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Circulating procoagulant microparticles (MPs) arising from cell activation or fragmentation during apoptosis retain procoagulant properties and are increased in severe thrombotic states. We investigated whether circulating procoagulant MP levels would be increased in nonvalvular atrial fibrillation (AF). Using a hospital case-control study design, circulating procoagulant MP levels were measured in 45 patients with permanent and/or persistent AF who were not receiving anticoagulant therapy and 90 age-matched control subjects (45 with cardiovascular risk factors and 45 without). Annexin V-positive MP levels (expressed as nanomoles per liter of phosphatidylserine equivalent) were higher in patients with AF (median 9.3, interquartile range 6.8 to 17.3 nmol/L) than in control subjects with cardiovascular risk factors (median 4.9, interquartile range 3.7 to 8.4 nmol/L) and control subjects without cardiovascular risk factors (median 3.2, interquantile range 2.3 to 4.6 nmol/L; p<0.001). Platelet-derived MPs (captured with antiglycoprotein Ib) and endothelial-derived MPs (captured with anti-CD31) were similar in patients with AF and control subjects with cardiovascular risk factors but were significantly higher than in control subjects without cardiovascular risk factors. On multiple regression analysis, the presence of AF was a strong predictor of annexin V-positive MP level (p<.001). In conclusion, circulating procoagulant MPs are increased in persistent and/or permanent AF and might reflect a hypercoagulable state that could contribute to atrial thrombosis and thromboembolism.

Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

Atrial fibrillation, the most commonly encountered arrhythmia in clinical practice, is associated with substantial morbidity and mortality. Its incidence and prevalence are increasing, and it represents a growing clinical and economic burden. Recent research has highlighted new approaches to both pharmacological and non-pharmacological management. Pooled data from trials comparing antithrombotic treatment with placebo show that warfarin reduces the risk of stroke by 62% and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin was better than aspirin in preventing strokes, with a relative risk reduction of 36%, but the risk of major hemorrhage with warfarin was twice that with aspirin. Anticoagulation treatment needs to be tailored individually for patients on the basis of age, comorbidities, and contraindications. However, warfarin remains under-prescribed in clinical practice, for reasons related to patients (comorbidities) and physicians. The limitations of warfarin treatment have prompted the development of new anticoagulants with predictable pharmacokinetics that do not require as frequent monitoring. Ximelagatran, an oral direct thrombin inhibitor, was compared with warfarin in the SPORTIF program, which found both agents to be broadly effective in the prevention of embolic events, but observed abnormal liver function tests in 6% of patients on ximelagatran. Liver function monitoring during treatment is thus needed. Idraparinux, a factor Xa inhibitor administered by once weekly subcutaneous injections, is being evaluated in patients with atrial fibrillation. The ACTIVE trial is currently assessing the role of aspirin plus clopidogrel, compared with adjusted dose warfarin, in the prevention of vascular events in high-risk patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs interfere with atrial remodeling and show promise in atrial fibrillation, as suggested in the LIFE trial. Preliminary studies suggest that statins may reduce the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for occlusion of the left atrial appendage are currently under investigation in patients at high risk of thromboembolism but with contraindications for chronic warfarin.

Although transesophageal echocardiographically derived parameters, notably spontaneous echocardiographic contrast (SEC) in the left atrium or left atrial appendage (LAA), are known predictors of embolism in atrial fibrillation, their value is less well known in patients who have lone atrial fibrillation (LAF). This study describes transesophageal echocardiographic findings and identifies clinical predictors of SEC in the left atrium or LAA in a cohort of patients who had LAF. Eighty-two patients who had LAF and 289 patients who had non-LAF and underwent transesophageal echocardiography were enrolled from July 1998 to March 2002. LAA abnormality was defined as the presence of an LAA area >5 cm(2), emptying or filling LAA velocities <25 cm/s, or the presence of SEC or thrombus in the left atrium or LAA; LAA abnormalities were significantly less frequent in patients who had LAF than in those who had non-LAF. SEC in the left atrium or LAA was significantly less frequent in patients who had LAF than in those who had non-LAF (29.3% vs 49.8%, respectively, p <0.001). In patients who had LAF, SEC in the left atrium or LAA was significantly (p <0.05) less frequent in patients who were 60 years old (39.5%) and in patients who had paroxysmal LAF (5.9%) than in those who had persistent LAF (45.8%). On multivariate analysis, age and persistent LAF were the only clinical variables independently associated with SEC. Thus, transesophageal echocardiography detects thromboembolism risk markers in patients who have LAF. These abnormalities are less frequent in patients who have LAF than in those who are at low risk and have non-LAF; however, in patients who have LAF, older age and persistent atrial fibrillation are associated with these risk markers.