Systematic Review and Meta-Analysis of Prehospital Machine Learning Scores as Screening Tools for Early Detection of Large Vessel Occlusion in Patients With Suspected Stroke.

BACKGROUND: Enhanced detection of large vessel occlusion (LVO) through machine learning (ML) for acute ischemic stroke appears promising. This systematic review explored the capabilities of ML models compared with prehospital stroke scales for LVO prediction. METHODS AND RESULTS: Six bibliographic databases were searched from inception until October 10, 2023. Meta-analyses pooled the model performance using area under the curve (AUC), sensitivity, specificity, and summary receiver operating characteristic curve. Of 1544 studies screened, 8 retrospective studies were eligible, including 32 prehospital stroke scales and 21 ML models. Of the 9 prehospital scales meta-analyzed, the Rapid Arterial Occlusion Evaluation had the highest pooled AUC (0.82 [95% CI, 0.79-0.84]). Support Vector Machine achieved the highest AUC of 9 ML models included (pooled AUC, 0.89 [95% CI, 0.88-0.89]). Six prehospital stroke scales and 10 ML models were eligible for summary receiver operating characteristic analysis. Pooled sensitivity and specificity for any prehospital stroke scale were 0.72 (95% CI, 0.68-0.75) and 0.77 (95% CI, 0.72-0.81), respectively; summary receiver operating characteristic curve AUC was 0.80 (95% CI, 0.76-0.83). Pooled sensitivity for any ML model for LVO was 0.73 (95% CI, 0.64-0.79), specificity was 0.85 (95% CI, 0.80-0.89), and summary receiver operating characteristic curve AUC was 0.87 (95% CI, 0.83-0.89). CONCLUSIONS: Both prehospital stroke scales and ML models demonstrated varying accuracies in predicting LVO. Despite ML potential for improved LVO detection in the prehospital setting, application remains limited by the absence of prospective external validation, limited sample sizes, and lack of real-world performance data in a prehospital setting.

Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants in the Prevention of Ischaemic Stroke in Patients with Atrial Fibrillation.

Introduction Existing randomised controlled trials assessing the safety and efficacy of left atrial appendage occlusion (LAAO) in atrial fibrillation (AF) were of relatively small sample size, or included patients who could receive oral anticoagulant treatment after device implantation. We compared the outcomes of patients with newly diagnosed AF who received percutaneous LAAO or direct oral anticoagulants (DOAC) treatment, in a large population from a global federated health network (TriNetX). Methods Patients with AF treated with percutaneous LAAO were matched with those treated with DOAC between 1st December 2010 and 1st October 2018. Outcomes were all-cause mortality, ischaemic stroke and intracranial haemorrhage (ICH) at 5 years. Results We included 200 patients with AF, who received either LAAO or DOAC. The risk of all-cause mortality, ischaemic stroke and ICH at 5 years was not significantly different between the two groups (Risk Ratio [RR] for all-cause mortality: 1.52, 95% confidence interval (CI): 0.97- 2.38, RR for ischaemic stroke: 1.09, 95% CI: 0.51- 2.36, and RR for ICH: 1.0, 95% CI: 0.44- 2.30). Conclusion Patients newly diagnosed with AF, eligible for DOAC, showed similar 5-year risk of death, ischemic stroke, and ICH when comparing those who underwent percutaneous LAAO to those receiving DOAC. Future randomised controlled trials are needed to confirm the findings and advise changes in guidelines.

Outcomes in patients with ischaemic stroke undergoing endovascular thrombectomy: Impact of atrial fibrillation.

