Pulmonary Vein Region Research Articles

Low voltage area in the left atrial anterior wall predict Marshall-PLAN failure in patients with persistent atrial fibrillation

Abstract Background The most appropriate ablation strategy for persistent atrial fibrillation (PeAF) has not yet been determined. However, ethanol infusion of the vein of Marshall (VOM) combined with a linear set of ablation lesions (namely the Marshall-PLAN) has yielded encouraging results (1). Purpose Our study aimed at analyzing the relationship between low voltage areas (LVA) and arrhythmias recurrences in a PsAF population treated with the Marshall-PLAN. Methods we conducted a retrospective study on consecutive patients undergoing first catheter ablation (CA) for PsAF between 2021 and 2022 at our center. Pulmonary vein isolation (PVI), mitral isthmus ablation (VOM ethanol infusion, endocardial ablation and epicardial ablation in the great cardiac vein), left atrial (LA) roofline and cavo-tricuspid isthmus ablation were carried out in all the patients. Bidirectional block was validated for all the linear lesions as well as for PVI. Pre-ablation LA electroanatomic maps were built with CARTOv3 system and the PentaRay mapping catheter (minimum 3000 points). LVA were identified as areas >1cm2 (containing ≥3 neighboring points with ≤10mm distance) with bipolar voltage <0.5mV in SR and <0.24 mV in AF (2). All patients were followed for at least 12 months. Results Overall, 93 patients (69±7years, 30% female) with PsAF were included. Their left-ventricle ejection fraction and left atrial volume indexed for body surface area (LAVI) were 57% and 92±20 ml/m2. LA maps demonstrated at least one LVA in 70 subjects (75.3%). The mean relative surface of LA in which a LVA was evidenced was 8±14%. LVA were found within the anterior LA wall in 49 patients (53%), in the posterior wall in 33 patients (35.5%), in the inferior wall in 22 patients (24%), in the lateral wall in 14 patients (15.1%) and in the pulmonary vein region in 44 patients (47.3%). After 19±6 months of follow-up, 28 (30%) patients had AF recurrence. At Cox regression analysis (including LVA burden and LAVI dimensions), LVA localized within the anterior LA wall were predictive of arrhythmia recurrences (hazard ratio [HR] 2.0 [95% CI, 1.1–4.7], P=0.04). Kaplan-Meier estimates of survival free from recurrences at 20 months were 51% and 88% in patients with and without LVAs in the anterior LA wall (Log-rank 0.006). Conclusions The Marshall-PLAN led to a global AF-free survival of 70% after 19±6 months in our cohort of patients with PsAF. Importantly however, the data show that the subset of patients with LVA in the anterior LA wall (i.e., the LA region not targeted by the pre-specified ablation set here evaluated) have a 55%-only AF-free survival while that of patients without LVA in the anterior LA wall was of 88%. As a result, our study supports the relevance of atrial substrate assessment and the possibility of CA strategy optimization in the subset of patients with PsAF and LVA in the anterior LA wall (3).

Analysis of the effectiveness of the latest 4th-generation cryoballoon catheters in pulmonary vein isolation using high-resolution mapping

BackgroundLong-term data showed that up to 27% of pulmonary veins are reconnected using cryoballoon ablation. This study aimed to evaluate the efficacy of the latest 4th-generation cryoballoon catheters using ultra high-resolution mapping. MethodsIn patients with atrial fibrillation, a standard pulmonary vein isolation (PVI) with the latest 4th-generation cryoballoon catheter (Arctic Front Advance PRO, Medtronic Minneapolis, USA) and the spiral mapping catheter (Achieve Advance, Medtronic, Minneapolis, MN, USA) was performed. Subsequently, high-resolution mapping was achieved using the novel multipolar grid mapping catheter (Advisor HD Grid SE, Abbott Laboratories, USA). Follow-up was obtained after 6 months by means of a 7-day Holter electrocardiogram. ResultsIn our study, acute PVI was successfully achieved in all 31 patients. The latest 4th-generation cryoballoon catheter is safe in the acute phase of PVI. Additional high-resolution mapping (mean points per map 21,001 ± 4911) using the multipolar grid mapping catheter enabled us to identify residual gaps only in the carina pulmonary vein region; therefore, no additional ablation was performed. Three of 31 patients (10%) presented with atrial arrhythmia recurrence always related with pulmonary vein reconnection; using high-resolution mapping had no additional benefit in identifying pulmonary veins in which reconnection will occur. ConclusionThe utility of additional high-density mapping, facilitated by the HD Grid catheter after PVI with the 4th-generation cryoballoon catheter do not substantiate a discernible advantage over conventional mapping methodologies, particularly, the spiral mapping catheter. Residual carinal conduction was observed in a substantial cohort of patients (48%), highlighting a persistent challenge in achieving complete electrical isolation.

