Multielectrode Mapping Research Articles

Ventricular Electrophysiological Effects of Vagal Nerve Stimulation in Humans With and Without Structural Heart Disease

Background and ObjectiveClinical trials investigating the benefits of vagus nerve stimulation (VNS) in heart failure have shown mixed results. This variation maybe due to inconsistent stimulation parameters, which may fail to adequately stimulate cardiomotor fibers required for cardio‐protection. However, overstimulation of the vagus nerve may cause adverse off‐target effects. Thus, the aim of this study was to assess the beneficial effects of moderate frequency VNS in patients with structurally normal hearts (SNH) and those with cardiomyopathy (CM).HypothesisModerate frequency VNS (10 Hz) confers ventricular electrophysiological effects.MethodsPatients with SNH and supraventricular tachycardia (n = 5) and cardiomyopathy patients with ventricular tachycardia (CM, n = 5) undergoing electrophysiology procedures were recruited. A multi‐electrode circular electrophysiology catheter was advanced from the femoral to the right internal jugular vein via a long sheath. Bipolar electrode pairs were serially stimulated and capture/stimulation of the vagus nerve identified by a negative chronotropic response. Threshold current was defined as a 10‐15% decrease in heart rate (HR) at 20 Hz and 1 ms pulse‐width. Stimulation was then performed at threshold current for 10 seconds at 10 and 20 Hz. Endocardial unipolar electrograms were continuously recorded using ventricular multielectrode mapping catheters and used to calculate activation recovery intervals (ARI), a validated surrogate of local action potential duration (APD). Electrodes were designated as overlying scar, border zone, or viable myocardium based on standard bipolar voltage mapping criteria in CM patients. ARIs were corrected for HR by the Framingham method.ResultsThe current of stimulation was 13.2 ± 1.7 mA in SNH and 14.4 ± 3.1 mA in CM (p = ns). VNS at 20 Hz significantly decreased HR (p ≤ 0.01) in both SNH and CM patients (12.6 ± 1.4% in SNH vs 12.9 ± 1.7% in CM, p= ns) while significantly prolonging global ventricular ARIs (2.2 ± 0.4% in SNH vs 4.6 ± 1.0% in CM, p= ns). The chronotropic effects of 10 Hz VNS were similar to 20 Hz in SNH (12.0 ± 1.4% at 10 Hz vs 12.6 ± 1.4% at 20 Hz, p = ns) but blunted in CM patients (12.0 ± 1.4% in SNH vs 4.9 ± 2.4% in CM, p≤ 0.05). Surprisingly, despite reduced chronotropic responses, global ARI prolongation persisted (4.0 ± 0.7% at 10 Hz vs 4.6 ± 1.0% at 20 Hz, p= ns) in CM patients. Importantly, ARI prolongation was observed in scar (326 ± 23 to 340 ± 22 ms, p≤ 0.05) and border zone regions (312 ± 18 ms to 323 ± 17 ms, p≤ 0.05). Moreover, after correcting ARI for heart rate (ARIc), 10 Hz VNS in CM patients caused significantly greater prolongation in ARIc than 20 Hz (1.8 ± 0.6% at 10 Hz vs ‐1.0 ± 0.6% at 20 Hz, p≤ 0.05), suggesting that higher frequency VNS may potentially cause a net shortening of ventricular APD.ConclusionsAcute application of moderate frequency VNS (10 Hz) demonstrated ventricular electrophysiological effects, with ARI prolongation observed in scar and border zone regions in diseased hearts. This human data validates previously reported effects of moderate frequency VNS in large animal infarct models. Stimulation at 20 Hz is unnecessary and may have negative ventricular electrophysiological effects. Further clinical trials assessing electrophysiological effects of chronic VNS in humans are required.

PO-666-05 A NOVEL DIPOLE CHARGE DENSITY MAPPING SYSTEM INTEGRATED IN ROBOTICS OFFERS ADVANTAGES FOR ABLATION OF ATRIAL TACHYCARDIAS: FIRST-IN-HUMAN EXPERIENCE

Catheter ablation (CA) for atrial tachycardia (AT) and atrial flutter (AFL) offers favorable acute and long-term outcomes. Until recently, mapping of AT/AFL was only possible with sequential mapping methods using manually controlled catheters. Even by implementing multielectrode mapping, some limitations exist during mapping of short-lived arrhythmias and ATs with unstable CL. Remote magnetic navigation (RMN) with its atraumatic catheter design has superior safety profile and excellent accuracy.

Influence of respiration and tissue contact on ventricular substrate identification during high density mapping: Results from an ovine infarct model.

