State In Atrial Fibrillation Research Articles

MY APPROACH to a patient with atrial fibrillation and dementia

Atrial fibrillation (AF) is associated with multiple forms of dementia, including Alzheimer's disease. Although, on the surface, this association may seem an epiphenomenon derived from two diseases of aging, in our prior studies the youngest groups studied, who developed AF had the higher risks for cognitive impairment [1]. In addition, we found that the combined disease state of dementia and AF harbors a significant increased risk for all-cause mortality. As such, defining mechanisms that underlie the association as a means to explore therapeutic strategies of prevention, disease management, and risk reduction is essential. When I encounter a patient, who has AF and is experiencing early cognitive decline or has dementia, my clinical approach reflects our research into the disease states' association.

Stroke in atrial fibrillation and improving the identification of ‘high‐risk’ patients: the crossroads of immunity and thrombosis

Stroke in atrial fibrillation and improving the identification of ‘high‐risk’ patients: the crossroads of immunity and thrombosis

Association of hemostatic markers with atrial fibrillation: a meta-analysis and meta-regression.

BackgroundThere is growing evidence that indicates the presence of a prothrombotic state in atrial fibrillation (AF). However, the role of hemostatic markers in AF remains inconclusive.MethodsWe conducted a meta-analysis of observational studies to evaluate the association between hemostatic markers and AF. A meta-regression was performed to explore potential sources of heterogeneity.ResultsA total of 59 studies met our inclusion criteria for the meta-analysis. For platelet activation, increased circulating platelet factor-4, β-thromboglobulin (BTG) and P-selectin were significantly higher in AF cases compared with controls (standardized mean difference [SMD][95% confidence interval (CI)]: 1.72[0.96–2.49], 1.61[1.03–2.19] and 0.50[0.23–0.77], respectively). For coagulation activation, increased levels of plasma D-dimer, fibrinogen, thrombin-antithrombin, prothrombin fragment 1+2, and antithrombin-III were significantly associated with AF (SMD[95% CI]: 1.82[1.38–2.26], 0.72[0.55–0.89], 0.42[0.13–0.72], 1.00 [0.00–1.99] and 1.38[0.16–2.60], respectively). For fibrinolytic function, tissue-type plasminogen activator and plasminogen activator inhibitor-1 were significantly increased in AF cases compared with controls (SMD[95% CI]: 0.86[0.04–1.67] and 0.87[0.28–1.47], respectively) but the associations became nonsignificant after performing subgroup analysis by anticoagulants treatment status. For endothelial function, increased von Willebrand factor was significantly associated with AF (SMD, 0.79; 95% CI, 0.60–0.99); however, no association was observed for soluble thrombomodulin (SMD, 0.60; 95% CI, -0.13–1.33).ConclusionsIncreased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF. Future research is necessary to elucidate the precise mechanism of the prothrombotic state and how hemostatic markers promote thromboembolism in AF.

Relation of Reduced Expression of MiR-150 in Platelets to Atrial Fibrillation in Patients With Chronic Systolic Heart Failure

Atrial fibrillation (AF) is associated with poor prognosis in patients with heart failure (HF). Although platelets play an important role in rendering a prothrombotic state in AF, the exact mechanism by which the effect is mediated is still debated. MicroRNAs (miRNAs), which have been shown to be involved in a variety of cardiovascular conditions, are abundant in platelets and in a cell-free form in the circulation. In the present study, we performed a genome-wide screen for miRNA expression in platelets of patients with systolic HF and in controls without cardiac disease, in pursuit of specific miRNAs that are associated with the presence of AF. MiRNA expression was measured in platelets from 50 patients with systolic HF and 50 controls, of which, samples from 41 patients with HF and 35 controls were used in the final analysis because of a quality control process. MiR-150 expression was 3.2-fold lower (p = 0.0003) in platelets of patients with HF with AF relative to those without AF. A similar effect was seen in serum samples from the same patients, in which miR-150 levels were 1.5-fold lower (p = 0.004) in patients with HF with AF. Furthermore, the serum levels of miR-150 were correlated to platelet levels in patients with AF (r = 0.65, p = 0.0087). In conclusion, miR-150 expression levels in platelets of patients with systolic HF with AF are significantly reduced and correlated to the cell-free circulating levels of this miRNA.