Interactions between calcium-induced arrhythmia triggers and the electrophysiological-anatomical substrate underlying the induction of atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is sustained by spontaneous focal excitations and re-entry. Spontaneous electrical firing in the pulmonary vein (PV) sleeves is implicated in AF generation. The aim of this simulation study was to identify the mechanisms determining the localisation of AF triggers in the PVs and their contribution to the genesis of AF. A novel biophysical model of the canine atria was used that integrates stochastic, spontaneous subcellular Ca2+ release events (SCRE) with regional electrophysiological heterogeneity in ionic properties and a detailed three-dimensional model of atrial anatomy, microarchitecture and patchy fibrosis. Simulations highlighted the importance of the smaller inward rectifier potassium current (IK1 ) in PV cells compared to the surrounding atria, which enabled SCRE more readily to result in delayed-afterdepolarisations that induced triggered activity. There was a leftward shift in the dependence of the probability of triggered activity on sarcoplasmic reticulum Ca2+ load. This feature was accentuated in 3D tissue compared to single cells (Δ half-maximal [Ca2+ ]SR =58μM vs. 22μM). In 3D atria incorporating electrical heterogeneity, excitations preferentially emerged from the PV region. These triggered focal excitations resulted in transient re-entry in the left atrium. Addition of fibrotic patches promoted localised emergence of focal excitations and wavebreaks that had a more substantial impact on generating AF-like patterns than the PVs. Thus, a reduced IK1 , less negative resting membrane potential, and fibrosis-induced changes of the electrotonic load all contribute to the emergence of complex excitation patterns from spontaneous focal triggers. KEY POINTS: Focal excitations in the atria are most commonly associated with the pulmonary veins, but the mechanisms for this localisation are yet to be elucidated. We applied a multi-scale computational modelling approach to elucidate the mechanisms underlying such localisations. Myocytes in the pulmonary vein region of the atria have a less negative resting membrane potential and reduced time-independent potassium current; we demonstrate that both of these factors promote triggered activity in single cells and tissues. The less negative resting membrane potential also contributes to heterogeneous inactivation of the fast sodium current, which can enable re-entrant-like excitation patterns to emerge without traditional conduction block.

Predictive utility of the impedance drop on AF recurrence using digital intraprocedural data linked to electronic health record data

Local impedance drop in cardiac tissue during catheter ablation may be a valuable measure to guide atrial fibrillation (AF) ablation procedures for greater effectiveness. The study sought to assess whether local impedance drop during catheter ablation to treat AF predicts 1-year AF recurrence and what threshold of impedance drop is most predictive. We identified patients with AF undergoing catheter ablation in the Mercy healthcare system. We downloaded AF ablation procedural data recorded by the CARTO system from a cloud-based analytical tool (CARTONET) and linked them to individual patient electronic health records. Average impedance drops in anatomical region of right and left pulmonary veins were calculated. Effectiveness was measured by a composite outcome of repeat ablation, AF rehospitalization, direct current cardioversion, or initialization of a new antiarrhythmic drug post-blanking period. The association between impedance drop and 1-year AF recurrence was assessed by logistic regression adjusting for demographics, clinical, and ablation characteristics. Bootstrapping was used to determine the most predictive threshold for impedance drop based on the Youden index. Among 242 patients, 23.6% (n = 57) experienced 1-year AF recurrence. Patients in the lower third vs upper third of average impedance drop had a 5.9-fold (95% confidence interval [CI] 1.81-21.8) higher risk of recurrence (37.0% vs 12.5%). The threshold of 7.2 Ω (95% CI 5.75-7.7 Ω) impedance drop best predicted AF recurrence, with sensitivity of 0.73 and positive predictive value of 0.33. Patients with impedance drop ≤7.2 Ω had 3.5-fold (95% CI 1.39-9.50) higher risk of recurrence than patients with impedance drop >7.2 Ω, and there was no statistical difference in adverse events between the 2 groups of patients. Sensitivity analysis on right and left wide antral circumferential ablation impedance drop was consistent. Average impedance drop is a strong predictor of clinical success in reducing AF recurrence but as a single criterion for predicting recurrence only reached 73% sensitivity and 33% positive predictive value.

