Atrial Fibrillation Risk Assessment after Embolic Stroke of Undetermined Source.

OBJECTIVE: Approximately 20% of strokes are embolic strokes of undetermined source (ESUS). Undetected atrial fibrillation (AF) remains an important cause. Yet, oral anticoagulation in unselected ESUS patients failed in secondary stroke prevention. Guidance on effective AF detection is lacking. Here, we introduce a novel, non-invasive AF risk assessment after ESUS. METHODS: Catch-Up ESUS is an investigator-initiated, observational cohort study conducted between 2018 and 2019 at the Munich University Hospital. Besides clinical characteristics, patients received ≥72 h digital electrocardiogram recordings to generate the rhythm irregularity burden. Uni- and multivariable regression models predicted the primary endpoint of incident AF, ascertained by standardized follow-up including implantable cardiac monitors. Predictors included the novel rhythm irregularity burden constructed from digital electrocardiogram recordings. We independently validated our model in ESUS patients from the University Hospital Tübingen, Germany. RESULTS: A total of 297 ESUS patients were followed for 15.6 ± 7.6 months. Incident AF (46 patients, 15.4%) occurred after a median of 105 days (25th to 75th percentile 31-33 days). Secondary outcomes were recurrent stroke in 7.7% and death in 6.1%. Multivariable-adjusted analyses identified the rhythm irregularity burden as the strongest AF-predictor (hazard ratio 3.12, 95% confidence interval 1.62-5.80, p < 0001) while accounting for the known risk factors age, CHA2 DS2 -VASc-Score, and NT-proBNP. Independent validation confirmed the rhythm irregularity burden as the most significant AF-predictor (hazard ratio 2.20, 95% confidence interval 1.45-3.33, p < 0001). INTERPRETATION: The novel, non-invasive, electrocardiogram-based rhythm irregularity burden may help adjudicating AF risk after ESUS, and subsequently guide AF-detection after ESUS. Clinical trials need to clarify if high-AF risk patients benefit from tailored secondary stroke prevention. ANN NEUROL 2023;93:479-488.

A critical assessment of the current pharmacotherapy for the treatment of embolic strokes of undetermined source.

INTRODUCTION: 'Embolic stroke of undetermined source' (ESUS) is a term coined to identify non-lacunar stroke whose mechanism is likely to be embolic, and the source remains unidentified. The best antithrombotic treatment for preventing stroke recurrence in this population has not been delineated. AREAS COVERED: The authors summarize and critically appraise the currently available evidence about the antithrombotic treatment for preventing stroke recurrence in patients with ESUS. Randomized trials addressing this topic were identified through MEDLINE (accessed by PubMed, as of November 2021, week 4). EXPERT OPINION: Recent randomized trials have failed to demonstrate a significant benefit of direct oral anticoagulants over aspirin in reducing the recurrence of cerebral infarctions in unselected cohorts of patients with ESUS. The heterogeneity and often overlap of embolic sources may be possible explanations for the overall absence of a benefit of oral anticoagulants in ESUS as a single homogeneous entity. The results of these trials and their subgroup analyses have provided important cues to understand the pathophysiology of ESUS. They have, furthermore, increased in the interest in researchers in identifying distinct etiological phenotypes within this stroke population. There is a good rationale for ongoing and future investigations in order to tailor antithrombotic treatment according to individual features of patients with ESUS.

Simultaneous assessment of plaque morphology, cerebral micro-embolic signal status and platelet biomarkers in patients with recently symptomatic and asymptomatic carotid stenosis.

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation.We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray-Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as 'MES+ve' or 'MES-ve'. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets.Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (25 vs. 30; P = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 109/L), neutrophil-platelet (3.3 vs. 2.7%), monocyte-platelet (6.3 vs. 4.55%) and lymphocyte-platelet complexes (2.91 vs. 2.53%) than 'asymptomatic patients with GSM-echodense plaques' (P ≤ 0.03).Recently, symptomatic carotid stenosis patients with 'GSM-echodense plaques' have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

Thrombectomy of Ventricular Assist Device-Originated Embolic Stroke: A Clinical Decision Model.

