Number Of Atrial Fibrillation Episodes Research Articles

Atrial fibrillation is perpetuated by human heart secretome in ex-vivo langendorff-perfused hearts

Abstract Introduction Atrial fibrillation (AF) confers high morbidity and mortality, yet parts of the underlying pathophysiology remain elusive. Left atrial (LA) pressure is altered by the presence of AF and vice-versa. The cardiac secretome might be influenced by LA pressure and potentially alters the susceptibility of the atria to AF. We investigated the effect of the human cardiac secretome on atrial electrophysiology in a translational ex-vivo setting. Methods We obtained venous (coronary sinus) serum samples during AF and in sinus rhythm (SR) in patients hospitalized for pulmonary vein isolation (PVI). Moreover, LA tissue was collected from patients undergoing cardiac surgery and coronary sinus serum samples were collected before (CTRL) and after intraoperative volume challenge (VC). Single cardiomyocytes were isolated from human LA tissue and Ca2+ dependent excitation-contraction coupling (ECC) was studied using confocal line-scan imaging with CTRL or VC. Moreover, a modified Langendorff-Setup with the ability to monitor and control intra-cardiac pressure was utilized to perfuse mouse hearts with AF and SR serum. A multielectrode array (MEA) was placed on the epicardial aspect of the left atrium to measure electrical signals in a spatiotemporal fashion. External bipolar burst pacing protocols were applied to test AF inducibility. Results Ca2+ dependent ECC (i.e. Ca2+ amplitude and release) in human cardiomyocytes was unaltered with exposure to VC serum. Upon introducing a modified version of the Langendorff setup with the ability of linear pressure adjustment, a burst pacing protocol to test for AF inducibility was successfully implemented in mice atria. Atria perfused with human AF serum showed significantly increased AF inducibility as compared to SR serum. Moreover, both, total AF duration as well as number of AF episodes (i.e. AF burden) were increased in AF vs. SR serum upon several different pacing protocols. Conclusion Cardiac secretome during increased LA pressure had no significant effect on Ca2+ dependent ECC in human cardiomyocytes. However, secretome during AF conferred pro-arrhythmogenic properties as compared to SR, further strengthening the concept of "AF begets AF". Ongoing experiments test the hypothesis of potential differences in the multi-level omics profile of AF serum as the underlying mechanism.

Impact of sodium-glucose cotransporter-2 (SLGT2) inhibitors treatment initiation on the reduction of atrial and ventricular arrhythmias in patients with implanted cardiac devices

Abstract Introduction Sodium-glucose cotransporter-2 (SLGT2) inhibitors have demonstrated benefits on survival and hospital admissions in patients with heart failure and reduced ejection fraction. However, their impact on the burden of ventricular (VA) and atrial arrhythmias (AA) is unknown. Methods Retrospective multicentric study of heart failure patients with implantable cardiac defibrillator device (ICD) from 2015 to 2020 with or without cardiac resynchronization therapy (CRT) receiving SGLT2 inhibitors. Device-registered arrhythmic events were analyzed and compared during one year following SLGT2 inhibitor initiation and during one year before initiation. Relevant VA were defined as the occurrence of any sustained VT (SVT) (>30 seconds), ventricular fibrillation (VF), or appropriate therapy (antytachycardia pacing or shock). All VA included all the relevant VA and the occurrence of non-sustained ventricular tachycardia (NSVT). AA included atrial fibrillation (AF) burden, and episodes of more than 24 hour of AF. Results 147 patients (67 ± 10 years, 82.3% males, LVEF 30.3 ± 11%, CRT 39.3%), were included in the study. 77.6% had complete remote tele-monitoring during the entire follow up and there was no difference in the antiarrhythmic therapy between the two periods. Following SGLT2 inhibitor initiation, there was a significant reduction in the percentage of patients with relevant VA (19.7% pre vs 10.9% post; p=0.019) and all VA (47.6% pre vs 30.6% post; p<0.001) (Figure 1 and 2). There was a reduction in the prevalence of NSVT (40.1% pre vs. 27.2% post; p<0.001), of SVT (17.7% vs 8.8%; p<0.001), of VF (4.1% vs 2%; p=NS) and appropriate therapies (14.3% vs 9.5%; p=NS). Among patients with any VA, there was a significant reduction in the incidence of NSVT (p<0.001), but not in the incidence of SVT or appropriate therapies (p=NS). There was no impact on atrial fibrillation burden or in the number of AF episodes lasting more than 24 hours (p=NS). Conclusions In our study, initiation of a SGLT2 inhibitor in patients with heart failure, was associated with a reduction in the prevalence of relevant VA and any VA, with a significant reduction in the number of NSVT per patient. There was no impact on AF burden or the number of AF episodes lasting more than 24 hours. Prospective studies should be performed to sustain these conclusions.Relevant ventricular arrhythmiasAny ventricular arrhythmia

Detection of Atrial Fibrillation Using Insertable Cardiac Monitors in Patients With Cryptogenic Stroke in Japan (the LOOK Study): Protocol for a Prospective Multicenter Observational Study

Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. DERR1-10.2196/39307.