Association Between C‐Reactive Protein and Atrial Fibrillation Recurrence After Catheter Ablation: A Meta‐analysis

Atrial fibrillation (AF) is associated with inflammation. Increased serum C-reactive protein (CRP) levels are important representatives of an inflammatory state of AF. A variety of studies have evaluated whether increased CRP levels have an association with AF recurrence after catheter ablation. However, the results remain inconsistent, therefore, this meta-analysis was conducted to offer suggestions. Increased baseline CRP have an association with AF recurrence after catheter ablation. Electronic databases including PubMed, Embase, Medline, ISI Web of Knowledge, and ScienceDirect were searched until December 31, 2012 for any CRP-associated studies. Overall and subgroup analyses were performed. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the associations between CRP levels and postablation AF recurrence. Statistical analysis was performed with Review Manager 5.2 and Stata 11.0. Seven available studies were identified, which included 526 patients (179 recurrence vs 347 no recurrence). Overall, increased baseline CRP levels had significant positive association with postablation AF recurrence. The SMD in the CRP levels was 0.65 units (95% CI: 0.30-0.99), and the z-score for overall effect was 3.70 (P = 0.0002). The heterogeneity test showed that there were moderate differences between individual studies (P = 0.006, I(2) = 67%). Metaregression revealed that different sample sizes of studies possibly accounted for the heterogeneity. Positive associations were also found in subgroup analyses based on sample size. When stratifying for ethnicity, similarly significant associations were found in both European (Caucasian) and Asian populations. Investigations demonstrate that baseline CRP levels are greater in patients with postablation AF recurrence. Further studies with larger sample size and delicate design for CRP should be conducted.

第13回 頻拍症カンファランス 心房細動における易血栓性:心房内皮細胞の視点から

第13回 頻拍症カンファランス 心房細動における易血栓性:心房内皮細胞の視点から

Microparticles Contribute to the Prothrombotic State in Atrial Fibrillation

Microparticles Contribute to the Prothrombotic State in Atrial Fibrillation

A Study of blood soluble P-selectin, fibrinogen, and von Willebrand factor levels in idiopathic and lone atrial fibrillation

A prothrombotic state with elevated levels of soluble P-selectin (sP-sel), fibrinogen, von Willebrand factor (vWf), and other haemostatic indices has been reported in some patients with atrial fibrillation (AF). Whether these changes are due to AF itself or coexistent cardiovascular diseases remains a matter of debate. Therefore, in the present study, the differences in plasma levels of sP-sel, fibrinogen, and vWf between patients with idiopathic/lone AF and sex-, age-, and risk factor-matched controls were investigated to determine whether AF itself might be associated with a hypercoagulable state. Ninety consecutive patients (63 males, 54.1 ± 10.1 years) with idiopathic AF were studied, 60 (43 males, 48.8 ± 7.5 years) of whom were diagnosed as lone AF. Plasma sP-sel and vWf were measured by enzyme-linked immunosorbent assay. Plasma fibrinogen was measured by chromometry. These indices in AF patients were compared with those in sex-, age- and risk factor-matched controls. Compared with the controls, patients with idiopathic AF had higher levels of sP-sel (AF vs. control: 33.4 ± 7.4 vs. 29.2 ± 6.5 ng/mL, P < 0.001) and fibrinogen (AF vs. control: 3.3 ± 0.9 vs. 3.0 ± 0.6 g/L, P = 0.02), but not vWf, whether with the adjustment of covariates or not. As for those < 60 years, between lone AF and age-matched controls, significant difference existed in the levels of sP-sel (AF vs. control: 34.5 ± 7.3 vs. 30.2 ± 7.3 ng/mL, P = 0.002), but not in those of fibrinogen and vWf, whether with the adjustment of covariates or not. Both platelet activation and abnormal changes in coagulation were suggested in idiopathic AF and a platelet activation state in lone AF. This supports the notion that AF per se contributes to a state of hypercoagulation.

