Persistent Non-valvular Atrial Fibrillation Research Articles

Usefulness of platelet to lymphocyte ratio for predicting recurrence of atrial fibrillation after direct current cardioversion.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder with the associated risks of stroke and mortality. The usefulness of platelet to lymphocyte ratio (PLR), a recently described inflammatory marker, in predicting adverse cardiovascular events has been demonstrated in several studies. In the current study, we investigated the role of PLR in predicting recurrence after successful electrical cardioversion (ECV) in patients with non-valvular persistent AF. A total of 287 patients with non-valvular persistent AF achieving restoration of the sinus rhythm after successful ECV were included in this study. At study entry, complete blood count, routine biochemistry tests, and transthoracic echocardiography (TTE) were performed routinely in all subjects. Patients were followed up for 6months following the procedure and comparisons were performed between patients who recurred and who maintained the sinus rhythm (SR). At 6months of follow-up, AF recurred in 108 patients, corresponding to a recurrence rate of 39%. Mean PLR values in the "AF recurrence group" (mean age 57.4±12.0years, 47.6% [n=80] female) and in "SR maintenance" group (mean age 65.0±9.4years, 55.6% [n=60] female) were 184.8±44.2 and 103.3±44.2, respectively, with a significant difference between the two groups (p<0.001). In multiple regression analyses, PLR emerged as a risk factor associated with AF recurrence during the 6-month follow-up period after successful ECV (odds ratio [OR]: 3.029 (1.013-9.055 95% confidence interval [CI]), p = 0.047). When a cutoff value of 147 was used, the sensitivity and specificity of PLR for predicting AF recurrence were 83.3% and 84.5%, respectively. Elevated PLR is a marker of increased inflammation and may serve as a practical and inexpensive predictor for recurrence during 6months of follow-up in patients with non-valvular persistent AF who had restoration of the sinus rhythm after successful ECV.

Epicardial fat thickness: A new predictor of successful electrical cardioversion and atrial fibrillation recurrence.

In recent years, epicardial fat tissue (EFT) has been found to be strongly associated with the development of atrial fibrillation (AF) and post-ablation long-term recurrence. The current study investigated the procedural success rate of electrical cardioversion (ECV) and potential predictors of treatment failure in patients with nonvalvular persistent AF. A total of 262 nonvalvular persistent AF patients who were scheduled for elective ECV were included in this prospective study. Routine transthoracic echocardiography was performed before the procedure and EFT thickness was measured. The presence of left atrial appendage thrombus was evaluated by transesophageal echocardiography. The patients were followed up for 6months to examine any recurrence after ECV. The success rate of ECV was 85% and the recurrence rate was 35% during the 6-month follow-up period. The mean EFT thickness was 8.67±1.2mm in the persistent AF group with unsuccessful ECV and 6.81±0.8 in the patients in whom sinus rhythm (SR) was maintained, the EFT was significantly thicker in the AF group (P=0.001). EFT (P=0.001) and left ventricular end-diastolic diameters (LVEDD) (P=0.001) were significantly different between those who had maintained SR and those with recurrent AF during the 6-month follow-up period after ECV. In the multiple logistic regression analysis, LVEDD (odds ratio [OR]: 1.320 (1.023-1.703 95% confidence interval [CI]), P=0.032)] and EFT [OR: 3.029 (1.013-9.055 95% CI), P=0.047)] were identified as independent predictors of successful ECV. Epicardial fat tissue thickness can be effectively used for the prediction of successful ECV and AF recurrence during follow-up in AF patients.

Clinical analysis of antithrombotic treatment and occurrence of stroke in elderly patients with nonvalvular persistent atrial fibrillation.

Atrial fibrillation (AF) is common in elderly patients and is associated with ischemic stroke. We sought to explore the current status of antithrombotic therapy in elderly patients with nonvalvular persistent AF. This is a retrospective study and data were collected from the First Hospital of China Medical University. A total of 300 patients were enrolled from January 2015 to June 2017. Patients were divided into two groups: Group 1 (from 65-74) and Group 2 (older than 75). The status of antithrombotic treatment was recorded. Follow-ups were done at 7, 90 , 180, and 360 days after discharge. The occurrence of stroke was recorded. For 287 patients with a CHA2 DS2 -VASc score ≥2, 41.10% received oral anticoagulants (OAC), 27.20% received new oral anticoagulants (NOAC), 42.20% received antiplatelet agents, 16.70% received no antithrombotic treatment. From 2015 to the first half 2017, the ratio of OAC was 25.90%, 51.89%, and 49.30%, respectively; ratio of NOAC were 16.90%, 30.19%, and 39.10%, respectively. During the four times follow-up, percentage of patients who had good treatment compliance was 65%, 49.2%, 38.5%, and 25% stroke rate was 6.7% in total 300 patients. Logistic regression analysis showed age older than 75 (odds ratio [OR] 4.812), prior stroke (OR 4.109) were risk factors of stroke, and OAC treatment (OR 0.021) could prevent stroke. Ratio of antithrombotic therapy in elderly patients with nonvalvular persistent AF was low and drug compliance was poor. Age, prior history of stroke, and OAC treatment are the important predictive factors of stoke in elderly patients.