Multielectrode mapping (MEM) and automated point collection are important enhancements to substrate mapping in ventricular tachycardia ablation. The effects of tissue contact and respiration on electrogram voltage with differing depolarization wavefronts with MEM catheters are unclear. Bipolar and unipolar voltages were collected from control (n = 5) and infarcted (n = 7) animals with a multispline MEM catheter. Electro-anatomic maps were created in sinus rhythm, and right and left ventricular pacing. Analysis was performed across three collections: standard settings (SS), respiratory-phase gating (RG), and electrode-tissue proximity (TP). Comparison was made to scar detected by cardiac MRI (cMRI). Compared to SS and RG acquisition, median bipolar and unipolar voltages were higher using TP, regardless of the depolarization wavefront. In infarct animals, bipolar voltages were 30.7%-50.5% higher for bipolar and 8.7%-13.8% higher on unipolar voltages with TP, compared to SS. The effect of RG on bipolar and unipolar voltages was minimal. Percentage of local abnormal ventricular activities was not impacted by acquisition settings or wavefront direction in infarct animals. Compared with cMRI defined scar, all three acquisition settings overestimated scar area using standard voltage-based cutoffs. RG improved the low voltage area concordance with MRI by 1.6%-5.1% whereas TP improved by 5.9%-8.4%. High density voltage mapping with a MEM catheter is influenced by point collection settings. Tissue contact filters reduced low voltage areas and improved agreement with cMRI fibrosis in infarcted ovine hearts. These findings have critical implications for optimizing filter settings for high density substrate mapping in the left ventricle.

616 Endocardial lead placement guided by high resolution voltage mapping in a patient with recurrent failure of transvenous pacing system

Abstract Methods and results A 58 years-old man was admitted to our intensive care unit for syncope due to inconstant capture of epicardial ventricular lead. His cardiovascular history began 20 years before when he underwent single chamber pacemaker implantation with insertion of a passive fixation ventricular lead for symptomatic complete atrio ventricular block (AVB). Electrical parameters were good at implantation. However, during follow-up a gradual and progressive increase of pacing threshold occurred, with no changes in impedance values, finally leading to complete loss of ventricular capture. Hence, 2 years later, the lead was extracted and a new transvenous ventricular lead was placed in septal position. All electrical parameters were optimal at the end of the procedure. However, in the following months threshold values gradually increased as previously observed. The referring clinicians decided to surgically extract both the device and transvenous lead and to implant an epicardial ventricular lead connected to an abdominal generator. The pacemaker worked properly for about 17 years until he was transferred to our institution with evidence of inconstant lead capture at maximum pacing outputs. A temporary transvenous pacemaker was immediately inserted. Clinical examination, laboratory exams, and echocardiography were normal. Cardiac magnetic resonance (MRI) was not feasible due to the epicardial lead. Thus, in order to obtain cardiac substrate characterization, we decided to perform high density multielectrode voltage mapping of the right ventricular endocardium with HD Grid multielectrode mapping catheter (HD Grid mapping catheter sensor enabled, Abbott Technologies, Minneapolis, MN). Electroanatomic voltage map allows distinction of areas of healthy myocardium (>1.5 mV) from scar tissue (<0.5 mV). Unexpectedly, voltage mapping highlighted no scar zones, showing a globally normal endomyocardial surface. Therefore, a new endocavitary pacemaker was inserted in right prepectoral region and an active fixation right ventricular lead was placed on mid-ventricular septum. A backup pacing lead was placed in a more apical position in an area of endocardial healthy myocardium. Post-procedural sensing, impedance and capture threshold were optimal (0.3 V × 0.4 ms for mid-septal lead and 0.3 × 0.4 ms for the other one). At 1 month follow-up mid-septal lead’s threshold was slightly increased (1.0 V × 0.4 ms) and further increase was observed at 3-month outpatient visit (1.75 V × 0.4 ms). Capture threshold of the other lead and other parameters were stable. The patient received remote monitoring for home surveillance of the implanted system. Home monitoring shows a trend toward a progressive increase of pacing threshold of the mid-septal lead and stable value of the other electrode. Conclusions The present report suggests an innovative use of high-density mapping with HD Grid catheter to characterize endocardial right ventricular myocardium in a patient with contraindication to cardiac MRI and recurrent failure of previous implanted pacing systems for unknown reason and to guide effective lead placement in areas of normal endocardial voltage. Combined use of telemedicine and high-resolution mapping technique allowed us to avoid unnecessary high risk reintervention for novel epicardial lead placement.

