Atrial Fibrillation Cycle Length Research Articles

Persistent Atrial Fibrillation FromtheOnset: A Specific Subgroup of Patients With Biatrial Substrate Involvement and Poorer Clinical Outcome.

This study sought to characterize the clinical characteristics, atrial substrate, and prognosis in a subgroup of patients with persistent atrial fibrillation (AF) from the onset (PsAFonset). Patients with AF frequently progress from trigger-driven paroxysmal arrhythmias to substrate-dependent persistent arrhythmias. Patients referred for persistent AF (PsAF) ablation were enrolled from 3 centers. Consecutive patients with PsAFonset (n= 129) were compared with patients with PsAF that progressed from paroxysmal AF (n= 231). In addition, 90 patients (30 patients with PsAFonset and 60 control subjects) were studied with noninvasive mapping to characterize the AF drivers. The degree of fractionation and endocardial voltages were assessed invasively. Patients with PsAFonset were younger (p= 0.047) and more obese (p< 0.001); there were more men (p=0.034), more patients with hypertension (p= 0.044), and these patients had larger left (p< 0.05) and right atria (p< 0.05). Baseline AF cycle length was shorter in the PsAFonset group (p< 0.01); the degree of fractionation was higher (p< 0.001 for both atria), and the endocardial voltage was lower (p< 0.05 for both atria). Patients with PsAFonsethad higher a number of re-entrant driver regions (p< 0.001) and extrapulmonary vein regions that had re-entrant drivers (p< 0.05), whereas control subjects displayed more focal driver regions (p= 0.029). The acute AF termination rate was lower in the PsAFonset group (42% vs. 81%; p< 0.001). During a mean follow-up of 17 ± 11 months fromthelast procedure, patients with PsAFonset had significantly higher AF, atrial tachycardia (AT), and AF/AT recurrence rates (p< 0.01). Patients with PsAFonset represent a distinct subgroup defined by specific demographics, underlying diffuse biatrial substrate disease, and worse clinical outcome. The findings highlight the importance of defining criteria for early detection of atrial substrate disease.

Ablation of Persistent Atrial Fibrillation Targeting Low-Voltage Areas With Selective Activation Characteristics

Complex-fractionated atrial electrograms and atrial fibrosis are associated with maintenance of persistent atrial fibrillation (AF). We hypothesized that pulmonary vein isolation (PVI) plus ablation of selective atrial low-voltage sites may be more successful than PVI only. A total of 85 consecutive patients with persistent AF underwent high-density atrial voltage mapping, PVI, and ablation at low-voltage areas (LVA < 0.5 mV in AF) associated with electric activity lasting > 70% of AF cycle length on a single electrode (fractionated activity) or multiple electrodes around the circumferential mapping catheter (rotational activity) or discrete rapid local activity (group I). The procedural end point was AF termination. Arrhythmia freedom was compared with a control group (66 patients) undergoing PVI only (group II). PVI alone was performed in 23 of 85 (27%) patients of group I with low amount (< 10% of left atrial surface area) of atrial low voltage. Selective atrial ablation in addition to PVI was performed in 62 patients with termination of AF in 45 (73%) after 11 ± 9 minutes radiofrequency delivery. AF-termination sites colocalized within LVA in 80% and at border zones in 20%. Single-procedural arrhythmia freedom at 13 months median follow-up was achieved in 59 of 85 (69%) patients in group I, which was significantly higher than the matched control group (31/66 [47%], P < 0.001). There was no significant difference in the success rate of patients in group I with a low amount of low voltage undergoing PVI only and patients requiring PVI+selective low-voltage ablation (P = 0.42). Ablation of sites with distinct activation characteristics within/at borderzones of LVA in addition to PVI is more effective than conventional PVI-only strategy for persistent AF. PVI only seems to be sufficient to treat patients with left atrial low voltage < 10%.

