Rare cardiovascular diseases represent a heterogeneous group of conditions that are individually uncommon but collectively significant. They include inherited cardiomyopathies, infiltrative and metabolic disorders, channelopathies, aortopathies, as well as rare vascular syndromes and some congenital heart diseases. Over the last decade, major advances in multimodality imaging, genetic testing, and targeted therapies have substantially improved diagnostic accuracy and clinical outcomes. Patient-tailored management and disease‑modifying treatments, particularly for cardiomyopathies and selected metabolic disorders, illustrate the transition towards precision medicine in the field. Despite these scientific advances, important organisational challenges remain. In Belgium, eight centres are recognised as reference hospitals for rare diseases since 2014, but high‑level expertise and advanced technologies are available in more tertiary centres and care pathways for rare cardiovascular diseases remain fragmented. The recent Plan rare disease 2026-2030 with a development of a Central Rare Disease Registry and the extension of structured rare disease event registration to all medical services represent important steps towards improved epidemiological monitoring and coordination. However, formally organising a national network dedicated to rare cardiovascular diseases is a challenge to offer uniform access to specialised care. The framework for collaboration of the reference centres with the different partners over the lines of care, the establishment and support of multidisciplinary clinics, the development of generic and personalised care pathways and national registries are key steps towards more coordinated, equitable, and efficient management of patients with rare cardiovascular diseases in Belgium.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are widely used for lowering blood pressure, but the optimal choice of RAAS inhibitors in reducing cardiovascular events remains unclear.

We aimed to compare the efficacy of RAAS inhibitors on cardiovascular outcomes in hypertensive population.

A systematic literature search was performed in PubMed and the Central Cochrane Library. The primary efficacy outcome was major adverse cardiovascular events (MACE). Individual components of MACE including cardiovascular mortality, myocardial infarction, stroke, and heart failure were also analyzed. Network meta-analyses were conducted via a random-effects model within frequentist framework.

We analyzed 43 randomized controlled trials. Mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of MACE compared with placebo [risk ratio (RR) 0.82; 95% confidence interval (CI) 0.75-0.90] and were superior to angiotensin receptor blockers (ARBs; RR 0.87; 95% CI 0.78-0.99) and direct renin inhibitors (DRIs; RR 0.83; 95% CI 0.70-0.99). MRAs showed a nonsignificant trend toward benefit compared with angiotensin-converting enzyme inhibitors (ACEIs; RR 0.91; 95% CI 0.78-1.05). After excluding trials that specifically enrolled patients with heart failure, protective effect of MRAs was not significant, but suggested a trend toward benefit (RR 0.89; 95% CI 0.78-1.01). Subgroup analyses for diabetes and chronic kidney disease consistently showed significant MACE reduction with MRAs, regardless of whether patients had these comorbidities at baseline or not, while other RAAS inhibitors showed inconsistent results in the subgroup analysis. For individual events, MRAs showed higher efficacy in reducing cardiovascular mortality (RR 0.80; 95% CI 0.72-0.88) and heart failure (RR 0.83; 95% CI 0.70-0.98) compared with placebo, while ACEIs were more effective in reducing myocardial infarction (RR 0.65; 95% CI 0.51-0.82) and ARBs showed higher efficacy in reducing stroke (RR 0.88; 95% CI 0.80-0.98) compared with placebo.

MRAs outperformed ARBs and DRIs in reducing MACE in patients with hypertension, with a nonsignificant trend toward benefit compared with ACEIs. This benefit was most pronounced in populations with heart failure and MRAs provided consistent cardiovascular protection across subgroups with diabetes or renal comorbidities. Given the current positioning of the guidelines, MRAs may merit earlier consideration in hypertension management, pending confirmatory outcome-driven randomized trials.

PROSPERO identifier number CRD42023473004, registered on 28 October 2023.

To describe the laparoscopic intraoperative fascial traction (IFT) in the repair of scrotal hernia with loss of domain (LoD), focusing on the prevention of abdominal compartment syndrome (ACS).

A multicenter retrospective analysis was conducted on nine consecutive patients with S2 and S3 LoD scrotal hernia, eligible for IFT, treated between November 2023 and August 2024 in eight European hospitals (Italy, Germany and Portugal). Technical details of laparoscopic IFT were documented. Postoperative intra-abdominal pressure (IAP), ventilatory parameters, complications, and recurrence were assessed.

The median Tanaka index was 0.57 and all patients underwent Lichtenstein repair; in two cases, a simultaneous preperitoneal mesh was added due to extensive inguinal defects. Median operative time was 210 min, with median IFT duration of 70 min and a traction force of 18 kg. Postoperative ACS did not occur. IAP was monitored in 55% of patients, with a median postoperative value of 11.4 mmHg. The median peak ventilation pressure before and after hernia reallocation was 16 and 19.5 mmHg respectively with a median differential of 3,5 mmHg (range 0-8). The median Intensive Care Unit (ICU) monitoring was 1 day, and the median hospital stay was 9.5 days. Five patients developed Clavien-Dindo grade I and II complications, with no recurrence detected after a median follow-up of 19 months.

