Transient Ischemic Attack Research Articles

Prevalence, determinants, and impact of significant shunt after percutaneous patent foramen ovale closure

Abstract Introduction Percutaneous closure of patent foramen ovale closure is increasingly performed for secondary prevention of PFO-related arterial embolic event. The clinical significance of postclosure residual right-to-left significant shunt remains unclear. Purpose To describe the prevalence, determinants, and clinical impact of a significant post-closure. Methods The AIR-FORCE is an ongoing prospective international registry of patients undergoing PFO closure from 19 centers in France, Canada and Italy. Only patients undergoing PFO for secondary prevention of an arterial embolic event with at least one available post-closure contrast transthoracic echocardiography (TTE) with agitated saline injection and Valsalva maneuvers were analyzed. Residual shunt was categorized according to the number of bubbles in the left atrial within 3 cardiac cycles at the first available contrast TTE as small (<10), moderate (10-20) or severe (> 20). Determinants of the presence of moderate or severe shunt were evaluated with multivariate logistic regression and its impact on the primary outcome (stroke, transient ischemic attack or peripheral arterial emboly) was evaluated with Cox model adjusted on age and sex. Results A total of 2413 patients, with a median age of 49.3 [40.4-57.4] years, 56% male, undergoing PFO closure between 2001 and 2023 were included. The first contrast TTE, which was performed after a median delay of 3.4 [0.9-5.8] months, reported the presence of moderate or severe residual shunt in 214 (8.9% 95%CI 7.8-10.1) patients. Determinants of the presence of moderate or severe residual shunt at the first contrast TTE were decreased body mass index (per 1kg/m², aOR 0.96 95%CI 0.93-0.99), severe shunt prior to PFO closure (aOR 3.54 95%CI 2.25-5.55) and increased device left disc diameter (per 1mm, aOR 1.08 95%CI 1.05-1.12). With a median follow-up of 2.2 [0.9-4.9] years, a total of 60 events were reported and the presence of moderate or severe residual shunt was associated with an increased risk of the primary outcome (aHR 2.46 95%CI 1.15-5.24) (Figure 1). Conclusions A moderate to severe residual right-to-left intracardiac shunt is not uncommon after PFO percutaneous closure and seems to be associated with an increased risk of arterial emboly recurrence.

Direct synchronized cardioversion not independently associated with infarcts on cerebral magnetic resonance imaging and clinical outcomes in patients with atrial fibrillation

Abstract Background Direct synchronized cardioversion (DCV) is frequently performed in atrial fibrillation (AF). In general, DCV is considered a safe procedure. A rare, but feared complication following DCV is an overt ischemic stroke resulting from embolization of a left atrial clot to the cerebral circulation. Purpose The aim of the present study was to assess the association of DCV with infarcts on brain magnetic resonance imaging (bMRI) and clinical outcomes. Methods 2386 patients of the Swiss AF cohort were included. 1731 patients were evaluated by bMRI. DCVs were recorded by questionnaire. Patients were categorized by number of DCVs performed before enrollment (0,1,≥2). BMRI were conducted at baseline and after 2 years (n=1227) and analyzed for large noncortical or cortical infarcts (LNCCI) and small noncortical infarcts (SNCI). Clinical outcomes were recorded during follow-up. Associations of DCV and outcome-measures were assessed by multivariate analyses. Results There was no independent association between the number of DCV and infarct prevalence (LNCCI + SNCI) on baseline bMRI (DCV 1 vs. 0: OR 0.95 [95% CI 0.73-1.26]; DCV ≥2 vs. 0: OR 1.04 [0.73-1.51]) or between DCV performed during follow-up and new infarcts on bMRI at 2 years (OR 1.46 [0.54-3.31]). DCVs were not associated with overt stroke or transient ischemic attack (DCV 1 vs. 0: HR 1.35 [0.87-2.03]; DCV ≥2 vs. 0: HR 1.54 [0.95-2.49]), hospitalization for heart failure (DCV 1 vs. 0: HR 1.03 [0.80-1.33]; DCV ≥2 vs. 0: HR 1.03 [0.77-1.37]), or death (DCV 1 vs. 0: HR 0.85 [0.67-1.09]; DCV ≥2 vs. 0: HR 0.92 [0.70-1.22]). Conclusions There was no association between DCV performed before enrollment and cerebral infarcts on baseline bMRI or between DCV performed during follow-up and new infarcts at 2 years. Moreover, DCV were not associated with clinical events.

