Cerebral Thromboembolic Events Research Articles

A Dual-Pathogen Mitral Valve Endocarditis Caused by Coxiella burnetii and Streptococcus gordonii-Which Came First?

Infective endocarditis (IE) is still a life-threatening disease with high morbidity and mortality. While usually caused by a single bacterium, poly-microbial infective endocarditis (IE) is rare. Here, we report a (blood-culture-negative) dual pathogen mitral valve IE caused by Coxiella burnetii and Streptococcus gordonii: A 53-year-old woman was presented to an internal medicine department with abdominal pain for further evaluation. Within the diagnostic work up, transthoracic echocardiography (TTE) revealed an irregularly shaped echogenic mass (5 × 13 mm) adherent to the edge of the posterior mitral valve leaflet and protruding into the left atrium. As infected endocarditis was suspected, blood cultures were initially obtained, but they remained negative. Chronic Q fever infection was diagnosed using serologic testing. After the occurrence of cerebral thromboembolic events, the patient was admitted for mitral valve surgery. Intraoperatively, a massively destructed mitral valve with adhering vegetations was noted. Examination of the mitral valve by broad-range bacterial polymerase chain reaction (PCR) and amplicon sequencing confirmed Coxiella burnetii infection and yielded Streptococcus gordonii as the second pathogen. Based on the detailed diagnosis, appropriate antibiotic therapy of both pathogens was initiated, and the patient could be discharged uneventfully on the 11th postoperative day after a successful minimal-invasive mitral valve replacement.

Anesthetic management of patients undergoing cardiac myxoma resection: a single-center retrospective analysis.

Myxomas are the most common primary cardiac tumors. Intracardiac myxomas, although benign, could cause serious consequences such as tricuspid or mitral valve obstruction, hemodynamic collapse, and acute heart failure, which pose challenges during anesthetic management. The current study was designed to summarize the anesthetic management of patients undergoing cardiac myxoma resection. This study was performed retrospectively from the perioperative period of patients who underwent myxoma resection. Patients were divided into two groups according to whether the myxoma prolapsed into the ventricle (groupO) or not (group N) to evaluate the impact of tricuspid or mitral valve with obstruction. 110 patients, aged 17-78 years, undergoing cardiac myxoma resection between January 2019 and December 2021 were collected, and their perioperative characteristics were recorded. In the preoperative evaluation, common clinical symptoms included dyspnea and palpitation, whereas embolic events occurred in 8 patients, including 5 (4.5%) cerebral thromboembolic events, 2 (1.8%) femoral artery, and 1 (0.9%) obstructive coronary artery. According to the echocardiography, left atrial myxoma was detected in 104 (94.5%) patients, the average dimension of myxoma was 4.03 cm ± 1.52 cm in the largest diameter, and 48 patients were divided into group O. During intraoperative anesthetic management, hemodynamic instability occurred in 38 (34.5%) patients after anesthesia induction. More patients in group O had hemodynamic instability (47.9% vs. 24.2%, p = 0.009) than in group N. The mean postoperative length of stay in the hospital was 10.64 ± 3.01 days, and most of the patients made an uneventful postoperative recovery. Anesthetic management for myxoma resection can be composed by assessing the myxoma, particularly the echocardiography evaluation and preventing cardiovascular instability. Typically, tricuspid or mitral valve with obstruction is a premier ingredient in anesthetic management.

Association of Neutrophil Extracellular Traps with Plaque Instability in Patient with Carotid Artery Stenosis

Vulnerable carotid plaques are related to cerebral thromboembolic and ischemic events. Neutrophil extracellular traps (NETs) can induce endothelial dysfunction and induce inflammation and coagulation. The aim of the present study was to investigate NETs in patients with carotid artery plaques. Carotid plaques were collected by carotid endarterectomy (CEA) from 26 symptomatic and 8 asymptomatic patients between August 2017 and January 2021. The specimens were stained with hematoxylin-eosin and Elastica-van Gieson. Immunohistochemistry was performed staining by CD31 for identifying endothelial cells. NETs were detected by digoxigenin-labeled antihistone H3 (HH3) (citrulline R2+R8+R17). The relationships between the presence of NETs and patient profile and histopathological findings were assessed. HH3-positive cells were detected in 17 (asymptomatic=2 symptomatic=15) of 34 carotid plaques (median=9.7/mm). The number of NETs was correlated with the number of diffusion-weighted imaging high-intensity lesions [P=0.01], plaque rupture [P=0.001], intraplaque hemorrhage [P=0.02], intra luminal thrombus [P=0.001], and thin fibrous cap [P=0.001]. The presence of NETs was associated with the instability of carotid plaques, intraluminal thrombus, which may lead to subsequent cerebral infarction. Clarifying the roles of NETs in carotid plaques may improve the treatment of carotid artery disease.

