Atrial Cycle Length Research Articles

Atrial fibrillation cycle-length (AF-CL) inside the pulmonary veins predicts paroxysmal AF ablation success- the INDUCE-AF study.

A novel method to measure atrial fibrillation cycle length (AF-CL) was recently described, based on the average of 10 consecutive signals (FARS10). FARS10 accurately identified pulmonary vein isolation (PVI)-responders among patients with persistent AF. Whether this method is applicable to patients with paroxysmal AF is unknown. The aim of this study is to evaluate the prognostic value of FARS10 measurements in patients with paroxysmal AF. We enrolled paroxysmal AF patients undergoing PVI in a prospective multicenter study. After AF induction with a standardized protocol, the AF-CL was measured using FARS-10 method. The primary endpoint was AF/AT-recurrence. One-hundred and four patients were included (61 ± 14years, 25% females). After a mean follow-up of 12 ± 4months, AF/AT recurrence rate was 20%. The fastest PV CL (fPV-CL) was independently associated with the primary endpoint at multivariate analysis (HR 1.02, p < 0.001). Every 10ms increase in fPV-CL, AF recurrences increased by 20%. The value of 160ms was found to be the optimal cut-off (specificity 81%, sensitivity 76%). Patients with fPV-CL < 160ms experienced lower AF recurrences as compared to patients with fPV-CL > 160ms (8% vs. 32% at 1year; HR = 0.17, p < 0.001). Progression to persistent AF was observed in 13% of patients with fPV-CL > 160ms. fPV-CL measured with the FARS-10 method accurately predicts PVI success in paroxysmal AF patients undergoing PVI. Patients with slow PV activity (fPV-CL > 160ms) experience higher AF recurrence rate after PVI and more frequent progression to persistent AF.

Posterior Wall Isolation Improves Outcomes for Persistent AF With Rapid Posterior Wall Activity: CAPLA Substudy

BackgroundPulmonary vein isolation (PVI) is less effective in persistent atrial fibrillation (PerAF) than in paroxysmal atrial fibrillation (AF). However, the CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The CAPLA randomized clinical trial) of PVI vs posterior wall isolation (PWI) did not support empiric PWI in PerAF. We examined pulmonary vein (PV) and posterior wall (PW) electrical characteristics to determine if select patients may benefit from additional PWI. ObjectivesThis study sought to determine the impact of PV and PW electrical characteristics on AF ablation outcomes in the CAPLA randomized study. MethodsParticipants in spontaneous AF at the time of ablation were included from the CAPLA study. The mean, shortest, and longest PV, PW, and left atrial (LA) appendage cycle length measurements were annotated preablation using a multipolar catheter for 100 consecutive cycles. Next, cardioversion was performed with a high-density LA voltage map completed. Cox proportional hazards regression was utilized to determine clinical and electroanatomic predictors of AF recurrence overall and according to ablation strategy. Follow-up included twice daily single-lead electrocardiograms or continuous monitoring for 12 months. ResultsA total of 151 patients (27% female, age 65 ± 9 years, 18% long-standing PerAF, LA volume index 52 ± 16 mL/m2, median AF duration 5 months [IQR: 2-10 months]) were in AF on the day of procedure and were randomized to PVI alone (50%) or PVI+PWI (50%) according to the CAPLA randomized clinical trial protocol. Baseline clinical, echocardiographic, and electroanatomic parameters were comparable between groups (all P > 0.05) including PV and PW characteristics. After 12 months, freedom from AF off antiarrhythmic drug therapy was 51.7% in PVI and 49.7% in PVI+PWI (log-rank P = 0.564). Rapid PW activity was defined as less than the median of the shortest PW cycle length (140 ms) and rapid PV activity was defined as less than the median of the shortest PV cycle length (126 ms). In those with rapid PW activity, the addition of PWI was associated with greater arrhythmia-free survival (56.4%) vs PVI alone (38.6%) (HR: 0.78; 95% CI: 0.67-0.94; log-rank P = 0.030). Moreover, in those undergoing PVI only, the risk of AF recurrence was higher in those with rapid PW activity (55.3% vs 46.5% in slower PW activity; HR: 1.50, 95%CI 1.11-2.26; log-rank P = 0.036). Rapid PV activity and PV cycle length (individual PVs or average of all 4 PVs) were not associated with outcome (all P > 0.05) regardless of ablation strategy. There was no correlation between PW cycle length and posterior low voltage (r = −0.06, P = 0.496). The addition of PWI did not improve arrhythmia-free survival in subgroups with LA enlargement (LA volume index >34 mL/m2) (HR: 0.69; 95% CI: 0.39-1.25; P = 0.301), posterior low-voltage zone (HR: 1.06; 95% CI: 0.68-1.66; P = 0.807), or long-standing PerAF (HR: 1.10; 95% CI: 0.71-1.72; P = 0.669). ConclusionsRapid PW activity is associated with an increased risk of AF recurrence post–catheter ablation. The addition of PWI in this subgroup was associated with a significant improvement in freedom from AF compared with PVI alone. The presence of rapid PW activity may identify patients with PerAF likely to benefit from PWI.