OBJECTIVES: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in ischaemic stroke, but the risk of intracerebral haemorrhage (ICH) and mortality remains common following ischaemic stroke. The effect of concomitant atrial fibrillation (AF) on clinical outcomes following acute ischaemic stroke in patients receiving EVT remains unclear. The aim is to investigate associations between AF and intracerebral haemorrhage and all-cause mortality at 90 days in patients with ischaemic stroke undergoing EVT. MATERIALS AND METHODS: A retrospective cohort was conducted using TriNetX, a global health research network. The network was searched for people aged ≥18 years with ischaemic stroke, EVT and AF recorded in electronic medical records between 01/09/2018 and 01/09/2021. These patients were compared to controls with ischaemic stroke, EVT and no AF. Propensity score matching for age, sex, race, comorbidities, National Institutes of Health Stroke Scale (NIHSS) scores, and prior use of anticoagulation was used to balance the cohorts with and without AF. RESULTS: In total 3,106 patients were identified with history of ischaemic stroke treated by EVT. After propensity-score matching, 832 patients (mean age 68 ± 13; 47% female) with ischaemic stroke, EVT and AF, were compared to 832 patients (mean age 67 ± 12; 47% female) with ischaemic stroke, EVT and no history of AF. In the cohort with AF, 11.5% (n = 96) experienced ICH within 90 days following EVT, compared with 12.3% (n = 103) in patients without AF (Odds Ratio (OR) 0.92, 95% confidence interval (CI) 0.68-1.24; p = 0.59). In the patients with AF, mortality within 90 days following EVT was 18.7% (n = 156), compared with 22.5% in patients without AF (n = 187) (OR 0.79, 95% CI 0.63-1.01; p = 0.06). CONCLUSION: In patients with ischaemic stroke undergoing EVT, AF was not significantly associated with intracerebral haemorrhage or all-cause mortality at 90-day follow-up.

Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy: a narrative review.

INTRODUCTION: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in patients with ischemic stroke, but the impact of EVT on clinical outcomes in patients with ischemic stroke with and without atrial fibrillation (AF), and the effect of adjunctive pharmacological therapies with EVT, remains unclear. AREAS COVERED: The goal of this narrative review is to provide an overview of studies which have examined: 1) associations between EVT and outcomes for patients following ischemic stroke, 2) associations between EVT and outcomes for patients following ischemic stroke with and without AF , including function, reperfusion, hemorrhage, and mortality, 3) the effect of adjunctive pharmacological therapies peri- and post-thrombectomy, and 4) integration of prehospital care on endovascular treatment outcomes. EXPERT OPINION: There is little evidence from randomized controlled trials on the effect of AF on stroke outcomes following EVT and the safety and efficacy of AF treatment in the peri-EVT such as tirofiban or Intravenous thrombolysis with Non-vitamin K Antagonist Oral Anticoagulant. The available evidence from observational studies on AF and EVT outcomes is inconsistent, but factors such as procedural EVT devices, the center volume, clinician experience, stroke recognition, and inclusion criteria of studies have all been associated with poorer clinical outcomes. Enhancing the clinical network among prehospital and hospitals will facilitate direct transfer to EVT centers, reducing stroke onset to EVT time and optimizing stroke outcomes.

Paramedic Ability in Interpreting Electrocardiogram with ST-segment Elevation Myocardial Infarction (STEMI) in Saudi Arabia.

Objective: To evaluate paramedic ability in recognizing 12-lead Electrocardiogram (ECG) with ST-segment Elevation myocardial infarction (STEMI) in Saudi Arabia. Methods: This is a quantitative exploratory cross-sectional study using an electronic survey of paramedics was conducted between June and September 2021. The survey included demographics, educational and clinical experiences, and multiple 12-lead ECG strip questions to assess participants' ability to recognize STEMI. We reported the overall sensitivity, specificity, and correct proportions with 95% Confidence Intervals (CI). Results: Eighty-four paramedics completed the survey, and 65% of them were between 24 and 29 years old, with a median, of three years of field experience. Overall sensitivity and specificity were 58.39% (95% CI, 50.4% to 66.1%) and 29.01% (95% CI, 25.15% to 33.1%), respectively. In total, 67.1% correctly identified inferior STEMI, whereas only 50% correctly identified lateral STEMI. Both STEMIs were correctly identified by 41%, and the majority misinterpreted STEMI mimics (ECG rhythms with similar ECG morphology to STEMI). The proportion who correctly recognized left bundle branch block was 14.8%, pericarditis was 10.9%, and ventricular pacing was 1.4%. However, almost third of participants correctly identified right bundle branch block (32.9%) and left ventricle hypertrophy (30.7%). Overall, there was no correlation between the correct ECG interpretation of STEMIs and educational and clinical experiences. Conclusion: Paramedics were able to identify STEMI events in prehospital settings with moderate sensitivity and low specificity with limited ability to differentiate between STEMI and STEMI mimics. Therefore, additional training in ECG interpretation could improve their clinical decision-making, and to ensure that proper care and treatment is provided. Further research on a large, representative sample of paramedics across the country could provide more definitive evidence to establish a greater degree of accuracy in detecting STEMI in prehospital settings.

