Nonvalvular Atrial Fibrillation Group Research Articles

NLRP3 Expression and Its Predictive Role in Heart Failure with Preserved Ejection Fraction among Non-Valvular Atrial Fibrillation Patients.

The aim of this study was to investigate the expression and predictive value of NOD-like receptor thermal protein domain-related protein 3 (NLRP3) in patients with non-valvular atrial fibrillation (NVAF) with heart failure with preserved ejection fraction (HFpEF). This was a retrospective analysis of 121 patients diagnosed with NVAF. According to the occurrence of HFpEF, 81 patients were assigned to the NVAF group and 40 patients to the NVAF/HFpEF group. The levels of NLRP3, B natriuretic peptide (BNP), and interleukin-1β (IL-1β) were determined using ELISA. Independent predictors for HFpEF in NVAF were determined using logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each factor. Expression levels of NLRP3, BNP, and IL-1β in the NVAF/HFpEF group, as well as the H2FPEF score were significantly higher than those in the NVAF group. Pearson analysis showed that NLRP3, BNP, and IL-1β expression levels in NVAF patients and the H2FPEF score was positively correlated (r = 0.409, r = 0.244, r = 0.299, p < 0.001). Multivariate logistic regression analysis showed that the NLRP3, BNP, or H2FPEF score can be used as independent factor for predicting the occurrence of HFpEF in NVAF. ROC curves showed that the areas under the curve of NLRP3, BNP, and H2FPEF scores for predicting the occurrence of HFpEF in NVAF patients were 0.856, 0.831, and 0.811, respectively. The NLRP3 level is elevated in the peripheral blood of NVAF patients with HFpEF and is positively correlated with the H2FPEF score. NLRP3 may serve as a potential predictor of HFpEF in patients with NVAF.

Clinical features of ischemic stroke in patients with nonvalvular atrial fibrillation combined with intracranial atherosclerotic stenosis.

Nonvalvular atrial fibrillation (NVAF) and intracranial atherosclerotic stenosis (ICAS) are major causes of ischemic stroke. Relatively few studies have focused on the risk factors and clinical features of ischemic stroke caused by NVAF combined with ICAS. We retrospectively evaluated NVAF and/or ICAS in patients with acute ischemic stroke admitted within 72h after stroke. All patients with acute ischemic stroke underwent diffusion-weighted magnetic resonance imaging (DWI), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and/or digital subtraction angiography (DSA). NVAF was detected by routine electrocardiogram or 24-h Holter examination, Doppler echocardiography, and contrast echocardiography of the right heart. Among the 635 enrolled patients, NVAF, ICAS, and NVAF+ICAS were diagnosed in 170 (26.77%), 255 (40.16%), and 210 (33.07%) patients, respectively. Patients in the NVAF+ICAS group were older (p<.001), specifically aged ≥75 years (p<.001). The admission time of the NVAF+ICAS group was shorter (p<.001) than that of the ICAS group. The admission NIHSS score of the NVAF group was higher than that of the NVAF+ICAS group (p<.001). HsCRP, NTpro-BNP, and LEVF levels were significantly different among the three groups (p<.001). NVAF+ICAS ischemic stroke occurred mainly in the right hemisphere (52.4%). NVAF with ICAS ischemic stroke is more likely to occur in older patients. Infarctions occurred mainly in the right cerebral hemisphere. Neurological deficits in NVAF are more severe than those in NVAF combined with ICAS and in simple ICAS ischemic strokes. HsCRP, LEVF, andNTpro-BNP seem to be closely associated with NVAF+ICAS ischemic stroke.

N-terminal pro-B-type natriuretic peptide and D-dimer combined with left atrial diameter to predict the risk of ischemic stroke in nonvalvular atrial fibrillation.

We aimed to explore the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP), d-dimer, and the echocardiographic parameter left atrial diameter (LAD) in identifying and predicting the occurrence of ischemic stroke (IS) in patients with nonvalvular atrial fibrillation (NVAF). We conducted a retrospective study of 445 patients with NVAF in the First Affiliated Hospital of Nanchang University. They were divided into the NVAF (309 cases) and NVAF with stroke (136 cases) groups according to whether acute ischemic stroke (AIS) occurred at admission. Multivariate logistic regression was used to analyze the odds ratio (OR) of NT-proBNP, d-dimer, and LAD for IS. The predictive value of NT-proBNP, d-dimer, and LAD in identifying the occurrence of IS in NVAF was determined by plotting the receiver operating characteristic (ROC) curves. NT-proBNP, d-dimer, and LAD levels were significantly higher in the NVAF with stroke group than in the NVAF group (p < .05). NT-ProBNP, d-dimer, and LAD were independently associated with IS in NVAF patients (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.08-1.16; OR = 1.87, 95% CI: 1.37-2.55; OR = 1.21, 95% CI: 1.13-1.28, p < .01). The optimal cutoff points for NT-ProBNP, d-dimer, and LAD levels to distinguish the NVAF group from the NVAF with stroke group were 715.0 pg/ml, 0.515 ng/ml, and 38.5 mm, respectively, with the area under the curve (AUC) being [0.801 (95% CI: 0.76-0.84); 0.770 (95% CI: 0.72-0.85); 0.752 (95% CI: 0.71-0.80), p < .01]. The combined score of NT-proBNP, d-dimer, and LAD improved the predictive efficacy of the single index, with an AUC of 0.846 (95% CI: 0.81-0.88, p < .01), sensitivity of 77.2%, and specificity of 76.4%. NT-proBNP, d-dimer, and the echocardiographic parameter LAD have outstanding value in predicting the risk of IS in patients with NVAF.