Usefulness of P-wave duration in patients with sick sinus syndrome as a predictor of atrial fibrillation.

BackgroundThis study aimed to clarify P‐wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure.MethodsWe retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day.ResultsIn the study population, 17 patients (23%) had worsening AF burden during the follow‐up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352‐21.523; P = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II <108 ms showed a significantly higher event‐free rate against worsening AF burden than those with PWD in lead II ≥108 ms (81% vs 9%, P = .005).ConclusionsProlonged PWD before pacemaker implantation was the most important independent predictor of worsening AF burden after the procedure. In patients with SSS, prolonged PWD can be a useful marker for predicting worsening of AF burden after pacemaker implantation.

Atrial fibrillation burden, episode duration and frequency in relation to quality of life in patients with implantable cardiac monitor.

To assess the relation between atrial fibrillation (AF) characteristics and health-related quality of life (QoL), and which AF characteristic had the greatest impact. The AF characteristics burden (percentage of time in AF), duration and number of AF episodes/month were obtained from implantable cardiac monitors during the 2-month run-in period in 150 patients included in the randomized CAPTAF trial comparing early ablation and antiarrhythmic drug therapy. The QoL was measured by the General Health and Vitality dimensions of the 36-Item Short-Form Health Survey. AF characteristics were analysed continuously and in quartiles (Q1-Q4). Greater AF burden (p=0.003) and longer AF episodes (p=0.013) were associated with impaired QoL (Vitality score only) in simple linear regression analyses. Greater AF burden was, however, the only AF characteristic associated with lower QoL, when adjusted for sex, type of AF, hypertension, heart rate above 110 beats per minute during AF, and beta-blocker use in multiple linear regression analyses. For every 10% increase in AF burden there was a 1.34-point decrease of Vitality score (95% confidence interval (CI) -2.67 to -0.02, p=0.047). The Vitality score was 12 points lower (95% CI -22.73 to -1.27, p=0.03) in patients with an AF burden>33% (Q4) versus those with<0.45% (Q1), but only in unadjusted analysis. AF burden had a greater impact on QoL (Vitality), than the duration and number of AF episodes, corroborating that AF burden may be the preferred outcome measure of rhythm control in trials including relatively healthy AF populations.

Effect of Perindopril on Atrial Fibrillation Recurrence and Burden: Results of the Canadian Trial of Atrial Fibrillation (CTAF)-2

BackgroundHypertension is a risk factor for the development and exacerbation of atrial fibrillation (AF). Angiotensin-converting enzyme inhibitors are a standard-of-care treatment option for patients with hypertension; however, there is conflicting evidence about their effects on AF recurrence. Therefore, our objective was to assess the efficacy of perindopril, compared with placebo, to reduce AF recurrence in patients with hypertension and AF. MethodsIn a multicenter, double-blind, placebo-controlled trial, patients with hypertension and symptomatic AF were randomly assigned (1:1) to perindopril or placebo based on a stratification factor of antiarrhythmic drug use. Patients with terminated AF were followed up from 30 days after randomization to 7 to 13 months. The primary endpoint was AF recurrence. Secondary endpoints included AF hospitalization, cardioversion, and blood pressure control. Recurrent events, AF burden, and safety endpoints were also investigated. ResultsA total of 315 patients were randomly assigned, and 301 patients were included in the modified intent-to-treat analysis (155 vs 146 patients in the perindopril and placebo groups, respectively). The mean follow-up was 336 ± 70 days, and 91.1% of patients were compliant to the treatment medication throughout the study. After adjustment for baseline antiarrhythmic drugs, there was no statistically significant difference in the hazards of AF recurrence (hazard ratio, 1.22; 95% confidence interval, 0.92-1.61), with similar blood pressure. The incidence of secondary endpoints and adverse events also did not differ between treatment arms. ConclusionsPerindopril does not reduce recurrence or the number of AF episodes in patients with hypertension and AF.

