Citations

Introduction Hypoplastic left heart syndrome and Fontan procedure predispose to cardiac thrombus formation in the venous pathways due to the unique hemodynamic and hematologic disturbances inherent to the Fontan circulation. Systemic venous blood is routed passively to the pulmonary arteries without a subpulmonary pump, resulting in chronic low‐velocity flow, elevated central venous pressure, and venous stasis—all elements of Virchow's triad that favor clot formation 1 . Additionally, these patients exhibit reduced levels of protein C, coagulation factors II, V, VII, and X, plasminogen, and antithrombin III, along with increased levels of factor VIII 2,3 . Once a thrombotic event occurs, the rationale for lifelong anticoagulation is compelling. We report a case of an adult man that underwent Fontan palliation in infancy, with acute cerebral and renal infarcts, and discuss stroke and systemic embolism prevention. Case presentation A 22‐year‐old male with history of hypoplastic left heart syndrome status post Fontan procedure in infancy with congestive splenomegaly and liver disease presented with acute abdominal pain and was found to have bilateral renal infarcts. Anticoagulation was not initiated acutely and within 24 hours he developed left face and arm weakness, dysarthria and mild aphasia. Intravenous Tenecteplase was administered within 1 hour of symptom onset and was followed by symptoms’ complete resolution within 30 minutes of administration. Brain MRI confirmed scattered cerebral infarcts in the bilateral middle cerebral artery territories. Transthoracic echocardiogram showed atrial level shunting, expected due to fenestrated IVC to left atrium from prior Fontan procedure, and no evidence of atrial or ventricular thrombus. Due to the patient having evidence of multiple infarcts in multiple vascular beds within the brain and kidneys, an extensive hypercoagulable workup was undertaken which was unremarkable. The patient's stroke etiology was presumed to be cardioembolic from his altered cardiac anatomy with susceptibility to form venous thrombi and known surgically‐induced atrial level shunt. Low intensity heparin drip without bolus was started initially, and was transitioned to therapeutic apixaban upon discharge with proposed life long anticoagulation. Conclusions Subjects with hypoplastic heart syndrome display persistent unfavorable hemodynamics and procoagulant state after Fontan procedure. Either antiplatelet or anticoagulants are recommended after performing risk stratification. In high‐risk patients (recent thromboembolic event or stent, recurrent atrial arrhythmias, mechanical valve), therapeutic anticoagulation with either warfarin or direct oral anticoagulant is indicated, given increased vulnerability to recurrent events 1 . In intermediate‐risk subjects, antiplatelet or prophylactic doses of anticoagulation is indicated, whereas in low‐risk patients, antiplatelet agent is preferred.

Background Retinal vascular imaging offers a non‐invasive window into the central nervous system health and has shown promise in the study of neurodegenerative diseases. Emerging evidence highlights that Parkinson's disease (PD) exhibits structural and functional changes in the retina, including vascular alterations. This pilot study evaluated whether retinal vascular morphological features, quantified using the deep learning tool Automorph, discriminate PD from non‐PD subjects in the UK Biobank cohort. Methods We analyzed color fundus photographs (CFPs) from 303 PD participants (mean age 62.6 ± 5.4 years, hypertension (HTN) = 67%, diabetes mellitus (DM) = 13%) and 516 non‐PD controls (age = 55.9±8.1, HTN = 22.8%, DM = 3%) enrolled in the UK Biobank. Six retinal vascular morphology features were quantified: fractal dimension, vessel density, average width, distance tortuosity, squared curvature tortuosity, and tortuosity density. General linear models were used to assess group differences while adjusting for age, hypertension, and diabetes. We also evaluated the association between retinal features and age, and the left‐right eye retinal fractal measures correlations using Pearson correlation and Fisher Z‐test. Results Compared to non‐PD individuals, PD patients showed significantly altered retinal vessel average width, both without (p = 0.001) and with (p = 0.002) vascular covariate adjustment. Group‐by‐age interaction effects were also significant for fractal dimension (p = 0.010) and vessel density (p = 0.023). Furthermore, inter‐eye correlation of vessel density differed significantly between groups (p = 0.034), suggesting altered bilateral vascular symmetry in PD. Conclusion Measurable alterations in retinal vascular morphology in PD support the potential of retina vascular imaging for non‐invasive neurodegenerative disease research. These results warrant further validation in larger cohorts, with improved analytic robustness and automated retinal vascular grading.

