Non-coronary atherosclerosis: a marker of poor prognosis in patients undergoing coronary artery bypass surgery.

Introduction: The presence of non-coronary atherosclerosis (NCA) in patients with coronary artery disease is associated with a poor prognosis. We have studied whether NCA is also a predictor of poorer outcomes in patients undergoing coronary artery bypass grafting (CABG). Materials and methods: This is an observational study involving 567 consecutive patients who underwent CABG. Variables and prognosis were analysed based on the presence or absence of NCA, defined as previous stroke, transient ischaemic attack (TIA), or peripheral artery disease (PAD) [lower extremity artery disease (LEAD), carotid disease, previous lower limb vascular surgery, or abdominal aortic aneurysm (AAA)]. The primary outcome was a combination of TIA/stroke, acute myocardial infarction, new revascularization procedure, or death. The secondary outcome added the need for LEAD revascularization or AAA surgery. Results: One-hundred thirty-eight patients (24%) had NCA. Among them, traditional cardiovascular risk factors and older age were more frequently present. At multivariate analysis, NCA [hazard ratio (HR) = 1.84, 95% confidence interval (CI) 1.27-2.69], age (HR = 1.35, 95% CI 1.09-1.67, p = 0.004), and diabetes mellitus (HR = 1.50, 95% CI 1.05-2.15, p = 0.025), were positively associated with the development of the primary outcome, while estimated glomerular filtration rate (HR = 0.86, 95% CI 0.80-0.93, p = 0.001) and use of left internal mammary artery (HR = 0.36, 95% CI 0.15-0.82, p = 0.035), were inversely associated with this outcome. NCA was also an independent predictor of the secondary outcome. Mortality was also higher in NCA patients (27.5% vs. 9%, p < 0.001). Conclusions: Among patients undergoing CABG, the presence of NCA doubled the risk of developing cardiovascular events, and it was associated with higher mortality.

Cognitive testing following transient ischaemic attack: A systematic review of clinical assessment tools.

Cognitive deficits are prevalent after transient ischaemic attack (TIA) and result in loss of function, poorer quality of life and increased risks of dependency and mortality. This systematic review aimed to synthesise the available evidence on cognitive assessment in TIA patients to determine the prevalence of cognitive deficits, and the optimal tests for cognitive assessment. Medline, Embase, PsychINFO and CINAHL databases were searched for relevant articles. Articles were screened by title and abstract. Full-text analysis and quality assessment was performed using the National Institute of Health Tool. Data were extracted on study characteristics, prevalence of TIA deficits, and key study findings. Due to significant heterogeneity, meta-analysis was not possible. Twenty-five full-text articles met the review inclusion criteria. There was significant heterogeneity in terms of cognitive tests used, definitions of cognitive impairment and TIA, time points post-event, and analysis methods. The majority of studies used the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) (n = 23). Prevalence of cognitive impairment ranged from 2% to 100%, depending on the time-point and cognitive domain studied. The MoCA was more sensitive than the MMSE for identifying cognitive deficits. Deficits were common in executive function, attention, and language. No studies assessed diagnostic test accuracy against a reference standard diagnosis of cognitive impairment. Recommendations on cognitive testing after TIA are hampered by significant heterogeneity between studies, as well as a lack of diagnostic test accuracy studies. Future research should focus on harmonising tools, definitions, and time-points, and validating tools specifically for the TIA population.

Clinical characteristics and prognosis in oldest old patients with ischaemic stroke or transient ischaemic attack in China.

BACKGROUND: Limited data are available about the prognosis of ischaemic stroke or transient ischaemic attack (TIA) in oldest-old patients, especially in China. We aimed to describe the clinical characteristics and prognosis of oldest-old patients with ischaemic stroke or TIA in China. METHODS: Patients with acute ischaemic stroke (AIS) or TIA were recruited between August 2015 and March 2018 in the Third China National Stroke Registry (CNSR-III). Clinical characteristics including demographic data, medical history, medication use and stroke aetiology, were obtained. The outcomes were one-year stroke recurrence, combined vascular events (stroke, myocardial infarction, and cardiovascular death), mortality, and poor functional outcome [modified Rankin scale (mRS) 3-6]. Oldest-old was defined as ≥80 years old. Clinical characteristics and prognosis were compared by different age groups (<65, 65-79, and ≥80 years). The association between age and prognosis was analysed using the multivariable Cox proportional hazards and logistic regression models. RESULTS: A total of 15,166 patients with AIS or TIA were included in this study with 929 (6.13%) oldest-old patients. Oldest-old patients had a higher likelihood of cardioembolic stroke or comorbid cardiac disease than other age groups. When compared with patients aged <65 years, oldest-old patients had higher risk of one-year stroke recurrence [adjusted hazard ratio (HR) 1.36; 95% confidence interval (CI): 1.06-1.73, P=0.014], combined vascular events [adjusted HR, 1.42; 95% CI, 1.13-1.79, P=0.003], mortality [adjusted odds ratio (OR), 4.25; 95% CI: 2.99-6.04, P<0.001] and poor functional outcome (adjusted OR, 4.25; 95% CI: 3.40-5.33, P<0.001) with P for trends <0.001 among age groups. CONCLUSIONS: Oldest-old patients differed from younger patients regarding clinical characteristics, stroke aetiology, and secondary preventive medication persistence with a poor clinical prognosis in China. Current information on profile of the oldest-old stroke patients is crucial to develop specific secondary prevention and treatment strategies.

Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic.

Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic. Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic. Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67-0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88-0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65-0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73-0.83) Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

Timing of carotid endarterectomy and clinical outcomes.

The timing of carotid endarterectomy (CEA) for symptomatic ipsilateral carotid artery stenosis has evolved in practice over time. Key landmark trials outlined the benefit of performing CEA in the recently symptomatic carotid artery stenosis, defined as revascularisation within 6 months of the index neurological event. Further evidence and sub-analysis demonstrate that performing CEA within 2 weeks of symptoms has the maximal benefit in reducing stroke free survival and is associated with a safe perioperative complication profile. This has translated into guideline recommendations and widespread clinical practice. The case for performing urgent CEA (within 48 hours of index neurological event) over early CEA (within 2 weeks) has been put forward and studied. Data examining perioperative complications for urgent CEA are mostly derived from retrospective single series studies. A moderate balance exists in the literature for the safety and risk of urgent CEA. Although many studies present acceptable perioperative stroke and mortality rates associated with urgent CEA, evidence still exists that the perioperative complications may not be insignificant. This is particularly the case if the presenting neurology is a stroke, rather than a transient ischaemic attack (TIA) or amaurosis fugax. This should be contextualised in the practice of modern aggressive medical therapy with dual antiplatelets and statins, with evidence suggesting a reduction in recurrent ischaemic events prior to surgical intervention. Careful patient selection, presenting neurology and medical therapy is likely to be a key feature in considering urgent CEA versus early CEA.

Audit of Transient Ischaemic Attack (TIA) inpatient management: a retrospective assessment

@#The aim of this retrospective study was to audit the management of transient ischaemic attack (TIA) patients admitted in 2012 compared to a previous audit (2009 to mid-2010). Data were obtained by reviewing the electronic clinical records of patients. Data on patient demographics, patient assessment and management according to TIA guidelines were collected. A total of 61 patients were admitted to hospital with primary diagnosis of TIA. One in four patients had an alternative diagnosis. TIA severity (ABCD2 score) was not calculated in 13% of the patients. Most patients had computed tomography (CT) brain imaging performed. Antiplatelet therapy was not adjusted in 10% of patients. Carotid doppler ultrasound was not considered in 20% of the patients. Most of the carotid dopplers were done within one week. Only 6.6% of the patients were referred for carotid endarterectomy. Blood pressure medications were not optimised in 57.4% of the patients. Only 27.9% were prescribed statin therapy. Not all patients had documented ECG findings or discussion regarding anticoagulation. There was a 32.8% 3-month readmission rate. In 2012 several aspects of TIA guideline management were not done appropriately compared to the previous audit. The areas of improvement identified in this assessment include optimising antiplatelet therapy and blood pressure management, as well as timely carotid ultrasound for anterior circulation TIA. Further education and reiteration of guideline-based TIA management is recommended. A follow-up audit of the service is warranted

Ceramides and sphingosine-1-phosphate as potential markers in diagnosis of ischaemic stroke.