BACKGROUND AND PURPOSE: The use of ventricular assist devices (VADs) for the treatment of heart failure has become increasingly common. These patients have a considerable risk of cerebral embolism. We describe such a patient and his successful treatment by thrombectomy, compare his attributes with those previously published, and describe the construct of a clinical decision model, whose results bear practical implications for patient management. METHODS: The details of our patient and his treatment are presented, followed by a literature review of all previously reported similar cases. Using this information, as well as that available from published series, we constructed a probabilistic decision tree, completed all calculations (ie, "folding back"), and, in order to assess the strength of the results, subjected them to multiple independent sensitivity analyses of each of the variables. RESULTS: The therapeutic success of our case, the 14th reported to date, when combined with previous reports, shows: (1) recanalization times of 184 minutes, (2) "successful" recanalization (ie, TICI = 2b or 3) achieved in 71% of procedures, (3) ultimate functional outcome (ie, mRS = 0-2) achieved in 57% patients, and (4) ultimate successful heart transplantations in 66% of cases. The clinical decision model showed the predicted utility of thrombectomy to be superior to conservative management (3.33 QALY vs. 2.56 QALY, respectively). The sensitivity analyses support the validity of these results. CONCLUSIONS: In conclusion, thrombectomy appears to be a safe and effective method (and often the only viable one) for urgent treatment of patients with VAD-originated cerebral embolism.

Comparative Stroke, Bleeding, and Mortality Risks in Older Medicare Patients Treated with Oral Anticoagulants for Nonvalvular Atrial Fibrillation.

BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are alternatives to warfarin in patients with nonvalvular atrial fibrillation. Randomized trials compared NOACs with warfarin, but none have compared individual NOACs against each other for safety and effectiveness. METHODS: We performed a retrospective new-user cohort study of patients with nonvalvular atrial fibrillation enrolled in US Medicare who initiated warfarin (n = 183,318), or a standard dose of dabigatran (150 mg twice daily; n = 86,198), rivaroxaban (20 mg once daily; n = 106,389), or apixaban (5 mg twice daily; n = 73,039) between October 2010 and September 2015. Propensity score-adjusted Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the outcomes of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding, and all-cause mortality, comparing each NOAC with warfarin, and with each other NOAC. RESULTS: Compared with warfarin, each NOAC was associated with reduced risks of thromboembolic stroke (20%-29% reduction; P = .002 [dabigatran], P < 0.001 [rivaroxaban, apixaban]), intracranial hemorrhage (35%-62% reduction; P < 0.001 [each NOAC]), and mortality (19%-34% reduction; P < .001 [each NOAC]). The NOACs were similar for thromboembolic stroke but rivaroxaban was associated with increased risks of intracranial hemorrhage (vs dabigatran: HR = 1.71; 95% CI, 1.35-2.17), major extracranial bleeding (vs dabigatran: HR = 1.32; 95% CI, 1.21-1.45; vs apixaban: HR = 2.70; 95% CI, 2.38-3.05), and death (vs dabigatran: HR = 1.12; 95% CI, 1.01-1.24; vs apixaban: HR = 1.23; 95% CI, 1.09-1.38). Dabigatran was associated with reduced risk of intracranial hemorrhage (HR = 0.70; 95% CI ,0.53-0.94) and increased risk of major extracranial bleeding (HR = 2.04; 95% CI, 1.78-2.32) compared with apixaban. CONCLUSIONS: Among patients treated with standard-dose NOAC for nonvalvular atrial fibrillation and warfarin users with similar baseline characteristics, dabigatran, rivaroxaban, and apixaban were associated with a more favorable benefit-harm profile than warfarin. Among NOAC users, dabigatran and apixaban were associated with a more favorable benefit-harm profile than rivaroxaban.

Patient-specific multiscale computational fluid dynamics assessment of embolization rates in the hybrid Norwood: effects of size and placement of the reverse Blalock-Taussig shunt.

The hybrid Norwood operation is performed to treat hypoplastic left heart syndrome. Distal arch obstruction may compromise flow to the brain. In a variant of this procedure, a synthetic graft (reverse Blalock-Taussig shunt) is placed between the pulmonary trunk and innominate artery to improve upper torso blood flow. Thrombi originating in the graft may embolize to the brain. In this study, we used computational fluid dynamics and particle tracking to investigate the patterns of particle embolization as a function of the anatomic position of the reverse Blalock-Taussig shunt. The degree of distal arch obstruction and position of particle origin influence embolization probabilities to the cerebral arteries. Cerebral embolization probabilities can be reduced by as much as 20% by optimizing graft position, for a given arch geometry, degree of distal arch obstruction, and particle origin. There is a tradeoff, however, between cerebral pulmonary and coronary embolization probabilities.

Aortic atheroma as a source of stroke - assessment of embolization risk using 3D CMR in stroke patients and controls.