Update on the Association of Inflammation and Atrial Fibrillation

Atrial fibrillation (AF) is a common arrhythmia and is associated with significant morbidity and mortality. The pathogenesis of AF remains incompletely understood and management remains a difficult task. Over the past decade there has been accumulating evidence implicating inflammation in the pathogenesis of AF. Inflammation appears to play a significant role in the initiation and perpetuation of AF as well as the prothrombotic state associated with AF. Inflammatory biomarkers (C-reactive protein and interleukin-6) have been shown to be associated with the future development, recurrence and burden of AF, and the likelihood of successful cardioversion. Therapies directed at attenuating the inflammatory burden appear promising. Animal and clinical studies have evaluated statins, angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers, and corticosteroids for the treatment or prevention of AF. The purpose of this review is to provide current evidence on the relationship between inflammation and AF and potential therapies available to modulate the inflammatory state in AF.

Persistent atrial fibrillation is not associated with thrombomodulin level increase in efficiently anticoagulated patients

IntroductionAtrial fibrillation (AF) is the most common arrhythmia and leads to a five-fold increased risk of stroke compared to persons with sinus rhythm. A soluble form of thrombomodulin (sTM) is a recognized marker of endothelial dysfunction and may contribute to the hypercoagulable state in AF. The aim of the study was to evaluate plasma concentration of sTM in persistent AF patients before and after sinus rhythm recovery following direct current cardioversion (CV).Material and methodsIn 45 effectively anticoagulated consecutive patients, with persistent non-valvular AF, and normal left ventricular function, CV was performed. Blood samples for sTM assessment were collected twice: 24 hours before and 24 hours after CV.ResultsIn 43 patients sinus rhythm was obtained. The mean plasma sTM level was significantly lower in AF patients compared to the control group with sinus rhythm and without anticoagulation (38.5 ±9.9 ng/ml vs. 44.1 ±9.1 ng/ml, p = 0.04). Plasma sTM levels did not change 24 hours after successful CV (36.7 ±9.5 ng/ml vs. 38.5 ±9.9 ng/ml, p = 0.16).ConclusionsPlasma sTM concentration was lower in patients with persistent AF and normal left ventricle systolic function than in patients with sinus rhythm, presumably due to chronic oral anticoagulant therapy in the AF group. CV has no impact on sTM plasma level evaluated 24 hours after sinus rhythm restoration.

Circulating progenitor cells in patients with atrial fibrillation and their relation with serum markers of inflammation and angiogenesis

The pathophysiological inter-relationships and underlying 'drivers' of a prothrombotic state in atrial fibrillation (AF) are complex but may include endothelial abnormalities. Circulating progenitor cells (CPCs) have been recently described as a cell population that may promote repair of endothelial damage. We hypothesised abnormalities in this cell population, alongside abnormal markers of endothelial damage/dysfunction (von Willebrand factor, soluble E-selectin), apoptosis (soluble Fas, soluble Fas ligand), angiogenesis (vascular endothelial growth factor) and inflammation (interleukin-6) in 135 consecutive AF patients (14 with lone AF), who were compared to 33 'disease controls' and 13 healthy controls. We also explored whether restoration of sinus rhythm would alter these indices. No significant differences in research indices were observed between AF and disease controls, apart from soluble Fas levels (p<0.001). Median CPC levels in lone AF were higher compared to 'non-lone AF' (that is, AF patients with co-morbidities) [p<0.001], apparently because of difference in age and presence of co-morbidities. There was an increase in CPC counts (p=0.007), but in not other markers following DC cardioversion. CPCs increased significantly in the 17 patients who were successfully cardioverted into sinus rhythm (p=0.003). In a stepwise multiple regression analysis, age (p=0.014), hyperlipidaemia (p=0.001) and use of statins (but not AF) was predictive of CPC counts (p=0.014). In conclusion, AF is unlikely to be independently associated with abnormalities in CPCs. Successful cardioversion is associated with a modest but significant increase in CPCs.

Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation

Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation

Abstract 650: Animal Study Results Support that Biometal Artificial Muscle Restores Atrial Kick and Could Replace Oral Anticoagulation in Permanent Atrial Fibrillation

Treatment of persistent atrial fibrillation (AF) consists of ventricular rhythm control and the use of anticoagulant agents to decrease the high risk of stroke. However, patients under lifetime anticoagulation therapy are exposed to hemorrhagic stroke (1–3% patients/year). The best treatment to prevent stroke may induce stroke itself. Because decreased flow within the fibrillating atrium is associated with spontaneous echo contrast, thrombus formation and embolic events, any device able to restore the atrial kick (AK) should significantly reduce the risk of stroke and eventually improve cardiac output (CO). A motorless, volume displacement pump based on artificial muscle technology could reproduce the AK when placed onto a fibrillating atrium. This study has been designed to assess mechanical effects of this pump on the right cavities in an animal model of AF. Atripump (Nanopowers SA, Switzerland) is a dome shape silicone coated biometal actuator 5 × 45mm. The biometal is electrically actuated by a pacemaker like control unit. In 10 sheep the right atrium (RA) was surgically exposed and the dome sutured onto it. AF was induced with rapid epicardial pacing (600 beats/min). RA ejection fraction (EF) and spontaneous echo contrast was assessed with intracardiac ultrasound in baseline, AF and assisted AF status. A flow meter placed on pulmonary artery measured CO. Results The dome’s contraction rate was 60/min. Mean temperature on the RA was 39±1.5 °C. RA EF was 30% in baseline, 5% in AF and 22% in assisted AF conditions. During the AF state, spontaneous echo contrast was present in all animals and in 2 a thrombus appeared in the right appendix. Neither spontaneous echo contrast nor thrombi were present in baseline and AF assisted status. Thrombi were washed out when the pump was turned on. CO was 5.3±0.3 l/min in baseline, 4.4±0.6 l/min in AF and 5.1±0.3 l/min in assisted AF status (p&lt;0.01). Placed on the right side, the artificial muscle restores the AK, improves CO and shows a mechanical anti coagulant effect. In patients with permanent AF, if implanted on both sides, it would improve CO and prevent embolism of cardiac origin. The implantation technique could be comparable to that of a pacemaker.

Acute Onset Human Atrial Fibrillation Is Associated With Local Cardiac Platelet Activation and Endothelial Dysfunction

The purpose of this study was to determine whether acute onset atrial fibrillation (AF), independent of other risk factors, predisposes to an early prothrombotic state. Several risk factors predispose to the hypercoagulable state in human AF, but whether acute onset AF alone is prothrombotic remains unclear. Patients with paroxysmal AF (n = 22) underwent radiofrequency catheter ablation. All patients presented in sinus rhythm. Baseline blood samples were obtained simultaneously from the femoral vein (systemic sample) and the coronary sinus (local cardiac sample). The AF was induced by burst atrial pacing in 14 patients (AF group). A control group (n = 8) underwent atrial pacing at 120 beats/min. Blood samples were recollected after 15 min. Platelet P-selectin expression (CD62) was measured using flow cytometry. Markers of thrombin generation (thrombin antithrombin complex, prothrombin fragment 1.2), inflammation (C-reactive protein, interleukin-6), and nitric oxide were measured using enzyme-linked immunosorbent assays. Neither local nor systemic platelet activation changed in the control group. In the AF group, local cardiac platelet activation (percent P-selectin [+] platelets) increased significantly (2.2 +/- 0.6% to 2.8 +/- 1.0%, p = 0.007); however, systemic platelet activation did not change. The AF group had increased local thrombin generation (thrombin antithrombin complex: 8.5 +/- 7.6 ng/ml to 33.2 +/- 17.4 ng/ml, p = 0.003; prothrombin fragment 1.2: 95.6 +/- 45.6 micromol/l to 243.8 +/- 120.1 micromol/l, p = 0.003), decreased nitric oxide production (25.2 +/- 10.8 micromol/l to 22.3 +/- 10.0 micromol/l, p < 0.02), and no change in inflammatory markers. Human AF causes local cardiac platelet activation within minutes of onset. The results demonstrate how AF alone, independent of other risk factors, may contribute to the hypercoagulable state.

