Mean Atrial Fibrillation Cycle Length Research Articles

Impact of Adenosine on Wavefront Propagation in Persistent Atrial Fibrillation: Insights From Global Noncontact Charge Density Mapping of the Left Atrium.

BackgroundAdenosine shortens action potential duration and refractoriness and provokes atrial fibrillation. This study aimed to evaluate the effect of adenosine on mechanisms of wavefront propagation during atrial fibrillation.Methods and ResultsThe study included 22 patients undergoing catheter ablation for persistent atrial fibrillation. Left atrial mapping was performed using the AcQMap charge density system before and after administration of intravenous adenosine at 1 or more of 3 time points during the procedure (before pulmonary vein isolation, after pulmonary vein isolation, and after nonpulmonary vein isolation ablation). Wave‐front propagation patterns were evaluated allowing identification and quantification of localized rotational activation (LRA), localized irregular activation, and focal firing. Additional signal processing was performed to identify phase singularities and calculate global atrial fibrillation cycle length and dominant frequency. A total of 35 paired maps were analyzed. Adenosine shortened mean atrial fibrillation cycle length from 181.7±14.3 to 165.1±16.3, (mean difference 16.6 ms; 95% CI, 11.3–21.9, P<0.0005) and increased dominant frequency from 6.0±0.7 Hz to 6.6±0.8 Hz (95% CI, 0.4–0.9, P<0.0005). This was associated with a 50% increase in the number of LRA occurrences (16.1±7.6–24.2±8.1; mean difference 8.1, 95% CI, 4.1–12, P<0.0005) as well as a 20% increase in the number of phase singularities detected (30.1±7.8–36.6±9.3; mean difference 6.5; 95% CI, 2.6–10.0, P=0.002). The percentage of left atrial surface area with LRA increased with adenosine and 42 of 70 zones (60%) with highest density of LRA coincided with high density LRA zones at baseline with only 28% stable across multiple maps.ConclusionsAdenosine accelerates atrial fibrillation and promotes rotational activation patterns with no impact on focal activation. There is little evidence that rotational activation seen with adenosine represents promising targets for ablation aimed at sites of stable arrhythmogenic sources in the left atrium.

Utility of Simultaneous Biatrial Atrial Anti-Tachycardia Pacing for the Termination of Atrial Fibrillation during Catheter Ablation of Atrial Fibrillation.

Background: Atrial anti-tachycardia pacing (A-ATP) of the right atrium (RA) has been shown to decrease the burden of atrial fibrillation (AF) in patients with dual-chamber pacemakers. The aim of this study is to identify the novel predictors of effective A-ATP for terminating AF in patients with AF undergoing catheter ablation. Methods: This study included 41 consecutive patients undergoing a first ablation procedure for paroxysmal (PAF: n = 21) or persistent (PEF: n = 20) AF. We prospectively evaluated predictors of AF termination after A-ATP. The coefficient of variation (CoV = SD/mean × 100) of the dominant frequencies (DFs) was calculated to evaluate the variability in atrial activation. Results: AF was terminated by A-ATP in 29% of PAF and 5% of PEF patients. In these patients, simultaneous high-rate pacing from the RA and the coronary sinus (CS) terminated AF in 71% of patients, in whom the mean AF cycle length (CL) before A-ATP was longer (214 ± 23 vs. 177 ± 35 ms, p = 0.02) and became slower after A-ATP (234 ± 37 vs. 176 ± 32 ms, p < 0.01), compared to unsuccessful patients. The CoV of the DFs before A-ATP were lower in both RA (6.2 ± 2.0 vs. 15.3 ± 7.9, p = 0.02) and CS (11.0 ± 7.9 vs. 24.3 ± 9.3, p < 0.01) in successful patients. Conclusions: Simultaneous biatrial A-ATP from the RA and CS could terminate AF in patients with PAF. The predictors for successful termination include longer AF CL and higher AF stability.