The laparoscopic IFT is a safe and useful adjunct in the surgical repair of LoD scrotal hernias. IFT may reduce the need for preoperative pneumoperitoneum and possibly prevent the development of postoperative ACS.

To assess the long-term clinical outcomes of a hybrid approach combining double-barrel superficial temporal artery to middle cerebral artery (STA-MCA) bypass with endovascular parent artery occlusion in the treatment of giant complex intracranial aneurysms. This retrospective observational study included patients with giant or fusiform intracranial aneurysms who underwent double-barrel STA-MCA bypass followed by endovascular occlusion of the parent artery between January 2019 and January 2025. The primary outcomes were bypass patency, aneurysm exclusion, and ischaemic complications. Secondary outcomes included postoperative neurological status (assessed using the modified Rankin Scale [mRS]), radiological follow-up results, and procedural complications. Follow-up was conducted at 1-, 3-, and 6-month post-procedure and annually thereafter, including clinical assessment and imaging with MRI/MRA or DSA. Seven patients (mean age, 44.7 ± 27.5 years; 57.1% male) were included in the analysis. Most aneurysms were fusiform (85.7%) and located in the MCA (71.4%). All patients underwent double-barrel bypass and endovascular occlusion. Postoperative DSA confirmed aneurysm exclusion and preserved perfusion in all cases. No permanent neurological deficits or bypass failures were observed. One patient developed transient hemiparesis, which was resolved spontaneously without intervention. In one emergency case, a double-barrel bypass was performed following coil prolapse and occlusion of both M2 segments during endovascular embolization; the patient was discharged with mild residual contralateral paresis. At long-term follow-up, all aneurysms remained completely occluded, and bypass patency was maintained in all patients. In appropriately selected cases, a hybrid approach combining double-barrel STA-MCA bypass with endovascular parent artery occlusion offers a safe and effective treatment option for complex intracranial aneurysms. This strategy provides reliable flow restoration and durable aneurysm exclusion, particularly when performed in a hybrid operating setting.

Obesity and type 2 diabetes (T2D) are metabolic diseases with shared pathophysiology. Traditional polygenic risk scores (PRSs) have focused on these conditions individually, yet the single-disease approach falls short in capturing the full dimension of metabolic dysfunction. We derived a biologically enriched metabolic PRS (MetPRS), a composite score that uses multi-ancestry genome-wide association studies of 20 metabolic traits from over 8.5 million individuals. MetPRS, optimized to predict obesity (O-MetPRS) and T2D (D-MetPRS), outperformed existing PRSs in predicting obesity and T2D across six ancestries. O-MetPRS and D-MetPRS effectively identify individuals at high risk for metabolic multimorbidity and predict clinical outcomes, including GLP-1 receptor agonist initiation. O-MetPRS and D-MetPRS showed an ∼2-fold increased risk of GLP-1 receptor agonist initiation for the top decile versus the middle quintile. The biologically enriched MetPRS has the potential to add an extra layer of information to disease prediction and management approaches for metabolic diseases.

Electrocardiogram (ECG) analysis is crucial for diagnosing cardiovascular conditions. While traditional classification models require large volumes of labeled data across multiple disease categories, anomaly detection offers a flexible alternative by identifying deviations from normal patterns-an approach particularly valuable given the rarity and diversity of cardiac conditions. However, existing anomaly detection methods often rely on R-peak detection or heartbeat segmentation, which increases preprocessing complexity and reduces robustness to signal variability. To address these limitations, we propose MMAE-ECG, a multi-scale masked autoencoder designed to capture both global and local dependencies without such preprocessing steps. MMAE-ECG integrates a multi-scale masking strategy and a multi-scale attention mechanism with distinct positional embeddings, enabling a lightweight Transformer encoder to efficiently model ECG signals. Additionally, an aggregation strategy is introduced to improve anomaly score estimation. Experiments demonstrate that MMAE-ECG achieves state-of-the-art performance in both anomaly detection and localization while significantly reducing computational costs. Specifically, it requires only approximately 1/78 of the inference FLOPs and 1/18 of the trainable parameters compared to the previous leading method. Ablation studies further validate the contributions of each component, demonstrating the potential of multi-scale masked autoencoders as an effective and efficient approach for ECG anomaly detection.