Mitral Valve Adaptation to Isolated Annular Dilation: Insights Into the Mechanism of Atrial Functional Mitral Regurgitation

ObjectivesThis study hypothesized that compensatory mitral leaflet area (MLA) adaptation occurs in patients with persistent atrial fibrillation (AF) without left ventricular (LV) dysfunction but has limitations that augment mitral regurgitation (MR). The study also explored whether asymmetrical annular dilation is matched by relative leaflet enlargement. BackgroundFunctional MR occurs in patients with AF and isolated annular dilation, but the relationship of MLA adaptation with annular area (AA) is unknown. MethodsThree-dimensional echocardiographic images were acquired from 86 patients with quantified MR: 53 with nonvalvular persistent AF (23 MR+ with moderate or greater MR, 30 MR−) without LV dysfunction or dilation and 33 normal controls. Comprehensive 3-dimensional analysis included total diastolic MLA, adaptation ratios of MLA to annular area and MLA to leaflet closure area, and annular and tenting geometry. ResultsTotal MLA was 22% larger in patients with AF than in controls, thus paralleling the increased AA. However, as AA increased, adaptive indices (MLA/AA ratio and ratio of MLA to closure area) plateaued, becoming lowest in MR+ patients (ratio of MLA to closure area = 1.63 ± 0.17 controls, 1.60 ± 0.11 MR−, 1.32 ± 0.10 MR+; p < 0.001). MR increased as the ratio of MLA to closure area decreased (R2 = 0.68; p < 0.001). The posterior-to-anterior MLA ratio remained constant, whereas the posterior-to-anterior mitral annulus perimeter increased (1.21 ± 0.16 controls, 1.32 ± 0.20 MR−, 1.46 ± 0.19 MR+; p < 0.001). Multivariate MR determinants were annular area, total MLA to closure area, and posterior-to-anterior perimeter ratios. ConclusionsMLA adaptively increases in AF with isolated annular dilation and normal LV function. This compensatory enlargement becomes insufficient with greater annular dilation, and the leaflets fail to match asymmetrical annular remodeling, thereby increasing MR. These findings can potentially help optimize therapeutic options and motivate basic studies of adaptive growth processes.

Association between left atrial phasic conduit function and early atrial fibrillation recurrence in patients undergoing electrical cardioversion

BackgroundDiastolic dysfunction promotes atrial fibrillation (AF) inducing left atrial (LA) remodeling, with chamber dilation and fibrosis. Predominance of LA phasic conduit (LAC) function should reflect not only chamber alterations but also underlying left ventricular (LV) filling impairment. Thus, LAC was tested as possible predictor of early AF relapse after electrical cardioversion (EC).Methods96 consecutive patients, who underwent EC for persistent non-valvular AF, were prospectively enrolled. Immediately after successful EC (3 h ± 15 min), an echocardiographic apical four-chamber view was acquired with transmitral velocities, annular tissue Doppler and simultaneous LV and LA three-dimensional full-volume datasets. Then, from LA–LV volumetric curves we computed LAC as: [(LV maximum − LV minimum) − (LA maximum − LA minimum) volume], expressed as % LV stroke volume. LA pump, immediately post-EC, was assumed and verified as being negligible. Sinus rhythm persistence at 1 month was checked with ECG-Holter monitoring.ResultsAt 1 month 62 patients were in sinus rhythm and 34 in AF. AF patients presented pre-EC higher E/é values (p = 0.012), no major LA volume differences (p = NS), but a stiffer LV cavity (p = 0.012) for a comparable LV capacitance (p = 0.461). Conduit contributed more (p < 0.001) to LV stroke volume in AF subpopulation. Multiple regression revealed LAC as the most significant AF predictor (p = 0.013), even after correction for biometric characteristics and pharmacotherapy (p = 0.008).ConclusionOur data suggest that LAC larger contribution to LV filling soon after EC reflects LA–LV stiffening, which skews atrioventricular interaction leading to AF perpetuation and makes conduit dominance a powerful predictor of early AF recurrence.

Relationship between exercise induced elevation of left ventricular filling pressure and exercise intolerance in patients with atrial fibrillation.