Catheter ablation of the left and right atrial appendages without isolation in persistent atrial fibrillation

Electrical isolation of the left atrial appendage (LAA) improves outcomes of patients with persistent atrial fibrillation (AF) but may increase the risk of thromboembolism. The purpose of this study was to describe a method to map and ablate appendage drivers without complete electrical isolation. One hundred thirteen patients underwent an ablation procedure for persistent AF. The procedure was performed during AF and consisted of pulmonary vein and posterior LA isolation as well as ablation of the LAA. The right atrium (RA) was targeted in patients with a right-to-left gradient in cycle length (CL). The end point of appendage ablation was CL slowing or AF termination but not complete isolation. Among the 113 patients (mean age 64.6 ± 8.6 years; ejection fraction 54% ± 13%; LA diameter 46 ± 6.5 mm), radiofrequency ablation terminated AF in 51 patients (45%). RA ablation was performed in 41 patients (36%) at the index or repeat procedure. The mean AF CL in the RA appendage (RAA) was shorter than that in the LAA (160 ± 32 ms vs 186 ± 29 ms; P < .01) in thesepatients. The most frequent target in the RA was the RAA (CLs approaching 50-60 ms). Discontinuing radiofrequency ablation upon AF termination or conduction slowing prevented LAA isolation. After a mean follow-up of 24 ± 15 months, 89 patients (78%) remained arrhythmia-free without antiarrhythmic medications. An ablation strategy guided by the AF CL addresses LAA drivers without complete electrical isolation and also helps identify the RAA as a source of persistent AF.

Extra pulmonary vein driver mapping and ablation in paroxysmal atrial fibrillation by electrogram dispersion analysis

The adjunctive approach is still unknown for atrial fibrillation (AF), which cannot be terminated after pulmonary vein isolation (PVI). We hypothesized that the driver ablation plus PVI was superior to PVI alone. A total of 98 patients with paroxysmal AF were enrolled in this study and were divided into two groups, with one group undergoing PVI (n = 49) and the other group undergoing PVI + driver ablation (n = 49). The driver regions were defined as clusters of bipolar electrograms that displayed spatial dispersion spread over mean AF cycle length at a minimum of three adjacent bipolars of a PentaRay catheter. During the procedure, the most prominent driver regions before PVI were the roof (n = 27; 55.1%), PV antrum (n = 23; 46.9%), and the inferoposterior wall (n = 11; 22.4%). PVI can eliminate all drivers at PV antrum, but only terminate 30.4% of AF in the driver group. The AF termination rate in the driver ablation group was significantly higher than that in conventional ablation (93.9% vs 40.6%; P < 0.001). The rate of freedom from atrial tachyarrhythmia episodes by a single procedure at 6 months was significantly higher in the driver group than in the conventional group (91.6% vs 72.4%; P = 0.02). The present method is effective for AF driver identification. It guided ablation adjunctive to PVI increasing the rate of AF termination and improving the outcomes in patients with paroxysmal AF.

Spatial Relation Between Left Atrial Anatomical Contact Areas and Circular Activation in Persistent Atrial Fibrillation.

Atrial low-voltage zones (LVZs) may be related to maintenance of atrial fibrillation (AF). The influence of left atrial (LA) contact areas (CoAs) on reentrant or rotor-like sources maintaining AF has not been investigated. Forty patients with persistent AF (PsAF) were analyzed. Three representative CoA regions in the LA (ascending aorta: anterior wall; descending aorta: left inferior pulmonary vein; and vertebrae: posterior wall) were visualized by enhanced CT. Using circular catheters, the LVZs (<0.5 mV) were assessed after restoration of SR, and local activation mapping and frequency domain analyses were performed after induction of AF. Circular activation during AF was visually defined as sites with ≥2 rotations by serial electrograms encompassing >80% of the mean AF cycle length. A pivot was defined as the core of the localized circular activation. Anterior (39/40 patients, 98%), left pulmonary vein antrum (27/40, 68%), and posterior (19/40, 48%) CoAs were identified, and 80% (68/85) of those sites were overlapped by or close (<3 mm) to LVZs. Thirty-six (90%) patients demonstrated circular activation (3.1±1.7 sites/patients) along with significantly higher organized dominant frequencies (6.3 ± 0.5 Hz, regularity-index: 0.26 [0.23-0.41]) within the LA, and the average electrogram amplitude of those pivots was 0.30 mV (0.18-0.52). Of those sites, 55% (66/120) were located at or close to CoA regions. Catheter ablation including of LVZs neighboring CoAs terminated AF in 9 (23%) patients. External anatomical structures contacting the LA may be related to unique conduction properties in diseased myocardium necessary for PsAF maintenance.

