Persistent Atrial Fibrillation Group Research Articles

THE RELATIONSHIP BETWEEN TLR2, HIF-1α, MMP-9 WITH THE OCCURRENCE AND MAINTENANCE OF ATRIAL FIBRILLATION

ObjectivesTo discuss the relation between TLR2, HIF-1α, MMP-9 as immunological and inflammatory factor in the occurrence and maintenance of atrial fibrillation.Methods57 cases of atrial fibrillation were chosen, 20 cases were...

CLINICAL RESEARCH OF THE RELATIONSHIP BETWEEN CARDIAC ANKYRIN REPEAT PROTEIN AND HIGH-SENSITIVITY C-REACTIVE PROTEIN WITH ATRIAL FIBRILLATION IN HYPERTENSION PATIENT

ObjectivesTo investigate the relationship between the CARP, hs-CRP levels with atrial fibrillation (AF) in hypertensive patients.MethodsThis prognostic analysis was performed on 178 hypertensive patients from May 2010 to May 2011...

Morphologies of the Atria and Pulmonary Veins in Relation to Lone Atrial Fibrillation Progression: A Dual‐Source Computed Tomography Scan Study

Atrial Remodeling and Lone Atrial Fibrillation. We sought to investigate the role of anatomic remodeling of the atria and pulmonary veins (PVs) in the progression of lone atrial fibrillation (AF) using dual-source computed tomography (DSCT). From 1,308 consecutive patients referred for an index ablation procedure for AF, we prospectively enrolled 29 consecutive patients with recently developed (<3 months) lone persistent AF (PsAF) and 23 consecutive patients with short-lasting (6-12 months) lone PsAF, all of whom had a history of paroxysmal AF (PAF). The control group consisted of 33 patients with lone PAF. On DSCT, the recently developed PsAF group showed more extensive atrial anatomic remodeling than the PAF group as shown by ∼40% higher spot biatrial volume, even though the mean duration of continuous AF was only 6 weeks. In contrast, the DSCT variables in the recently developed PsAF group and the short-lasting PsAF group were comparable, despite the fact that the mean duration of continuous AF in the latter group was 8 months. Series of cross-sectional areas of the ostial 1.5 cm of PV trunks were comparable in the PAF and PsAF groups in all but 3 ostial planes. A higher spot left atrial volume was the only independent factor associated with the progression of lone PAF to PsAF (OR: 1.06, 95% CI: 1.03-1.09, P<0.0001) on logistic regression. Prominent anatomic remodeling of the atria, rather than the PVs, underlies the mechanism of recent progression of lone paroxysmal AF to the persistent variety.

Left atrial pathological degeneration assessed by integrated backscatter transesophageal echocardiography as a predictor of progression to persistent atrial fibrillation: Results from a prospective study of three-years follow-up

BackgroundIt is recognized that one of the causes of atrial fibrillation (AF) is pathological degeneration of the left atrium (LA). However, prospective study that elucidated the relationship between the incidence of persistent AF and pathological degeneration has not been performed. The purpose of this study was to elucidate the usefulness of integrated backscatter (IBS) values for the prediction of progression from paroxysmal AF (PAF) to persistent AF.MethodsWe measured IBS values of the entire LA wall at 5 mm intervals (except the posterior wall) in 27 patients with paroxysmal AF and evaluated progression to persistent AF for three years. IBS values were acquired with transesophageal echocardiography (TEE) using a 4–7 MHz transducer. IBS values were calculated as the average power of the backscattered signal from regions of interest (ROI). Each IBS value was color-coded to construct three dimensional maps.ResultsAverage IBS values of total voxels in color-coded maps in the persistent AF group were significantly greater than those in the non-persistent AF group (25.8 ± 5.0 dB vs. 17.4 ± 10.2 dB, p = 0.047), whereas there was no significant difference in LA diameter between the persistent AF and the non-persistent AF group. There was significant difference in persistent AF-free survival after the baseline measurements in the subjects stratified by IBS value (<20 dB versus ≥20 dB) (univariate Cox regression analysis: hazard ratio: 8.74, p =0.046).ConclusionUsing IBS values measured by TEE, we can identify an increase in atrial degeneration that may predict the occurrence of persistent AF before LA dilation.

