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Non-valvular atrial fibrillation (NVAF) is the most common cause of cardioembolic stroke. The left atrial appendage (LAA) is the major source of cardiac emboli in patients with NVAF. Anticoagulation (AC) is the standard of care for stroke prevention in atrial fibrillation (AF), but many patients are intolerant of AC. Surgical exclusion of the LAA may result in incomplete closure and is associated with an increased risk of embolism. We report a case of a woman in her 50s with a history of persistent AF, mitral valve prolapse s/p repair with surgical LAA exclusion, and multifocal haemorrhagic stroke presented for elective LAA closure who underwent a Watchman placement successfully. This case demonstrates that a percutaneous approach for occlusion of the LAA when surgical exclusion was incomplete may be feasible with appropriate planning. Clinical outcome data for this patient group are needed.

Vascular injury is a common complication in firearm injuries; however, intravascular missile embolism is relatively rare. There are only 38 documented cases of intravascular missile embolisation to the heart. Bullet embolisms are difficult to diagnose even with multiple diagnostic modalities and even once identified, the most optimal choice of surgical management is debated. Our patient presented with a gunshot wound to the right posterior shoulder. Cardiac focused assessment with sonography for trauma, chest X-ray, CT and echocardiogram were performed, showing missile location adjacent to the right ventricle with inconclusive evidence of pericardial injury. Exploratory median sternotomy was performed, revealing intact pericardium and injury to the superior vena cava (SVC) with bullet embolisation to the right ventricle. The patient became temporarily asystolic secondary to haemorrhage from the SVC injury. Cardiac massage was performed, dislodging the missile into the inferior vena cava. A venotomy was performed to retrieve the bullet and vascular injuries were primarily repaired.

Background: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). Methods: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA 2 DS 2 -VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. Results: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0–3.0) for warfarin-treated patients was 44% (interquartile range, 23%–59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63–2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342–3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615–1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. Conclusions: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02942407.

Infective endocarditis is a life-threatening condition and is associated with embolic events. We aimed to evaluate the association of vegetation size, multiplicity, and position with cerebral embolism and late mortality in patients with infective endocarditis.We retrospectively reviewed patients with infective endocarditis who were admitted to a single institution between November 2005 and August 2017. A total of 419 patients with infective endocarditis were included in the study, 273 of whom had undergone surgery. The primary endpoint was all-cause mortality, and the secondary endpoint was cerebral embolism. Multivariate Cox regression and logistic regression analyses were performed to identify independent risk factors for 30-day mortality, late mortality, and cerebral embolism.Age (hazard ratio [HR] 1.02; 95% confidence interval [CI], 1.00 to 1.04), renal failure (HR 4.21; 95% CI, 2.67 to 6.65), surgery (HR 0.31; 95% CI, 0.21 to 0.46), and Acute Physiology and Chronic Health Evaluation II score (HR 1.08; 95% CI, 1.01 to 1.15) were associated with late mortality. Vegetation size, multiplicity, and position were not significantly associated with late mortality, but a mitral vegetation size of greater than 10 mm (odds ratio 2.25; 95% CI, 1.32 to 3.84) was an independent risk factor for cerebral embolism.A vegetation size of greater than 10 mm and the mitral position were found to be significant risk factors for cerebral embolism, and for this group, early surgery might be considered to prevent cerebral embolism.

Our aim was to analyze the incidence of P-wave abnormalities in embolic and non-embolic strokes, and evaluate its clinical usefulness for predicting stroke etiology.We included 376 consecutive patients hospitalized for acute ischemic stroke from January 2015 to September 2021. Among the patients in sinus rhythm at admission, 31 had ischemic stroke due to atrial fibrillation (AF)-related embolism, 59 had embolic stroke of unknown source (ESUS), and 143 had non-embolic stroke. P-wave abnormalities were defined as 1. P-wave axis abnormality (PWAA); 2. P-wave terminal force in Vsub1/sub(PTFV1) ≤ -4000 μV*ms; 3. advanced inter-atrial block (A-IAB).The prevalence of each type of abnormality was consistently lower in patients with non-embolic stroke than in those with AF-related embolism (AF-related vs. ESUS vs. non-embolic; PWAA, 45% vs. 20% vs. 14%; PTFV1, 36% vs. 37% vs. 15%; and A-IAB, 55% vs. 31% vs. 13%, respectively). The identification of at least one type of P-wave abnormality improved the sensitivity compared to using a single abnormality parameter (sensitivity 72%, specificity 62%), while at least two types of abnormality had low sensitivity, but high specificity (sensitivity 29%, specificity 95%). Multivariate regression analysis revealed that identification of at least one type of P-wave abnormality was independently associated with embolic stroke (odds ratio 3.11, 95%CI 1.46-6.63).The incidence of each type of P-wave abnormality was significantly lower in patients with non-embolic stroke. A combination of PWAA, PTFV1, and A-IAB parameters could be useful for distinguishing embolic from non-embolic stroke.