Integrated care using the ABC-stroke pathway improves cardiovascular outcomes and survival in patients with recent ischaemic stroke: a population-based cohort study

Abstract Background A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed the ABC-stroke pathway, a holistic and integrated care approach to optimise the post-stroke management for patients with recent stroke, and associated heart disease. The ABC-stroke pathway is based on 3 pillars: "A" Appropriate Antithrombotic therapy; "B" Better functional and psychological status; and "C" Cardiovascular risk factors and Comorbidity optimisation (including lifestyle changes). There are limited data on the impact of adherence to the ABC-stroke pathway on post-stroke patient outcomes. Purpose We aimed to investigate the potential impact of ABC-stroke pathway adherence in the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong. Methods The analysis included patients with new-onset ischaemic stroke recorded in CDARS between 1st June 2006 and 31st May 2022. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between adherence to the ABC-stroke pathway and the primary outcome. The primary endpoint was a composite outcome of recurrent ischaemic stroke, transient ischaemic attack, haemorrhagic stroke, myocardial infarction, heart failure and all-cause death. Secondary outcomes were the individual components of the composite outcome, and cardiovascular death. Results Of the 9,669 included patients with ischaemic stroke (mean age 69.6 ± 13.4 years; 42.5% female), 58.1% were adherent to all 3 main ABC-stroke pillars. After 1 year of follow-up, adherence to the ABC-stroke pathway was associated with a lower risk of the primary composite endpoint (HR: 0.80; 95% CI: 0.72–0.88). Risk reductions increased progressively with a higher number of ABC-stroke criteria obtained (Figure 1). On multivariate analyses of the secondary outcomes, ABC-stroke pathway-adherent care was associated with a reduced risk of all-cause mortality (HR: 0.72; 95% CI: 0.62–0.85), cardiovascular death (SHR: 0.64; 95% CI: 0.45–0.90), haemorrhagic stroke (SHR: 0.50; 95% CI: 0.38–0.67) and heart failure (SHR: 0.771; 95% CI: 0.596-0.998) (Table 1). Conclusion In a large cohort of patients with ischaemic stroke, adherence to the ABC-stroke pathway was associated with a reduction of the risk of adverse outcomes.

Health-related quality of life and long-term incidence of major adverse events in patients with acute coronary syndromes

Abstract Background Assessing health-related quality of life (HRQoL) in patients with acute coronary syndromes (ACS) could provide insight into predicting major adverse cardiovascular events (MACE) and all-cause death. Purpose To investigate the association of baseline HRQoL and its change within the first year post-ACS with the incidence of MACE and all-cause death. Methods Participants in the SPUM-ACS study, a multicenter cohort of patients hospitalized for ACS at four Swiss university hospitals from 2007 and 2021 and followed-up for a median duration of 6.6 years, were evaluated for HRQoL at baseline and one-year post-discharge using the EQ-5D-3L index and visual analogue scale (VAS). The EQ-5D-3L index is derived from five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Baseline HRQoL and its change within the first year post-ACS, alongside the individual health dimensions, were analyzed in relation to the risk of subsequent MACE (composite of myocardial infarction, stroke or transient ischemic attack, coronary revascularization, and cardiovascular death) and all-cause death using Cox proportional hazards models, adjusting for sociodemographic, lifestyle factors, and medical history. Results 2499 patients with ACS (mean age 62±12 years, 80% males), primarily undergoing percutaneous coronary revascularization, were included. Over a median follow-up of 6.6 years, 25% experienced MACE and 13% died from any cause. Overall, HRQoL improved in the first year post-ACS, with the EQ-5D-3L index increasing from 0.74 to 0.81 and the VAS from 68 to 76 (p<0.001). At baseline, 80% reported some problem in at least one health dimension, mainly anxiety/depression (36%), pain/discomfort (35%), and mobility (27%). By the first year, 58% had no problem or improved in one or more dimensions; however, 38% declined in at least one dimension, particularly in pain/discomfort (26%), or anxiety/depression (16%). The baseline VAS, but not EQ-5D-3L index, was inversely associated with the hazard of subsequent MACE and all-cause death (HR=1.06 [1.01, 1.11] per 0.1-unit and 1.10 [1.03, 1.19] per 10-unit decrease, respectively). Problems with pain/discomfort were associated with MACE (HR=1.20 [1.00, 1.44]); and mobility, self-care and usual activities with all-cause death (HR=1.36 [1.04, 1.79], 1.44 [1.04, 1.98] and 1.37 [1.04, 1.80], respectively) (Figure 1). First-year EQ-5D-3L index and VAS change were inversely associated with the hazard of MACE (HR=1.11 [1.04, 1.18] per 0.1-unit and 1.16 [1.07, 1.25] per 10-unit decrease) and all-cause death (HR=1.13 [1.04, 1.23] per 0.1 and 1.17 [1.06, 1.30] per 10-unit decrease, respectively) (Figure 2). Conclusion HRQoL at baseline and its change within the first year after ACS are associated with the risk of adverse events, suggesting HRQoL might be a valuable predictive indicator for long-term outcomes in patients with ACS.Figure 1Figure 2