Safety and Efficacy of Direct-Acting Oral Anticoagulation (DOACs) Based on BMI

Introduction:Direct oral anticoagulants (DOACs) are indicated for stroke prevention in non-valvular atrial fibrillation (NVAF) and treatment of venous thromboembolism (VTE). Safety parameters, namely major bleeding and clinically relevant non-major bleeds (CRNMB) are shown to be lower in patients taking DOACs as compared to vitamin-K antagonists (VKAs). Several phase III trials performed subgroup analyses in obese patients, and found no difference in efficacy when compared to conventional VKAs or enoxaparin. Given global prevalence of obesity and paucity of safety data in this population, we aim to evaluate the safety and efficacy of therapeutic DOACs based on BMI (kg/m2).Methods:We performed a retrospective chart review of Medstar Washington Hospital Center EMR to include adult patients who were on apixaban, rivaroxaban or dabigatran for NVAF stroke prophylaxis or VTE in 2015. Patients were followed for 6 months in VTE group and up to 2 years for NVAF group. Patients were excluded if there was incomplete data. We categorized the patients based on WHO BMI classifications. Our primary safety outcome included major bleed and CRNMB. Efficacy was assessed in both NVAF and VTE patients as a secondary outcome.Statistical analysis was performed using Chi-square, fisher exact and logistic regression. A p-value <.05 was considered statistically significant.Results:Of 246 patients, 170 had NVAF whereas 76 had VTE. Baseline characteristics are reported in Table 1. VTE patients were generally younger than the NVAF group and were more likely to be African American. 48% of the patients had a BMI >30mg/m2 and 10% were above 45mg/m2. Dabigatran numbers were too small for any statistical evaluation.Nonvalvular Atrial fibrillationThe mean follow up time was 22.5±10.3 months. Slightly more major bleeding was noted in patients receiving apixaban (3.5%) than rivaroxaban (1.5%), but this was not statistically different across BMI groups. Eight patients had CRNMB in the apixaban group, which was not statistically significant across BMI groups. However, in patients taking rivaroxaban, there was a statistically significant relationship between BMI and CRNMB with a p-value 0.0004. In logistic regression analysis, BMI class I and class II predicted CRNMB with odds ratios of 0.08 (95% CI 0.008-0.781) and 0.097 (95% CI 0.010-0.971) respectively. This remains statistically significant when age adjusted. The association persists when all patients are combined (VTE and NVAF) with a p value of 0.04. There were only three stroke events, which were not significantly different across BMI groups.VTEAfter 6 months, there was a total five major bleeds (one in the apixaban group and four in rivaroxaban group). No patients in the apixaban group had CRNMB compared to 12.5% patients taking rivaroxaban. There was no statistically significant relationship found between BMI and either safety outcomes. VTE occurred in seven patients, however no relationship was found between either DOAC amongst BMI groups.Discussion:We present the first study specifically analyzing safety and efficacy of DOAC therapy based on BMI categories with good distribution across all groups. No differences were found across BMI groups, most importantly in BMI >40 kg/m2, further supporting previously published subgroup analyses of major clinical trials. Interestingly, we did find reduced CRNMB risk in patients with larger BMIs (Obese Class 1 and 2) taking rivaroxaban. Perhaps, this could be explained by lower peak concentrations and shortened half lives of DOACs in obese patients that have been suggested by some pharmacological studies. This difference was not seen in patients taking apixaban possibly due to a reduced dose (2.5mg) that is sometimes used in NVAF patients. Although this data supports that DOACs demonstrate similar efficacy and safety across BMI categories, prospective data is still needed to make more definitive conclusions about DOAC use in the obese population. [Display omitted] DisclosuresFitzpatrick:Pfizer Honorarium: Honoraria.

Adherence to the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline on the Use of Oral Anticoagulant Agents in Middle Eastern Patients with Atrial Fibrillation: The Jordan Atrial Fibrillation (JoFib) Study.