Correlation of atrial fibrillation cycle length and fractionation is associated with atrial fibrillation free survival

AimsFractionation of electrograms in atrial fibrillation (AF) is associated with structural and electrical remodeling. We hypothesized that fractionation can also be associated with the AF cycle length (AFCL). This study was aimed at calculating the mean AFCL to fractionation correlation coefficient (mAFCC) and assessing its association with AF free survival after pulmonary vein isolation (PVI). MethodsIn twenty-eight patients, 15-second electrograms during AF were recorded with a twenty-polar catheter at the left and right atrial appendages. The AFCL was determined manually and the number of activations per second was automatically calculated into a fractionation score. The correlation between AFCL and fractionation was assessed with the mAFCC. ResultsMean age was 53±8years and 86% had paroxysmal AF. 64% of patients were AF free after a median follow-up of 5.5years. Baseline characteristics, mean AFCL and fractionation score were not associated with AF free survival after PVI. The mAFCC assessed at the left atrial appendage predicted long-term AF free survival (area under the curve: 0.871. P=0.002), but the mAFCC recorded at the right atrial appendage did not (0.690, P=0.131). ConclusionThe mean AFCL mAFCC recorded at the left atrial appendage was a significant predictor of long-term AF free survival. Although not a significant predictor of AF free survival, there was a significant association between mAFCC recorded at the right atrial appendage and AF free survival.

Atrial fibrillation cycle length as a predictor for the extent of substrate ablation.

Atrial fibrillation (AF) cycle length (CL) has been demonstrated to be one of the predictors for termination during ablation for AF. We evaluated the AF CL gradient between right atrium (RA) and left atrium (LA) and their mean AF CL in predicting the extent of substrate ablation. One-hundred and thirty-six patients undergoing first ablation for persistent AF were studied. Stepwise ablation, sequentially in the following order: pulmonary veins (PV), LA, and RA, was performed to achieve AF termination. Stepwise ablation terminated AF in 110 patients (81%). In the AF termination group, AF was terminated by PV isolation (PVI) (Group P), PVI plus LA ablation (Group L), and PVI plus LA plus RA ablation (Group R) in 14 patients (13%), 49 patients (44%), and 47 patients (43%), respectively. Group R had much shorter mean AF CL than Group L (156 ± 18 vs. 174 ± 24 ms, P < 0.001) and mean AF CL in Group L was much shorter than Group P (174 ± 24 vs. 209 ± 36 ms, P = 0.004). The RA to LA AF CL gradient was not significantly different between left-side ablation (Group P + Group L) and additional RA ablation (Group R) (P = 0.177). Mean AF CL >180.50 ms predicted AF termination by PVI (Group P) with 79% sensitivity and 84% specificity while mean AF CL >165.25 ms predicted AF termination by left-side ablation (Group P + Group L) with 67% sensitivity and 75% specificity. After a mean follow-up of 15 ± 7 months, freedom from arrhythmia recurrence was significantly higher in left-side ablation (Group P + Group L) than additional RA ablation (Group R) (P = 0.024). Baseline mean AF CL may identify the subset of patients in whom persistent AF can be terminated by different extent of substrate ablation, which may in turn predict the chance of recurrence. However, baseline RA to LA AF CL gradient cannot predict the need for additional RA ablation.

Influence of detomidine on atrial fibrillation cycle length measured by intracardiac electrogram recording and by colour tissue Doppler imaging in horses