Neurologic recurrence after transcatheter PFO closure in patients with cryptogenic stroke

Abstract Background Patent foramen ovale (PFO) is associated with an increased risk of cryptogenic stroke, and interventional closure is recommended for secondary prevention. However, there is limited real-world data on long-term results. Our objective was to evaluate outcomes following successful transcatheter PFO occlusion. Methods Data from patients undergoing PFO closure for cryptogenic stroke between 2010 and 2015 were analysed to determine short- and long-term outcomes and to identify potential predictors of neurological recurrence. Results 330 patients underwent successful PFO closure. The mean age of patients was 49 (standard deviation (SD) ±12) years, and 55.5% were male. Any in-hospital adverse event was observed in eight patients (2.4%). During a median follow-up of 9.85 (SD ±2.5) years, the combined outcome of transient ischemic attack (TIA), stroke, or death from stroke was observed in 3.6% of patients (0.38 events per 100 person-years). After 5, 10, and 12 years the percentage of patients free of the composite outcome was 97.5%, 96.2%, and 96.2% respectively (Figure 1). New onset atrial fibrillation was detected in 10 patients (3.0%). A thorough analysis of the neurologic recurrences revealed a total number of six cryptogenic strokes (1.8%). Our results revealed that the Risk of Paradoxical Embolism (RoPE) score (adjHR: 0.70, 95% confidence interval [CI]: 0.52 to 0.95; p=0.022) and the number of prior neurologic events (adjHR: 9.78, 95% CI: 2.66 to 35.99; p<0.001) were strong independent predictors of future recurrent neurologic events. Kaplan Meier survival analysis stratified by number of previous neurologic events proved to be statistically significant (p<0.001; Figure 2). Conclusion In this real-world cohort of patients with cryptogenic stroke we observed excellent safety and good efficacy of percutaneous PFO closure, similar to randomized controlled trials or other long-term cohort studies. The rate of recurrent neurological events was low, especially cryptogenic strokes. The RoPE score confirmed good predictive power; in particular, the number of previous neurological events should be taken more into account when determining the indication for closure.

Cardiac amyloidosis and left atrial appendage closure: a multicenter retrospective study

Abstract Background Thromboembolic stroke risk remains a clinical challenge in cardiac amyloidosis (CA) patients with atrial fibrillation because of the increased prevalence of left atrial appendage thrombi irrespective of CHA2DS2-VASc score and a higher prevalence of factors that increase the risk of bleeding with anticoagulation. Left atrial appendage closure (LAAC) is an effective option in patients with atrial fibrillation and high bleeding risk; however, data describing a LAAC strategy for stroke prevention in patients with CA is limited. Among non-CA patients, procedural success and serious complication rates are around 98% and 3% respectively. Purpose In this multicenter retrospective study, we aimed to investigate whether left atrial appendage closure (LAAC) could reduce the risk of bleeding complications and ischemic cerebrovascular events in patients with CA. Methods In an international multi-center retrospective study, patients with CA that underwent LAAC were included. The diagnosis of CA was established on the basis of histologic confirmation or advanced multimodality cardiac imaging as per current consensus statements. Results A total of 28 patients (93% male; 87% ATTR-CA; 13% AL-CA; mean age 80 years) met inclusion criteria. At baseline, mean CHA2DS2-VASc and HAS-BLED scores were 4 and 3 respectively, mean left ventricular ejection fraction was 50%, and mean indexed left atrial volume was 58 mL/m2. 21% of patients had a prior history of ischemic stroke, 14% prior history of hemorrhagic stroke, 7% prior transient ischemic attack, and 54% had a prior history of major or minor bleeding. Procedural success was achieved in 26 patients (93%) with procedural complications occurring in 2 patients (vascular access site bleeding and cardiac tamponade). Regarding in-hospital and follow-up complications, 0% ischemic stroke, 0% hemorrhagic stroke, and major or minor bleeding in 4% of patients. During follow up, device thrombosis occurred in only 1 patient. Conclusion LAAC is a feasible and effective alternative to anticoagulation in patients with CA and excessive bleeding risk, with procedural success and complication rates similar to reported studies of non-CA patients.