Background There is a scarcity of studies that evaluate adherence to the utilization of guideline-recommended oral anticoagulant agents (OACs) in patients with atrial fibrillation (AF) in the Middle East. The Jordan Atrial Fibrillation (JoFib) Study evaluated baseline clinical profiles and the utilization of OACs, including vitamin K antagonists (VKAs) and direct OACs (DOACs), in patients with valvular AF (VAF) and nonvalvular AF (NVAF) according to the 2019 focused update of the 2014 AHA/ACC/HRS guidelines. Methods Consecutive patients with AF were enrolled in 29 hospitals and outpatient clinics. The use of OACs was evaluated in patients with VAF and NVAF according to the prespecified guideline. Results Of 2000 patients, 177 (8.9%) had VAF and 1823 (91.1%) had NVAF. A VKA was prescribed for 88.1% of the VAF group. In the NVAF group, 1468 (80.5%) of patients had a high CHA2DS2-VASc score, i.e., a score of ≥3 in women and ≥2 in men; 202 (11.1%) patients had an intermediate CHA2DS2-VASc score, i.e., a score of 2 in women and 1 in men; and 153 (8.4%) patients had a low CHA2DS2-VASc score, i.e., a score of 1 in women and 0 in men. Of patients with a high CHA2DS2-VASc score, 1204 (82.0%) received OACs, including DOACs for 784 (53.4%) and VKA for 420 (28.6%) patients. Among patients with an intermediate score, OACs were prescribed for 148 (73.3%) patients, including 107 (53.0%) who received DOACs and 41 (20.3%) patients who received VKA. In patients with a low score, OACs were omitted in 94 (61.4%) patients and prescribed for 59 (38.6%) patients. Multivariate analysis showed that age between 50 and 70 years, CHA2DS2-VASc score of ≥2, a diagnosis of stroke or systemic embolization, and nonparoxysmal AF were significantly associated with increased odds of OAC prescription. Conclusions The current status of the utilization of OACs in Middle Eastern AF patients appears to be promising and is consistent with the 2019 focused update of the 2014 AHA/ACC/HRS guideline. This trial is registered with NCT03917992.

Diagnostic value of N-terminal pro B-type natriuretic peptide for nonvalvular atrial fibrillation in acute ischemic stroke patients: A retrospective multicenter case-control study

BackgroundThe detection of Nonvalvular atrial fibrillation (NVAF) in AIS patients may be elusive and require further investigation such as electrocardiography (ECG) and Holter monitoring. The objective of this study is to evaluate the N-terminal pro B-type natriuretic peptide (NT-proBNP) diagnostic value for NVAF and the clinical outcome of AIS patients. MethodsWe conducted a retrospective study of AIS patients in ten hospitals of the Shaanxi province. All NVAF patients and matched patients without NVAF admitted within 7 days after stroke onset were included in our study. The admission NT-proBNP receiver operating characteristic curve was drawn to determine the discriminative power of NT-proBNP in NVAF identification. Multivariate logistic regression analysis was used to examine the odds ratios (OR) of NT-proBNP for NVAF and identify the potential factors associated with the clinical outcomes in AIS patients. ResultsA total of 275 NVAF cases and 275-matched controls were included in the current study. NT-proBNP was independently associated with NVAF (OR = 64.047, 95% confidence interval [CI]: 30.298–135.390, p < .001) in AIS patients. The optimal cutoff point for the NT-proBNP level to distinguish the NVAF group from the non-NVAF group was 431.0 pg/ml, with an area under curve [AUC] of 0.910 (95% CI: 0.885–0.935, p < .001). The high NT-proBNP level (OR: 3.284, 95% CI: 1.830–5.896, p < .001) was an independent indicator that was positively related to hospitalization mortality. ConclusionThe rise of the serum NT-proBNP level at first admission added great contributions to the NVAF diagnosis after AIS, and was independently associated with the hospitalization mortality of AIS patients.

P4799Long-term thromboembolic risk in patients with postoperative atrial fibrillation after left-sided heart valve surgery