Abstract 12053: Age is a Predictor of Right Atrial Drivers in Human Persistent Atrial Fibrillation

Introduction: Persistent atrial fibrillation (perAF) may be maintained by localized extra-pulmonary vein (PV) drivers. Most clinical studies have focused on left atrial (LA) sources ablation, but right atrial (RA) arrhythmogenic substrate, due to certain comorbidities, may also maintain perAF. Hypothesis: Patient (Pt)-specific characteristics and comorbidities may predict occurrence of RA AF drivers. Methods: Consecutive Pts (n=105) underwent driver ablation in addition to PV isolation for perAF after panoramic multi-electrode mapping (MEM) at a single medical center. Logistic regression (LR) models were used to characterize the relationship between Pt characteristics and presence of AF drivers in each atrium. LR was used to predict 12-month AF-free survival. Results: Pts were 63.1±9.9 years old, 24.8% female, 21.9% in HF, 76.2% had HTN, 24.8% had DM, 22.9% had CAD and 59.0% had OSA. MEM identified a mean of 1.6±1.2 LA drivers and 1.4±1.2 RA drivers per Pt. Forty two Pts had drivers in both LA and RA, 19 in RA only, and 26 in LA only. Older age was a predictor of RA drivers presence (p=0.06), factors that predicted presence of LA drivers were female gender (p=0.19), HTN (p=0.03), and comorbidity score (p = 0.07). CHADS 2 -VASc score and LVEF predicted both LA and RA drivers. Following ablation, 75% of the Pts sustained sinus rhythm after 6 months, 70% after 12 months and 72% after 18 months. AF recurrence within 12 months of ablation was associated with DM (p=0.03), BMI (p=0.03) and RV systolic pressure (p=0.07). Presence of RA drivers was not associated with the 12 and 18-months freedom from AF. Conclusions: In this cohort of perAF patients, older age and higher CHADS 2 -VASc score predicted RA driver occurrence. These preliminary findings suggest that patient-specific clinical characteristics may uniquely impact LA vs RA myocardium by promoting development of chamber-specific arrhythmogenic structural and functional substrates of AF drivers.

B-PO05-017 IN VIVO TO EX VIVO HIGH RESOLUTION OPTICAL MAPPING AND CONTRAST ENHANCED MAGNETIC RESONANCE IMAGING TO REVEAL ATRIAL FIBRILLATION DRIVERS AND IMPROVE IDENTIFICATION OF ARRHYTHMOGENIC STRUCTURAL SUBSTRATES IN PERSISTENT ATRIAL FIBRILLATION CANINE MODEL

Persistent AF (perAF) may be maintained by reentrant drivers within arrhythmogenic fibrotic substrates. Conventional multielectrode mapping (MEM) and delayed enhancement (DE) magnetic resonance imaging (MRI) are suffering to identify drivers and their substrates and require rigorous validation. Define AF driving mechanism in vivo and ex vivo using near-infrared optical mapping (NIOM) in a perAF canine model and correlate driver locations with fibrosis architecture detected by histology validated 3D DE MRI. Canines (n=5) were imaged via DE MRI prior to perAF (induced by rapid atrial pacing) and after 4 months of self-sustained perAF. Atria were mapped with NIOM and MEM in vivo and ex vivo (Figure). Regional histology sections validated chamber-specific fibrosis thresholds on DE MRI. In all animals, AF was maintained by 2 localized temporally competing reentrant drivers in the left atrium (LA) visualized both in vivo and ex vivo. Ex vivo targeted ablation terminated or converted AF to slower tachycardia. MEM and NIOM showed comparable AF cycle length in vivo and ex vivo with driver regions faster than LA non-drivers and right atria (p<0.05). Histology validated DE MRI showed AF induced heterogeneous biatrial fibrosis upregulation, with higher fibrotic content in driver regions. In canine perAF model, integration of in vivo to ex vivo NIOM, MEM and DE MRI revealed that localized AF reentrant drivers within fibrotic substrates maintain AF. The higher imaging acuity of in vivo NIOM and histology validated DE MRI could allow to define fingerprints of arrhythmogenic fibrotic driver hubs for patient-specific targeted AF ablation.