Treating Atrial Fibrillation: Pulmonary Vein Isolation with the Cryoballoon Technique

Cryoballoon ablation is a recently introduced technique to isolate the pulmonary veins in patients with atrial fibrillation (AF). It can potentially reduce procedural times and serious complications associated with radiofrequency ablation. We present data for 200 consecutive patients who underwent cryoballoon ablation for symptomatic AF with a mean follow-up of 16 months. Over 214 procedures that involved cryoballoon technique the mean procedure and fluoroscopy times fell to 130 and 30 min, respectively. 93.6% of pulmonary veins targeted were isolated with the cryoballoon only and 97.7% could be isolated with the addition of a radiofrequency ablation catheter. At one year 70% of patients in the paroxysmal AF group and 59% of patients in the persistent AF group were free from symptomatic recurrence. Three percent of patients experienced phrenic nerve palsy that persisted beyond the procedure. The major complication rate in this study was 0.9%. This represents the earliest and largest experience with cryoballoon ablation for AF in Australia. The major complication rate was low with no pulmonary vein stenosis, atrio-oesophageal fistula, stroke or cardiac tamponade in this series. The majority of patients were free from symptomatic recurrence at two years follow up.

Calcium- and integrin-binding protein-1 and calcineurin are upregulated in the right atrial myocardium of patients with atrial fibrillation

The aim of this study was to determine whether altered expression and distribution of calcium- and integrin-binding protein-1 (CIB1) is involved in the pathogenesis of different types of patients with atrial fibrillation (AF) associated with valvular heart disease (VHD). Right atrial specimens obtained from 65 patients undergoing valve replacement surgery were divided into three groups: sinus rhythm group (n= 24), paroxysmal atrial fibrillation group (PaAF; n= 10), and persistent atrial fibrillation group (PeAF; AF lasting >6 month; n= 31). The expression levels of mRNA and protein content for CIB1, calcineurin B, calcineurin A, and Na(+)-Ca(2+) exchanger-1 (NCX1) were measured. We also measured the combination of CIB1 with calcineurin B, L-type Ca(2+) channel, and NCX1 using immunoprecipitation. Expression of mRNA and protein content of CIB1, calcineurin B, calcineurin A, and NCX1 was increased in the AF group. Calcium- and integrin-binding protein-1 interacted with calcineurin B and L-type Ca(2+) channel. Surprisingly, CIB1 also combined with NCX1. The CIB1 and calcineurin expression was increased in AF atrial tissue and was related to the type of AF. This finding suggests that CIB1 may be involved in the pathogenesis of AF in VHD patients.

Persistent Atrial Fibrillation is Associated with a Poor Prognosis in Patients with Atrioventricular Block and Dual‐Chamber Pacemaker

The prognostic significance of development of persistent atrial fibrillation (AF) in patients with atrioventricular (AV) block and dual chamber (DDD) pacemakers has not been separately investigated. We sought to determine whether persistent AF influences clinical outcome in these patients. Three hundred-eight consecutive patients with second- or third-degree AV block and implanted a DDD pacemaker were followed for 36 ± 20 months and retrospectively divided into two groups. Thirty-four patients who developed persistent AF formed persistent AF group, and 278 patients who remained free of this arrhythmia control group. Clinical and outcome data of the two groups were compared. The primary outcome was cardiovascular death. The primary outcome occurred more often among the patients in the persistent AF group (6.8% per year) than among those in the control group (2.9% per year; P = 0.028). This difference was primarily because of higher rate of heart failure-related deaths in the persistent AF group (P = 0.009). Secondary outcomes, hospitalization for heart failure and paroxysmal AF episode ≥5 minutes, occurred also more often among the patients in the persistent AF group (P = 0.008 and P < 0.001, respectively), although the risk of nonfatal stroke was similar in both groups (P = 0.628). In patients with second- or third-degree AV block and DDD pacemaker, the development of persistent AF is associated with an increased risk of cardiovascular death and heart failure.

Does atrial fibrillation burden measured by continuous monitoring during the blanking period predict the response to ablation at 12-month follow-up?