Patients with coronary and cerebral atherosclerosis are characterized by increased levels of total serum calcium, ionized calcium, and phosphate, against a background of reduced levels of total serum protein and albumin. Here we aimed to develop a rapid diagnostic assay for mineral homeostasis disorders, based on assessing capacity of the acidic plasma proteins to bind excess calcium and phosphate ions. Plasma from bony fish, amphibians, reptiles, birds, mice, and patients with myocardial infarction was incubated with excess concentrations of calcium and phosphate at 37°C for varying time periods. The following assay readouts were defined: (i) plasma optical density after supersaturation with calcium and phosphate ions, reflecting excessive formation of calciprotein particles (CPPs); and (ii) CPP concentration in plasma. CPPs were formed in all vertebrates. The most pronounced plasma calcification propensity was observed in the human and mouse plasma, suggesting an evolutionary significance of CPP formation as a mechanism for clearance of excess circulating calcium and phosphate ions in mammals. Among the 11 protocols of supersaturation with calcium and phosphate ions, stable increase in plasma optical density at 620 nm wavelength (normalized OD₆₂₀, a measure of plasma calcification propensity) was achieved by adding solutions of CaCl₂ (+2 mmol/L, +50 µL), Na₂HPO₄·12H₂O (+2 mmol/L, +50 µL), and NaCl (+15.4 mmol/L, +20 µL) to plasma (80 µL). Increase in the normalized OD₆₂₀ was consistently detected within 10 min from the reaction onset during incubation in a microplate shaker (37°C), with mild-to-moderate variability across the parallel or sequential measurements and between the different operators. These results support relevance of validating the developed diagnostic assay for assessing mineral homeostasis disorders in the expanded cohorts of patients with myocardial infarction and ischemic stroke.

Long-term real-world effects of sacubitril/valsartan (S/V) and the impact of S/V dose reduction or discontinuation are less defined. We assessed longitudinal changes after S/V initiation and the association of dose changes with major adverse cardiovascular events (MACE).

Multicenter retrospective study of 592 HFrEF outpatients starting S/V (83% men; age 68±10 years; LVEF 32±7%). NT-proBNP, Kansas City Cardiomyopathy Questionnaire (KCCQ) and echocardiography were collected at baseline, 12 months and last follow-up. MACE was analyzed with Kaplan-Meier and Cox models.

NT-proBNP decreased from 1,000 (494-2,333) to 751 (304-1,726) and 735 (215-1,980) pg/mL (p<0.001). KCCQ improved from 53±15 to 62±14 and 66±15 (p<0.001). LVEF increased from 32±7 to 36±8 and 37±9% (p<0.001) and GLS improved from -10.8±3.2 to -12.3±3.1 and -14.0±2.9% (p<0.001). During a median follow-up of 3.72 years, 225 patients (38%) experienced MACE (36 deaths; 134 HF hospitalizations). MACE incidence was higher in patients with S/V discontinuation and with dose reduction (log-rank p=0.013 and p=0.014). In multivariable Cox analysis, S/V discontinuation (HR 1.52, 95% CI 1.28-1.97; p=0.040), change in GLS (HR 0.81, 95% CI 0.67-0.98; p=0.028) and change in KCCQ (HR 0.95, 95% CI 0.92-0.98; p=0.001) were independently associated with MACE.

S/V initiation was associated with sustained improvements in NT-proBNP, quality of life and cardiac remodeling. S/V discontinuation or dose reduction identified patients at higher MACE risk.

Accidental hypothermia after environmental exposure and/or impaired thermoregulation resulting in significant decrease in body temperature and cardiac arrest (CA) is linked to 1,500 deaths annually in the United States. Hypothermic CA treatment has specific presentation and clinical features. With appropriate treatment, its survival can reach 27-70%, contrasting ~ 10% in medical CA. Majority of accidental hypothermic CA survivors recover with favourable neurologic outcome. An integrated, dedicated multi-disciplinary team-approach is essential to maximize the chances of survival. We report on a 91-year-old female who was found outside and unresponsive in freezing temperatures. During transport, she required bag-and-mask ventilation. An esophageal temperature recorded 24.5 °C. Shortly after rapid sequence intubation, she developed CA. She was successfully resuscitated with chest compressions, epinephrine, atropine, and two defibrillations. Due to persistent hypothermia and bradycardia, she was rewarmed using extracorporeal membrane oxygenation. Perioperative transesophageal echocardiography showed normal cardiac function. She was extubated the next day. She remained stable for the rest of her hospital stay without focal neurological deficits on serial examinations. However, her post-arrest stay was complicated by acute delirium, likely from underlying dementia, with a waxing and waning level of consciousness, confusion, agitation and hallucinations. She was discharged on post-operative day 5. Her long-term recovery was complicated by repeated aspiration pneumonias, and gradual decline of her mental status due to Alzheimer's dementia. She died approximately two years later at the age of 93. Thus, full neurologic recovery remains possible after CA induced by severe hypothermia from environmental exposure, despite extreme age and frailty.