BACKGROUND: Brain imaging in stroke diagnostics is a powerful tool, but one that can fail in more challenging cases, and one that is not particularly useful in identifying transient ischaemic attacks (TIAs). Thus, new reliable blood biomarkers of cerebral ischaemia are constantly sought. OBJECTIVE: We studied the potential usefulness of sphingolipids (SFs) as biomarkers of acute ischaemic stroke and TIA. MATERIAL AND METHODS: Levels of individual ceramide species and sphingosine-1-phosphate (Sph-1-P) in blood serum of patients with acute ischaemic stroke, TIA, and age-matched neurological patients without cerebral ischaemia, were assessed by tandem mass spectrometry liquid chromatography (LC- MS / MS). RESULTS: We found significant increases of several sphingolipid levels, with particularly strong elevations of Cer-C20:0 in patients with acute stroke. Cer-C24:1 was the only ceramide species to decrease as a result of acute stroke. Moreover, its levels inversely correlated with the number of days after stroke onset, suggesting that Cer-C24:1 is an independent parameter related to the course of stroke. To increase the sensitivity of sphingolipid-based tests in stroke diagnostics, we calculated the values of ratios of Sph-1-P / individual ceramide species and Cer-C24:1 individual ceramide species. We found several ratios significantly changed in stroke patients. Two ratios, Sph-1-P / Cer-C24:1 and Cer-C24:0 / Cer-C24:1, presented especially strong increments in patients with acute stroke. Moreover, Sph-1-P / Cer-C24:1 values were augmented in TIA patients. CONCLUSION: Serum SFs could be good candidates to be ischaemic stroke biomarkers. We have identified two SF ratios, Sph-1-P / Cer-C24:1 and Cer-C24:0 / Cer-C24:1, with strong diagnostic potential in ischaemic stroke. We found Sph-1-P / Cer-C24:1 ratio to be possibly useful in TIA diagnostics, also in the long term after ischaemic incidence.

Hospital use in survivors of transient ischaemic attack compared with survivors of stroke in central China: a nested case-control study.

OBJECTIVES: There is a lack of knowledge regarding post-discharge hospitalisation utilisation after transient ischaemic attack (TIA) in China. The aim of this study is to quantify rehospitalisation use in survivors of TIA compared with their own previous hospital use and matched survivors of stroke. DESIGN: Nested case-control study of electronic medical records datasets. SETTING: 958 hospitals in Henan, China, from July 2012 to December 2015. PARTICIPANTS: In total, 4823 survivors of stroke were matched to the TIA cohort (average age: 64.5 years; proportion of men: 48.4%) at a 1:1 ratio. All subjects with an onset of stroke/TIA were recorded with a 1-year look-back and follow-up. OUTCOME MEASURES: Adjusted difference-in-differences (DID) values in 1-year hospital lengths of stay (LOSs) and readmission within 7, 30 and 90 days. RESULTS: There was an increase in hospital admissions in survivors of TIA in the year after the index hospitalisation compared with the prior year. Of the 2449 rehospitalisation events that occurred during the first year after TIA, stroke (20.6%) was the most common reason for rehospitalisation. There was no difference in the stroke-specific readmission rates between the TIA and stroke cohorts (p=0.198). The TIA cohort had fewer readmissions within 30 days and 90 days after all-cause discharge compared with the controls. The corresponding covariate-adjusted DID values were -3.5 percentage points (95% CI -5.3 to -1.8) and -4.5 (95% CI -6.5 to -2.4), respectively. A similar trend was observed in the 1-year LOS. In the stratified analysis, the DID reductions were not significant in patients with more comorbidities or in rural patients. CONCLUSIONS: Compared with survivors of stroke, survivors of TIA use fewer hospital resources up to 1 year post-discharge. Greater attention to TIAs among patients with more comorbidities and rural patients may provide an opportunity to reduce hospital use.

The role of the GP in managing suspected transient ischaemic attack: a qualitative study.

BACKGROUND: National guidelines recommend patients with suspected transient ischaemic attack (TIA) should be seen by a specialist within 24 h. However, people with suspected TIA often present to non-specialised services, particularly primary care. Therefore, general practitioners (GPs) have a crucial role in recognition and urgent referral of people with suspected TIA. This study aims to explore the role of GPs in the initial management of suspected TIA in the United Kingdom (UK). METHODS: One-to-one, semi-structured interviews with GPs, TIA clinic staff and patients with suspected TIA from two sites in the UK: Cambridge and Birmingham. Thematic analysis was undertaken to explore views on the role of the GP in managing suspected TIA. Thirty semi-structured interviews were conducted with stroke patients (n = 12), GPs (n = 9) and TIA clinic hospital staff (n = 9) from two hospitals and nine GP practices in surrounding areas. RESULTS: Three overarching themes were identified: (1) multiple management pathways for suspected TIA; (2) uncertainty regarding suspected TIA as an emergency or routine situation; and (3) influences on the urgency of GP management. CONCLUSIONS: Guidelines on the primary care management of TIA describe only a small proportion of the factors which influence GP management and referral of suspected TIA. Efforts to improve treatment, appropriate referral and patient experience should use a real rather than idealised model of the GP role in managing suspected TIA.

Effect of small-vessel disease on cognitive trajectory after atrial fibrillation-related ischaemic stroke or TIA.

