Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study). Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Association between atrial fibrillation and appropriate implantable cardioverter defibrillator therapy: results from a prospective study. Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction. The Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk: The TRENDS Study Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: Data from the GISSI-AF trial Long-term cardiovascular outcomes in patients with atrial fibrillation and atherothrombosis in the REACH Registry. Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation. Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: Rationale, design, and clinical characteristics of the initially enrolled cohort The IMPACT study. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Atrial thrombi-a prospective follow-up study over 3 years with transesophageal echocardiography and cranial magnetic resonance imaging. Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry
Stroke associated with atrial fibrillation ( AF ) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage ( LAA ) . Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography ( TEE ) in patients with AF have not been defined . To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events , we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study . Patient features , TEE findings , and subsequent cardioembolic events were correlated with velocity by multivariate analysis . Patients in AF during TEE displayed lower peak ante grade ( emptying ) flow velocity ( Anu(p ) ) than those with intermittent AF in sinus rhythm during TEE ( 33 cm/s vs 61 cm/s , respectively , P < .0001 ) . Anu(p ) < 20 cm/s was associated with dense spontaneous echocardiographic contrast ( P < .001 ) , appendage thrombus ( P < .01 ) , and subsequent cardioembolic events ( P < .01 ) . Independent predictors of Anu(p ) < 20 cm/s included age ( P = .009 ) , systolic blood pressure ( P < .001 ) , sustained AF ( P = .01 ) , ischemic heart disease ( P = .01 ) , and left atrial area ( P = .04 ) . Multivariate analysis found both Anu(p ) < 20 cm/s ( relative risk 2.6 , P = .02 ) and clinical risk factors ( relative risk 3.3 , P = .002 ) independently associated with LAA thrombus . LAA Anu(p ) is reduced in AF and associated with spontaneous echocardiographic contrast , appendage thrombus , and cardioembolic stroke . Systolic hypertension and aortic atherosclerosis , independent clinical predictors of stroke in patients with AF , also correlated with LAA Anu(p ) . Our results support the role of reduced LAA Anu(p ) in the generation of stasis , thrombus formation , and embolism in patients with AF , although other mechanisms also contribute to stroke As previously reported , 1007 patients with chronic atrial fibrillation participated in the Copenhagen AFASAK study . Before inclusion to trial , they all had a physical examination , chest roentgenogram , and echocardiogram with determination of left atrial size . This study evaluated the importance of cardiovascular risk factors for development of thromboembolic complications . To exclude any treatment effects on occurrence of thromboembolic complications , we included only the 336 patients from the placebo group . Using Cox 's regression model , previous myocardial infa rct ion was a significant risk factor for development of thromboembolic complications . Age , gender , heart failure , chest pain , hypertensive heart disease , diabetes , systolic and diastolic blood pressure , smoking , relative heart volume , and left atrial size were all without statistical importance BACKGROUND Atrial fibrillation ( AF ) is a major risk factor ( RF ) for ischemic stroke . Its prevalence and prognostic impact in patients with atherothrombosis are unclear . METHODS Risk factors , drug usage , and 1-year cardiovascular ( CV ) outcomes ( CV death , myocardial infa rct ion [ MI ] , and stroke ) were compared in  AF and non-AF patients from the REduction of Atherothrombosis for Continued Health ( REACH ) Registry , an international , prospect i ve cohort of 68,236 stable out patients with established atherothrombosis or > or=3 atherothrombotic RFs . RESULTS Atrial fibrillation and 1-year follow-up data are available for 63,589 patients . The prevalence of AF was , 12.5 % , 13.7 % , 11.5 % , and 6.2 % among coronary artery disease , CV disease , peripheral artery disease , and RF-only patients , respectively . Of the 6,814 patients with AF , 6.7 % experienced CV death , nonfatal MI , or nonfatal stroke within a year . The annual incidence of nonfatal stroke ( 2.4 % vs 1.6 % , P<.0001 ) and unstable angina ( 6.0 % vs 4.0 % , P<.00001 ) was higher , and