Systematic review and meta-analysis of stroke and thromboembolism risk in atrial fibrillation with preserved vs. reduced ejection fraction heart failure.

BACKGROUND: Stroke and thromboembolism (TE) are significant complications in patients with atrial fibrillation (AF) and heart failure (HF). The impact of ejection fraction status on these risks remains unclear. This study aims to compare the risk of stroke and TE in patients with AF and HF with preserved (HFpEF) or reduced (HFrEF) ejection fraction. METHODS: Literature search of PubMed, Embase, and Scopus databases was done for studies in adult (20 years or more) population of AF patients. Included studies had reported on the incidences of stroke and/or TE in patients with AF and associated HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Cohort (prospective and retrospective), case-control studies, and studies that were based on secondary analysis of data from a trial were eligible for inclusion. Methodological quality was assessed using the Newcastle Ottawa Scale (NOS). Pooled hazard ratio (HR) with 95% confidence intervals (CI) were reported. Exploratory analysis was conducted based on the different cut-offs used to define HFrEF and HFpEF. RESULTS: Twenty studies were analyzed. In the overall analysis, HFrEF in AF patients was associated with a significantly reduced risk of stroke and systemic TE (HR 0.88, 95% CI: 0.81, 0.96; n = 20, I2 = 86.6%), compared to HFpEF. However, most studies showed comparable risk of stroke among the two groups of patients except for two studies that had documented significantly reduced risk. Upon doing the sensitivity analysis by excluding these two studies, we found similar risk among the two group of subjects and with no heterogeneity (HR 1.01, 95% CI: 0.99, 1.03; n = 18, I2 = 0.0%). Exploratory analysis also showed that the risk of stroke and systemic thromboembolism was similar between those with HFpEF and HFrEF. CONCLUSION: The findings suggest that there is no significantly different risk of stroke and systemic thromboembolism in cases of AF with associated HFpEF or HFrEF. The finding does not support integration of left ventricular ejection fraction into stroke risk assessments.

Stroke after heart valve surgery: a single center institution report.

INTRODUCTION: Stroke is a potentially debilitating complication of heart valve replacement surgery, with rates ranging from 1 to 10%. Despite advancements in surgical techniques, the incidence of postoperative stroke remains a significant concern, impacting patient outcomes and healthcare resources. This study aims to investigate the incidence, risk factors, and outcomes of in-hospital adverse neurologic events, particularly stroke, following valve replacement. The analysis focuses on identifying patient characteristics and procedural factors associated with increased stroke risk. METHODS: This retrospective study involves a review of 417 consecutive patients who underwent SVR between January 2004 and December 2022. The study cohort was extracted from a prospectively recorded cardiac intensive care unit database. Preoperative and perioperative data were collected, and subjects with specific exclusion criteria were omitted from the analysis. The analysis includes demographic information, preoperative risk factors, and perioperative variables. RESULTS: The study identified a 4.3% incidence of postoperative stroke among SVR patients. Risk factors associated with increased stroke susceptibility included prolonged cardiopulmonary bypass time, aortic cross-clamp duration exceeding 90 min, prior stroke history, diabetes mellitus, and mitral valve annulus calcification. Patients undergoing combined procedures, such as aortic valve replacement with mitral valve replacement or coronary artery bypass grafting with AVR and MVR, (OR = 10.74, CI:2.65-43.44, p-value = < 0.001) and (OR = 11.66, CI:1.02-132.70, p-value = 0.048) respectively, exhibited elevated risks. Internal carotid artery stenosis (< 75%) and requiring prolonged inotropic support were also associated with increased stroke risk(OR = 3.04, CI:1.13-8.12, P-value = 0.026). The occurrence of stroke correlated with extended intensive care unit stay (OR = 1.12, CI: 1.04-1.20, P-value = 0.002) and heightened in-hospital mortality. CONCLUSION: In conclusion, our study identifies key risk factors and underscores the importance of proactive measures to reduce postoperative stroke incidence in surgical valve replacement patients.

Association of diabetes and white blood cell count with stroke in patients with carotid artery dissection.