Abstract Background New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are sparse. In addition, data on stroke prophylaxis in this setting are lacking. Objective To assess the long-term risk of thromboembolism in patients developing new-onset POAF following isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). Methods Using data from the Eastern Danish Heart Surgery Database and Danish nationwide registries, we identified patients who developed POAF following isolated left-sided heart valve surgery (i.e. biologic aortic/mitral valve replacement or aortic/mitral valve repair) from 2000 through 2015. These patients were matched with patients with nonsurgical NVAF in a 1:4 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Long-term risk of thromboembolism was examined by the Aalen-Johansen estimator and cause-specific Cox regression models adjusted for comorbidities, concomitant pharmacotherapy, and oral anticoagulation therapy as a time-dependent covariate. Results A total of 1,539 patients undergoing isolated left-sided heart valve surgery were identified. Of these, 716 (46.5%) patients developed POAF after surgery. A total of 630 patients with POAF were matched with 2,520 patients with NVAF. In the matched study population, the median age was 71 years (25th-75th percentile 66–77 years) and 59.5% were men. Oral anticoagulation therapy was initiated within 30 days post-discharge in 62.7% and 51.4% of these patients, respectively. Compared with NVAF, POAF was not associated with a significantly different 5-year absolute risk of thromboembolism (10.7% [95% confidence interval [CI], 8.0%-13.9%] versus 8.9% [95% CI, 7.6%-10.2%] in the POAF and NVAF group, respectively) (Figure). In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio [HR] 1.01 [95% CI, 0.71–1.44]). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (HR 0.45 [95% CI, 0.18–0.99]) as well as NVAF (HR 0.58 [95% CI, 0.42–0.80]) compared with no anticoagulation therapy. Conclusions New-onset POAF following isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism compared with NVAF. Future studies addressing the role of oral anticoagulation therapy in POAF after heart valve surgery are warranted to examine the efficacy and safety as well as the timing and duration of anticoagulation therapy.

Clinical Outcomes of Valvular versus Nonvalvular Atrial Fibrillation in Acute Anterior Circulation Occlusive Stroke Undergoing Endovascular Treatment

BackgroundThrombectomy is the first choice for cardioembolism due to atrial fibrillation (AF), however, whether valvular AF and nonvalvular AF had different safety and functional outcomes has not been reported yet. We aimed to investigate the differences between patients with valvular AF and patients with nonvalvular AF on safety and functional outcomes in acute large artery occlusion undergoing thrombectomy. MethodsValvular AF refers to patients with mitral stenosis or artificial heart valves and valve repair. Rate of symptomatic intracerebral hemorrhage [sICH], modified Rankin Scale Score (mRS), and death at 90 days were compared between valvular AF and nonvalvular AF groups. Univariate and multivariable logistic regression was performed to identify the predictors for unfavorable functional outcome (mRS 3-6). Results18.8% (51/271) of AF were valvular AF. The valvular AF group had significantly higher proportion of mRS 0-2 (49% [25/51] versus 33.3% [73/219], P = .04) and less death (21.6% [11/51] versus 38.4% [84/219], P = .02) comparing with nonvalvular AF group. The rates of sICH between both groups were nonsignificantly different (21.5% [47/219] for nonvalvular AF versus 13.7% [7/51] for valvular AF, P = .46). Valvular AF was not an independent predictor for unfavorable functional outcome (odds ratio .67, 95% confidence interval: .24-1.84) with age, collateral flow, chronic heart failure, NIHSS at admission, recanalization status, glucose at admission, occlusion site, ASPECTS, and ICH as covariates. ConclusionsValvular AF and nonvalvular AF have similar safety and functional outcomes in patients with acute anterior circulation large artery occlusion undergoing thrombectomy.

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery and Patients With Nonvalvular Atrial Fibrillation

New-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking. To examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). This cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018. The proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism. A total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24). New-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.

Leukocyte TRP channel gene expressions in\xa0patients with non-valvular atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls. mRNA was extracted from blood samples, and real-time polymerase chain reaction was performed for gene expressions by using a dynamic array system. Low levels of TRP channel expressions in the controls were markedly potentiated in NVAF group. We observed marked increases in MCOLN1 (TRPML1), MCOLN2 (TRPML2), MCOLN3 (TRPML3), TRPA1, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, TRPV6, and PKD2 (TRPP2) gene expressions in NVAF patients (P < 0.05). However, there was no change in PKD1 (TRPP1) gene expression. This is the first study to provide evidence that elevated gene expressions of TRP channels are associated with the pathogenesis of NVAF.

Predictive role of CHA2DS2-VASc score for cardiovascular events and death in patients with arterial hypertension and stable sinus rhythm.

