Brain magnetic resonance imaging and cognitive alterations after ablation in patients with atrial fibrillation.

Catheter ablation is an important non-pharmacological intervention for atrial fibrillation (AF), but its effect on the incidence of asymptomatic cerebral emboli and long-term effects on cognitive function remain unknown. We prospectively enrolled 101 patients who underwent AF ablation. Brain magnetic resonance imaging (MRI) (72 patients) and neuropsychological assessments (66 patients) were performed 1-3 days (baseline) and 6 months after ablation. Immediately after ablation, diffusion-weighted MRI and 3-dimensional double inversion recovery (3D-DIR) detected embolic microinfarctions in 63 patients (87.5%) and 62 patients (86.1%), respectively. After 6 months, DIR lesions disappeared in 41 patients. Microbleeds (MBs) increased by 17%, and 65% of the de novo MBs were exactly at the same location as the microinfarctions. Average Mini-Mental State Examination scores improved from 27.9 ± 2.4 to 28.5 ± 1.7 (p = 0.037), and detailed neuropsychological assessment scores showed improvement in memory, constructional, and frontal lobe functions. Ejection fraction, left atrial volume index and brain natriuretic peptide level improved from baseline to 3-6 months after ablation. Despite incidental microemboli, cognitive function was preserved 6 months after ablation.

Recovery of Hypoxic Regions in a Rat Model of Microembolism.

OBJECTIVES: Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke. Despite successful recanalization, a limited subset of patients benefits from the new treatment. Human MRI studies have shown that during removal of the thrombus, a shower of microclots is released from the initial thrombus, possibly causing new ischemic lesions. The aim of the current study is to quantify tissue damage following microembolism. MATERIALS AND METHODS: In a rat model, microembolism was generated by injection of a mixture of polystyrene fluorescent microspheres (15, 25 and 50 µm in diameter). The animals were killed at three time-points: day 1, 3 or 7. AMIRA and IMARIS software was used for 3D reconstruction of brain structure and damage, respectively. CONCLUSIONS: Microembolism induces ischemia, hypoxia and infarction. Infarcted areas persist, but hypoxic regions recover over time suggesting that repair processes in the brain rescue the regions at risk.

Enhancing vigilance for cerebral air embolism after pneumonectomy: a case report.

BACKGROUND: Vascular air embolism (VAE) is a rare but important complication that has not been paid enough attention to in the medical process such as surgery and anesthesia. CASE PRESENTATION: We report for the first time that a 54-year-old male patient with central lung cancer developed severe complications of CAE after right pneumonectomy. After targeted first-aid measures such as assisted breathing, mannitol dehydration and antibiotic treatment, the patient gradually improved. The patient became conscious at discharge after 25 days of treatment but left limb was left with nerve injury symptoms. CONCLUSION: We analyzed the possible causes of CAE in this case, and the findings from this report would be highly useful as a reference to clinicians.

Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.

Determination of cerebral blood flow velocity and microembolic signals in essential thrombocytosis by transcranial doppler ultrasonography.

OBJECTIVES: The goal of treatment in essential thrombocytosis (ET) is to prevent vascular complications such as thrombosis and hemorrhage. This study aimed to evaluate the risk of cerebrovascular microembolism in ET patients due to detection of microembolic signals (MES) and measure cerebral blood flow velocity (CBFV) by Transcranial Doppler (TCD) ultrasonography. MATERIAL AND METHODS: In this prospective case-control study, forty patients with diagnosed ET and age and sex-matched forty healthy controls were examined by the TCD sonography. RESULTS: The ET group had a higher rate of MES (8/40) in the right MCA than that in the control group (none), as measured by TCD. Five patients had MES at the left MCA compared to that in no subjects in the control group. The comparison of the ET and control groups in terms of CBFV parameters showed significantly lower end-diastolic FV at the right MCA in the ET group compared to that in the control group (p < 0.05). On the other hand; both pulsatility and resistance indices in the right and left MCA and the ratios of systolic to diastolic blood flow rates in the right and left MCA were significantly higher in the ET group than that in the control group. DISCUSSION: This study revealed that MES seems to be more common in patients with ET despite treatment. We could suggest that ET patients should be monitored more closely to address the potential risk of developing a cerebrovascular disease, which can be estimated by detection MES and raised CBFV, combine antiplatelet therapies to standard treatments.