BACKGROUND: Carotid artery dissection is an important cause of stroke. However, the predictors of ischemic stroke in patients with carotid artery dissection are controversial. The study aimed to analyze the predictors of ischemic stroke in patients with carotid artery dissection through retrospective medical records. METHODS: Data of discharged patients diagnosed with carotid artery dissection during 2019-2023 were retrospectively collected. Based on the occurrence of ischemic stroke, the patients were divided into the ischemic stroke or non-ischemic stroke groups. Based on the results of univariate analyses, variables with an associated P value < 0.05 were introduced into the multivariable logistic regression analysis. . RESULTS: A total of 165 patients were included in the study, with an average age of 55.00 (48.00, 66.00) years, including 86 patients with internal carotid artery dissection and 79 patients with vertebral artery dissection. Ischemic stroke occurred in 69 patients with carotid artery dissection. Multivariate logistic regression analysis indicated that diabetes (odds ratio [OR]: 3.144, 95% confidence interval [CI]: 1.552-6.508, P<0.002) and high white blood cells count (OR: 1.157, 95% CI: 1.02-1.327,P = 0.028) were related to the incidence of ischemic stroke in patients with carotid artery dissection. CONCLUSION: Ischemic stroke caused by carotid artery dissection causes severe damage to the nervous system. This study found that diabetes and high white blood cells count were associated with the incidence of ischemic stroke in patients with carotid artery dissection. Therefore, monitoring and controlling blood glucose levels and infections is essential in patients with carotid artery dissection to reduce the incidence of stroke.

Associations of Rest-Activity Rhythm Disturbances With Stroke Risk and Poststroke Adverse Outcomes.

BACKGROUND: Many disease processes are influenced by circadian clocks and display ~24-hour rhythms. Whether disruptions to these rhythms increase stroke risk is unclear. We evaluated the association between 24-hour rest-activity rhythms, stroke risk, and major poststroke adverse outcomes. METHODS AND RESULTS: We examined ~100 000 participants from the UK Biobank (aged 44-79 years; ~57% women) assessed with actigraphy (6-7 days) and 5-year median follow-up. We derived (1) most active 10-hour activity counts across the 24-hour cycle and the timing of its midpoint timing; (2) the least active 5-hour count and its midpoint; (3) relative amplitude; (4) interdaily stability; and (5) intradaily variability, for stability and fragmentation of the rhythm. Cox proportional hazard models were constructed for time to (1) incident stroke (n=1652) and (2) poststroke adverse outcomes (dementia, depression, disability, or death). Suppressed relative amplitude (lowest quartile [quartile 1] versus the top quartile [quartile 4]) was associated with stroke risk (hazard ratio [HR], 1.61 [95% CI, 1.35-1.92]; P<0.001) after adjusting for demographics. Later most active 10-hour activity count midpoint timing (14:00-15:26; HR, 1.26 [95% CI, 1.07-1.49]; P=0.007) also had higher stroke risk than earlier (12:17-13:10) participants. A fragmented rhythm (intradaily variability) was also associated with higher stroke risk (quartile 4 versus quartile 1; HR, 1.26 [95% CI, 1.06-1.49]; P=0.008). Suppressed relative amplitude was associated with risk for poststroke adverse outcomes (quartile 1 versus quartile 4; HR, 2.02 [95% CI, 1.46-2.48]; P<0.001). All associations were independent of age, sex, race, obesity, sleep disorders, cardiovascular diseases or risks, and other comorbidity burdens. CONCLUSIONS: Suppressed 24-hour rest-activity rhythm may be a risk factor for stroke and an early indicator of major poststroke adverse outcomes.

Association Between Oral Anticoagulant Adherence and Serious Clinical Outcomes in Patients With Atrial Fibrillation: A Long-Term Retrospective Cohort Study.

BACKGROUND: Patients with atrial fibrillation are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and atrial fibrillation clinical outcomes using methods not previously applied to this problem. METHODS AND RESULTS: Retrospective observational cohort study of incident cases of atrial fibrillation from population-based administrative data over 23 years. The exposure of interest was proportion of days covered during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, transient ischemic attack, or death and several secondary outcomes. A total of 44 172 patients were included with median follow-up of 6.7 years. For direct OACs (DOACs), each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, transient ischemic attack, or death. For vitamin K antagonist (VKA) the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the proportion of days covered spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels. CONCLUSIONS: Even small reductions in OAC adherence in patients with atrial fibrillation were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