Vagal response during pulmonary vein isolation: Re-recognized its characteristics and implications in lone paroxysmal atrial fibrillation

BackgroundThe role of autonomic innervation around the pulmonary vein (PV) antrum in the genesis of atrial fibrillation (AF) has been demonstrated but the characteristics of radiofrequency induced vagal response (VR) in the PV antrum and its clinical impact on pulmonary vein isolation (PVI) for paroxysmal AF need to be further elucidated. MethodOf 995 consecutive patients with symptomatic paroxysmal AF undergoing PVI at a single center over a 2-year period, 516 met exclusion criteria and the remaining 479 patients, 156 positive VR (PVR) and 323 negative VR (NVR), underwent 12-month follow-up. The primary endpoint was freedom from AF or other sustained atrial tachycardia (AT), verified by monthly visits and electrocardiographic monitoring. The frequency-domain analysis was performed to evaluate the autonomic activity before and after the procedure. ResultsVR was most commonly elicited during PVI at the LSPV roof (65.4%) and anterior RSPV (44.9%, with a >5s sinus pause in 37/70 [52.8%] cases). Compared with the NVR group, ablation was associated with reduced AF recurrence at 12months in the PVR (hazard ratio: 0.53, 95% confidence interval: 0.22–0.89). Furthermore, the PVR group showed a significantly abbreviated AF cycle length at the left PV, and significantly lower HF and LF parameters with stable LF/HF ratio during follow-up. ConclusionComplete elimination of vagal response, most commonly elicited by radiofrequency application around the roof of LSPV and anterior RSPV, appeared associated with reduced 12-month recurrence of AF and with marked heart rate variability changes consistent with autonomic nervous withdrawal.

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.

Antiarrhythmic effect of vernakalant in electrically remodeled goat atria is caused by slowing of conduction and prolongation of postrepolarization refractoriness

Vernakalant inhibits several potassium currents and causes a rate- and voltage-dependent inhibition of the sodium current. The aim of this study was to evaluate the antiarrhythmic mechanism of vernakalant in normal and electrically remodeled atria. Fourteen goats were instrumented with electrodes on both atria. Drug effects on refractory period (ERP), conduction velocity (CV), and atrial fibrillation cycle length (AFCL) were determined in normal goats (control) and after 2 (2dAF) or 11 (11dAF) days of pacing-induced atrial fibrillation (AF) in awake goats. To evaluate the contribution of changes in conduction and ERP, the same experiments were performed with flecainide and AVE0118. In a subset of goats, monophasic action potentials were recorded during anesthesia. Vernakalant dose-dependently prolonged ERP and decreased CV in CTL experiments. Both effects were maintained after 2dAF and 11dAF. After 11dAF, conduction slowed down by 8.2 ± 1.5 cm/s and AFCL increased by 55 ± 3 ms, leading to AF termination in 5 out of 9 goats. Monophasic action potential measurements revealed that ERP prolongation was due to enhanced postrepolarization refractoriness. During pacing, vernakalant had comparable effects on CV as flecainide, while effect on ERP was comparable to AVE0118. During AF, all compounds had comparable effects on median AFCL and ERP despite differences in their effects on CV during pacing. The antiarrhythmic effect of vernakalant in the goat, at clinically relevant plasma concentrations, is based on both conduction slowing and ERP prolongation due to postrepolarization refractoriness. These electrophysiological effects were not affected by long-term electrical remodeling of the atria.

Left-sided Noninvasive Vagus Nerve Stimulation Suppresses Atrial Fibrillation by Upregulating Atrial Gap Junctions in Canines.