BACKGROUND: It was our purpose to identify vulnerable plaques in the thoracic aorta using 3D multi-contrast CMR and estimate the risk of cerebral embolization using 4D flow CMR in cryptogenic stroke patients and controls. METHODS: One hundred patients (40 with cryptogenic stroke, 60 ophthalmologic controls matched for age, sex and presence of hypertension) underwent a novel 3D multi-contrast (T1w, T2w, PDw) CMR protocol at 3 Tesla for plaque detection and characterization within the thoracic aorta, which was combined with 4D flow CMR for mapping potential embolization pathways. Plaque morphology was assessed in consensus reading by two investigators and classified according to the modified American-Heart-Association (AHA) classification of atherosclerotic plaques. RESULTS: In the thoracic aorta, plaques <4 mm thickness were found in a similar number of stroke patients and controls [23 (57.5%) versus 33 (55.0%); p = 0.81]. However, plaques ≥4 mm were more frequent in stroke patients [22 (55.0%) versus 10 (16.7%); p < 0.001]. Of those patients with plaques ≥4 mm, seven (17.5%) stroke patients and two (3.3%) controls (p < 0.001) had potentially vulnerable AHA type VI plaques. Six stroke patients with vulnerable AHA type VI plaques ≥4 mm had potential embolization pathways connecting the plaque, located in the aortic arch (n = 3) and proximal descending aorta (n = 3), with the individual territory of stroke, which made them the most likely source of stroke in those patients. CONCLUSIONS: Our findings underline the significance of ≥4 mm thick and vulnerable plaques in the aortic arch and descending aorta as a relevant etiology of stroke. CLINICAL TRIAL REGISTRATION: Unique identifier: DRKS00006234 ; date of registration: 11/06/2014.

Assessment of cerebral embolism and vascular reserve parameters in patients with carotid artery stenosis.

AIM: Carotid artery stenosis can result in the brain tissue injury related to the intracranial aterial flow disturbances as well as microembolic complications. The choice of the proper therapy in patients with carotid artery stenosis, especially asymptomatic, remains still a significant clinical problem. The study aim was an assessment of the cerebral embolism and brain vascular reserve parameters in patients with carotid artery stenosis regarding the occurrence of the clinical symptoms, the degree of stenosis as well as plaque morphology. METHODS: The study included 60 patients, with internal carotid artery stenosis. The degree of stenosis, the atherosclerotic plaque surface and morphology were assessed by the means of Duplex Doppler ultrasound. Cerebrovascular reactivity (vasomotor reactivity reserve test and Breath Holding Index) and monitoring of the microembolic signals (MES) were assessed with transcranial Doppler ultrasound examination (TCD). RESULTS: The vasoreactivity parameters were significantly lower in the group of patients with stenosis ≥70% and in patients with ulcerations on the plaque surface. Microembolic signals were recorded significantly more often in symptomatic patients; in patients with stenosis ≥70%; in patients with ulcerations on the plaque surface and those with hypoechogenic plaque structure. CONCLUSIONS: Microembolic signals in patients with symptomatic carotid stenosis are one of the ultrasound features of unstable carotid stenosis. Worse reactivity parameters of the cerebral arteries are associated with the presence of a large degree of carotid artery stenosis.

Risk factors associated with cerebrovascular recurrence in symptomatic carotid disease: a comparative study of carotid plaque morphology, microemboli assessment and the European Carotid Surgery Trial risk model.

BACKGROUND: The European Carotid Surgery Trial (ECST) risk model is a validated tool for predicting cerebrovascular risk in patients with symptomatic carotid disease. Carotid plaque hemorrhage as detected by MRI (MRIPH) and microembolic signals (MES) detected by transcranial Doppler (TCD) are 2 emerging modalities in assessing instability of the carotid plaque. The aim of this study was to assess the strength of association of MES and MRIPH with cerebrovascular recurrence in patients with symptomatic carotid artery disease in comparison with the ECST risk prediction model. METHODS AND RESULTS: One hundred and thirty-four prospectively recruited patients (mean [SD]: age 72 [9.8] years, 33% female) with symptomatic severe (50% to 99%) carotid stenosis underwent preoperative TCD, MRI of the carotid arteries to assess MES, PH, and the ECST risk model. Patients were followed up until carotid endarterectomy, recurrent cerebral event, death, or study end. Event-free survival analysis was done using backward conditional Cox regression analysis.Of the 123 patients who had both TCD and MRI, 82 (66.7%) demonstrated PH and 46 (37.4%) had MES. 37 (30.1%) cerebrovascular events (21 transient ischemic attacks, 6 amaurosis fugax, and 10 strokes) were observed. Both carotid PH (HR=8.68; 95% CI 2.66 to 28.40, P<0.001) as well as MES (HR=3.28; 95% CI 1.68 to 6.42, P=0.001) were associated with cerebrovascular event recurrence. Combining MES and MRIPH improved the strength of association (HR=0.74, 95% CI 0.65 to 0.83; P<0.001). The ECST risk model was not associated with recurrence (HR=0.86; 95% CI 0.45 to 1.65; P=0.65). CONCLUSIONS: The presence of carotid plaque hemorrhage is better associated with recurrent cerebrovascular events in patients with symptomatic severe carotid stenosis than the presence of microembolic signals; combining MES and MRIPH, further improves the association while the ECST risk score was insignificant.