Association of chronic kidney disease with postoperative outcomes: a national surgical quality improvement program (NSQIP) multi-specialty surgical cohort analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with higher incidence of major surgery. No studies have evaluated the association between preoperative kidney function and postoperative outcomes across a wide spectrum of procedures. We aimed to evaluate the association between CKD and 30-day postoperative outcomes across surgical specialties. METHODS: We selected adult patients undergoing surgery across eight specialties. The primary study endpoint was major complications, defined as death, unplanned reoperation, cardiac complication, or stroke within 30 days following surgery. Secondary outcomes included Clavien-Dindo high-grade complications, as well as cardiac, pulmonary, infectious, and thromboembolic complications. Multivariable regression was performed to evaluate the association between CKD and 30-day postoperative complications, adjusted for baseline characteristics, surgical specialty, and operative time. RESULTS: In total, 1,912,682 patients were included. The odds of major complications (adjusted odds ratio [aOR] 2.14 [95% confidence interval (CI): 2.07, 2.21]), death (aOR 3.03 [95% CI: 2.88, 3.19]), unplanned reoperation (aOR 1.57 [95% CI: 1.51, 1.64]), cardiac complication (aOR 3.51 [95% CI: 3.25, 3.80]), and stroke (aOR 1.89 [95% CI: 1.64, 2.17]) were greater for patients with CKD stage 5 vs. stage 1. A similar pattern was observed for the secondary endpoints. CONCLUSION: This population-based study demonstrates the negative impact of CKD on operative outcomes across a diverse range of procedures and patients.

Could Madelung disease be a cause of stroke? A rare case report.

Multiple symmetric lipomatosis (MLS), also known as Launois-Bensaude syndrome or Madelung disease, is a rare metabolic condition characterized by generally symmetrical, non-encapsulated fat accumulations in the patient's body.

Lipid on stroke in intracranial artery atherosclerotic stenosis: a mediation role of glucose.

Objective: Expanding on previous investigations, this study aims to elucidate the role of lipid metabolism disorders in the development of intracranial atherosclerotic stenosis (ICAS) and the determination of stroke risk. The primary objective is to explore the connections between lipid parameters and acute ischemic stroke (AIS), while also examining the potential mediating influence of fasting glucose levels. Methods: Retrospectively, we collected data from symptomatic ICAS patients at the First Affiliated Hospital of Soochow University, including their baseline information such as medical histories and admission blood biochemical parameters. Stenotic conditions were evaluated using magnetic resonance imaging, computed tomography angiography, or digital subtraction angiography. The associations between lipid parameters and AIS risks were investigated via multivariate logistic regression analysis. Results: A total of 1103 patients with symptomatic ICAS were recruited, among whom 441 (40.0%) suffered new ischemic events during hospitalization. After adjusting for confounding factors, the RCS curves exhibited a dose-response relationship between the atherogenic index of plasma (AIP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and AIS. Further multivariate analysis revealed significant associations between these parameters and AIS. Furthermore, mediation analysis indicated that fasting blood glucose (FBG) acted as a mediator in the association between lipid parameters (AIP, TC, and TG) and AIS. Conclusion: Higher lipid parameters in ICAS patients, particularly AIP, TC, and TG, were associated with an increased AIS risk. Additionally, FBG may mediate stroke risk in ICAS patients, highlighting the need for further exploration of underlying mechanisms.

A systematic review and meta-analysis of differences between men and women in short-term outcomes following coronary artery bypass graft surgery.

We provide an update regarding the differences between men and women in short-term postoperative mortality after coronary artery bypass grafting (CABG) and highlight the differences in postoperative risk of stroke, myocardial infarction, and new onset atrial fibrillation. We included 23 studies, with a total of 3,971,267 patients (70.7% men, 29.3% women), and provided results for groups of unbalanced studies and propensity matched studies. For short-term mortality, the pooled odds ratio (OR) from unbalanced studies was 1.71 (with 95% CI 1.69-1.74, I2 = 0%, p = 0.7), and from propensity matched studies was 1.32 (95% CI 1.14-1.52, I2 = 76%, p < 0.01). For postoperative stroke, the pooled effects were OR = 1.50 (95% CI 1.35-1.66, I2 = 83%, p < 0.01) and OR = 1.31 (95% CI 1.02-1.67, I2 = 81%, p < 0.01). For myocardial infarction, the pooled effects were OR = 1.09 (95% CI = 0.78-1.53, I2 = 70%, p < 0.01) and OR = 1.03 (95% CI = 0.86-1.24, I2 = 43%, p = 0.18). For postoperative atrial fibrillation, the pooled effect from unbalanced studies was OR = 0.89 (95% CI = 0.82-0.96, I2 = 34%, p = 0.18). The short-term mortality risk after CABG is higher in women, compared to men. Women are at higher risk of postoperative stroke. There is no significant difference in the likelihood of postoperative myocardial infarction in women compared to men. Men are at higher risk of postoperative atrial fibrillation after CABG.

The pathophysiology of patent foramen ovale and its related complications.