BackgroundElevated left ventricular filling pressure (LVFP) is an important cause of exercise intolerance in patients with atrial fibrillation (AF). Exercise stress echocardiography could assess LVFP during exercise. The objective of this study was to investigate the relationship between exercise induced elevation of LVFP and exercise capacity in patients with AF.MethodsThis study included 145 consecutive patients (81 men and 64 women; mean age 65.5 ± 8.0 years) with persistent non-valvular AF and normal left ventricular systolic function (left ventricular ejection fraction ≥ 50%). All patients underwent a symptom-limited cardiopulmonary exercise test (CPET). Doppler echocardiography was performed both at rest and immediately after exercise. Five consecutive measurements of early diastolic mitral inflow velocity (E) and early diastolic mitral annular velocity (e') were taken and averaged. E/e' ratio was calculated. Elevated LVFP was defined as E/e' > 9, and patients with elevated LVFP at rest were excluded.ResultsPatients were classified into two groups according to LVFP estimated by E/e' ratio after exercise: 39 (26.9%) with elevated LVFP after exercise and 106 (73.1%) with normal LVFP. As compared with patients with normal LVFP, the ones with elevated LVFP after exercise had significantly lower peak oxygen uptake (VO2 peak) (21.7 ± 2.3 vs. 26.4 ± 3.8 mL/min per kilogram, P < 0.001), lower anaerobic threshold (19.9 ± 2.5 vs. 26.0 ± 4.0 mL/min per kilogram, P < 0.001), and shorter exercise time duration (6.2 ± 0.8 vs. 7.0 ± 1.3 min, P < 0.001). Multivariate analysis showed that age, gender and E/e' after exercise were significantly correlated with VO2 peak.ConclusionElevated LVFP estimated by E/e' ratio after exercise is independently associated with reduced exercise capacity in AF patients.

The prevalence of obesity in patients with non-valvular persistent atrial fibrillation during long observations

А im: to study the prevalence of obesity in patients with non-valvular persistent atrial fibrillation (AF) who underwent electrical cardioversion (ECV) in Municipal Institution of Dnipropetrovsk regional council Dnipropetrovsk regional clinical center of cardiology and cardiac surgery. Methods and results . 104 patients (mean age 63.2±0.4 years) with non-valvular persistent AF were included in the study. The average duration of a history of arrhythmia was 3.0±0.3 years. AF was associated with arterial hypertension (76.9%) and coronary artery disease (22.1%), 13.4% of patients had no cardiac disease. Transthoracic echocardiography (TTE) was held according to ASA recommendations before ECV. Conclusion: obesity as a comorbid condition was diagnosed in 61% of patients with non-valvular persistent AF. Only 10% of patients had normal body weight. Most people were obese class I (33.8%) and class II (17.9%). Body mass index (BMI) above 40 kg/m2 was in 9.5% of patients. BMI is directly correlated with the level of diastolic blood pressure (r=0.35; p<0,001) and echocardiographic parameters that indicated ventricular hypertrophy: left ventricular mass (r=0,4; p<0,001), interventricular septum thickness (r=0.41; p<0.001) and left ventricular (LV) posterior wall thickness (r=0.4; p<0.001). Patients with persistent non-valvular AF and obesity need to reduce the body mass index.

Echocardiographic diastolic function assessment is of modest utility in patients with persistent and longstanding persistent atrial fibrillation

BackgroundDetection of concurrent diastolic dysfunction (DD) may be beneficial in patients with persistent and longstanding persistent atrial fibrillation (AF). The role of transthoracic echocardiography (TTE) in assessing DD in patients with AF has not been well characterized. We sought to determine the utility of TTE in detecting elevated left atrial pressure (LAP) in patients with persistent and longstanding persistent non-valvular AF using directly measured LAP as the reference standard. MethodsWe retrospectively studied 157 patients with persistent AF and preserved left ventricular ejection fraction who underwent pulmonary vein isolation (PVI). LAP was determined in conjunction with trans-septal puncture at the time of catheter ablation. TTE was performed 1day after PVI and included two dimensional, pulse wave spectral Doppler and tissue Doppler assessments. ResultsThe clinical parameter that strongly correlated with elevated LAP is longstanding persistent AF. Four strongest TTE parameters identified to moderately correlate with LAP include 1. left atrial minimum volume (LAVmin), 2. peak velocity of early mitral diastolic inflow velocity (E), 3. pulmonary vein systolic flow velocity (PVS), and 4. ratio of early diastolic transmitral inflow velocity to mitral annular velocity at the lateral site (E/E′ lateral). ConclusionAccurate assessment of diastolic dysfunction in patients with persistent and longstanding persistent AF is difficult using TTE. A combination of LAVmin, PVS, and E might be helpful to determine elevated LAP.