Actual management costs of patients with non-valvular atrial fibrillation treated with percutaneous left atrial appendage closure or oral anticoagulation

Abstract Background Left atrial appendage closure (LAAC) is a safe and efficacious alternative to oral anticoagulation (OAC) therapy in patients with non-valvular atrial fibrillation (AF) who are at high risk for both stroke and bleeding. Data on cost-effectiveness of LAAO are limited and existing studies on the topic are based on simulation model approaches rather than on real-world costs. Purpose To compare actual management costs in patients with non-valvular AF treated with LAAC or OAC only. Methods Percutaneous LAAC was performed only in patients with at least one cerebral thromboembolic event, one major bleeding episode while under OAC, and with absolute contraindication to prolonged OAC. AF patients undergoing percutaneous LAAC were matched with AF patients treated with OAC only. Matching variables were gender, age, and Diagnosis Related Groups (DRG) clinical complexity level. Costs for cardiovascular outpatient clinic visits and hospitalizations were derived from the actual medical claims and reimbursement records. Data were prospectively collected and retrospectively analyzed. Results Between 1/2012 and 12/2016, 8478 patients with non-Valvular AF were referred to our institution: 7801 (92%) were managed with OAC only and 677 (8%) with LAAC. A total of 559 patients (279 per group) were matched. Mean age was 74.9±7.5 years, 244 were female (43.7%), and mean DRG clinical complexity level was 1.8±1.1. Median annualized management cost before LAAC was €3110 (IQR €1281–8127). Median hospitalization cost for LAAC was €9601 (IQR: €9393–10007). After a mean follow-up of 4.5±1.4 years, median annualized management cost was €1297 (€607–2735) in patients with sole OAC and €1013 (IQR €0–4770) in patients after LAAC (p=0.003). Undergoing LAAC was the strongest independent determinant to reduce follow-up management costs (linear regression: beta = −0.335; CI: −1.09 to −0.682; p<0.0001). Estimated 3-year survival was similar in the LAAC (92%) and OAC patients (90%) (p=0.7). Conclusion LAAC significantly reduces management costs of patients with non-valvular AF. In patients referred for percutaneous LAAC, the drastic reduction in management costs following LAAC justifies the procedural costs. In spite of their complex comorbid profile, LAAC patients show a follow-up survival rate similar to those of patients solely treated with OAC. Management costs of patients solely on OAC are significantly higher than management costs of patients after LAAC. Future studies are necessary to investigate the potential net economic and clinical benefit of LAAC in patients that are treated with OAC only. Funding Acknowledgement Type of funding sources: None.

Cerebral Coagulation Complications Following COVID-19 Adenoviral Vector Vaccines: A Systematic Review

Emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak identified in late 2019 in Wuhan, China, was declared a pandemic in March 2020. High fatality rate in afflicted patients prompted scientists and physicians to develop various vaccines against the virus. While administration of millions of doses of the adenoviral vector vaccines (e.g., Oxford-AstraZeneca (ChAdOx1 nCoV-19) and Janssen/Johnson & Johnson (Ad26.COV2. S)) has helped control the disease, numerous cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia have been reported in vaccinated individuals. In this article, we aim to review the cases reported thus far and further discuss the association between the vaccine administration and subsequent cerebral thromboembolic events. Our study was performed and reported based on the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Google Scholar and Norris Medical Library databases were searched using the following terms: coronavirus disease 2019 (COVID-19) vaccines (“AstraZeneca” or “AZD1222 COVID vaccine” or “ChAdOx1 nCoV-19 COVID-19 vaccine” or “Janssen” or “Johnson & Johnson COVID vaccine” or “Ad26.COV2 COVID vaccine”), coagulopathy (“cerebral venous sinus thrombosis (CVST)” and “vaccine-induced immune thrombotic thrombocytopenia (VITT)” or “cerebral venous thrombosis (CVT)”) and thrombocytopenia. All the relevant studies within the English literature up to August 1, 2021, were included. Fourteen most recent articles reporting on 66 patients with CVST and VITT after adenoviral vector vaccination were reviewed by two independent authors. Age of the patients ranged from 18 to 60 years. The majority of cases were women (43 females versus 14 males). Platelet count was between 5 and 127 × 10 9 /L. Above-normal D-dimer was found in 86% of the patients. A total of 68% of the patients had positive platelet factor 4 IgG assay in the absence of prior exposure to heparin. Among CVST cases following COVID vaccination, 44% succumbed to death. Early diagnosis and treatment of CVST plays a fundamental role in decreasing morbidity and mortality. Health care professional should be familiar with this rare complication post vaccination against COVID-19. Given the rarity of CVST after the COVID-19 vaccine, the benefit of vaccination outweighs the potential harm. J Neurol Res. 2021;11(5):69-76 doi: https://doi.org/10.14740/jnr700