Mechanism of Stroke According to the Severity and Location of Atherosclerotic Middle Cerebral Artery Disease.

BACKGROUND AND PURPOSE: Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease. METHODS: We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated. RESULTS: A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p < 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005). CONCLUSIONS: The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion.

Atrial fibrillation and Alzheimer's disease: A conundrum.

During ageing, the prevalence of Alzheimer's disease (AD) and of cardiovascular disease CVD) increases. Our aim is to investigate the relationship between AD and CVD and its risk factors, with a view to explaining the underlying mechanisms of this association. This review is based on the material obtained via MEDLINE (PubMed), Embase and Clinical Trials databases, from January 1980 until May 2019. The search term used was "Alzheimer's disease", combined with "cardiovascular disease", "hypertension", "dyslipidaemia", "diabetes mellitus", "atrial fibrillation", "coronary artery disease", "heart valve disease", "heart failure". Out of the 1328 papers initially retrieved, 431 duplicates and 216 records in languages other than English were removed; thus, only 98 papers were included in our research material. We have found that AD and CVD are frequently associated, while both of them, alone may be considered deleterious to health, the study of their combination constitutes a clinical challenge. Further research will help to clarify the real impact of CVD and its risk factors on AD, in order to better comprehend the effects of subclinical and clinical cardiovascular diseases on the brain. It may be hypothesized that there are various mechanisms underlying the association between AD and CVD, the main ones being: hypoperfusion and emboli, atherosclerosis, furthermore in both the heart and brain of AD patients, amyloid deposits may be present, thus causing damage to these organs. We need to clarify the real impact of these underlying hypothesized mechanisms and to investigate gender issues.

Angiographic And Clinical Response Of Intracranial Atherosclerotic Disease Large Vessel Occlusion Stroke Undergoing Mechanical Thrombectomy.

OBJECTIVES: To identify whether intracranial atherosclerotic disease large vessel occlusion strokes differ compared to embolic large vessel occlusion strokes in angiographic response to mechanical thrombectomy and clinical course. METHODS: Retrospective analysis of acute ischemic stroke patients with large vessel occlusion, due to intracranial atherosclerotic disease or embolic etiology, who underwent mechanical thrombectomy in a primary stroke center from 11/2015 to 4/2018. We categorized patients into intracranial atherosclerotic disease or embolic large vessel occlusion based on the procedural findings. We compared pretreatment, procedural variables, and post-procedural outcomes. RESULTS: Ninety-five patients were included, 13 with intracranial atherosclerotic disease large vessel occlusion strokes and 82 with embolic large vessel occlusion strokes. Between the two groups, there was no statistically significant difference in angiographic success (100% for intracranial atherosclerotic disease and 89% for embolic large vessel occlusion strokes); first pass success (38% for intracranial atherosclerotic disease and 34% for embolic large vessel occlusion strokes); puncture-to-first-pass time; puncture-to-recanalization time (68 minutes for intracranial atherosclerotic disease and 62 minutes for embolic large vessel occlusion strokes); number of passes; or clinical outcomes. Intracranial angioplasty was performed in 6 (46%) of intracranial atherosclerotic disease large vessel occlusion patients, and in 5 (6%) of embolic large vessel occlusion patients (p < 0.0001). CONCLUSIONS: Similar angiographic success and procedural time metrics are achievable with intracranial atherosclerotic disease large vessel occlusion and embolic large vessel occlusion therapy. This occurred with more frequent intracranial angioplasty for intracranial atherosclerotic disease large vessel occlusion strokes.