Impact of intensive follow-up visit on Warfarin anticoagulant in patient with nonvalvular atrial fibrillation

Objective To explore the impact of intensive follow-up visit in patients with nonvalvular atrial fibrillation taking Warfarin in process of anticoagulant therapy. Methods A total of 100 patients with persistent nonvalvular atrial fibrillation were randomly divided them into intensive follow-up group and regular follow-up group on average. We compared the treatment compliance, INR value, embolism and hemorrhage between two groups. Results The INR qualified rate was 86.0% after 6 months taking medication in the intensive follow-up group and 72.0% in the regular follow-up group (χ2=4.570, P<0.05). The incidence rate of hemorrhage was 12% in the intensive follow-up group and 28% in the regular follow-up group (χ2=4.000, P<0.05). Conclusions With the function of propaganda, education, supervision, promotion and attention on patients, follow-up visit makes patients taking Warfarin receive normative, effective anticoagulant treatment and improves the safety of medicine use, thus the effect of preventing stroke can be achieved. Key words: Atrial fibrillation; Intensive follow-up visit; Anticoagulant therapy; Warfarin

Impact of left atrium size on left atrial thrombus in patients with non-valvular persistent atrial fibrillation

This study sought to investigate the impact of left atrium size on left atrial (LA) thrombus in patients with non-valvular persistent atrial fibrillation (AF). In a prospectively established database, patients with AF underwent transesophageal echocardiography prior to AF ablation were screened from January 2007 to June 2010. Exclusive criteria included paroxysmal AF, vavular AF, deep vein thrombus, pulmonary embolism, on warfarin, redo procedure. Of 1 524 patients, 367 patients (male 267, female 100) with age 26-89 (mean 56±11) were enrolled. The patients were divided into LA thrombus group and non-thrombus group. Receptor-operating curves were used to test the value of CHA2DS2Vasc score and LA diameter predicting LA thrombus. Logistic analysis were used to find the independent predictor of LA thrombus. Thirty-two (8.7%) patients had LA thrombus. The LA diameter, left ventricular end diastolic diameter, left ventricular end systolic diameter were significantly larger in thrombus group than non-thrombus group. Left ventricular ejection fraction was significantly lower in thrombus group than non-thrombus group. CHA2DS2Vasc score did not differ between the two groups. The area under the receptor-operating curve for LA diameter predicting LA thrombus was 0.656 (0.563-0.750), the best cut-off point was 42.5 mm. The incidence of LA thrombus was significantly higher in patients with LA diameter≥42.5 mm than those with LA<42.5 mm (14.0% vs. 5.1%, χ2=8.888, P=0.003). In univariate analysis, LA diameter≥42.5 mm increased the risk of LA thrombus with odds ratio 3.05 (95% confidence interval 1.42-6.53, P=0.004. The sensitivity and specificity of LA diameter≥42.5 mm in predicting LA thrombus were 67.7% and 61.5%, respectively. In multivariate analysis, after adjustment of CHA2DS2Vasc score, left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular ejection fraction, LA diameter≥42.5 mm was an independent risk factor of LA thrombus (odds ratio 2.77, 95% confidence interval 1.17-6.57, P=0.021). LA enlargement is an independent risk factor of LA thrombus in patients with non-vavular persistent AF.

Проґнозування тривалого утримання синусового ритму після кардіоверсії у пацієнтів з неклапанною персистентною фібриляцією передсердь

Проґнозування тривалого утримання синусового ритму після кардіоверсії у пацієнтів з неклапанною персистентною фібриляцією передсердь

The Measure of Plasma Concentrations Is Crucial in Managing Dabigatran Treatment in Non-Valvular Atrial Fibrillation