How sex affects the sinus rhythm heartbeat

BackgroundThere is increasing awareness of sex-specific differences in epidemiology and pathophysiology of atrial fibrillation (AF). It is, however, unknown whether males and females differ in atrial electrophysiological properties during sinus rhythm (SR). The aim of this study was therefore to investigate sex-based (regional) differences in electrophysiological properties during SR of the right (RA) and left (LA) atrium including Bachmanns Bundle (BB) and pulmonary vein region (PVA). MethodsIntra-operative, high resolution mapping during SR was performed in 53 matched females with males (without a history of AF), to measure lines of conduction block (CB), continuous conduction delay and block (cCDCB), conduction velocities (CV), total atrial activation times (TAT), unipolar potential voltages and percentage of low voltage areas (LVA). ResultsCompared to males, females have significantly 1) lower unipolar potential voltages and slower CV at both RA and BB, 2) more LVAs, CB and cCDCB lines and longer CB and cCDCB lines at the RA only (all P < 0.05). ConclusionsElectrophysiological properties of the atria during SR differ between males and females. These sex-based differences are particularly present at the RA and to a lesser degree at BB. In females, both the RA and BB contained more areas of conduction disorders and low voltage potentials. Future studies are required to investigate whether these areas play a role in sex-based differences in vulnerability to arrhythmias such as atrial fibrillation.

Detection of the most dominant drivers of atrial fibrillation based on repetitive activity in sequential electro-anatomical mapping

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work is part of Personalize AF. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974, This work was also supported by the Swiss National Supercomputing Centre (CSCS), project s1074. Introduction Detecting and targeting the most dominant drivers of atrial fibrillation (AF) might improve the outcome of AF ablation procedures. We hypothesize that dominant drivers entrain their vicinity in a temporally and spatially stable manner resulting in local as well as adjacent repetitive activation patterns. Purpose We present a novel approach to detect the most dominant drivers of AF based on driver repetitiveness and the degree to which they entrain their vicinity. Methods We retrospectively analyzed a dataset of high-density bi-atrial sequential mapping in ablation-naive persistent AF patients (n=13, 30s recording per site). Candidate drivers (focal activity or re-entry) were detected based on local activation time analysis of unipolar electrograms. Focal activity was defined as radial spread of activation, re-entry as a circular activation sequence on at least 4 splines of the mapping catheter that covered &amp;gt;50% of the AF cycle length. As a measure of driver stability, we determined the driver's local repetitiveness (in % of recording). As a measure of driver-associated entrainment, we determined the directionally coherent repetitiveness of adjacent recordings within 30 mm (Figure 1). Following our hypothesis, most dominant drivers can be recognized by their high local and directional coherent adjacent repetitiveness. Results A total of 459 recordings were analyzed (35±5 per patient). We detected 130 focal activities (10±3 per patient) and 42 re-entries (4±2 per patient) in total. The spatial distribution of all drivers is shown in Figure 2 (blue bars). Focal activities were more repetitive than re-entries (Figure 2, median [IQR] 3.2% [1.9%, 5.6%] vs. 1.8% [1.8%, 2.2%], p&amp;lt;0.001 Mann-Whitney U-test). When applying a 90th percentile threshold (8.2%) to both the local and directional coherent adjacent repetitiveness to detect the most dominant drivers, we were able to detect 9 dominant drivers (all focal activities, 7 patients). Most dominant drivers were located in the upper right atrium or left pulmonary vein region (Figure 2). Interestingly, only 9 of the 130 initially detected drivers (7%) showed an activation pattern in line with a repetitive entrainment of their vicinity. Furthermore, in 6 patients (46%), no dominant drivers were detected. This might indicate that not all patients have temporally and spatially stable drivers. Conclusion In this abstract we present a novel methodology to detect the most dominant drivers of AF. Using this method, we found that some (but not all) patients have temporally and spatially stable drivers that are able to entrain their vicinity.