We have previously shown that right-sided low-level tragus nerve stimulation (LL-TS) is an effective approach for the treatment of atrial fibrillation (AF) induced by rapid atrial pacing (RAP) and acts by preventing the loss of atrial connexins (Cxs). Whether a left-sided approach would achieve the same effect remains unknown. We hypothesized that left-sided LL-TS would inhibit AF by preserving atrial Cxs as effectively as right-sided LL-TS. Bilateral thoracotomies allowed the attachment of multielectrode catheters to the pulmonary vein and non-pulmonary vein sites in 32 anaesthetized beagles. The dogs were randomly divided into 3 groups: RAP group (9 hours of RAP at the left appendage, n = 10), LL-TS group (9-hour RAP plus LL-TS, n = 12), and control group (sham RAP without LL-TS, n = 10). Alligator clips were clipped on the tragus of the left ear for electrical stimulation (20 Hz, 1 millisecond square waves). A voltage of stimulation setting at 80% below the threshold that slowed the sinus rate was defined as LL-TS. Electrophysiological parameters were measured at baseline and 9 hours after pacing. Connexin proteins from atrial tissues were measured at the end of the protocol. RAP induced a significant reduction in the effective refractory period and an increase in AF inducibility (P < 0.05). However, left-sided LL-TS reversed the effective refractory period reduction induced by RAP and the increase in AF inducibility. It also shortened the AF duration and prolonged the AF cycle length, which are associated with Cx40 and Cx43 upregulation (P < 0.05). We propose that left-sided LL-TS exerts its anti-AF effects through upregulation of Cxs as effectively as right-sided LL-TS, suggesting that LL-TS for AF suppression is not unique to the right tragus nerve.

Abstract 18526: Electrogram Amplitude is Reduced at Rotor Sites Critical to Maintenance of Human Persistent Atrial Fibrillation

Introduction: Increasing studies find human AF is driven by rotors, but their detection remains challenging. Theoretically, rotor cores display low amplitude and multiphasic signals, but human AF rotors fail to display such signatures. This may reflect rotor precession (obscuring analysis site chosen), poor basket contact or bipoles (that do not register orthogonal wavefronts). We hypothesized that studying unipolar signals at rotor precession areas may reveal hitherto hidden electrogram signatures. Methods: We studied 22 persistent AF patients (60±11 years, CHADS2=1.9), in whom phase mapping of 64 pole basket signals revealed rotors/sources where ablation terminated AF (fig A). Unipolar electrograms over the rotor precession area were measured by 3 blinded observers for spectral dominant frequency (DF), peak-to-peak amplitude and duration. This was compared to a paired source in each patient where ablation did not terminate AF (‘controls’) (fig B). Results: Patients had 3.3±1.7 AF rotor/focal sources. At the index source, AF terminated to sinus rhythm (n=14) or atrial tachycardia by targeted ablation (mean 4.0 mins). Compared to control areas, AF sustaining rotors/sources had lower amplitude (fig C) (0.60±0.30mV vs. 0.87±0.70mV, p=0.02). Conversely, electrogram spectra (90±45Hz vs. 80±46Hz, p=ns), duration (125±45ms vs. 116±47ms, p=ns) and AF cycle length (174±8ms vs. 174±6ms, p=ns) did not differ. Conclusions: Rotors/sources that maintain human persistent AF have lower unipolar amplitude than non-termination sites. This is the first identified electrogram signature for functionally critical human AF rotors, and motivates definition of structure/function correlations at these sites.

Abstract 10865: Online Multielectrode Catheter-enabled Temporal Tctivation Electrogram Enalysis for Localization of Atrial Fibrillation Rotor Regions: Substrate HD Study

