Non-anticoagulated Atrial Fibrillation Patients Research Articles

Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

ABC-AF-Stroke score predicts thromboembolism in non-anticoagulated patients following successful atrial fibrillation ablation: a report from the Chinese Atrial Fibrillation Registry.

The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations. A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate. After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population. In this real-world study enrolling non-anticoagulated AF patients following successful ablations, age, prior history of stroke/TIA, level of NT-proBNP, and cTnT-hs were independently associated with an increased risk of thromboembolism. The ABC-AF-Stroke score was well-calibrated and statistically significantly outperformed the CHA2DS2-VASc score in predicting thromboembolism risk.

Impact of metabolic syndrome on the risk of ischemic stroke in non-anticoagulated atrial fibrillation patients having low CHA2DS2-VASc scores

Abstract Background Metabolic syndrome (MetS) predisposes to a thromboembolic state. However, conflicting results have been reported on whether MetS confers an increased risk of ischemic stroke in atrial fibrillation (AF), especially in patients with low CHA2DS2-VASc score who are not indicated for oral anticoagulant therapy. Purpose We investigated the risk of ischemic stroke according to the presence of MetS, the number of MetS components (metabolic burden), and the individual metabolic components in non-anticoagulated AF patients with low CHA2DS2-VASc score. Methods A total of 76,015 oral anticoagulant-naïve AF patients with low CHA2DS2-VASc score (0,1 in male and 1 in female) were included from the Korean National Health Insurance Service database. The status of MetS and individual metabolic components were evaluated based on health examination data within two years of AF diagnosis. We estimated the risk of ischemic stroke according to MetS, metabolic burden, and an individual component of MetS using Cox proportional-hazards models. Results The mean age was 49.8±11.1 years and 52,388 (68.9%) were male. The average CHA2DS2-VASc score was 0.7±0.5 and MetS was prevalent among 21,570 (28.4%) of the study population. During a mean follow-up of 5.1 years, ischemic stroke was developed in 1,395 (1.84%) patients. MetS was associated with a higher risk of ischemic stroke after adjustment for age, sex, lifestyle behaviors, low income, and cardiovascular comorbidities: adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) 1.06–1.33, p=0.002. A positive linear correlation was observed between metabolic burden and ischemic stroke risk. Patients with five MetS components showed the highest aHR of 1.55 (95% CI 1.14–2.11, Figure 1 and Figure 2), whereas those with a single MetS component had a marginal risk of ischemic stroke (aHR 1.18, 95% CI 0.99–1.41). Among individual metabolic components, elevated blood pressure and increased waist circumference was significantly associated with an increased risk of ischemic stroke: aHR (95% CI), 1.45 (1.30–1.62), p<0.001, and 1.15 (1.03–1.30), p=0.016, respectively. Conclusions Among AF patients initially with CHA2DS2-VASc score 0 and 1 with no anticoagulation, the presence of MetS is associated with an increased risk of ischemic stroke. Given the linear incremental correlation between metabolic burden and ischemic stroke, special attention to the care of metabolic derangements is required in AF patients who are not indicated for anticoagulation. Funding Acknowledgement Type of funding sources: None.

Thromboembolic risk in non-anticoagulated atrial fibrillation patients with valvular heart disease and low CHA2DS2-VASc scores: are these patients truly low risk of stroke?