The endothelium and atrial fibrillation

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, which confers a high risk of mortality and morbidity from stroke and thromboembolism. The precise mechanisms by which AF causes thromboembolism and subsequent cerebrovascular events have attracted much research interest, and are yet to be fully elucidated. Nonetheless, it is well recognised that AF fulfils Virchow's triad for thrombogenesis, with abnormal flow conditions with loss of atrial contractility and an irregularly irregular cardiac output, (i. e. flow abnormalities), as well as structural heart disease with endocardial damage (i. e. abnormal vessel wall) and abnormalities in platelet and haemostatic variables (i. e. abnormal blood constituents). This review is to summarise the evidence so far for the role of coagulation and fibrinolytic components, platelets and inflammation (that is blood constituents) in the generation of the prothrombotic state in AF, with particular focus on the endothelium and AF.

Is early cardioversion for atrial fibrillation safe in patients with spontaneous echocardiographic contrast?

The 2006 American Heart Association guidelines for management of patients with atrial fibrillation state "For patients with no identifiable thrombus in the left atrium (LA) or left atrial appendage (LAA), cardioversion (CV) is reasonable immediately after anticoagulation with unfractionated heparin. Thereafter, continuation of oral anticoagulation is reasonable for an anticoagulation period of at least 4 weeks". For patients with thrombus identified by transesophageal echocardiography, guidelines recommend therapeutic oral anticoagulation for 3 weeks prior to and 4 weeks after elective cardioversion. Patients with spontaneous echo contrast (SEC) identified by TEE have a high risk of thromboembolic events,1-8 however, the guidelines do not address whether patients with SEC without thrombus can be safely cardioverted. This paper reviews the literature describing the pathogenesis of SEC, how it is detected, and whether elective cardioversion is safe. On the basis of our review, we believe that the risk of cardioembolic stroke after cardioversion of a patient with SEC is low, regardless of anticoagulation. The safe conclusion is that patients with SEC on TEE should receive therapeutic anticoagulation prior to cardioversion if possible and early cardioversion is not contraindicated.

Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation

Background The present study was conducted to investigate the relation between the accumulation of the risk factors of thromboembolism and the levels of hemostatic markers in patients with nonvalvular atrial fibrillation (NVAF). Methods Five hundred ninety-one NVAF patients and 129 control subjects were categorized into low, moderate or high risk of thromboembolism, according to CHADS 2 index. One point each was given to patients with advanced age (≥ 75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with CHADS 2 score of 0, 1 or 2, and ≥ 3 were classified as low, moderate and high risk, respectively. Levels of hemostatic markers (platelet factor 4, β-thromboglobulin, prothrombin fragment F1 + 2 and D-dimer) were determined. Results Of 591 patients with NVAF, 302 were treated with warfarin (mean international normalized ratio 1.88). D-dimer levels increased as the risk level increased irrespective of warfarin use. Particularly, NVAF patients without receiving warfarin ( n = 289) had significantly higher D-dimer levels than control patients (e.g., for high risk patients, 175 ± 144 vs 75 ± 87 ng/ml, p < 0.001), while NVAF patients receiving warfarin had intermediate levels (136 ± 156 ng/ml). F1 + 2 levels increased as the risk level increased, and were significantly suppressed by warfarin. Levels of markers of platelet activation (platelet factor 4 and β-thromboglobulin) were increased in NVAF patients but not affected by the risk level. Conclusion Coagulation and fibrinolytic activity is increased along with the accumulation of the risk factors of thromboembolism in NVAF patients.