Electromechanical Cycle Length Mapping for atrial arrhythmia detection and cardioversion success assessment

Background:Direct current cardioversion (DCCV) is an established treatment to acutely convert atrial fibrillation (AF) to normal sinus rhythm. Yet, more than 70% of patients revert to AF shortly thereafter. Electromechanical Cycle Length Mapping (ECLM) is a high framerate, spectral analysis technique shown to non-invasively characterize electromechanical activation in paced canines and re-entrant flutter patients. This study assesses ECLM feasibility to map and quantify atrial arrhythmic electromechanical activation rates and inform on 1-day and 1-month DCCV response. Methods:Forty-five subjects (30 AF; 15 healthy sinus rhythm (SR) controls) underwent transthoracic ECLM in four standard apical 2D echocardiographic views. AF patients were imaged within 1 h pre- and post-DCCV. 3D-rendered atrial ECLM cycle length (CL) maps and spatial CL histograms were generated. CL dispersion and percentage of arrhythmic CLs≤333ms across the entire atrial myocardium were computed transmurally. ECLM results were subsequently used as indicators of DCCV success. Results:ECLM successfully confirmed the electrical atrial activation rates in 100% of healthy subjects (R2=0.96). In AF, ECLM maps localized the irregular activation rates pre-DCCV and confirmed successful post-DCCV with immediate reduction or elimination. ECLM metrics successfully distinguished DCCV 1-day and 1-month responders from non-responders, while pre-DCCV ECLM values independently predicted AF recurrence within 1-month post-DCCV. Conclusions:ECLM can characterize electromechanical activation rates in AF, quantify their extent, and identify and predict short- and long-term AF recurrence. ELCM constitutes thus a noninvasive arrhythmia imaging modality that can aid clinicians in simultaneous AF severity quantification, prediction of AF DCCV response, and personalized treatment planning.

Site-specific effects of dobutamine on cardiac conduction and refractoriness.

Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature. To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS. From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing. For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted. In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.

Patterns of pulmonary vein activity that may help identify patients who need further ablation beyond pulmonary vein isolation in persistent AF

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation Background Pulmonary vein isolation (PVI) is the cornerstone interventional treatment for AF. While this strategy is effective in paroxysmal AF, the success rate of this approach is more limited in persistent AF (PsAF). In these pts, the main challenge is to discriminate those who will respond to PVI only, from those who may require an extended ablation strategy. Purpose We aimed to evaluate whether the analysis of the electrical activity recorded within the PV may provide the key to discriminate passive PV from PV playing an active role. Methods Three-subgroups of consecutive pts who underwent first-time PVI for PsAF were considered based on the mechanism of AF: 1) definitely related to PV, based on procedural AF termination during PVI (the "PV-term" group) 2) likely PV-dependent, based on the absence of AF recurrence &amp;gt; 18 months off-antiarrhythmic drugs after PVI only (the "PV-dep" group) 3) definitely/likely independent of the PV, based on PsAF recurrence despite isolated PV or at least one redo consisting of PV reisolation only, respectively ("PV-indep"). PV activity during AF was assessed using Lasso recordings before ablation. An automatic detection algorithm was developed to extract atrial activations from intra-cardiac electrograms in order to perform further analyses. Epochs of 60-sec were used. Different methods based on the atrial cycle length variability were assessed to best characterize the potential markers of PV activity such as the occurrence of intermittent bursts of rapid activity. Each PV and the left atrial appendage (LAA) were evaluated. Results A total of 40 pts were included (mean age: 60.0 ± 9.9 years, mean PsAF duration: 4.4 ± 4.3 years) (PV-term group (n=10), PV-dep group (n=17), PV-indep group (n= 13)). The dynamics of PV activation intervals was assessed using the envelope of the PV intervals time series (Figure 1A shows representative examples of each group). Among all features evaluated, the best feature that could discriminate similarly both the PV-term and the PV-dep group from the PV-indep group, was the standard deviation of the inferior envelope relative to the median CL of the vein (p &amp;lt;0.001 and p = 0.005, respectively) (Figure 1B). Cut-off selected by ROC analysis provided a 100% sensitivity and 85% specificity to discriminate the PV-term from the PV-indep group (AUC 0.931) and a 88% sensitivity and 77% specificity to discriminate the PV-dep from the PV-indep group (AUC 0.805). We compared this feature with the Fastest PV run (mean CL of the fastest 10-beat run) as recently described (p = 0.04, AUC = 0.762 and p = 0.03, AUC = 0.738, respectively) (Figure 2). Conclusions The assessment of the CL variations recorded within the PV before PsAF ablation may provide the key to discriminate pts who may be cured by PVI only.

