Optimal Secondary Prevention Research Articles

Efficacy and safety of edoxaban in patients with cardioembolic stroke

Ischemic strokes due to cardiogenic embolism are associated with an increased risk of death or permanent disability, which emphasizes the importance of their prevention. Edoxaban is a Xa inhibitor that is widely used globally as a new oral anticoagulant to prevent thromboembolic complications in patients with atrial fibrillation and an increased risk of stroke. The purpose of this review is to summarize data on the efficacy and safety of edoxaban in the secondary stroke prevention. The literature review was conducted using PubMed and Medscape databases to search for publications on clinical trials and clinical guidelines on oral anticoagulant treatment for stroke prevention. The results of clinical trials show that in patients with atrial fibrillation, edoxaban is non-inferior to warfarin in efficacy for primary and secondary stroke prevention, but compared to warfarin, edoxaban treatment is much safer (significantly reduces the risk of serious bleedings, including intracranial ones). The safety profile of edoxaban makes it one of the best drugs for the treatment of elderly patients and those with chronic kidney disease. In general, the results of recent clinical trials indicate that in cardioembolic stroke due to atrial fibrillation, the early initiation of treatment with direct oral anticoagulants is safe and reduces the risk of recurrent embolic events. Timely determination of the etiological subtype of ischemic stroke, in particular the detection of paroxysmal atrial fibrillation, and consideration of individual patient characteristics are the key to an optimal secondary prevention strategy that minimizes the risk of recurrent brain damage and improves the quality of life after stroke.

Recent and future advances in intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is defined by the rupture of a cerebral blood vessel and the entry of blood into the brain parenchyma. With a global incidence of around 3.5 million, ICH accounts for almost 30 % of all new strokes worldwide. It is also the deadliest form of acute stroke and survivors are at risk of poor functional outcome. The pathophysiology of ICH is a dynamic process with key stages occurring at successive times: vessel rupture and initial bleeding; hematoma expansion, mechanical mass effect and secondary brain injury (peri-hematomal edema). While deep perforating vasculopathy and cerebral amyloid angiopathy are responsible for 80 % of ICH, a prompt diagnostic work-up, including advanced imaging is require to exclude a treatable cause. ICH is a neurological emergency and simple therapeutic measures such as blood pressure lowering and anticoagulant reversal should be implemented as early as possible as part of a bundle of care. Although ICH is still devoided of specific treatment, recent advances give hope for a cautious optimism. Therapeutic approaches under the scope are focusing on fighting against hemorrhage expansion, promoting hematoma evacuation by minimally invasive surgery, and reducing secondary brain injury. Among survivors, the global vascular risk is now better established, but optimal secondary prevention is still unclear and is based on an individual benefit-risk balance evaluation.

Clinical profile and management of patients with acute myocardial infarction admitted to cardiac care units: The EYESHOT-2 registry

BackgroundThe clinical governance of patients with acute myocardial infarction (AMI) has markedly changed in the last few years. We sought to assess the contemporary in-hospital management patterns of patients with AMI at a country level. MethodsEYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units)-2 was a nationwide, prospective registry aimed to evaluate the current management of patients admitted to intensive cardiac care units (CCUs) for an AMI in Italy. ResultsOver a 4-week period (February 1st-29th, 2024), 183 CCUs enrolled 2806 consecutive patients: 52.6 % with non-ST elevation myocardial infarction (NSTEMI) and 47.4 % with ST-elevation myocardial infarction (STEMI). The median time from hospital admission to angiography in NSTEMI was 22.3 h (IQR 10.9–46.1), while for STEMI was 1.1 h (IQR 0.5–2.2) with significant difference between hospitals with and without catheterization laboratories. In both NSTEMI and STEMI patients, percutaneous coronary intervention (PCI) was the preferred management strategy (73.3 % and 94.2 %, respectively). An optimal secondary prevention therapy, including dual antiplatelet therapy, inhibition of the renin-angiotensin system, a beta-blocker and a high-intensity statin was prescribed at discharge in more than 75 % of patients with AMI. In-hospital major bleedings occurred in 2.0 % and 2.3 % (p = 0.58), while death in 1.8 % and 2.8 % (p = 0.09) of NSTEMI and STEMI patients, respectively. ConclusionsThe EYESHOT-2 registry shows the current management strategies and outcome of AMI patients admitted to Italian CCUs and provides insights to improve the clinical care of such patients.Clinical Trial Registration. URL: http://www.clinicaltrials.gov. Unique identifier: NCT06316128.