Abstract Background Patients with atrial fibrillation and valvular heart disease (VHD) beyond moderate-to-severe mitral stenosis and/or a mechanical prosthetic valve, so-called EHRA Type 2 VHD, have been associated with a higher risk of thromboembolism compared with patients with atrial fibrillation and no VHD. A minor but important proportion of patients with atrial fibrillation and EHRA Type 2 VHD has 0 or 1 coexisting CHA2DS2-VASc stroke risk factors, and are therefore not strongly recommended oral anticoagulant therapy according to guidelines. Whether these patients are “truly low” risk of stroke has not been investigated. We aimed to describe the risk of thromboembolism in non-anticoagulated atrial fibrillation patients with and without EHRA Type 2 VHD and with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score. Methods Cohort study of atrial fibrillation patients with and without EHRA Type 2 VHD identified in nationwide Danish registries from 2000–2018. 1-year risk of thromboembolism was estimated for the study population divided into four subgroups in relation to non-sex CHA2DS2-VASc score comorbidities (except for previous thromboembolism) and age category (<65 or 65–74 years). Results We identified 1,907 and 53,707 incident atrial fibrillation patients with and without EHRA Type 2 VHD. Median age was 57 years and 55 years in patients with and without EHRA Type 2 VHD and 0 comorbidities and 67 years in patients with and without EHRA Type 2 VHD and 1 comorbidity. Percentage of females was approximately 44% in patients with and without EHRA Type 2 VHD and 0 comorbidities and 33% and 36% in patients with and without EHRA Type 2 VHD and 1 comorbidity. In patients with 1 comorbidity, the most prevalent stroke risk factor of the CHA2DS2-VASc score was hypertension. Cumulative incidence of thromboembolism according to presence of EHRA Type 2 VHD and age category in patients with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score are presented in the figure (the curve for patients with EHRA Type 2 VHD aged 65–74 years and with 0 comorbidities was omitted due to few events). At 1 year after atrial fibrillation diagnosis, patients with and without EHRA Type 2 VHD aged <65 or 65–74 years and with 0 or 1 comorbidity of the CHA2DS2-VASc score had a risk of thromboembolism ranging 1.3–2.2% and 0.5–1.7% according to age category and number of comorbidities of the CHA2DS2-VASc score. In patients with EHRA Type 2 VHD aged <65 years with 0 or 1 comorbidity, the risk was 1.5% and 2.2% at 1 year after the diagnosis of atrial fibrillation. Conclusion In atrial fibrillation patients with EHRA Type 2 VHD, we observed a risk of thromboembolism that may exceed the level above which oral anticoagulation is considered beneficial. No trial has specifically examined patients with EHRA Type 2 VHD and low CHA2DS2-VASc scores and, therefore, our observations may be important to patients who are not recommended oral anticoagulant therapy according to contemporary guidelines. Figure 1. Cumulative incidence of thromboembolism Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The study was supported by “The BMS/Pfizer European Thrombosis Investigator Initiated Research Program (ERISTA) 2018” and the Obel Family Foundation.

Thromboembolic Risk in Nonanticoagulated Patients With Atrial Fibrillation and Valvular Heart Disease.

This study sought to describe the risk of thromboembolism in nonanticoagulated atrial fibrillation patients with Evaluated Heartvalves, Rheumatic or Artificial (EHRA) Type 2 valvular heart disease (VHD)<65 or 65 to 74 years of age and with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score. A minor, but important, proportion of patients with atrial fibrillation and VHD beyond moderate-to-severe mitral stenosis and/or a mechanical prosthetic valve, so-called EHRA Type 2 VHD, have 0 or 1 coexisting non-sex comorbidities of the CHA2DS2-VASc score, and are therefore not strongly recommended oral anticoagulant therapy according to guidelines. Whether these patients are truly low risk of thromboembolism has not been investigated. This was a cohort study of 55,613 patients identified in nationwide Danish registries from 2000 to 2018, of which 1,907 patients had EHRA Type 2 VHD. Risk of thromboembolism after 1 and 5 years of follow-up were calculated. At 1 year after atrial fibrillation diagnosis, patients with EHRA Type 2 VHD had a risk of thromboembolism between 1.2% and 1.5%, according to age group (<65 or 65 to 74 years of age), and number of non-sex comorbidities of the CHA2DS2-VASc score (0 or 1). Interestingly, in patients with EHRA Type 2 VHD<65 years of age with 0 or 1 comorbidity, the risk was 1.5% (95% confidence interval: 0.7% to 2.8%) and 1.5% (95% confidence interval: 0.6% to 3.4%) at 1 year after the atrial fibrillation diagnosis. These observations suggest that in atrial fibrillation patients with EHRA Type 2 VHD, who are not currently recommended oral anticoagulant therapy according to guidelines, the risk of thromboembolism may exceed the level above which oral anticoagulation is considered beneficial.

Chronic Kidney Disease and Its Impact on a Prothrombotic State in Patients with Atrial Fibrillation.