PO-02-169 PATTERNS OF PULMONARY VEIN ACTIVITY RECORDED DURING PERSISTENT AF MAY HELP IDENTIFY THEIR CONTRIBUTION TO THE MECHANISM OF AF

Pulmonary vein isolation (PVI) is the cornerstone interventional treatment for AF but the success of this approach is more limited in persistent AF (PsAF). In these pts, the main challenge is to discriminate those who will respond to PVI only, from those who may require an extended ablation strategy. We sought to characterize the patterns of the electrical activity recorded within the PVs based on their postulated contribution to the mechanism of PsAF. Three subgroups of consecutive pts who underwent PVI for PsAF were considered based on the mechanism of AF: 1) definitely PV-related: procedural AF termination during PVI (“PVI-term” group) 2) likely PV-related: absence of AF recurrence > 18 months off-AAD after PVI only (“PVI-success” group) 3) definitely/likely PV-unrelated: PsAF recurrence despite isolated PV or at least one redo, respectively (“PVI-failure” group). Each PV and the left atrial appendage were evaluated before ablation. An automatic detection algorithm was developed to extract atrial activations from intra-cardiac electrograms in order to perform further analyses. Epochs of 60-sec were used. Different methods based on the atrial cycle length (CL) variability were assessed to best characterize the potential markers of PV activity such as the occurrence of bursts of rapid activity. A total of 40 pts were included (mean age: 60 ± 10 years, mean AF duration: 11 ± 10 months): PVI-term group (n=10), PVI-success group (n=17), PVI-failure group (n= 13). The dynamics of PV activation intervals was assessed using the envelope of the PV intervals time series. Among all features evaluated, the best feature that could discriminate similarly both the PVI-term and the PVI-success group from the PVI-failure group, was the standard deviation of the inferior envelope relative to the median CL of the PV (p <0.001 and p = 0.005, respectively) (Fig. A-B). Cut-off selected by ROC analysis provided a 100% sensitivity and 85% specificity to discriminate the PVI-term from the PV-failure group (AUC 0.931) and a 88% sensitivity and 77% specificity to discriminate the PVI-success from the PV-failure group (AUC 0.805). This feature performed better than the recently reported “Fastest PV run” (mean CL of the fastest 10-beat run) (AUC = 0.762 and AUC = 0.738, respectively) (Fig. C). Patterns of the electrical activity recorded within the PV differ according to the mechanism of PsAF. Their evaluation may provide the key to discriminate pts who may be cured by PVI only.

Abstract 15706: Non-Invasive 3D Electromechanical Cycle Length Mapping for Macroreentrant Atrial Flutter Characterization

Introduction: Arrhythmia localization prior to catheter ablation is critical for clinical decision making. The current standard of 12-lead EKG interpretation lacks spatial specificity and is anatomically limited. Electromechanical Cycle Length mapping (ECLM) is a high frame rate, echocardiography-based frequency analysis mapping technique, that can noninvasively map, localize and characterize cardiac activation frequencies in 3D. Hypothesis: Accurate localization prior to ablation may facilitate pre-op planning, reduce procedural times and fluoroscopic exposure. In this study we access ECLM feasibility for 3D mapping and quantifying macroreentrant atrial flutter (AFL) activation rates. Methods: Four patients (N = 4; 65 ± 9yo; 3 M) presented with AFL and were referred to RF ablation. Patients underwent pre-op transthoracic ECLM with simultaneous 3-lead EKG. 3D atrial ECLM cycle length (CL) maps were rendered and areas with arrhythmic CL were identified (100-330 ms). ECLM AFL and Ventricular CLs were defined as the dominant CL of the arrhythmic region and the region that remains synchronized with the ventricular activation respectively. ECLM findings were compared against identified origins and CLs on intracardiac electroanatomic mapping (EAM). Results: ECLM successfully identified and localized the presence of atrial typical CTI flutter in all four subjects when compared against successful RF ablation. An ECLM map in a CTI AFL case is shown on Fig. 1a with the CTI circuit in the right atrium. ECLM CLs exhibited excellent agreement with both the CL of the 3-lead EKG (Atrial CL: r 2 = 0.91, Ventricular CL r 2 = 0.99) and the EAM AFL CL (r 2 = 0.92). Conclusions: ECLM can localize, map and quantify the electromechanical CLs in AFL in excellent agreement with the clinical electrical CL rates and propagation patterns obtained by clinical albeit invasive procedures, providing thus a clinical noininvasive, non-ionizing mapping tool for RF ablation planning.