Transient atrial mechanical dysfunction assessed in acute phase of embolic stroke of undetermined source.

BACKGROUND AND PURPOSE: Paroxysmal atrial fibrillation (PAF) has been suggested as a major cause of embolic stroke of undetermined source (ESUS). Transient atrial mechanical dysfunction (stunning) frequently occurs after conversion of atrial fibrillation to sinus rhythm. The study aim was to determine if reversible atrial mechanical dysfunction in ESUS could help elucidate the mechanism of stroke. METHODS: Eighty-five consecutive patients with acute ischemic stroke were enrolled according to the following inclusion criteria: [1] ≥55 years old; [2] normal sinus rhythm upon admission; [3] no apparent embolic source; and [4] transthoracic echocardiographic evaluation had been performed in both the early phase (<72 h) and late phase (>7 days) after stroke onset. There were 27 patients in the lacunar or atherothrombotic infarction group (controls), 22 in the PAF group, and 36 in the ESUS group. To determine atrial stunning, transmitral flow velocity profiles (Doppler peak E- [early diastolic] and A- [atrial systolic] waves) were obtained. RESULTS: In the early phase, an E/A velocity ratio ≥ 1.0 was less common in the control group (1 patient, 3.7%) than in the PAF group (19 patients, 86.4%; p < 0.001) and ESUS group (10 patients, 27.8%; p < 0.05). In the late phase, the E/A ratio decreased to less than 1.0 in six patients (31.6%) who had PAF and in eight patients (80.0%) who had ESUS. CONCLUSION: Transient atrial mechanical dysfunction could be a helpful finding for elucidating the stroke mechanism in patients with ESUS, and early echocardiographic assessment could improve its detection.

Most High-Intensity Transient Signals Are Not Associated With Specific Surgical Maneuvers.

BACKGROUND: Mortality after congenital heart defect surgery has dropped dramatically in the last few decades. Current research on long-term outcomes has focused on preventing secondary neurological sequelae, for which embolic burden is suspected. In children, little is known of the correlation between specific surgical maneuvers and embolic burden. Transcranial Doppler ultrasound is highly useful for detecting emboli but has not been widely used with infants and children. METHODS: Bilateral middle cerebral artery blood flow was continuously monitored from sternal incision to chest closure in 20 infants undergoing congenital heart defect repair or palliative surgery. Embolus counts for specific maneuvers were recorded using widely accepted criteria for identifying emboli via high-intensity transient signals (HITS). RESULTS: An average of only 13% of all HITS detected during an operation were correlated with any of the surgical maneuvers of interest. The highest mean number of HITS associated with a specific maneuver occurred during cross-clamp removal. Cross-clamp placement also had elevated HITS counts that significantly differed from other maneuvers. CONCLUSIONS: In this study of infants undergoing cardiac surgery with cardiopulmonary bypass, the great majority of HITS detected are not definitively associated with a specific subset of surgical maneuvers. Among the measured maneuvers, removal of the aortic cross-clamp was associated with the greatest occurrence of HITS. Future recommended research efforts include identifying and confirming other sources for emboli and longitudinal outcome studies to determine if limiting embolic burden affects long-term neurological outcomes.

Cerebral vasomotor reactivity in migraine: effect of patent foramen ovale and aerogenic microembolism.