Recurrences are common within the first months following atrial fibrillation (AF) ablation. However, prior studies using only intermittent ECG recording have not shown a powerful correlation with ultimate response. The purpose of this study was to use continuous AF monitoring with an implanted monitor to assess the AF burden measured continuously during the first months postablation and the relationship to subsequent AF recurrences. Six hundred thirteen patients with symptomatic drug-refractory AF (17% with persistent AF) were part of this retrospective analysis. All patients underwent circumferential pulmonary vein isolation and were implanted with a subcutaneous AF monitor (Reveal XT, Medtronic) for collecting data on AF burden (AF%) during a 12-month follow-up period. AF freedom (responders) was defined as AF% ≤0.5% during each monthly telemetric follow-up. A receiver operating characteristic curve analysis was performed to identify the value in AF% during the first months in the postablation blanking period that was predictive of later recurrence of AF. Sensitivity of 90% was selected as the target value. After the first ablation procedure, 396 of the 613 patients (65%) were responders (AF ≤0.5%) at 12 months: 346 of 508 (68%) in the paroxysmal AF group and 50 of 105 (47%) in the persistent AF group. Using the receiver operating characteristic curve, the specificity corresponding to 90% sensitivity was 85% for AF% at 2 months. The corresponding threshold in the AF burden during the blanking period able to identify patients at risk for late recurrences was 4.5%, corresponding to a cumulative 65.9 hours (2.75 days) spent in AF during the first 2 months. In a multivariate analysis, AF% <4.5% during the first 2 months was highly significant (P <.001), and the odds ratio of responders/nonresponders was 39.8 (95% CI, 19.1-82.9). The AF burden measured during the blanking period can predict the response to catheter ablation at 12 months. AF% ≥4.5% at 2 months assessed by continuous monitoring is a powerful predictor of subsequent AF recurrences after initial ablation, thus providing relevant clinical information to select patients for early reintervention.

POSTER PRESENTATIONS

POSTER PRESENTATIONS

Analysis methods on clinical data drawn from persistent atrial fibrillation

Background The persistent atrial fibrillation (PAF) is one of the most common arrhythmia. Its incidence is increasing recently. PAF is an important issue in our social, economic life and it...

Differential Structural Remodeling of the Left‐Atrial Posterior Wall in Patients Affected by Mitral Regurgitation with or Without Persistent Atrial Fibrillation: A Morphological and Molecular Study

Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex disease where multiple factors may induce left-atrial structural remodeling (SR). We explored the differential SR of the left-atrial posterior wall (LAPW) of patients affected by MR with or without persistent AF, and the expression of key proteins involved in its pathogenesis. Light microscopy of LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and capillary density; RT-PCR and Western blotting were used to assess the mRNA and protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1 had more myocytolytic myocytes (20.8 ± 5.6% vs 14.7 ± 4.5%; P < 0.0001), increased interstitial fibrosis (10.4 ± 5.1% vs 7.5 ± 4.2%; P < 0.05), and decreased capillary density (923 ± 107 No/mm(2) vs 1,040 ± 100 No/mm(2); P < 0.0001). All of the proteins were more expressed in groups 1 and 2 than in controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were higher in group 1 than in group 2. The LAPW of MR patients with or without AF shows considerable SR. The former has more severe histopathological changes and higher levels of proteins involved in SR, thereby reaching a threshold beyond which the sinus impulse cannot normally activate atrial myocardium.

A noninvasive index of atrial remodeling in patients with paroxysmal and persistent atrial fibrillation: a pilot study