Comparative Study of Methods for Cycle Length Estimation in Fractionated Electrograms of Atrial Fibrillation.

Atrial cycle length (CL) is an important feature for the analysis of electrogram (EGM) characteristics acquired during catheter ablation (CA) of atrial fibrillation (AF), the commonest cardiac arrhythmia. Nevertheless, a robust ACL estimator requires the precise detection of local activation waves (LAWs), which still remains a challenge. This work aims to compare the performance in (CL) estimation, especially under fractionated EGMs, of three different LAW detection methods relying on different operation strategies. The methods are based on the hyperbolic tangent (HT) function, an adaptive amplitude threshold (AAT) and a (CL) iteration (ACLI), respectively. For each method, LAW detection has been assessed with respect to manual annotations made by two experts and performance has been estimated by confusion matrix and mean and individual (CL) error calculation by EGM types of fractionation. The influence of EGM length on the individual (CL) error has been additionally considered. For the HT method, accuracy, sensitivity and precision were 92.77–100%, while for the AAT and ACLI methods they were 78.89–99.91% for all EGM types. The CL error on the HT method was lower than AAT and ACLI methods (up to 12 ms versus up to 20 ms), with the difference being more prominent in complex EGMs. The HT method also showed the lowest dependency on EGM length, presenting the lowest and least variable error values. Therefore, the HT method achieves higher performance in (CL) estimation in comparison with previous LAW detection techniques. The high robustness and precision demonstrated by this method suggest its implementation on CA mapping devices for a more successful location of ablation targets and improved results during CA procedures.

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.

Influence of atrial cycle length and site of origin on the peak frequency of bipolar electrograms to discriminate isthmus conduction in atrial scar

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Background Peak frequency (PF) of conventional bipolar electrograms is a novel parameter which may distinguish between near-field (NF) and far-field (FF) signals. However, the influence of activation rate and the direction of the activation front on it is unknown. Purpose 1. To study the influence of atrial cycle length and wavefront origin on PF to detect residual conduction in a well-defined model of narrow isthmus of conduction such as subacute pulmonary vein (PV) reconnection following atrial fibrillation ablation. 2. To compare this influence with that found for Bipolar voltage (BiV). Methods Baseline maps were acquired in redo PV isolation (PVI) procedures with a 16-pole grid catheter (HD-Grid) during low rate sinus rhythm (SR), low rate coronary sinus pacing at 500 ms cycle length (CSLR) and high rate coronary sinus pacing at 300 ms cycle length (CSHR). PFs were retrospectively computed. PVI sites requiring ≤3 radiofrequency applications were included, with EGMʼs ≤1cm from the PVI site classified as GAP (vs &amp;gt;1cm, No-GAP). Results 28 GAPs were found in 12 of 14 consecutive patients in the study. 3976 EGMʼs (1547 GAP vs 2429 No-GAP) were analyzed. In both GAP and No-GAP, PF was similar in SR vs CSLR (GAP: 363±132 Hz -SR vs 345±135 Hz -CSLR, P=NS ; No-GAP: 196±110 Hz -SR vs 181±116 Hz -CSLR, P=NS). PF was slightly higher for CSLR vs CSHR. (GAP: 345±135 Hz -CSLR vs 317±154 Hz -CSHR, P&amp;lt;0.001; No-GAP 181±116 mV -CSLR vs 162±129 mV -CSHR, P&amp;lt;0.01). (Panel A). BiV was significantly higher in SR vs CS pacing but similar between CSLR and CSHR (GAP: 1.86±2.11 mV -SR vs 0.87±1.19 mV -CSLR vs 0.74±0.92 mV -CSHR, P= NS, No-GAP: 0.62±1.22 mV -SR vs 0.33±0.68 mV - CSLR vs 0.27±0.48 mV - CSHR, P=NS. (Panel B). ROC GAP discrimination for PF was similar between SR and CSLR (AUCʼs: 0.86-SR, 0.84-CSLR) and slightly lower for CSHR (AUC: 0.81) with optimal cutoffs of 260, 240 and 220 Hz, respectively. ROC GAP discrimination for BiV was lower vs PF in all rhythm modes (AUCʼs: 0.77-SR, 0.74-CSLR, 0.75-CSHR), with optimal cutoffs of 0.3, 0.2 and 0.15 mV, respectively. Conclusion ROC gap discrimination was significantly higher for all rhythm modes with PF vs BiV. PF showed slightly decreasing cutoff values for SR, CSLR and CSHR respectively, whereas BiV showed a greater relative decrease in cutoffs for SR, CSLR and CSHR.