Chronic Illness and visiting clinic before hospitalization at the onset of Stroke: Shiga Registry

Abstract Background Prompt action at stroke onset is required to improve prognosis. Some previous studies indicated that visiting local clinics may initially delay access to specialized care. We examined the relationship between the presence of chronic diseases known as risk factors for stroke and visiting a local clinic before admission to the hospital for acute stroke care. Methods This study utilized data from stroke patients aged 18 and older who were registered in the Shiga Stroke and Heart Attack Registry (SSHR) from January 2011 to December 2015. We excluded cases with onset during hospitalization or those with impaired consciousness assessed by the Japan Coma Scale (JCS > =10). The presence of comorbid chronic diseases was determined based on the past history and medications presented at admission. Local clinics are defined as clinics or hospitals that are not equipped to provide acute stroke treatment. Multivariate logistic regression analyses, adjusting for sex, age, modified Rankin Scale score before onset, and stroke subtypes, were performed to calculate odds ratios and 95% confidence intervals for visiting a clinic before hospitalization according to the presence of chronic diseases such as hypertension, diabetes, dyslipidemia, and atrial fibrillation, respectively. Results Data from 11,111 out of 14,620 registered cases were analyzed. Among these participants, 5,774 had hypertension, 1,951 had diabetes, 2,111 had dyslipidemia, and 882 had atrial fibrillation. A total of 2,405 (21.6%) cases visited a local clinic at stroke on set. The adjusted odds ratios for visiting clinics by the presence of hypertension were (1.22, 95% CI: 1.11 -1.34), diabetes (1.14, 1.01-1.28), dyslipidemia (1.07, 0.95 -1.20), and atrial fibrillation (0.80, 0.67 -0.95). Conclusions The present study indicated that individuals with hypertension and/or diabetes are more likely to initially visit a local clinic at stroke onset, whereas those with atrial fibrillation were not. Key messages • Approximately 20% of mild stroke patients first consult local or primary care doctors at stroke onset. This trend was particularly observed in individuals with hypertension and diabetes. • Emphasizing the need for direct access to specialized emergency care for individuals with chronic diseases is important to avoid delays in acute stroke care.

Pooled comparative analysis of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients with left ventricular assist device.

A thorough literature search was conducted on patients with Left Ventricular Assist Device (LVAD) and aortic insufficiency undergoing transcatheter aortic valve replacement (TAVR). We identified all original research studies that compared the long-term outcomes of surgical transcatheter aortic valve replacement (SAVR) versus TAVR for patients with LVAD, published between 1990 and 2023. The primary endpoint was the composite of in-hospital mortality, stroke, transient ischemic attack, myocardial infarction (MI), pacemaker implantation, vascular complications and cardiac tamponade. Secondary endpoints were the median overall survival (OS), the incidence of acute kidney injury (AKI), any bleeding needing transfusions or reintervention and cost. A total of fourteen studies and 358 patients were included (TAVR: 242; SAVR: 116). The composite outcome, the incidence of AKI, the bleeding needing transfusion, along with cost were significantly higher in the SAVR group. In addition, there was no significant difference between TAVR and SAVR in terms of median OS. The median OS in the TAVR group was 18 months. Finally, the most common causes of death were progression of heart failure and pneumonia. The present meta-analysis indicates that TAVR is associated with enhanced outcomes compared to SAVR for patients with LVAD presenting aortic insufficiency. Further well-designed original studies with greater sample sizes are necessary to validate our findings.