Does Atrial Septal Anatomy Still Matter in the Etiological Evaluation of Ischemic Stroke Beyond the Age of 60?

Patent foramen ovale (PFO) is causally associated with stroke in some patients younger than 60 years, especially when it is large or associated with an atrial septal aneurysm (ASA). After 60 years of age, this association is less well understood. We assessed the relationships between detailed atrial septal anatomy and the cryptogenic nature of stroke in this population. We reviewed all patients aged 60 to 80 years admitted to our stroke center for ischemic stroke who underwent contrast echocardiography between 2016 and 2021. The atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection(ASCOD) classification was used to reevaluate the etiological workup. Associations between cryptogenic stroke and (1) PFO presence or (2) categories of PFO anatomy (nonlarge PFO without ASA, nonlarge PFO with ASA, large PFO without ASA, and large PFO with ASA) were assessed using logistic regression. Among 533 patients (median National Institutes of Health Stroke Scale score=1), PFO was present in 152 (prevalence, 28.5% [95% CI, 24.9-32.5]). Compared with noncryptogenic stroke, cryptogenic stroke (n=218) was associated with PFO presence (44.5% versus 17.5%; P<0.0001). Among patients with a PFO, septal anatomy categories were associated with cryptogenic stroke (P=0.02), with a strong association for patients with both large PFO and ASA (38.1% versus 14.5%, P=0.002). PFO presence remains strongly associated with cryptogenic stroke between 60 and 80 years of age. Large PFO, ASA, and their association were strongly associated with cryptogenic stroke in this age group. Our results support performing contrast echocardiography even after 60 years of age, although the optimal secondary prevention therapy in this population remains to be determined in randomized trials.

Thromboembolism in peripartum cardiomyopathy: a systematic review.

Women with peripartum cardiomyopathy (PPCM) are at an increased risk of arterial and venous thromboembolic events. The review summarizes the evidence on the incidence of thromboembolic complications in women with PPCM, diagnostic approaches, related outcomes, and effects of therapies that have been used. English articles were retrieved from Web of Science and PubMed using search terms to capture studies related to PPCM (or postpartum cardiomyopathy) and all combinations of thrombosis- and embolism-related keywords. A total of 347 articles from PubMed and 85 from Web of Science were obtained, and after removing duplicates, 327 articles were screened for original data and classified into four domains: epidemiology, risk factors, diagnosis, and therapy of thromboembolism in PPCM. Ultimately, 30 articles were included. Data were synthesized in summary tables for each domain. Studies in the United States and Europe reported varying incidence for thromboembolism in PPCM, up to 14% in 6 months. Risk factors include elevated levels of coagulation factors, decreased protein C and S activity, decreased fibrinolysis, and a low left ventricular ejection fraction (LVEF). Cesarean delivery and post-operative status were correlated with a higher incidence of thromboembolic complications. Diagnosis relied mostly on ultrasonography and magnetic resonance and depended on the suspected location of thrombus. Anticoagulation has been used mostly for PPCM patients with a reduced LVEF, with the duration varying across guidelines and healthcare systems. Unfractionated heparin and low molecular weight heparin (LMWH) were considered safe choices during pregnancy, while warfarin and novel oral anticoagulants (NOACs) were used postpartum. The association of bromocriptine with risk of thromboembolic complications remains debated. There are important gaps in our understanding of the epidemiology, risk stratification, and optimal secondary prevention of thromboembolism in PPCM. Larger prospective studies with detailed phenotyping are required.