Background The CHA2DS2-VASc score well stratifies the risk for thromboembolic events in non-valvular atrial fibrillation (NVAF) patients. This score may also predict thromboembolic events in sinus rhythm populations. Purpose The purpose of this study was to assess the prognostic role of CHA2DS2-VASc in a Caucasian community population of patients with arterial hypertension and sinus rhythm. Methods A total of 12,599 arterial hypertension residents not receiving anticoagulation were selected from a community population in Trieste between November 2009 and October 2014: 11,159 sinus rhythm and 1440 NVAF patients. We considered thromboembolic events, cardiovascular hospitalisation and all-cause death in all patients divided according to CHA2DS2-VASc. Results Sinus rhythm patients were 74 (interquartile range 65-81) years old, 50% were women, 32% with CAD, mean CHA2DS2-VASc 3.68 ± 1.47 points, significantly lower than NVAF patients (4.26 ± 1.50, P < 0.001). After 37 months follow-up, an increasing CHA2DS2-VASc corresponded to a higher rate of thromboembolic events in sinus rhythm patients, ranging from 0% in patients with a score of 1 or 2 to 2.6% in those with a score of 6 or greater ( P < 0.0001). A similar trend was found in the reference NVAF group. At Cox multivariable analysis, CHA2DS2-VASc predicted thromboembolic events (hazard ratio (HR) 2.12), cardiovascular hospitalisation (HR 1.55) and all-cause death (HR 1.57). The predictive accuracy of CHA2DS2-VASc was similar in sinus rhythm and NVAF patients for thromboembolic events, cardiovascular hospitalisation and all-cause death (area under the curve statistic 0.76 vs. 0.76, 0.68 vs. 0.66, 0.64 vs. 0.64, respectively). Conclusions In a community population of Caucasian arterial hypertension patients in sinus rhythm, CHA2DS2-VASc rather well stratifies for adverse clinical events at mid-term follow-up with a similar accuracy to NVAF patients. These results might be clinically relevant in this setting of sinus rhythm patients.

Phosphatidylserine Exposing-Blood Cells and Microparticles Induce Procoagulant Activity in Non-Valvular Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice, contributing directly to morbidity and mortality largely through thromboembolism events such as stroke. The risk of stroke in patients with AF is five times higher than in patients without AF. The pathophysiological of thromboembolism in AF is multifactorial and is not only related to stasis in a poorly contractile left atrium. Indeed, there is an increasing body of evidence to support that Virchow triad, including abnormal blood stasis, endothelial damage, and changes in blood constituents, is the main cause of thromboembolism or prothrombotic state in AF patients. However, relatively little is known about the precise role of phosphatidylserine (PS), one of the blood constituents, in the pro-thrombotic state or hypercoagulability of non-valvular AF (NVAF). Our objectives were to study the increased PS exposure on microparticles (MPs) and the outer membrane of MP-origin blood cells in NVAF patients, and to evaluate their procoagulant activity (PCA).Methods: Our study included NVAF patients without (n = 60) and with left atrial thrombosis (n = 30) and healthy controls (n = 30). PS exposure on MPs and blood cells was analyzed with flow cytometry and confocal microscopy. PCA was evaluated using clotting time, extrinsic/intrinsic FXa and prothrombinase production, and fibrin formation assays. Inhibition assays of PCA of PS+ MPs and blood cells were performed using lactadherin.Results: The number of PS+ MPs was significantly higher in NVAF patients (1.8-fold, P < 0.001) and NVAF patients with left atrial thrombosis (2.7-fold, P < 0.001) compared with healthy subjects, respectively. Furthermore, the number of PS+ MPs in NVAF patients with left atrial thrombosis was significantly higher than that in NVAF patients without (1.4-fold, P < 0.01, Figure 1A). Moreover, the PS+ MPs were originated from platelets (CD41a+, PMPs), neutrophils (CD66b+, NMPs), mononuclear cells (CD14+, MMPs), lymphocytes (CD3/19+, LMPs), erythrocytes (CD235a+, ErMPs), and endothelial cells (CD31+ CD41a-, EMPs) (Figure 1B). The levels of PS+ platelets, neutrophils, mononuclear cells, lymphocytes, and erythrocytes were significantly higher (all P < 0.001) in each NVAF group than those in healthy controls. And the levels of PS+ platelets, neutrophils, and erythrocytes in NVAF patients with left atrial thrombosis were significantly higher than those in NVAF patients (all P < 0.01, Figure 1C). In addition, circulating PS+ MPs cooperated with PS+ blood cells, contributing to markedly shortened coagulation time and dramatically increased FXa/thrombin generation and fibrin formation in each NVAF group (all P < 0.01). Moreover, blockade of exposed PS on MPs and blood cells with lactadherin inhibited PCA by approximately 80%.Conclusions: Our results suggest that increased PS exposure on MPs and blood cells play a procoagulant role in NVAF patients with or without left atrial thrombosis. Blockade of PS prior to left atrial thrombosis could become a novel therapeutic strategy to prevent thrombosis in these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of β1-Adrenergic, M2-Muscarinic Receptor Autoantibody with Occurrence and Development of Nonvalvular Atrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is independently associated with increased risk of stroke and death. Although the exact mechanisms of AF are not completely elucidated, a large number of evidences demonstrate that autoimmunity may play an important role in the initiation, the progression, and the maintenance of AF. In this study, we aimed to compare anti-β1-adrenergic receptor autoantibody (anti-β1-R) and anti-M2-muscarinic receptor autoantibody (anti-M2-R) levels between nonvalvular AF patients and healthy control subjects. The levels of serum anti-β1-R, antinuclear antibodies, and anti-M2-R were measured in both groups by enzyme-linked immunosorbent assay (ELISA). High-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentration were measured, respectively, by immunoturbidimetry and chemiluminescence. Anti-β1-R and anti-M2-R levels were significantly higher in patients with nonvalvular AF than in healthy controls (anti-β1-R 221.11 [132.38-291.69] ng/mL vs 198.14 [125.70-278.40] ng/mL, P < 0.01; anti-M2-R 271.81 [144.99-378.20] ng/mL vs 235.01 [121.53-358.99] ng/mL, P < 0.01). Compared with the control group, the serum levels of IL-6 and hs-CRP were higher in the nonvalvular AF group (IL-6 19.65 ± 5.6pg/mL vs 6.79 ± 1.09 pg/mL, hs-CRP 6.03 ± 1.35 mg/L vs 2.73 ± 0.63 mg/L, P < 0.05). Antinuclear antibody (ANA) levels were similar between two groups (ANA 10.55 [1.86-271.8] U/mL vs 10.49 [1.303-161.7]U/mL, P > 0.05). The baseline value of serum anti-β1-R (odds ratio [OR]: 13.176, P < 0.001), anti-M2-R (OR: 4.41, P < 0.001), IL-6 (OR: 6.126, P < 0.05) levels, and left atrial diameter (OR: 5.781, P < 0.05) were independent predictors of nonvalvular AF by multivariable analyses. We found a significant association between circulating serum anti-β1-R, anti-M2-R, IL-6 levels, and nonvalvular AF. We presume that the autoimmunity and inflammation might take part in electrical remodeling and structural remodeling of left atrium.