PO-04-081 ISOLATION OF PERSISTENT LEFT SIDED SUPERIOR VENA CAVA USING PULSED FIELD ABLATION

Pulmonary vein foci account for more than 90% of triggers for atrial fibrillation, most commonly treated with complete pulmonary vein isolation. Non–pulmonary vein triggers are the drivers of atrial fibrillation in a subgroup of patients. One such trigger is a persistent left superior vena cava (SVC), which may contain remnant muscular and pacemaker tissue carried over from embryonic life. However, reported complications of radiofrequency ablation of this structure are significant, including vein stenosis, tamponade and phrenic nerve injury. Pulsed field ablation is a promising new technology that may be uniquely suited to avoid such a complications. This case illustrates the first known application of pulsed field ablation of a left sided SVC. N/A The patient is a fifty-two year old male with a history of coronary artery disease and persistent atrial fibrillation refractory to medical therapy including rate and rhythm control strategies. He is status post multiple cardioversions with restoration to normal sinus rhythm for a relatively short period of time. The patient underwent an ablation procedure at which time it was discovered that he had an isolated persistent left sided SVC. Pulmonary vein isolation was performed using a combined radiofrequency and pulsed field ablation lattice tip catheter (Affera inc., Watertown, MA). Accordingly to study protocol, lesions were placed using radiofrequency anteriorly and pulsed field lesions posteriorly in the left atrium around the pulmonary veins resulting in complete isolation. The patient also developed a counterclockwise typical atrial flutter which was ablated. Given the propensity for triggers from the SVC, pulsed field ablation was performed by creating a circumferential lesion set superiorly beyond the left superior pulmonary vein region and inferiorly near the mid coronary sinus below the left inferior pulmonary vein. A linear lesion set connecting these two regions was also performed along the atrial portion of the coronary sinus, with subsequent confirmation of exit block and elimination of all local electrograms. In patients with persistent left SVC, pulsed field ablation is feasible without the risk of phrenic nerve injury or tamponade from excessive contact force. Further studies are necessary to examine whether the complications associated with LSVC isolation can be minimized.

Regional Differences in Ca2+ Signaling and Transverse-Tubules across Left Atrium from Adult Sheep.

Cardiac excitation-contraction coupling can be different between regions of the heart. Little is known at the atria level, specifically in different regions of the left atrium. This is important given the role of cardiac myocytes from the pulmonary vein sleeves, which are responsible for ectopic activity during atrial fibrillation. In this study, we present a new method to isolate atrial cardiac myocytes from four different regions of the left atrium of a large animal model, sheep, highly relevant to humans. Using collagenase/protease we obtained calcium-tolerant atrial cardiac myocytes from the epicardium, endocardium, free wall and pulmonary vein regions. Calcium transients were slower (time to peak and time to decay) in free wall and pulmonary vein myocytes compared to the epicardium and endocardium. This is associated with lower t-tubule density. Overall, these results suggest regional differences in calcium transient and t-tubule density across left atria, which may play a major role in the genesis of atrial fibrillation.

Mechanisms of persistent atrial fibrillation and recurrences within 12 months post-ablation: Non-invasive mapping with electrocardiographic imaging.

Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient. Seventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 months of ablation and underwent a follow-up ECGI. Driver locations and movies were compared for pre- and post-ablation AF. A total of 243 focal drivers were mapped during pre-ablation AF. 62% of the drivers were mapped in the left atrium (LA). The pulmonary vein region harbored most of the drivers (43%). 35% of the drivers were mapped in the right atrium (RA). 59% (10/17) and 53% (9/17) of patients had repetitive sources in the left pulmonary veins (LPV) and left atrial appendage (LAA), and the lower half of RA, respectively. All patients had focal drivers. 29% (5/17) of patients had macro-reentry waves. 24% (4/17) of patients had rotors. Activation patterns during persistent AF varied from single macro-reentry to complex activity with multiple simultaneous wavefronts in both atria, resulting in frequent wave collisions. A total of 76 focal driver activities were mapped in 7/8 patients during recurrence. 59% of the post-ablation AF drivers were mapped in the LA. The pulmonary vein region harbored 50% of total drivers. 39% of sources were mapped in the RA. AF complexity remained similar post-ablation. 58% (44/76) of pre-ablation sources persisted during recurrence. 38% (3/8) of patients had macro-reentry and one patient had rotors. ECGI provides patient-specific information on mechanisms of persistent AF and recurrent arrhythmia. More than half pre-ablation sources repeated during post-ablation recurrence. This study provides direct evidence for drivers that persist days and months after the ablation procedure. Patient-tailored bi-atrial ablation is needed to successfully target persistent AF and prevent recurrence. ECGI can potentially predict recurrence and assist in choice of therapy.