Frequency & factors associated with elevated lipoprotein-a among Ghanaian stroke survivors

BackgroundIndigenous Africans are genetically predisposed to elevated lipoprotein-a (Lp(a)), a veritable risk factor for ischemic stroke. Recent studies have demonstrated the promising efficacy of therapeutic interventions for addressing elevated Lp(a) among patients at high risk of atherosclerotic cardiovascular events. It is important to assess the burden of elevated Lp(a) among stroke survivors of African ancestry aimed at addressing potential unmet therapeutic gaps for optimal secondary prevention. PurposeTo assess the frequency of elevated lipoprotein-a among Ghanaian stroke survivors and factors associated with it. MethodsA prospective study conducted at the Neurology clinic of the Komfo Anokye Teaching Hospital among ischemic stroke survivors aged ≥18 years. Serum lipoprotein-a concentrations were measured using ELISA kits. A multivariate regression analysis was fitted to identify factors independently associated with elevated lipoprotein-a concentration > 30 mg/dl. ResultsAmong 116 stroke survivors, 35 (30.2%) had elevated Lp(a). The adjusted odds ratio (95% CI) of factors associated with elevated Lp(a) were female sex 3.09 (1.05–9.12), p = 0.04, diabetes mellitus 3.52 (1.32–9.40), p = 0.01, urban dwelling 4.64 (1.61–13.39), p = 0.005 and total cholesterol 1.85 (1.28–2.67), p = 0.001. Whereas the LDL cholesterol significantly decreased from baseline to month 12 among a subset of participants, the Lp(a) levels significantly increased from a baseline value of 29.38 ± 15.32 mg/dl to 40.97 ± 29.72 mg/dl, p = 0.032. ConclusionApproximately 1 in 3 Ghanaian ischemic stroke survivors harbor an elevated Lp(a) associated with female sex, urban residence, diabetes mellitus and raised cholesterol. This burden highlights an unmet therapeutic gap in secondary risk reduction in this resource-limited setting.

Stroke awareness among community health workers from rural health blocks of Thiruvananthapuram, India.

Secondary prevention of stroke largely depends on risk factor control and lifestyle modification. Optimal secondary prevention strategies are limited in rural settings due to the shortage of primary care physicians and neurologists. Awareness of community health workers (CHWs) regarding stroke and its management remains largely unexplored. The current cross-sectional study aimed at assessing the knowledge, attitude, and practice (KAP) of CHWs regarding stroke care. A structured KAP questionnaire was administered among 510 CHWs from randomly selected rural health blocks of Thiruvananthapuram, Kerala, India. Knowledge assessment showed that the CHWs possessed an average knowledge of stroke care. The mean attitude and practice scores were higher, indicating a favorable attitude and good practice. The overall mean (standard deviation) KAP scores of CHWs were 13.54 (4.43) against a total score of 23. The KAP scores were highest among palliative care nurses. The stroke awareness of the accredited social health activists was comparatively lower than other CHWs. Factors such as age and years of work experience were not correlated to the KAP scores. Recurrent strokes remain a major challenge in primary care. Overall, the health workers demonstrated average knowledge, favorable attitudes, and positive practices. The study highlights the importance of training accredited social health activists (ASHAs) and other CHWs in stroke to improve secondary prevention strategies.

Association between inflammation, body mass index, and long-term outcomes in patients after percutaneous coronary intervention: A large cohort study.

Association between inflammation, body mass index, and long-term outcomes in patients after percutaneous coronary intervention: A large cohort study.