It is unclear whether chronic kidney disease (CKD) increases thromboembolism in atrial fibrillation (AF). We conducted a retrospective cross-sectional analysis of 502 non-anticoagulated AF patients (median age, 66 (60–73) years, median CHA2DS2-VASc score, 3.0 (2.0–4.0)) with an estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2. Endogenous thrombin potential (ETP), clot permeability (Ks), and clot lysis time (CLT), among others, were determined. Patients with stage 4 CKD (n = 87; 17.3%) had higher ETP and prolonged CLT compared with those with stage 3 CKD. In patients with stages 3 to 4 CKD (n = 180; 35.9%) N-terminal pro-B-type natriuretic peptide predicted low Ks (the lowest quartile, odds ratio [OR] per 100 pg/mL: 1.03, 95% confidence interval [CI]: 1.01–1.06) and prolonged CLT (the top quartile, OR per 100 pg/mL: 1.05, 95% CI: 1.02–1.08), but not high ETP. In the whole cohort, after adjustment for CHA2DS2-VASc score, stage 4 CKD, but not stage 3 CKD, predicted high ETP (OR: 9.06; 95% CI: 4.44−18.46) and prolonged CLT (OR: 3.58; 95% CI: 1.76–7.28), but not low Ks. compared to the reference eGFR category. This study is the first to demonstrate the prothrombotic and antifibrinolytic alterations in AF patients with stage 4 CKD, but not stage 3 CKD irrespective of clinical stroke risk factors.

Thromboembolic and bleeding outcomes in patients with atrial fibrillation and valvular heart disease: A descriptive nationwide cohort study.

The risks of thromboembolism and bleeding in patients with atrial fibrillation (AF) and valvular heart disease (VHD) are sparsely described. We described the risk of events in non-anticoagulated and anticoagulated patients with AF and VHD according to the evaluated heart valves, rheumatic or artificial valve classification (EHRA classification), EHRA Type 1 and Type 2 VHD, and within subgroups of EHRA Type 1 and Type 2 VHD. Cohort study of AF patients with coexisting VHD, identified in nationwide Danish registries from 2000 to 2018. Risk of thromboembolism and bleeding after 1year of follow-up were calculated in each group. We identified 28 770 incident AF patients with VHD. Not surprisingly, we observed the highest risks of thromboembolism in the non-anticoagulated AF patients with EHRA Type 1 and Type 2 VHD (4.9% vs 2.6% and 3.2% vs 1.9%) and the highest risks of bleeding in the anticoagulated AF patients with EHRA Type 1 and Type 2 VHD (6.6% vs 4.3% and 6.1% vs 4.9%). However, within the subgroups of AF patients with EHRA Type 1 and Type 2 VHD, we observed a large proportion of non-anticoagulated patients (32.9%-49.2%), despite a CHA2 DS2 -VASc score of 2≤ in the majority of these patients (81.9%-95.6%). When using data reflecting contemporary clinical practice, we observed markedly different risks of thromboembolism and bleeding in EHRA Type 1 and Type 2 VHD. Additionally, we observed a potential underuse of oral anticoagulation within the subgroups of AF patients with EHRA Type 1 and Type 2 VHD, underlining need for further attention on this patient group.

Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study.

Contemporary guidelines suggest anticoagulant treatment decisions in atrial fibrillation (AF) patients to be based on risk stratification for stroke. However, guidelines do not agree on the threshold for treatment initiation. We explored the variation in thromboembolic event rates in a non-anticoagulated AF population, according to different guideline threshold and methodological approaches. AF patients between 1998 and 2014 free from anticoagulant treatment were identified. Event rates for ischemic stroke and ischemic stroke/systemic embolism were explored. The overall ischemic stroke rate was 3.20 per 100 person-years (‘formal rate assessment’). For patients with a CHA2DS2-VASc score of 1 the ischemic stroke rate was 0.97 when using a ‘formal rate assessment’, 0.62 when using a ‘conditioning on the future’ approach, and 0.93 when using a ‘censoring approach’. Rates for thromboembolism for the ‘European treatment threshold’ (CHA2DS2-VASc score of 1, males only) ranged 1.17 to 1.53. Rates for the ‘U.S. treatment threshold’ (CHA2DS2-VASc of 2) ranged from 1.95 to 2.33. Thromboembolic event rates differed markedly in non-anticoagulated AF patients according to the conflicting European and U.S. guideline treatment thresholds. Second, the choice of methodological approach has implications, thus we recommend using the censoring approach for event rate estimation among AF patients not on treatment.