Shortening of atrial fibrillation cycle length (AFCL) is a marker of atrial electrical remodelling due to atrial fibrillation (AF). To investigate the effect of administration of detomidine on AFCL measured invasively from an intra-atrial electrogram (AFCLEGM) and noninvasively by tissue Doppler imaging (AFCLTDI). We hypothesised that detomidine would have no effect on AFCL but would improve the ease of TDI measurements and facilitate noninvasive AFCL determination. Prospective clinical study. Measurements were performed before and after i.v. administration of 7.5 μg/kg bwt detomidine in 33 episodes of AF in 32 horses (582 ± 64 kg bwt, 10 ± 3 years old) referred for electrical cardioversion. The AFCLEGM was measured from a right atrial intracardiac electrogram. The AFCLTDI was measured from atrial colour tissue velocity curves in 5 atrial wall regions. Mean AFCLEGM and AFCLTDI without and with sedation were compared using a repeated-measures linear mixed model with Bonferroni correction for multiple comparisons and calculation of the Bland-Altman mean bias and limits of agreement between AFCLEGM and AFCLTDI. The mean AFCL was significantly increased after sedation, but this increase was very small (mean difference +4 ms). For AFCLTDI measurements, sedation significantly improved the quality of the atrial myocardial velocity curves and the number of AF cycles that could be measured per cardiac cycle. The Bland-Altman bias between AFCLEGM without sedation and AFCLTDI with sedation ranged from -18 to +15 ms depending on wall region. Bland-Altman limits of agreement were similar between AFCLEGM without sedation and AFCLTDI without and with sedation. Therefore, noninvasive AFCLTDI measurements with sedation can be used to estimate the atrial fibrillatory rate. Sedation facilitates noninvasive AFCL measurements but causes a slight increase in AFCL. Noninvasive AFCL measurements can be used as an indicator of atrial electrical remodelling, to study AF pathophysiology and to investigate the effect of anti-arrhythmic drugs.

Abstract 297: Paroxysmal And Sustained Atrial Fibrillation In A New Large Animal Model Of Nonischemic Heart Failure

Introduction: Atrial fibrillation is common in heart failure (HF). Understanding of the mechanisms of atrial fibrillation (AF) is limited by the paucity of large animal AF models, especially in the failing heart. We developed a large animal model of nonischemic heart failure (HF) in dogs by combined aortic insufficiency and aortic constriction and observed that a number of HF dogs developed paroxysmal AF on holter monitor. Here we characterize the spontaneously-occurring pAF in these HF dogs and perform electrophysiologic (EP) assessment of atrial refractoriness and AF inducibility along with echocardiographic imaging of left ventricle (LV) and left atrium (LA). Methods: HF was induced in dogs by aortic insufficiency and aortic constriction, and serial echocardiography (for LV fractional shortening (FS) and LA size) and Holter monitoring was performed. In control and HF dogs, EP study of atrial refractory period (AERP) and AF inducibility (duration and atrial cycle length (CL)) was performed. Results: By Holter monitoring, paroxysmal AF was noted in 5 dogs with episodes ranging from 15 to 94 beats long (mean of 49±27 beats, n=12). In EP studies, control dogs (N=3) exhibited AERP of 176±8 ms. Burst pacing resulted in AF of very brief duration (mean 32±24 sec) and a mean AF CL of 138±6 ms. LV FS averaged 37% and LA size averaged 4.3 cm2. HF dogs (N=5) exhibited RAERP of 150±8 (p=0.05 vs control). Two of these dogs had sustained AF with ventricular response up to 230 bpm on Holter monitor. In the other 3 HF dogs, burst pacing induced AF with a mean duration of 232±185 sec (at times with conversion to atrial flutter) and with a mean AF CL = 110±4 ms (p=0.002 vs control). Echo data showed LVFS averaged 30% and LA area of 14.9 cm2 (p=0.05 vs control). Conclusion: Thus we have developed a novel large animal model of HF that exhibits paroxysmal and sustained AF. This model will provide an opportunity for the study of underlying AF mechanisms, the progression of remodeling in HF hearts leading to AF, and the assessment of human-scale interventions to better treat and prevent this arrhythmia.

Multistage Electrotherapy Delivered Through Chronically-Implanted Leads Terminates Atrial Fibrillation With Lower Energy Than a Single Biphasic Shock

The goal of this study was to develop a low-energy, implantable device-based multistage electrotherapy (MSE) to terminate atrial fibrillation (AF). Previous attempts to perform cardioversion of AF by using an implantable device were limited by the pain caused by use of a high-energy single biphasic shock (BPS). Transvenous leads were implanted into the right atrium (RA), coronary sinus, and left pulmonary artery of 14 dogs. Self-sustaining AF was induced by 6 ± 2 weeks of high-rate RA pacing. Atrial defibrillation thresholds of standard versus experimental electrotherapies were measured in vivo and studied by using optical imaging in vitro. The mean AF cycle length (CL) in vivo was 112 ± 21 ms (534 beats/min). The impedances of the RA-left pulmonary artery and RA-coronary sinus shock vectors were similar (121 ± 11 Ω vs. 126 ± 9 Ω; p = 0.27). BPS required 1.48 ± 0.91 J (165 ± 34 V) to terminate AF. In contrast, MSE terminated AF with significantly less energy (0.16 ± 0.16 J; p < 0.001) and significantly lower peak voltage (31.1 ± 19.3 V; p < 0.001). In vitro optical imaging studies found that AF was maintained by localized foci originating from pulmonary vein-left atrium interfaces. MSE Stage 1 shocks temporarily disrupted localized foci; MSE Stage 2 entrainment shocks continued to silence the localized foci driving AF; and MSE Stage 3 pacing stimuli enabled consistent RA-left atrium activation until sinus rhythm was restored. Low-energy MSE significantly reduced the atrial defibrillation thresholds compared with BPS in a canine model of AF. MSE may enable painless, device-based AF therapy.