Safety of beta-blocker discontinuation after acute coronary syndromes with preserved or mildly reduced left ventricular ejection fraction: a target trial emulation from a real-world cohort.

The benefit of long-term beta-blocker therapy after acute coronary syndromes (ACS) without heart failure in the reperfusion era is uncertain. Two recent randomized trials found conflicting results. The present study assessed the safety of beta-blocker discontinuation within 12 months following ACS with LVEF ≥40%. In a multicentre prospective real-world cohort (N=3,762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers within 12 months post-ACS using target trial emulation and inverse probability weighting over an additional four-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of four-year cardiovascular death, myocardial infarction, stroke, transient ischemic attack, unplanned coronary revascularization, or unstable angina hospitalization. Of 2,077 patients, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at one year. The risk of primary endpoint was similar in both groups (14.1% versus 14.3% with beta-blocker discontinuation versus continuation; adjusted hazard ratio [aHR]=0.98; 95% confidence interval, 0.72-1.34, P=0.91). Subgroup analysis suggested a higher risk of primary endpoint with beta-blocker discontinuation after STEMI (aHR=1.46 [0.99-2.16]) compared to NSTEMI (aHR=0.70 [0.40-1.22], Pinteraction=0.033), whereas there was no interaction with LVEF (Pinteraction=0.68). Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared to long-term beta-blocker therapy. Subgroup analysis suggested potential risk in STEMI patients. Discontinuing beta-blockers 12 months after ACS appears safe in patients with LVEF ≥40%, particularly after NSTEMI.

Stroke recurrence after transcatheter PFO closure in patients with cryptogenic stroke.

Patent foramen ovale (PFO) closure is recommended for secondary prevention of cryptogenic stroke. However, data on long-term results are limited. We aimed to evaluate safety and efficacy of transcatheter PFO closure and predict neurologic recurrence. Data from patients undergoing PFO closure between 2010 and 2015 was collected to assess the combined endpoint of transient ischemic attack (TIA), stroke, or death from stroke at short- and long-term follow-up. 330 patients were included, mean age was 49 (±12) years and 55.5% were male. Before PFO closure, 86% experienced a stroke and 19% multiple neurological events. Procedure-related complications occurred in 2.4% of patients. Over a median follow-up of 10 years, the combined endpoint occurred in 3.6%, with a recurrence rate of 0.38 per 100 patient-years. Freedom from the combined endpoint at 5 and 10 years was 97.5% and 96.2%, respectively. New-onset atrial fibrillation was detected in 3%. The Risk of Paradoxical Embolism (RoPE) score (adjHR: 0.68; p=0.032), the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system (adjHR: 0.37; p=0.042), and a history of prior neurological events (adjHR: 9.94; p<0.001) were independent predictors of future recurrent neurologic events. Age, sex, and cardiovascular risk factors did not influence outcomes. In this real-world cohort, transcatheter PFO closure was associated with low long-term recurrence of neurologic events, especially cryptogenic strokes. The RoPE score, the PASCAL score and history of previous neurological events were predictive of recurrent events. This study supports the safety and efficacy of PFO closure for secondary prevention of cryptogenic strokes, and underscores the importance of patient selection.

Intravenous thrombolysis or antiplatelet therapy for acute nondisabling ischemic stroke: A systematic review and network meta-analysis.

Uncertainties remain on the optimal treatment for acute minor stroke with nondisabling symptoms. The two most common therapeutic approaches are intravenous thrombolysis (IVT) and antiplatelet therapy, notably dual antiplatelet therapy (DAPT). We synthesized data from the literature to compare IVT to DAPT and identify the best treatment for this population. We systematically searched Pubmed, Web of Science and the Cochrane Library for randomized trials and observational studies comparing IVT, aspirin, and/or DAPT, started within 24 h of symptom onset in patients with minor stroke (NIHSS ⩽ 5) and nondisabling symptoms. Random-effects Bayesian network meta-analysis was conducted. The primary outcome was excellent functional outcome at 3 months (mRS 0-1). Secondary outcomes included mRS 0-2, symptomatic intracranial hemorrhage, mortality, and recurrent stroke. Four randomized trials and 2 observational studies (5897 patients for the analysis of the primary outcome) were included. Compared with IVT (alteplase), DAPT (clopidogrel + aspirin) was significantly associated with higher odds of mRS 0-1 (OR = 1.52, 95% CrI, 1.09-2.35), but aspirin alone was not (OR = 1.36, 95% CrI, 0.87-2.30). DAPT was also associated with lower odds of symptomatic intracranial hemorrhage than alteplase (OR = 0.14, 95% CrI, 0.03-0.91). There were no significant differences between treatment groups regarding the other outcomes. For each outcome, the ranking for the best treatment was DAPT, then aspirin, and then IVT. This network meta-analysis suggests that DAPT may be the optimal treatment for acute nondisabling stroke, with higher odds of excellent functional outcome compared with IVT.Registration: PROSPERO ID: CRD42024522038.

