Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent.

Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery in vivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.

Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Parabiosis Discriminates the Circulating, Endothelial, and Parenchymal Contributions of Endogenous Tissue-Type Plasminogen Activator to Stroke.

BACKGROUND: Intravenous injection of alteplase, a recombinant tPA (tissue-type plasminogen activator) as a thrombolytic agent has revolutionized ischemic stroke management. However, tPA is a more complex enzyme than expected, being for instance able to promote thrombolysis, but at the same time, also able to influence neuronal survival and to affect the integrity of the blood-brain barrier. Accordingly, the respective impact of endogenous tPA expressed/present in the brain parenchyma versus in the circulation during stroke remains debated. METHODS: To address this issue, we used mice with constitutive deletion of tPA (tPANull [tPA-deficient mice]) or conditional deletion of endothelial tPA (VECad [vascular endothelial-Cadherin-Cre-recombinase]-Cre∆tPA). We also developed parabioses between tPANull and wild-type mice (tPAWT), anticipating that a tPAWT donor would restore levels of tPA to normal ones, in the circulation but not in the brain parenchyma of a tPANull recipient. Stroke outcomes were investigated by magnetic resonance imaging in a thrombo-embolic or a thrombotic stroke model, induced by local thrombin injection or FeCl3 application on the endothelium, respectively. RESULTS: First, our data show that endothelial tPA, released into the circulation after stroke onset, plays an overall beneficial role following thrombo-embolic stroke. Accordingly, after 24 hours, tPANull/tPANull parabionts displayed less spontaneous recanalization and reperfusion and larger infarcts compared with tPAWT/tPAWT littermates. However, when associated to tPAWT littermates, tPANull mice had similar perfusion deficits, but less severe brain infarcts. In the thrombotic stroke model, homo- and hetero-typic parabionts did not differ in the extent of brain damages and did not differentially recanalize and reperfuse. CONCLUSIONS: Together, our data reveal that during thromboembolic stroke, endogenous circulating tPA from endothelial cells sustains a spontaneous recanalization and reperfusion of the tissue, thus, limiting the extension of ischemic lesions. In this context, the impact of endogenous parenchymal tPA is limited.

Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial.

BACKGROUND: The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS. METHODS: CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors. RESULTS: The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; P=0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; P<0.01). The P value was 0.56 for the treatment × ESUS status interaction effect. CONCLUSIONS: In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles and were classified as ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Eyes Wide Shut: A Cohort Study Questioning the Role of Fundoscopy in Infective Endocarditis Diagnosis.

In this retrospective/prospective study, we assessed the role of fundoscopy in 711 episodes with suspected infective endocarditis (IE); 238 (33%) had IE. Ocular embolic events (retinal emboli or chorioretinitis/endophthalmitis) and Roth spots were found in 37 (5%) and 34 (5%) episodes, respectively, but had no impact on IE diagnosis.

Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke.

BACKGROUND: Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM). METHODS: We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS2 score. RESULTS: Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5-76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397-827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend P<0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24-3.58) and 3.23 (95% CI, 2.07-5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14-5.74) and 4.25 (2.14-8.47), respectively. CONCLUSIONS: The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke.

Thrombotic and bleeding complications in patients with AL amyloidosis.

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were reported in 6% and arterial embolic events (AEEs) in 5% of patients, respectively, during a 55-month median follow-up. Lower albumin, lower eGFR, higher BM infiltration, soft tissue involvement, IMiD-based therapy and prior thrombosis were associated with VTE risk. Prior thrombosis was the only independent prognostic variable (HR 9.3, p = 0.001). Coronary arterial disease, prior AEE, 24-h proteinuria and higher platelet counts were associated with AEE risk. Significant bleeding events were reported in 9%, and associated mortality was 19%. Liver involvement, higher serum creatinine and higher baseline VWF:Ag levels were linked to bleeding risk. Using competing risk analysis, the cumulative probability of thrombosis/bleeding was higher during the first year following diagnosis, but a stable lower risk for both events remained for the duration of follow-up. In AL amyloidosis patients, the risk of thrombotic/arterial embolic events is significant, but the bleeding risk is also high. A multiparametric assessment is required to initiate anti-thrombotic or anti-platelet therapy appropriately.