Post-stroke dementia is common but has heterogenous mechanisms that are not fully understood, particularly in patients with atrial fibrillation (AF)-related ischaemic stroke or TIA. We investigated the relationship between MRI small-vessel disease markers (including a composite cerebral amyloid angiopathy, CAA, score) and cognitive trajectory over 12 months. We included patients from the CROMIS-2 AF study without pre-existing cognitive impairment and with Montreal Cognitive Assessment (MoCA) data. Cognitive impairment was defined as MoCA < 26. We defined "reverters" as patients with an "acute" MoCA (immediately after the index event) score < 26, who then improved by ≥ 2 points at 12 months. In our cohort (n = 114), 12-month MoCA improved overall relative to acute performance (mean difference 1.69 points, 95% CI 1.03-2.36, p < 0.00001). 12-month cognitive impairment was associated with increasing CAA score (per-point increase, adjusted OR 4.09, 95% CI 1.36-12.33, p = 0.012). Of those with abnormal acute MoCA score (n = 66), 59.1% (n = 39) were "reverters". Non-reversion was associated with centrum semi-ovale perivascular spaces (per-grade increase, unadjusted OR 1.83, 95% CI 1.06-3.15, p = 0.03), cerebral microbleeds (unadjusted OR 10.86, 95% CI 1.22-96.34, p = 0.03), and (negatively) with multiple ischaemic lesions at baseline (unadjusted OR 0.11, 95% CI 0.02-0.90, p = 0.04), as well as composite small-vessel disease (per-point increase, unadjusted OR 2.91, 95% CI 1.23-6.88, p = 0.015) and CAA (per-point increase, unadjusted OR 6.71, 95% CI 2.10-21.50, p = 0.001) scores. In AF-related acute ischaemic stroke or TIA, cerebral small-vessel disease is associated both with cognitive performance at 12 months and failure to improve over this period.

Current management aspects in adult congenital heart disease: non-surgical closure of patent foramen ovale.

A patent foramen ovale (PFO) is a remnant interatrial communication, best diagnosed with transoesophageal echocardiography (TOE) and bubble study. Although quite common and often asymptomatic, PFO is associated with cryptogenic stroke and migraine. Approximately one-half of patients with a cryptogenic stroke have a PFO, and the dilemma regarding whether or not to proceed with percutaneous device closure, to reduce the risk of future recurrent events due to paradoxical embolism, has been subject to debate for nearly two decades. Despite promising observational data, initial randomised clinical trials failed to demonstrate superiority of closure over medical therapy. However, long-term follow-up data from one of these early trials, combined with two new randomised trials, have provided more evidence for the benefits of closure in selected patients. This new evidence suggests that younger patients with high-risk features such as an atrial septal aneurysm (ASA) or large interatrial shunt are more likely to benefit from PFO closure, after fastidious exclusion of an alternative cause for the index stroke. However, issues which require further clarification include whether anticoagulant therapy is preferable to antiplatelet therapy for medical management, and which particular type of closure device is optimal. Finally, despite promising retrospective observational data suggesting improvement in migraine attacks after PFO closure, high quality evidence is lacking in this regard.

Device closure for patent foramen ovale following cryptogenic stroke: a survey of current practice in the UK.

Patent foramen ovale (PFO) closure for cryptogenic stroke remains controversial due to a lack of conclusive randomised controlled data. Many experts feel PFO closure is indicated in selected cases; however, national and international guideline recommendations differ. We surveyed the UK cardiologists, stroke physicians and neurologists, seeking to determine specialist interpretation of the evidence base, and to gain an insight into the current UK practice. The British Cardiac Society and British Society of Stroke physicians distributed our survey which was performed using an online platform. 120 physicians (70 stroke physicians, 23 neurologists, 27 cardiologists) completed the survey. Most (89%) felt PFO closure should be considered in selected patients. Atrial fibrillation (86.6%), significant carotid stenosis (86.6%), diabetes (38.4%) and hypertension (36.6%) were considered exclusion criteria for cryptogenic stroke diagnosis. More stroke physicians than cardiologists considered an age cut-off when considering PFO as the stroke aetiology (70.4%vs 54.5%p=0.04). Anatomical features felt to support PFO closure were aneurysmal septum (89.6%), shunt size (73.6%), prominent Eustachian valve (16%). 60% discuss patients in multidisciplinary meetings prior to PFO closure, with more cardiologists than stroke physicians/neurologists favouring this approach (76.9% vs 54.8%; p=0.05). After PFO closure, patients receive Clopidogrel (72.3%), aspirin (50%) or anticoagulants (17%). 63.2% continue therapy for a limited period after PFO closure, while 34% prefer life-long therapy (14.8% cardiologists vs 40.5% non-cardiologists; p=0.02). While experts support selective PFO closure in cryptogenic stroke, current practice remains variable with significant differences in perceptions of cardiologists and neurologists/stroke physicians.