One of the most popular features utilized to promote direct oral anticoagulants diffusion in stroke prevention in non-valvular atrial fibrillation is that these drugs do not require monitoring of their anticoagulant activity or plasma level measurements. We believe that there are clinical scenarios in which monitoring can help guide clinical management. Here we describe a clinical case in which close monitoring of thrombin inhibitor dabigatran peak plasma levels helped in maintaining the patient drug administration schedule, despite the interference of mirabegron, a beta-3 adrenergic agonist, utilized for the symptomatic treatment overactive bladder (OAB) syndrome, and of amiodarone, an effective and commonly prescribed antiarrhythmic drug. These P-glycoprotein (P-gp) inhibitors drugs may increase the blood levels and effects of dabigatran. Combining these medications may increase the risk of bleeding complications and anemia, especially when associated to mild to moderate renal insufficiency.Dabigatran etexilate is a pro-drug that has a low (3%-7%) bioavailability. Once dabigatran etexilate is absorbed, the pro-drug is hydrolyzed to the active drug, dabigatran, by carboxylesterases in the bloodstream. Dabigatran etexilate is a substrate of the efflux transporter P-gp, but dabigatran, the active drug, is not. P-gp is present on the luminal side of absorptive cells in the small intestine and takes drug molecules from the cell cytoplasm and transports them back into the intestinal lumen for excretion. An inhibitor of P-gp, as mirabegron or amiodarone, will increase bioavailability of a P-gp substrate by reducing drug efflux.Our patients suffers from persistent non-valvular atrial fibrillation, complicated by ischemic stroke. He has been assigned a dabigatran 150 mg b.i.d. treatment in may 2014. His creatinine clearance was 75 mL/min. One month later, due to OAB syndrome, he started mirabegron, a drug which might potentially increase the risk of bleeding and which generally causes to stop dabigatran administration. We decided instead to set up a monitoring plan, utilizing plasma-diluted thrombin time to measure dabigatran concentrations. Calibration material consisted of pooled normal plasma with known quantities of dabigatran. By using this calibration material, we constructed a dose-response curve ranging from 0 to 500 ng/mL of dabigatran. An examination of the published literature of the pharmacology of dabigatran indicated that the expected peak steady-state concentration of dabigatran in patients with atrial fibrillation (150 mg, 2 times daily) was approximately 180 ng/mL with a trough of approximately 90 ng/mL (12 hours after last dose).After 4 weeks of mirabegron administration, dabigatran plasma trough level of our patient was 126.4 ng/mL. We therefore decided not to modify the 150 mg b.i.d. treatment.Three weeks later, patient suffered from acute cardiac failure associated to a creatinine clearance reduction to 41 mL/min. As a consequence, mirabegron treatment was stopped. At this point, dabigatran plasma trough level was 148.6 ng/mL. Again, we decided not to modify the 150 mg b.i.d. treatment.Six weeks later, due to an elevated cardiac rate (140/min) a treatment with 300 mg o.d. of amiodarone was started. A week later dabigatran plasma trough level was 219.6 ng/mL, with a creatinine clearance of 58mL/min. We decided then to reduce the administration of dabigatran to 110 mg twice daily.After two weeks, dabigatran plasma trough level lowered to 120.2 ng/mL.Our patient is still on dabigatran treatment which has so far never been stopped.At this time, studies addressing the correlation of dabigatran concentration with risk of bleeding (overdose) or breakthrough thrombosis (underdosing) are unavailable. The lack of such studies currently limits the predictive power of the plasma-diluted thrombin time to determine hemorrhage/thrombosis risk. However, we believe that in situations like our patient’s the adoption of this assay would be a valuable tool to aid adjusting dabigatran treatment. With access to appropriate pharmacodynamic and pharmacokinetic data and relevant calibration material, the plasma–diluted thrombin time assay can easily be applied for use in the monitoring dabigatran etexilate. DisclosuresNo relevant conflicts of interest to declare.

Left Atrial Appendage Percutaneous Closure with Watchman Device: Single Centre Experience and a Review of Literature

Background: Left Atrial Appendage (LAA) is the main source of left atrial thrombi causing embolic strokes in patients with Non Valvular Atrial Fibrillation (NVAF). Since many patients carry contraindications to Oral Anticoagulation (OAC), percutaneous devices for closure of LAA have been introduced, to avoid peripheral thromboembolism in absence of OAC. Methods: From March 2012 to March 2014 we enrolled patients which had permanent and persistent NVAF and high thromboembolic risk with absolute contraindication to OAC. They were subjected to insertion of Boston Scientific Watchman device in LAA under transesophageal and fluoroscopic guide, with continuous heparin administration to maintain constant activated clotting time (ACT) of 300-350 sec and under general anesthesia. Patients were discharged with indication to double antiplatelet therapy with Aspirin and Clopidogrel for 6 months and Aspirin thereafter, avoiding Warfarin at all. Follow-up Transesophageal Echocardiography (TEE) was performed 2 months, six months and 12 months after implantation. Results: We enrolled 21 patients, aging 49 to 80 yrs. (mean 67.61± 8.2), with high thromboembolic risk (CHADsVasc 3.23 ± 1.33), and with different contraindications to OAC, in most cases due to severe bleeding risk and difficulty in keeping stable INR values (HASBLED 3 ± 1.09). The mean size of the device implanted was 24.75 ± 2.56 mm, the mean total procedure time was 67.78 ± 18 min, the mean fluoroscopy time was 16.81 ± 2.53 min. In all cases LAA was successfully occluded at first TEE, performed within 2 months from the procedure, while we noticed a trend towards development of non-pathological leaks in the next control TEEs, with patients always free from embolic events at mean follow-up of 13.09 ± 6.04 months. Moreover, we noticed a trend towards reduction of left atrial spontaneous echo contrast after LAA closure. Conclusion: Percutaneous LAA closure followed by administration of DAPT appears to be safe and effective at mid-term follow-up in patients with absolute contraindications to OAC. Long term safety and efficacy will be demonstrated with longer follow-up and with more patients enrolled.

