Non-paroxysmal atrial fibrillation mapping: characterization of the electrophysiological substrate using a novel integrated mapping technique.

AIMS: Clinical outcomes after radiofrequency catheter ablation (RFCA) remain suboptimal in the treatment of non-paroxysmal atrial fibrillation (AF). Electrophysiological mapping may improve understanding of the underlying mechanisms. To describe the arrhythmia substrate in patients with persistent (Pers) and long-standing persistent (LSPers) AF, undergoing RFCA, using an integrated mechanism mapping technique. METHODS AND RESULTS: Patients underwent high-density electroanatomical mapping before and after catheter ablation. Integrated maps characterized electrogram (EGM) cycle length (CL) in regions with repetitive-regular (RR) activations, stable wavefront propagation, fragmentation, and peak-to-peak bipolar voltage. Among 83 patients (72% male, 60 ± 11 years old), RR activations were identified in 376 regions (mean CL 180 ± 31 ms). PersAF patients (n = 43) showed more RR sites per patient (5.3 ± 2.4 vs. 3.7 ± 2.1, P = 0.002) with faster CL (166 ± 29 vs. 190 ± 29 ms; P < 0.001) and smaller surface area of fragmented EGMs (15 ± 14% vs. 27 ± 17%, P < 0.001) compared with LSPersAF. The post-ablation map in 50 patients remaining in AF, documented reduction of the RR activities per patient (1.5 ± 0.7 vs. 3.7 ± 1.4, P < 0.001) and area of fragmentation (22 ± 17% vs. 8 ± 9%, P < 0.001). Atrial fibrillation termination during ablation occurred at RR sites (0.48 ± 0.24 mV; 170.5 ± 20.2 ms CL) in 31/33 patients (94%). At the latest follow-up, arrhythmia freedom was higher among patients receiving ablation >75% of RR sites (Q4 82.6%, Q3 63.1%, Q2 35.1%, and Q1 0%; P < 0.001). CONCLUSION: The integrated mapping technique allowed characterization of multiple arrhythmic substrates in non-paroxysmal AF patients. This technique might serve as tool for a substrate-targeted ablation approach.

Characterizing left ventricular mechanical and electrical activation in patients with normal and impaired systolic function using a non-fluoroscopic cardiovascular navigation system.

PURPOSE: Cardiac disease frequently has a degenerative effect on cardiac pump function and regional myocardial contraction. Therefore, an accurate assessment of regional wall motion is a measure of the extent and severity of the disease. We sought to further validate an intra-operative, sensor-based technology for measuring wall motion and strain by characterizing left ventricular (LV) mechanical and electrical activation patterns in patients with normal (NSF) and impaired systolic function (ISF). METHODS: NSF (n = 10; ejection fraction = 62.9 ± 6.1%) and ISF (n = 18; ejection fraction = 35.1 ± 13.6%) patients underwent simultaneous electrical and motion mapping of the LV endocardium using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, Abbott). Motion trajectories, strain profiles, and activation times were calculated over the six standard LV walls. RESULTS: NSF patients had significantly greater motion and systolic strains across all LV walls than ISF patients. LV walls with low-voltage areas showed less motion and systolic strain than walls with normal voltage. LV electrical dyssynchrony was significantly smaller in NSF and ISF patients with narrow-QRS complexes than ISF patients with wide-QRS complexes, but mechanical dyssynchrony was larger in all ISF patients than NSF patients. The latest mechanical activation was most often the lateral/posterior walls in NSF and wide-QRS ISF patients but varied in narrow-QRS ISF patients. CONCLUSIONS: This intra-operative technique can be used to characterize LV wall motion and strain in patients with impaired systolic function. This technique may be utilized clinically to provide individually tailored LV lead positioning at the region of latest mechanical activation for patients undergoing cardiac resynchronization therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01629160.

Mapping-guided characterization of mechanical and electrical activation patterns in patients with normal systolic function using a sensor-based tracking technology.

