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Background: In patients with coronary artery disease and concomitant asymptomatic severe carotid stenosis, combined simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) has been widely performed despite lack of evidence from randomized trials. We recently showed that the risk of stroke or death within 30 days was higher following CABG+CEA compared with CABG alone. Here, we report long-term outcomes following CABG with versus without CEA. Methods: The CABACS (Coronary Artery Bypass Graft Surgery in Patients With Asymptomatic Carotid Stenosis Study) is a randomized, controlled, multicenter, open trial. Patients with asymptomatic severe (≥70%) carotid stenosis undergoing CABG were allocated either CABG+CEA or CABG alone, and follow-up was 5 years. Major secondary end points included nonfatal stroke or death, any death and any nonfatal stroke. Due to low recruitment, the study was stopped prematurely after randomization of 127 patients in 17 centers. Results: By 5 years, the rate of stroke or death did not significantly differ between groups (CABG+CEA 40.6% [95% CI, 0.285–0.536], CABG alone 35.0% [95% CI, 0.231–0.484]; P =0.58). Higher albeit statistically nonsignificant rates of nonfatal strokes occurred at any time following CABG+CEA versus CABG alone (1 year: 19.3% versus 7.1%, P =0.09; 5 years: 29.4% versus 18.8%, P =0.25). All-cause mortality up to 5 years was similar in both groups (CABG+CEA: 25.4% versus CABG alone: 23.3%, hazard ratio, 1.148 [95% CI, 0.560–2.353]; P =0.71). Subgroup analyses did not reveal any significant effect of age, sex, preoperative modified Rankin Scale and center on outcome events. Conclusions: During 5-years follow-up, combined simultaneous CABG+CEA was associated with a higher albeit statistically nonsignificant rate of stroke or death compared with CABG alone. This was mainly due to a nonsignificantly higher perioperative risk following CABG+CEA. Since the power of our study was not sufficient, no significant effect of either procedure could be observed at any time during follow-up. Registration: URL: http://www.controlled-trials.com ; Unique identifier: ISRCTN13486906.

ZusammenfassungMigräne ist die häufigste neurologische Erkrankung und kann mit einem hohen Grad der Beeinträchtigung einhergehen. Neben nichtmedikamentösen Ansätzen zur Reduktion der Migränefrequenz stehen medikamentöse Migräneprophylaxen zur Verfügung. Zur Indikation und Anwendung liegen evidenzbasierte Leitlinien der Deutschen Migräne- und Kopfschmerzgesellschaft (DMKG) und Deutschen Gesellschaft für Neurologie (DGN), Österreichischen Kopfschmerzgesellschaft (ÖKSG) sowie Schweizer Kopfwehgesellschaft (SKG) vor. Für therapierelevante Fragen wie z. B. der notwendigen und sinnvollen Dauer einer medikamentösen Migräneprophylaxe können aus bisherigen Studiendaten keine Rückschlüsse gezogen werden. Ziel dieser Übersicht ist die Formulierung von Empfehlungen zur Therapiedauer bei wirksamer medikamentöser Migräneprophylaxe, die die aktuelle Datenlage und – bei fehlenden Daten – die Expertenmeinungen berücksichtigen.

The online 2021 Asian-Pacific Heart and Brain Summit was organized to present and discuss experiences within leading Asian-Pacific centers with regard to institutional heart and brain teams managing the diagnosis, treatment, and follow-up of cryptogenic stroke (CS) patients with patent foramen ovale (PFO). This manuscript presents a narrative review of presentations and discussions during the summit meeting. Percutaneous PFO closure is an established therapy for CS patients in whom PFO is considered to be causal. Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure with the involvement of several clinical specialties, including neurology, cardiology, and hematology. It is also recommended that the patient be closely involved in this process. The heart and brain team is a collaborative platform that facilitates such a multidisciplinary decision-making process and patient involvement. It also creates opportunities for education and evaluation of the healthcare provided to patients with CS. This review provides insights into the implementation, composition, organization, and operation of a heart and brain team. Methods and metrics are suggested to evaluate the team’s role. We suggest that an efficient heart and brain team can implement guideline-recommended multidisciplinary clinical decision-making with regard to PFO closure in CS patients and play an important role in the management of these patients.