PurposeThis study aims to develop a noninvasive atrial remodeling index (RI) to separate patients presenting paroxysmal atrial fibrillation (ParAF) from those with sustained persistent atrial fibrillation (PerAF), that is, AF episodes interrupted 7 days or more after the onset. MethodsSignal-averaged P-wave duration (SAPWd) and left atrial anteroposterior diameter (LADd) were measured in 33 ParAF patients, in 26 sustained PerAF patients, and in 18 control subjects. By using SAPWd and LADd, a dichotomous (0/1) RI was created. A logistic regression model on the probability of having a sustained PerAF vs a ParAF episode was estimated, including the RI, sex, age, and cardiac comorbidities as covariates. ResultsSignal-averaged P-wave duration was significantly longer in sustained PerAF (153 ± 15 milliseconds) than in ParAF patients (142 ± 13 milliseconds, P < .001) and in both ParAF and sustained PerAF groups vs control group (123 ± 7 milliseconds, P < .001). Left atrial anteroposterior diameter was larger both in sustained PerAF (43 ± 6 mm) vs ParAF patients (38 ± 5 mm, P = .002) and in sustained PerAF group vs control group (38 ± 2 mm, P = .004), but no differences were observed between ParAF patients and controls (P = .6). A 12-fold increase (odds ratio, 11.8; 95% confidence interval, 2.2-63.5) in the odds of having a sustained PerAF vs a ParAF episode was observed in patients with RI equal to 1. ConclusionsP-wave duration and left atrium diameter enabled to define a noninvasive atrial RI to separate patients with ParAF from those with sustained PerAF. This could be a useful tool to select a suitable strategy for AF treatment.

Arrhythmia Type After Persistent Atrial Fibrillation Ablation Predicts Success of the Repeat Procedure

The aim of the study was to investigate whether the type of arrhythmia recurrence after ablation of persistent atrial fibrillation (AF) has an impact on the maintenance of sinus rhythm after the repeat ablation procedure. Included were 78 consecutive patients (82% men; mean age, 61±10 years; mean left atrial diameter, 47±4 mm) with persistent AF who underwent ≥1 repeat ablation. The initial ablation procedure had consisted of pulmonary vein isolation with additional substrate modification (ablation of complex fractionated atrial electrograms [n=63] or linear lesions [n=15]). Patients presented for reablation either with persistent atrial tachycardia (AT) (group 1, n=36), persistent AF (group 2, n=37), or paroxysmal AF (group 3, n=5). The primary end point was freedom from any arrhythmia off antiarrhythmic drugs 6 and 9 months after the reablation procedure. Estimated proportions of patients reaching the primary end point were 59% for group 1, 28% for group 2, and 100% for group 3 at 6 months and 51%, 23%, and 100%, for groups 1, 2, and 3, respectively, at 9 months (P=0.002). In patients presenting for a repeat procedure after ablation of persistent AF, the occurrence of AT is associated with a significantly better outcome compared with recurrent persistent AF. These results suggest that AT might be considered as a step toward sinus rhythm.

Role of oral amiodarone in patients with atrial fibrillation and congestive heart failure

Amiodarone is recognized as the most effective therapy for maintaining sinus rhythm (SR) post cardioversion in patients with atrial fibrillation (AF). It is also recommended for controlling AF in patients with congestive heart failure (CHF). We retrospectively examined the efficacy and safety of oral amiodarone in patients with AF and CHF. Forty-eight consecutive AF patients whose left ventricular ejection fraction (LVEF) was less than 50% and B-type natriuretic peptide (BNP) was higher than 100 pg/ml were investigated retrospectively, and divided into 3 groups: paroxysmal AF, 16 patients; persistent AF, 9 patients; and permanent AF, 23 patients. The permanent AF group had a longer history of AF, larger left ventricular end-diastolic diameter (LVDd) and left atrial diameter (LAD) than paroxysmal and persistent AF groups (p<0.05). After median follow-up of 265 days, amiodarone suppressed paroxysms in 88% of paroxysmal AF patients, while SR was maintained in all persistent AF patients, and 35% of permanent AF patients. Of the 32 persistent and permanent AF patients, 12 (71%) out of 17 maintained SR after successful electrical cardioversion, and conversion to SR occurred spontaneously in 5 (33%) out of 15. The effective group had significantly smaller LVDd and LAD than the ineffective group. In the effective group, BNP decreased significantly from 723±566 pg/ml to 248±252 pg/ml, (p<0.0005) and LVEF increased significantly from 33±7% to 50±13% (p<0.0005) during follow up, while no changes were observed in the ineffective group. The patients with low LVEF (≤30%) benefited comparably from amiodarone to the patients with LVEF >30%. Complications occurred in 24 (50%) patients leading to discontinuation of amiodarone in 11 (23%). Oral amiodarone helped restore SR in paroxysmal and persistent AF patients with CHF. The successful rhythm control by amiodarone resulted in the improvement of LV function and the decrease of BNP levels.