Relation of Low Vitamin D to Nonvalvular Persistent Atrial Fibrillation in Chinese Patients

Low vitamin D status has been associated with increased risk of cardiovascular disease. Atrial fibrillation (AF) is the most common cardiac arrhythmia. We evaluated the association between low vitamin D and AF. We analyzed data from 162 Chinese patients with nonvalvular persistent AF and no other cardiovascular disease whose serum 25-hydroxyvitamin D [25(OH)D] levels were measured in our hospital (AF group). Healthy subjects without AF who underwent health screening at our hospital served as controls (non-AF group, n = 160). 25(OH)D was measured by chemiluminescence assay. The serum 25(OH)D level was significantly lower in the AF group than in the non-AF group (18.5 ± 10.3 vs 21.4 ± 10.7 ng/mL, P < 0.05). The high-sensitivity C-reactive protein (hsCRP) level was significantly higher in the AF group than in the non-AF group (0.35 ± 0.19 vs 0.2 ± 0.17 mg/dL, P < 0.01). The average left atrial diameter was significantly larger in the AF group than in the non-AF group (P < 0.01). The serum 25(OH)D level showed a negative correlation with left atrial diameter, hsCRP level, and pulmonary artery systolic pressure. Logistic regression analysis identified that 25(OH)D was related to AF. Patients whose vitamin D levels were in the lowest 25(OH)D category (<20 ng/mL) were more often in the AF group, with their incidence about twofold higher than those in the highest 25(OH)D category (>30 ng/mL). Low vitamin D levels are associated with AF. It may be involved in its development.

Prevalence, morphologic characteristic and predictors of organization of atrial auricle thrombi four weeks after anticoagulant preparation to scheduled electrical cardioversion of atrial fibrillation.

Goal: to study thrombosis prevalence and predictors of thrombi organization in atrial auricles in persistent non-valvular atrial fibrillation (NVAF) in patients undergoing transesophageal echocardiography (TEE) 4 weeks after oral anticoagulant therapy (OAC). Materials and methods: a total of 133 consecutive patients with NVAF, who underwent TЕE before electrical cardioversion (ECV) were included in the study. Results: The mean age of the participants was 60,3±0,9 years, 95 (71,4%) were men. The mean term of the last AF episode was 6,5±0,6 months. Duration of AF less than 1 year was in 47 (35,3%) patients, from 1 to 5 years – in у 61 (45,8%) patients, over 5 years – in 25 (18,8%) patients. 14 (10,5%) patients had underlying coronary artery disease (CAD), 84 (63,2%) patients had arterial hypertension, 31 (23,3%) had both CAD and arterial hypertension, 4 (3,0%) had cardiomyopathy, 80 (60,2%) were obese. NYHA I FC of heart failure (HF) was diagnozed in 8 (6,0%) patients, II FC – in 94 (70,7%) patients and III FC – in 31 (23,3%) patients. GFR > 90 ml/min/1,73m² was in 9 (6,8%) patients, in 74 (55,6%) it was decreased to 60-89 ml/min/1,73m², in 50 (37,6%) patients GFR was 30-59 ml/min/1,73m². In stratification of risk of thromboembolism complications (TEC) 91 (68,4%) fell into the high-risk group with the CHA2DS2-VASc score ≥ 2, 32 (24,1%) patients were in the moderate-risk group and 10 (7,5%) had CHA2DS2-VASc score 0. TEE was performed in all patients 4 weeks after effective OAC therapy. In 40 (37,6%) patients thrombi were detected in the left atrial auricle and in 26 (65,0%) patients they were organized. In 10 (7,5%) patients thrombis were detected in right atrial auricles and in 7 (70,0%) patients they were organized. In 63 (47,4%) patients thrombi were found in both atrial auricles and in 25 (39,7%) patients they were organized. Correlation was found between detection of non-organized thrombi, duration of AF less than 1 year and increase of total cholesterol. Thrombus organization was assotiated with AF duration more than 1 year. Conclusions: Clinical predictors linked with detection of non-organized atrial auricles thrombi in NVAF patients 4 weeks after OAC therapy are duration of AF less than 1 year, increase of total cholesterol, while thrombi organization is assotiated with AF duration more than 1 year.