OBJECTIVE: The first data on the effect of presence of patent foramen ovale (PFO) with high-volume right-to-left shunt (RLS) on cerebral vasomotor reactivity (CVMR) in migraineurs are herein presented. In addition, the immediate effect of air microbubbles on CVMR has been determined. METHODS: Breath-holding index (BHI) and percent velocity decrease during hyperventilation (HPV) tests were performed before and after agitated saline injections in bilateral middle and posterior cerebral arteries (MCA and PCA) in 38 migraineurs (19 with aura) and 18 control subjects. RESULTS: Presence of PFO correlated with a significant decrease of MCA BHI (1.43 ± 0.39 vs 1.04 ± 0.67, p = 0.032) and marginal reduction of PCA BHI (1.25 ± 0.46 vs. 1.01 ± 0.39, p = 0.090) in migraineurs. After agitated saline injection, PCA BHI significantly decreased from 1.03 to 0.78 (p = 0.007) in patients with PFO, from 1.15 to 0.91 (p = 0.014) in those without PFO, and from 1.01 to 0.76 (p = 0.023) in subjects with migraine and PFO. No significant MCA BHI difference was noted soon after bubble injection. CONCLUSIONS: The presence of high grade RLS is associated with reduced vasodilatory CVMR in migraineurs. Further decrease of CVMR of PCA upon aerogenic microemboli passage may support the mechanism of 'facilitation with subclinical cerebral ischemia caused by microembolism', hypothesis explaining the onset of migraine. ABBREVIATIONS: BHI: Breath-holding index; BHT: Breath Holding Test; CVMR: Cerebral vasomotor reactivity; EDV: End-diastolic velocity; HIT-6: Headache Impact Test; HPV: Hyperventilation; MCA: Middle cerebral artery; MIDAS: migraine disability Assessment score; PCA: Posterior cerebral artery; PFO: Patent foramen ovale; PI: Pulsatility index; PSV: Peak systolic velocity; RLS: Right-to-left shunt; TCD: Transcranial Doppler; Vmean: Mean velocity.

Diagnostic accuracy of acute infarcts in multiple cerebral circulations for cardioembolic stroke: Literature review and meta-analysis.

OBJECTIVE: To determine the diagnostic value of acute infarcts in multiple cerebral circulations (AIMCC) on MRI diffusion-weighted imaging (DWI) for cardioembolism (CE) stroke subtype in adult patients hospitalized with acute ischemic stroke, we conducted a systematic literature review and meta-analysis. METHODS: MEDLINE was searched via PubMed for articles reporting patients hospitalized with acute ischemic stroke with MRI DWI categorized as AIMCC vs other and use of Trial of Org 10172 in Acute Stroke Treatment (TOAST) Criteria for cardioembolism subtype. Measures of diagnostic accuracy were calculated from the retrieved studies. RESULTS: Seven eligible articles comprised 5813 patients. Bivariate random effects models estimated sensitivity 0.19 (95% CI, 0.13 to 0.27), specificity 0.89 (0.86 to 0.91), positive predictive value 0.37 (0.30 to 0.45), negative predictive value 0.76 (0.7 to 0.82), positive likelihood ratio 1.70 (1.13 to 2.57) and negative likelihood ratio 0.91 (0.83 to 1). INTERPRETATION: The pattern of AIMCC on DWI is of limited diagnostic value. It is not sufficiently accurate to exclude cardiac pathology by a negative test nor does a positive test indicate a major increase in the probability of identifying a potential cardioembolic source.

Cerebral Protection Using Percutaneous Normothermic Bilateral Antegrade Cerebral Perfusion During Total Arch TEVAR in a Patient With Shaggy Aorta.

Purpose: To report a technique of global cerebral embolic protection (CEP) designed for use during thoracic endovascular aortic repair (TEVAR). Technique: Arterial cannulas are inserted percutaneously in the right axillary artery (12-F) and left common carotid artery (LCCA; 10-F) to provide normothermic antegrade cerebral perfusion during TEVAR with neuromonitoring. Inferior vena cava blood is drawn using a 19-F femoral cannula, filtered, oxygenated, and delivered through independent roller pumps to the arterial cannulas. Static CEP is obtained by balloon occlusion of the 3 aortic arch branches proximally, resulting in complete separation of aortic and cerebral blood flow; static CEP is used during aortic endograft delivery and deployment. Dynamic CEP, obtained by creating flow reversal in the innominate artery and proximal LCCA, is used at all other times. Successful use of this CEP technique is illustrated in a patient with shaggy aorta undergoing fenestrated total arch TEVAR. Conclusion: Percutaneous normothermic bilateral antegrade cerebral perfusion provides effective CEP during TEVAR.