"Irregular" tachycardia atrial cycle length and activation sequence with relatively constant ventricular cycle length: What is the mechanism?

"Irregular" tachycardia atrial cycle length and activation sequence with relatively constant ventricular cycle length: What is the mechanism?

Tachycardia atrial cycle length equal to that during sinus rhythm: What is the mechanism?

A 64-year-old woman with frequent palpitations presented for atrial fibrillation radiofrequency catheter ablation (RFCA). She had not been administered any antiarrhythmic medication before admission to the hospital. After RFCA, a routine electrophysiological study was performed. Three catheters were positioned: a quadripolar catheter at the high right atrium (HRA), a quadripolar catheter at the His bundle region, and a decapolar catheter in the coronary sinus (CS) (CS 7-8 at the CS ostium). The baseline sinus cycle length was 628 milliseconds (ms), the atrial-His (AH) interval was 87 ms, and the His-ventricular (HV) interval was 52 ms. Antegrade atrioventricular (AV) nodal conduction showed decremental and dual pathways during atrial extrastimulus testing, but no tachycardia was induced. Retrograde ventriculoatrial (VA) conduction showed VA disassociation. Figure 1 shows a narrow QRS complex tachycardia with AV 1:1 conduction that was induced by two spontaneous ventricular extrasystoles. The corresponding intracardiac recording showed that the atrial cycle length oscillated between 627?30 ms (recorded by the HRA catheter) and 626?33 ms (recorded by the CS 7-8 catheter), which was approximately the same as that during sinus rhythm (SR) (Figure 2). How was the tachycardia induced and what is the mechanism of the tachycardia? This article is protected by copyright. All rights reserved.

Reproducibility and predictive value of a simple novel method to measure atrial fibrillation cycle length in persistent atrial fibrillation - FARS-AF study.

Different methods are used for atrial fibrillation (AF) cycle length (CL) measurement with variable results. Previous studies of pulmonary vein (PV) CL measurement showed contradictory results on predicting PV isolation (PVI) efficacy. A novel simple method of measuring the average of 10 consecutive Fastest Atrial Repetitive Similar morphology signal (FARS10 )-CL to characterize local atrial activity rate was evaluated prospectively. The intra-observer reproducibility of FARS10 -CL and traditional AF-CL measurement of continuously fragmented coronary sinus (CS) signals were tested. We prospectively enrolled 100 consecutive patients (62 ± 10 years, 72% male) undergoing wide antral PVI only ablation for persistent AF, measured PV-FARS10 -CLs, and evaluated long-term outcome. The Kendall area correlation between repeated traditional AF-CL measurements was -0.006 and between repeated FARS10 -CL measurements in the right and left atrial appendages, CS and PVs were 0.944, 0.859, 0.882, 0.675-0.955, respectively. Patients with recurrent atrial tachyarrhythmia had significantly longer fastest PV-FARS10 -CL (172 ± 41 vs. 156 ± 41 ms, p = .047). Patients with high burden of spontaneous low-voltage zone (LVZ) had significantly longer fastest PV-FARS10 -CL. Freedom from recurrent tachyarrhythmia at 24 months was 85% versus 59% in patients with fastest PV-FARS10 -CL ≤ 140 versus >140 ms, p = .0018, respectively. In multivariable analysis fastest PV-FARS10 -CL ≤ 140 ms was the only significant predictor of freedom from recurrent tachyarrhythmia. FARS10 -CL measurements have a high reproducibility in contrast to traditional AF-CL measurement of continuously fragmented CS signals. Patients with high burden of LVZ have longer fastest PV-FARS10 -CLs. Fastest PV-FARS10 -CL ≤ 140 ms is associated with a high success of wide antral PVI-only ablation approach in persistent AF.