B-011-23 QRS CHARACTERISTICS DURING LEFT BUNDLE BRANCH PACING WITH AND WITHOUT BIDIRECTIONAL LEFT INTRAHISIAN BLOCK

LBB (left bundle branch) pacing has been proposed as a novel modality to achieve cardiac resynchronization. However, selective capture of the left bundle is physiologically expected to produce a wide QRS, with variability based on the integrity of retrograde right bundle conduction. To study QRS characteristics during left bundle branch pacing with and without bidirectional left intrahisian block. 27 patients underwent multielectrode mapping of the left conduction system with pacing from the region of the left bundle branch. QRS duration was compared between selective and nonselective LBB pacing, in addition to the S-His interval to assess for the presence of retrograde LBB block at the left in the left His fibers. Amongst 27 patients with antegrade LBB, pacing from the selective LBB resulted in wider QRS compared to nonselective pacing (147± 21ms vs 130±17 ms, p=0.02). Left intrahisian block was bidirectional in 100% of cases of LBBB with complete conduction block with long stimulus to His intervals (148±42 in nonselective LBB pacing vs 176±42ms in selective LBB pacing, p<0.001). In patients with intact Purkinje activation, pacing more distally in the left conduction system resulted in progressively wider QRS due to smaller contribution from retrograde right bundle resynchronization. The stimulus to left ventricular activation time became shorter as pacing more distal LBB. In patients with right bundle branch block, same QRS width with pacing different site of LBB due to the failure of RBB resynchronization. Due to the presence of bidirectional intrahisian left bundle branch block, wide QRS paced morphologies were uniformly observed during selective LBB capture. Nonselective LBB capture results in shorter QRS duration due to myocardial fusion with more rapid engagement of the right bundle. The physiology of LBB pacing for CRT is predicated upon fusion with intrinsic QRS and nonselective myocardial capture.

B-PO03-030 EFFICACY OF ESTROGEN SUPPLEMENT ON VENTRICULAR SUBSTRATE IN A RABBIT MODEL OF MENOPAUSE

Sympathetic hyperactivity in menopausal subjects may lead to autonomic dysfunction and arrhythmic vulnerability. Estrogen supplement has beneficial effects on the cardiovascular diseases, however, the efficacy of hormone therapy is questionable. We aimed to evaluate the efficacy of estrogen supplements in the myocardial substrates of menopausal rabbits with ovariectomy (OVX). Eight-teen New Zealand female rabbits were randomized into control (n=6), OVX (n=6), and OVX-Estrogen (OVX-E) group (n=6). The menopause model was done by bilateral OVX. All rabbits received blood samples, EP studies, and VT inducibility tests (Max output with shortest 1:1 cycle length pacing) with a high-density contact multielectrode mapping after induction of sustained VT. Myocardium was harvest for Trichrome and tyrosine stain. The estrogen and progesterone levels of the 3 groups are shown in Figure A. The atrial and ventricular ERPs in the OVX group were significantly longer than the control and OVX+E group (Fig. B, C). The VT inducibility of the OVX-E group was significantly higher than the control group (18.41±1.88% vs. 7.01±1.65%, p=0.035). The ventricular fibrotic tissue of the OVX group was significantly higher than OVX-E and control group (Fig. D). The LV and RV sympathetic innervation in the OVX group were significantly increased than the control and OVX+E group (Fig. E). Menopause leads to cardiac remodeling and increases ventricular arrhythmogenicity. Estrogen supplements can improve vulnerability to VT, decrease fibrosis formation, and decrease sympathetic innervation.

B-PO03-202 ABLATION OF ATRIAL FIBRILLATION AND FLUTTER IN ADULT CONGENITAL HEART DISEASE: PROCEDURAL ASPECTS AND OUTCOMES

Patients with ACHD have increased risk of arrhythmia due to underlying condition and prior surgeries. To assess ablation success of atrial fibrillation and flutter in ACHD. All ACHD patients who underwent EP ablation for atrial fibrillation or flutter from 12/2013 to 11/2020 were included, for a total of 46 subjects and 58 ablations. Median age was 58.0 (IQR = 41.0 - 68.0), 67.4% were male and 80.4% had prior corrective surgery. Prior to ablation, 67.4% failed an average of 1.39 antiarrhythmic drugs (AAD). Of the 58 ablations performed, 22 (37.3%) had atrial fibrillation, 21 (35.6%) had atrial flutter and 16 (27.1%) had both. At the end of procedure, acute success rate was 81.1%, with 18.9% requiring cardioversion. Twelve patients had second ablation, with total recurrence rate of 41.3%, at follow up of 38.7 +/- 23.4 months. Rate of recurrence was not significantly different among patients who had atrial fibrillation, flutter or both (χ2 = .804, p = .669). Recurrence predictors (by logistic regression) revealed use of smart touch catheter with lower rate of arrhythmia recurrence (OR = .0702, p = .014) and DCCV with higher rate (OR = 4.50, p = .027). Multielectrode mapping decreased mean RF time by 1,130 seconds (t = 2.19, p = .0338). One year after ablation, 17.4% of subjects were on AAD, for a 74.2% decrease (z = 4.56, p < .001). Four (8.7%) subjects died during the study period, ranging 103 to 1260 days after ablation. Four (8.7%) subjects required pacemaker. Atrial arrhythmia ablation is safe and recommended in patients with ACHD, reducing need for AAD. Successful ablation without arrhythmia recurrence remains a challenge.

Does merged three-dimensional mapping improve contact force and long-term procedure outcome in atrial fibrillation ablation? (MICRO-AF study): a prospective randomized controlled study.

