Citations

Background/Objectives: Idiopathic intracranial hypertension (IIH) often features dural venous sinus stenosis; venous sinus stenting (VSS) improves venous outflow and intracranial pressure, but most stents are off-label, and few are engineered for intracranial venous anatomy. The aim was to synthesize animal models relevant to IIH/VSS, catalogue stents used clinically for VSS and summarize corresponding animal data, appraise current preclinical VSS research, and propose a pragmatic preclinical evaluation framework. Methods: We performed a targeted search (PubMed, Web of Science, Scopus; through to May 2025), dual-screened the records in Nested Knowledge, and extracted the model/device characteristics and outcomes as per the predefined criteria. Results: We identified 65 clinical VSS studies; most were retrospective and used off-label carotid/peripheral/biliary stents (Precise, Zilver, and Wallstent were the most frequent). Recent dedicated systems (River, BosStent) have limited animal evidence; VIVA has GLP porcine venous peripheral data demonstrating its patency, structural integrity, and benign healing outcomes. Rodent models reproduce obesity/androgen drivers with modest, sustained ICP elevation; large animal models show the technical feasibility of in sinus implantation, but no chronic focal venous stenosis model fully mirrors the IIH condition. Conclusions: Despite broad clinical uptake, the translational underpinnings of VSS in IIH remain incomplete: most devices lack intracranial venous-specific preclinical validation, and there is no existing animal model that recapitulates both IIH biology and focal sinus stenosis.

Background Guide catheter (GC) placement, whether distal or proximal, may influence the efficacy and safety of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, definitions of placement and procedural strategies vary across studies, limiting clarity. Methods We systematically searched PubMed, Embase, Scopus, and Web of Science from inception to September 1, 2024. Comparative studies of adult patients with anterior circulation AIS-LVO undergoing MT that reported GC placement were included. Both balloon GCs (BGCs) and non-BGCs were eligible. Data were pooled using random-effects models in R. Outcomes included functional independence (modified Rankin Scale 0–2 at 90 days), successful reperfusion (modified thrombolysis in cerebral infarction ≥2b or expanded thrombolysis in cerebral infarction ≥2c), first-pass recanalization (FPR), mortality, puncture-to-recanalization (PTR) time, and complications. Subgroup analyses were performed by thrombectomy technique and catheter type. Results Seven retrospective studies comprising 2148 patients (1042 proximal, 1106 distal) were analyzed. Distal placement was associated with higher rates of functional independence (risk ratio (RR): 1.25, 95% confidence interval (CI): 1.10–1.42), successful reperfusion (RR: 1.13, 95% CI: 1.04–1.22), and FPR (RR: 1.35, 95% CI: 1.15–1.58), as well as lower 90-day mortality (RR: 0.52, 95% CI: 0.28–0.82). PTR time was shorter with distal placement (mean difference: −7.7 min, 95% CI: −10.8 to −4.6). No significant differences were observed for symptomatic intracranial hemorrhage (RR: 0.96, 95% CI: 0.55–1.65) or emboli to new territory (RR: 0.84, 95% CI: 0.28–2.52). Benefits were consistent across both BGCs and non-BGCs. Heterogeneity existed in outcome definitions and techniques, and publication bias could not be excluded. Conclusions Distal GC placement is associated with improved reperfusion, efficiency, and functional outcomes in MT for anterior circulation AIS-LVO, without increased complications. Given the retrospective nature of included studies, anatomic confounding, and inconsistent outcome definitions, findings should be considered preliminary. Multicenter trials are needed to confirm whether catheter position independently predicts MT outcomes.

Abstract Valvular heart disease (VHD) is emerging as the next major epidemic in cardiovascular care, driven by the ageing population. The advent of less invasive alternatives to surgery—namely, transcatheter therapies—has revolutionized patient management, while simultaneously introducing new layers of complexity. Artificial intelligence (AI) holds significant promise to transform the care of patients with VHD across all dimensions, including diagnosis, prognostication, disease progression, and therapeutic decision-making. In this review, we provide a comprehensive overview of the current evidence, and discuss the challenges, risks, and future directions associated with the integration of AI in the management of VHD.