CV death was more than double ( 3.2 % vs 1.4 % , P<.0001 ) , in AF versus non-AF patients . In these patients with or at high risk of atherothrombosis , most patients with AF received antiplatelet agents , but only 53.1 % were treated with oral anticoagulants . Even with high CHADS2 ( congestive heart failure , hypertension , aging , diabetes mellitus , and stroke ) scores , anticoagulant use did not exceed ( 59 % ) . The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients ( 1.5 % vs 0.8 % , P<.0001 ) , possibly related to the more frequent use of anticoagulants ( 53.1 % vs 7.1 % ) . CONCLUSIONS Atrial fibrillation is common in patients with atherothrombosis , associated with more frequent fatal and nonfatal CV outcomes , and underuse of oral anticoagulants INTRODUCTION  Atrial fibrillation ( AF ) is associated with significant morbidity and mortality that may be related to hemodynamic impairment , thromboembolic events , or enhanced electrical instability of the ventricular myocardium . There is , however , a lack of data concerning the association of AF and ventricular tachyarrhythmias . METHODS AND RESULTS Consecutive patients with indication for an implantable cardioverter defibrillator ( ICD ) were classified for the presence or absence of persistent AF at the time of device implantation .  Incidence of device therapy , stored electrograms , and clinical events during follow-up were evaluated prospect ively . Two hundred fifty patients were included . During follow-up ( 20+/-14 months ) , patients in AF experienced appropriate device therapy for recurrent ventricular arrhythmias more frequently compared with patients in sinus rhythm ( SR ) ( 63 % vs 38 % , P = 0.01 ) . On multivariate analysis , AF was an independent predictor of appropriate ICD therapy ( relative risk 1.8 ; 95 % confidence interval [ CI ] 1.2 to 2.9 ) and inappropriate device therapy ( relative risk 2.3 ; 95 % CI 1.2 to 4.5 ) . Predefined clinical events ( cluster endpoint : death , syncope , and hospitalizations ) were observed more frequently in AF than in SR patients ( 55 % vs 31 % , P = 0.01 ) . Analysis of device-stored electrograms revealed a higher incidence of short-long-short cycles preceding ventricular arrhythmias in AF compared with SR patients ( 50 % vs 16 % , P = 0.002 ) . Baseline heart rate preceding ventricular arrhythmias did not differ between the two groups . CONCLUSION AF is an independent predictor of recurrent ventricular arrhythmias in ICD recipients . The underlying electrophysiologic mechanism seems to be irregular rather than rapid ventricular activation , with a high incidence of short-long-short sequences preceding ventricular tachyarrhythmias in AF patients AIMS To characterize the relationship between known and newly diagnosed atrial fibrillation ( AF ) and the risk of death and major cardiovascular ( CV ) events in patients with acute myocardial infa rct ion ( MI ) complicated by heart failure ( HF ) and /or left ventricular systolic dysfunction ( LVSD ) . METHODS The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and /or LVSD .  AF was assessed at presentation and at r and omization ( median 4.9 days after symptom onset ) . Primary outcomes were risk of death and major CV events 3 years following acute MI . RESULTS A total of 1812 with current AF ( AF between presentation and r and omization ) , 339 patients with prior AF ( history of AF without current AF ) , and 12,509 without AF were enrolled . Patients with AF were older ; had more prior HF , angina , and MI , and received beta-blockers and thrombolytics less often than those without AF . Three-year mortality estimates were 20 % in those without AF , 37 % with current AF , and 38 % with prior AF . Compared with patients without AF , the multivariable adjusted HR of death was 1.25 ( 1.03 - 1.52 ; p=0.03 ) for prior AF and 1.32 ( 1.20 - 1.45 ; p<0.0001 ) for current AF . HR for major CV events was 1.15 ( 0.98 - 1.35 ; p=0.08 ) and 1.21 ( 1.12 - 1.31 ; p<0.0001 ) . CONCLUSION AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD Background —It is unknown if brief episodes of device-detected atrial fibrillation ( AF ) increase thromboembolic event ( TE ) risk . Methods and Results —TRENDS was a prospect i ve , observational study enrolling patients with ≥1 stroke risk factor ( heart failure , hypertension , age ≥65 years , diabetes , or prior TE ) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden ( defined as the longest total AT/AF duration on any given day during the prior 30-day period ) . This time-varying exposure was up date d daily during follow-up and related to TE risk . Annualized TE rates were determined according to AT/AF burden subsets : zero , low ( < 5.5 hours [ median duration of