Cerebral Coagulation Complications Following COVID-19 Adenoviral Vector Vaccines: A Systematic Review

Emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak identified in late 2019 in Wuhan, China, was declared a pandemic in March 2020. High fatality rate in afflicted patients prompted scientists and physicians to develop various vaccines against the virus. While administration of millions of doses of the adenoviral vector vaccines (e.g., Oxford-AstraZeneca (ChAdOx1 nCoV-19) and Janssen/Johnson & Johnson (Ad26.COV2. S)) has helped control the disease, numerous cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia have been reported in vaccinated individuals. In this article, we aim to review the cases reported thus far and further discuss the association between the vaccine administration and subsequent cerebral thromboembolic events. Our study was performed and reported based on the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Google Scholar and Norris Medical Library databases were searched using the following terms: coronavirus disease 2019 (COVID-19) vaccines (“AstraZeneca” or “AZD1222 COVID vaccine” or “ChAdOx1 nCoV-19 COVID-19 vaccine” or “Janssen” or “Johnson & Johnson COVID vaccine” or “Ad26.COV2 COVID vaccine”), coagulopathy (“cerebral venous sinus thrombosis (CVST)” and “vaccine-induced immune thrombotic thrombocytopenia (VITT)” or “cerebral venous thrombosis (CVT)”) and thrombocytopenia. All the relevant studies within the English literature up to August 1, 2021, were included. Fourteen most recent articles reporting on 66 patients with CVST and VITT after adenoviral vector vaccination were reviewed by two independent authors. Age of the patients ranged from 18 to 60 years. The majority of cases were women (43 females versus 14 males). Platelet count was between 5 and 127 × 109/L. Above-normal D-dimer was found in 86% of the patients. A total of 68% of the patients had positive platelet factor 4 IgG assay in the absence of prior exposure to heparin. Among CVST cases following COVID vaccination, 44% succumbed to death. Early diagnosis and treatment of CVST plays a fundamental role in decreasing morbidity and mortality. Health care professional should be familiar with this rare complication post vaccination against COVID-19. Given the rarity of CVST after the COVID-19 vaccine, the benefit of vaccination outweighs the potential harm.

Cefalea persistente in una bambina con rettocolite ulcerosa: pensa alla trombosi venosa

Patients with inflammatory bowel disease have an increased risk of thromboembolic complications, especially during the active phase of the disease. Cerebral thromboembolism is a rare extra-intestinal complication, associated with high risk of morbidity and mortality. Due to the nonspecific clinical presentation and low incidence, a cerebral thromboembolic event may be undiagnosed. For this reason neurological symptoms, such as headache, should not be underestimated in inflammatory bowel disease patients. The paper describes a case of a three-year-old girl with ulcerative colitis complicated by cerebral thrombosis.

Efficacy and safety of left atrial appendage electrical isolation during catheter ablation of atrial fibrillation: an updated meta-analysis.