The foramen ovale plays a vital role in sustaining life in-utero; however, a patent foramen ovale (PFO) after birth has been associated with pathologic sequelae in the systemic circulation including stroke/transient ischemic attack (TIA), migraine, high altitude pulmonary edema, decompression illness, platypnea-orthodeoxia syndrome (POS) and worsened severity of obstructive sleep apnea. Importantly, each of these conditions is most commonly observed among specific age groups: migraine in the 20 to 40s, stroke/TIA in the 30-50s and POS in patients >50 years of age. The common and central pathophysiologic mechanism in each of these conditions is PFO-mediated shunting of blood and its contents from the right to the left atrium. PFO-associated pathologies can therefore be divided into (1) paradoxical systemic embolization and (2) right to left shunting (RLS) of blood through the PFO. Missing in the extensive literature on these clinical syndromes are mechanistic explanations for the occurrence of RLS, including timing and the volume of blood shunted, the impact of age on RLS, and the specific anatomical pathway that blood takes from the venous system to the left atrium. Visualization of the flow pattern graphically illustrates the underlying RLS and provides a greater understanding of the critical flow dynamics that determine the frequency, volume, and pathway of flow. In the present review, we describe the important role of foramen ovale in in-utero physiology, flow visualization in patients with PFO, as well as contributing factors that work in concert with PFO to result in the diverse pathophysiological sequelae.

Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design.

BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. CONCLUSION: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757869.

Association Between Exercise Systolic Blood Pressure and Risk of Stroke in Men With and Without Cardiovascular Disease.

PURPOSE: We tested the hypothesis that an exaggerated exercise systolic blood pressure (ESBP) would be associated with the risk of stroke in men with and without a history of cardiovascular disease (CVD). METHODS: An ESBP was defined as a maximal systolic blood pressure (SBP) ≥ 210 mmHg during graded exercise testing on a stationary bike until volitional fatigue in 2410 men aged 42 to 61 yr at baseline. RESULTS: Over a median 27-yr follow-up, 419 incident stroke events occurred. In a multivariable adjusted model, men with an ESBP had a significantly increased risk of stroke in the entire cohort (HR = 1.41: 95% CI, 1.15-1.74). This association was still significant following further adjustment for resting SBP (HR = 1.25: 95% CI, 1.01-1.56). In subgroup analysis, ESBP was modestly associated with an increased risk of stroke in men with a history of CVD (HR = 1.37: 95% CI, 0.98-1.93), with no strong evidence of an association in men without a history of CVD (HR = 1.20: 95% CI, 0.90-1.60). CONCLUSIONS: These findings suggest that the heightened risk of stroke related to ESBP response in a general population-based sample of men may be primarily driven by a history of CVD. The results underscore the importance of considering exercise blood pressure response when interpreting stress tests, particularly in individuals with pre-existing CVD.

Incidence and Predictors of Cerebrovascular Accidents in Patients Who Underwent Transcatheter Mitral Valve Repair With MitraClip.

Transcatheter mitral edge-to-edge repair (TEER) with transcatheter devices has become a mainstay in the minimally invasive treatment of patients with severe mitral regurgitation at increased surgical risk. Despite its apparently favorable risk profile, there is uncertainty on the risk and features of cerebrovascular accidents (CVAs) early and long after transcatheter mitral valve repair. We aimed to appraise the incidence and predictors of CVA in patients who underwent TEER. We explicitly queried the data set of an ongoing multicenter prospective observational study dedicated to TEER with MitraClip (Abbott Vascular, Santa Clara, California). The incidence of CVAs after TEER was formally appraised, and we explored potential predictors of such events. Descriptive, bivariate, and diagnostic accuracy analyses were performed. Of 2,238 patients who underwent TEER, CVAs occurred in 33 patients (1.47% [95% confidence interval 1.02% to 2.06%]), including 6 (0.27% [0.10% to 0.58%]) in-hospital strokes and 27 events after discharge (0.99% [0.66% to 1.44%]), over a median follow-up of 14 months. Most CVAs were major ischemic strokes during and after the in-hospital phase. Overall, CVAs were more common in patients with atrial fibrillation (p = 0.018), renal dysfunction (p = 0.032), higher EuroSCORE II (p = 0.033), and, as expected, higher CHA2DS2-VASc score (p = 0.033), despite the limited prognostic accuracy of the score. Notably, the occurrence of CVA did not confer a significantly increased risk of long-term (p = 0.136) or cardiac death (p = 0.397). The incidence of CVA in patients who underwent TEER is low, with most events occurring after discharge and being associated with preexisting risk features. These findings, although reassuring on the safety of TEER, call for proactive antithrombotic therapy whenever CVA risk is increased before and after TEER.

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial.

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.