Electroanatomic Properties of the Pulmonary Veins: Slowed Conduction, Low Voltage and Altered Refractoriness in AF Patients

Rapid PV activity is critical in initiating and maintaining AF. The underlying substrate responsible for this remains uncertain. We sought to identify if patients with paroxysmal (PAF) and persistent atrial fibrillation (PeAF) have an abnormal substrate within the pulmonary veins (PVs). Thirty-nine patients with AF (21 PAF, 18 PeAF) were compared with 15 age-matched controls with left-sided accessory pathways (AVRT). High-density 3D electroanatomic maps of the PVs were created. PV voltage, conduction, PV muscle sleeve length, effective refractory periods (ERPs) of the PVs, posterior left atrium (PLA), left atrial appendage (LAA) and distal coronary sinus (CSd), and signal complexity were assessed. Compared with controls, the PVs of AF patients had (1) lower mean-voltage and a higher % low-voltage; (2) shorter PV muscle sleeves; (3) slower conduction; (4) shorter ERP; and (5) more prevalent complex signals. Compared with the PAF group, the PeAF group had (1) higher % low voltage; (2) slower conduction; and (3) more complex signals. In PAF patients, the PLA and LAA ERPs were longer than controls and the PV ERP was shorter than controls; in PeAF patients PLA and LAA ERPs were reduced, but to a lesser extent than in the PVs. AF induction occurred during PV ERP testing in both AF groups, but not controls. PAF and PeAF patients demonstrate electrical and electroanatomic remodeling of the PVs compared to control patients without prior AF. Some of these changes were more marked in PeAF.

Shift in the pattern of autonomic atrial innervation in subjects with persistent atrial fibrillation

Atrial fibrillation (AF) is a multifactorial disease of the atria. We studied the differences in the atrial autonomic innervation pattern in subjects with AF compared with sinus rhythm (SR). Preparation of postmortem isolated hearts of subjects with documented persistent AF (group A) and SR (group B) included: (1) histological sectioning of predefined areas and quantification of nerve density, and (2) differentiation using immunohistochemistry in adrenergic (sympathetic, tyrosine-hydroxylase antibody), cholinergic (parasympathetic, choline-acetyltransferase antibody) and mixed (adrenergic and cholinergic staining) nerves. Characteristics of subjects in group A (N = 15) and group B (N = 24) did not differ. The mean overall nerve density was similar between groups (A: 0.31 ± 0.25/mm(2); B: 0.35 ± 0.25/mm(2); P = .87). Nerve density appeared higher in the region of the pulmonary vein ostia and antrum (group A: 0.38 ± 0.21/mm(2); group B: 0.32 ± 0.19/mm(2),) compared with other locations of the right and left atrium. A total of 2,224 (group A: 685; group B: 1539) nerves were differentiated using immunohistochemistry. There was a high degree of colocalization of adrenergic and cholinergic nerves (group A: 80% mixed staining, group B: 69% mixed staining). In group A hearts there was a significantly lower density of predominantly cholinergic nerves (0.025 ± 0.052/mm(2) vs. 0.058 ± 0.099/mm(2); P = .008) and a higher density of nerves containing adrenergic components (0.24 ± 0.18/mm(2) vs. 0.18 ± 0.17/mm(2), P = .046). Overall autonomic nerve density did not differ between atria with persistent AF compared with SR. On a morphological level, we detected a shift toward a lower density of cholinergic nerves and a higher density of nerves containing adrenergic components in AF subjects.

Increased serum high mobility group box 1 protein in patients with atrial fibrillation

Background Inflammatory process has been associated with development and recurrence of atrial fibrillation (AF). High mobility group box 1 protein (HMGB1) has been proved to be as a novel pro-inflammatory cytokine in cardiovascular diseases. This study investigated whether the serum HMGB1 level was increased in AF patients. Methods A total of 88 consecutive AF patients were enrolled in this study. Thirty age- and sex-matched healthy people were considered as control group. Serum HMGB1 concentration in AF patients and healthy people was measured by ELISA. Results HMGB1 level in persistent AF group (8.62 ± 2.18 ng/ml) was higher than that in control group (2.22 ± 0.63 ng/ml) and paroxysmal AF group (5.29 ± 1.43 ng/ml) (both P < 0.05). HMGB1 level in paroxysmal AF group was higher than that in control group ( P < 0.05). There was significantly positive correlation between HMGB1 and hs-CRP in AF patients ( n = 88, r = 0.629, P < 0.05). Conclusion The present study showed that serum HMGB1 level was markedly increased in paroxysmal and persistent AF patients.

