Nonvalvular Atrial Fibrillation Thromboembolism Research Articles

The Risk Factors for Thromboembolism in Nonvalvular Atrial Fibrillation and CHADS2 Scoring in Japan

The Risk Factors for Thromboembolism in Nonvalvular Atrial Fibrillation and CHADS2 Scoring in Japan

The Risk Factors for Thromboembolism in Nonvalvular Atrial Fibrillation and CHADS2 Scoring in Japan

The Risk Factors for Thromboembolism in Nonvalvular Atrial Fibrillation and CHADS2 Scoring in Japan

Anticoagulation orale en pratique gériatrique

Purpose. – Atrial fibrillation and venous thromboembolism are particularly frequent in the elderly. Whether or not prescribe oral anticoagulant treatment in the elderly is therefore a common question for the physician. Despite the benefits of anticoagulation demonstrated in clinical trials, oral anticoagulant therapy is underused in the elderly. Current knowledge and key points. – Indications for oral anticoagulation are discussed specifically in the elderly with a literature review. Only the length of anticoagulation treatment after a venous thromboembolism remained a purpose of discussion regarding the severity of the pathology. The frequency of systemic thromboembolism in nonvalvular atrial fibrillation is increasing with age. Oral anticoagulation reduces this risk. This benefice is to compare with the increasing rate of major bleeding complications in the elderly and in patient who had stroke, hyper-tension, diabetes mellitus or gastrointestinal bleeding. The objective of this article is to focus on the mode to measure oral anticoagulant benefice/risk ratio in the elderly and to propose several ways to minimize the risk for bleeding. Future prospects and projects. – The potential drug side effect severity of oral anticoagulation must lead to find the “reasonable” clinical indications in term of benefice/risk ratio and what measures should be take to increase the safety of oral anticoagulation in the elderly. The comprehensive geriatric evaluation should be considered as a decision-aid tool in long-term oral anticoagulation in the frail elderly. Anticoagulation clinics, informatics'-prescription coupled with dose-adaptation decision-aid adapted to the elderly should be helpful in this research of quality. Finally, prescribers education supports must insist on the early course of therapy that is at higher risk of bleeding.

Letters to the Editor

Stroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. They should not exceed 1000 words (excluding references) and may be subject to editing or abridgment. Please submit letters in duplicate, typed double-spaced. Include a fax number for the correspondling author and a completed copyright transfer agreement form (published in the January and July issues) . To the Editor: We wish to congratulate Hart and Halperin1 on their excellent overview of the current “concepts and controversies” surrounding atrial fibrillation (AF) and stroke. In discussing the formation of thrombus within the left atrial appendage (LAA), they focus a large part of their discussion on the issue of blood stasis in the LAA that occurs in AF, suggesting this mechanism of thrombogenesis to perhaps be of greatest importance, although conceding that “many questions remain about the formation and embolism of left atrial …

Influence of age on left atrial appendage function in patients with nonvalvular atrial fibrillation.

Age is an independent risk factor for thromboembolism in nonvalvular atrial fibrillation (NVAF). An association between low left atrial appendage (LAA) Doppler velocities and thromboembolic risk in NVAF has been reported. The study was undertaken to identify age-related differences in LAA function that may explain the higher thromboembolic rates in older patients with NVAF. Forty-two consecutive patients (age 69+/-2 years [range 42-92], 24 [57%] men) with NVAF underwent transthoracic and transesophageal echocardiography. The following were compared in 22 patients younger and 20 older than 70 years: left ventricular (LV) diameter, mass and ejection fraction, left atrial (LA) diameter and volume, LAA area and volume, LAA peak emptying (PE) and peak filling (PF) velocities, presence and severity of spontaneous echo contrast (SEC) and mitral regurgitation (MR). Left atrial diameter (4.6+/-0.1 vs. 4.5+/-0.2 cm), LA volume (105+/-10 vs. 92+/-8 ml), LAA area (6.8+/-0.6 vs. 5.2+/-0.8 cm2), and LAA volume (5.6+/-0.9 vs. 3.9+/-1.0 ml) were similar (p>0.05) in both groups. Older patients had lower LAA PE (26+/-2 vs. 34+/-3 cm/s, p = 0.02) and PF (32+/-2 vs. 41+/-4 cm/s, p = 0.04) velocities, lower LV mass (175+/-13 vs. 234+/-21 gm, p = 0.02), higher relative wall thickness (0.52+/-0.02 vs. 0.43+/-0.03, p = 0.02), smaller LV diastolic diameter (4.3+/-0.1 vs. 5.2+/-0.2 cm, p < 0.001), and higher LV ejection fraction (62+/-2 vs. 55+/-2%, p = 0.025). Frequency and severity of SEC and MR were similar in both groups. Multivariate analysis identified older age as the only significant predictor of reduced LAA velocities. Compared with younger patients, older patients with NVAF have lower LAA velocities despite higher LV ejection fraction, smaller LV size, and similar LA and LAA volumes. These findings may explain the higher thromboembolic rates in older patients with NVAF.