A 31-year-old male with acute blurred vision and respiratory distress occurring three days after a penile filler injection was found to have outer plexiform layer hyperreflectivity on optical coherence tomography (OCT), consistent with paracentral acute middle maculopathy (PAMM). He was diagnosed with diffuse bilateral pneumonitis and silicone embolism syndrome requiring inpatient management. Following systemic stabilization, his vision and OCT findings improved. PAMM may be associated with silicone embolism syndrome in the presence of acute central scotomas and minimal retinal findings. Penile filler injections could contribute to retinal vaso-occlusion via an embolic process. PAMM may be self-limited and result in functional vision. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:635–638.]

Several landmark trials have reported that direct oral anticoagulants (DOACs) are more effective in preventing stroke and systemic embolism than vitamin K antagonists. However, nonadherence to DOACs worsens prognosis in patients with nonvalvular atrial fibrillation (NVAF) despite the effectiveness of the drugs. The purpose of this study was to evaluate the effects of a pharmacist-led educational interventional program involving motivational interviewing on medication adherence, as assessed by electronic monitoring, in patients receiving DOACs for the treatment of NVAF.This prospective, randomized, interventional study was conducted at outpatient cardiology clinics at general hospitals and pharmacies in Japan. Patients with NVAF who were treated with a once-daily DOAC (edoxaban) or a twice-daily DOAC (apixaban) were randomized to receive either: (1) an educational interventional program involving motivational interviewing regarding adherence to anticoagulants; or (2) standard medication counseling. The primary end point was the change in the medication adherence rate, calculated as the number of days that patients appropriately took the drug, as assessed by an electronic monitoring device, divided by the total number of days that the drug was prescribed, from a 12-week observation period to a 12-week intervention period. The secondary end points were tolerability outcomes. The effect of the educational interventional program on the primary end point was analyzed in subgroups stratified by gender and type of DOAC received.A total of 268 patients completed the observation period and were randomly assigned to one of the two study groups. The difference in the primary end point between the educational interventional program group and the standard medication counseling group was not significant (mean [SD], 2.9% [7.5%] vs 3.4% [8.3%]). On multiple linear regression analysis, the difference in DOAC adherence between the two groups was not significant, but that adherence to apixaban was significantly improved among men in the educational interventional program (β = 0.219; P = 0.012). Two patients died of causes considered unrelated to treatment; no stroke/systemic embolism or major bleeding events were observed.In this randomized, controlled study of the effects of a pharmacist-led educational interventional program using motivational interviewing on adherence to DOACs among patients with NVAF, adherence to DOACs, as assessed using an electronic monitoring device, was not improved with the educational interventional program compared to standard medication counseling . However, adherence to twice-daily apixaban was improved among men, but not among women, in the educational interventional program group. In this study, the selection of DOACs was not randomized, and the lack of assessment of the association between adherence to DOACs and clinical outcomes was a limitation. Japan Registry of Clinical Trials (jRCT) indentifier: jRCTs031180142.

Myxomas are rare tumors in neonates and tend to have a different presentation compared to adults. We present an infant with a left atrial myxoma presenting with episodic tachycardia who underwent successful surgical excision. In addition, we performed a review of the literature, identifying 17 cases of neonatal myxomas. Unlike adults, neonatal myxomas are more common in males and occur more often on the right side of the heart. Constitutional symptoms such as fever or embolism are rare among neonates. Most patients have favorable outcomes following surgical excision, refuting earlier claims that neonatal myxomas are associated with poor outcomes.