Background: Patients who had a cryptogenic stroke (CS) suspected to be causally related to a patent foramen ovale (PFO) are candidates for percutaneous PFO closure. In such patients, it is important to screen for atrial fibrillation (AF). Limited guidance is available regarding AF monitoring strategies in CS patients with PFO addressing optimal monitoring technology and duration. Aim: To provide a narrative review of cardiac rhythm monitoring in CS patients considered for PFO closure, including current practices, stroke recurrences after CS, findings from monitoring studies in CS patients, and predictors for AF detection published in the literature. To propose a personalized strategy for cardiac monitoring in CS patients, accounting for aspects predicting AF detection. Summary of review: AF detection in CS patients is predicted by age, left atrial enlargement, prolonged PR interval, frequent premature atrial contractions, interatrial conduction block, diabetes, prior brain infarctions, leukoaraiosis, elevated B-type natriuretic peptide (BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and a family history of AF, as well as composed scores (e.g. CHA2DS2-VASc, atrial fibrillation in embolic stroke of undetermined source (AF-ESUS)). The causal role of the PFO may be accounted for by the risk of paradoxical embolism (RoPE) score and/or the PFO-Associated Stroke Causal Likelihood (PASCAL) classification. Conclusion: A personalized approach to AF detection in CS patients is proposed, accounting for the likelihood of AF detection and aimed at obtaining sufficient confidence regarding the absence of AF in patients considered for PFO closure. In addition, the impact of high-risk PFO features on the monitoring strategy is discussed.

Background There is no clear consensus on whether aspirin offers better outcomes in terms of secondary cardiovascular disease prevention compared with clopidogrel. Objective The aim of the study was to compare the safety and efficacy of clopidogrel versus aspirin in patients with established cardiovascular disease. Methods A systematic review of MEDLINE (via PubMed), Scopus, and Cochrane Library databases (last search date: August 28, 2021) was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement for randomized control trials (RCTs) of clopidogrel versus aspirin as monotherapy in patients with established cardiovascular disease. Random-effects meta-analyses were performed. Results Five RCTs incorporating 26,855 patients (clopidogrel: 13,426; aspirin: 13,429) were included. No statistically significant difference was observed between clopidogrel and aspirin in terms of all-cause mortality (odds ratio [OR]: 1.01 [95% confidence interval, CI: 0.91–1.13]; p = 0.83), ischemic stroke (OR: 0.87 [95% CI: 0.71–1.06]; p = 0.16), and major bleeding rates (OR: 0.77 [95% CI: 0.56–1.06]; p = 0.11). Patients receiving clopidogrel had borderline lower risk for major adverse cardiovascular events (MACE) (OR: 0.84 [95% CI: 0.71–1.00]; p = 0.05) and lower risk for nonfatal myocardial infarction (OR: 0.83 [95% CI: 0.71–0.97]; p = 0.02, relative risk reduction = 16.9%, absolute risk reduction = 0.5%, number needed to treat = 217 for a mean period of 20 months) compared with patients receiving aspirin. Conclusion In patients with established cardiovascular disease, clopidogrel was associated with a 17% relative-risk reduction for nonfatal MI, borderline decreased risk for MACE, and similar risk for all-cause mortality, stroke, and major bleeding compared with aspirin. Protocol Registration PROSPERO CRD42021283866.

Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge.

Objective The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. Methods This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords “COVID 19” or “vaccine” and “headache” to assess the appropriateness of all published articles for their inclusion in the review. Results Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. Conclusions The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

Objective: To evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH). Background: MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. Methods: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36). Results: A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was “much” or “very much” improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores. Conclusions: This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes.

In diesem Artikel waren die Adressdaten für den Autor Lars Neeb falsch angegeben. Statt „Neurologische Klinik und Poliklinik, Institut für Public Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin und Humboldt Universität zu Berlin, Berlin, Deutschland“ hätten sie „Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Klinik und Hochschulambulanz für Neurologie, Berlin, Deutschland“ lauten sollen.