Symptomatic carotid webs require aggressive intervention.

OBJECTIVE: Carotid web (CaWeb) is a rare form of fibromuscular dysplasia that can produce embolic stroke. Misdiagnosis of symptomatic CaWeb as "cryptogenic stroke" or "embolic stroke of unknown source" is common and can lead to recurrent, catastrophic neurologic events. Reports of CaWeb in the literature are scarce, and their natural history is poorly understood. Appropriate management remains controversial. METHODS: CaWeb was defined as a single, shelf-like, linear projection in the posterolateral carotid bulb causing a filling defect on computed tomography angiography (CTA) or cerebral angiography. Cases of symptomatic CaWeb at a single institution with a high-volume stroke center were identified through collaborative evaluation by vascular neurologists and vascular surgeons. RESULTS: Fifty-two patients with symptomatic CaWeb were identified during a 6-year period (2016-2022). Average age was 49 years (range, 29-73 years), 35 of 52 (67%) were African American, and 18 of 52 (35%) were African American women under age 50. Patients initially presented with stroke (47/52; 90%) or transient ischemic attack (5/52; 10%). Stenosis was <50% in 49 of 52 patients (94%) based on NASCET criteria, and 0 of 52 (0%) CaWebs were identified with carotid duplex. Definitive diagnosis was made by CTA examined in multiple planes or cerebral angiography examined in a lateral projection to adequately assess the posterolateral carotid bulb, where 52 of 52 (100%) of CaWebs were seen. Early in our institutional experience, 10 of 52 patients (19%) with symptomatic CaWeb were managed initially with dual antiplatelet and statin therapy or systemic anticoagulation; all suffered ipsilateral recurrent stroke at an average interval of 43 months (range, 1-89 months), and five were left with permanent deficits. Definitive treatment included carotid endarterectomy in 27 of 50 (56%) or carotid stenting in 23 of 50 (46%). Two strokes were irrecoverable, and intervention was deferred. Web-associated thrombus was observed in 20 of 50 (40%) on angiography or grossly upon carotid exploration. Average interval from initial stroke to intervention was 39 days. After an average follow-up of 38 months, there was no reported postintervention stroke or mortality. CONCLUSIONS: To our knowledge, this is the largest single-institution analysis of symptomatic CaWeb yet reported. Our series demonstrates that carotid duplex is inadequate for diagnosis, and that medical management is unacceptable for symptomatic CaWeb. Recurrent stroke occurred in all patients managed early in our experience with medical therapy alone. We have since adopted an aggressive interventional approach in cases of symptomatic CaWeb, with no postoperative stroke reported over an average follow-up of 38 months. In younger patients presenting with cryptogenic stroke, especially African American women, detailed review of lateral cerebral angiography or multi-planar, fine-cut CTA images is required to accurately rule out or diagnose CaWeb and avoid recurrent neurologic events.

Multi-Level Thrombotic/Embolic Burden and Its Role in Sex-Related Outcomes in Acute Limb Ischemia (ALI).