Introduction: Multi-electrode electrogram temporal activation and fractionation have been used to localize atrial fibrillation (AF) drivers. Yet, the feasibility of a simplified “online” analysis and its usefulness to ablate AF remain to be investigated. Hypothesis: Evaluating a simplified “online” electrogram analysis approach designed to localize and ablate AF drivers. Methods: 105 patients undergoing AF ablation (77% with persistent AF, 3 centres) were prospectively enrolled. AF was first mapped in both atria with the 20-pole contact electrode catheter PentaRay® (Biosense Webster, Inc.) in order to identify regions with a temporal activation pattern compatible with the presence of rapidly rotating rotors. Specifically, regions with consecutive activations spanning the majority of the AF cycle length (including examples of rapid and continuously fractionated electrograms) were visually selected (“hot zone”).The endpoints were AF termination acutely, and freedom from long-term AF (single procedure). Off-line, electrogram cycle length values were compared between “hot” and “non-hot” regions and a numerical simulation of PentaRay-enabled unipolar recordings of a stable rotor driving AF was conducted Results: Visually selected “hot” regions located mostly in the left atrium (6.5 ±4.2/patient; ~70% of ”hot” regions). “Hot” regions were activated at a significantly shorter cycle length than “non-hot” regions (171.8 ± 4.8 vs. 193.0 ± 6.3 ms, p=0.01, N=20). 95.6% of the “hot regions” were automatically labelled CFAEs (automated analysis, Carto). However, 4.5±3.4 distinct CFAEs regions/patient were also labelled in “non-hot” regions. Ablation at “hot” regions terminated AF in 99/104 patients (95.2%), 46 [21-72] min after the 1st radiofrequency application within 20 [10-37] min of RF. Also, numerical simulations show that a simplified PentaRay®-enabled activation analysis is sufficient to distinguish rotor and non-rotor regions. After 9+3 [6-11], months of median [Q1-Q3] follow-up, 87 % were free from AF after 1 procedure and 53 % still under antiarrhythmic drugs. Conclusions: With this simplified “online” analysis, we could successfully localize rotor regions and perform efficient AF ablation. Clinical trial.gov: NCT02093949

Use of antiarrhythmic drugs during ablation of persistent atrial fibrillation: observations from a large single-centre cohort.

Catheter ablation of complex fractionated atrial electrograms (CFAE), also known as defragmentation ablation, may be considered for the treatment of persistent atrial fibrillation (AF) beyond pulmonary vein isolation (PVI). Concomitant antiarrhythmic drug (AAD) therapy is common, but the relevance of AAD administration and its optimal timing during ablation remain unclear. Therefore, we investigated the use and timing of AADs during defragmentation ablation and their possible implications for AF termination and ablation success in a large cohort of patients. Retrospectively, we included 200 consecutive patients (age: 61±12years, LA diameter: 47±8mm) with persistent AF (episode duration 47±72weeks) who underwent de novo ablation including CFAE ablation. In all patients, PVI was performed prior to CFAE ablation. The use and timing of AADs were registered. The follow-ups consisted of Holter ECGs and clinical visits. Termination of AF was achieved in 132 patients (66%). Intraprocedural AADs were administered in 168/200 patients (84%) 45±27min after completion of PVI. Amiodarone was used in the majority of the patients (160/168). The timing of AAD administration was predicted by the atrial fibrillation cycle length (AFCL). At follow-up, 88 patients (46%) were free from atrial arrhythmia. Multivariate logistic regression analysis revealed that administration of AAD early after PVI, LA size, duration of AF history, sex and AFCL were predictors of AF termination. The administration of AAD and its timing were not predictive of outcome, and age was the sole independent predictor of AF recurrence. The administration of AAD during ablation was common in this large cohort of persistent AF patients. The choice to administer AAD therapy and the timing of the administration during ablation were influenced by AFCL, and these factors did not significantly influence the moderate single procedure success rate in this retrospective analysis.

Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: A multicenter experience

New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM). Studies of this technology with short-term follow-up have shown favorable outcomes. The purpose of this study was to characterize the long-term results of FIRM ablation in a cohort of patients treated at 2 academic medical centers. All FIRM-guided ablation procedures (n = 43) at UCLA Medical Center and Virginia Commonwealth University Medical Center performed between January 2012 and October 2013 were included for analysis. During AF, FIRM software constructed phase maps from unipolar atrial electrograms to identify putative AF sources. These sites were targeted for ablation, along with pulmonary vein isolation in 77% of patients. AF was paroxysmal in 56%, and 67% had prior AF ablation. All patients had rotors identified (mean 2.6 ± 1.2 per patient, 77% in LA). Prespecified acute procedural end-point was achieved in 47% of patients (n = 20): AF termination in 4, organization in 7, >10% slowing of AF cycle length in 9. Acute complications occurred in 4 patients (9.3%). At 18 ± 7 months of follow-up, 37% were free from documented recurrent AF after a 3-month blanking period; 21% were free from documented atrial tachyarrhythmias and off antiarrhythmic drugs. Multivariate analysis did not reveal any significant predictors of AF recurrence, including pattern of AF, acute procedural success, or prior failed ablation. Long-term clinical results after FIRM ablation in this cohort of patients showed poor efficacy, different from previously published studies. Randomized studies are needed to evaluate the efficacy and clinical utility of this ablation approach for treating AF.