Role of intermediate-conductance calcium-activated potassium channels in atrial fibrillation in canines with rapid atrial pacing.

The aim of the present study was to explore the role of intermediate-conductance Ca2+-activated K+ (SK4) in atrial fibrillation (AF) inducibility in canines with rapid atrial pacing. Eighteen dogs were divided into the control group, the pacing group and the stellate ganglion ablation (SGA) + pacing group. In the pacing group, dogs were subjected to rapid atrial pacing, and the atrial effective refractory period (AERP) and AF inducibility were measured. After cessation of 7-h pacing, SK4 inhibitor (TRAM-34) was administered. After SGA, the SGA + pacing group received the same procedure of pacing and electrophysiological measurement as the pacing group. The expression of SK4 was measured in the left atrium (LA) and the right atrium (RA) in the three groups. The duration of the AERP decreased, while the number of AF episodes, the duration of induced AF, and the amplitude of stellate ganglion neural activity all increased after rapid atrial pacing. TRAM-34 completely inhibited AF induction in the pacing group. There was no significant difference in AERP shortening or AF vulnerability between the SGA + pacing group and the control group. The expression of SK4 in the LA and RA was higher in the pacing group than in the control and SGA + pacing groups. However, there was no significant difference in the expression of SK4 in the LA or the RA between the SGA + pacing group and the control group. The higher expression of SK4 plays an important role in AF induction and the increased expression of SK4 in the atrium is related to SG activity during rapid atrial pacing.

P345Catheter ablation for atrial fibrillation is associated with lower incidence of stroke, major bleeding and death: data from Korean health registries

Abstract Background Compared with antiarrhythmic drug therapy, catheter ablation of AF reduces the number of AF episodes, prolongs the time in sinus rhythm, and improves quality of life. However, it is still unclear if catheter ablation for atrial fibrillation (AF) affects the prognosis or merely is a symptomatic treatment. Our objective was to compare long-term outcome regarding stroke, major bleeding and death in AF patients with and without ablation, and in relation to long-term exposure to anticoagulants. Methods We identified all 800,084 patients with a diagnosis of AF from 2006 to 2015 in the Korean national health insurance service database. During a 10-year period, 10,979 AF ablations were performed among 9,768 individuals. Propensity scores for the likelihood of AF ablation were obtained by logistic regression. Propensity score (PS) matching was used to construct two cohorts of equal size (n=9,768) with similar characteristics in 16 dimensions. Results Patients who had undergone catheter ablation were younger (57.2 vs. 65.6 years, P&lt;0.001) and healthier (mean CHA2DS2-VASc scores 2.5±1.7 vs. 3.6±2.1, P&lt;0.001) than other patients with AF. Mean follow-up was 5.5±3.1 years. After propensity score matching, in the ablated group, 472 patients suffered ischemic stroke/systemic embolism (SE) compared with 1,682 in the matched non-ablated (annual rates 2.92 vs. 1.10%, P&lt;0.001). Major bleeding occurred in 439 and 1,219 patients in ablated and non-ablated (annual rates 2.07 vs. 1.01%, P&lt;0.001). A total of 306 ablated and 1,439 non-ablated patients died (annual rates 2.31 vs. 0.69%, P&lt;0.001). After multivariable adjustments, catheter ablation was associated with lower risk of ischemic stroke [hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.38–0.67), lower risk of major bleeding (HR 0.65, 95% CI 0.57–0.75) and with lower mortality risk (HR 0.39, 95% CI 0.34–0.46). The reduction of stroke/SE and mortality was observed after AF ablation regardless thromboembolic risk. Major bleeding was reduced only among patients with CHA2DS2-VASc score ≥2 (HR 0.70, 95% CI 0.59–0.84). Conclusion We found a strong association between ablation and survival. Ablation may be associated with lower incidence of ischemic stroke and major bleeding in patients with AF. The reduction of stroke/SE and mortality was observed regardless thromboembolic risk after AF ablation. But the risk of major bleeding was reduced only in patients with high thromboembolic risk factors.