The Liverpool Heart And bRain Project (L-HARP): Protocol for an Observational Cohort Study of Cardiovascular Risk and Outcomes Following Stroke.

Further research is needed to refine risk prediction models for adverse cardiovascular outcomes following stroke in contemporary clinical practice, such as incident atrial fibrillation (AF), recurrent stroke, and cognitive impairment and dementia. The aims of this study are to prospectively investigate cardiovascular outcomes and risk factors for incident cardiovascular disease in a post-stroke cohort, and to externally validate, refine and expand current risk prediction models for cardiovascular and cardiovascular-related outcomes. The study sample size was based on the development of post-stroke risk prediction models for AF and was calculated as 1222 participants. The study design is a multicentre, prospective, observational cohort study. Participants will be adult patients admitted for ischaemic stroke confirmed by stroke physician or transient ischaemic attack (TIA) confirmed by MRI. Routinely collected data will be used in addition to the completion of simple validated questionnaires by the participants. Follow-up will be undertaken 12-months from the date of admission to hospital, in addition to linkage to routinely collected follow-up hospitalisation and mortality data. The primary outcomes are cardiovascular outcomes (including incident AF, stroke, TIA and myocardial infarction) at 12-month follow-up, all-cause mortality and mortality from cardiovascular causes, and incident cognitive impairment and dementia. Secondary outcomes include changes in function, depression, anxiety, fatigue and quality of life. The study has received approval from the Health Research Authority Research Ethics Committee (21/WA/0209), and is registered on https://www.clinicaltrials.gov/ (Identifier NCT05132465). Recruitment for the study began in October 2021 with completion of recruitment at all participating centres anticipated by October 2022.

Corrigendum: Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

[This corrects the article DOI: 10.3389/fcvm.2020.591946.].

Anti-angiogenesis in cancer therapeutics: the magic bullet.

BACKGROUND: Angiogenesis is the formation of new vascular networks from preexisting ones through the migration and proliferation of differentiated endothelial cells. Available evidence suggests that while antiangiogenic therapy could inhibit tumour growth, the response to these agents is not sustained. The aim of this paper was to review the evidence for anti-angiogenic therapy in cancer therapeutics and the mechanisms and management of tumour resistance to antiangiogenic agents. We also explored the latest advances and challenges in this field. MEDLINE and EMBASE databases were searched for publications on antiangiogenic therapy in cancer therapeutics from 1990 to 2020. Vascular endothelial growth factor (VEGF) is the master effector of the angiogenic response in cancers. Anti-angiogenic agents targeting the VEGF and HIF-α pathways include monoclonal antibodies to VEGF (e.g. bevacizumab), small-molecule tyrosine kinase inhibitors (TKIs) e.g. sorafenib, decoy receptor or VEGF trap e.g. aflibercept and VEGFR2 inhibitors (e.g. ramucirumab). These classes of drugs are vascular targeting which in many ways are advantageous over tumour cell targeting drugs. Their use leads to a reduction in the tumour blood supply and growth of the tumour blood vessels. Tumour resistance and cardiovascular toxicity are important challenges which limit the efficacy and long-term use of anti-angiogenic agents in cancer therapeutics. Tumour resistance can be overcome by dual anti-angiogenic therapy or combination with conventional chemotherapy and immunotherapy. Emerging nanoparticle-based therapy which can silence the expression of HIF-α gene expression by antisense oligonucleotides or miRNAs has been developed. Effective delivery platforms are required for such therapy. SHORT CONCLUSION: Clinical surveillance is important for the early detection of tumour resistance and treatment failure using reliable biomarkers. It is hoped that the recent interest in mesenchymal cell-based and exosome-based nanoparticle delivery platforms will improve the cellular delivery of newer anti-angiogenics in cancer therapeutics.

Cardiovascular Safety and Superiority of Anti-Obesity Medications.

Over the past few decades, several anti-obesity medications have demonstrated an association with adverse cardiovascular outcomes, leading to their market withdrawal. This has caused researchers to investigate the cardiovascular safety of such medications in cardiovascular outcome trials. However, the data from these trials are limited, and their outcomes are not promising. Therefore, the aim of this review is to provide an overview of the current and past Food and Drug Administration-approved medications for weight loss, including novel diabetes medications (glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) and non-diabetes medications, and to highlight the current designs of cardiovascular outcome trials and their importance in the evaluation of the overall safety concerns associated with these anti-obesity medications. The limitations of the trials and opportunities for improvement were also evaluated. Finally, we also briefly describe cardiovascular safety and risks in this review.