subsets with nonzero burden ] ) , and high ( ≥5.5 hours ) . A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy . Patients ( n=2486 ) had at least 30 days of device data for analysis . During a mean follow-up of 1.4 years , annualized TE risk ( including transient ischemic attacks ) was 1.1 % for zero , 1.1 % for low , and 2.4 % for high burden subsets of 30-day windows . Compared with zero burden , adjusted hazard ratios ( 95 % CIs ) in the low and high burden subsets were 0.98 ( 0.34 to 2.82 , P=0.97 ) and 2.20 ( 0.96 to 5.05 , P=0.06 ) , respectively . Conclusions —The TE rate was low compared with patients with traditional AF with similar risk profiles . The data suggest that TE risk is a quantitative function of AT/AF burden . AT/AF burden ≥5.5 hours on any of 30 prior days appeared to double TE risk . Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden Abstract Chronic atrial fibrillation ( AF ) in the presence or absence of rheumatic valvular heart disease is associated with an increased incidence of stroke . 1,2 We reported in a prospect i ve study that at 27-month follow-up , echocardiographic left ventricular ( LV ) hypertrophy in elderly patients with systolic or diastolic hypertension was associated with an increased incidence of new atherothrombotic brain infa rct ion . 3 We also demonstrated in a prospect i ve study that at 3-year follow-up , risk factors for atherothrombotic brain infa rct ion were cigarette smoking , systolic or diastolic hypertension and diabetes mellitus in elderly men and systolic or diastolic hypertension , diabetes mellitus and obesity in elderly women . 4 This report correlates in elderly patients with chronic AF the prevalence of thromboembolic ( TE ) stroke with the presence or absence of rheumatic mitral stenosis , mitral anular calcium , valvular aortic stenosis , systolic or diastolic hypertension , prior myocardial infa rct ion , left atrial enlargement and LV hypertrophy The Canadian Cardiovascular Society ( CCS ) published the complete set of 2010 Atrial Fibrillation ( AF ) Guidelines in the January , 2011 issue of the Canadian Journal of Cardiology . During its deliberations , the CCS Guidelines Committee engaged to a timely review of future evidence , with periodic composition of focused up date s to address clinical ly important advances . In 2011 , results were published from 3 pivotal AF trials : the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) , the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) study , and the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of St and ard Therapy ( PALLAS ) , comparing dronedarone with placebo in patients with permanent AF and additional cardiovascular disease risk-factor burden . Each of these large r and omized trials provided clear results with major implication s for AF management . Other important evidence that has emerged since the 2010 Guidelines includes findings about prediction instruments for AF-associated stroke and bleeding risk , stroke risk in paroxysmal-AF patients , risk-benefit considerations related to oral anticoagulation in patients with chronic kidney disease , and risk/benefit considerations in the use of antiplatelet agents , alone and in combination with each other or with oral anticoagulants , in AF patients . The Guidelines Committee judged that this extensive and important new evidence required focused updating of the 2010 Guidelines with respect to stroke prevention and rate/rhythm control . This report presents the details of the new recommendations , along with the background and rationale Background Few data on the thromboembolic ( TE ) risk of paroxysmal and persistent atrial fibrillation ( AF ) are available . This study aim ed to assess the incidence of TE events in paroxysmal and persistent AF . Methods We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter , prospect i ve , r and omized , double-blind , placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician . TE and major outcome events were central ly vali date d. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions . Results Eighty-five percent of patients had a history of hypertension , and the 7.7 % had heart failure , left ventricular dysfunction , or both .  