Left atrial appendage electrical isolation (LAAEI) has been shown to improve freedom from all-atrial arrhythmiarecurrence in patients with non-paroxysmal atrial fibrillation (AF). The aim of this study is to investigate the long-term efficacy and safety outcomes of LAAEI in patients with non-paroxysmal AF undergoing catheter ablation. A systematic review of Medline, Cochrane, and Embase was performed for clinical studies evaluating the benefit of LAAEI in non-paroxysmal AF. Nine studies with a total of 2336 patients were included (mean age: 65 ± 9 years, 63% male). All studies included patients with persistent AF, long-standing persistent AF, or both. At a mean follow-up of 40.5 months, patients who underwent LAAEI had significantly higher freedom from all-atrial arrhythmiarecurrence than patients who underwent standard ablation alone [69.3% vs. 46.4%; risk ratio (RR) 0.54; 95% confidence interval (CI) 0.42-0.69; P < 0.0001]. A 46% relative risk reduction and 22.9% absolute risk reduction in atrial-arrhythmia recurrence was noted with LAAEI. Rates of cerebral thromboembolism were not significantly different between the two groups (LAAEI 3% vs. standard ablation 1.6%, respectively; RR 1.76; 95% CI 0.61-5.04; P = 0.29). Furthermore, there was no significant difference in the acute procedural complication rates between the two groups (LAAEI 4% vs. standard ablation 3%, respectively; RR 1.29; 95% CI 0.83-2.02; P = 0.26). At long-term follow-up, LAAEI led to a significantly higher improvement in freedom from all-atrial arrhythmiarecurrence in patients with non-paroxysmal AF, when compared to standard ablation alone. Importantly, this benefit was achieved without an increased risk of acute procedural complications or cerebral thromboembolic events.

Impact of access route to the left ventricle on asymptomatic periprocedural brain injury: the results of a randomized trial in patients undergoing catheter ablation of ventricular tachycardia.

Catheter ablation of ventricular tachycardia (VT) is an effective treatment in patients with structural heart disease (SHD) and recurrent arrhythmias. However, the procedure is associated with the risk of complications, including both manifest and asymptomatic cerebral thromboembolic events. We hypothesized that periprocedural asymptomatic brain injury (ABI) can be reduced by using transseptal instead of the retrograde access route to the left ventricle (LV). Consecutive patients undergoing VT ablation for SHD were randomized 1:1 to either retrograde or transseptal LV access. All patients underwent radiofrequency ablation in conscious sedation with the use of an irrigated tip catheter. The degree of brain damage was evaluated by serum level of biomarker S100B. Significant ABI was defined as a post-ablation relative increase of S100B level >30%. A total of 144 patients (66 ± 9 years; 14 females; 90% coronary artery disease; LV ejection fraction: 30 ± 8%) were enrolled and 72 were allocated to each study groups. Symptomatic neurological complication of the procedure was not observed in any subject. A significant ABI was detected in 19.4% of patients. It was more commonly observed in subjects randomized to retrograde vs. transseptal LV access (26.4% vs. 12.5%, P = 0.04). In a multivariate analysis, only retrograde LV access and advanced age were independent determinants of significant ABI. Significant ABI after ablation of VT in patients with SHD can be detected in one-fifth of subjects. Retrograde access to LV is associated with a two-fold higher probability of significant ABI.

Correlation of platelet inhibition and cerebral thromboembolic events, as expressed with number of high-intensity transient signals,during Transcatheter Aortic valve Implantation

Abstract Background It has been shown that high Residual Platelet Reactivity (RPR) may contribute to platelet aggregation which propagates thrombosis on implanted materials. Therefore, we evaluated whether high RPR may predispose to an increased number of cerebrovascular emboli during Transcatheter Aortic valve Implantation (TAVI). Methods Consecutive patients who underwent transfemoral TAVI with a self-expandable valve were prospectively studied. A loading dose of P2Y12 inhibitor 24 hours preprocedurally was given. Additionally, aspirin was started one week prior to procedure in all patients. Platelet inhibition was assessed with P2Y12 reaction units (PRU) (Verify Now assay) as well as percentage of inhibition 30 minutes prior to procedure initiation. The number of High intensity transient signals (HITS) was assessed with Rimed Digi-Lite™ transcranial Doppler, setting a threshold for detection of HITS at 3dB, continuously, on both middle cerebral arteries during the whole procedure. Two observers reviewed offline the number of HITS. Results In total, 84 patients underwent TAVI (53 males, mean age=81.9yrs old ±8,98). Mean baseline PRU and percentage of platelet inhibition was 258,24±43,03 (156–376) and 48,51%±40.05 (0–100%) respectively. In the treated patients the mean absolute total number of HITS and the number of HITS per minute recorded, was 566,63±272,32, (136–1432) and 6.7/min±3.3 (2.09–13.24) respectively. Significant positive correlation was found between baseline PRU levels and number of total HITS (r=0.261, p=0.017), (Figure 1). Multivariate regression analysis revealed that PRU was independent prognostic factor of total HITS (β=0.708, p=0.06), In order to clarify the predictive role of platelet inhibition in the total number of recorded HITS a ROC analysis was performed, obtaining an area under the curve of 0.646 (95% CI 0.518 to 0.773, p=0.047). PRU-levels≥169 were shown to predict number of HITS at the upper quartile with 76% sensitivity and 65% specificity. Conclusion High RPR after dual antiplatelet loading with a P2Y12 inhibitor and aspirin, resulted in larger burden of embolic HITS during TAVI procedure. A cut off point of 169 PRU units with 76% sensitivity and 65% specificity predicted detection of HITS at the higher quartile. PRU-HITS Correlation Funding Acknowledgement Type of funding source: None