Myelomeningocele a congenital disease in Chiapas

Introduction: Neural tube defects are congenital defects of the central nervous system, the result of inadequate closure in some area of the neural tube, such as Spina Bifida, Anencephaly or Myelomeningocele, which are a group of conditions that occur during the embryological period of the human being. preventable and greatly affect the population. In Latin America and Mexico they are among the main causes of infant morbidity and mortality. Material and Methods: Analysis of data series of newborns with NTD in Tuxtla Gutiérrez Chiapas, Mexico from 2021-2023 generated from the data and evidence collected at the Dr. Rafael Pascacio Gamboa Regional Hospital and with information from the Tube Defects Epidemiological Surveillance System Neural and Craniofacial (SINAVE/DGE/Salud/2020.). 4 cases with NTD were included, specifically Myelomeningocele who were born and reside in the State. The annual rates of cases with NTD were exposed to identify possible factors that affect or increase said affections with the purpose of preventing said defects or, in that case, ensuring optimal secondary and tertiary prevention for the life of the affected individuals. Results: In the period studied, which was 2021-2023, the NTD with the highest incidence was MMC with 4 cases generated with diseases associated with hydrocephalus and microcephaly, of which only 10% of the cases consumed folic acid in a timely manner during the first trimester. of pregnancy. 100% of the cases are low-income and do not have higher education, as well as popular insurance. 90% attended 6 prenatal consultations or less. Conclusions: NTDs are one of the most frequent problems in newborns, they require study, treatment and permanent surveillance, they can be treated with therapies or go as far as immobilization of the patient's upper and lower limbs, and even death. They represent with great force a morbidity and mortality in childhood that affects the individuals who suffer from them, these conditions are very difficult to bear in the economic, neurological, behavioral, social, emotional, psychological and physical aspect of the people who suffer from it and suffer as much as the affected individuals as well as their families, friends, society, and the health system. Especially because it is preventable, and the information on how to avoid it is of vital use in family planning and to provide more data on this group of diseases where there are more and more new data, methods and techniques on what they are and how to avoid them, cope with them with the purpose of reducing its incidence in the Mexican and general population around the world. Keywords: Mielomeningocele; Neural Tube Defects, Spina Bifida, Tuxtla.

A Novel Mechanism of the “Three Territory Sign” in Acute Ischemic Stroke (P14-5.014)

<h3>Objective:</h3> To present an atypical mechanism for multi-territorial infarction, the “Three Territory Sign” (TTS), in patients with Acute Ischemic Stroke and malignancy. <h3>Background:</h3> Multi-focal ischemic infarcts are often associated with cardioembolism. However, bilateral anterior circulation and posterior circulation infarcts are known as the TTS which is most commonly associated with hypercoagulable state due to malignancy Two commonly recognized mechanisms for the TTS in this setting are localized DIC and embolization of vegetations from non-bacterial thrombotic endocarditis. We present a third possible mechanism for the TTS. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 67-year-old woman with history of Stage IV metastatic melanoma presented to the emergency department with one-day history of fine motor dysmetria and weakness of the right hand. Brain MRI revealed extensive scattered infarcts throughout the bilateral anterior and posterior circulation. A routine stroke work-up including vessel imaging, lipid panel, A1C, TTE and TEE were unrevealing. Due to persistent eosinophilia, she then underwent cardiac MRI to assess for possible chemotherapy-induced eosinophilic myocarditis. While this was not present, her cardiac MRI revealed a left-ventricular intramural metastasis with necrotic core directly invading the ventricular surface. No other cardiac sources were discovered and the most likely source of this patient’s embolic strokes was felt to be thrombosis superimposed upon the necrotic intraventricular tumor. <h3>Conclusions:</h3> Intraventricular cardiac metastasis is an uncommon mechanism of malignancy-associated TTS. Physicians should consider evaluation for cardiac metastases in patients with TTS if it will change optimal secondary stroke prevention or cancer treatment. <b>Disclosure:</b> Dr. Figueroa has nothing to disclose. Dr. Kazmirczak has nothing to disclose. Dr. Ramezani Hashtjin has nothing to disclose. Dr. Streib has nothing to disclose.

Prevalence and Therapeutic Implications of Clonal Hematopoiesis of Indeterminate Potential in Young Patients With Stroke.