INTRODUCTION: The impact of sex upon outcomes in acute limb ischemia (ALI) remains disputed. We aim to quantify the effect of sex upon amputation-free survival (AFS) after a percutaneous-first approach for ALI. METHODS: Two-center retrospective review of ALI managed via a percutaneous-first approach. Demographics, comorbidities, and clinical characteristics were analyzed (Table I). The Kaplan-Meier and Cox regression were used to estimate AFS, limb-salvage and overall survival. RESULTS: Over nine years, 170 patients (87, 51% males; median age 67 IQR 59, 77 years) presented with ALI. Rutherford Classification was I in 56 (33%); IIa in 85 (50%); IIb in 20 (12%) and III in 9 (5%). Thirty-day mortality, major amputation rate and fasciotomy rates were 8% (N=13); 6.5% (N=11), and 4.7% (N=8), respectively. Among revascularized limbs, 92% were patent at 30 days. Length of stay was 7 (IQR 3-11) days. Complications included 13 bleeding episodes (8%), 4 cases of atrial fibrillation (2%), and 3 re-thrombosis/clot extension events (1.7%). No differences were noted in complication rates when stratified by sex. Females were older than males (median age 70 IQR 62, 79 vs 65 IQR 56, 76 years; p=0.02) and more likely to present with atrial fibrillation (20.5% vs 8%, p 0.02); and hyperlipidemia (72% vs 57%, p = 0.04). Females also more frequently presented with multi-level thrombotic/embolic burden compared to males (56% vs 43%; p=0.03), and required both aspiration thrombectomy and thrombolysis (27% versus 14%; p 0.02). Kaplan-Meier estimated median AFS, limb salvage, and overall survival were 425 (IQR 140, 824 days); 314 (IQR 72, 727 days); and 342 (IQR 112, 762 days). When stratified by sex, females had worse survival (median 270 IQR 92, 636 versus 406 IQR 140, 937 days; p=0.005); and limb salvage (median 241 IQR 88, 636 versus 363 IQR 49, 822 days; p=0.04) compared to males. Univariate Cox regression showed female sex (HR = 1.46 95% CI 1.04-2.05; p=0.03); multi-level thrombotic/embolic burden (HR 1.64 95% CI 1.17-2.31; p=0.004) and Rutherford Class (HR 1.37 95% CI 1.08-1.73; p=0.009) predicted major amputation/death. By multivariable Cox regression, multi-level thrombotic/embolic burden (HR 1.54 95% CI 1.09-2.17; p=0.01), Rutherford Class (HR 1.34 95% CI 1.07-1.69; p=0.01), and female Sex (HR = 1.45 95% CI 1.03-2.05; p=0.03) were each independently predictive of major amputation/death. CONCLUSIONS: A percutaneous-first strategy is safe and efficacious in the overall ALI population. Similar to prior works, female versus male ALI patients in our cohort have higher rates of mortality and major amputation. In our multivariable model, multi-level thrombotic/embolic burden was independently associated with a greater than 45% increased hazard of major amputation/ death at last follow up. Further prospective analysis is warranted to elucidate the underlying factors contributing to the higher prevalence of multi-level thrombotic/embolic burden in female ALI patients, and to further define the optimal percutaneous-first approach for ALI in consideration of patient sex and extent of clot burden.

Clinical impact of cerebral protection during transcatheter aortic valve implantation.

BACKGROUND: Embolization of debris can complicate transcatheter aortic valve implantation (TAVI) causing stroke. Cerebral embolism protection (CEP) devices can divert or trap debris. PURPOSE: To evaluate the efficacy of CEP during TAVI vs the standard procedure. DATA SOURCES: PubMed, SCOPUS and DOAJ 1/01/2014-04/12/2023. STUDY SELECTION: Randomized and observational studies comparing CEP versus standard TAVI, according to PRISMA. PRIMARY OUTCOME: stroke. SECONDARY OUTCOMES: death, bleeding, vascular access complications, acute kidney injury and infarct area. DATA EXTRACTION: Two investigators independently assessed study quality and extracted data. DATA SYNTHESIS: Twenty-six articles were included (540.247 patients). The primary endpoint was significantly lower (RR = 0.800 95%CI:0.682-0.940; p = 0.007) with CEP. Similarly, death rates were significantly lower with CEP (RR = 0.610 95%CI:0.482-0.771; p < 0.001). No difference was found for bleeding (RR = 1.053 95%CI:0.793-1.398; p = 0.721), vascular complications (RR = 0.937 95%CI:0.820-1.070; p = 0.334) or AKI (RR = 0.982 95%CI:0.754-1.279; p = 0.891). CONCLUSIONS: Use of CEP during TAVI is associated with improved outcomes. Future studies will identify patients who benefit most from CEP.

Determinants of Mortality and Mid-Term Outcomes After Transcarotid Artery Revascularization and Transfemoral Carotid Artery Stenting.