AIMS: In times of evolving cardiac resynchronization therapy, intra-procedural characterization of left ventricular (LV) mechanical activation patterns is desired but technically challenging with currently available technologies. In patients with normal systolic function, we evaluated the feasibility of characterizing LV wall motion using a novel sensor-based, real-time tracking technology. METHODS AND RESULTS: Ten patients underwent simultaneous motion and electrical mapping of the LV endocardium during sinus rhythm using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, SJM). Epicardial motion data were also collected simultaneously at corresponding locations from accessible coronary sinus branches. Displacements at each mapping point and times of electrical and mechanical activation were combined over each of the six standard LV wall segments. Mechanical activation timing was compared with that from electrical activation and preoperative 2D speckle tracking echocardiography (echo). MediGuide-based displacement data were further analysed to estimate LV chamber volumes that were compared with echo and magnetic resonance imaging (MRI). The lateral and septal walls exhibited the largest (12.5 [11.6-15.0] mm) and smallest (10.2 [9.0-11.3] mm) displacement, respectively. Radial displacement was significantly larger endocardially than epicardially (endo: 6.7 [5.0-9.1] mm; epi: 3.8 [2.4-5.6] mm), while longitudinal displacement was significantly larger epicardially (endo: 8.0 [5.0-10.6] mm; epi: 10.3 [7.4-13.8] mm). Most often, the anteroseptal/anterior and lateral walls showed the earliest and latest mechanical activations, respectively. 9/10 patients had concordant or adjacent wall segments of latest mechanical and electrical activation, and 6/10 patients had concordant or adjacent wall segments of latest mechanical activation as measured by MediGuide and echo. MediGuide's LV chamber volumes were significantly correlated with MRI (R2= 0.73, P < 0.01) and echo (R2= 0.75, P < 0.001). CONCLUSION: The feasibility of mapping-guided intra-procedural characterization of LV wall motion was established. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; Unique identifier: CT01629160.

Insights into new-onset atrial fibrillation following open heart surgery and implications for type II atrial flutter.

AIMS: Postoperative atrial fibrillation (POAF), new-onset AF after open heart surgery (OHS), is thought to be related to pericarditis. Based on AF studies in the canine sterile pericarditis model, we hypothesized that POAF in patients after OHS may be associated with a rapid, regular rhythm in the left atrium (LA), suggestive of an LA driver maintaining AF. The aim of this study was to test the hypothesis that in patients with POAF, atrial electrograms (AEGs) recorded from at least one of the two carefully selected LA sites would manifest a rapid, regular rhythm with AEGs of short cycle length (CL) and constant morphology, but a selected right atrial (RA) site would manifest AEGs with irregular CLs and variable morphology. METHODS AND RESULTS: In 44 patients undergoing OHS, AEGs recorded from the epicardial surface of the RA, the LA portion of Bachmann's bundle, and the posterior LA during sustained AF were analysed for regularity of CL and morphology. Sustained AF occurred in 15 of 44 patients. Atrial electrograms were recorded in 11 of 15 patients; 8 of 11 had rapid, regular activation with constant morphology recorded from at least one LA site; no regular AEG sites were present in 3 of 11 patients. CONCLUSIONS: Atrial electrograms recorded during sustained POAF frequently demonstrated rapid, regular activation in at least one LA site, consistent with a driver maintaining AF.

Intraoperative characterization of interventricular mechanical dyssynchrony using electroanatomic mapping system--a feasibility study.

BACKGROUND: Interventricular mechanical dyssynchrony (VVMD) is a strong predictor of cardiac resynchronization therapy (CRT) response. However, no simple and reliable clinical method of measuring VVMD during CRT implant is currently available. We tested the hypothesis that the EnSite™ NavX™ system (St. Jude Medical, St. Paul, MN, USA) can be used intraoperatively to determine VVMD, thereby facilitating CRT optimization. METHODS: During CRT implant, the leads in the right atrium (RA), right ventricle (RV), and left ventricle (LV) were connected to the EnSite™ NavX™ system to record the real-time 3D motion of the lead electrodes. The distances from RA to RV lead electrodes (RA-RV) and RA to LV lead electrodes (RA-LV) were computed over ten cardiac cycles during each of RV pacing and biventricular (BiV) pacing, respectively. The degree of synchrony was computed from the distance waveforms between RA-RV and RA-LV by a cross-covariance method to characterize VVMD. Septal-to-posterior wall motion delay (SPWMD) from M-mode echocardiography (echo) was measured for reference at each pacing intervention. VVMD was present in all five patients undergoing CRT implant. RESULTS: Four of the five patients demonstrated clear improvement in EnSite™ NavX™-derived VVMD during BiV versus RV pacing, which corresponded to the SPWMD results by echo. CONCLUSIONS: It is feasible to characterize VVMD and resynchronization in CRT patients with the EnSite™ NavX™ system during implant, demonstrating its potential as a tool for intraoperative CRT optimization.

Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.

BACKGROUND: Vanoxerine is a promising, new, investigational antiarrhythmic drug. The purpose of this study was to test the hypothesis that oral dosing of vanoxerine would first terminate induced atrial flutter (AFL) and atrial fibrillation (AF), and then prevent their reinduction. METHODS: In 5 dogs with sterile pericarditis, on the fourth day after creating the pericarditis, we performed electrophysiologic (EP) studies at baseline, measuring atrial excitability, refractoriness (AERP), and conduction time (CT) when pacing from the right atrial appendage, Bachmann's bundle (BB), and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms. Then, after induction of AFL or AF, all dogs received hourly oral doses of vanoxerine: 90 mg, followed by 180 mg and 270 mg. Blood was obtained to determine plasma vanoxerine concentrations at baseline, every 30 minutes, when neither AFL nor AF were inducible, and, finally, 1 hour after the 270 mg dose. Then we repeated the baseline EP studies. RESULTS: Four dogs had inducible, sustained AFL, and 1 dog only had induced, nonsustained AF. In 4 AFL episodes, oral vanoxerine terminated the AFL and then rendered it noninducible after an average of 111 minutes (range 75-180 minutes) after the first dose was administered. The mean vanoxerine plasma level at the point of noninducibility was 84 ng/mL, with a narrow range of 76-99 ng/mL. In the dog with induced, nonsustained AF, it was no longer inducible at a drug level of 75 ng/mL. Vanoxerine did not significantly (1) prolong the AERP except at BB, and then only at the faster pacing CLs; (2) change atrial excitability thresholds; (3) prolong atrial conduction time, the PR interval, the QRS complex or the QT interval. CONCLUSIONS: Orally administered vanoxerine effectively terminated AFL and rendered it noninducible. It also suppressed inducibility of nonsustained AF. These effects occurred at consistent plasma drug levels. Vanoxerine's insignificant or minimal effects on measured electrophysiologic parameters are consistent with little proarrhythmic risk.

Characterization of atrial activation (A-A) intervals during atrial fibrillation due to a single driver: do they reflect atrial effective refractory periods?

BACKGROUND: The mean, median, and minimum local atrial activation (A-A) intervals have been used to determine the local atrial effective refractory period (AERP) during atrial fibrillation (AF), the underlying assumption being that AF is due to multiple reentrant wavelets. OBJECTIVE: We tested the hypothesis that when AF is due to a single, rapid, stable reentrant circuit (driver), the minimum and mean local A-A intervals will be similar at sites in the reentrant circuit, but will vary widely at sites with fibrillatory conduction, making these latter intervals unreliable indicators of AERP. METHODS: During sustained AF due to a left atrial (LA) driver in 6 sterile pericarditis dogs, electrograms were recorded from 186 bipolar electrodes from both atria. A-A intervals were measured from each recording site during 1.2 seconds of AF. Minimum A-A intervals as well as temporal (within site) and spatial (between sites) variability were determined from all sites. RESULTS: A-A intervals from each site during AF demonstrated that (1) 90-100% of right atrial (RA) sites and 18-39% of LA sites showed considerable (SD > 6 ms) temporal variability; (2) RA and LA sites with fibrillatory conduction (SD > 6 ms) showed considerable (a) spatial variability (RA: 9-36 ms; LA: 5-27 ms) and (b) variability of the minimum A-A intervals (RA: 14-35 ms; LA 11-28 ms). CONCLUSION: During AF due to a driver, areas with fibrillatory conduction manifested considerable variability in the mean and the minimum A-A intervals. Therefore, it is unlikely that any of the A-A intervals reflect AERP.