Undetermined stroke etiology hampers optimal secondary prevention in a large proportion of young patients. We explored whether genetic screening for clonal hematopoiesis of indetermined potential (CHIP), a novel risk factor for stroke, could identify patients with myeloid precursor lesions or covert myeloid neoplasm requiring specific treatment. We performed targeted sequencing on 56 genes recurrently mutated in hematologic neoplasms in a prospective cohort of patients with acute brain ischemia between 18 and 60 years. CHIP prevalence was compared with age-matched healthy controls from the Nijmegen Biomedical Study (n=1604) and the UK Biobank (n=101 678). Patients with suspicion of high-risk CHIP or myeloid neoplasm were invited for further hematologic evaluation. We included 248 consecutive patients (39% women) of whom 176 (71%) had cryptogenic stroke etiology. Fifty-one (21%) patients had CHIP, 3-fold more than in the general population (7.7% versus 2.6% for the Nijmegen Biomedical Study and 11.9% versus 4.1% for UK Biobank; P<0.001 for both). Patients with CHIP were older (median [interquartile range], 53 [50-59] versus 51 [41-56] years; P<0.001), had higher carotid intima-media thickness (0.68 [0.58-0.80] versus 0.59 [0.51-0.73] mm; P=0.009), and had higher burden of atherosclerosis (29.4% versus 16.7%; P=0.04). We invited 11 patients (4.4%) for further hematologic assessment, which in 7 led to the diagnosis of high-risk CHIP and in 2 to the new diagnosis of a myeloproliferative neoplasm with indication for cytoreductive therapy. Using genetic screening for myeloid disorders in patients with stroke of predominantly undetermined etiology, we found a 3-fold higher CHIP prevalence than in the general population. We identified high-risk CHIP and previously covert myeloproliferative neoplasms as potential stroke etiologies in 4.4% and 1% of patients, respectively. Our findings demonstrate the diagnostic and therapeutic yield of genetic screening in young patients with stroke. Future studies should investigate the role of CHIP for stroke recurrence and optimal secondary prevention.

390 Real World Analysis of Outcomes After Revascularization Surgery for Symptomatic Non-stenotic Carotid (SyNC) Artery Disease

INTRODUCTION: Symptomatic non-stenotic carotid (SyNC) artery disease is emerging as one of the primary causes of embolic stroke of unknown source. The optimal secondary prevention strategies including medical therapy and revascularization (Carotid Endarterectomy (CEA) versus Carotid Artery Stenting (CAS)) continue to be controversial. METHODS: The National Surgical Quality Improvement Program (NSQIP) targeted dataset for CEA and CAS was queried for symptomatic patients with &lt;50% stenosis of the ipsilateral carotid artery undergoing CEA and CAS between 2012-2019. Data analysis for continuous and categorical variables was carried out. RESULTS: A total of 363 symptomatic patients with &lt;50% stenosis of the ipsilateral carotid artery were identified of which 22 underwent CAS and 341 underwent CEA. Statistical analysis showed that patients undergoing CEA were more likely to be male as compared to those undergoing CAS (68% vs 54.5%, p &lt; 0.001). Additionally, patients in the CAS group were more likely to present with high-risk anatomy features compared to patients in the CEA group (31.8% vs 11.7%, p = 0.007) whereas patients undergoing CEA were more likely to have &lt;50% stenosis contralateral ICA stenosis when compared to patients undergoing CAS (65.1% vs 36.4%, p = 0.001). Furthermore, patients undergoing CAS were more likely to experience post procedural stroke at 30 days compared to those undergoing CEA (13.6% vs 3.8%, p = 0.03). Upon multivariable analysis, CEA was associated with lower odds of post procedural stroke as compared to CAS (OR = 0.17, 95% CI 0.033-0.82, p = 0.027). CONCLUSIONS: Carotid revascularization for SyNC is being performed despite current guidelines and CEA is associated with lower odds of post-procedural stroke compared to CAS.

Underlying causes of cryptogenic stroke and TIA in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study – the importance of comprehensive clinical evaluation

BackgroundCryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management.MethodsProspective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis.ResultsAfter 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091).ConclusionCryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal.Trial registrationClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Secondary Pharmacological Prevention of Coronary Artery Disease among Patients Submitted to Clinical Management, Percutaneous Coronary Intervention, or Coronary Artery Bypass Graft Surgery.

Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

A prospective, randomized, controlled, multicentre trial for secondary prevention in patients with chronic coronary syndrome using a smartphone application for digital therapy: the CHANGE study protocol.

Coronary artery disease (CAD) remains the leading cause of death worldwide. 'Stable' CAD is a chronic progressive condition, which recent European guidelines recommend referring to as 'chronic coronary syndrome' (CCS). Despite therapeutic advances, morbidity and mortality among patients with CCS remain high. Optimal secondary prevention in patients with CCS includes optimization of modifiable risk factors with behavioural changes and pharmacological therapy. The CHANGE study aims to provide evidence for optimization of secondary prevention in CCS patients by using a smartphone application (app). The CHANGE study is designed as a prospective, randomized, controlled trial with a 1:1 allocation ratio, which is currently performed in nine centres in Germany in a parallel group design. 210 patients with CCS will be randomly allocated either to the control group (standard-of-care) or to the intervention group, who will be provided the VantisTherapy* app in addition to standard-of-care to incorporate secondary prevention into their daily life. The study will be performed in an open design. Outcomes will be assessed using objective data from three in-person visits (0, 12, and 24 weeks). Primary outcomes will involve adherence to secondary prevention recommendations and quality of life (QoL). The recruitment process started in July 2022. The CHANGE study will investigate whether a smartphone-guided secondary prevention app, combined with a monitor function compared with standard-of-care, has beneficial effects on overall adherence to secondary prevention guidelines and QoL in patients with CCS. The study is listed at the German study registry (DRKS) under the registered number DRKS00028081.

The Attributable Risk of Nonstenotic Cervical Carotid Plaque in Cryptogenic Embolic Stroke

Nonstenotic plaque (NSP) of a cervical artery feeding the territory of acute cerebral infarction is increasingly recognized as a cause of cryptogenic stroke. While these atherosclerotic lesions are not associated with significant luminal stenosis (&lt;50%), the probability of finding such plaque exceeds chance and is more common in parent vessels rather than vessels supplying brain regions remote from infarction. More than 20%–30% of patients with unilateral hemispheric embolic stroke of undetermined source may be attributable to cervical internal or common carotid NSP. For these patients, randomized clinical trials have not shown a significant benefit of revascularization (endarterectomy or stenting), and optimal secondary prevention strategies rely on risk factor modification and antiplatelet therapy. Heightened awareness of this subtle finding may inform second‐tier diagnostic testing recommendations for occult stroke mechanisms (eg, monitoring for paroxysmal atrial fibrillation or hypercoagulability testing). Furthermore, recognition of NSP as a culprit lesion may lead to more targeted pharmacologic strategies aimed at stabilizing plaque. Recent guidelines have also incorporated evidence of plaque vulnerability (eg, intraplaque hemorrhage or lipid‐rich necrotic core) in decision making regarding revascularization approaches. In this review, the epidemiology and management of NSP in patients with cryptogenic embolic infarction is summarized, with an emphasis on recognition of NSP such that future clinical trials can be designed to test novel interventional strategies against current medical management of embolic stroke of undetermined source.

Advanced Echocardiography With Left Atrial Strain and Indexed Left Atrial Three-Dimensional Volume for Predicting Underlying Atrial Fibrillation After Cryptogenic Stroke