Integration of electroanatomical map (EAM) with preacquired three-dimensional (3D) cardiac images provides detailed appreciation of the complex anatomy of the left atrium (LA) and pulmonary vein (PV). High-density (HD) multi-electrode mapping catheters have enabled creating more accurate EAM reflecting real-time volume-rendered LA-PV geometry during atrial fibrillation (AF) ablation. However, no study has compared the outcomes of AF ablation using HD-EAM versus 3D-merged map. We aimed to investigate the procedural and clinical outcomes of AF ablation with HD-EAM (HD-EAM group) versus 3D-merged map (Merge group). One hundred patients (59.5 ± 11.5 years, 53% with paroxysmal AF [PAF]) were randomly assigned (1:1) to HD-EAM or Merged group. HD multi-electrode mapping and contact force (CF)-sensing catheters were used to create virtual LA-PV chamber and to perform wide antral circumferential ablation (WACA), respectively. The two groups showed no significant differences in baseline characteristics and procedural data including ablation time, fluoroscopy time, LA voltage, and CF. PV isolation with a single WACA line was achieved in 21 (42%) and 27 (54%) patients in the Merge and HD-EAM groups, respectively (P = NS). CF was significantly lower in lesions with gap than lesions without gap after a single WACA (7.3 ± 7.3g vs. 16.0 ± 8.3, respectively, P < 0.001). During the 12-month follow-up, no significant difference in AF recurrence was observed between two groups, irrespective of AF type. In multivariate analysis, non-PAF was an independent risk factor for AF recurrence. Integration of 3D cardiac imaging did not improve procedural and clinical outcomes. HD-EAM provides an accurate real-time LA geometry.

Real-time multielectrode mapping of pulmonary vein gap closure.

Real-time multielectrode mapping of pulmonary vein gap closure.

Pattern Matching Filter and multielectrode mapping catheter - A new approach for complex premature ventricular contraction ablation.

Our goal was to assess usefulness of Pattern Matching Filter (PMF) software combined with the PentaRay catheter for complex premature ventricular contraction (PVC) ablation. A prospective observational study of consecutive patients referred for complex PVC ablation at our tertiary center from January to September 2018. Patients underwent ablation using a pre-specified mapping strategy with the PMF and the PentaRay catheter (PVCs with ≥97% correlation with the template morphology were collected). Procedural endpoints and acute and 12-months success rates were assessed and compared to a retrospective cohort of patients who also underwent a complex PVC ablation with standard activation mapping performed with a Thermocool SmartTouch catheter. During the nine-month enrollment period, seven patients fulfilled our inclusion criteria, while there were four patients in the control group. Patients treated with the PMF and PentaRay had a fivefold number of points acquired (507±213 vs. 90±62) and a halved procedure time (67±42 vs.130±54 min), required a shorter radiofrequency ablation time (294±112 vs.706±613 sec) and had a higher overall success rate (100% vs.75%) when compared to the standard approach. No major complications occurred in either group. In this first study assessing the combined use of the PentaRay catheter and the PMF for complex PVCs ablation, we demonstrate how this approach can improve the level of detail, accuracy and reliability of the activation map, while reducing the number of radiofrequency applications and procedural time. Further studies are warranted to confirm whether this approach can lead to improved outcomes.

Outcome of catheter ablation of arrhythmias in adult congenital heart disease with high density multi-electrode mapping with automatic annotation algorithm

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Arrhythmias are frequently encountered in adult congenital heart disease (ACHD) and respond poorly to pharmacological therapies. Catheter ablation is challenging due to anatomical variation and complexity of the arrhythmia substrate. High density multi electrode mapping (MEM) with automatic annotation of activation time may aid mapping of arrhythmia, decrease procedure time and improve the accuracy of targeting of ablation therapy. Purpose To compare the acute and long term outcomes and procedural characteristics of catheter ablation in ACHD patients with and without automatic annotation of activation with MEM. Methods Retrospective analysis of the acute and long term outcomes of ACHD patients in a single centre undergoing ablation procedures from 1 Jan 2014 to 18 August 2017 was undertaken. 2 groups were identified. Group 1 included patients who had arrhythmia mapping performed with the CARTO 3D electroanatomic mapping system without the use of automatic signal annotation. Most patients in this group had sequential mapping performed with the ablation catheter (78%), the rest had multi-electrode mapping with the PentaRay 20 pole catheter. Group 2 included patients who had arrhythmia mapping performed with the CARTO 3D electroanatomic mapping system using the automated CONFIDENSE mapping algorithm. Results Group 1: n = 27, mean age 44.6 +/-3 years. Male 46.6%. Group 2: n = 38, mean age 44.0 +/- 1.9 years. Male 56.7%. All patients had CHD of at least moderate complexity. 25% of patients in group 1 and 45% in group 2 were repeat ablations. 45 arrhythmias were induced in group 1 of which 29 were targeted and 74 arrhythmias were induced in group 2 of which 46 were targeted. Acute success rates (after attempts at reinduction) were 96.3% in group 1 and 94.7% in group 2. Recurrences of arrhythmia occurred significantly less in patients in group 2 compared to group 1 (44.7% and 70.4% respectively, p &amp;lt; 0.05) after a follow up duration of 17.3+/-0.43 months in group 2 and 45.3 +/-1.19 months in group 1. Fluoroscopy time, procedure time and ablation time were not significantly different between groups. Conclusions The use of multi-electrode mapping with an automatic annotation algorithm was associated with a significantly lower risk of recurrence during the follow up period of this study.