527Myocardial fibrosis is a predictor of atrial fibrillation in dilated cardiomyopathy- role of cardiovascular magnetic resonance

Methods 44 consecutive pts (38±11 years-old, 29 men) with DCM were included, after exclusion of ischemic heart disease (coronary angiography), secondary cardiomyopathies (clinical and laboratory investigation), non-sinus rhythm and contraindications to CMR. Functional class and plasmatic NT-pro-BNP were assessed. All pts underwent CMR: a) short-axis SSFP for left atrial area and left ventricle (LV) volumes and ejection fraction (EF); b) LGE (segmented inversion-recovery fast gradient-echo sequence), 10-15 mn after 0.2mmol/kg of Gd-DTPA acquired in long-axis and short-axis views; LGE was classified as subendocardial or midwall and quantified using plannimetry of LGE contours, 6SD from remote myocardium; a fibrosis index was obtained from LGE volume/myocardial volume. All underwent 24-hours Holter monitoring, less than one month from CMR, and the number of atrial fibrillation episodes was assessed. Results 26 pts were in NYHA class II and 18 in class III. Mean NT-pro-BNP was 551±180pg/ml, atrial area was 35.8±11.0 cm2, LV end-diastolic volume was 155 ±44mL/m2, mean EF was 33±8%. LGE was found in 29 patients (69%) located in midwall, involving a mean of 7 segments per pt (range 3-14). Holter monitoring showed AF episodes in 26 pts. In comparison with pts without AF, pts with AF had higher NT-pro-BNP (836±110 vs 474±132 pg/ml, p=0.01), larger atrial area (44.1±10.1 vs 31.2±9,2 cm2, p=0.002), larger LV end-diastolic volumes (172±31 vs 153±35ml/m2, p=0.03) and more frequent LGE (p=0.0003). In pts with AF, no correlation was found between the functional class or the fibrosis index and the number of AF episodes. Using multivariate analysis, the atrial area and the presence of LGE were independent predictors of occurrence of AF episodes.

The pattern of 24-hour Holter ECG monitoring parameters and features of structural and functional state of the myocardium depending on aldosterone level in patients with arterial hypertension and frequent recurrences of atrial fibrillation

In recent times great attention of researchers has been focused on the heart electrical and structural remodeling features study in patients with atrial fibrillation (AF). First of all, the electrocardiography Holter monitoring (ECG HM) and echocardiography are used as methods for these changes assessment. Aim of the work – to estimate the features of heart rhythm disorders according to the ECG HM data and intracardiac hemodynamics features registered by echocardiography in patients with arterial hypertension (AH) and frequent recurrences of AF. Materials and methods. 146 patients with AH stage II were examined. 26 patients with AH stage II without AF were examined as a comparison group. Paroxysmal form of AF was in 56 (38.4 %) patients and persistent form of AF was in 90 (61.6 %) patients. The vagally induced variant of AF was determined in 31 (21.2 %) patients, the adrenal variant of AF in 70 (47.9 %) and mixed variant of AF in 45 (30.9 %). All patients underwent ECG HM and transthoracic echocardiography according to the standard protocol. The level of aldosterone in serum was determined by ELISA. The relatively low level of aldosterone (RLLA) was defined as 184 pg/ml, intermediate level of aldosterone (ILA) was 62–184 pg/ml. Based on the aldosterone levels, 3 groups of patients were identified: 1 – patients with RLLA (n = 37), 2 – with ILA (n = 72) and 3 – with RHLA (n = 37). Statistical analysis of the study was carried out using standard methods with the software package StatSoft Statistica v. 12.0. Results. The 24-hour heart rate (Р = 0.04) and circadian index (CI) (P = 0.03) were increased in the RHLA group in comparison with the RLLA group. The CI value was significantly higher in the ILA group in comparison with the RLLA group (P = 0.02). The part of supraventricular paroxysmal tachycardia (SVPT) episodes was significantly higher in the RHLA group in comparison with the ILA and RLLA groups (P = 0.05 and P = 0.04, respectively). The number of AF episodes registered throughout a 24-hour period was higher in patients with RHLA and ILA in comparison to the RLLA group of (P = 0.02 and P = 0.03, respectively). The total duration of these episodes throughout a 24-hour period was significantly higher in the RHLA group in comparison with the ILA and RLLA groups (P = 0.001 and P = 0.007, respectively). The number of patients with ventricular premature contractions (VPC) was significantly higher in the group with RHLA in comparison with the RLLA group (P = 0.009). The percentage of couplets and salvos VPC in the RHLA group was higher in comparison with the other patient groups (P = 0.05 and P = 0.04, respectively). The moderate mitral regurgitation was observed more frequently in the group with RHLA in comparison with the RLLA group (P = 0.02). The tricuspid regurgitation was observed more frequently in patients with RHLA in comparison with the ILA and RLLA groups (P = 0.01 and P = 0.02, respectively). The frequency of moderate tricuspid regurgitation was significantly higher in the RHLA group in comparison with the other patient groups the (P = 0.05 and P = 0.004, respectively). Conclusions. In patients with AH stage II and frequent recurrences of AF the RHLA (>184 pg/ml) is associated with the signs of atriums and ventricles increased electrical instability, characterized by higher 24-hour heart rate and CI; increased frequency of SVPT and AF episodes registration, number and total duration of AF episodes throughout a 24-hour period; increased frequency of VPC registration, including couplets and salvos VPC. In patients with AH stage II and frequent recurrences of AF the RHLA is associated with increased frequency of moderate mitral and tricuspid regurgitation registration.