Abstract 11153: Association of β1-Adrenergic,M2-Muscarinic Receptor Autoantibody With Occurrence of Nonvalvular Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia and confers an independent increased risk of stroke and death. Although the exact mechanisms behind AF are not completely elucidated, A large number of evidence demonstrates that autoimmunity may play an important role in the initiation, the progression and the maintenance of AF. Hypothesis: In this study, we aimed to compare anti-β 1 -R and anti-M 2 -R levels between non-valvular AF patients and healthy control subjects Methods: Seventy-one patients with non-valve atrial fibrillation(age: 62.69±11.23 years, 54% male),along with 71healthy control subjects(age: 61.86±11.90 years, 52% male) were included . Enzyme-linked immunosorbent assay tests to measure serum anti-β 1 -R and anti-M 2 -R levels were performed in both groups. Hs-CRP concentration was measured by immunoturbidimetry.IL-6 concentration was measured by chemiluminescence. Results: Anti-β 1 -R and anti-M 2 -R levels were significantly higher in patients with non-valvular AF compared to healthy controls[anti-β 1 -R 221.11(132.38-291.69) vs. 198.14(125.70-278.40) ng/ml, P&lt;0.01; anti-M 2 -R 271.81(144.99-378.20) vs. 235.01(121.53-358.99) ng/ml, P&lt;0.01]. Compared with the control group, the serum level of IL-6,hs-CRP were higher in the non-valvular AF group(IL-6 19.65±5.6pg/mL vs 6.79±1.09pg/mL,hs-CRP 6.03±1.35mg/Lvs 2.73±0.63mg/L P&lt;0.05).After multivariable analyses , the baseline value of serum anti-β 1 -R (OR: 13.176, p&lt;0.001),anti-M 2 -R (OR:4.41, p&lt;0.001),IL-6(OR:6.126, p&lt;0.05) levels and LA diameter(OR:5.781, p&lt;0.05) were independently predictors of non-valvular AF. Conclusions: We found a significant association between circulating serum anti-β1-R,anti-M2-R,IL-6 levels and non-valvular AF. The possible mechanism is that the autoimmunity and inflammation might take part in electrical remodeling and structural remodeling of left atrium. Larger studies are warranted to further investigate their role in these settings.

Evaluation of transesophageal echocardiography on the morphology and function of the left atrial appendage in nonvalvular atrial fibrillation

Objective To investigate the application value of the transesophageal echocardiography (TEE) in patients with nonvalvular atrial fibrillation about the size, lobes, morphology and function of left atrial appendage (LAA). Methods One hundred and forty-two patients underwent TEE were divided into nonvalvular atrial fibrillation group (98 cases) and non atrial fibrillation group (44 cases). The orifice diameter, depth, volume, peak emptying velocity (PEV) of the LAA and the 1eft atrial dimension (LAD) were measured. The form and lobes of LAA, thrombus and spontaneous echo contrast (SEC) in LAA were observed. Results The LAA orifice diameter, depth, volume and LAD of patients with atrial fibrillation were significantly higher than those in the group without atrial fibrillation, which showed statistical significance (P<0.05). Forty-one cases in atrial fibrillation group were found with the SEC, and the number with thrombus in LAA was 22. The differences of PEV between chicken wings and non-chicken wings were statistically significant (P<0.05). The SEC in LAA and the lobe number of LAA had no relevance. Conclusions It was reliable to analyze the size, morphologies, lobes and hemodynamic parameters of LAA in patients with atrial fibrillation by TEE, which provided reference for percutaneous LAA occlusion and anticoagulation therapy for the patients with atrial fibrillation. Key words: Echocardiography, transesophageal; Atrial fibrillation; Left atrial appendage