Atrial high-rate episodes: clinical significance, prognostic impact and clinical management

The rapid increase in cardiac implantable electronic device (CIED) implants and their ability to monitor atrial activity significantly contributed to a parallel increase in the occasional detection of atrial tachyarrhythmias, termed as atrial high-rate episodes (AHREs). These episodes of atrial tachyarrhythmia are usually asymptomatic and they are often diagnosed incidentally during the regular follow-up of patients with CIEDs or during the diagnostic work-up for patients affected by cryptogenic stroke. Over the past 20 years, numerous studies attempted to demonstrate the clinical significance and prognostic impact of these episodes, but their clinical management remains unclear. However, AHREs are not only significantly associated with a greater risk of developing clinical atrial fibrillation over time, but are also associated with an increased risk of cerebral and/or systemic thromboembolic events. Therefore, if deemed favorable, the use of oral anticoagulant therapy may be reasonable. The purpose of this review is to perform a state of the art analysis focusing on the clinical management of AHREs, their prognostic impact, the risks and benefits of anticoagulation and the critical issues that have emerged in the last years of studies.

Cerebral thromboembolic risk in atrial fibrillation ablation: a direct comparison of vitamin K antagonists versus non-vitamin K-dependent oral anticoagulants.

Cerebral thromboembolic events are well-known complications of pulmonary vein isolation (PVI) and can manifest as stroke or silent cerebral embolic lesions. The aim of this study was to compare the incidence of cerebral embolic lesions (including silent cerebral embolism and stroke) after AF ablation in patients on vitamin K antagonists versus patients on non-vitamin K-dependent oral anticoagulants, and to identify corresponding clinical and procedural risk factors. A total of 421 patients undergoing PVI were prospectively included into the study. Of these, 43.7% were on VKA and 56.3% on NOAC treatment (dabigatran, rivaroxaban, apixaban, and edoxaban). In the NOAC group, 38% of patients had an interruption of anticoagulation for 24-36h. All patients underwent pre- and postprocedural cerebral magnetic resonance imaging. Periprocedural cerebral lesions occurred in 13.1% overall. Of these, three (0.7%) resulted in symptomatic cerebrovascular accidents and 52 (12.4%) in silent cerebral embolic lesions. Incidence of cerebral lesions was significantly higher in patients on NOAC compared with VKA (16% vs. 9.2%, respectively, p = 0.04), and in patients who had intraprocedural cardioversions compared with no cardivoersions (19.5% vs. 10.4%, respectively, p = 0.03). In multivariate analysis, both parameters were found to be independent risk factors for cerebral embolism. No significant difference between interrupted and uninterrupted NOAC administration could be detected. In patients undergoing AF ablation, we identified the use of NOAC and intraprocedural cardioversion as independent risk factors for the occurrence of periprocedural cerebral embolic lesions.

Catheter ablation of atrial fibrillation with uninterrupted anticoagulation: a meta-analysis of six randomized controlled trials.

Uninterrupted anticoagulation is recommended during the ablation of atrial fibrillation. This meta-analysis compared the safety and efficacy of uninterrupted direct oral anticoagulants (DOACs) to uninterrupted vitamin K antagonists (VKAs) during atrial fibrillation ablation. The meta-analysis included eligible randomized controlled trials from 2009 to 2019. Odds ratios (ORs) and 95% confidence intervals were pooled using a random effects model and a sensitivity analysis was performed by sequentially removing one study or DOAC at a time. Six studies were included; 1288 received DOAC and 1081 VKA. Pooled ORs indicated a lower nonsignificant incidence in DOACs vs. VKA of composite outcome of major bleeding, stroke, or transient ischemic attack, and mortality (0.69; 0.28-1.71; 31 vs. 45 events), major bleeding alone (0.66; 0.30-1.47; 27 vs. 41 events), and cardiac tamponade (0.56; 0.21-1.45; eight vs. 13 events) with a slightly higher occurrence of minor bleeding (1.17; 0.89-1.56; 139 vs. 106 events) and silent cerebral thromboembolic events (1.12; 0.75-1.66; 72 vs. 58 among 442 and 376 patients performing MRI study). Sensitivity analyses confirmed overall results: pooled ORs ranged from 0.56 to 1.00 for the composite outcome and from 0.54 to 0.92 for major bleedings. Uninterrupted DOAC is a safe and effective alternative to uninterrupted VKA during atrial fibrillation ablation.