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time.

Combination of&#x0D; omega-3 polyunsaturated fatty acids and statins for the prevention of atrial fibrillation after coronary bypass surgery

Aim. To evaluate the influence of combination of omega-3 polyunsaturated fatty acids and atorvastatin on the risk of atrial fibrillation (AF) after coronary bypass surgery (CBS). Material and methods. The study included 114 patients divided into 2 groups, one comprised of 59 ones (75,6% men of mean age 62,0±7,3 yr given conventional medication), the other including 55 patients (80,0% men of mean age 59,4±6,7 yr given omega-3 polyunsaturated fatty acids 5 days before (2 g/d) and during 3 weeks after CBS (1 g/d)). All patients were treated with atorvastatin at the outpatient stage. IL-6,8, 10 and C-reactive protein (CRP), fibrinogen, troponin, NT-proBNP, superoxide dismutase (SOD), and myeloperoxidase were measured at admittance and on day 3.7±1.4 after surgery. Results. AF developed on day 5.9±4.9 (mean) after surgery. Patients of group 2 tended to have fewer new episodes of arrhythmia although no significant difference between the groups was documented (9,1% vs 18,6%, р=0,12). Group 2 included more smokers (74,5% vs 45,8%, р=0,002) and patients with atherosclerosis of lower limb arteries (87,3% vs 71,2%, р=0,03) but fewer those consuming nitrates (39,0% vs 18,2%, р=0,01) and Ca antagonists (45,8% vs 21,8%, р=0,006).Mean dose of atorvastatin given to patients of groups 1 and 2 was 24.7±12.5 and 25.1±10.5 mg/d respectively (р=0,2), duration of its intake 14.6±12.7 and 21.5±19.3 months (р&lt;0,001). There. was no significant difference between leukocyte count, leukogram, IL-8, IL-10, NT-proBNP, and troponin levels before and after CBS. Surgical myocardial revascularization caused a rise in leukocyte count, shifted the leukogram toward predominance of stab and segmented cells, increased IL-8, IL-10, fibrinogen, NT-proBNP, CRP, and troponin levels in both groups. IL-8 and IL-10 levels remained normal before and after surgery. Preoperative IL-6 level in group 1 was significantly higher than in group 2 (21,7±13,0 vs 2.5±2,2 pg/ml, р&lt;0,001). Postoperatively, the difference was absent. The CRP level before surgery was high in both groups (3122.7±2175.8 vs 3670.8±2490.0 U/g) but decreased after CBS although remained higher in group 1 (1957.6±1660.3 vs 1069.8±630.2 U/g, р&lt;0,001). Myeloperoxidase level increased postoperatively in both groups but the difference was insignificant. Fibrinogen and CRP in the postoperative period increased more significantly in group 2 than in group 1 (4,9±1,4 vs 4,4±1,1 g/l, р=0,02 and 8,6±2,2 vs 5,4±2,3 mg/l respectively, р&lt;0,001). Conclusion. The study revealed an insignificant decrease in the number of AF episodes in the early post-CDS period in patients treated with omega-3 polyunsaturated fatty acids and atorvastatin compared with those given the latter medication alone. Also, fibrinogen and CRP levels as markers of inflammation increased while SOD antioxidative activity decreased.