Cost-Utility Analysis of Low-Dose Pioglitazone in a Population With Prediabetes and a History of Stroke or Transient Ischemic Attack.

Pioglitazone significantly reduces the risk of stroke in people with diabetes, and in those with prediabetes, it markedly reduces the risk of stroke/myocardial infarction and new-onset diabetes. Low-dose pioglitazone provides most of the clinical benefits of high-dose pioglitazone, with fewer adverse effects. We report an economic evaluation of the cost-effectiveness of low-dose pioglitazone versus placebo from a Canadian public payer perspective in 2023 Canadian dollars. A Markov model was developed at a lifetime horizon with an annual cycle length and 5 health states (event-free, myocardial infarction, stroke, new-onset diabetes, and death). Transition probabilities were extracted from the IRIS (Insulin Resistance Intervention in Stroke) trial. Health state costs and utilities were based on public sources. Annual discount rates of 1.5% were applied in the reference-case analysis. Probabilistic analyses were conducted to deal with parameter uncertainty through 5000 simulations. The costs were estimated as $24 887 (interquartile range [IQR], $14 632-$41507) for low-dose pioglitazone and $57 301 (IQR, $48 730-$67368) for placebo, resulting in a cost saving of -$30 287 (IQR, -$43 374 to -$14 587) in favor of low-dose pioglitazone. Quality-adjusted life years were estimated as 25.99 (IQR, 24.56-26.81) for the low-dose pioglitazone and 19.44 (IQR, 18.68-20.13) for placebo, resulting in a difference of 6.37 (IQR, 5.07-7.36) in favor of low-dose pioglitazone. Consistent findings were observed from scenario analyses and 1-way probability sensitivity analyses. Holding across a wide range of values in modeling parameters, low-dose pioglitazone is found as the dominant strategy versus a placebo.

Neuronal plasma biomarkers in acute ischemic stroke.

Early imaging-based detection of acute ischemic stroke (AIS) has improved in the era of reperfusion therapy. Despite of this, prognosis of outcome after AIS remains a challenge. Therefore, parameters that support clinical decision making are sought. Blood-based biomarkers have the potential to provide valuable information in addition to the established prognostic factors. Neuronal biomarkers of acute or degenerative neuronal injury have shown to be reliably detected in plasma. These biomarkers are well-established in neurodegenerative pathology, such as Alzheimer's disease. In this study, we explored the association between stroke diameter and plasma biomarkers for neuronal injury and tau pathophysiology (brain-derived tau [BD-tau], phosphorylated-tau-217 [p-tau21] and neurofilament light [NfL]) in patients (n = 193) admitted to the acute ward, Akershus University Hospital. All patients received a final diagnosis of AIS, transient ischemic attack or stroke mimics. Blood samples were obtained the day after admission. We find that levels of BD-tau (p = .004) and NfL (p = .011) were higher after AIS than in patients with stroke mimics. The cortical stroke diameter correlated with BD-tau (tau-b = 0.64, p < .001) and p-tau217 (tau-b = 0.36, p = .003). Linear regression confirmed BD-tau to be the strongest variable associated with stroke diameter, pointing to the potential clinical value of plasma BD-tau in outcome prediction after AIS.

Performance of Atrial Fibrillation Burden Trends for Stroke Risk Stratification.