ABSTRACT Aims The impact of treatment for tricuspid regurgitation (TR) across different levels of left ventricular ejection fraction (LVEF) remains uncertain. This study aimed to compare the outcomes of surgical and transcatheter tricuspid valve interventions (TTVI) to conservative (medical) management across LVEF categories. Methods and results Patients with severe isolated TR from the TRIGISTRY, a multicentre international registry, were categorized based on LVEF (preserved ejection fraction [pEF]: ≥50%, mildly reduced ejection fraction [mrEF]: 41–49%, and reduced ejection fraction [rEF]: ≤40%). We assessed the impact of treatment modality and procedural success (mild-to-moderate or lower residual TR) on 2-year survival within each LVEF category. Among 2384 patients, 1383 had pEF, 400 had mrEF, and 601 had rEF. Compared to conservative management, surgery (p < 0.0005) and TTVI (p < 0.0001) were associated with a survival benefit in patients with pEF. No significant survival advantage was observed in patients with mrEF (p = 0.28 for both), nor in those with rEF (p = 0.76 and p = 0.22, respectively). Similar results were obtained when surgical and transcatheter interventions were grouped (p < 0.0001, p = 0.17 and p = 0.29 in patients with pEF, mrEF and rEF, respectively). Patients with residual TR after TTVI exhibited a trend toward worse survival compared to those managed conservatively across all LVEF categories (p = 0.47, p = 0.33 and p = 0.008 in pEF, mrEF and rEF, respectively). Conclusions Transcatheter tricuspid valve intervention, whether surgical or transcatheter-based, was associated with improved survival in patients with pEF but not in those with mrEF or rEF. Residual TR remained a significant prognostic factor across the entire LVEF spectrum. These findings highlight the need for careful patient selection when considering TTVI in individuals with rEF.

Abstract Background and Aims Type 1 short QT syndrome (SQT1) is a genetic channelopathy caused by gain-of-function variants in KCNH2, resulting in shortened cardiac repolarization and QT intervals, which predispose patients to ventricular arrhythmias and sudden cardiac death. This study aimed to investigate the therapeutic efficacy of KCNH2-specific suppression-and-replacement (KCNH2-SupRep) gene therapy in a transgenic rabbit model of SQT1. Methods KCNH2-SupRep was developed by combining a KCNH2-shRNA with its corresponding shRNA-immune KCNH2-cDNA into an AAV9 vector, delivered directly into the aortic root (1 × 1010 vg/kg). Therapeutic efficacy was evaluated in vivo by electrocardiogram, ex vivo by optical mapping, and at cellular levels by patch-clamp, calcium imaging, and qPCR in ventricular cardiomyocytes (VCMs). Results In vivo, KCNH2-SupRep normalized the heart rate-corrected QT interval (QTc) in SQT1 rabbits, without affecting repolarization heterogeneity. Ex vivo, KCNH2-SupRep corrected the action potential duration (APD90) and resolved the increased apicobasal APD90 heterogeneity observed in untreated (UT)-SQT1 hearts, supporting an antiarrhythmic effect, which was further validated by reduced re-entry formation in silico. At cellular levels, KCNH2-SupRep prolonged APD90 in VCMs from SupRep-SQT1 rabbits closer to wildtype levels compared with UT- and sham-SQT1. Additionally, KCNH2-SupRep restored the cellular surrogate of the electro-mechanical window and normalized IKr in nearly 50% of VCMs, in line with a 50%–60% suppression of the mutant KCNH2 transcript. Conclusions This proof-of-concept study is the first to demonstrate the efficacy of gene therapy for SQT1 in a medium-sized animal model. KCNH2-SupRep gene therapy successfully corrected the pathologic phenotype in vivo, ex vivo, and at cellular levels in transgenic SQT1 rabbits.