The mean CHADS2 score was 1.41±0.84 . TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up ( 0.97 % and 0.81 % , respectively ) . The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE , major bleeding events or mortality in paroxysmal and persistent AF patients . TE events were more common among women than men ( p=0.02 ) . The follow-up examination showed under- or overtreatment with warfarin in many patients , according to guideline suggestions . Warfarin was more frequently prescribed to patients with persistent AF ( p<0.0001 ) and patients with AF recurrences ( p<0.0001 ) . AF recurrences were noninvasively detected in 632 ( 51.2 % ) patients . In patients without AF recurrences , the TE event rate was 0.5 % versus 1.74 % , 1.28 % , and 1.18 % for those with only symptomatic , only asymptomatic or both symptomatic and asymptomatic AF recurrences , respectively , but the difference was not statistically significant , even after adjusting for warfarin treatment and the CHADS2 score ( HR 2.93 ; CI 95 % ; 0.8 - 10.9 ; p=0.11 ) . Conclusions TE and major bleeding events showed a very low incidence in the GISSI-AF trial population , despite under- or overtreatment with warfarin in many patients . TE events had a similar rate in paroxysmal and persistent AF.Trial registration Trial registration number : BACKGROUND Patients with atrial fibrillation ( AF )  are at increased risk of thromboembolic events . The long-term prognostic implication s of AF in patients with atherothrombosis are unknown . METHODS We compared 4-year CV outcomes in patients with and without a history of AF recorded at their baseline visit in the REACH Registry , an international , prospect i ve cohort of patients with established atherosclerotic arterial disease ( CAD , CVD , PAD ) or at least 3 risk factors ( RFO ) . RESULTS AF status and 4 year follow-up data were available on 44,518 patients . The prevalence of AF at baseline was 10.3 % ( n=4582 ) . Overall , patients with AF had approximately a 2-fold increase in the composite of CV death , MI , or stroke compared with patients without AF after adjustment for age , gender , prior ischemic event , vascular disease , congestive heart failure , diabetes , smoking , body mass index , region , aspirin and statin use ( 18.9 % vs. 9.4 % , p<0.0001 ) . This increased risk was observed both in patients with established atherothrombosis ( CAD : 15.5 % vs. 8.0 % , p=0.0001 ; CVD : 23.6 % vs. 13.6 % , p<0.0001 ; PAD : 24.3 % vs. 13.5 % , p=0.089 ) and those with multiple risk factors ( RFO : 12.1 % vs. 5.9 % , p=0.017 ) . Only 52 % of patients with a history of AF at baseline were receiving anticoagulation at 4 years . CONCLUSIONS Patients with a history of both AF and atherothrombosis have particularly high long-term CV risk . Despite this increased risk , almost half of all patients with AF do not receive guideline recommended anticoagulation , highlighting an important public health priority Background — Atrial fibrillation ( AF ) is common among patients with heart failure and preserved ejection fraction ( HFpEF ) , but its clinical profile and impact on exercise capacity remain unclear . RELAX ( Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF ) was a multicenter r and omized trial testing the impact of sildenafil on peak VO2 in stable out patients with chronic HFpEF . We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm ( SR ) or AF . Methods and Results — RELAX enrolled 216 patients with HFpEF , of whom 79 ( 37 % ) were in AF , 124 ( 57 % ) in SR , and 13 in other rhythms . Participants underwent baseline cardiopulmonary exercise testing , echocardiogram , biomarker assessment , and rhythm status assessment before r and omization . Patients with AF were older than those in SR but had similar symptom severity , comorbidities , and renal function . & bgr;-blocker use and chronotropic indices were also similar . Despite comparable left ventricular size and mass , AF was associated with worse systolic ( lower EF , stroke volume , and cardiac index ) and diastolic ( shorter deceleration time and larger left atria ) function compared with SR . Pulmonary artery systolic pressure was higher in AF . Patients with AF had higher N-terminal pro-B-type natriuretic peptide , aldosterone , endothelin-1 , troponin I , and C-telopeptide for type I collagen levels , suggesting more severe neurohumoral activation , myocyte necrosis , and fibrosis . Peak VO2 was lower in AF , even after adjustment for age , sex , and chronotropic response , and VE/VCO2 was higher . Conclusions — AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity . These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00763867 The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin  would prove superior to  combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) . BACKGROUND Atrial fibrillation ( AF ) is widely accepted as a direct cause of cardioembolic stroke from left atrial ( LA ) thrombus formation . However , the relationship between LA thrombus and transient ischemic attack ( TIA ) in patients with AF is less well established . METHODS Two hundred sixty-one adult patients ( mean age 66 + /- 11 years , 220 men and 41 women ) with AF undergoing transesophageal