Assessment of reverse flow as a means of cerebral protection during carotid artery stent placement with diffusion-weighted and transcranial Doppler imaging.

PURPOSE: To assess the effectiveness of flow reversal as an alternative means of cerebral protection by using transcranial Doppler recordings and diffusion-weighted imaging (DWI) as surrogate markers of brain injury. MATERIALS AND METHODS: Eighteen patients with symptomatic carotid artery disease were recruited. Magnetic resonance imaging was performed before the intervention and at 3 and 24 hours and 30 days after the intervention to detect new ischemic lesions with DWI. Transcranial Doppler recordings were made during the procedure to assess for microembolic signals (MESs). Data were compared against data from a historical control cohort of patients who underwent CAS placement with or without filter protection (n = 15 each) under the same protocol in a different study. RESULTS: There were fewer periprocedural new lesions on DWI in the reverse-flow cohort compared with the historical control cohort with filter protection (P = .084). Reverse flow revealed significantly fewer MESs during the whole procedure compared with the filter-protected group (P = .01) but not the unprotected group (P = .55). There was a marked decrease in MES counts for reverse flow protection during the embologenic stages of the procedure (P = .004). CONCLUSIONS: Use of the reverse flow device was associated with fewer overall lesions on DWI and proportionately fewer positive scans compared with the use of filter-type devices (P = .08, not significant). Transcranial Doppler recordings demonstrated a significant reduction in embolization to the brain during carotid artery stent placement with the use of reverse-flow cerebral protection.

[Social impact of stroke due to atrial fibrillation]. / Impacto social del ictus producido por fibrilación auricular.

Atrial fibrillation (AF) is the most frequent heart arrhythmia and causes a substantial proportion of ischemic strokes. AF has a marked impact on stroke severity, as well as on morbidity and mortality in these patients. The importance of AF as an etiologic factor of stroke increases in the elderly and in the last few years its detection has increased. The presence of AF leads to more severe initial neurological involvement, longer hospitalization, greater disability and a lower probability of discharge to home. In addition, AF is an independent risk factor for mortality, especially in women and the elderly. All these factors lead to a higher social and economic impact among stroke patients with AF.

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status.

BACKGROUND: 'Silent' cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). OBJECTIVE: To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). METHODS: Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. RESULTS: New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and catheterisation time (r=0.45, p=0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.4±6.2 vs 36.5±7.2; p=0.03) with no significant change in mental component summary (43.5±11.7 vs. 43.1±14.3; p=0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.56±0.26 vs. 0.59±0.31; p=0.70, and 54.2±19 vs. 58.2±24; p=0.43). CONCLUSION: Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were 'silent' with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Economy class stroke syndrome after a long drive.

Economy class stroke syndrome is a cardiovascular complication associated with long periods of travel, only a few cases have been reported after long drives, however. The patient, a 62-year-old professional driver, had driven a truck for 2 days with minimal rest. While driving, he noted left foot paresis and numbness, along with geographical disorientation. Magnetic resonance imaging of the brain revealed multiple cerebral embolisms in the bilateral cerebral hemisphere. The only complications representing a stroke risk in this patient were a patent foramen ovale and an anterior septal aneurysm, as detected by transesophageal echocardiography. The patient was diagnosed with paradoxical cerebral embolism following his long drive. This case report examines the paradoxical cerebral emboli documented in a patient following a long period of driving.

Assessment of silent microembolism by magnetic resonance imaging after cardioversion in atrial fibrillation.