Introduction : Umbilical access in laparoscopic surgery has been cited as a factor for increased complications in low-birth-weight infants and those less than three months old. In a previous series, 10.6% of pediatric surgeons reported complications in this population associated with umbilical access, citing carbon dioxide (CO2) embolism as the most common complication. To further examine the safety of this technique, we report our outcomes with blunt transumbilical laparoscopic access at our institution over four years. Methods : A retrospective review was performed of patients less than three months of age who underwent laparoscopic pyloromyotomy or inguinal hernia repair from 2016-2019. Operative reports, anesthesia records, and postoperative documentation were reviewed for complications related to umbilical access. Complications included bowel injury, vascular injury, umbilical vein cannulation, CO2 embolism, umbilical surgical site infection (SSI), umbilical hernia requiring repair, and death. Results : Of 365 patients, 246 underwent laparoscopic pyloromyotomy, and 119 underwent laparoscopic inguinal hernia repairs. Median age at operation was 5.9 weeks [4.3,8.8], and median weight was 3.9 kg [3.4,4.6]. Nine complications (2.5%) occurred: 5 umbilical SSIs (1.4%), 1 bowel injury upon entry requiring laparoscopic repair (0.2%), 1 incisional hernia repair 22 days postoperatively (0.2%), and 2 cases of hypotension and bradycardia upon insufflation that resolved with desufflation (0.5%). There were no intraoperative mortalities or signs/symptoms of CO2 embolism. Conclusion : In this series, umbilical access for laparoscopic surgery in neonates less than three months of age was safe, with minimal complications. Although concern for umbilical vessel injury, cannulation, and CO2 embolism exists, these complications are not exclusively associated with umbilical access technique.

Microfluidic devices have developed a wide range of applications in the fields of biomedicine, chemistry, and analytical science. But it is easy to form and accumulate bubbles in microfluidic devices. These bubbles could decrease the detection sensitivity, cause inaccurate analysis results, and even damage the functional region of the device. Inspired by the embolism repair mechanism of angiosperms and the permeability of gas permeable materials, this work proposes a bioinspired permeation-enhanced degassing method. Bionic redundant pits are used in this method to keep bubbles from spreading between microchannels and maintain the continuity of the flow. A hydrophobic gas permeable material is used to enhance the bubble capture capability and accelerate the degassing process. This method can eliminate bubbles automatically and continuously in real time without auxiliary equipment. Compared to the bubble removal only depending on solution in water, the degassing effect of the permeation-enhanced degassing method shows about 1.6 times improvement in the same conditions, and the capability of trapping bubbles is improved by 1.33 times. In this paper, this method was integrated into a concentration gradient generator and a cell culture device. The results show that the concentration gradient generator with degassing structures can dissolve bubbles in a rapid way and reach the stability of the concentration gradient within 5-15 min. The degassing method can run for a long time and improve the cell density and cell viability of HeLa cells up to 2.64 and 1.12 times, respectively. The method has a broad application prospect in microfluidic fields including biomedical fluid processing, virus detection, and microscale reactor operation.

Idarucizumab, a dabigatran-specific reversal agent, was launched in Japan in 2016. The J-Dabigatran Surveillance 2 study was designed to assess the characteristics and outcomes of dabigatran-treated patients after the launch of idarucizumab.Patient characteristics and outcomes, including thromboembolic and bleeding events, of dabigatran-naïve patients with non-valvular atrial fibrillation (NVAF) who received dabigatran etexilate [110 mg or 150 mg twice-daily (b.i.d.)] for the prevention of ischemic stroke and systemic embolism were investigated and presented descriptively. Absolute standardized differences (ASD) in baseline characteristics compared with the first J-Dabigatran Surveillance (J-Dabi1; 2011-2013) study were included.In total, 5660 patients were enrolled and 5436 were analyzed in this study; 3516 and 1898 received 110 mg b.i.d. and 150 mg b.i.d. dabigatran, respectively; 22 received other doses. The overall duration of follow-up (mean ± standard deviation) was 287 ± 179 days. Baseline characteristics, including stroke/bleeding-risk scores, were typical of this patient population. Overall, paroxysmal, persistent, permanent, and symptomatic atrial fibrillation were observed for 53.2%, 27.1%, 13.7%, and 53.9% of patients, respectively (J-Dabi1 ASD: 0.2, 0.0, 0.3, and 0.2, respectively). Catheter ablation was selected in 27.9% of patients (J-Dabi1 ASD: 0.6). Rates of clinical outcomes were low in the study (mostly2%/year). The incidence rate of major bleeding was 1.1%/year (n = 46) and stroke/transient ischemic attack/systemic embolism was 1.7%/year (n = 71). Twelve (0.2%) patients received idarucizumab, commonly for serious bleeding events, and most recovered.Dabigatran continues to be safe and well tolerated in patients with NVAF for stroke and systemic embolism prevention and continues to be prescribed appropriately. Treatment outcomes have not changed since the availability of idarucizumab. Since the J-Dabi1 study, treatment guidelines for anticoagulation use in NVAF have been updated based on emerging clinical evidence, accounting for differences in patient characteristics, and making dabigatran a preference for distinct patient populations.