Evaluation of the impact of warfarin time in therapeutic range on outcomes of patients with atrial fibrillation in Turkey: perspectives from the observational, prospective WATER Registry.

Warfarin is highly efficacious in reducing stroke risk in patients with atrial fibrillation (AF). However, its safety and efficacy in stroke prevention is markedly influenced by its time in therapeutic range (TTR). The quality of anticoagulant therapy varies considerably among countries. Representative data concerning the quality of anticoagulant therapy and its effects on clinical outcomes in Turkey are lacking. Warfarin in Therapeutic Range (WATER) registry is a prospective, observational study which followed 572 AF patients (mean age 67.3 ± 12 years; females 60%; 71% non-valvular AF) treated with warfarin. At a median of 22-month follow-up, the mean TTR value was 42.3 ± 18% (median: 40%) for the whole population and lower in non-valvular AF su group than valvular AF subgroup (40.3 ± 18 vs. 46.9 ± 19, respectively, p < 0.001). Death, cardiac hospital-ization and minor bleeding rates were higher in the group with TTR value < 40% than the group with > 40% (3.4% vs. 5.9%; 28.6% vs. 35.4%; 36.5% vs. 41.7%, respectively, all of them p < 0.001). A correlation analysis showed a negative correlation between age and TTR value (r = -0.178, p < 0.001). Mean CHA2DS2VASc score was 3.63 ± 1.5 and mean HASBLED score was 2.38 ± 1.01 in the non-valvular AF group. A negative correlation was observed between TTR levels and CHA2DS2VASc score. WATER provides insight into the anticoagulation control status of AF patients in Turkey. The quality of anticoagulation was poor. Strategies should be undertaken by clinicians and patients to improve TTR. New oral anticoagulant agents may be perfect alternatives for non-valvular AF patients.

Elevated levels of RDW is associated with non-valvular atrial fibrillation

Red cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) have been found to be associated with cardiovascular diseases. Only a few trials have investigated the correlation of these parameters with postoperative atrial fibrillation (AF). However, the correlation of these parameters in non-valvular AF is still unclear. We retrospectively analyzed consecutive AF patients from medical records and included 117 non-valvular AF patients (103 paroxysmal and 14 chronic AF). All subjects underwent physical examination and echocardiographic imaging. Complete blood counts (CBCs) were analyzed for hemoglobin, RDW, neutrophil and lymphocyte counts as well as mean corpuscular volume. Results of CBC tests within the previous year were also included and the averages were used. The demographic and echocardiographic properties of non-valvular AF group were comparable to the control group except for left atrial volumes which were increased in AF (median 33.1, IQR 26.3-41.1cm(3) vs. median 26.4, IQR 24.2-28.9cm(3); p=0.01). RDW levels were significantly higher in the AF group (median 13.4%, IQR 12.9-14.1%) compared to the control (median 12.6%, IQR 12.0-13.1%; p=0.01). NLR was not statistically different in the AF group and the controls (2.04±0.94 vs. 1.93±0.64, respectively; p=0.32). Hs-CRP levels were higher in the AF group compared to the controls (median 0.84, IQR 0.30-1.43mg/L vs. median 0.29, IQR 0.18-0.50mg/L, respectively; p=0.01). Multivariate logistic regression analysis revealed RDW (OR 4.18, 95% CI 2.15-8.15; p=0.01), hs-CRP (OR 3.76, 95% CI 1.43-9.89; p=0.01) and left atrial volume (OR 1.31, 95% CI 1.06-1.21; p=0.01) as the independent markers of non-valvular AF. Multivariate linear regression analysis revealed that hemoglobin levels (standardized β coefficient=-0.252; p=0.01) and the presence of AF (standardized β coefficient=0.336; p=0.01) were the independent correlates of RDW levels. Elevated RDW levels, not NLR, may be an independent risk marker for non-valvular AF.