Recurrence quantification analysis applied to spatiotemporal pattern analysis in high-density mapping of human atrial fibrillation.

Spatiotemporal complexity of atrial fibrillation (AF) patterns is often quantified by annotated intracardiac contact mapping. We introduce a new approach that applies recurrence plot (RP) construction followed by recurrence quantification analysis (RQA) to epicardial atrial electrograms, recorded with a high-density grid of electrodes. In 32 patients with no history of AF (aAF, n=11), paroxysmal AF (PAF, n=12) and persistent AF (persAF, n=9), RPs were constructed using a phase space electrogram embedding dimension equal to the estimated AF cycle length. Spatial information was incorporated by 1) averaging the recurrence over all electrodes, and 2) by applying principal component analysis (PCA) to the matrix of embedded electrograms and selecting the first principal component as a representation of spatial diversity. Standard RQA parameters were computed on the constructed RPs and correlated to the number of fibrillation waves per AF cycle (NW). Averaged RP RQA parameters showed no correlation with NW. Correlations improved when applying PCA, with maximum correlation achieved between RP threshold and NW (RR1%, r=0.68, p <; 0.001) and RP determinism (DET, r=-0.64, p <; 0.001). All studied RQA parameters based on the PCA RP were able to discriminate between persAF and aAF/PAF (DET persAF 0.40 ± 0.11 vs. 0.59 ± 0.14/0.62 ± 0.16, p <; 0.01). RP construction and RQA combined with PCA provide a quick and reliable tool to visualize dynamical behaviour and to assess the complexity of contact mapping patterns in AF.

Quantitative analysis of localized sources identified by focal impulse and rotor modulation mapping in atrial fibrillation.

New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM) mapping, and initial results reported with this technique have been favorable. We sought to independently evaluate the approach by analyzing quantitative characteristics of atrial electrograms used to identify rotors and describe acute procedural outcomes of FIRM-guided ablation. All FIRM-guided ablation procedures (n=24; 50% paroxysmal) at University of California, Los Angeles Medical Center were included for analysis. During AF, unipolar atrial electrograms collected from a 64-pole basket catheter were used to construct phase maps and identify putative AF sources. These sites were targeted for ablation, in conjunction with pulmonary vein isolation in most patients (n=19; 79%). All patients had rotors identified (mean, 2.3±0.9 per patient; 72% in left atrium). Prespecified acute procedural end point was achieved in 12 of 24 (50%) patients: AF termination (n=1), organization (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1 cm of 54% of left atrial surface area, and a mean of 31 electrodes per patient showed interpretable atrial electrograms. Offline analysis revealed no differences between rotor and distant sites in dominant frequency or Shannon entropy. Electroanatomic mapping showed no rotational activation at FIRM-identified rotor sites in 23 of 24 patients (96%). FIRM-identified rotor sites did not exhibit quantitative atrial electrogram characteristics expected from rotors and did not differ quantitatively from surrounding tissue. Catheter ablation at these sites, in conjunction with pulmonary vein isolation, resulted in AF termination or organization in a minority of patients (4/24; 17%). Further validation of this approach is necessary.

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.