Characteristics of atrial fibrillation cycle length predict restoration of sinus rhythm by catheter ablation

Successful termination of atrial fibrillation (AF) during catheter ablation (CA) is associated with arrhythmia-free follow-up. Preablation factors such as mean atrial fibrillation cycle length (AFCL) predict the likelihood of AF termination during ablation but recurring patterns and AFCL stability have not been evaluated. To investigate novel predictors of acute and postoperative ablation outcomes from intracardiac electrograms: (1) recurring AFCL patterns and (2) localization index (LI) of the instantaneous fibrillatory rate distribution. Sixty-two patients with AF (32 paroxysmal AF; 45 men; age 57 ± 10 years) referred for CA were enrolled. One-minute electrogram was recorded from coronary sinus (CS; 5 bipoles) and right atrial appendage (HRA; 2 bipoles). Atrial activations were detected automatically to derive the AFCL and instantaneous fibrillatory rate (inverse of AFCL) time series. Recurring AFCL patterns were quantified by using recurrence plot indices (RPIs): percentage determinism, entropy of determinism, and maximum diagonal length. AFCL stability was determined by using the LI. The CA outcome predictivity of individual indices was assessed. Patients with terminated atrial fibrillation (T-AF) had higher RPI (P < .05 in CS7-8) and LI than did those with nonterminated atrial fibrillation (P < .005 in CS3-4; P < .05 in CS5-6, CS7-8, and HRA). Patients free of arrhythmia after 3-month follow-up had higher RPI and LI (all P < .05 in CS7-8). All indices except percentage determinism predicted T-AF in CS7-8 (area under the curve [AUC] ≥ 0.71; odds ratio [OR] ≥ 4.50; P < .05). The median AFCL and LI predicted T-AF in HRAD (AUC ≥ 0.75; OR ≥ 7.76; P < .05). The RPI and LI predicted 3-month follow-up in CS7-8 (AUC ≥ 0.68; OR ≥ 4.17; P < .05). AFCL recurrence and stability indices could be used in selecting patients more likely to benefit from CA.

Atrial Fibrillation Inducibility in the Absence of Structural Heart Disease or Clinical Atrial Fibrillation

Background— Inducibility of atrial fibrillation (AF) after pulmonary vein isolation has been used to guide additional left atrial ablation in paroxysmal AF. The sensitivity and specificity of AF induction in this setting remains uncertain. We examined the incidence and characteristics of inducible AF in patients without structural heart disease or clinical AF and the effect of different induction protocols on AF inducibility. Methods and Results— In 44 patients with supraventricular tachycardia with no history of AF or risk factors for AF, atrial refractoriness and conduction were measured, followed by AF induction attempts (10/patient). Each induction was performed after a waiting time that exceeded twice the duration of induced AF from the preceding induction. AF ≥1 minute was considered inducible, and ≥5 minutes as sustained. Burst pacing (at 200 ms for 10 seconds) was compared to decremental pacing (from 200 ms to shortest cycle length, resulting in 1:1 atrial capture for 10 seconds). After 10 inductions, AF was inducible in 49.5%, and sustained in 29.5% of patients. The incidence of both inducible and sustained AF increased with each induction. Apart from male gender, no clinical or electrophysiological features were associated with sustained AF. Decremental pacing was associated with a higher incidence of sustained AF (41.2% versus 14.8%, P =0.049), longer duration of AF ( P =0.006), and shorter mean AF cycle length ( P &lt;0.001) compared with burst pacing. Conclusions— Inducible and sustained AF is common in patients in the absence of structural heart disease or clinical AF, and its incidence varies according to gender, method of induction, and number of inductions. There is a direct relationship between AF persistence and number of inductions, which has not reached a plateau after 10 inductions.