Inflammation was involved in the thrombosis of left atrium in patients with atrial fibrillation

Purpose: We tried to find out if inflammation was related to the thrombosis of left auricle in patients with persistent atrial fibrillation (AF). Methods: 158 Consecutive inward patients with persistent non-valvular AF undergoing catheter ablation (RFCA) during 2009 were enrolled. Transesophageal echocardiography (TEE), echocardiography and blood sample collecting for hsCRP and TNF-αtesting had been carried out. Patients were separated into thrombosis or control group according to the result of TEE. 10 patients with persistent AF and left atrial appendage thrombus undergoing cardiac surgery were enrolled too. Tissue of left and right atrial appendages was cut intraoperation for western blot, real time PCR (RT-PCR) and inmunohistochemistry (ICH) analysis of TNF-α. Result: 31 patients (21.3%) were found thrombus in left auricle while 3 (1.9%) in right auricle and 2 (1.3%) in both. Totally 36 patients were enrolled into study group. The Left atrial diameter (LAD) and right atrial diameter (RAD) were greater in the study group (46.42±6.05 vs. 39.68±5.77mm, P=0.000; 56.08±8.04 vs. 51.92±6.80mm, P=0.002). Serum concentration of hsCRP and TNF-αincreased in the study group too (4.80±2.23 vs. 2.36±1.03 (mg/L), P=0.000; 9.87±3.33 vs. 5.23±2.14 (ng/ml), P=0.000). Levels of hsCRP and TNF-α were positively correlate to LAD (r=0.618 and r=0.596 separately, P<0.01). Western blot, ICH and RT-PCR analysis showed that the protein and mRNA expression of TNF-αupregulated in left auricular appendage tissue (0.765±0.483 vs. 0.428±0.156, P=0.000; 0.094±0.020 vs. 0.027±0.021, P=0.000; 0.137±0.029 vs. 0.111±0.023, P=0.043 respectively). ![Figure][1] Protein expression of TNF-α Conclusion: Inflammation and atrial structure remodeling play important role in thrombosis of auricle in patients with persistent AF. [1]: pending:yes

Cardio-vascular risk in patients with non-valvular persisting atrial fibrillation

Results of cardiovascular risk factors assessment of 133 patients with persisting non-valvular atrial fibrillation (AF) (main group) being admitted for electrical cardioversion performance and comparison of these risk factors with cardiovascular risk profile of 6535 AF patients from Cohort 1 of the international GARFIELD registry (group of comparison) are revealed in the article. Patients in the main group were older than 65 years (33,8%), in European population of GARFIELD registry the majority of patients older than 65 years – 73,8%; p<0,001. There were more women in European population of GARFIELD registry in comparison with our patients (44,8% vs 28,6%; р<0,001 ). With regard to co-morbidity characteristics, patients in our study had higher BMI ( 31,9 ± 5,7 vs 28,5 ± 5,2 ; p<0,001 ) , hypercholesterolaemia (72,9% vs 46,1%; p<0,001), moderate renal dysfunction (GFR 30-59 mL/min) (36,8% vs 12,1%; p<0,001) and alcohol abuse (6,8% vs 1,1% ) . Number of patients with the risk of thromboembolism complications (TEC) ≥ 2 score by CHA2DS2-VASc was higher in European population of GARFIELD registry ( 86,0% vs 68,4%, <0,001), that is explained by prevalence of elderly patients in this group. The use of oral anticoagulants for thromboembolism prevention in high risk patients was low in both groups (approximately 70,0%), a large majority of patients in both groups were not treated effectively (64,1% vs. 55%, p = 0,148). Prevalence of TEC in case-history was similar in both groups (11,4% vs 15,9%, p = 0,141). So in our study patients with persistent non-valvular AF are characterized by higher cardiovascular risk in younger age in comparison with European population of AF patients from GARFIELD registry. For identification of “truly low-risk” patients with TEC, further improvement of risk stratification is required.

Percutaneous left atrial appendage closure after resolution of left atrial appendage thrombi with dabigatran

The "gold standard" of the prevention of atrial fibrillation related thromboembolic events is anticoagulation therapy with oral vitamin K antagonists. A certain proportion of high-risk patients with atrial fibrillation are not receiving effective antithrombotic therapy because of problems associated with its use. Resolution of subsequent left atrial appendage thrombi is quite a great challenge in patients who are not tolerating "standard" antithrombotic drugs. According to the knowledge of the authors, this is the first report of a patient with non-valvular persistent atrial fibrillation and high stroke risk, who was intolerant to "standard" anticoagulant therapy and had persistent left atrial appendage thrombi following the use of a wide variety of "standard" anticoagulants. Successful resolution of left atrial appendage thrombi with dabigatran and successful percutaneous left atrial appendage closure were performed in this case.

