Poli, Sven

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: 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.

ImportanceAtrial fibrillation (AF) is the most common, chronic, cardiac arrythmia in older US adults. It is not known whether AF is independently associated with increased risk of retinal stroke (central retinal artery occlusion), a subtype of ischemic stroke that causes severely disabling visual loss in most cases and is a harbinger of further vascular events.ObjectiveTo determine whether there is an association between AF and retinal stroke.Design, Setting, and ParticipantsThis retrospective cohort study was performed between July 2023 and May 2024 using computerized inpatient, outpatient, emergency department, and skilled nursing facility claims files for a 5% sample of US fee-for-service Medicare beneficiaries aged 66 years and older between 2000 and 2020. Follow-up ended at death, conclusion of fee-for-service Medicare coverage, end of the study period, or loss to follow-up of 85% of the study cohort.ExposureAF, based on validated International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes.Main Outcomes and MeasuresThe primary end point was incident retinal stroke in the primary diagnostic position of a single claim in any venue of care. Secondary end points included retinal stroke in any position of a single claim, 1 positive control end point (cerebral ischemic stroke), and 4 negative control end points (central retinal vein occlusion, urinary tract infection, humeral fracture, and cataract). Unadjusted and adjusted hazard ratios (HRs) and rate differences were computed across matched and overlap-weighted cohorts with and without AF (defined as 1 inpatient claim or 2 outpatient claims within a 365-day period).ResultsIn total, 1 090 144 patients (591 400 female [54.3%]; mean [SD] age, 76.92 [7.09] years) were included in the study; 545 072 patients had AF and 545 072 were matched controls. The median (IQR) follow-up was 45 (18 to 90) months. In total, 1333 patients with AF (rate, 0.55 per 1000 person-years) and 1082 AF-free matched controls (rate, 0.50 per 1000 person-years) experienced retinal stroke. The cause-specific, adjusted HR of retinal stroke after overlap weighting was 1.14 (95% CI, 1.02 to 1.28; adjusted rate difference, 0.05 [95% CI, −0.01 to 0.11]). AF was associated with cerebral ischemic stroke (adjusted HR, 1.73 [95% CI, 1.69 to 1.76]; adjusted rate difference, 10.11 [95% CI, 9.72 to 10.49]). Of 4 prespecified negative control end points, AF was not associated with central retinal vein occlusion but was associated with urinary tract infection, cataract, and humeral fracture.Conclusions and RelevanceIn this cohort study of Medicare beneficiaries aged 66 years and older, AF was independently associated with retinal stroke. The magnitude of the association was small, and a contribution from residual, unmeasured confounding could not be excluded.

Objectives: Elevated intracranial pressure and inadequate cerebral perfusion pressure may contribute to poor outcomes in hypertensive intraventricular hemorrhage. We characterized the occurrence of elevated intracranial pressure and low cerebral perfusion pressure in obstructive intraventricular hemorrhage requiring extraventricular drainage. Design: Prospective observational cohort. Setting: ICUs of 73 academic hospitals. Patients: Four hundred ninety-nine patients enrolled in the CLEAR III trial, a multicenter, randomized study to determine if extraventricular drainage plus intraventricular alteplase improved outcome versus extraventricular drainage plus saline. Interventions: Intracranial pressure and cerebral perfusion pressure were recorded every 4 hours, analyzed over a range of thresholds, as single readings or spans (≥ 2) of readings after adjustment for intracerebral hemorrhage severity. Impact on 30- and 180-days modified Rankin Scale scores was assessed, and receiver operating curves were analyzed to identify optimal thresholds. Measurements and Main Results: Of 21,954 intracranial pressure readings, median interquartile range 12 mm Hg (8–16), 9.7% were greater than 20 mm Hg and 1.8% were greater than 30 mm Hg. Proportion of intracranial pressure readings from greater than 18 to greater than 30 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 70 mm Hg were associated with day-30 mortality and partially mitigated by intraventricular alteplase. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and intracranial pressure greater than 20 mm Hg in spans were associated with both 30-day mortality and 180-day mortality. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 60 mm Hg were associated with poor day-30 modified Rankin Scale, whereas cerebral perfusion pressure less than 65 and less than 75 mm Hg were associated with poor day-180 modified Rankin Scale. Conclusions: Elevated intracranial pressure and inadequate cerebral perfusion pressure are not infrequent during extraventricular drainage for severe intraventricular hemorrhage, and level and duration predict higher short-term mortality and long-term mortality. Burden of low cerebral perfusion pressure was also associated with poor short- and long-term outcomes and may be more significant than intracranial pressure. Adverse consequences of intracranial pressure-time burden and cerebral perfusion pressure-time burden should be tested prospectively as potential thresholds for therapeutic intervention.