Purpose White matter hyperintensity (WMH) is associated with heterogeneous pathologies. In neurodegeneration, the prevailing hypothesis is that WMH primarily reflects vascular pathology, exerting an additive effect in AD. Alternatively, a subset of WMH may arise secondary to AD‐related pathophysiology. APOE4 genotype, the greatest genetic risk factor for late‐onset AD, impacts the blood‐brain barrier and WMH burden. Herein, we investigate the association between regional WMH burden and APOE4 allelic dosage in cognitively normal individuals. Methods We used deep learning to automatically segment WMH from T2‐FLAIR MRI from 154 cognitively intact individuals older than 50. We mapped WMH to 4 specific brain regions (lobar, periventricular, basal ganglia and infratentorial, further parcellated into sub‐regions, Table 1) using atlas‐based registration and FastSurfer. WMH volumes were adjusted for total intracranial volume and normalized using log transformation. The APOE4 groups were compared for WMH burden using linear regression, controlling for age and vascular risk factors (hypertension, diabetes, hypercholesterolemia, cigarette smoking). For brain regions where more than 20% of participants had no WMH, a two‐part hurdle model was applied. Results We included 13 APOE4 homozygotes, 50 heterozygotes (ε4/ ε3) and 91 non‐carriers. Compared to non‐carriers, APOEε4 homozygotes exhibited significantly greater WMH burden in the whole brain, periventricular (posterior) and lobar regions (Figure 1a). Homozygotes exhibited a significantly greater WMH burden in the whole brain and posterior periventricular region, when compared to heterozygotes (Figure 1b). No significant whole‐brain or region‐specific differences were observed between heterozygotes and non‐carriers (Figure 1c). Conclusion In cognitively intact individuals at risk for AD, APOE4 homozygosity is associated with significantly greater WMH burden, particularly in the posterior periventricular space, after controlling for age and vascular risk factors. The relationship between regional‐specific WMH burden and neurodegeneration warrants further investigation. image image

Background: In younger patients (<60 years) with cryptogenic stroke (CS) presumed to be patent foramen ovale (PFO)-related, the standard approach involves transcatheter PFO closure combined with antithrombotic therapy. However, due to their exclusion from randomized clinical trials (RCTs), no formal recommendations exist for patients ⩾60 years. This study had two objectives (1) to compare the efficacy and safety of PFO closure versus antithrombotic therapy alone (ATA) exclusively in older patients (⩾60 years) and (2) to assess the outcomes of PFO closure in patients ⩾ 60 years versus < 60 years. Methods: We searched PubMed, Embase, Web of Science, and ScienceDirect databases to obtain articles in all languages from January 2004 until July 2025. The primary outcome was risk of recurrent stroke during follow-up. Secondary outcomes were risk of new-onset atrial fibrillation (AF), all-cause mortality, and in-hospital complications. PROSPERO registration ID: CRD420250652870. Results: Only one RCT (post hoc evaluation of the DEFENSE-PFO trial) and 11 observational studies were included. In patients aged ⩾ 60 years, risk of recurrent stroke was lower when PFO was closed compared with ATA (5.48% vs 10.05%, respectively, hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.45–0.80, p < 0.001, I 2 = 45.6%). All-cause mortality was also lower for PFO closure versus ATA (1.73% vs 7.59%, respectively, HR = 0.41; 95% CI = 0.19–0.90, p = 0.02; I 2 = 43.8%). There was no difference between PFO closure and ATA in risk of new-onset AF (HR = 1.13, 95% CI = 0.53–2.44, p = 0.74). Compared with patients < 60 years, individuals ⩾ 60 years who underwent PFO closure had a higher risk of recurrent stroke (2.94% vs 1.04%, respectively, HR = 3.47; 95% CI = 1.61–7.48; p = 0.001), new-onset AF (4.86% vs 1.01%, respectively, HR = 4.12; 95% CI = 1.90–8.95; p < 0.001), and all-cause mortality during follow-up (8.32% vs 0.39%, respectively, HR = 8.24; 95% CI = 3.49–19.46; p < 0.0001). In-hospital complications after PFO closure were comparable between two age groups. Due to insufficient data, we were not able to perform a subgroup analysis based on anatomic features of PFO, antithrombotic regimen, or occluder devices. Conclusion: Based on available data, which is predominantly derived from observational studies, PFO closure is associated with a reduced risk of recurrent stroke compared to ATA in patients over 60 years. However, these findings are subjected to limitations, including the potential for selection bias, unmeasured confounding, and insufficient long-term follow-up. Furthermore, long-term randomized trials are essential to definitively confirm efficacy and establish clinical guidelines for PFO closure in this older population.