Background and ObjectivesGuidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardioaortic sources of embolism than transthoracic echocardiography (TTE).MethodsWe performed a prospective, single-center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent the routine stroke workup, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardioaortic source of embolism on cardiac CT vs TTE in patients undergoing both investigations.ResultsBetween May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5–7) minutes with poor scan quality in only 3%. In total, 350 of the 452 patients (77.4%) underwent TTE, 99 of whom were performed in an outpatient setting. Reasons for not undergoing TTE were death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardioaortic source of embolism was detected in 40 of the 350 patients (11.4%) on CT, compared with 17 of the 350 (4.9%) on TTE (odds ratio 5.60, 95% CI 2.28–16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 55 of the 452 (12.2%). Among the 175 patients with cryptogenic stroke after the routine workup, cardiac CT identified a cause of the stroke in 11 (6.3%).DiscussionCardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared with TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism.

Background: We determined the long-term event incidence among elderly patients with nonvalvular atrial fibrillation in terms of history of stroke/transient ischemic attack (TIA) and oral anticoagulation. Methods: Patients aged ≥75 years with documented nonvalvular atrial fibrillation enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were divided into 2 groups according to history of stroke/TIA. The primary end point was the occurrence of stroke/systemic embolism within 2 years, and secondary end points were major bleeding and all-cause death within 2 years. Cox models were used to determine whether there was a difference in the hazard of each end point in patients with/without history of stroke/TIA, and in ischemic stroke/TIA survivors taking direct oral anticoagulants versus those taking warfarin. Results: Of 32 275 evaluable patients (13 793 women [42.7%]; median age, 81.0 years), 7304 (22.6%) had a history of stroke/TIA. The patients with previous stroke/TIA were more likely to be male and older and had higher hazard rates of stroke/systemic embolism (adjusted hazard ratio, 2.25 [95% CI, 1.97–2.58]), major bleeding (1.25, 1.05–1.49), and all-cause death (1.13, 1.02–1.24) than the other groups. Of 6446 patients with prior ischemic stroke/TIA, 4393 (68.2%) were taking direct oral anticoagulants and 1668 (25.9%) were taking warfarin at enrollment. The risk of stroke/systemic embolism was comparable between these 2 groups (adjusted hazard ratio, 0.90 [95% CI, 0.71–1.14]), while the risk of major bleeding (0.67, 0.48–0.94), intracranial hemorrhage (0.57, 0.39–0.85), and cardiovascular death (0.71, 0.51–0.99) was lower among those taking direct oral anticoagulants. Conclusions: Patients aged ≥75 years with nonvalvular atrial fibrillation and previous stroke/TIA more commonly had subsequent ischemic and hemorrhagic events than those without previous stroke/TIA. Among patients with previous ischemic stroke/TIA, the risk of hemorrhagic events was lower in patients taking direct oral anticoagulants compared with warfarin. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: UMIN000024006.

Background Randomized controlled trials evaluating patent foramen ovale (PFO) percutaneous closure only included patients with recent embolic event. We aimed to evaluate outcomes following percutaneous PFO closure outcomes according to the delay from the last embolic episode. Methods This international ambispective cohort included consecutive patients from two centers in France and Canada undergoing PFO percutaneous closure for secondary prevention of paradoxical embolic event. The primary endpoint was the composite of stroke or transient ischemic attack (TIA). Logistic regression model was used to evaluate determinants of late PFO closure procedures. Results A total of 1,179 patients (mean age 49±12.7 years; 44.4% female) underwent PFO closure from 2001 to 2021 (Figure 1). The median delay from last embolic event to procedure was 6.0 (3.4–11.2) months. Determinants of late PFO closure procedure were the center (France versus Canada) adjusted Odds Ratio (aOR) 1.65 95% confidence interval (CI) 1.25–2.19, year of procedure (≥2018 versus Conclusion This analysis provides indirect evidence that delay from last ischemic event does not impact outcomes following PFO percutaneous closure for secondary prevention. Funding Acknowledgement Type of funding sources: None.