echocardiography ( TEE )  were prospect ively followed up for TIA ( mean duration 30.3 + /- 20.6 months ) . RESULTS LA thrombus was present in 18 % ( n = 46 ) and LA spontaneous echocardiographic contrast in 50 % ( n = 131 ) of the group . Nineteen of 261 patients had TIA during follow-up . Multivariate logistic regression showed congestive heart failure ( CHF ) as the only predictor of TIA when a model of clinical variables was constructed ( odds ratio [ OR ] 2.7 , P = .04 ) . Age , sex , hypertension , and use of warfarin or aspirin were not predictors . When TEE variables were added to the model , LA thrombus became the only predictor of TIA ( OR 7.7 , P = .0001 ) . Survival free of TIA ( Kaplan-Meier ) was significantly less ( P = .0001 ) in patients with LA thrombus compared with those without , and the annual TIA event rate was 9.2 % per year versus 1.9 % per year ( P < .0001 ) , respectively . CONCLUSIONS To our knowledge , this is the first prospect i ve study documenting an association between LA thrombus and TIA in patients with AF . Other TEE variables , including aortic atheromata , and clinical parameters were not independently predictive . These data support a likely thromboembolic mechanism for TIA from LA thrombus in patients with AF Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors .  Anticoagulation ameliorates stroke risk , but because these arrhythmias may occur intermittently without symptoms , initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained . The IMPACT study is a multicenter , r and omized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator ( CRT-D ) devices design ed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke , systemic embolism , and major bleeding compared with conventional clinical management . For those in the intervention group , early detection of atrial high-rate episodes ( AHRE ) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification . Subsequently , freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding . Patients in the control arm are managed conventionally , the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up . The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke . In this report , we describe the study design and baseline demographic and clinical features of the initial cohort ( 227 patients ) AIMS The impact of some risk factors for stroke and bleeding , and the value of stroke and bleeding risk scores , in atrial fibrillation ( AF ) , has been debated , as clinical trial cohorts have not adequately tested these . Our objective was to investigate risk factors for stroke and bleeding in AF , and application of the new CHA(2)DS(2)-VASc and HAS-BLED schemes for stroke and bleeding risk assessment s , respectively . METHODS AND RESULTS We used the Swedish Atrial Fibrillation cohort study , a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008 , who were prospect ively followed for an average of 1.5 years ( 260 000 years at risk ) . With the use of the National Swedish Drug Registry , all patients who used an oral anticoagulant  anytime during follow-up were identified . Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants .  Risk factors for stroke , the composite thromboembolism endpoint ( stroke , TIA , or systemic embolism ) , and bleeding , and the performance of published stroke and bleeding risk stratification schemes were investigated . On multivariable analysis , significant associations were found between the following ' new ' risk factors and thromboembolic events ; peripheral artery disease [ hazard ratio ( HR ) 1.22 ( 95 % CI 1.12 - 1.32 ) ] , ' vascular disease ' [ HR 1.14 ( 1.06 - 1.23 ) ] , prior myocardial infa rct ion [ HR 1.09 ( 1.03 - 1.15 ) ] , and female gender [ HR 1.17 ( 1.11 - 1.22 ) ] . Previous embolic events , intracranial haemorrhage ( ICH ) , hypertension , diabetes , and renal failure were other independent predictors of the composite thromboembolism endpoint , while thyroid disease ( or hyperthyroidism ) was not an independent stroke risk factor . C-statistics for the composite thromboembolic endpoint with the CHADS(2 ) and CHA(2)DS(2)-VASc schemes were 0.66 ( 0.65 - 0.66 ) and 0.67 ( 0.67 - 0.68 ) , respectively . On multivariable analysis , age , prior ischaemic stroke or thromboembolism , prior major bleeding events , and hypertension were significant predictors of ICH and major bleeding . Heart failure , diabetes , renal failure , liver disease , anaemia or platelet/coagulation defect , alcohol abuse , and cancer were other significant predictors for major bleeding , but not ICH . The ability for predicting ICH and major bleeding with both bleeding risk schemes ( HEMORR(2)HAGES , HAS-BLED ) were similar , with c-statistics