Silent Cerebral Infarcts and Cerebral White Matter Lesions in Patients with Nonvalvular Atrial Fibrillation

Nonvalvular atrial fibrillation (NVAF) is a well-known strong risk factor for stroke, although few studies have examined silent cerebral ischemic lesions in patients with NVAF. We investigated silent cerebral infarcts (SCIs) and cerebral white matter lesions and risk factors for stroke in NVAF patients. Subjects included 71 consecutive patients with NVAF and 71 sex-and age-matched controls with sinus rhythm who had undergone MRI. Number, size, and localization of SCIs and severity of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) on magnetic resonance imaging were analyzed. The risk factors and CHADS2 score for stroke were also investigated. The number of SCIs was significantly larger and the rates of SCIs in the cortex/subcortex and deep white matter were higher in the NVAF group than in the control group. The DSWMH grade was also significantly higher in the NVAF group. NVAF was an independent risk factor for SCIs and DSWMH. The number of cortical and subcortical SCIs was significantly correlated with CHADS2 score. Cortical/subcortical and deep white matter SCIs were more frequent and DSWMH grades were higher in NVAF patients compared with control subjects. CHADS2 score was an effective scheme not only in stroke risk but also in risk of SCI.

Lysophosphatidic Acid Level and the Incidence of Silent Brain Infarction in Patients with Nonvalvular Atrial Fibrillation

Lysophosphatidic acid (LPA), which is proposed to play an important role in normal physiological situations such as wound healing, vascular tone, vascular integrity and reproduction, may be involved in the etiology of some diseases such as atherosclerosis, cancer, obesity or myocardial infarction. Abnormal findings, including silent brain infarction (SBI), are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is a relationship between LPA level and the prevalence of SBI has not been extensively studied. In the present study, the association between them was investigated. 235 patients with NVAF, 116 cases of SBI without NVAF and 120 cases of healthy volunteers (control group), who did not receive any antithrombotic therapy, were enrolled in this study. Plasma LPA levels in the NVAF with SBI group were significantly higher than that in the control group (p < 0.01), NVAF without SBI group (p < 0.01) and SBI without NVAF group (p < 0.01). The LPA levels are lower in the control group than in the NVAF without SBI and SBI without NVAF groups (p < 0.01), however, the latter two groups did not significantly differ from each other for LPA levels (p > 0.05) There were significant differences in the positive rate of platelet activation between each of the groups (p < 0.01). The positive rate of platelet activation was significantly higher in the NVAF with SBI group. We suggest that LPA might be a novel marker for estimation of the status of platelet activation and the risk factor for SBI onset in NVAF patients. We expected that plasma LPA levels could predict the occurrence of SBI in NVAF patients.

The effect of Levoisimendan on the D-dimer level in chronic atrial fibrillation cases with cardiac failure

We determined the short-term effects of Levoisimendan, on the D-dimer level in patient’s decompensated heart failure (HF) with non valvular atrial fibrillation (NVAF). The study population consisted of 62 chronic HF patients (24 women and 38 men, mean age: 67.5 ±16.5 years) with New York heart association (NYHA) III-IV and a left ventricular ejection fraction (EF) lower than 35%. Patients were divided into two groups, group I (sinus rhythm, 38 patients) and Group II (chronic NVAF, 24 patients). A loading dose of Levoisimendan (12 μg/kg) was administered over 10 min, followed by an infusion (0.1 μg/kg per minute) for 50 min in all patients, the rate was increased to 0.2 μg/kg per minute for an additional 23 h as tolerated. Plasma cardiac D-Dimer levels were measured at pre-treatment period and 5 days after treatment. Demographic variables were similar in both groups. The difference in hemodynamic parameters was not significant with respect to arterial systolic blood pressure and heart rate. However, diastolic blood pressure was significantly low in the NVAF group (p = 0.008). As for biochemical parameters, while there was no difference in baseline creatinine, serum sodium(Na), serum potassium (K), uric acid (UA) and blood urea nitrogen (BUN) value was detected to be higher in the atrial fibrillation (AF) group (p = 0.03). The left ventricular ejection fraction was 26.6 ± 5.5 and 29.2 ± 5.0% in the group with and without NVAF, respectively, no difference was observed (p > 0.05). The D-dimer levels in the NVAF group were upper than sinus rhythm groups (p > 0.05).However, there was no statistically significant difference between the pre-infusion and post-infusion values of d-dimer 1749 vs 1824 ng/ml, p = 0.69. Furthermore, plasma D-dimer levels increased after Levoisimendan infusion, but D-dimer levels showed non significant correlation with atrial fibrillation group. The clinical improvement as reflected in the patients’ NYHA classification was found to be higher in the sinus rhythm group than in NVAF group (p = 0.045). No relationship was found between the NYHA class and the D-dimer levels (p > 0.05) both in general and within the treatment groups. The results of our study show that the effect of Levoisimendan on both clinical response and thrombogenicity is limited compared to sinus rhythm in decompensated HF patients with NVAF in the acute period. Further studies are required to evaluate the results of this association in the long-term. Key words: Levoisimendan, atrial fibrillation, heart failure, D-dimer.