Prospective evaluation of iatrogenic atrial septal defect after cryoballoon or radiofrequency catheter ablation of atrial fibrillation-"EVITA" study.

Iatrogenic atrial septal defect (IASD) after catheter ablation (CA) for atrial fibrillation (AF) due to transseptal puncture (TSP) can occur. The aim of this prospective study was to describe the incidence of IASD and to detect any cerebrovascular accident (CVA) after radiofrequency (RF) and cryoballoon (CB) CA. Between July 2014 and September 2016, 94 patients (pts) (RF; 48, CB; 46, 30 (31.9%) women, mean age = 60 ± 9.7years) with paroxysmal AF were enrolled who underwent CA procedure for the first time. During RF ablation a single (n= 30, 62.5%) or double (n= 18, 37.5%) TSP was performed. Transoesophageal echocardiography before the procedure and at the 3-month and 12-month follow-up (FU) was accomplished. During the FU period, we evaluated the occurrence of any postprocedural CVA. At the 3-month FU, IASD was detected in 17/94 (18.1%) pts; in 9/48 (18.8%) pts in the RF while in 8/46 (17.4%) pts in the CB group (p= 0.866), all of them with left-to-right shunt. In the RF group, 6/30 (20%) pts with a single TSP while 3/18 (16.7%) pts in the double TSP group had IASD (p= 0.780). 14/17 (82.4%) IASDs showed high spontaneous closure rate at the 12-month FU. None of the pts died or suffered from CVA. Persistent IASD can occur rather frequently following AF CA. No significant difference was observed between the RF and CB techniques concerning the presence of IASD at 3-month. IASDs showed a high spontaneous closure rate. No cerebral thromboembolic event was observed in the 12-month FU period.

PF431 CLINICAL CHARACTERISTICS, TREATMENT PATTERNS, AND THROMBOEMBOLIC RISK OF PATIENTS WITH COLD AGGLUTININ DISEASE (CAD) IN JAPAN

Background:CAD is a rare form of autoimmune hemolytic anemia with a prevalence in Northern Europe of 16 cases per 1 million inhabitants (Berentsen S. Semin Hematol 2018). Ig M autoantibodies bind to red blood cells and trigger hemolysis via activation of the classical complement pathway. Although clinical and epidemiological studies are limited, recent evidence indicates that CAD patients in Europe and North America have an increased risk of thromboembolic events (TE) (Bylsma LC, et al. EHA 2018; Broome C, et al. Blood 2017). The 1‐year case‐fatality of TE has been reported as 23% (Tagalakis V, et al. Am J Med 2013). There are no studies evaluating the clinical course and risk of TE in CAD patients in Japan or other Asian populations.Aims:To describe clinical characteristics, treatment patterns, and risk of TE in CAD patients in Japan.Methods:Patients were retrospectively identified from 2008 to 2017 using a hospital‐based administrative claims database (Medical Data Vision), representing approximately 300 hospitals and 20 million patients in Japan. CAD cohort inclusion required age ≥18 years and CAD diagnosis (Japanese Disease Code 2830009) entry on ≥3 separate occasions within the study period. The first CAD diagnostic code entry was used as the index date. Patients in the comparison cohort had no history of CAD and were matched 10:1 to patients in the CAD group by age, sex, year and season of diagnosis, follow‐up time, and comorbidities using the Charlson Comorbidity Index. Conditional logistic regression was used to adjust for these variables when comparing cohorts.Results:344 CAD patients were identified with a slight female preponderance (53.2%), mean age of 66.8 years and 18.9‐month mean duration of follow‐up. The most frequently used treatment was steroids (34.2%). Other treatments included cytotoxic chemotherapy (6.9%), rituximab (5.9%), and immunosuppressants (5.9%). A total of 3440 patients with matching characteristics were included in the control group to compare the risk of TE among cohorts. Overall, CAD patients had an increased rate of TE versus patients without CAD (34.8% vs 17.9%, respectively; P &lt; 0.0001) (Figure). The rate of arterial and venous TE was also higher in CAD versus non‐CAD cohorts (25.0% vs 4.6% and 8.4% vs 4.0%, respectively; P &lt; 0.0001 for both analyses). Most cases of arterial TE in CAD patients corresponded to myocardial infarctions (87.2%). There was no difference in cerebral TE among the CAD and non‐CAD groups (10.4% vs 11.9%, respectively). The overall odds ratio (OR [95% confidence interval]) for development of TE in the CAD cohort versus non‐CAD cohort was 2.81 (2.18–3.61). Corresponding ORs for arterial and venous TE were 8.59 (6.16–11.98) and 2.37 (1.56–3.62), respectively.Summary/Conclusion:This study is the first to evaluate the clinical characteristics, treatment practices, and TE risk of CAD patients in Japan. Our results indicate that the CAD treatment approach used in Japan (ie, predominantly with steroids) differs from that reported for other countries. However, in accordance with recent reports from non‐Asian populations, this study demonstrates an increased risk of TE in the Japanese population. Interestingly, the rate of arterial TE was higher in Japan, which was mostly attributed to the high prevalence of myocardial infarctions in our CAD cohort. Japanese healthcare providers should be aware of these risks to properly monitor their CAD patients. Prospective studies are needed to further evaluate these findings.image