Left atrial pressure and dominant frequency of atrial fibrillation in humans

Atrial stretch is thought to play a role in the development of atrial fibrillation (AF). However, the precise mechanism by which stretch contributes to AF maintenance in humans is unknown. The purpose of this study was to determine the impact of left atrial (LA) pressure on AF frequency in patients undergoing catheter ablation of AF. The subjects of this study were 58 consecutive patients with persistent AF (n = 40) or paroxysmal AF (n = 18) undergoing LA ablation. LA pressure was measured before ablation. Both atria and the coronary sinus were mapped, and regional dominant frequency (DF) was determined. Mean LA pressure in the persistent AF group was significantly higher than in the paroxysmal AF group (18 ± 5 vs 10 ± 4 mmHg, P <.0001). Mean DF in the persistent AF group was also higher than in the paroxysmal AF group (6.36 ± 0.51 Hz and 5.83 ± 0.54 Hz, P = .0006). In patients with persistent AF, there was a significant correlation between LA pressure and DF at the LA appendage (r = 0.55, P = .0002). DF(max) was found at the LA appendage region in 24 (60%) of the 40 patients with persistent AF (P = .0006). In multivariate analysis, LA pressure was the only independent predictor of DF(max) in the LA appendage (P = .04, odds ratio 1.41, 95% confidence interval 1.02-1.94). Higher LA pressure in patients with persistent AF implies that these patients are more vulnerable to stretch-related remodeling than are patients with paroxysmal AF. The DF of AF was directly related to LA pressure in patients with persistent AF. This finding suggests that atrial stretch may contribute to the maintenance of AF in humans by stabilizing high-frequency sources.

E0676 Value of serum adiponectin level in atrial fibrillation patients and clinical significance

ObjectiveTo investigate the level of plasma adiponectin (APN) in atrial fibrillation (AF) patients and clinical value.Methods1. 40 AF patients hospitalised in cardiology department in our hospital divided into two groups...

Natriuretic peptides and right atrial fibrosis in patients with paroxysmal versus persistent atrial fibrillation

Natriuretic peptides (NPs) are excellent diagnostic and prognostic markers of heart failure, but their roles in atrial fibrillation (AF), particularly of isolated cardiac valvular origin, are unclear. We assessed the mRNA and protein content of pro-atrial natriuretic peptide (pro-ANP) and pro-brain natriuretic peptide (pro-BNP) in right atrial appendages (RAAs) and their N-terminal fragments (nt-proANP and nt-proBNP) in the plasma of 30 patients with paroxysmal AF (PaAF) and 40 patients with persistent AF (PeAF) matched with 34 patients in sinus rhythm (SR) undergoing isolated valvular replacement. To explore the underlying mechanism, fibrosis related examinations were simultaneously carried out in RAAs. Unexpectedly, atrial expression of pro-NPs mRNA was notably augmented in the PaAF subgroup, but not so pronounced in the PeAF subgroup. Atrial content of pro-NPs proteins and plasma nt-proNPs, between which surprisingly strong positive correlations were found (pro-ANP and nt-proANP: r = 0.918, p < 0.001; pro-BNP and nt-proBNP: r = 0.913, p < 0.001), were increased analogously in PaAF and PeAF subgroups. We identified significantly increasing gradients of atrial collagen volume fraction (CVF), levels of collagen I and III in the SR, PaAF and PeAF groups, and convincing negative linear correlations between CVF, levels of collagen I and III, and atrial transcripts of pro-NPs. These findings suggest that the discordance between transcripts and protein contents of pro-NPs was possibly due to the more outstanding atrial fibrosis in PeAF, and that circulating nt-proNPs levels could reflect the corresponding atrial pro-NPs contents in this report.