Integrated Backscatter Assessment of Left Atrial Spontaneous Echo Contrast in Chronic Nonvalvular Atrial Fibrillation: Relation with Clinical and Echocardiographic Parameters

Integrated backscatter (IB) provides the quantitative assessment of left atrial spontaneous echo contrast (SEC). The IB intensity of the left atrial cavity relative to the left ventricular cavity is related to atrial thrombus in patients with atrial fibrillation (AF) or sinus rhythm. However, little is known about the relation between the quantitative SEC value of the left atrial cavity and variables implying thromboembolism in nonvalvular AF. To examine this relation, we performed transesophageal echo-cardiography with IB analysis in 65 patients with chronic nonvalvular AF. The quantitative SEC value of the left atrial cavity was defined as the difference between atrial IB intensity and ventricular IB intensity (corrected IB intensity). The corrected IB intensity was correlated with the left atrial dimension (r = 0.25, P =.049), the left atrial appendage velocity (r = –0.41, P <.001), and the duration of AF (r = 0.23, P =.023). The corrected IB intensity was higher in patients who had a history of hypertension (3.2 ± 2.2 dB versus 2.0 ± 1.6 dB, P =.018), SEC (3.9 ± 1.9 dB versus 1.4 ± 1.1 dB, P =.002), and left atrial thrombus (4.5 ± 2.7 dB versus 2.2 ± 1.7 dB, P <.001) when compared with those who did not have these abnormalities. The corrected IB intensity was significantly lower in patients with significant mitral regurgitation than in those without it (1.1 ± 1.2 dB versus 2.7 ± 2.0 dB, P =.036). When the cutoff value of the corrected IB intensity was set at ≥2.0 dB, the sensitivity for left atrial thrombus was 78% and the specificity was 55%. In patients with chronic nonvalvular AF, the quantitative SEC value of the left atrial cavity depends on the duration of AF as well as the left atrial dimension and appendage velocity. Although IB may be capable of identifying patients with higher risk of cardiogenic embolism, a large-scale prospective study is needed to actually establish this. (J Am Soc Echocardiogr 2000;13:666-73.)

Prevalence and clinical characteristics of patients with atrial fibrillation: analysis of 20,000 cases in Japan.

In Japan, data on the epidemiological and clinical features of atrial fibrillation (AF) are rather sparse; even less data are available on the risk of thromboembolism in nonvalvular AF. The present study enrolled 19,825 patients who visited the cardiovascular clinics of the 13 hospitals in Hokkaido, Japan, between March and July 1995. The prevalence of AF, the clinical characteristics of AF patients, and the occurrence of ischemic events were examined during the 2 year follow-up period. The prevalence of AF increased with age, and the overall prevalence was 14%. Antithrombotic therapy was used in 57% of AF patients and the incidence of ischemic events during the follow-up period was 4.6% in all AF patients. Warfarin reduced the risk of ischemic events in both the valvular and nonvalvular AF groups. A history of cerebrovascular accidents, advanced age, and the presence of underlying heart disease were each associated with a significantly increased risk of ischemic events in the nonvalvular AF group. These results show a lower incidence of ischemic events and more frequent use of antiplatelet drugs in the nonvalvular AF group. Further prospective studies are needed to determine the best preventive methods for thromboembolic complications in Japanese patients with nonvalvular AF.

Pathophysiologic Correlates of Thromboembolism in Nonvalvular Atrial Fibrillation: II. Dense Spontaneous Echocardiographic Contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] Study)

We analyzed transesophageal echocardiograms from 772 participants in the Stroke Prevention in Atrial Fibrillation (SPAF-III) study, characterizing spontaneous echocardiographic contrast (SEC) in the left atrium or appendage as faint or dense. The association of dense SEC with stroke risk factors and anatomic, hemodynamic, and hemostatic parameters related to specific thromboembolic mechanisms was evaluated by multivariate analysis. Spontaneous echocardiographic contrast was present in 55% of patients and was dense in 13%. Age (odds ratio [OR] 2.4/decade, P < .001), constant atrial fibrillation (OR 6.9, P < .001), history of hypertension (OR 3.2, P < .001), and current tobacco smoking (OR 2.6, P = .04) were independent clinical predictors of dense SEC. Multivariate analysis of clinical, echocardiographic, and hemostatic parameters yielded age as the sole independent clinical predictor of dense SEC (OR 2.4/decade, P < .001). Other independent predictors were measures of left atrial/appendage flow dynamics, left atrial size (OR 2.4/cm diameter, M-mode, P < .001), atherosclerotic aortic plaque (OR 2.8, P = .002), and plasma fibrinogen >350 mg/dL ( P < .001). Results were similar when SEC of any density was analyzed. In conclusion, SEC occurred in more than half of these patients with prospectively defined nonvalvular atrial fibrillation but was usually faint. Dense SEC was strongly associated with previously reported clinical predictors of stroke, linking them to thromboembolism through atrial stasis. Diverse pathophysiologic factors including atrial stasis, fibrinogen level, and aortic plaque influence SEC. (J Am Soc Echocardiogr 1999;12:1088-96.)