Left Atrial Enlargement is Associated with Stroke Severity with Cardioembolic and Cryptogenic Subtypes in a Chinese Population.

BACKGROUND: Left atrial enlargement is associated with increased risk for stroke. However, few studies that evaluated the correlation between left atrial size and ischemic stroke severity. In this study, we aim to evaluate the association between left atrial size and stroke severity, especially with cardioembolic and cryptogenic stroke in the Chinese population. METHODS: A total of 1271 patients with acute ischemic stroke were included in this study. Echocardiographic left atrial diameter was measured and indexed to height. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Moderate-to-severe neurologic deficit was defined as NIHSS greater than or equal to 5. Patients were divided into mild, moderate, or severe abnormal left atrial size by tertile distribution. Binary logistic regression analysis was used to identify independent predictors of severe stroke after adjustment. RESULTS: Among all enrolled patients, 328 (25.8%) were classified into moderate-to severe stroke severity (NIHSS ≥ 5). In the multivariable model, compared with the lowest tertile of left atrial size, the odds ratio for moderate-to-severe neurologic deficit was 0.902 (95% CI, 0.644-1.264, P = .550) when left atrial size was the highest tertile. Of all patients, 190 patients were further categorized as cardioembolic and cryptogenic subtypes, and 70 (36.8%) were classified into moderate-to-severe stroke severity. After adjusting for confounders, compared with the lowest tertile, the top tertile of left atrial size was significantly associated with moderate-to-severe stroke (3.156, 95% CI, 1.143-8.711, P = .027). CONCLUSION: Left atrial enlargement was associated with more severe initial neurologic deficits of embolic subtypes (cardioembolic and cryptogenic stroke) in patients with acute ischemic stroke.

Analysis of human emboli and thrombectomy forces in large-vessel occlusion stroke.

OBJECTIVE: This study's purpose was to improve understanding of the forces driving the complex mechanical interaction between embolic material and current stroke thrombectomy devices by analyzing the histological composition and strength of emboli retrieved from patients and by evaluating the mechanical forces necessary for retrieval of such emboli in a middle cerebral artery (MCA) bifurcation model. METHODS: Embolus analogs (EAs) were generated and embolized under physiological pressure and flow conditions in a glass tube model of the MCA. The forces involved in EA removal using conventional endovascular techniques were described, analyzed, and categorized. Then, 16 embolic specimens were retrieved from 11 stroke patients with large-vessel occlusions, and the tensile strength and response to stress were measured with a quasi-static uniaxial tensile test using a custom-made platform. Embolus compositions were analyzed and quantified by histology. RESULTS: Uniaxial tension on the EAs led to deformation, elongation, thinning, fracture, and embolization. Uniaxial tensile testing of patients' emboli revealed similar soft-material behavior, including elongation under tension and differential fracture patterns. At the final fracture of the embolus (or dissociation), the amount of elongation, quantified as strain, ranged from 1.05 to 4.89 (2.41 ± 1.04 [mean ± SD]) and the embolus-generated force, quantified as stress, ranged from 63 to 2396 kPa (569 ± 695 kPa). The ultimate tensile strain of the emboli increased with a higher platelet percentage, and the ultimate tensile stress increased with a higher fibrin percentage and decreased with a higher red blood cell percentage. CONCLUSIONS: Current thrombectomy devices remove emboli mostly by applying linear tensile forces, under which emboli elongate until dissociation. Embolus resistance to dissociation is determined by embolus strength, which significantly correlates with composition and varies within and among patients and within the same thrombus. The dynamic intravascular weakening of emboli during removal may lead to iatrogenic embolization.

Cardiac-Neurovascular Adverse Effects Responsible to Contrast Transcranial Doppler: A Case Report.