Atrial fibrillation (AF) is associated with an increased risk of stroke, yet the limitations of conventional monitoring have restricted our understanding of AF burden risk thresholds. Predictive algorithms incorporating continuous AF burden measures may be useful for predicting stroke. This study evaluated the performance of temporal AF burden trends as predictors of stroke from a large cohort with insertable cardiac monitors. Using deidentified data from Optum Clinformatics Data Mart (2007-2019) linked with the Medtronic CareLink insertable cardiac monitor database, we identified patients with an insertable cardiac monitor for AF management (n=1197), suspected AF (n=1611), and cryptogenic stroke (n=2205). Daily AF burden was transformed into simple moving averages, and temporal AF burden trends were defined as the comparison of unique simple moving average pairs. Classification trees were used to predict ischemic stroke, and AF burden significance was quantified using bootstrapped mean variable importance. Of 5013 patients (age, 69.2±11.7 years; 50% male; CHA2DS2-VASc, 3.7±1.9) who met inclusion criteria, 869 had an ischemic stroke over 2 409 437 days total follow-up. Prior stroke or transient ischemic attack (variable importance, 13.13) was the number 1 predictor of future stroke followed by no prior diagnosis of AF (7.35) and AF burden trends in follow-up (2.59). Temporal proximity of AF and risk of stroke differed by device indication (simple moving averages: AF management, <8 days and suspected AF and cryptogenic stroke, 8-21 days). Together, baseline characteristics and AF burden trends performed optimally for the area under the receiver operating characteristic curve (0.73), specificity (0.70), and relative risk (5.00). AF burden trends may provide incremental prognostic value as leading indicators of stroke risk compared with conventional schemes.

Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial.

The addition of antiplatelet therapy to anticoagulant therapy in patients with stroke with non-valvular atrial fibrillation (NVAF) and atherothrombotic disease may increase bleeding risk without reducing recurrent stroke risk. To evaluate the clinical benefits of anticoagulant monotherapy compared to combination therapy with anticoagulants and antiplatelet agents. This is an investigator-initiated prospective multicenter, randomized, open-label, parallel-group clinical trial. Patients with NVAF and atherothrombotic disease who have had a recent ischemic stroke or transient ischemic attack will be eligible to participate in this trial. The primary outcome is a composite of ischemic cardiovascular events, including cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization, and major bleeding events within 2 years after randomization. This study will enroll 400 patients, 200 receiving anticoagulant monotherapy and 200 receiving combination therapy. This sample size will provide 90% power (one-sided p = 0.025) to detect a risk reduction in outcome events within 2 years, assuming event rates of 13 and 27% for each group, respectively, and a 10% loss to follow-up at a 2.5% significance level with one-sided log-rank tests at an interim analysis and a final analysis. This will be the first study to assess the net clinical benefit of oral anticoagulant monotherapy in ischemic stroke patients with NVAF and atherothrombosis. https://clinicaltrials.gov/study/NCT03062319, NCT03062319; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029222, UMIN000025392; https://jrct.niph.go.jp/latest-detail/jRCTs051180202, jRCTs051180202.

Comparative Effectiveness of Devices for Interventional Patent Foramen Ovale Closure: Insights from a 23-Year Monocentric Analysis.

Background/Objectives: Patent foramen ovale (PFO) is a congenital heart defect affecting up to 25% of the population, associated with an increased risk of cryptogenic stroke. Percutaneous PFO closure is a minimally invasive procedure aimed at reducing stroke risk by eliminating the right-to-left shunt. Methods: This monocentric, retrospective study analyzed 716 patients who underwent PFO closure between January 2000 and February 2023. Data collected included demographics, indications for closure, procedural details, and outcomes. Key endpoints were complications at the puncture site, pericardial effusion, recurrent stroke or transient ischemic attack (TIA), thrombi on the device, new-onset atrial fibrillation, and death. Results: The cohort had a mean age of 50.6 ± 12.6 years, with 60.8% female. Four devices were used: Occlutech PFO occluder (n = 106), Amplatzer PFO occluder (n = 227), Gore septal occluder (n = 296), and Cardia PFO-Star (n = 87). The initial procedural success rate was 98.9%, with no significant differences between devices. Complication rates were low across all devices. Residual shunt incidence decreased from 17.9% in 1 month to 3.4% in 12 months. Device-specific complications included late-onset pericardial effusion (p = 0.01), erosions (Cardia PFO-Star), and device thrombus formation (Gore septal occluder). Conclusions: PFO closure is a safe and effective method for preventing recurrent strokes, with high success rates and varying specific complication profiles, depending on the device. Further long-term studies are needed to evaluate newer devices and optimize patient outcomes.