Abstract 14729: Weight Loss Reduces Atrial Fibrillation Inducibility and Burden in Severe Obesity Induced by Either High-Fat Diet or Genetic Hyperphagia in Mice

Introduction: Atrial fibrillation (AF), the most common sustained arrhythmia worldwide, is associated with increased morbidity and mortality. Obesity is increasingly recognized as an important risk factor to develop AF and heart disease with a diet rich in fats leading to morbid obesity. Melanocortin-4 receptor (MC4R) gene is a critical regulator of energy homeostasis, and homozygous loss-of-function mutations cause hyperphagia and morbid obesity. Hypothesis: We hypothesized that obesity and its comorbidities can create a profibrillatory substrate for AF in high fat diet-induced obese (DIO) and MC4R knock-out (MC4R-KO) mice, and that this substrate can be reversed by weight loss. Methods: Transesophageal rapid pacing was performed using atrial burst pacing (cycle length: 50-15 ms, for 15 s) to determine AF inducibility (% of mice that develop AF) and AF burden (number of AF episodes and total AF duration/mouse) in lightly anesthesized normotensive mice (C57bl6 mice [LEAN], DIO, and MC4R-KO), with continuous ECG monitoring. Transthoracic echocardiography was performed to assess right (R) and left (L) atrial appendage (AA) sizes. Results: Atrial burst pacing induced AF in 91% of DIO and 100% of MC4R-KO vs. 50% of LEAN (P&lt;0.01, N=8 mice/group). Compared to LEAN, both DIO and MC4R-KO exhibited greater number of inducible AF episodes (0.7±0.2 vs. 1.8±0.2 vs. 1.8±0.1, P&lt;0.01, N=15 mice/group) with longer duration (17.9±3 vs. 196±22 vs. 244±34 s, P&lt;0.0001, N=15 mice/group; Figure). Both DIO and MC4R-KO had greater LAA volumes as compared with LEAN (5.2±0.2 vs. 6.7±0.4 vs. 4.1±0.1 μl, P&lt;0.01, N=8 mice/group). RAA volume was similar across groups. After 20% weight loss, both AF burden and LAA volumes were significantly reduced to those seen in LEAN (22±5 s, 4.5±0.1 μl, P&lt;0.001, N=8 mice/group). Conclusions: High-fat diet or genetic hyperphagia-induced obesity increases LAA volume and creates a profibrillatory substrate for AF that can be reversed with weight loss.

Can treatment with beta blockers trigger episodes of atrial fibrillation in healthy patients?

We present 2 patients with no cardiac history who were prescribed beta blockers for extracardiac disease. The first patient was a 47-yearold man who engaged in moderate aerobic sports 2– 3t imes aw eek, a musician by profession, who took 20 mg of propranolol every 12 h daily for treatment of emotional tremors. The second patient was a 55-year-old man recently diagnosed with mild mitral prolapse with no significant regurgitation but with symptoms of short sporadic palpitations attributed to low-density isolated supraventricular extrasystole detected with a Holter monitor, he was prescribed treatment with bisoprolol 5 mg daily for this condition. After a short treatment period (between 1 and 2 months), both patients experienced a first episode of atrial fibrillation and were highly symptomatic, with rapid palpitations, in both cases nocturnal and after a large dinner. In the emergency department, they were diagnosed with paroxysmal atrial fibrillation, which resolved spontaneously in one of the patients and after a 100mg oral dose of flecainide in the other. A complete cardiac study was performed, which ruled out potential cardiac or systemic triggers as causes of the atrial fibrillation. In the clinical follow-up, both patients presented similar recurrences a few weeks later of nocturnal episodes of rapid atrial fibrillation during sleep, which resolved after the oral ingestion of 200-mg flecainide. In both cases, use of flecainide 100 mg every 12 h was initiated after the clinical recurrence. However, rapid andprogressive clinicalworseningoccurred, witha continuousincrease in the number of atrial fibrillation episodes within a few weeks. These episodes were generally triggered in conditions of vagal predominance (postprandial, evenings, alcohol intake), were highly symptomatic and preceded by focal extrasystolic bigeminy (verified in Holter), with a periodicity of up to 6–7 episodes daily. In many cases, these episodes wereself-limitingto20–30min.Atothertimes,theepisodeswerepharmacologically cardioconverted with extra doses of oral flecainide a few hours after its start. Both patients were assessed in the cardiology department, and both cases were diagnosed as vagal focal atrial fibrillation due to the clinical characteristics. Beta-blocker treatment was discontinued and pulmonary vein ablation was scheduled. Three to 4 days after discontinuing the beta-blocker treatment, both patients had full remission of the symptoms; the procedure was therefore postponed.Afterremainingasymptomaticfor6months,thepatients'antiar

Abstract 12650: Unexpected Response to Atrial Fibrillation Reduction in Patients With Cardiac Resynchronization Therapy