Atrial and left atrial appendage thrombosis in patients with atrial fibrillation: from pathophysiology to treatment

Atrial fibrillation (AF) is the most frequent sustained cardiac arrhythmia, and its prevalence is increasing, partly due to the progressive aging of the population. AF predisposes to thrombus formation in the atria and the atrial appendage through a complex interaction among local, systemic and hemodynamic factors, significantly increasing the risk for cerebral and systemic thromboembolic events. These complications have a major impact in terms of morbidity and mortality, and numerous therapeutic strategies have been proposed to reduce such risk. Systemic anticoagulation is the main strategy in the prevention of atrial and left atrial appendage thrombosis, and the advent of non-vitamin K antagonist oral anticoagulants (NOACs) has been a significant step forward, especially for safety, compared to warfarin. While prevention of atrial appendage thrombosis with NOACs has been widely explored, their role in the resolution of thrombi is less clear. The use of NOACs in this setting is largely unexplored, and some studies are underway to clarify their effectiveness. The objective of this paper is to review the literature on atrial and left atrial appendage thrombosis, describing pathophysiological mechanisms and current treatment strategies using NOACs.

Epidemiology of stroke and cerebral protection in patients undergoing transcatheter aortic valve replacement

The introduction into clinical practice of transcatheter aortic valve implantation (TAVI) has led to a significant change in the therapeutic paradigm for patients with valvular aortic stenosis. However, in parallel with the benefits obtained in prognosis and quality of life, an inherent risk of major cerebral thromboembolic events has been observed. In different studies this risk has been estimated between 2% and 6%. In order to reduce the incidence of cerebrovascular accidents during TAVI, several brain protection systems have been developed but, to date, none has obtained sufficient clinical evidence to be implemented on a large scale, and they are therefore used only in selected cases. Furthermore, periprocedural drug therapy and follow-up are still the subject of extensive discussion in the scientific community. This paper reviews the topic of stroke prevention in patients undergoing TAVI for both the periprocedural and postprocedural aspects.

Neurological complications in childhood nephrotic syndrome: A systematic review.

Nephrotic syndrome (NS) in childhood can be accompanied by serious neurological complications increasing the morbidity of disease. The study aimed to assess the spectrum of neurological complications in children with in terms of clinical presentation, contributory risk factors, and outcome. In this systematic review, we searched for articles in PubMed, providing individual patient-level data for any neurological complication in children and adolescents with primary NS, between January 1, 1990 and April 30, 2018. The search yielded 63 articles, involving 103 patients. Events occurred more frequently during nephrotic state relapses; 71.6% of cerebral thromboembolic (TE) events and 81.2% of posterior reversible encephalopathy (PRES) cases. Median duration of disease before a cerebral TE event was 3 months (IQR 0-27), and 18 months (IQR 1-37.5) for PRES. Among cases with TE, 73.1% presented with cerebral sinovenous thrombosis (CSVT), and 16.9% parenchymal lesions. 70% of patients had a risk factor for neurological complication including NS-associated thrombophilia, hypertension, and treatment with immunosuppressive agents. Outcome was favorable in 93.8% of the patients with PRES. In patients with cerebral TE outcome was favorable in 95.8% of the cases with CSVT only, and in 64.7% of the cases with parenchymal lesions. Neurological complications may occur in children with primary NS and risk factors during nephrotic state relapses. The outcome for PRES has been reported favorable. Outcome in cerebral TE events may differ by the presence of venous or artery infarct. Recognition of additional protrombotic state risk factors may help to lower the incidence of neurological complications.