Coronary artery embolism (CAE) is a rare, non-atherosclerotic cause of acute myocardial infarction (MI). Atrial fibrillation (AF) is the most frequent cause of CAE, and can be associated with multiple embolisms, particularly in the brain.To characterize CAE-related myocardial injury, assess the proportion of cardiocerebral infarction and characterize brain injuries associated with dual embolism.In this prospective study, patients with CAE-associated MI underwent (1) cardiac magnetic resonance imaging (MRI) to assess the extent of infarct transmurality and myocardial necrosis size and (2) brain MRI to assess the proportion of simultaneous cardiocerebral infarction. We screened 1401 consecutive patients with de novo acute MI from January 2019 to June 2021. CAE was diagnosed based on clinical, angiographic and diagnostic imaging criteria.Overall, 29/1401 patients presented with CAE (2.1%), of whom 21 underwent cardiac and cerebral MRI. Of these, nine (43%) had an ischaemic stroke, and AF was the leading cause of CAE in 14 patients (67%). Multiple CAE were common at coronary angiography (33%). Four patients (19%) had left atrial appendage thrombus - 4/9 patients (44%) with a stroke but 0/12 patients without a stroke. On cardiac MRI, the median (interquartile range) number of segments with acute infarction was 3 (0-11) in patients with stroke and 3 (1-6) in those without. Most acute ischaemic strokes (78%) were localized in the superficial sylvian territory and only 2/21 patients (10%) had stroke sequelae.MI-related to CAE was associated with infarctions of average size but multiple locations. Systematic brain MRI revealed that 33% of cases were associated with a stroke, which was generally asymptomatic. Further studies are required to better characterize the pathophysiology, clinical course and prognostic value of CAE. Moreover, optimal management strategies remain to be determined.

The differential diagnosis of acute onset flank pain include renal colic, papillary necrosis, pyelonephritis and renal infarction from renal artery thrombosis or embolism. Here, we describe a case of acute onset flank pain caused by unilateral renal vein thrombosis (RVT) in a previously healthy

Purpose of review: Atrial fibrillation (AF) is a major risk factor for systemic embolism and ischaemic stroke. Furthermore, AF-related strokes are associated with higher mortality, greater disability, longer hospital stays and lower rates of hospital discharge than strokes caused by other reasons. The aim of this review to summarise the existing evidence on the association of AF with ischemic stroke and provide insights on the pathophysiological mechanisms and the clinical management of patients with AF in order to reduce the burden of ischemic stroke.Recent findings: Beyond Virchow's triad, several pathophysiological mechanisms associated with structural changes in the left atrium, which may precede the identification of AF, may contribute to the increased risk of arterial embolism in AF patients. Individualised thromboembolic risk stratification based on CHA2DS2-VASc score and clinically relevant biomarkers provides essential tool towards a personalised holistic approach in thromboembolism prevention. Anticoagulation remains the cornerstone of stroke prevention moving from vitamin K antagonists (VKA) to safer non-vitamin K direct oral anticoagulants in the majority of AF patients. Despite the efficacy and safety of oral anticoagulation, still the equilibrium between thrombosis and haemostasis in AF patients remains suboptimal and future directions in anticoagulation and cardiac intervention may provide novel treatment options in stroke prevention. This review summarises the pathophysiologic mechanisms of thromboembolism, aiming the current and potential future perspectives in stroke prevention in AF patients. Purpose of review: Atrial fibrillation (AF) is a major risk factor for systemic embolism and ischaemic stroke. Furthermore, AF-related strokes are associated with higher mortality, greater disability, longer hospital stays and lower rates of hospital discharge than strokes caused by other reasons. The aim of this review to summarise the existing evidence on the association of AF with ischemic stroke and provide insights on the pathophysiological mechanisms and the clinical management of patients with AF in order to reduce the burden of ischemic stroke.Recent findings: Beyond Virchow's triad, several pathophysiological mechanisms associated with structural changes in the left atrium, which may precede the identification of AF, may contribute to the increased risk of arterial embolism in AF patients. Individualised thromboembolic risk stratification based on CHA2DS2-VASc score and clinically relevant biomarkers provides essential tool towards a personalised holistic approach in thromboembolism prevention. Anticoagulation remains the cornerstone of stroke prevention moving from vitamin K antagonists (VKA) to safer non-vitamin K direct oral anticoagulants in the majority of AF patients. Despite the efficacy and safety of oral anticoagulation, still the equilibrium between thrombosis and haemostasis in AF patients remains suboptimal and future directions in anticoagulation and cardiac intervention may provide novel treatment options in stroke prevention. This review summarises the pathophysiologic mechanisms of thromboembolism, aiming the current and potential future perspectives in stroke prevention in AF patients.