OBJECTIVES: The potential benefit of transcarotid artery revascularization (TCAR) over transfemoral carotid artery stenting (tfCAS) has been studied in the perioperative period with lower rates of stroke and death; however, data on mid-term outcomes are limited. We aimed to evaluate 3-year outcomes after TCAR and tfCAS and determine the primary predictors of 30-day and 1-year mortality following TCAR. METHODS: Data from the Vascular Quality Initiative for patients undergoing TCAR or tfCAS from January 2016 to December 2022 were analyzed. 1:1 propensity score matching using the nearest-neighbor method was used to adjust baseline demographics and clinical characteristics. Kaplan-Meier survival analysis and Cox Proportional Hazard Regression were used to evaluate long-term outcomes. Iterative stepwise multiple logistic regression analysis and Cox Proportional Hazard Regression were used to identify predictors of 30-day and 1-year mortality, respectively, based upon preoperative, intraoperative, and postoperative factors. RESULTS: A total of 70 237 patients were included in analysis (TCAR=58.7%, tfCAS=41.3%). Transcarotid artery revascularization patients were older and had higher rates of comorbid conditions and high-risk medical and anatomic features than tfCAS patients. Propensity score matching yielded 22 322 pairs with no major differences between groups except that TCAR patients were older (71.6 years vs 70.8 years). At 3 years, TCAR was associated with a 24% reduction in hazard of death compared with tfCAS (hazard ratio [HR]=0.76, 95% confidence interval [CI]=0.71-0.82, p<0.001), for both symptomatic and asymptomatic patients. This survival advantage was established in the first 6 months (HR=0.59, 95% CI=0.53-0.62, p<0.001), with no difference in mortality risk from 6 months to 36 months (HR=0.95, 95% CI=0.86-1.05, p=0.31). Transcarotid artery revascularization was also associated with decreased hazard for 3-year stroke (HR=0.81, 95% CI=0.66-0.99, p=0.04) and stroke or death (HR=0.81, 95% CI=0.76-0.87, p<0.001) compared with tfCAS. The top predictors for 30-day and 1-year mortality were postoperative complications. The primary independent predictor was the occurrence of postoperative stroke. CONCLUSIONS: Transcarotid artery revascularization had a sustained mid-term survival advantage associated over tfCAS, with the benefit being established primarily within the first 6 months. Notably, our findings highlight the importance of postoperative stroke as the primary independent predictor for 30-day and 1-year mortal. CLINICAL IMPACT: The ongoing debate over the superiority of TCAR compared to tfCAS and CEA has been limited by a lack of comparative studies examining the impact of pre-operative symptoms on outcomes. Furthermore, data are scarce on mid-term outcomes for TCAR beyond the perioperative period. As a result, it remains uncertain whether the initial benefits of stroke and death reduction observed with TCAR over tfCAS persist beyond one year. Our study addresses these gaps in the literature, offering evidence to enable clinicians to assess the efficacy of TCAR for up to three years. Additionally, our study seeks to identify risk factors for postoperative mortality following TCAR, facilitating optimal patient stratification.

Paradoxical Embolic Stroke Following Percutaneous Transluminal Angioplasty in a Hemodialysis Patient.

Paradoxical embolism is a medical condition characterized by the migration of an embolus from a venous source into the systemic circulation. This occurs through a specific cardiac abnormality known as a right-to-left shunt, ultimately resulting in the possibility of arterial embolism. Patent foramen ovale (PFO) is the most common cause of intracardiac shunting. We reported a rare case of a 56-year-old man on hemodialysis with PFO and arteriovenous fistula dysfunction who suffered a paradoxical embolic ischemic stroke after percutaneous transluminal angioplasty. This case emphasized the potential risk of paradoxical embolism in hemodialysis patients with vascular access problems. We aimed to highlight the importance of searching for PFO, as it may serve as a possible source of embolism in these patients.

Unusual subacute endocarditis following herpes zoster infection. a case report.