Rate control strategies for atrial fibrillation.

Atrial fibrillation (AF) is one of the main cardiac arrhythmias associated with higher risk of cardiovascular morbidity and mortality. AF can cause adverse symptoms and reduced quality of life. One of the strategies for the management of AF is rate control, which can modulate ventricle rate, alleviate adverse associated symptoms and improve the quality of life. As primary management of AF through rate control or rhythm is a topic under debate, the purpose of this review is to explore the rationale for the rate control approach in managing AF by considering the guidelines, recommendations and determinants for the choice of rate control drugs, including beta blockers, digoxin and non- dihydropyridine calcium channel blockers for patients with AF and other comorbidities and atrioventricular nodal ablation and pacing. Despite the limitations of rate control treatment, which may not be effective in preventing disease progression or in reducing symptoms in highly symptomatic patients, it is widely used for almost all patients with atrial fibrillation. Although rate control is one of the first line management of all patient with atrial fibrillation, several issues remain debateable.

Catheter ablation superiority over the pharmacological treatments in atrial fibrillation: a dedicated review.

Atrial fibrillation globally affects roughly 33.5 million people, making it the most common heart rhythm disorder. It is a crucial arrhythmia, as it is linked with a variety of negative outcomes such as strokes, heart failure and cardiovascular mortality. Atrial fibrillation can reduce quality of life because of the potential symptoms, for instance exercise intolerance, fatigue, and palpitation. There are different types of treatments aiming to prevent atrial fibrillation and improve quality of life. Currently, the primary treatment for atrial fibrillation is pharmacology therapy, however, these still show limited effectiveness, which has led to research on other alternative strategies. Catheter ablation is considered the second line treatment for atrial fibrillation when the standard treatment has failed. Moreover, catheter ablation continues to show significant results when compared to standard therapy. Hence, this review will argue that catheter ablation can show superiority over current pharmacological treatments in different aspects. It will discuss the most influential aspects of the treatment of atrial fibrillation, which are recurrence and burden of atrial fibrillation, quality of life, atrial fibrillation in the setting of heart failure and mortality and whether catheter ablation can be the first line treatment for patients with atrial fibrillation.

Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

Background: People of South Asian and African Caribbean ethnicities living in UK have a high risk of cardiometabolic disease. Limited data exist regarding detailed cardiometabolic phenotyping in this population. Methods enabling this are widely available, but the practical aspects of undertaking such studies in large and diverse samples are seldom reported. Methods: The Southall and Brent Revisited (SABRE) study is the UK's largest tri-ethnic longitudinal cohort. Over 1,400 surviving participants (58-85 years) attended the 2nd study visit (2008-2011); during which, comprehensive cardiovascular phenotyping, including 3D-echocardiography [3D-speckle-tracking (3D-STE)], computed tomography, coronary artery calcium scoring, pulse wave velocity, central blood pressure, carotid artery ultrasound, and retinal imaging, were performed. We describe the methods used with the aim of providing a guide to their feasibility and reproducibility in a large tri-ethnic population-based study of older people. Results: Conventional echocardiography and all vascular measurements showed high feasibility (>90% analyzable of clinic attendees), but 3D-echocardiography (3DE) and 3D-STE were less feasible (76% 3DE acquisition feasibility and 38% 3D-STE feasibility of clinic attendees). 3D-STE feasibility differed by ethnicity, being lowest in South Asian participants and highest in African Caribbean participants (p < 0.0001). Similar trends were observed in men (P < 0.0001) and women (P = 0.005); however, in South Asians, there were more women with unreadable 3D-images compared to men (67 vs. 58%). Intra- and inter-observer variabilities were excellent for most of conventional and advanced echocardiographic measures. The test-retest reproducibility was good-excellent and fair-good for conventional and advanced echocardiographic measures, respectively, but lower than when re-reading the same images. All vascular measures demonstrated excellent or fair-good reproducibility. Conclusions: We describe the feasibility and reproducibility of detailed cardiovascular phenotyping in an ethnically diverse population. The data collected will lead to a better understanding of why people of South Asian and African Caribbean ancestry are at elevated risk of cardiometabolic diseases.