Background: Cardiac resynchronization therapy (CRT) is known to improve left ventricular (LV) systolic function and symptoms of systolic heart failure. The effect of CRT on atrial fibrillation (AF) burden is less clarified. Methods: 18 patients mean age of 77 ± 11 (72% male) underwent CRT implantations. There were no changes to concomitant anti-arrhythmic medication and permanent AF patients were excluded. Echocardiograms were obtained six month before and after device implantation. LV ejection fraction (LVEF), LV end diastolic dimension (LVEDd), left atrial (LA) dimension, and magnitude of mitral regurgitation (MR) were measured by echocardiogram before and after CRT. The burden of AF was evaluated by 24-hour Holter monitoring before and by device arrhythmic log after implantation. There were no concomitant medication changes. The results were later divided into presence (Group I) and absence (Group II) of paroxysmal or persistent AF. No patient was in permanent AF at the time of CRT implantation. Results: LVEF improved after CRT in both groups. Patients with AF showed the most beneficial effects of LVEF with average improvement of 41% (P-value=0.004) in comparison to 13% improvement in patients without AF (P-value=0.044). The LVEDd was improved by 11.9% in patients with AF (P-value=0.01) while it was improved by only 5.6% in patients without AF (P-value=0.08). LA Dimension was decreased by 4.4% in patients with AF (P-value=0.038). MR was reduced on average from moderate to mild for both groups. The number of AF episodes and duration of the AF were also decreased in all of our AF patients. The pre and post effect of CRT in patients with and without AF is shown in the table below: Conclusions: The AF burden in patients who received CRT was significantly reduced. There were excellent correlations between improvement of LVEF, LVEDd, LA dimension, and AF burden. This may be due to LV and LA remodeling. Further studies need to elaborate the mechanisms of this finding.

Central sympathetic inhibition to reduce postablation atrial fibrillation recurrences in hypertensive patients: a randomized, controlled study.

The autonomic system is an important determinant of atrial arrhythmogenesis. Current evidence indicates that a combined sympathovagal drive is most commonly responsible for eliciting atrial fibrillation (AF) episodes. The purpose of this study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, can lead to a reduction in postablation AF recurrence. This was a prospective, double-blinded, randomized study of 291 hypertensive patients with symptomatic paroxysmal AF who were scheduled to undergo pulmonary vein isolation. Patients were randomly assigned to receive either moxonidine (0.2-0.4 mg daily) or placebo, along with standard antihypertensive treatment. No significant differences in blood pressure levels were observed between the 2 groups. In the primary outcome analysis, mean recurrence-free survival was 467 days (95% CI, 445-489 days) in the moxonidine group as compared with 409 days (95% CI, 381-437 days) in control subjects (log rank test, P=0.006). The calculated 12-month recurrence rate estimates were 36.9% in the control group and 20.0% in the moxonidine group (P=0.007). Moxonidine treatment was associated with lower recurrence risk after adjustment for age, body mass index, number of AF episodes in the previous year, and left atrial diameter (adjusted hazard ratio, 0.35 [95% CI, 0.22-0.55]; P<0.001). Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drug-refractory AF in patients with hypertension. The observed effect does not appear to depend on the antihypertensive action of this agent. http://www.clinicaltrials.gov. Unique identifier: NCT01791699.

Abstract 18444: Constitutive Expression of a Dominant Negative TGF-β Type II Receptor in the Posterior Left Atrium Interrupts Heart Failure Induced Conduction Changes, with a Resulting Decrease in Atrial Fibrillation

Introduction: Fibrosis is thought to be a key contributor to the conduction slowing and heterogeneity seen in the heart failure (HF) atrium, providing a substrate for atrial fibrillation (AF). Hypothesis: Since the TGF-β pathway contributes to the creation of atrial fibrosis, we hypothesized that decreasing TGF-β signaling in the HF posterior left atrium (PLA) by expressing a dominant-negative TGF-β type II receptor (TGF-β-II-DN) will, by attenuating formation of fibrosis, decrease conduction slowing and in-homogeneity and thereby decrease AF. Methods: 17 dogs underwent injection+electroporation in the PLA of either an HA-tagged plasmid expressing TGF-β-II-DN (pUBc-TGFβdnRII) (Group A, N=8) or control vector (pUBc-LacZ) (Group B, N=7), followed by 3-4 weeks of right ventricular tachypacing (240 bpm) to induce HF. The following were assessed both at baseline and the terminal study: left atrial effective refractory periods (ERPs), high density activation maps of the PLA, and the number of AF episodes &gt;30s by burst pacing. Total activation time and a conduction in-homogeneity index were determined from the activation maps. Tissue was assayed for gene expression and fibrosis (Trichrome staining). Results: RT-PCR and western blotting showed robust gene expression in the PLA. Group A developed significantly less fibrosis as a percentage of the PLA than group B (41.6±5.6 vs. 56.4±4.5%, p=0.05). ERP increases after ventricular tachypacing were equal in both groups (32 vs. 34.5 ms, p=NS). Ventricular tachypacing significantly increased the PLA activation time in Group B (from 22.8±2.9 to 43.3±8.6 ms, p&lt;0.002), but not in Group A (from 25.3±5.2 to 28.7±11.3, p=0.6). The in-homogeneity index was also significantly increased in Group B (from 1.9±0.9 to 4.4±1.9, p=0.05) but not in Group A (p=0.12). This was accompanied by a lower number of sustained AF episodes in Group A compared to Group B (0.33±0.21 vs. 3±1.1, p&lt;0.05). Conclusions: Targeted non-viral gene-therapy aimed at reducing TGF-β signaling - and consequent development of fibrosis - in the PLA interrupts the development of conduction slowing and in-homogeneity in the HF atrium, with a significant decrease in AF. Further optimization of this gene therapy approach may translate into effective AF therapies.