Limitations and Pitfalls of Substrate Mapping for Ventricular Tachycardia.

The fundamental hypothesis of substrate mapping for scar-mediated ventricular tachycardia is that surrogates of the isthmus can be identified and targeted with ablation during sinus rhythm. These surrogates include electrocardiographic indications for electric discontinuity such as fractionation, split, late, and long potentials, also evident as sites displaying activation slowing. However, ablation strategies targeting these surrogates during sinus rhythm have resulted in unacceptably high rates of clinical failures, promoting the idea that a more widespread ablation may be required. High-resolution mapping technologies provide an opportunity to examine the substrate at greater detail; however, their use has not yet translated into improved clinical outcomes. This may be related to ongoing efforts to examine the same surrogates at higher resolution instead of using high-resolution technologies for discovering new and potentially more specific surrogates. This article reviews common limitations and pitfalls of substrate mapping and discusses new opportunities for high-resolution mapping to increase the accuracy of substrate mapping: 1) multielectrode mapping catheters provide an opportunity to rapidly examine the substrate during electrophysiological conditions that more closely simulate ventricular tachycardia by means of activation from different directions and coupling intervals; 2) electrogram annotation methods based on the maximal negative derivative of the extracellular potential or maximal voltage are often inaccurate in nonuniform anisotropic tissue. The use of multielectrode catheters may improve the accuracy of electrogram annotation by using spatiotemporal dispersion of single-beat acquisitions and a localized indifferent reference; and 3) resetting and entrainment remain important methods for studying re-entry for and guiding ablation.

Novel approaches to mechanism-based atrial fibrillation ablation.

Modern cardiac electrophysiology has reported significant advances in the understanding of mechanisms underlying complex wave propagation patterns during atrial fibrillation (AF), although disagreements remain. One school of thought adheres to the long-held postulate that AF is the result of randomly propagating wavelets that wonder throughout the atria. Another school supports the notion that AF is deterministic in that it depends on a small number of high-frequency rotors generating three-dimensional scroll waves that propagate throughout the atria. The spiralling waves are thought to interact with anatomic and functional obstacles, leading to fragmentation and new wavelet formation associated with the irregular activation patterns documented on AF tracings. The deterministic hypothesis is consistent with demonstrable hierarchical gradients of activation frequency and AF termination on ablation at specific (non-random) atrial regions. During the last decade, data from realistic animal models and pilot clinical series have triggered a new era of novel methodologies to identify and ablate AF drivers outside the pulmonary veins. New generation electroanatomical mapping systems and multielectrode mapping catheters, complimented by powerful mathematical analyses, have generated the necessary platforms and tools for moving these approaches into clinical procedures. Recent clinical data using such platforms have provided encouraging evidence supporting the feasibility of targeting and effectively ablating driver regions in addition to pulmonary vein isolation in persistent AF. Here, we review state-of-the-art technologies and provide a comprehensive historical perspective, characterization, classification, and expected outcomes of current mechanism-based methods for AF ablation. We discuss also the challenges and expected future directions that scientists and clinicians will face in their efforts to understand AF dynamics and successfully implement any novel method into regular clinical practice.

Pattern Matching Filter and multielectrode mapping catheter – A new approach for complex premature ventricular contraction ablation