Should Atrial Fibrillation Patients With Only 1 Nongender-Related CHA2DS2-VASc Risk Factor Be Anticoagulated?

There is some uncertainty about treating patients with atrial fibrillation (AF) with 1 nongender-related (NGR) stroke risk factor (CHA2DS2-VASc [ie, congestive heart failure, hypertension, age (≥75 years; 2 points), diabetes, stroke/transient ischemic attack (2 points), vascular disease, age (65-74 years), sex (female)] score of 1 in males and 2 in females) with oral anticoagulation (OAC). We investigated adverse outcomes and calculated the net clinical benefit of OAC use in a community-based cohort of unselected AF patients with 0 compared with 1 NGR stroke risk factor (CHA2DS2-VASc 0 versus 1 in males; and 1 versus 2 in females). Among 8962 patients with AF, 2208 (25%) had 0 or 1 NGR stroke risk factors, of which 45% were not prescribed OAC. During a follow-up of 1028±1189 days (median, 495; interquartile range, 5-1882 days), the yearly rate of the combined end point of stroke/systemic embolism in nonanticoagulated AF patients with 1 NGR stroke risk factor was 2.09% (95% confidence interval, 1.37-3.18). This corresponded to an adjusted hazard ratio of 2.82 (95% confidence interval, 1.32-6.04) relative to the group with 0 NGR stroke risk factor. When the benefit of ischemic stroke reduction was balanced against the increased risk of intracranial hemorrhage among patients with 1 NGR stroke risk factor, the net clinical benefit was positive in favor of OAC use versus no antithrombotic therapy or antiplatelet therapy use. The net clinical benefit was negative for antiplatelet therapy use versus no antithrombotic therapy. Among AF patients with 1 NGR stroke risk factor (ie, CHA2DS2-VASc 1 in males or 2 in females), OAC use as indicated according to the guidelines was associated with a positive net clinical benefit for the prevention of stroke and thromboembolic events.

Female Sex, Time in Therapeutic Range, and Clinical Outcomes in Atrial Fibrillation Patients Taking Warfarin.

Female patients have higher risk for stroke than male patients in nonanticoagulated atrial fibrillation patients, but limited data are available on sex differences in stroke and bleeding outcomes among patients with anticoagulated atrial fibrillation on warfarin, especially in relation to quality of anticoagulation control, as reflected by the time in therapeutic range (TTR). We investigated adverse outcomes in females (n=791) and males (n=1501) among 2292 patients with atrial fibrillation taking warfarin arm in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. The combined end point of cardiovascular death and stroke/systemic embolism (SSE) was similar in females versus males. There was no sex differences in either cardiovascular death or SSE. Compared with males, females had a lower risk of major bleeding (hazard ratio, 0.39; 95% confidence interval, 0.18-0.87; P=0.02). No differences were seen in mortality and stroke outcomes between females and males either in the prespecified age subgroups or in relation to TTR categories. TTR was negatively correlated with any clinically relevant bleeding in both females (r=-0.86; P=0.03) and males (r=-0.94; P=0.005). On Cox regression, TTR (but not female sex) emerged as an independent predictor for combined cardiovascular death/SSE and clinically relevant bleeding events. Anticoagulated female patients with atrial fibrillation had a similar rate of cardiovascular death and SSE, but a lower risk of major bleeding, compared with males. TTR (but not female sex) was an independent predictor for combined cardiovascular death and SSE and clinically relevant bleeding events.