Low-Level Transcutaneous Electrical Vagus Nerve Stimulation Suppresses Atrial Fibrillation

BackgroundTranscutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines. ObjectivesThis study examined the antiarrhythmic and anti-inflammatory effects of LLTS in humans. MethodsPatients with paroxysmal AF who presented for AF ablation were randomized to either 1 h of LLTS (n = 20) or sham control (n = 20). Attaching a flat metal clip onto the tragus produced LLTS (20 Hz) in the right ear (50% lower than the voltage slowing the sinus rate). Under general anesthesia, AF was induced by burst atrial pacing at baseline and after 1 h of LLTS or sham treatment. Blood samples from the coronary sinus and the femoral vein were collected at those time points and then analyzed for inflammatory cytokines, including tumor necrosis factor alpha and C-reactive protein, using a multiplex immunoassay. ResultsThere were no differences in baseline characteristics between the 2 groups. Pacing-induced AF duration decreased significantly by 6.3 ± 1.9 min compared with baseline in the LLTS group, but not in the control subjects (p = 0.002 for comparison between groups). AF cycle length increased significantly from baseline by 28.8 ± 6.5 ms in the LLTS group, but not in control subjects (p = 0.0002 for comparison between groups). Systemic (femoral vein) but not coronary sinus tumor necrosis factor (TNF)-alpha and C-reactive protein levels decreased significantly only in the LLTS group. ConclusionsLLTS suppresses AF and decreases inflammatory cytokines in patients with paroxysmal AF. Our results support the emerging paradigm of neuromodulation to treat AF.

Catheter-based renal denervation reduces atrial nerve sprouting and complexity of atrial fibrillation in goats.

Atrial fibrillation (AF) leads to structural and neural remodeling in the atrium, which enhances AF complexity and perpetuation. Renal denervation (RDN) can reduce renal and whole-body sympathetic activity. Aim of this study was to determine the effect of sympathetic nervous system modulation by RDN on atrial arrhythmogenesis. Eighteen goats were instrumented with an atrial endocardial pacemaker lead and a burst pacemaker. Percutaneous catheter-based RDN was performed in 8 goats (RDN-AF). Ten goats undergoing a sham procedure served as control (SHAM-AF). AF was induced and maintained by burst pacing for 6 weeks. High-resolution mapping was used to record epicardial conduction patterns of the right and left atrium. RDN reduced tyrosine hydroxylase-positive sympathetic nerve staining and resulted in lower transcardiac norepinephrine levels. This was associated with reduced expression of nerve growth factor-β, indicating less atrial nerve sprouting. Atrial endomysial fibrosis content was lower and myocyte diameter was smaller in RDN-AF. Median conduction velocity was higher (75 ± 9 versus 65 ± 10 cm/s, P = 0.02), and AF cycle length was shorter in RDN-AF compared with SHAM-AF. Left atrial AF complexity (4.8 ± 0.8 fibrillation waves/AF cycle length versus 8.5 ± 0.8 waves/AF cycle length, P = 0.001) and incidence of breakthroughs (2.0 ± 0.3 versus 4.3 ± 0.5 waves/AF cycle length, P = 0.059) were lower in RDN-AF compared with SHAM-AF. Blood pressure was normal and not significantly different between the groups. RDN reduces atrial sympathetic nerve sprouting, structural alterations, and AF complexity in goats with persistent AF, independent of changes in blood pressure.

Sinus rhythm restoration and arrhythmia noninducibility are major predictors of arrhythmia-free outcome after ablation for long-standing persistent atrial fibrillation: a prospective study.

The impact of restoring sinus rhythm (SR) by initial ablation in patients with long-standing persistent atrial fibrillation (LSPAF) is not fully established. The purpose of this study was to investigate the prognostic value of SR restoration at the initial procedure and arrhythmia noninducibility at the final repeat procedure for long-term outcome. A total of 203 patients (22% female; age 59 ± 9 years) underwent stepwise catheter ablation for LSPAF. The procedural end-point of SR restoration was achieved in 50% of patients. During follow-up (median 48 months) and after 1.7 procedures per patient, 72% of patients were free from arrhythmia off antiarrhythmic drugs. Failure to restore SR was independently predicted by left atrial (LA) long-axis diameter ≥68 mm (relative risk [RR] 1.55, P = .03], proportion of high-voltage LA sites <20% (RR 1.62, P = .02), and left atrial appendage (LAA) atrial fibrillation cycle length (AFCL) <155 ms (RR 1.5, P = .05). Arrhythmia recurrence after the initial procedure was predicted by SR nonrestoration (RR 2.99, P <.000001) and LAA AFCL ≥155 ms (RR 1.90, P = .0002). Arrhythmia recurrence after the final procedure was predicted by SR nonrestoration at the initial procedure (RR 2.83, P = .0007), persistent AF duration ≥24 months (RR 2.74, P = .002), LAA outflow velocity <40 cm/s (RR 2.21, P = .006), and LAA AFCL ≥155 ms (RR 1.92, P = .02). In 115 patients with repeat procedure(s), failure to achieve arrhythmia noninducibility at the final procedure (19% of patients) was associated with arrhythmia recurrence (RR 8.9, P < .000001). SR restoration at the initial procedure and arrhythmia noninducibility at the last repeat procedure were major predictors of arrhythmia-free outcome after ablation for LSPAF.