Infective endocarditis (IE) is a morbid condition with high mortality. We investigated predictors of in-hospital mortality and embolic phenomena in a contemporary Australasian cohort.We identified all patients with IE admitted between January 2017 and 30th April 2020 (40 months). Patient characteristics, risk factors and clinical outcomes were retrospectively collected and analysed.One hundred and seventy-two consecutive patients (mean age: 56.8 ± 17.9 years, male: 63%, 114/172) were included. Causative organisms were Staphylococcus aureus (44%, 75/172), Enterococcus faecalis (15%, 26/172), Streptococcus mitis (6%, 10/172) and Staphylococcus epidermidis (3%, 6/172). In-hospital mortality was 15% (25/172). Embolic complications were found among 57% (98/172) of patients, the most common being stroke (23%, 40/172), septic pulmonary emboli (17%, 29/172), splenic and/or renal emboli (17%, 26/172) and peripheral limb emboli (15%, 25/172). Sixty (35%, 60/172) patients underwent cardiac surgery. On multivariable analysis, independent predictors of in-hospital mortality were: increased age (odds ratio: 1.064, per year older, P = 0.001), ICU admission independent of cardiac surgery (OR 9.81, P 0.001), moderate or severe LV impairment (OR 5.19, P = 0.012) and any sign of embolic phenomena to limbs (OR 5.02, P = 0.006). Multivariable predictors of embolic complications were S. aureus bacteraemia (OR 3.22, P = 0.001) and large vegetation10 mm (OR 3.04, P = 0.002).We demonstrate predictors of in-hospital mortality and embolic phenomena in our cohort. Though age remains a consistent predictor of mortality, surprisingly, signs of embolic phenomena to the limbs was established as an independent predictor of mortality. The mechanism of this is unclear and warrants further evaluation.

Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT.We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed.Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.

Aims Patients with atrial fibrillation (AF) treated with oral anticoagulation still suffer from cardiovascular complications including cardiovascular death, stroke, and major bleeding. To identify risk factors for predicting stroke and bleeding outcomes in anticoagulated patients, we assessed 2-year outcomes in patients with AF treated with edoxaban in routine care. We also report the age-adjusted risk predictors of clinical outcomes. Methods and results The Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF) Europe (NCT02944019) is a prospective, multi-centre, post-authorisation, observational study with an overall 4-year follow-up conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Of the 13 133 patients with AF (mean age: 73.6 ± 9.5 years), 5682 (43.3%) were female. At the 2-year follow-up, 9017/13 133 patients were still on edoxaban; 1830 discontinued treatment including 937 who died (annualised event rate of all-cause death was 3.87%). 518 (2.14%) patients died of cardiovascular causes; 234 (0.97%) experienced major bleeding and 168 (0.70%) experienced stroke or systemic embolic events (SEE). Intracranial haemorrhage was noted in 49 patients (0.20%). History of transient ischaemic attack (TIA) at baseline was the strongest predictor of ischaemic stroke or SEE (Wald χ2: 73.63; P Conclusion Patients treated with edoxaban in ETNA-AF-Europe reported low 2-year event rates in unselected AF patients. Prior stroke, reduced kidney function, and HF identify patients at high risk of stroke, bleeding and all-cause/cardiovascular death, respectively.

Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for stroke prevention in atrial fibrillation (SPAF). Outcome data on clinical effectiveness and safety in routine care are increasing.In the prospective, non-interventional DRESDEN NOAC REGISTRY a network of 230 physicians enrolled5000 NOAC patients who received prospective central follow. All reported outcome events (stroke/transient ischemic attack/systemic embolism; ISTH bleeding; death) were adjudicated using standard definitions.Between 2016 and 2021, 1258 SPAF patients receiving edoxaban were followed for 927.1 ± 562.2 days with a mean edoxaban exposure of 790.3 ± 577.2 days. Edoxaban was discontinued by 274 patients (10.1/100 patient-years; 95% CI 8.9-11.3). The combined endpoint of stroke/TIA/systemic embolism occurred at a rate of 1.7/100 patient-years (95% CI 1.3-2.3) in the intention-to-treat analysis and at 1.3/100 patient-years (95% CI 0.9-1.9) in the on-treatment analysis (censored 3 days after last edoxaban intake). On-treatment rates of ISTH major bleeding were comparable for patients receiving edoxaban 30 mg OD (3.6/100 patient-years; 95% CI 2.2-5.5) or 60 mg OD (2.5/100 patient-years; 95% CI 1.8-3.2). A total of 151 patients (12.0%) died (4.7/100 patient-years; 95% CI 4.0-5.5), with non-stroke cardiovascular events (n = 50), infection/sepsis (n = 40) and terminal malignant disease (n = 31) being the leading causes of death.Overall rates of effectiveness and safety outcomes were in line with latest real-world data (such as ETNA-AF registry) and confirm findings of the phase-III ENGAGE-AF trial. Non-thrombotic cardiovascular events and infectious diseases were the leading causes of death, whereas fatal stroke and fatal bleeding were rare.

