.007) were significant predictors of death. Competing risk regression shows that no independent risk factor for recurrence has been identified. The complication rate was not different between the two groups (17.6% vs. 13.6%, p = 0.70). Obesity is a positive prognostic factor for survival after pulmonary metastasectomy for colorectal cancer. Overweight patients do not experience more post-operative complications. Our results need to be confirmed by large multicenter studies.

Background and aim Classical and paradoxical low-flow, low-gradient (LFLG) aortic stenosis (AS) are the most challenging subtypes of AS. The current therapeutic options are aortic valve replacement (AVR) and conservative management: AVR promotes long-term survival but is invasive, while conservative management yields a poor prognosis but is noninvasive since it uses no aortic valve replacement (noAVR). The present meta-analysis investigated the rate of survival of patients with LFLG AS undergoing either AVR or noAVR interventions. Methods The meta-analysis compared the outcomes of AVR with those of noAVR in terms of patient survival. In both groups, a meta-regression was conducted to investigate the impact on patient survival of the left ventricular ejection fraction (LVEF), either preserved (paradoxical LFLG AS) or reduced (classical LFLG AS). Results The relative risk of survival between the AVR and noAVR groups was 1.99 [1.40, 2.82] (p = .0001), suggesting that survival tends to be better in AVR patients than in noAVR patients. The meta-regression revealed that a reduced LVEF may be related to a higher survival in AVR patients when compared to a preserved LVEF (p = .04). Finally, the analysis indicated that LVEF seems not to be prognostic of survival in noAVR patients (p = .18). Conclusions Patients with LFLG AS have better survival if they undergo AVR. In AVR patients, reduced LVEF rather than preserved LVEF is related to better survival, whereas there seems to be no difference in prognostic value between reduced and preserved LVEF in noAVR patients.

Aim The aim was to use a propensity score-based analysis to determine the impact of peripheral artery disease (PAD) on early outcomes after coronary artery bypass surgery grafting (CABG) in patients with PAD. Method We conducted a multicentre retrospective analysis of 11,311 consecutive patients who underwent CABG between 1997 and 2017. Patients with previous or concomitant vascular surgery were excluded. The main endpoints were death, stroke, and limb ischaemia requiring percutaneous or surgical revascularisation. Subgroup analyses were performed to test the interaction of PAD with concomitant factors. Results There was no difference in mortality in patients with and without PAD (p=0.06 and p=0.179, respectively). Patients with PAD had a greater incidence of stroke (p=0.04), acute kidney disease (p=0.003), and limb ischaemia requiring interventions (p<0.001) than those without PAD. The use of off-pump or no-touch aortic techniques did not influence the effect of PAD on the outcomes. Early mortality rate increased in patients with PAD when associated with long cardiopulmonary bypass, cross-clamp times (both p<0.001), and postoperative low cardiac output (p=0.01). Conclusions The presence of PAD is associated, independently of other factors, with greater incidence of stroke, acute kidney disease, and limb ischaemia following CABG, irrespective of the technique employed. Operative mortality was greater in patients with PAD only when associated with long cardiopulmonary bypass and aortic cross-clamp times, and low cardiac output.

•MR Recurrence was not influenced by the ring employed.•IMR-ETlogix showed the lowest MR recurrence rate.•LV Reverse remodeling was comparable in planar and non-planar rings.•Symmetric rings showed higher LV remodeling.