INTRODUCTION AND OBJECTIVES: To study electrical cardioversion in patients with atrial fibrillation as a potential cause of acute ischemic brain lesions. METHODS: We performed prospective analysis of 62 consecutive patients (62 [10] years, 16 female). All of them were anticoagulated for at least 3 weeks with an international normalized ratio of 2.69 (0.66). In all cases a magnetic resonance imaging of the brain was performed before and 24h after the cardioversion, including diffusion-weighted sequences. A neurological exploration was also performed before and after the procedure, using the modified Ictus on the National Institute of Health Stroke Scale and the modified Rankin scale. Written informed consent was obtained in all cases. RESULTS: Of the 62 patients, 51 (85%) reverted to sinus rhythm. The neurological examination showed no changes after cardioversion. The pre-procedure magnetic resonance imaging showed microvascular disease in 35 (56%), including 2 patients with known cerebrovascular disease, and did not depict new clinically silent ischemic areas after cardioversion. CONCLUSIONS: After electrical cardioversion no acute ischemic lesions in the brain nor alteration in the neurological scales were found. Nevertheless, in 35 patients (56%) with persistent atrial fibrillation, the magnetic resonance imaging showed clinically silent ischemic lesions.

Development of a scoring system for atrial fibrillation in acute stroke and transient ischemic attack patients: the LADS scoring system.

INTRODUCTION: Detection of atrial fibrillation in patients presenting with ischemic stroke or transient ischemic attack (TIA) is important for the prevention of future events. We sought to develop a scoring system that would identify those patients most likely to have atrial fibrillation. METHODS: Records from an inpatient stroke and TIA database and echocardiographic data were reviewed. Consecutive acute stroke and TIA patients over the age of 18 who were admitted during a two-year period were studied. Univariate and multivariable analyses were performed to identify variables associated with atrial fibrillation. Logistic regression analyses were used to develop a scoring system for atrial fibrillation. RESULTS: 953 patient charts were reviewed; 145 patients (15%) had atrial fibrillation. In univariate and multivariate analyses, variables that were significantly associated with atrial fibrillation included left atrial diameter, age, and diagnosis of stroke. A history of smoking showed an inverse association. A 6-point scoring system based on these variables (with the acronym of LADS) was developed. A score of 4 or greater was associated with a sensitivity of 85.5% and a specificity of 53.1%. Approximately 47% of stroke and TIA patients would be excluded from further investigation using this score. CONCLUSIONS: We describe a system of scoring that identifies acute stroke and TIA patients with a greater chance of having atrial fibrillation. An inverse relationship with smoking was found. Further prospective studies are required to determine the clinical utility and cost-effectiveness of this scoring system in clinical practice and to investigate the inverse relationship between smoking and atrial fibrillation in this population.

Radiofrequency catheter ablation of atrial fibrillation: a cause of silent thromboembolism? Magnetic resonance imaging assessment of cerebral thromboembolism in patients undergoing ablation of atrial fibrillation.

BACKGROUND: Radiofrequency left atrial catheter ablation has become a routine procedure for treatment of atrial fibrillation. The aim of this study was to assess with preprocedural and postprocedural cerebral magnetic resonance imaging the thromboembolic risk, either silent or clinically manifest, in the context of atrial fibrillation ablation. The secondary end point was the identification of clinical or procedural parameters that correlate with cerebral embolism. METHODS AND RESULTS: A total of 232 consecutive patients with paroxysmal or persistent atrial fibrillation who were candidates for radiofrequency left atrial catheter ablation were included in the study. Pulmonary vein isolation or pulmonary vein isolation plus linear lesions plus atrial defragmentation with the use of irrigated-tip ablation catheters was performed. All of the patients underwent preprocedural and postablation cerebral magnetic resonance imaging. A periprocedural symptomatic cerebrovascular accident occurred in 1 patient (0.4). Postprocedural cerebral magnetic resonance imaging was positive for new embolic lesions in 33 patients (14). No clinical parameters such as age, hypertension, diabetes mellitus, previous history of stroke, type of atrial fibrillation, and preablation antithrombotic treatment showed significant correlation with ischemic cerebral embolism. Procedural parameters such as activated clotting time value and, in particular, electric or pharmacological cardioversion to sinus rhythm correlated with an increased incidence of cerebral embolism. Cardioversion was also associated with an increased risk of 2.75 (95 confidence interval, 1.29 to 5.89; P=0.009). CONCLUSIONS: Radiofrequency left atrial catheter ablation carries a low risk of symptomatic cerebral ischemia but is associated with a substantial risk of silent cerebral ischemia detected on magnetic resonance imaging. Independent risk factors for cerebral thromboembolism are the level of activated clotting time and, in particular, the electric or pharmacological cardioversion to sinus rhythm during the procedure.