Atrial fibrillation classification with artificial neural networks

The acquired 72 normal sinus rhythm ECGs and 80 ECGs with atrial fibrillation (AF) are decomposed with ‘db10’ Daebauchies wavelets at level 6 and power spectral density was calculated for each decomposed signal with Welch method. Average power spectral density was calculated for six subbands and normalized to be used as input to the neural network. Levenberg–Marquart backpropagation feed forward neural network was built from logarithmic sigmoid transfer functions in three-layer form. The trained network was tested on 24 normal and 28 AF state ECGs. The classification performance was accomplished as 100% accurate.

A longitudinal population-based study of prothrombotic factors in elderly subjects with atrial fibrillation: the Rotterdam Study 1990-1999.

A prothrombotic or hypercoagulable state in atrial fibrillation may contribute to stroke and thromboembolism. Results of longitudinal population-based studies in elderly people with atrial fibrillation are not yet available. In the Rotterdam Study, a population-based prospective cohort study, 162 participants with atrial fibrillation at baseline, aged 55 years and over, were matched for age and gender with 324 people in sinus rhythm. Associations were examined between three coagulation factors and the risk of total and cardiac mortality and stroke. Hazard rate ratios were calculated with 95% confidence intervals using Cox's proportional hazards model, adjusted for potential confounders. Plasma von Willebrand factor was, age- and gender-adjusted, associated with cardiac mortality in the total population (relative risk 1.16; 1.06-1.27, per 10 IU dL(-1) increase), but statistical significance was lost after additional adjustments. A strong association (1.27; 1.08-1.50, per 5-unit increase) was found between soluble P-selectin (sP-sel) and cardiac mortality in atrial fibrillation patients but not in participants in sinus rhythm. Furthermore, the expected association between fibrinogen and cardiac mortality was observed only in those in sinus rhythm (2.60; 1.69-4.01, per unit increase), and not in atrial fibrillation. No associations were found between coagulation factors and stroke. In this population-based study, plasma levels of sP-sel predicted clinical adverse outcomes in atrial fibrillation, suggesting a role of platelets in the prothrombotic state associated with atrial fibrillation. Fibrinogen was a risk factor of cardiac and all-cause mortality in sinus rhythm, but not in atrial fibrillation.

Atrial Fibrillation Burden During the Post‐Implant Period After CRT Using Device‐Based Diagnostics

AF Burden After CRT Implantation. Cardiac resynchronization therapy (CRT) is increasingly used in congestive heart failure (CHF) patients (with cardiac dyssynchrony). In addition to delivering therapy, CRT devices offer a variety of diagnostic tools for continuous long-term monitoring of clinically relevant information (i.e., occurrence and duration of arrhythmia episodes). Eighty-four patients with drug-refractory CHF in NYHA-class II-IV received a CRT device. The response to CRT was assessed by determining NYHA class at baseline and at 3 months follow-up. Atrial fibrillation (AF) burden (defined as time of AF per day) was continuously measured by the device. A significant gradual reduction of AF burden (from 9.88 +/- 12.61 to 4.20 +/- 9.24 [hours/day]) and number of patients experiencing AF episodes (from 26 to 13) were observed during CRT. (1) Diagnostic features for long-term monitoring of physiological variables provide useful information on the state and course of AF and may improve disease management. (2) AF burden reduces over time during the first 3 months after CRT implantation.