COMPARISON OF DIRECT COSTS OF DABIGATRAN AND WARFARIN THERAPY IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION DURING PREPARATION FOR ELECTIVE CARDIOVERSION IN THE REAL CLINICAL PRACTICE

Aim. To compare direct medical costs of dabigatran and warfarin therapy in patients with non-valvular atrial fibrillation (NVAF) during preparation for elective cardioversion. Material and methods. An open non-randomized study was conducted to evaluate direct medical costs (cost of drug, cost of the international normalized ratio (INR) adjust- ment in outpatient clinic, cost of visits to cardiologist). Patients (n=62) with persistent NVAF (AF paroxysm duration &gt; 48 hours) were enrolled. All of them requested medical as- sistance and were decided to perform an elective cardioversion. The patients received warfarin (n=32) or dabigatran (n=30). The patients of the both groups were similar in the main clinical characteristics and thromboembolic risk levels according to CHA2DS2-VASc scale. Results. Treatment duration before elective cardioversion was 21±2 and 30.5±4.5 days for dabigatran and warfarin groups, respectively (p&lt;0.05). Average costs of visits to cardiologists were 3,720 and 744 RUB in warfarin and dabigatran groups, respectively (p&lt;0.05), and drug costs were 53.63 and 1,172.01 RUB, respectively (p&lt;0.05). The costs of laboratory INR monitoring were 3,058 RUB in warfarin group. Total costs per patient were 6,831.63 and 1,916.01 RUB in warfarin and dabigatran groups, respectively (p&lt;0.05). Conclusion. In the real clinical practice in patients with NVAF dabigatran antithromboembolic therapy substantially reduces direct medical costs in comparison with warfarin ther- apy during preparation for elective cardioversion. Dabigatran therapy reduces time from the decision of elective cardioversion and antithromboembolic therapy start to car- dioversion performance.

Complex questions command complex analyses: comparative effectiveness of drug treatment strategies in atrial fibrillation

Among the randomized clinical trials (RCTs) comparing rhythm- with ratecontrol trials conducted in the past 10 years [3–7], the AFFIRM trial is regarded as the most important, owing to its large sample size (4060 participants) and long follow-up (up to 6 years) [7]. Overall, the AFFIRM study showed that the strategy of restoring and maintaining sinus rhythm had no clear advantage in reducing overall mortality over the strategy of controlling the ventricular rate and allowing the AF to persist [7]. This conclusion held after combining the results of AFFIRM [7], and four other smaller trials [3–6], in a single meta-ana lysis estimate (OR: 0.87; 95% CI: 0.74–1.02 vs 1.12; 95% CI: 0.64–1.94 in the pooled ana lysis that included/excluded the AFFIRM trial) [8]. However, many clinicians feel uncomfortable with the rate-control strategy as the main therapeutic approach for AF. For some, the trial results do not mean that the rhythm control is not beneficial, but merely highlight the limitations of the current treatments to achieve and maintain sinus rhythm [9], while others believe the trial results are not generalizable to the full population of AF patients [8]. Such a conundrum demands more evidence through comparative effectiveness studies. To our knowledge, our group has published the first observational comparative effectiveness study of rhythm- versus rate-control drug strategies, published in July 2012 [10]. In this study, we used population-based administrative databases from Quebec (Canada) from 1999 to 2007 to select patients aged ≥66 years, hospitalized with an AF diagnosis who did not have AF-related drug prescriptions in the year before the admission, but received a prescription within 7 days of discharge. The study included 30,664 hospitalized AF patients who were followed-up for up to 8 years and, similar to the trials [7,8], found no difference in mortality between the rhythm- and rate-control drug treatment strategies in the first 3 - years post-treatment initiation. However, our long-term results differed from those of the clinical trials [7,8]; while the AFFIRM trial found no mortality difference at 5 years between the rhythm- and rate-control strategies [7], we found a significant 12% mortality reduction in the rhythm-control group found after 5 years of follow-up and a significant 23% reduc tion after 8 years. In the face of contradictory results between observational studies and RCTs trials, the observational design is oftentimes dismissed as being flawed due to poor control of confounding. We argue here, as others have done before us [11,12], that RCTs and observational studies are complementary designs and that much can be learned by examining results from different study designs and analyses [13,14]. Bias, due to unobserved confounding, is the Achilles’ heel of observational studies of drug effects [15–20], with lack of randomization being a particular concern in studies