Fast-slow atrioventricular nodal reentrant tachycardia phenotype mimicking the slow-slow type

Abstract Background Fast-slow (F/S-) atrioventricular (AV) nodal reentrant tachycardia (AVNRT) is characterized by a short atrio-His (AH) interval and the earliest site of atrial activation (EAA) in the proximal coronary sinus (EAA-CS), while slow-slow (S/S-) AVNRT presents a long AH interval and EAA-CS. Those intracardiac appearances are initial indicators for making a diagnosis. Purpose To identify an unknown phenotype of F/S-AVNRT. Methods Among 46 consecutive patients with F/S-AVNRT, 6 patients (1 man, age 59±9) had an apparent but not typical (pseudo-) S/S-AVNRT during an electrophysiologic study. In 2 patients, pseudo-S/S-AVNRT was clinically documented. Results In all 6 patients, the diagnosis of F/S-AVNRT was made by an exclusion of atrial tachycardia with findings of 1) a V-A-V response following ventricular entrainment or 2) termination without atrial capture by ventricular pacing, and an exclusion of AV reentrant tachycardia with a ventriculoatrial dissociation during an initial (so-called QRS transition) zone of ventricular entrainment. An initial A-A-V activation sequence on atrial induction of F/S-AVNRT observed in 1 patient and Wenckebach-type AV block during ongoing F/S-AVNRT developing in 3 patients suggested the presence of the lower common pathway (LCP). Like the typical S/S-AVNRT, pseudo-S/S-AVNRT was induced with atrial stimulation after a jump in the AH interval or double ventricular response. However, in all patients, the pseudo-S/S-AVNRT transited to F/S-AVNRT following AV block in a single cycle and/or pseudo-S/S-AVNRT transited from spontaneously or triggered by atrial contractions. Importantly, on these transitions, the atrial cycle length (CL) and EAA-CS remained unchanged, that is, the atrial CL of S/S-AVNRT was almost identical to that of F/S-AVNRT, suggesting that the essential circuit of both tachycardias was identical. Actually, both tachycardias were cured by ablation at a single site in the traditional slow pathway (SP). Collectively, the pseudo-S/S-AVNRT was diagnosed as another phenotype of F/S-AVNRT accompanied by sustained antegrade conduction via another bystander (likely the left-sided or superior) SP breaking through the His bundle owing to the repetitive antegrade block at the LCP occurring by linking phenomenon, thus representing a long AH interval during the ongoing F/S-AVNRT. When the antegrade conduction is blocked at the bystander SP during the pseudo-S/S-AVNRT, releasing the linking phenomenon, the subsequent antegrade conduction reach the His-bundle via the fast pathway, thus returning to F/S-AVNRT. Conclusions An unknown, but not rare F/S-AVNRT phenotype exists that apparently mimics the typical S/S-AVNRT and is also an unknown subtype of apparent S/S-AVNRT. The presence of this pseudo-S/S-AVNRT suggests the limitation of classifying types of AVNRT based on AH and HA intervals during tachycardia. Understandings of this phenotype can advance a diagnosis of atypical AVNRT with multiple phenotypes. Funding Acknowledgement Type of funding sources: None.

Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.

AimsPharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145.Methods and resultsEight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred.ConclusionAP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.

Effects of Ranolazine and its Combination with Amiodarone on Rapid Pacing-induced Reentrant Atrial Tachycardia in Rabbits.

Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation in intact animals; however, its efficacy in the setting of atrial tachycardia (AT) is unknown. The purpose of this study was to investigate the effects of RAN alone or in combination with amiodarone (AMIO) on rapid pacing-evoked right AT in rabbit hearts. Right atrial monophasic action potentials (MAPs) were recorded in 11 anesthetized rabbits, using combination MAP pacing catheters. Vulnerability to AT was tested by employing consecutive trains of rapid burst pacing prior to and after 2.4 mg/kg of RAN alone delivered intravenously and then in combination with 3 mg/kg of AMIO as a 15-minute infusion. Primary endpoints were postdrug AT reproducibility as well as cycle length (CL) and tachycardia duration. MAP duration at 75% repolarization and the effective refractory period (ERP) were assessed during programmed pacing to calculate the atrial postrepolarization refractoriness (aPRR = ERP – MAPD75%). AT was elicited in eight out of 11 rabbits; only these animals were included for further investigation. RAN did not abolish the inducibility of AT in any experiment; however, it prolonged its CL (baseline vs. RAN: 120 ± 16 ms vs. 138 ± 18 ms; p = 0.053). Supplemental AMIO further increased the AT CL (baseline vs. RAN + AMIO: 120 ± 16 ms vs. 152 ± 23 ms; p = 0.006), without affecting arrhythmia reinducibility. Slowing of the tachycardia after RAN or RAN + AMIO was associated with spontaneous termination of the arrhythmia. RAN prolonged the aPRR significantly, while AMIO in addition to RAN potentiated this effect. Neither RAN alone nor its combination with AMIO abolished the elicitation of AT in this model. However, both agents synergistically prolonged the aPRR, resulting in the slowing of AT and promoting spontaneous termination of the arrhythmia.

Inhibition of Small-Conductance Calcium-Activated Potassium Current (I K,Ca) Leads to Differential Atrial Electrophysiological Effects in a Horse Model of Persistent Atrial Fibrillation.

BackgroundSmall-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current—and thereby the efficacy of small-conductance Ca2+-activated K+ current (IK,Ca) inhibition—might be negatively related to AF duration and the extent of AF-induced remodeling.Experimental Approach and MethodsTo address the hypothesis of the efficacy of IK,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the IK,Ca inhibitor NS8593 (5 mg/kg) and its influence on atrial conduction were studied using epicardial high-density contact mapping in horses with persistent AF. Eleven Standardbred mares with tachypacing-induced persistent AF (42 ± 5 days of AF) were studied in an open-chest experiment. Unipolar AF electrograms were recorded and isochronal high-density maps analyzed to allow for the reconstruction of wave patterns and changes in electrophysiological parameters, such as atrial conduction velocity and AF cycle length. Atrial anti-arrhythmic properties and adverse effects of NS8593 on ventricular electrophysiology were evaluated by continuous surface ECG monitoring.ResultsIK,Ca inhibition by NS8593 administered intravenously had divergent effects on right and left AF complexity and propagation properties in this equine model of persistent AF. Despite global prolongation of AF cycle length, a slowing of conduction in the right atrium led to increased anisotropy and electrical dissociation, thus increasing AF complexity. In contrast, there was no significant change in AF complexity in the LA, and cardioversion of AF was not achieved.ConclusionsIntra-atrial heterogeneity in response to IK,Ca inhibition by NS8593 was observed. The investigated dose of NS8593 increased the AF cycle length but was not sufficient to induce cardioversion. In terms of propagation properties during AF, IK,Ca inhibition by NS8593 led to divergent effects in the right and left atrium. This divergent behavior may have impeded the cardioversion success.

Superior-Type Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Phenotype Mimicking the Slow-Fast Type.

Superior-type fast-slow (sup-F/S-) atrioventricular nodal reentrant tachycardia (AVNRT) is a rare AVNRT variant using a superior slow pathway (SP) as the retrograde limb. Its intracardiac appearance, characterized by a short atrio-His (AH) interval and the earliest site of atrial activation in the His-bundle, is an initial indicator for making a diagnosis. Among 22 consecutive patients with sup-F/S-AVNRT, 3 (age, 68-81 years) patients had an apparent slow-fast (S/F-) AVNRT characterized by a long AH interval and the earliest site of atrial activation in or superior to the His-bundle region (tachy-long-AH). The diagnosis of sup-F/S-AVNRT was based on the standard criteria in 2 patients and on the occurrence of Wenckebach-type atrioventricular block during tachycardia, which was attributable to a block at the lower common pathway (LCP) below the circuit of the AVNRT, detected owing to the lower common pathway potentials, in one patient. As with the typical S/F-AVNRT, tachy-long-AH was induced after a jump in the AH interval. In contrast to typical S/F-AVNRT, fluctuation in the ventriculoatrial interval was observed during the tachy-long-AH. Ventricular overdrive pacing was unable to entrain or terminate the tachy-long-AH. Moreover, the tachy-long-AH reciprocally transited to/from sup-F/S-AVNRT spontaneously or was triggered by ventricular contractions while the atrial cycle length and earliest site of atrial activation remained unchanged. Both tachycardias were cured by ablation at a single site in the right-side para-Hisian region of 2 patients and the noncoronary aortic cusp of one patient. Collectively, the essential circuit of both tachycardias was identical, and the tachy-long-AH was diagnosed as another phenotype of sup-F/S-AVNRT accompanied by sustained antegrade conduction via another bystander slow pathway breaking through the His-bundle owing to the repetitive antegrade block at the lower common pathway, thus representing a long AH interval during the ongoing sup-F/S-AVNRT. An unknown sup-F/S-AVNRT phenotype exists that apparently mimics the typical S/F-AVNRT and is also an unknown subtype of apparent S/F-AVNRT.