Patients with interatrial shunts (patient foramen ovale/atrial septal defect) are potentially at increased risk for paradoxical air embolism following computed tomography (CT) scans with intravenous (IV) contrast media injection. IV in-line filters aim to prevent such embolisms but are not compatible with power injection required for diagnostic CT.The purpose of this study was to determine whether the incidence of paradoxical embolism to the heart and brain in patients with an interatrial shunt is higher compared with controls within 48 hours following injection of IV contrast media without IV in-line filter.This is a retrospective cohort study conducted at a large tertiary academic center, which included a total of 2929 consecutive patients who underwent 8983 CT scans with IV contrast media injection between July 1, 2000 and April 30, 2018. Diagnosis of an interatrial shunt was confirmed by transthoracic or transesophageal echocardiography. Incidence and risk of cardiac embolic events (new troponin elevation,0.1 ng/mL) and neurological embolic events (new diagnosis of stroke/transient ischemic attacks) were evaluated.Among the 2929 patients analyzed (mean±SD age, 61±14 y), 475/2929 (16.2%) patients had an interatrial shunt. After applying the exclusion criteria, new elevated troponin was found in 8/329 (2.4%; 95% confidence interval [CI]: 1.1-4.7) patients with an interatrial shunt compared with 25/1687 (1.5%; 95% CI: 0.9-2.2) patients without an interatrial shunt. New diagnosis of stroke occurred in 2/169 (1%; 95% CI: 0.3-4.2) of patients with an interatrial shunt compared with 7/870 (0.8%; 95% CI: 0.4-1.7) without interatrial shunt.Among patients with echocardiographic evidence of an interatrial shunt, IV CT contrast administration without an in-line filter does not increase the incidence of cardiac or neurological events.

We describe the case of a 64 years old patient, known for an Enterococcus faecalis endocarditis on a 25 mm Edwards-Carpentier biological aortic valve in 2020, who was re-hospitalized one year later in cardiac surgery for a recurrence of Enterococcus faecalisbacteriemia. During hospitalization, the patient presented a cardiac arrest. The coronarography revealed an acute occlusion of the left coronary artery. The autopsy confirmed an Enterococcus faecalis thrombus on aortic valve and left coronary artery. Although systemic embolism is a common complication of infective endocarditis, septic embolism is an unsual cause of acute coronary syndrome and a very rare cause of cardiac arrest. Our case highlights a rare and potentially fatal complication of infective endocarditis: acute coronary syndrome on septic coronary embolism.

Peri-operative antiplatelet therapy (APT) aims to prevent thrombotic events such as stroke. High platelet reactivity ,despite the use use of APT, increases the risk of thrombotic events. Transcranial Doppler imaging (TCD) is used to detect peri-operative microembolic signals (MES) during carotid endarterectomy (CEA). Peri-operative MES are associated with an increased risk of procedural stroke and new silent lesions on diffusion weighted magnetic resonance imaging following surgery. The main components of TCD detected MES are platelet aggregates, and therefore patients displaying multiple MES during surgery could have benefited from more stringent APT. This study investigated whether the use of flow cytometry based platelet reactivity measurements were correlated with the incidence of pre-operative MES and thereby in the future suitable to predict patients at increased risk of peri-operative thrombotic events.Bilateral TCD with MES detection was performed in 197 patients undergoing CEA. Platelet reactivity was assessed with a flow cytometry based platelet reactivity assay measuring platelet response in whole blood. High on treatment platelet reactivity status was assessed for all patients. The secondary outcome was major adverse cardiovascular events (MACE) within one year.In total, 197 patients were included, 49 had peri-operative MES. The platelet response to adenosine diphosphate (ADP) correlated with MES (p = .021), and high on treatment platelet reactivity after adenosine diphosphate stimulation was associated with MACE (OR 2.34, 95% confidence interval 1.126 - 4.890, p = .023).Pre-operative platelet reactivity determined by flow cytometry after ADP stimulation correlated with the occurrence of intra-operative MES and post-operative MACE. Clopidogrel treatment showed the most substantial effect on reducing MES frequency and platelet reactivity measured by flow cytometry.