PurposeOur goal was to assess usefulness of Pattern Matching Filter (PMF) software combined with the PentaRay catheter for complex premature ventricular contraction (PVC) ablation. MethodsA prospective observational study of consecutive patients referred for complex PVC ablation at our tertiary center from January to September 2018. Patients underwent ablation using a pre-specified mapping strategy with the PMF and the PentaRay catheter (PVCs with ≥97% correlation with the template morphology were collected). Procedural endpoints and acute and 12-months success rates were assessed and compared to a retrospective cohort of patients who also underwent a complex PVC ablation with standard activation mapping performed with a Thermocool SmartTouch catheter. ResultsDuring the nine-month enrollment period, seven patients fulfilled our inclusion criteria, while there were four patients in the control group. Patients treated with the PMF and PentaRay had a fivefold number of points acquired (507±213 vs. 90±62) and a halved procedure time (67±42 vs.130±54 min), required a shorter radiofrequency ablation time (294±112 vs.706±613 sec) and had a higher overall success rate (100% vs.75%) when compared to the standard approach. No major complications occurred in either group. ConclusionsIn this first study assessing the combined use of the PentaRay catheter and the PMF for complex PVCs ablation, we demonstrate how this approach can improve the level of detail, accuracy and reliability of the activation map, while reducing the number of radiofrequency applications and procedural time. Further studies are warranted to confirm whether this approach can lead to improved outcomes.

Abstract 15311: Drivers Associated With Dense Fibrotic Regions Are Critical Targets in Extra-Pulmonary Vein Ablation in Persistent Atrial Fibrillation

Background: Multielectrode mapping (MEM) of extra-pulmonary vein (PV) targeted ablation of persistent atrial fibrillation (PsAF) drivers suffers from false positives. Early studies suggest that true AF drivers are anchored to arrhythmogenic fibrosis, which can be visualized with late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) to distinguish them from false positive drivers on MEM. Hypothesis: Driver regions integral to AF correlate with high atrial fibrosis; therefore, ablation of MEM-defined drivers within fibrotic regions may lead to better outcomes than MEM-defined drivers outside fibrosis. Methods: Pre-ablation, 10 PsAF patients (Pts) (70% male; 65±11 y/o) underwent LGE-CMR at 3T (0.625x0.625x1.25mm 3 , 0.2mmol/kg gadolinium). During ablation, MEM (64-electrode basket catheter) was used to identify Pt-specific extra-PV drivers. Retrospectively, both left (LA) and right atria (RA) were analyzed with atria-specific fibrosis masks (voxels exceeding an intensity of 3-3.5 standard deviations above the mean intensity of nonfibrotic atrial wall). Ablated drivers were classified as fibrotic driver (dense or patchy) or nonfibrotic driver by LGE-CMR and MEM correlation. Results: 30 drivers were ablated in 10 PsAF Pts (2±1 LA drivers/Pt, 1±1 RA drivers/Pt) and were classified if anchored to dense (n=16, 45.4±31.7%, 2.6±1.8cm 2 ), patchy (n=11, 8.9±13.5%, 2.0±2.5cm 2 ), or no (n=3, 2.3±2.0%) fibrosis. At follow-up (13±7 mos), 7/10 Pts remained free from AF and atrial flutter, all of whom had at least one dense fibrosis driver ablated and all but 1 Pt had ablations limited to fibrotic drivers. 2/3 patients with failure at follow-up had a nonfibrotic driver ablated. Conclusion: Our results suggest that limiting ablation of AF drivers to those anchored to dense fibrotic substrate may improve long-term AF-free survival. Identification of Pt-specific fibrotic substrate by LGE-CMR may help specificity of MEM ablation targets for successful PsAF treatment.

Abstract 14897: Activation Dyssynchrony Between Contact Multielectrode Mapping and Subsurface Near-Infrared Optical Mapping During Human Atrial Fibrillation

Due to complex 3D human atrial structure, atrial fibrillation (AF) mapping with multielectrode arrays (MEA) mostly represents surface activation. Therefore, MEA may not properly visualize patient specific AF mechanisms, which impairs ablation outcomes. Conversely, near-infrared optical mapping (NIOM) visualizes subsurface intramural activation and can efficiently reveal reentrant drivers responsible for AF maintenance. Delay between surface activation seen by MEA electrograms (EGMs) vs subsurface activation seen by NIOM optical action potentials (OAPs) occurs due to dyssynchrony between myocardium layers, especially during AF. Coronary perfused explanted human atria (n=7) were mapped with NIOM (0.3-0.9mm 2 resolution) and 64-electrode MEA (3mm 2 resolution). Unipolar EGMs were analyzed for the steepest negative deflection. The delay between [-dV/dtmax] of unipolar EGMs and corresponding optical action potentials (OAPs) was compared in 500ms and 300ms pacing and AF. Subsequent structural analysis was done by 9.4T MRI (154-180μm 3 resolution) with gadolinium enhancement and histology. Delay between EGM and OAP local activation times rate-dependently and heterogeneously increased from 6±3 ms and 10±4 ms during 500ms and 300ms pacing to 15±11 ms (with maximum delay 47±18 ms) during pacing induced AF (average cycle length 124±65ms). Large local OAP-EGM delay, seen during AF, correlates with higher fibrosis percentage and fiber twist (p&lt;0.05). NIOM identified reentrant drivers maintaining AF, which were incorrectly visualized as multiple breakthroughs in 68% of MEA maps (n=22). Higher frequency leads to an increased activation discrepancy between EGM and NIOM caused by increased dyssynchrony in regions of higher fibrosis percentage and fiber twist, which may prevent MEA from proper identification of AF drivers in diseased fibrotic human atria. Reannotation of EGM activation based on NIOM may be required for correct AF mechanisms visualization.