Age Threshold for Increased Stroke Risk Among Patients With Atrial Fibrillation: A Nationwide Cohort Study From Taiwan

BackgroundRecent studies from Asia have suggested that the risk of ischemic stroke for patients with atrial fibrillation (AF) with a “low-risk” congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74, female (CHA2DS2-VASc) score of 0 (for males) or 1 (for females) might be higher than that for non-Asians. ObjectivesThis study hypothesized that the age threshold (65 years) used in the CHA2DS2-VASc system for initiating oral anticoagulants (OACs) might be lower in Taiwanese AF patients than in non-Asians. MethodsWe used the National Health Insurance Research Database in Taiwan to study 186,570 nonanticoagulated AF patients. There were 9,416 males with a CHA2DS2-VASc score of 0 and 6,390 females with a CHA2DS2-VASc score of 1. Their risk of ischemic stroke was analyzed with stratification on the basis of age. ResultsThe annual risks of ischemic stroke for males (score 0) and females (score 1) were 1.15% and 1.12%, respectively, and continuously increased from younger to older age groups, with an increment in stroke risk evident for patients >50 years of age. At a cutoff of 50 years, patients could be further stratified into 2 subgroups with different stroke risks (>50 years of age: 1.78%/year; vs. <50 years of age: 0.53%/year). This observation was consistent for males (1.95%/year vs. 0.46%/year, respectively) and females (1.58%/year vs. 0.64%/year, respectively) with AF. In a subgroup analysis, the annual risks of ischemic stroke for males and females with AF 50 to 54 years of age were 1.47% and 1.07%, respectively. ConclusionsFor Taiwanese patients 50 to 64 years of age, the annual stroke risk was 1.78%, which may exceed the threshold for OAC use for stroke prevention. The annual risk of ischemic stroke for AF patients <50 years of age was 0.53%, which was truly low-risk, and OACs could be omitted. Whether resetting the age threshold to 50 years could refine current clinical risk stratification for Asian AF patients deserves further study.

Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES.

The pattern of atrial fibrillation (AF) occurrence-paroxysmal, persistent, or permanent-is associated with progressive stages of atrial dysfunction and structural changes and may therefore be associated with progressively higher stroke risk. However, previous studies have not consistently shown AF pattern to predict stroke but have been hampered by methodological shortcomings of low power, variable event ascertainment, and variable anticoagulant use. We analysed the rates of stroke and systemic embolism in 6563 aspirin-treated patients with AF from the ACTIVE-A/AVERROES databases. There was thorough searching for events and adjudication. Multivariable analyses were performed with the adjustment for known risk factors for stroke. Mean age of patients with paroxysmal, persistent, and permanent AF was 69.0 ± 9.9, 68.6 ± 10.2, and 71.9 ± 9.8 years (P < 0.001). The CHA2DS2-VASc score was similar in patients with paroxysmal and persistent AF (3.1 ± 1.4), but was higher in patients with permanent AF (3.6 ± 1.5, P < 0.001). Yearly ischaemic stroke rates were 2.1, 3.0, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjusted hazard ratio of 1.83 (P < 0.001) for permanent vs. paroxysmal and 1.44 (P = 0.02) for persistent vs. paroxysmal. Multivariable analysis identified age ≥ 75 year, sex, history of stroke or TIA, and AF pattern as independent predictors of stroke, with AF pattern being the second strongest predictor after prior stroke or TIA. In a large population of non-anticoagulated AF patients, pattern of AF was a strong independent predictor of stroke risk and may be helpful to assess the risk/benefit for anticoagulant therapy, especially in lower risk patients.

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States (1). Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 (2). Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke (3). The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF (3). Rate control is achieved by administration of pharmacological agents, such as β-blockers, that lower the heart rate until it reaches a less symptomatic state (3). Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods (4-6). In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects (3), or even increases in mortality in patients with structural heart defects (7). Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue (8), but don't reliably prevent thromboembolic events (6). Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism (9,10). However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding (2). As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke (10). Other alternatives to warfarin, such as dabigatran (11) or rivaroxaban (12) demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue (13-15). Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) (2), one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released.

The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 2. Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke 3. The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF 3. Rate control is achieved by administration of pharmacological agents, such as β-blockers, that lower the heart rate until it reaches a less symptomatic state 3. Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods 4-6. In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects 3, or even increases in mortality in patients with structural heart defects 7. Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue 8, but don't reliably prevent thromboembolic events 6. Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism 9,10. However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding 2. As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke 10. Other alternatives to warfarin, such as dabigatran 11 or rivaroxaban 12 demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue 13-15. Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) 2, one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released.