Background Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. Methods A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. Results We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Conclusion Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Background The optimal timing of anticoagulation following acute ischaemic stroke or TIA in patients with atrial fibrillation (AF) is a frequent challenge. Early initiation of anticoagulation can reduce the risk for recurrent ischaemic events, but may lead to an increased risk for intracerebral haemorrhage. Aim The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study was initiated to investigate outcome events under antithrombotic therapy after ischaemic stroke or TIA in patients with AF. The main objective is to compare the three-month rates of major haemorrhagic events between early (≤ 7 days) versus late (> 7 days) administration of dabigatran or treatment with vitamin-K antagonists started at any time. Occurrences of ischaemic and major haemorrhagic events will be evaluated to determine the optimal time point for initiation or resumption of anticoagulation. Design and Methods PRODAST is a prospective, multicenter, observational, non-interventional post-authorization safety study. 10,000 patients with recent (≤ 1 week from index event) ischaemic stroke or TIA and non-valvular AF were recruited at 86 German sites starting in July 2015. The observational plan includes a baseline visit, documentation of data during hospitalization and a telephone-based, central follow-up at three months after the index event. The primary endpoint is the major bleeding rate within three months. Secondary endpoints include rates of recurrent ischaemic or haemorrhagic stroke, TIA, systemic embolism, myocardial infarction and death. Summary PRODAST will provide important real-world data on safety and efficacy of antithrombotic therapy after acute stroke and TIA in patients with AF.

Objective To identify grey matter alterations in patients suffering new daily persistent headache to enrich the pathophysiological concept of this rare headache disorder characterised by a distinct, clearly remembered onset and its instant chronification. Method Magnetic resonance-based voxel-based and surface-based morphometry was used to investigate 23 patients suffering from new daily persistent headache and 23 age- and gender-matched healthy controls with 1.5 Tesla MRI. Independent statistical analysis was performed at three sites using statistical parametric mapping, as well as FSL(FMRIB Software Library)-based approaches. Results No grey matter changes were detected using this sophisticated and cross-checked method. Conclusion The absence of structural brain changes in patients with new daily persistent headache contribute to the recent discussion regarding structural alterations in primary headache disorders in general and does not provide evidence for grey matter changes being associated with the pathophysiology of new daily persistent headache. Future research will have to determine the underlying pathophysiological mechanisms of this disorder.

BACKGROUND: Major bleeding (MB) events are independent predictors of mortality after cardiac interventional procedures. The clinical relevance of MB following left atrial appendage occlusion (LAAO) remains unclear.AIMS: This study aimed to investigate the incidence and clinical impact of MB after LAAO in a real-world population at high risk for bleeding and contraindicated to anticoagulation.METHODS: The two-year results of the Amplatzer Amulet Observational Post-Market Study were analysed. An independent committee adjudicated MBs according to the Bleeding Academic Research Consortium scale. Cox proportional hazards regression identified variables associated with MB events and mortality.RESULTS: The MB rate was 7.2%/year, with a rate of 10.1%/year during year one, decreasing to 4.0%/year over year two. The most common bleeding location was gastrointestinal, accounting for 48% of MBs. Pre-LAAO MB was associated with an increased risk for post-LAAO MB (HR 2.34, 95% CI: 1.37-3.99). The occurrence of post-LAAO MB was associated with increased mortality (37.3% vs 12.7%; pCONCLUSIONS: In real-world patients at high bleeding risk, MB following LAAO was not uncommon and associated with a significant increase in mortality, without increasing the risk of stroke. ClinicalTrials.gov Identifier: NCT02447081. https://clinicaltrials.gov/ct2/show/NCT02447081.

Background We hypothesized that stroke outcome is related to multiple baseline hydration‐related factors including volume contracted state (VCS) and diuretic use. Methods and Results We analyzed a prospective cohort of subjects with ischemic stroke Conclusions A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.

Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab. Methods Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or ≥75% reduction in monthly migraine days were evaluated. Results Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation ( Conclusion Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes. Trial registration ClinicalTrials.gov NCT03308968 (FOCUS).