A New Attempt to Scrutinize the Culprit CFAE Using Antiarrhythmic Drugs Aiming at Optimal Defragmentation

Background: Ablation of complex fractionated atrial electrograms (CFAE) is now performed in patients with persistent atrial fibrillation (AF). However, extensive ablation is often necessary to eliminate all CFAE or to terminate AF. The purpose of this study was to evaluate the effects of antiarrhythmic drug on CFAE. Methods and Results: Thirty patients, including 19 with longstanding persistent AF and 11 with persistent AF, underwent box isolation. After box isolation, CFAE maps were created before and after infusion of a pure IKr blocker, nifekalant (0.3 mg/kg). Nifekalant terminated AF in 10 (33%) patients. In the remaining patients, nifekalant prolonged the mean AF cycle length (from 149 to 212 ms, p<0.0001) and decreased the proportion of CFAE. Ablation of CFAE localized by nifekalant terminated AF in 8 (27%) patients. After a single ablation procedure, 2 of 18 patients (11%) with AF termination showed a recurrence of AF. In contrast, 6 of 12 (50%) patients without AF termination showed a recurrence of AF. A second ablation procedure was performed in 6 patients. At 12±3 months after the last ablation procedure, 28 (93%) patients were free of AF. Conclusions: Nifekalant may scrutinize the culprit CFAE. This approach may be feasible and effective for decreasing the unnecessary ablation of bystander CFAE.

Role of Progressive Widening of the Temporal Excitable Gap for Perpetuation of Atrial Fibrillation in the Goat

Previous studies suggest that a short temporal excitable gap exists between the fibrillation waves during atrial fibrillation (AF). The aim of this study was to investigate the role of that gap in the development of sustained AF in goats. Eight female goats were instrumented with left atrium (LA) electrodes, and sustained AF (>24 h) was induced by intermittent rapid atrial pacing for 9.3+/-4.6 days. In the process of sustained AF development, the atrial effective refractory period (AERP), refractory period during AF (RP(AF)), mean AF cycle length (AFCL), temporal excitable gap during AF (EG(AF) = AFCL - RP(AF)) and degree of fractionation of fibrillation electrograms at LA were studied. When the induced AF lasted for 3-10 min, AFCL, RP(AF) and EG(AF) were 98.3+/-11.0 ms, 90.5+/-13.2 ms and 7.8+/-2.4 ms, respectively. During sustained AF, the values were 84.9+/-5.2 ms, 63.0+/-4.8 ms and 21.9+/-3.5 ms, respectively (P<0.05). Percentage of single potentials was 94.2+/-3.9% and 75.6+/-5.5%, respectively (P<0.05). In this model progressive shortening of atrial refractoriness and widening of the temporal excitable gap induced by electrical remodeling created an electrophysiologic substrate for the perpetuation of AF.

Increase in organization index predicts atrial fibrillation termination with flecainide post-ablation: spectral analysis of intracardiac electrograms

The mechanism of the action of flecainide in the termination of human atrial fibrillation (AF) is not fully understood. We studied the acute effects of flecainide on AF electrograms in the time and frequency domain to identify factors associated with AF termination. Patients who were still in AF at the end of catheter ablation for AF were given intravenous flecainide. Dominant frequency (DF) and organization index (OI) were obtained by fast Fourier transform of electrograms from the coronary sinus catheter over 10 s in AF, before and after flecainide infusion. Mean AF cycle length (CL) was also calculated. Twenty-six patients were studied (16 paroxysmal AF and 10 persistent AF). Seven converted to sinus rhythm (SR) with flecainide. In all patients, mean CL increased from 211 +/- 44 to 321 +/- 85 ms (P < 0.001). Mean DF decreased from 5.2 +/- 1.03 to 3.6 +/- 1.04 Hz (P < 0.001). Mean OI was 0.33 +/- 0.13 before and 0.32 +/- 0.11 after flecainide (P = 0.90). Comparing patients who converted to SR with those who did not, OI post-flecainide was 0.41 +/- 0.12 vs. 0.29 +/- 0.10 (P = 0.013), and the relative change in OI was 29 +/- 33 vs. -3.9 +/- 27% (P = 0.016), respectively. No significant difference was noted in the change in CL and DF in the two groups. Increase in OI, independent of changes to CL and DF, appears critical to AF termination with flecainide. Increase in OI holds promise as a sensitive predictor of AF termination.