Background Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. Methods A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. Results Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high‐risk sources of embolism for the primary outcome in the unmatched and matched analyses. Conclusions Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.

BACKGROUND: This individual participant data meta-analysis aimed to determine whether time to treatment influences the effect of intraarterial thrombolysis (IAT), intravenous thrombolysis, and conservative standard therapy on visual outcomes in nonarteritic central retinal artery occlusion. METHODS: We searched MEDLINE, CENTRAL, and Embase up to June 2023 for studies reporting treatment modality and peri-treatment best-corrected visual acuity (BCVA) for ≥5 participants, excluding patients with nonsevere vision loss (BCVA <1.0 logarithm of the minimum angle of resolution [logMAR]) or treated after 24 hours of symptom onset. The primary outcome was recovery from severe vision loss (final BCVA <1.0 logMAR). We used mixed-effect models and local polynomial regression to investigate nonlinear relationships between time to treatment and recovery from severe vision loss. RESULTS: Of 4074 screened studies, individual participant data were sought from 52, with 35 contributing individual participant data for 1038 participants. In total, 783 patients met inclusion criteria (age, 64.8±13.3 years; 35.5% female; baseline BCVA, 2.3±0.5 logMAR). For every hour decrease in time to treatment, thrombolysis was associated with greater improvement in BCVA (intraarterial, 0.02 logMAR [95% CI, 0–0.04]; intravenous, 0.04 logMAR [95% CI, 0.00–0.07]) than conservative standard therapy (0.01 logMAR [95% CI, 0–0.02]). A nonlinear relationship was detected for intraarterial thrombolysis with a changepoint at 8 hours (95% CI, 6.7–9.4). Thrombolysis was associated with increased recovery from severe vision loss compared with conservative standard therapy (intraarterial within 6 hours: odds ratio, 2.72 [95% CI, 1.02–7.28], 27.2% versus 12.0%; intravenous within 4.5 hours: odds ratio, 3.32 [95% CI, 1.24–8.92], 28.8% versus 11.1%). Findings were consistent in subgroup analysis restricted to patients receiving recombinant tissue-type plasminogen activator. Monte-Carlo simulations showed that a randomized controlled trial would require 95 participants per group to achieve 80% power to detect an odds ratio of 3.0 for recovery from severe vision loss. CONCLUSIONS: Early intervention in nonarteritic central retinal artery occlusion is associated with improvement in visual recovery, with intraarterial thrombolysis and intravenous thrombolysis outperforming nonthrombolytic treatments. These findings warrant confirmation in sufficiently powered randomized controlled trials.

Background Prompt diagnosis of acute central retinal artery occlusion (CRAO) is crucial for therapeutic management and stroke prevention. However, most stroke centers lack onsite ophthalmic expertise before considering fibrinolytic treatment. This study aimed to develop, train, and test a deep learning system to detect hyperacute CRAO on retinal fundus photographs within the critical 4.5‐hour treatment window and up to 24 hours after visual loss to aid in secondary stroke prevention. Methods Our retrospective, cross‐sectional study included 1322 color fundus photographs from 771 patients with acute visual loss due to CRAO, central retinal vein occlusion, nonarteritic anterior ischemic optic neuropathy, and healthy controls. Photographs were collected from 9 expert neuro‐ophthalmology centers in 6 countries, including 3 randomized clinical trials. Training included 1039 photographs (517 patients), followed by testing on 2 data sets: (1) hyperacute CRAO (54 photographs, 54 patients) and (2) CRAO within 24 hours after visual loss (110 photographs, 109 patients). Results The deep learning system achieved an area under the receiver operating characteristic curve of 0.96 (95% confidence interval (CI), 0.95–0.98), a sensitivity of 92.6% (95% CI, 87.0–98.0), and a specificity of 85.0% (95% CI, 81.8–92.8) for detecting CRAO at hyperacute stage, with similar results within 24 hours. The deep learning system outperformed stroke neurologists on a subset of hyperacute testing data set (120 photographs, 120 patients). Conclusions A deep learning system can accurately detect hyperacute CRAO on retinal photographs within a time window compatible with urgent fibrinolysis. If further validated, such systems could improve patient selection for fibrinolytic trials and optimize secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06390579.