Plasma von Willebrand Factor Levels Are an Independent Risk Factor for Adverse Events Including Mortality and Major Bleeding in Anticoagulated Atrial Fibrillation Patients

The purpose of this study was to evaluate the prognostic value of plasma von Willebrand factor (vWF) levels and fibrin d-dimer in a large cohort of anticoagulated permanent atrial fibrillation (AF) patients. In nonanticoagulated AF patients, plasma vWF levels have been related to stroke and vascular events. There are limited data on the prognostic role of biomarkers in anticoagulated AF patients in relation to adverse events (including thromboembolism), mortality, and major bleeding. We studied 829 patients (50% male; median age 76 years) with permanent AF who were stabilized (for at least 6 months) on oral anticoagulation therapy (international normalized ratio: 2.0 to 3.0). Plasma d-dimer and vWF levels were quantified by enzyme-linked immunosorbent assay. Patients were followed for 2 years, and adverse events (thrombotic and vascular events, mortality, and major bleeding) were recorded. Patients were followed for a median of 828 days (range 18 to 1,085 days). On multivariate analysis, age 75 years and older, previous stroke, heart failure, and high plasma vWF levels (≥ 221 IU/dl) were associated with future adverse cardiovascular events (all p values <0.05). High plasma vWF levels, elderly patients, diabetes, hypercholesterolemia, and current smoking were associated with mortality (all p values <0.05). High plasma vWF levels were also an independent predictor of major bleeding (hazard ratio: 4.47, 95% confidence interval: 1.86 to 10.75; p < 0.001). High plasma vWF levels were able to refine clinical risk stratification schema for stroke (CHADS₂ [Congestive heart failure, Hypertension, Age ≥ 75, Diabetes mellitus, and prior Stroke or transient ischemic attack (doubled)], CHA₂DS₂-VASc [Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65 to 74 years, Sex category]) and bleeding (HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly]). d-dimer did not show any significant impact on adverse events. High plasma vWF levels (≥221 IU/dl) are an independent risk factor for adverse events in anticoagulated permanent AF patients. This biomarker may potentially be used to refine stroke and bleeding clinical risk stratification in AF.

Relationship of Soluble CD40 Ligand to Vascular Endothelial Growth Factor, Angiopoietins, and Tissue Factor in Atrial Fibrillation: A Link Among Platelet Activation, Angiogenesis, and Thrombosis?

The precise pathophysiologic processes underlying the prothrombotic or hypercoagulable state in patients with atrial fibrillation (AF) remain uncertain. We hypothesized a relationship among abnormal platelet activation, angiogenic factors, and coagulation, thereby contributing to increased thrombogenecity.Plasma levels of soluble CD40 ligand (sCD40L [an index of platelet activation]) and tissue factor (TF [an index of coagulation]), as well as the angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1, and Ang-2, were measured by enzyme-linked immunosorbent assay in 59 patients with chronic AF. Data were compared to 40 age-matched and sex-matched healthy control subjects who were in sinus rhythm.AF patients had significantly higher levels of sCD40L (p = 0.038), VEGF (p = 0.023), and Ang-2 (p < 0.001), but not Ang-1 (p = 0.363), compared to control subjects. In non-anticoagulated AF patients (n = 28), TF levels were also higher (p = 0.043), in addition to high sCD40L, VEGF, and Ang-2, compared to control subjects. Among AF patients, sCD40L levels correlated strongly with levels of VEGF (r = 0.919; p < 0.001) and Ang-2 (r = 0.546; p = 0.002). VEGF levels were significantly correlated with levels of Ang-2 (r = 0.490; p < 0.001) and TF (r = 0.298; p = 0.044). In multivariate regression analysis, sCD40L levels were independently associated with levels of VEGF (p = 0.003) and Ang-2 (p = 0.005).Plasma levels of sCD40L are elevated in patients with AF, and are related to levels of VEGF, Ang-2, and TF. This interaction among platelets, angiogenic markers, and TF may play a role in the generation of the prothrombotic state associated with AF.