of ~0.6 . CONCLUSION Several independent risk factors ( prior ICH , myocardial infa rct ion , vascular disease , and renal failure ) predict ischaemic stroke and /or the composite thromboembolism endpoint in AF , but thyroid disease ( or hyperthyroidism ) was not an independent risk factor for stroke . There is a better performance for CHA(2)DS(2)-VASc over CHADS(2 ) schemes for the composite thromboembolism endpoint . While both tested bleeding risk schemes have similar predictive value , the HAS-BLED score has the advantage of simplicity BACKGROUND Patients with atrial fibrillation ( AF ) and atrial thrombi have an increased risk for cerebral embolism . However , there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients under oral anticoagulation . METHODS Consecutive patients with persistent or permanent AF and left atrial ( LA ) thrombi were included in the study . We performed serial and prospect i ve transesophageal echocardiography , cranial magnetic resonance imaging , and clinical examinations during a period of 3 years . Oral anticoagulation was continued or initiated in all patients . A target INR of 2.5 was intended in all patients . RESULTS Forty-three patients with LA thrombi and persistent or permanent AF were included . During the follow-up period 31(72 % ) of the thrombi disappeared . Patients with disappearance of thrombi had significantly smaller thrombi ( P < 0.01 ) , a lower echogenicity of thrombi ( P < 0.01 ) , and a lower LA volume ( P = 0.02 ) . Twenty-two ( 51 % ) patients suffered from cerebral embolism and /or death during the observation period . Five patients died due to embolic events . The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage ( P < 0.001 ) and a history of previous thromboembolism ( P < 0.01 ) . CONCLUSIONS Patients with persistent or permanent AF and atrial thrombi have a high long-term risk of cerebral embolism and /or death ( 51 % ) even despite the oral anticoagulation therapy . Thrombus size may predict thrombus resolution under continued anticoagulation Background and Purpose — There is controversy on the relationship of the type of atrial fibrillation ( AF ) to stroke . Although several studies show that patients with paroxysmal AF ( PAF ) have a stroke risk similar to those with persistent or permanent AF , recent studies suggest that PAF is associated with a lower rate of stroke . Limited data on stroke risk associated with PAF are evident in Asian population s. Methods — The Registry Study of Atrial Fibrillation Patients in Fushimi-ku ( Fushimi AF Registry ) is a community-based survey of patients with AF in Fushimi-ku , Kyoto , Japan . Patients were categorized into 2 types of AF : PAF or sustained ( persistent or permanent ) AF . We compared clinical events between PAF  ( n=1588 ) and  sustained AF ( n=1716 ) . Results — Patients with PAF were younger , had less comorbidities , and received oral anticoagulants ( OAC ) less commonly . A lower risk of stroke/systemic embolism during follow-up period in the patients with PAF was consistently observed ( non-OAC users : hazard ratio , 0.45 ; 95 % confidence intervals , 0.27–0.75 ; P<0.01 and OAC users : hazard ratio , 0.59 ; 95 % confidence interval , 0.35–0.93 ; P=0.03 ) . The composite end point of stroke/systemic embolism/all-cause mortality was also lower in PAF , whether among OAC users ( hazard ratio , 0.77 ; 95 % confidence interval , 0.59–0.99 ; P=0.046 ) or non-OAC users ( hazard ratio , 0.59 ; 95 % confidence interval , 0.46–0.75 ; P<0.01 ) . On multivariate analysis , PAF was an independent predictor of lower stroke/systemic embolism risk . Conclusions — In this large cohort of Japanese patients with AF , PAF was independently associated with lower incidence of stroke/systemic embolism than sustained AF . This may aid decision making for anticoagulation , especially in those patients with AF with few stroke risk factors . Clinical Trial Registration — URL : http://www.umin.ac.jp/ctr/index.htm . Unique identifier : UMIN000005834
AF in CF-LVAD patients was not associated with overall TE , stroke , or device thrombosis events .
These findings might be explained by the highly thrombogenic property of CF-LVADs that exceeds the thromboembolic risk driven by AF
Atrial fibrillation ( AF ) is a well-established risk factor of thromboembolism ( TE ) .
Thromboembolism is one of the most common complications in patients supported by continuous-flow left ventricular assisted devices ( CF-LVADs ) .
However , the association between AF and TE complications in this population is controversial .
We conducted a systematic review and meta- analysis to assess the association between AF and overall TE , stroke , and device thrombosis events in CF-LVAD patients .