A Decade of CFAE Mapping: Still Seeking More Specific Tools to Identify Sources and Substrate of Persistent Atrial Fibrillation.

A decade after its first description as ‘the electrophysiological substrate’ of atrial fibrillation,1 mapping complex fractionated atrial electrogram (CFAE) as an ablation target for atrial fibrillation (AF) remains highly controversial. Early high-density mapping studies of induced AF in humans revealed distinct mechanisms that underlie electrogram fractionation: collision areas of distinct wavefronts, sites of wavelet pivoting, anisotropic/slow conduction and conduction block.2 Further mapping studies revealed the functional nature of electrogram fractionation that implies important variations in distribution of fractionated activity within the same atria during different rhythms (AF versus sinus rhythm or paced rhythm).3 The recent multicentre randomised trial STAR-AF II failed to reveal any added benefit of CFAE ablation when performed in addition to pulmonary vein isolation in patients with persistent AF.4 Importantly, in that study only CFAE sites were targeted by ablation that were detected by the NavX ‘CFEmean’ algorithm (St Jude Medical). Previous studies have shown that the CFEmean algorithm detects fractionated activity at high voltage (>0.5 mV) – i.e. underdetecting CFAE within low voltage sites.3 Similarly, another randomised clinical study failed to show an added value of CFAE ablation when using the CFEmean algorithm.5 Multiple distinct types of CFAE may be observed during AF or regular rhythms. Although some CFAE patterns as continuous activity or presence of activation gradients between neighbouring bipoles6 have been described to have a greater impact with regard to AF termination or cycle length prolongation, their identification depends on the subjective judgment of the operator, because automatic CFAE algorithms fail to specifically differentiate these active CFAE types from passive ones. CFAE may be intermittent versus continuous versus high voltage (>0.5 mV) versus low voltage (<0.5 mV).7 Identification of the active CFAE sites that correspond to active AF driver sites remains a major challenge of future mapping techniques and developments. In this issue of the journal Sohal and colleagues8 give a comprehensive overview of the distinct CFAE types and difficulties in their distinction that depends on the electrode size, the mode of electrogram filtering/recording (unipolar vs bipolar) and the CFAE detection algorithm used. They provide a future perspective on a novel, promising non-invasive mapping tool enabling detection of sources and drivers of AF: the ECVUE Mapping System (CardioInsight Technologies).8,9 Recent clinical data have identified AF drivers to CFAE sites within low voltage areas that display prolonged electrical activity when using simultaneous regional mapping with multi-electrode catheters with smaller electrodes and higher local mapping resolution than a 4 mm tip ablation catheter.7,10 Future studies on persistent AF need to assess clinical efficacy of the novel AF mapping tools to identify the active CFAE sites from the passive ones, as well as impact of novel voltage-based substrate mapping/ablation strategies on rate of arrhythmia freedom.7,10,11

Temporal stability of the atrial fibrillation cycle length in persistent human atrial fibrillation and its relationship to drivers: a high density epicardial mapping study

Temporal stability of the atrial fibrillation cycle length in persistent human atrial fibrillation and its relationship to drivers: a high density epicardial mapping study

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.