OBJECTIVE: This paper presents a rare case of subacute bacterial endocarditis (SBE) following a herpes zoster (HZ) episode, with no prior records found in the existing literature. PATIENT INFORMATION: Specifically, we describe a case of a 76-year-old female whose diagnosis of SBE was hindered by the concurrent manifestation of HZ symptoms, which had emerged 3 weeks before the onset of SBE indicators. FOLLOW-UP AND OUTCOMES: This delay in diagnosis resulted in profound complications, including a cerebrovascular accident and significant mitral valve destruction. DISCUSSION: HZ episodes have not conventionally been linked in the medical literature to the occurrence of SBE. Nonetheless, it is noteworthy that HZ infections have been associated with the development of other consequential bacterial infections, such as pneumonia and necrotizing fasciitis.This case underscores the necessity for medical practitioners to recognize the possibility of HZ symptoms obscuring indications of critical underlying conditions and infections. The implications of this report highlight the significance of maintaining heightened vigilance for signs of other severe infections when managing patients presenting with HZ symptoms.

Predictors of atrial fibrillation after embolic stroke of undetermined source in patients with implantable loop recorders.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), underlying subclinical atrial fibrillation (AF) is often suspected. Previous studies identifying predictors of AF have been limited in their ability to diagnose episodes of AF. Implantable loop recorders enable prolonged, continuous, and therefore more reliable detection of AF. The aim of this study was to identify clinical and ECG parameters as predictors of AF in ESUS patients with implantable loop recorders. METHODS: 101 ESUS patients who received an implantable loop recorder between 2012 and 2020 were included in this study. Patients were followed up regularly on a three-monthly outpatient interval. RESULTS: During a mean follow-up of 647 ± 385 days, AF was detected in 26 patients (26%). Independent risk factors of AF were age ≥ 60 years (HR 2.753, CI 1.129-6.713, p = 0.026), P-wave amplitude in lead II ≤ 0.075 mV (HR 3.751, CI 1.606-8.761, p = 0.002), and P-wave duration ≥ 125 ms (HR 4.299, CI 1.844-10.021, p < 0.001). In patients without risk factors, the risk of developing AF was 16%. In the presence of one risk factor, the probability increased only slightly to 18%. With two or three risk factors, the risk of AF increased to 70%. CONCLUSION: AF was detected in about one in four patients after ESUS in this study. A comprehensive evaluation involving multiple parameters and the existence of multiple risk factors yields the highest predictive accuracy for detecting AF in patients with ESUS.

An autopsy case of intravascular large B-cell lymphoma showing a rapid transition to embolic strokes with occlusion of the major cerebral arteries.

Intravascular large B-cell lymphoma can induce central nervous system manifestations, including strokes, due to small-vessel occlusion caused by lymphoma cells. However, involvement in large-sized vessels is rare. Here, we present an unusual autopsy case of an 88-year-old man showing a rapid transition from multiple strokes due to small vessel occlusion, typical of intravascular lymphoma, to progressive embolic strokes caused by the occlusion of major cerebral arteries. Magnetic resonance angiography demonstrated the major cerebral arteries associated with those multiple progressive strokes, including the right posterior cerebral artery, left anterior cerebral artery, and right middle cerebral artery, but the detectability was poor. A random skin biopsy at the abdomen confirmed the diagnosis of intravascular large B-cell lymphoma. The patient died 106 days after hospitalization despite intensive treatment. An autopsy revealed broad liquefactive necrosis in the area governed by the major cerebral arteries and multiple small infarctions caused by intravascular lymphoma cells in the small-sized vessels. In addition, the major cerebral arteries showed multiple thromboembolism with partial organization and clusters of intravascular lymphoma cells. Notably, those cells were shown aggregated and attached along the vascular wall of the basilar artery, which might have caused focal hypercoagulation in the near vessels. This aggregation might have disseminated widely in the other major cerebral arteries. Moreover, the cluster of intravascular lymphoma cells in the basilar artery was positive for tumor necrosis factor α, and similar histopathology findings were observed in the splenic veins. However, the pathogenesis of this rare phenomenon involving these cells remains unknown. From a clinical perspective, we should consider the possibility that intravascular lymphoma cells may provoke similar progressive embolic strokes.

3-D transesophageal echocardiography aids in assessment of embolic stroke due to aortic atherosclerotic plaque: A case series.