Retinal angiography: noninvasive, real-time bubble assessment from the ocular fundus.

Formation of bubbles in tissue and vasculature from a sudden reduction in ambient pressure is likely an underlying cause of the clinical symptoms of decompression sickness (DCS). Thus, tools detecting bubbles in the vasculature may be important for evaluating DCS. Sheep were air-compressed to 6.0 ATA (30 minutes bottom time) then rapidly decompressed to the surface. A fundus camera was quickly positioned for continuous observation of the retinal vasculature. Bubbles were observed in the retinal vasculature of 25.8% (n = 31) of the sheep. Bubble onset time ranged from 5-22 minutes post-chamber and lodge time ranged from 0-70+ minutes. Bubbles were visualized mostly in the arteries of the retinal circulation. Severe vasoconstriction was captured using red-free angiography in two sheep. In two other sheep, fluorescein angiography demonstrated occluded blood flow caused by arterial gas emboli. This study demonstrates that retinal angiography is a practical tool for real-time, noninvasive detection of bubbles in the retinal circulation, a visible window to the cerebral circulation. Thus retinal angiography may prove invaluable in the early detection of arterial gas emboli in the cerebral circulation, the resolution of which is imperative to favorable neurological outcomes. This study also presents for the first time images of bubbles in the retinal circulation associated with DCS captured by a fundus camera.

Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help?

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) accounts for a majority of long-term morbidity and mortality associated with bleeding while on warfarin. Both ICH and warfarin-related ICH appear to have a genetic component. Furthermore, advanced neuroimaging using MRI can now identify individuals at increased risk of ICH. We explore whether screening strategies that include genetic profiling and neuroimaging might improve the safety of chronic anticoagulation for atrial fibrillation by identifying individuals from whom warfarin should be withheld. METHODS: We used a Markov state transition decision model. Effectiveness was measured in quality-adjusted life-years. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles along with empirical data from our institutions. The base case was a 69-year-old man with newly diagnosed nonvalvular atrial fibrillation. RESULTS: For patients at average risk for thromboembolic events and known to possess a hypothetical genetic profile increasing risk for warfarin ICH, anticoagulation remains the preferred strategy until the relative hazard of ICH exceeds 23.8. Genetic profiling would be favored for patients at low risk of thromboembolism (1.5% per year) if the hypothetical gene variant(s) conferred a relative risk of ICH >4.1. Screening strategies in which patients underwent genotyping and MRI before anticoagulation did not improve aggregate patient outcomes unless the predictive power of MRI exceeded current best guess estimates and patients were at low to moderate risk of thromboembolism. CONCLUSIONS: Currently identified genetic markers of bleeding risk do not confer a risk of ICH sufficiently high to warrant routine genetic testing for patients at average risk of thromboembolism. Even if patients undergo screening with MRI as well as genotyping, currently available data on the role of MRI on risk of ICH and warfarin ICH do not support use of these tests for withholding anticoagulation in patients with atrial fibrillation.

Transcranial Doppler and acoustic pressure fluctuations for the assessment of cavitation and thromboembolism in patients with mechanical heart valves.

The formation and collapse of vapor-filled bubbles near a mechanical heart valve is called cavitation. Such microbubbles are suspected to have strong pro-coagulant effects. Therefore, cavitation may be a contributing factor to the pro-thrombotic effects of mechanical valves. Herein, we systematically review the available evidence linking cavitation and thrombosis. We also critically appraise the potential usefulness of transcranial Doppler and other new non-invasive diagnostic methods to study cavitation and cerebral embolism in mechanical valve patients. Experimental studies indicate that cavitation microbubbles cause platelet aggregation, complement-activation, fibrinolysis, release of tissue-factor, and endothelial damage. Administration of 100% oxygen to mechanical valve patients during transcranial Doppler examination can transiently decrease the counts of Doppler-detected cerebral microemboli compared with room air. This is associated with removal of most circulating gaseous emboli from cavitation. This method may therefore be applied to the study of cavitation and thromboembolism. Additionally, the analysis of high-frequency acoustic-pressure fluctuations detected from the implosion of cavitation bubbles is a promising method for assessment of cavitation in vivo; however, this requires further development. A better understanding of cavitation is important in order to adequately investigate its role in the overall pro-thrombotic effects in mechanical valve patients. Such studies may allow establishing guidelines for new valve designs.