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)

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 antegrade (emptying) flow velocity (Aν p) than those with intermittent AF in sinus rhythm during TEE (33 cm/s vs 61 cm/s, respectively, P < .0001). Aν 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 Aν 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 Aν 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 Aν 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 Aν p. Our results support the role of reduced LAA Aν p in the generation of stasis, thrombus formation, and embolism in patients with AF, although other mechanisms also contribute to stroke. (J Am Soc Echocardiogr 1999;12:1080-7.)

Transesophageal Echocardiographic Correlates of Clinical Risk of Thromboembolism in Nonvalvular Atrial Fibrillation

Objectives. This study explored the mechanisms linking clinical and precordial echocardiographic predictors to thromboembolism in atrial fibrillation (AF) by assessing transesophageal echocardiographic (TEE) correlations.Background. Clinical predictors of thromboembolism in patients with nonvalvular AF have been identified, but their mechanistic links remain unclear. TEE provides imaging of the left atrium, its appendage and the proximal thoracic aorta, potentially clarifying stroke mechanisms in patients with AF.Methods. Cross-sectional analysis of TEE features correlated with low, moderate and high thromboembolic risk during aspirin therapy among 786 participants undergoing TEE on entry into the Stroke Prevention in Atrial Fibrillation III trial.Results. TEE features independently associated with increased thromboembolic risk were appendage thrombi (relative risk [RR] 2.5, p = 0.04), dense spontaneous echo contrast (RR 3.7, p < 0.001), left atrial appendage peak flow velocities ≤20 cm/s (RR 1.7, p = 0.008) and complex aortic plaque (RR 2.1, p < 0.001). Patients with AF with a history of hypertension (conferring moderate risk) more frequently had atrial appendage thrombi (RR 2.6, p < 0.001) and reduced flow velocity (RR 1.8, p = 0.003) than low risk patients. Among low risk patients, those with intermittent AF had similar TEE features to those with constant AF.Conclusions. TEE findings indicative of atrial stasis or thrombosis and of aortic atheroma were independently associated with high thromboembolic risk in patients with AF. The increased stroke risk associated with a history of hypertension in AF appears to be mediated primarily through left atrial stasis and thrombi. The presence of complex aortic plaque distinguished patients with AF at high risk from those at moderate risk of thromboembolism.

Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation

Objectives. This study examined the relation between left atrial spontaneous echo contrast, hematologic variables and thromboembolism in patients with nonvalvular atrial fibrillation.Background. Left atrial spontaneous echo contrast is associated with left atrial stasis and thromboembolism in patients with nonvalvular atrial fibrillation. However, its hematologic determinants in patients with nonvalvular atrial fibrillation are unknown.Methods. Clinical, hematologic and echocardiographic variables were prospectively measured in 135 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography.Results. Patients with left atrial spontaneous echo contrast (n = 74, 55%) had an increased fibrinogen concentration (p = 0.029), platelet count (p = 0.045), hematocrit (p = NS) and left atrial dimension (p = 0.005). Multivariate analysis showed that left atrial spontaneous echo contrast was independently related to hematocrit (odds ratio = 2.24, p = 0.002), fibrinogen concentration (odds ratio = 2.08, p = 0.008) and left atrial dimension (odds ratio = 1.90, p = 0.004) but not platelet count. It was also associated with left atrial thrombus (n = 15, p = 0.001) and with recent embolism (n = 40, p < 0.001). In 40 clinically stable outpatients without previous embolism, left atrial spontaneous echo contrast was significantly related to hematocrit (p = 0.005), fibrinogen concentration (p = 0.035) and left atrial dimension (p = 0.029) but not to congulation factor VII, D-dimer, erythrocyte sedimentation rate, platelet count, plasma beta-thromboglobulin, plasma glycocalicin or glycocalicin index.Conclusions. Left atrial spontaneous echo contrast in patients with nonvalvular atrial fibrillation is independently related to hematocrit, fibrinogen concentration and left atrial dimension, indicating a relatively hypercoagulable state in addition to stasis. These findings support the hypothesis that left atrial spontaneous echo contrast is due to erythrocyte aggregation. Hematologic factors may contribute to its association with thromboembolism.