Atherosclerosis is the most common cause of heart disease and stroke. Plaque thickness ≥4 mm in the ascending aorta or aortic arch is strongly correlated with cerebral embolic events and ischemic stroke. However, despite imaging workup, the cause of embolic stroke remains unidentified in many patients. Transesophageal echocardiography (TEE) is the preferred echocardiographic method for the evaluation of cardiac source of emboli. 2D TEE imaging evaluates aortic root and aortic arch in a single plane or two planes with biplane imaging. However, 2D TEE often fails to detect mobile or complex components in the ascending aorta and aortic arch plaques. The routine availability of 3D TEE in current ultrasound systems may significantly improve the assessment of aortic plaques as a potential embolic source. In this case series, we present four consecutive patients with stroke who underwent TEE by a single cardiologist for possible cardioembolic source. Some of these patients may have been labelled as "cryptogenic stroke" or "embolic stroke of undetermined source" (ESUS) due to the presence of insignificant or nonmobile ascending aortic or aortic arch plaques on 2D TEE imaging. In our four consecutive patients with ESUS who underwent TEE by a single operator, 3D TEE showed complex aortic arch plaques with ulceration with mobile components and established these plaques as the likely source of embolic stroke.

Comparison of echocardiographic and clinical characteristics in embolic stroke and migraine patients with patent foramen ovale.

BACKGROUND: This single-center observational study aimed to compare the echocardiographic and clinical features in patients diagnosed with migraine and embolic stroke of undetermined source (ESUS) who presented with a known patent foramen ovale (PFO). METHODS: Two-dimensional and color Doppler images were obtained using various transthoracic echocardiography views for both migraine and ESUS patients. Suspected PFO cases underwent further assessment through contrast echocardiography and transesophageal echocardiography (TEE). High-risk PFO characteristics were evaluated using TEE, and the Risk of Paradoxical Embolism (RoPe) score was calculated. RESULTS: The study included 310 participants (age range: 18-60, 73.2% female), with 43.5% diagnosed with migraine and 56.5% with ESUS. Common comorbidities included diabetes (26.1%). High-velocity shunting through the interatrial septum was observed in 35.5% of patients. ESUS patients were older, with higher rates of diabetes and hypertension, while active smoking was more prevalent among migraine patients. Basic echocardiographic parameters were mostly similar, except for elevated pulmonary artery systolic pressure in ESUS. ESUS patients exhibited a greater occurrence of large microbubble passage through the interatrial septum and longer PFO lengths compared to migraine patients. However, the RoPe and High-risk PFO scores were similar between the groups. CONCLUSIONS: ESUS patients, characterized by older age and higher rates of diabetes and hypertension, demonstrated increased pulmonary artery pressure, more significant microbubble crossings, and longer PFO lengths. Conversely, migraine patients had a higher prevalence of active smoking. Despite differing clinical profiles, the risk scores for PFO-related embolic events were comparable between the groups. These findings underscore potential distinctions between ESUS and migraine patients with PFO and their implications for management strategies.

Management of atrial arrhythmias identified by cardiac devices.

Implantable cardiac devices have shown that atrial fibrillation (AF) is more frequent than previously assumed, with subclinical, asymptomatic, self-limiting manifestations called atrial high-rate events (AHREs) or subclinical AF. The clinical significance and correct therapeutic management of these episodes of subclinical AF is less well defined than in the case of clinically manifest AF. Two important randomized studies on the topic have recently been published, NOAH-AFNET 6 and ARTESIA, which, however, have not definitively clarified the topic. In patients with AHRE or subclinical AF, the average thrombo-embolic risk is lower than that in patients with clinically manifest AF and is ∼1%. For this reason, in these patients, the possibility that the benefit of anticoagulant therapy is overshadowed by the risk of bleeding is very high. Therefore, while waiting for new tools that allow a better stratification of low-risk patients, we must rely on individual clinical evaluation and overcome the qualitative dichotomy (AHRE yes vs. AHRE no), preferring instead an approach that is as quantitative as possible and takes into account the number of episodes, their duration, and the patient's CHADSVASC score, before deciding, in each individual case, whether or not to use anticoagulant therapy.