Abstract 14900: Human Atrial Fibrillation Drivers Revealed by Machine Learning Using Multicomponent Electrograms and 3D CE-MRI Structural Features

Introduction: Conventional multielectrode mapping is not sufficient to reveal subsurface intramural activation. Thus, atrial fibrillation (AF) driver identification remains challenging. To overcome these limitations we utilized machine learning (ML) to identify AF drivers based on the combination of electrogram (EGM) and 3D structural magnetic resonance imaging (MRI) features. Hypothesis: Detailed electrogram features analysis, including minor deflections, combined with local structural features, can be used to define AF driver. Methods: Sustained AF was mapped in coronary perfused explanted human atria (n=7) with near-infrared optical mapping (NIOM) (0.3-0.9mm 2 resolution) and 64-electrode mapping catheter (3mm 2 resolution). Unipolar EGMs were analyzed for multiple features of the steepest negative deflection and the 2nd-4th steepest deflections in multicomponent EGMs. Atria underwent 9.4T MRI (154-180μm 3 resolution) with gadolinium enhancement and histology validation of fibrosis. Both 3D structural and EGM data from NIOM defined driver and non-driver regions were processed by ML algorithms (LR; PLSDA; GBM; CRF; PSVM; RSVM) using double cross-validation. Results: AF drivers’ reentrant tracks were defined by NIOM activation mapping, the gold-standard, and confirmed by targeted ablation. The best performing ML algorithm (PLSDA) correctly classified mapped driver region with 76.1% accuracy on the testing data. The most important features included sub-endocardial fibrosis, sub-epicardial fiber orientation, local wall thickness, beat-to-beat variability of multicomponent EGM deflections. Conclusions: The ML models pre-trained on combined EGM and structural features allow efficient classification of AF driver vs non-driver regions defined by the NIOM gold-standard. The results suggest that AF driver substrates formed by the combination of 3D fibrotic structural features, which correlate with local EGM characteristics.

Circuit Determinants of Ventricular Tachycardia Cycle Length: Characterization of Fast and Unstable Human Ventricular Tachycardia.

Fast ventricular tachycardias (VTs) have historically been attributed to shorter path lengths with smaller reentrant circuit dimensions in animal models. The relationship between the dimensions of the reentrant VT circuit and tachycardia cycle length (TCL) has not been examined in humans. This study aimed to analyze the determinants of the rate of human VT with comparison of circuit dimensions and conduction velocity (CV) across a wide range of both stable and unstable VTs delineated by high-resolution mapping. Fifty-four VTs with complete circuit delineation (>90% TCL) by high-resolution multielectrode mapping were analyzed in 49 patients (men, 88%; age, 65 years [58-71 years]; nonischemic, 47%). Fast VT was defined as TCL <333 milliseconds (rate >180 bpm). Unstable VT was defined by hemodynamic deterioration with an intrinsic mean arterial pressure <60 mm Hg during a sustained episode. The median TCL of VT was 365 milliseconds (306-443 milliseconds), and 24 fast VTs were characterized. A wide range of CVs was observed within the entrance (0.03-0.55 m/s), common pathway (0.03-0.77 m/s), exit (0.03-0.53 m/s), and outer loop (0.17-1.13 m/s). There were no significant differences in the median dimensions of the isthmus and path length between fast and slow VTs and between unstable and stable VTs. The outer loop CV was the only circuit component that correlated with TCL in both ischemic cardiomyopathy (r=-0.5, P=0.006) and nonischemic cardiomyopathy (r=-0.45, P=0.028). The duration of the longest diastolic electrogram was inversely correlated with the dimensions of common pathway (length: r=-0.46, P=0.001, width: r=-0.3, P=0.047) and predictive of rapid VT termination by a single radiofrequency application (r=-0.41, P=0.023). Because of a wide spectrum of CV observed within the reentrant path during human VT, the dimensions of the circuit were not predictive of VT cycle length. For the first time, we demonstrate that the CV of the outer loop, rather than isthmus, is the principal determinant of the rate of VT. The size of the circuit was similar between fast and slow VTs and between unstable and stable VTs. Long, continuous electrograms were indicative of spatially confined isthmus dimensions, confirmed by rapid termination of VT during radiofrequency delivery.