Cryptogenic stroke (CS) represents 1/3 of ischemic strokes. Atrial fibrillation (AF) can be detected in up to 30% of CS. Therefore, there is a clinical need for predicting AF to guide the optimal secondary prevention strategy. The evidence about the role of advanced echocardiography, including left atrial 3-dimensional (3D) index volume and left atrial strain (LAS) techniques, to predict underlying AF in this setting is lacking. From April 2019 to November 2021, 78 consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography was performed during admission. All patients underwent 15 days of wearable Holter monitoring. The primary outcome measure was AF detection during follow-up. Twenty-two patients (28%) developed AF. Patients in the AF group were older (81 ± 6.3 vs 76.5 ± 7.8 years; p=0.012). Left atrial (LA) diastolic indexed volume was higher in the AF group (37.2 ± 12.8 vs 29.7 ± 11 ml/m2 p=0.01). Three-D LA indexed volume was also higher in patients with AF (41.4 ± 14 vs 32.2 ± 10 ml/m2 p=0.009). LAS reservoir, LAS conduct, and LAS contraction (LASct) were significantly lower in patients with AF (19 ± 5.6 vs 32% ± 10.3%; 9 ± 4.5 vs 15 ± 7.6; 10 ± 5.3 vs 17 ± 6.4, respectively, all p <0.001). On multivariate analysis, LASct <13.5% and LA 3D indexed volume >44.5 ml/m2 were independent predictors of AF (odds ratio 10.9 [95% confidence interval 1.09 to 108.2], p=0.042). In conclusion, LASct <13.5% and LA 3D indexed volume >44.5 ml/m2 are independent predictors of underlying AF in patients with CS. Our results show the usefulness of advanced echocardiography in this challenging clinical setting.

Searching for underlying atrial fibrillation using artificial intelligence-assisted MRI images from ischemic stroke patients

Abstract Background Nearly 30% of ischemic strokes are attributed to atrial fibrillation (AF) related cardiac thromboembolism. This subset of strokes are associated with higher recurrence rate, morbidity and mortality. As a result, current recommendation suggests a cardiac monitoring of variable intensity and duration to search for unknown AF after a stroke so that optimal secondary prevention could be administered. Unfortunately, it is reported that 24h Holter ECG monitoring for underlying AF is completed routinely in only a minority of stroke centers, making a huge gap between AF detection rate in clinical practice and estimated actual data (2–3% vs 23–30%). So, it is obvious that paroxysmal AF remains undetected in a significant proportion of patients after a stroke and an early and effective identification approach of cardiac disturbances is needed. Purpose We aim to develop an innovative end-to-end artificial intelligence model to rapidly search for atrial fibrillation in post ischemic stroke patients using MRI imaging data. Methods 489 patients diagnosed with ischemic stroke, 174 of which had a prior known history of AF or new AF detected by intensive ECG monitoring poststroke, from January 2018 to October 2021 were enrolled in this study. The MRI images obtained after their admission in the stroke unit were meticulously evaluated and acute ischemic stroke lesions on DWI sequences were segmented and confirmed by two senior neuroradiologists independently. These processed images were randomly split into training (n=315) and testing set (n=174) for the implementation and validation of our AI screening model. And the algorithm was based on the combination of radiomic features and semantic features extracted from convolutional neural network (CNN). The model performance was evaluated by accuracy, recall, precision, F-Measure and AUC. Also, heatmaps which indicate the attention mechanism of the model were generated for interpreting underlying patterns. Results The AUC of our model (COM) reached 0.8 (Figure 1A). Also, the algorithm yielded values for the accuracy, recall, precision and F-Measure of 70%, 92.5%, 63.8% and 75.5%, respectively, which showed satisfactory classification results. As to the interpretability of the AI model, we found that more “attention” was paid to the main lesions (Figure 1B) and radiomic features which indicated the minimum gray level intensity and the sphericity of the lesions (Figure 1C, D) were crucial to the classifier. Conclusions Our work revealed a potential correlation between brain ischemic lesion pattern on DWI images and underlying etiology of AF. Moreover, the AI model we developed may serve as a rapid screening tool for AF in clinical practice of stroke units. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Advanced echocardiography with left atrial strain and indexed left atrial 3D volume for predicting underlying atrial fibrillation after cryptogenic stroke