Dominant Frequency of Atrial Fibrillation Correlates Poorly With Atrial Fibrillation Cycle Length

Localized sites of high frequency during atrial fibrillation (AF) are used as target sites to eliminate AF. Spectral analysis is used experimentally to determine these sites. The purpose of this study was to compare dominant frequencies (DF) with AF cycle length (AFCL) of unipolar and bipolar recordings. Left and right atrial endocardial electrograms were recorded during AF in 40 patients with lone AF, using two 20-polar catheters. Mean age was 53+/-9.9 years. Unipolar and bipolar electrograms were recorded simultaneously during 16 seconds at 2 right and 4 left atrial sites. AFCLs and DFs were determined. QRS subtraction was performed in unipolar signals. DFs were compared with mean, median, and mode of AFCLs; 4800 unipolar and 2400 bipolar electrograms were analyzed. Intraclass correlation was poor for all spectral analysis protocols. Best correlation was accomplished with DFs from unipolar electrograms compared with median AFCL (intraclass correlation coefficient, 0.67). A gradient in median AFCL of >25% was detected in 16 of 40 patients. In 13 of 16 patients (81%) with a frequency gradient of >25%, the site with highest frequency was located in the left atrium (posterior left atrium in 8 patients). The site with shortest median AFCL and highest DF corresponded in 25% if unipolar and in 31% if bipolar electrograms were analyzed. DFs from unipolar and bipolar electrograms recorded during AF correlated poorly with mean, median, and mode AFCL. If a frequency gradient >25% existed, the site with highest DF corresponded to the site of shortest median AFCL in only 25% of patients. Because spectral analysis is being used to identify ablation sites, these data may have important clinical implications.

Effect of pulmonary vein isolation on the distribution of complex fractionated electrograms in humans

Targeting of complex fractionated electrograms (CFEs) has been used as an adjunctive strategy to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). However, it is unclear whether CFEs should be targeted before or after PVI. The purpose of this study was to examine the effect of PVI on CFE distribution in humans. We compared left atrial (LA) CFE maps acquired using the NavX system before and after PVI in patients with persistent AF. CFE maps were constructed from bipolar electrograms acquired from a circular mapping catheter. At each point, the mean AF cycle length (CL) was calculated automatically by averaging the intervals between deflections over a 4-second window. Sites with mean CL < or =120 ms were considered CFE+. A total of 22 consecutive patients (82% male, age 58 +/- 9 years) were studied. At baseline, 47% of the LA was encompassed by electrograms with CL <120 ms. PVI had a significant effect on CFE characteristics, with an increase in mean LA AF CL (144 ms pre-PVI vs. 214 ms post-PVI; P <.01) and a decrease in CFE+ LA surface area (47% vs 23%; P <.01). There was significant reduction in CFE burden after PVI in both PV (50% vs. 6%; P <.01) and non-PV (61% vs. 39%; P <.01) regions. In patients with persistent AF, PVI results in a significant decrease in both PV and non-PV areas of CFE. To limit extensive LA ablation, PVI should be performed before targeting CFE when a combined approach is pursued.

Complex Fractionated Electrogram Distribution and Temporal Stability in Patients Undergoing Atrial Fibrillation Ablation

Targeting of complex fractionated electrograms (CFEs) has been described as an approach for catheter ablation of atrial fibrillation (AF); however, the distribution and temporal stability of CFE regions remain poorly defined. In patients with persistent AF referred for ablation, we performed two consecutive left atrial (LA) CFE maps prior to AF ablation. Bipolar electrograms were acquired during AF, and the mean AF cycle length and electrogram voltage were automatically determined at each point. Sites with mean CL <or=120 ms were considered CFE positive. The two maps were then compared qualitatively and quantitatively. A total of 15 patients (93% male, age 56.1 +/- 9.0 years) undergoing AF ablation were studied. The two maps were separated in time by 31 +/- 10 minutes. There was no significant difference in the number of CFE-positive regions (12.3 +/- 5.2 vs 11.3 +/- 4.7; P = 0.06) between the maps. While CFEs were widely distributed within the LA, the PV/left atrial junction (73%) and left atrial appendage (77%) were most often CFE positive. The presence of CFEs at each region was concordant 78% of the time. There was a significant correlation between the two maps (r = 0.35 +/- 0.21, range 0.1-0.84; P < 0.001) with a percent difference of 17.5 +/- 9.4%. During persistent AF, most CFE regions are found in the vicinity of the PVs. There is a significant correlation between two CFE maps constructed 31 minutes apart, with 78% concordance of CFE sites.