Atriale en ventriculaire elektrische en contractiele “remodelling” en “reverse remodelling” van chronisch “pacing”-geïnduceerde atriale fibrillatie bij paarden: eerste resultaten

Na een langdurige periode van atriumfibrillatie neemt de elektrische en contractiele herstelperiode bij de mens meerdere weken in beslag. Momenteel is er maar weinig bekend over dit fenomeen bij het paard. In de voorliggende studie werden bij zes paarden een neurostimulator en een pacemaker ingepland om atriumfibrillatie (AF) te kunnen induceren en te onderhouden via een “burst-pacing”-mechanisme; en om de atriale en ventriculaire elektrofysiologie te kunnen bestuderen. Bij alle paarden ontstond persisterende AF na “burst pacing” gedurende twee tot vier weken. Parameters, zoals de atriale fibrillatiecyclus, de rechter atriale en ventriculaire refractaire periode en de gevoeligheid van het hart voor ritmestoornissen, zoals atriale aritmieën, atriale tachyaritmieën of AF, werden zowel voor en tijdens een AF-periode van vier maanden en gedurende een herstelperiode van twee maanden opgevolgd. De atriale en ventriculaire contractiliteit uitgedrukt in fractionele “shortening” en de grootte van de hartcompartimenten werden opgevolgd via 2D-echocardiografie. Bij twee van de zes paarden kon de procedure niet volledig opgevolgd worden ten gevolge van te hoge drempelwaarden (1 paard) of door een infectie ter hoogte van de “pocket” (1 paard). Bij de andere vier paarden konden er reeds na 48 uur van AF significante verschillen gemeten worden ten opzichte van de basale waarden. Tijdens de herstelperiode keerden alle waarden na één tot twee maanden naar de basale waarden terug. In dit onderzoek wordt aangetoond dat geïnduceerde chronische AF, elektrische en contractiele veranderingen teweegbrengt ter hoogte van het hart bij het paard maar dat deze veranderingen omkeerbaar zijn eens het sinusritme hersteld is. Deze resultaten suggereren dat er geen permanente schade veroorzaakt wordt door vier maanden pacing-geïnduceerde AF en dat een rustperiode van zes tot acht weken gunstig zou zijn alvorens het werk te hervatten.

Insights from atrial surface activation throughout atrial tachycardia cycle length: A new mapping tool

A novel "LUMIPOINT" software in the Rhythmia system (Boston Scientific) displays a histogram of activated area over the entire atrial tachycardia (AT) cycle length (CL) with a normalized score. The purpose of this study was to examine whether the pattern of this global activation histogram (GAH) identified reentrant vs focal AT and whether a decrease in atrial activation area, shown as valleys in the GAH, identifies isthmuses. One hundred eight activation maps of ATs (17 focal, 57 macroreentrant, 21 localized, 13 multiple loop) in 67 patients were reviewed retrospectively with the LUMIPOINT software. The ACTIVATION SEARCH feature highlighted the activated area in a given time period irrespective of the activation map. A 30-ms unit time interval was set, and the GAH patterns and electrophysiological properties of highlighted areas were examined. Focal ATs systematically displayed a plateau with GAH-Score <0.1 for at least 30% of the CL. Most reentrant ATs (90/91 [98.9%]) lacked this plateau and displayed activity covering the entire CL, with 2 [1-2] GAH-Valleys per tachycardia. Each GAH-Valley highlighted 1 [1-2] areas in the map. Among 264 highlighted areas, 198 (75.0%) represented slow conduction, 19 (7.2%) lines of block, 27 (10.2%) wavefront collision, 3 (1.1%) unknown, and 17 (6.4%) absence of activation in focal ATs. Practical ablation sites all matched one of the highlighted areas based on GAH-Valleys, and they corresponded better with areas highlighted by GAH-Score ≤0.2 (P <.0001). GAH shows focal vs reentrant mechanisms at first glance. Decrease in activated areas (displayed by GAH-Valleys) is mostly due to slow conduction and highlights areas of special interest, with 100% sensitivity for isthmus identification.