Abstract Introduction Cryptogenic stroke (CS) represents one-third of ischemic strokes. Atrial fibrillation (AF) can be detected in up to 30% of CS. Therefore, there is a clinical need for predicting AF to guide the optimal secondary prevention strategy. The evidence about the role of advanced echocardiography, including left atrial 3D index volume and left atrial strain (LAS) techniques, to predict underlying AF in this setting is lacking. Methods From April 2019 to November 2021 seventy-eight consecutive patients with ischemic stroke or transient ischemic attack with ABCD2 scale ≥4 of unknown etiology were prospectively recruited. Echocardiography was performed during admission. All patients underwent 15 days wearable Holter monitoring. The primary outcome measure was AF detection during follow-up. Results Twenty -two patients (28%) developed AF. Patients in the AF group were older (81±6.3 vs 76.5±7.8 years; p=0.012). Left atrial (LA) diastolic indexed volume was higher in AF group (37.2±12.8 vs 29.7±11 ml/m2 p=0.01). 3D LA indexed volume were also higher in patients with AF (41.4±14 vs 32.2±10 ml/m2 p=0.009). LAS reservoir, LAS conduct and LAS contraction (LASct) were significantly lower in patients with AF (19±5.6 vs 32±10.3%; 9±4.5 vs 15±7.6; 10±5.3 vs 17±6.4, respectively, all p&amp;lt;0.001). On multivariate analysis LASct &amp;lt;13.5% and LA 3D indexed volume &amp;gt;44.5 ml/m2 were independent predictors of AF (OR 10.9 [95% CI 1.09–108.2], p=0.042) (Table 1, Figure 1) Conclusion LASct &amp;lt;13.5% and LA 3D indexed volume &amp;gt;44.5 ml/m2 are independent predictors of underlying AF in patients with CS. Our results demonstrate the usefulness of advanced echocardiography in this challenging clinical setting. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Spanish Society of Cardiology

Association of Prior Intracerebral Hemorrhage With Major Adverse Cardiovascular Events

Patients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population. To evaluate the risk of a MACE for patients with a prior ICH compared with the general population. This cohort study identified 8991 patients with a first ICH in the Danish Stroke Registry from January 1, 2005, to June 30, 2018, who were aged 45 years or older and survived more than 30 days after an ICH. Patients in this ICH cohort were matched 1:40 on age, sex, and ICH-onset date with a comparison cohort of 359 185 individuals from the general population without a prior ICH. Both cohorts were followed up for 6 months or more until December 31, 2018, for outcomes using registry data. Data were analyzed from October 1, 2021, to July 19, 2022. Intracerebral hemorrhage identified by a nationwide clinical database. The main outcomes were ICH, ischemic stroke, myocardial infarction, and a composite of MACEs. For each outcome, a case-control study nested within the cohorts was also performed, adjusting for time-varying exposures and potential confounders. Crude absolute event rates per 100 person-years, adjusted hazard ratios (aHRs) and 95% CIs and, in the nested case-control analyses, crude and adjusted odds ratios and 95% CIs were calculated. The ICH cohort (n = 8991; 4814 men [53.5%]; mean [SD] age, 70.7 [11.5] years) had higher event rates than the comparison cohort (n = 359 185; 192 256 men [53.5%]; mean [SD] age, 70.7 [11.5] years) for MACEs (4.16 [95% CI, 3.96-4.37] per 100 person-years vs 1.35 [95% CI, 1.33-1.36] per 100 person-years; aHR, 3.13 [95% CI, 2.97-3.30]), ischemic stroke (1.52 [95% CI, 1.40-1.65] per 100 person-years vs 0.56 [95% CI, 0.55-0.57] per 100 person-years; aHR, 2.64 [95% CI, 2.43-2.88]), and ICH (1.44 [95% CI, 1.32-1.56] per 100 person-years vs 0.06 [95% CI, 0.06-0.07] per 100 person-years; aHR, 23.49 [95% CI, 21.12-26.13]) but not myocardial infarction (0.52 [95% CI, 0.45-0.60] per 100 person-years vs 0.48 [95% CI, 0.47-0.49] per 100 person-years; aHR, 1.12 [95% CI, 0.97-1.29]). Nested case-control analyses returned risk estimates of similar magnitude as the cohort analyses. The findings of this cohort study suggest that Danish patients with a prior ICH had statistically significantly higher rates of MACEs than the general population, indicating a need for attention to optimal secondary prevention with blood pressure lowering and antithrombotic and statin therapies after an ICH in clinical research and practice.