A meta-analysis of randomized controlled trials of uninterrupted periprocedural anticoagulation strategy in patients undergoing atrial fibrillation catheter ablation

BackgroundIn patients undergoing atrial fibrillation (AF) ablation, despite uninterrupted oral anticoagulants (OACs) have been recommended, no consensus has emerged regarding to whether uninterrupted novel oral anticoagulants (NOACs) are superior to uninterrupted vitamin K antagonists (VKAs) for the periprocedural antithrombotic management. This meta-analysis aimed to compare the efficacy and safety of uninterrupted NOACs and uninterrupted VKAs in patients undergoing AF ablation. MethodsDatabases were searched for articles published up to March 20, 2018. Only randomized controlled trials (RCTs) were selected. The data were analyzed with RevMan 5.3 using a fixed-effects method. Results6 RCTs and 1903 patients were included. There was no significant difference between NOACs group and VKAs group in incidence of stroke or TIA (OR = 1.00, 95% CI = 0.23–4.40, P = 1.00), silent cerebral thromboembolic events (OR = 1.09, 95% CI = 0.67–1.75, P = 0.74) or minor bleeding (OR = 1.01, 95% CI = 0.78–1.31, P = 0.93), which were consistent in subgroup analysis of individual NOAC vs. VKAs group. NOACs treatment was associated with reduced risk of major bleeding as compared with VKAs (OR = 0.45, 95% CI = 0.26–0.81, P < 0.01). In the subgroup analyses, only the dabigatran group showed significant lower incidence of major bleeding compared to VKAs group. ConclusionsIn patients undergoing AF ablation, uninterrupted NOACs is as effective as uninterrupted VKAs treatment, uninterrupted dabigatran (150 mg twice daily) may be superior to other uninterrupted OACs strategies.

Anticoagulation and Antiplatelet Strategies After On-X Mechanical Aortic Valve Replacement

BackgroundThe burden oral anticoagulation is a limitation of mechanical valve prostheses. ObjectivesThe aim of this study was to test whether patients could be safely managed with dual-antiplatelet therapy (DAPT) (aspirin 325 mg and clopidogrel 75 mg) or lower warfarin after On-X mechanical aortic valve replacement (mAVR). MethodsPROACT (Prospective Randomized On-X Anticoagulation Trial) (n = 576) is a multicenter (41 sites) noninferiority trial. From June 2006 through February 2014, 201 patients ≥18 years of age without thromboembolic risk factors undergoing mAVR were randomized to receive DAPT (n = 99) or standard warfarin plus aspirin (n = 102) 3 months after mAVR (low-risk arm). From June 2006 through October 2009, 375 patients with 1 or more thromboembolic risk factors were also randomized to lower intensity warfarin plus aspirin (international normalized ratio 1.5 to 2.0; n = 185) or standard warfarin plus aspirin (international normalized ratio 2.0 to 3.0; n = 190) 3 months after mAVR (high-risk arm). ResultsThe low-risk arm was terminated for excess cerebral thromboembolic events (3.12% per patient-year vs. 0.29% per patient-year, p = 0.02) in the DAPT group at up to 8.8-year follow-up (631.6 patient-years), with no differences in bleeding or all-cause mortality. High-risk arm patients experienced significantly lower major (1.59% per patient-year vs. 3.94% per patient-year, p = 0.002) and minor (1.27% per patient-year vs. 3.49% per patient-year, p = 0.002) bleeding up to 8.7-year follow-up (2,035.2 patient-years), with no differences in thromboembolism (0.42% per patient-year vs. 0.09% per patient-year, p = 0.20) and all-cause mortality. ConclusionsDAPT was associated with higher rates of thromboembolism and valve thrombosis compared with control in the low-risk arm. International normalized ratios were safely maintained at 1.5 to 2.0 in high-risk patients, without differences in mortality or thromboembolic complications. (Randomized On-X Anticoagulation Trial [PROACT]; NCT00291525)