How Much We Know about Dolicoarteriopathies

Vertebral and carotid artery dolicoarteriopathies, including elongation, kinking, and coiling, are linked to various cerebrovascular dysfunctions. Kinking, categorized by Metz, et al. is graded by angle severity: Grade 1 (90° - 60°), Grade 2 (60° - 30°), and Grade 3 (&lt; 30°). In Grades 2 and 3, reduced blood flow heightens ischemic risk, contributing to hemodynamic instability and cerebrovascular insufficiency. While most symptomatic cases undergo endovascular or surgical correction, some patients with severe kinking remain asymptomatic, questioning current understanding. In 150 cases of carotid or vertebral artery kinking, we observed stenosis in symptomatic patients, differing from the expected arterial enlargement seen in dolicoarteriopathies. This suggests two potential kinking types: stenotic and enlarged. A notable case presented bilateral Grade 3 internal carotid artery kinking, with right-sided stenosis and cerebral hypoperfusion, yet left-sided transient ischemic attacks occurred. This finding challenges existing classifications and suggests further investigation is warranted.

Twenty Years of Sustained Improvement in Quality of Care and Outcomes for Patients Hospitalized With Stroke or Transient Ischemic Attack: Data From The Get With The Guidelines-Stroke Program.

The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program. We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications. Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event (P<0.01 for all). In patients with acute ischemic stroke, large improvements were observed for anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022), smoking cessation counseling (44.7%-97.8%), dysphagia screening (53.8%-83.5%), thrombolytic treatment for patients arriving by 3.5 hours, treat by 4.5 hours (15.2%-92.9%), door-to-needle time within 60 minutes (19.0%-75.3%), and endovascular door-to-puncture time within 90 minutes (54.7%-62.8%). Similar improvements were also observed for measures relevant to patients with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack. Multivariable analysis showed that there was a sustained increase in odds of receiving each performance measure over time, independent of patient and hospital characteristics for each type of cerebrovascular event. After risk adjustment, there were temporal trends that patients were less likely to be discharged to a skilled nursing facility, and, for ischemic stroke only, more likely to be discharged directly home. During the first 20 years, Get With The Guidelines-Stroke participation was associated with sustained improvement in evidence-based care and outcomes for patients with stroke and transient ischemic attack in the United States.

Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.

Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemia attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first HF hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.

Microemulsion of Trichilia catigua A. Juss. (Meliaceae) improves memory recovery and reduces oxidative stress after cerebral ischemia in rats

We reported that a lyophilized ethyl-acetate fraction (EAF-L) of Trichilia catigua (popular ‘Catuaba’) facilitated memory recovery and reduced oxidative stress after cerebral ischemia in rats. However, oral doses as high as 400 mg/kg seem necessary to achieve those effects. Here we used an EAF microemulsion (EAF-ME) to evaluate whether a dose lower than that used previously can be suitable for memory neuroprotection. Intact rats were trained in the aversive radial maze (LRA) and subjected to transient global cerebral ischemia (TGCI). EAF-ME or EAF-L (100 mg/kg each) was administered at 4 hours of reperfusion and repeated in the next 6 days. Retrograde memory performance was assessed 7-, 14-, and 21-days postischemia. In a second experiment, a single EAF-ME dose was given at 4 h of reperfusion. Oxidative stress of brain tissue was assessed at 24 h of reperfusion. Lastly, after the FAE-ME treatment, the brain was examined for GFAP and Iba-1 immunoreactivity as neuroinflammation markers. The rats' ability to recall the AvRM task learned before ischemia was significantly reduced after ischemia (amnesia). Treatment with EAF-ME (100 mg/kg) mitigated this outcome, whereas the same dose of the EAF-L formulation did not. Furthermore, a single administration of the EAF-ME prevented oxidative stress by restoring SOD and CAT activities and reducing protein carbonylation and lipoperoxidation. Ischemia-induced glial cell immunoreactivity, however, was not precluded by the EAF-ME formulation. The current findings demonstrate that the neuroprotective efficacy of T. catigua can be improved by developing appropriate formulations that may enhance the bioavailability of polyphenolic constituents in the brain.