Atrial activation time and pattern of linear triple-site vs. single-site atrial pacing after cardioversion in patients with atrial fibrillation.

AIMS: Multisite atrial pacing has been suggested to be effective in suppressing atrial fibrillation (AF), however, the effect of linear triple-site atrial pacing (LTSP) in humans has not been evaluated. We compared the effects of LTSP to single-site atrial pacing (SSP) on the atrial activation and wavefront propagation pattern in patients with persistent AF. METHODS AND RESULTS: In 10 patients with persistent AF, the effects of LTSP and SSP were evaluated by left atrial (LA) endocardial non-contact multielectrode array mapping and multipolar catheters. LTSP and SSP were delivered from the high right atrium (HRA), the distal coronary sinus (CS), and within the LA at the site showing maximal overlay of low-voltage zones during sinus rhythm and pacing at HRA and CS. Atrial activation time and pattern, P wave duration, and the prevention of AF induced by burst pacing were assessed with these pacing interventions. Compared with SSP, LTSP at the HRA, CS, and LA shortened atrial activation times (183 +/- 24 vs. 174 +/- 24 ms, 186 +/- 29 vs. 166 +/- 28 ms, and 171 +/- 40 vs. 163 +/- 39 ms; P < 0.05, respectively). P wave duration was shorter with LTSP than SSP at all three sites (141.7 +/- 35.1 vs. 146.9 +/- 38.5 ms, 138.1 +/- 34.6 vs. 145.7 +/- 33.7 ms, and 142.7 +/- 33.4 vs. 151.3 +/- 35.1 ms; P < 0.05, respectively). LTSP initially depolarized a larger area than SSP, and produced more uniform and planar wavefront propagation. LTSP prevented the burst-induction of AF during LA pacing in 3 of 10 patients, while SSP was never successful. CONCLUSION: In patients with persistent AF, LTSP provided more rapid and uniform activation of the atria compared with SSP, which was associated with prevention of burst-induction of AF in some patients. Further study is required to determine whether LTSP can modify the substrate of chronic AF, leading to frank AF suppression.

Mapping of atrial activation during sustained atrial fibrillation in dogs with rapid ventricular pacing induced heart failure: evidence for a role of driver regions.

INTRODUCTION: Dogs with rapid ventricular pacing (RVP)-induced congestive heart failure (CHF) have inducible atrial tachycardia, flutter, and fibrillation (AF). We tested the hypothesis that rapid atrial activation in multiple regions and at different rates is responsible for sustained AF in this CHF model. METHODS AND RESULTS: We studied 12 episodes of sustained (>10 minutes) AF induced in 12 dogs with CHF produced by 3-6 weeks of RVP at 230 beats/minute. High-density mapping of AF was performed using 382 unipolar atrial electrograms recorded simultaneously from epicardial electrodes on the right (RA) and left atria (LA) and Bachmann's bundle. AF mechanisms were based on Fast Fourier Transform (FFT) analysis and activation sequence mapping. A driver was defined as a rapid stable activation region with a single dominant frequency peak in FFT analysis. During AF, three FFT and activation patterns were seen: (1) a single LA driver (7.8 +/- 1.1 Hz) near the pulmonary veins (PVs) with irregular activation in the rest of the atria (n = 4); (2) simultaneous, multisite, biatrial drivers at differing frequencies (LA vs RA dominant frequency gradient: 1.3 +/- 0.8 Hz) near the PVs (8.4 +/- 0.3 Hz) and high RA (8.5 +/- 1.5 Hz) (n = 7); and (3) biatrial irregular activation with multiple and/or broadband frequency peaks without a dominant frequency. (LA: 7.1-11.4 Hz; RA: 5.9-7.7 Hz) (n = 1). Atrial drivers had either a focal activation pattern or were due to a macroreentrant circuit around the PVs. CONCLUSIONS: In this CHF model, FFT analysis and activation sequence mapping demonstrate that sustained AF is characterized by single and multiple, stable LA and RA drivers with predominant sources in the PVs and high RA causing fibrillatory conduction.