The effect of atrial preference pacing on paroxysmal atrial fibrillation incidence in myotonic dystrophy type 1 patients: a prospective, randomized, single-bind cross-over study

Atrial Preference Pacing (APP) is a pacemaker (PM) algorithm that supports a continuous atrial stimulation instead of a spontaneous atrial rhythm to prevent supraventricular tachyarrhythmias. The role of the APP in the prevention of atrial fibrillation (AF) is still controversial. The aim of our study was to evaluate the effect of preventive atrial pacing on AF incidence in myotonic dystrophy type I patients during a 12-month follow-up period. We studied 40 patients with myotonic dystrophy type 1 (MD1) who underwent dual-chamber PM implantation for first- and second-degree atrioventricular block. After a 1-month stabilization period, they were randomized to APP algorithm programmed OFF or ON for 6 months each, using a cross-over design. The number of AF episodes during active treatment (APP ON phases) was lower than those registered during no treatment (APP OFF phases). No statistically significant difference was found in AF episodes duration between the two phases. During the APP OFF phases and APP ON phases, the atrial pacing percentage was 0 and 98%, respectively, while the ventricular pacing percentage did not show statistically significant difference (10 vs. 8%, P =0.2). Atrial premature beats count was significantly greater during APP OFF phases than during APP ON phases. Lead parameters remained stable over time and there were no lead-related complications. Based on these 12-month follow-up data, it is concluded that APP is an efficacy algorithm for preventing paroxysmal AF in MD1 patients who underwent dual-chamber PM implantation for atrioventricular conduction disorders.

POSTER PRESENTATIONS

POSTER PRESENTATIONS

Atrial fibrillation after typical atrial flutter ablation: a long-term follow-up

Although catheter ablation is an effective treatment for typical atrial flutter (TFL), atrial fibrillation may occur during follow-up. The aim of this study was to assess the frequency of postablation atrial fibrillation in patients with or without atrial fibrillation before TFL ablation. One hundred and ninety-two patients (135 men, age 68 ± 9 years) ablated for TFL were divided into two groups: group 1 (80 patients) with isolated TFL and group 2 (112 patients) with TFL and atrial fibrillation before ablation. The end-point of the study was the occurrence of documented atrial fibrillation after ablation. Several predetermined variables were tested with regard to atrial fibrillation occurrence. The patients' perception of the frequency and severity of arrhythmia-related symptoms was evaluated before and after ablation by means of the Symptom Checklist Frequency and Severity scale (SCFSS). At least one episode of atrial fibrillation was recorded in 18 (22.5%) group 1 and 52 (46%) group 2 patients (P = 0.001), during a follow-up of 1086 ± 825 and 1126 ± 962 days, respectively. On multivariate analysis, independent predictors of atrial fibrillation occurrence in group 1 were the number of preablation episodes of TFL and the younger age of the patients. The 37 group 2 patients who continued to have paroxysmal or persistent atrial fibrillation episodes after ablation showed a significant decrease in atrial fibrillation incidence and hospitalizations. SCFSS significantly improved in the 63 group 2 patients in whom it was evaluated. On long-term follow-up, after ablation of isolated TFL, more than three-quarters of patients remained free from atrial fibrillation. Conversely, in patients with preablation atrial fibrillation, TFL ablation reduced the number of atrial fibrillation episodes as well as the number of hospitalizations and arrhythmia-related symptoms.