Abstract 738: Role of the Pulmonary Veins in Experimental Paradigms of Remodeling- Basic Science Associated Atrial Fibrillation

Background : Pulmonary vein (PV) activity is crucial in some forms of clinical atrial fibrillation (AF), particularly paroxysmal lone AF. The precise importance of PVs in AF associated with structural heart disease is less clear. Some evidence suggests that PVs may be important for AF in experimentally-remodeled atrial substrates, e.g. atrial-tachycardia remodeling (ATR) and congestive heart failure (CHF)-induced structural remodeling, but contradictory findings also exist. This study assessed the role of PVs in canine remodeling-associated AF by evaluating the changes induced by PV-LA disconnection via encircling epicardial ablation. Methods: AF was induced before and after complete isolation of all PVs in dogs with: ATR induced by atrial tachypacing (400 bpm x 1 wk; with AV block and 80 bpm ventricular pacing to control ventricular rate, n=5); and CHF induced by ventricular tachypacing (VTP, 240 bpm x 2 wks, n=7). Electrophysiological measurements and AF mapping with 240 unipolar atrial electro-grams in both atria and all PVs were also obtained before and after PV isolation. Results ATR reduced atrial ERPs and ERP rate adaptation. The shortest AF cycle length (AFCL) in each ATR dog was recorded from PVs (mean 84±3 ms), but the mean AFCL in each of the PVs (range 97–103 ms) was not different from the mean AFCL at LA sites (98 –103 ms). PV ablation did not affect AF duration in ATR dogs (mean 284±265 pre- vs. 304±225 s post-ablation, P=NS), nor did it significantly alter RA or LA AFCL. In CHF dogs, ERPs and ERP rate adaptation were preserved. The shortest AFCL was recorded in PVs in 2 dogs (108,112 ms) and in the left side of Bachmann’s bundle in 3 (97–117 ms). PV ablation failed to alter AF duration in CHF dogs (mean 778±203 pre- vs. 644±206 s post-ablation), and increased AFCL in RA and LA slightly (10 –15%) but not significantly. Conclusions : Uncoupling of the PVs from the LA fails to significantly affect the AF substrate in 2 clinically-relevant animal paradigms of AF-promoting atrial remodeling. These findings suggest that in the presence of a favorable atrial substrate for AF the PVs are not needed for AF maintenance, and are consistent with clinical observations that complete PV isolation may not be essential for effective ablation therapy of all groups of AF patients.

Fibrillating Areas Isolated within the Left Atrium after Radiofrequency Linear Catheter Ablation

Nonpulmonary vein sources have been implicated as potential drivers of atrial fibrillation (AF). This observational study describes regions of fibrillating atrial tissue isolated inadvertently from the left atrium (LA) following linear catheter ablation for AF. We report four patients with persistent/permanent AF who underwent pulmonary vein isolation with additional linear lesions and who presented with recurrent AF (mean AF cycle length [AFCL] 175-270 ms). Further catheter ablation resulted in the inadvertent electrical isolation of significant areas of the LA in which AF persisted at the same AFCL as was measured prior to disconnection, despite the restoration of sinus rhythm (SR) in all other left and right atrial areas, strongly suggesting that these islands were driving the remaining atria into fibrillation. The disconnected areas were located in the lateral LA, including the left atrial appendage (LAA) in three patients (limited to the LAA in one) and in the posterior LA in one patient. These isolated fibrillating regions represented 15-24% of the global LA surface, as estimated by electroanatomic mapping. Fibrillation can be maintained within electrically isolated regions of the LA following catheter ablation of AF, demonstrating the importance of atrial drivers in the maintenance of AF. Further mapping of these drivers is needed to characterize their mechanism and thereby allow for a more specific ablation strategy.