Guidelines recommend surgery for left-sided infective endocarditis (LSIE) that is associated with large vegetations. Given that most patients who undergo surgery also have other indications (heart failure and/or uncontrolled infection), it is not settled whether surgery should be routinely recommended in patients with large vegetations but no other predictors of poor outcome.A total of 726 patients with definitive LSIE were included in our analysis. The mean age was 64.9 years, and 61% were male. Multivariate analysis of all patients was performed to determine whether vegetation size is related to death in LSIE. Then patients were divided into two groups according to vegetation size: group A (10 mm, n = 420) and group B (≤10 mm, n = 306). Univariate and multivariate analyses of group A patients were carried out to identify the variables related to death in this group. The impact of surgery on mortality in group A patients without heart failure or uncontrolled local infection (n = 139) was assessed.Age, Staphylococcus aureus, perivalvular complications, heart failure, kidney failure, and septic shock, but not vegetation size, were associated with death. Patients with large vegetations showed increased mortality (31.7% in group A vs 24.8% in group B; P = .045). Group A had more valve rupture and valve regurgitation than group B, but heart failure (55% vs 53%; P = .678), stroke (22% vs 17.0%, P = .091), systemic embolism (39% vs 32%; P = .074), perivalvular complication (28% vs 28%; P = .865), and septic shock (15% vs 13%; P = .288) were similar in both groups. In patients from group A without heart failure or uncontrolled infection, mortality was similar with and without surgery (n = 139; n = 70 with surgery and n = 69 without surgery; mortality, 18.6% vs 11.6%, respectively; P = .251).Large vegetations identify patients with poor outcomes in the context of LSIE. However, surgery is not associated with a better prognosis in patients with large vegetations if they do not present with another predictor of poor outcome such as heart failure or uncontrolled infection. These findings challenge whether vegetation size alone should be an indication for surgery in LSIE.

Infective endocarditis (IE) is a life-threatening disease with embolisms occurring in 20%-50% of cases. We aimed to evaluate the value of the systemic immune-inflammation index (SII) in predicting embolic events (EEs) in patients with infective endocarditis.A total of 186 patients diagnosed with definite IE, who admitted to the Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, were retrospectively identified from November 2011 to March 2019.The median (interquartile) age of the patients was 46 (32-57) years. Viridans group streptococci were the most common microorganism identified from blood culture (24.7%). The most frequent complication was heart failure (64.2%), followed by EEs (30.2%). Patients complicated with EEs presented a significantly higher SII than those without EEs (1605.38 versus 1039.61, P = 0.001). SII had an area under the curve (AUC) value for EEs of 0.661 (95% CI: 0.575-0.747, P = 0.001), which predicted the presence of EEs with a sensitivity of 42.6% and specificity of 86.3%. Multivariate logistic regression analysis revealed that SII (OR = 6.925; 95% CI: 1.035-46.318, P = 0.046) was an independent predictor of EEs in IE patients.We demonstrated that a high level of SII is associated with a higher likelihood of EEs. The SII may be a promising predictor for EEs in patients with IE.

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

Background and purpose Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Methods We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8-2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24-3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6-7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs. Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Background Patients receiving left ventricle assist devices (LVADs) as bridge to recovery remain a minority with 1%-5% of LVADs explanted after improvement of myocardial function. Nevertheless, considering the growing population of patients supported with LVADs, an increasing demand of new explantation strategies is expected in the near future. A novel plug for LVAD explantation has been developed and its biocompatibility profile needs to be proved. This study tested the biocompatibility of this novel plug in an in vivo ovine model. Methods Six adult Blackhead Persian female sheep received plug implantation on the cardiac apex via minimally invasive approach and were clinically observed up to 90 days. Echocardiography was performed to detect thrombus formation or further plug-related complications. After the observation period, euthanasia was performed and samples including the plug and the surrounding tissues were obtained to be analyzed with correlative light and electron microscopy. Organ necrosis, ischemia and peripheral embolism were investigated. Results Three animals survived surgery and completed the follow-up time without experiencing clinical complications. Echocardiographic controls excluded the presence of an intracavitary thrombus in the left ventricle (LV). Autopsy confirmed no signs of local infection, LV thrombus or peripheral embolism. Light and electron microscopy revealed an intact epithelium covering a layer of connective tissue on the plug surface facing the heart lumen. Conclusions This novel apical plug for LVAD explantation allows for endothelial and connective tissue growth on its ventricular side within 90 days from surgery. Further studies are required to fully demonstrate the biocompatibility of this apical plug and investigate the optimal anticoagulation regimen to be applied after implantation.