Introduction and Case Presentation: A 44-year-old female patient suffered migraines and underwent contrast-enhanced transcranial Doppler (c-TCD). During the rapid injection of contrast agent, she suffered chest tightness, palpitation, decreased consciousness, perimouth numbness, and headache, respectively. Meanwhile, "curtain" pattern of air embolic signals lasted up to 115 seconds in her decreased right middle cerebral artery accompanied with arrhythmia. The microair embolic signals lasted as long as 340 seconds. The patient's symptoms were relieved in 30 minutes. The aforementioned symptoms and signs occurred, lasted, then disappeared coinciding in time with changes of microbubbles. The woman was later found to have ventricular septal defect. Discussion: The adverse effects to cardiac-neurovascular system of c-TCD are reported for the first time, which arouse attention to safety of the procedure.

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study.

BACKGROUND: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). AIMS: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. METHODS: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. RESULTS: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. CONCLUSIONS: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.

Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.

Septal total atrial conduction time for prediction of atrial fibrillation in embolic stroke of unknown source: a pilot study.

BACKGROUND: Subclinical atrial fibrillation (AF) is the underlying cause in a relevant part of patients with embolic stroke of unknown source (ESUS). This pilot study aims to identify novel echocardiographic parameters predicting AF subsequently detected in patients originally hospitalized with ESUS. METHODS AND RESULTS: Patients with acute ischemic stroke [baseline diagnosis of ESUS (n = 69), stroke of macro- or microvascular cause (n = 16/25), stroke caused by AF (n = 5)] and controls with paroxysmal AF without acute ischemic stroke (n = 22) as well as healthy controls of young and old age (n = 21/17) in sinus rhythm were included (overall n = 175). Echocardiography was performed in all participants. Prolonged Holter-ECG-monitoring was performed in all stroke patients. In the overall cohort, septal total atrial conduction time (sPA-TDI), left atrial (LA) volume index to tissue Doppler velocity (LAVI/a`) and second negative peak strain rate during LA contraction (SRa), representing echocardiographic parameters of LA remodelling and function, were statistically significant different in patients with and without AF and predictive for subclinical AF (multivariate regression analysis: sPA-TDI: HR 1.06 [1.04-1.08], p < 0.001; LAVI/a`: HR 0.85, [0.74-0.97], p = 0.02; SRa: HR 2.35 [0.9-5.5], p = 0.05). Multivariate Cox regression analysis revealed sPA-TDI as an independent predictor of AF in ESUS patients (sPA-TDI: HR 1.10 [1.04-1.17], p = 0.001). A sPA-TDI of 126 ms strictly discriminated between presence and absence of subclinical AF within 48 h after initiation of Holter-ECG-monitoring in ESUS patients. CONCLUSIONS: sPA-TDI seems to be a strong independent predictor of subclinical AF in patients hospitalized for ESUS and might support risk-stratified clinical decision making in these patients. Septal Total Atrial Conduction Time (sPA-TDI) determined by echocardiography for prediction of Atrial Fibrillation in Embolic Stroke of Unknown Source (ESUS).

Novel Embolic Protection Device: a Feasibility Study.

Stroke is ranked as the second leading cause of death worldwide. Ischemic stroke commonly results from emboli that originate in the heart among high-risk patients, such as those who develop atrial fibrillation. Yet, treatment is currently limited to anticoagulants, which may be associated with life-threatening bleeding. Our aim was to develop an alternative, device-based approach for continuous stroke prevention in high-risk patients. To this end, a novel endovascular tubular mesh was designed to be implanted in the aortic arch and to reroute emboli away from critical cerebral arteries. The feasibility of this approach as a means of ischemic stroke prevention was tested in vitro. The simulated cerebral perfusion pressures were not affected by the device. Also, the device efficiently diverted clinically meaningful embolic particles away from the cerebral circulation. It is proposed that this device could be used to reroute cardio-emboli away from intracranial vessels as a means of stroke prevention among patients for which anticoagulants are contraindicated.