Dynamic electrophysiological mechanism in patients with long-standing persistent atrial fibrillation.

BackgroundImproved understanding of the mechanisms that sustain persistent and long-standing persistent atrial fibrillation (LSpAF) is essential for providing better ablation solutions. The findings of traditional catheter-based electrophysiological studies can be impacted by the sedation required for these procedures. This is not required in non-invasive body-surface mapping (ECGI). ECGI allows for multiple mappings in the same patient at different times. This would expose potential electrophysiological changes over time, such as the location and stability of extra-pulmonary vein drivers and activation patterns in sustained AF.Materials and methodsIn this electrophysiological study, 10 open-heart surgery candidates with LSpAF, without previous ablation procedures (6 male, median age 73 years), were mapped on two occasions with a median interval of 11 days (IQR: 8–19) between mappings. Bi-atrial epicardial activation sequences were acquired using ECGI (CardioInsight™, Minneapolis, MN, United States).ResultsBi-atrial electrophysiological abnormalities were documented in all 20 mappings. Interestingly, the anatomic location of focal and rotor activities changed between the mappings in all patients [100% showed changes, 95%CI (69.2–100%), p < 0.001]. Neither AF driver type nor their number varied significantly between the mappings in any patient (median total number of focal activities 8 (IQR: 1–16) versus 6 (IQR: 2–12), p = 0.68; median total number of rotor activities 48 (IQR: 44–67) versus 55 (IQR: 44–61), p = 0.30). However, individual zones showed a high number of quantitative changes (increase/decrease) of driver activity. Most changes of focal activity were found in the left atrial appendage, the region of the left lower pulmonary vein and the right atrial appendage. Most changes in rotor activity were found also at the left lower pulmonary vein region, the upper half of the right atrium and the right atrial appendage.ConclusionThis clinical study documented that driver location and activation patterns in patients with LSpAF changes constantly. Furthermore, bi-atrial pathophysiology was demonstrated, which underscores the importance of treating both atria in LSpAF and the significant role that arrhythmogenic drivers outside the pulmonary veins seem to have in maintaining this complex arrhythmia.

Improved procedural workflow for catheter ablation of paroxysmal AF with high-density mapping system and advanced technology: Rationale and study design of a multicenter international study.

BackgroundThe antral region of pulmonary veins (PV)s seems to play a key role in a strategy aimed at preventing atrial fibrillation (AF) recurrence. Particularly, low‐voltage activity in tissue such as the PV antra and residual potential within the antral scar likely represent vulnerabilities in antral lesion sets, and ablation of these targets seems to improve freedom from AF. The aim of this study is to validate a structured application of an approach that includes the complete abolition of any antral potential achieving electrical quiescence in antral regions.MethodsThe improveD procEdural workfLow for cathETEr ablation of paroxysmal AF with high density mapping system and advanced technology (DELETE AF) study is a prospective, single‐arm, international post‐market cohort study designed to demonstrate a low rate of clinical atrial arrhythmias recurrence with an improved procedural workflow for catheter ablation of paroxysmal AF, using the most advanced point‐by‐point RF ablation technology in a multicenter setting. About 300 consecutive patients with standard indications for AF ablation will be enrolled in this study. Post‐ablation, all patients will be monitored with ambulatory event monitoring, starting within 30 days post‐ablation to proactively detect and manage any recurrences within the 90‐day blanking period, as well as Holter monitoring at 3, 6, 9, and 12 months post‐ablation. Healthcare resource utilization, clinical data, complications, patients' medical complaints related to the ablation procedure and patient's reported outcome measures will be prospectively traced and evaluated.DiscussionThe DELETE AF trial will provide additional knowledge on long‐term outcome following a structured ablation workflow, with high density mapping, advanced algorithms and local impedance technology, in an international multicentric fashion. DELETE AF is registered at ClinicalTrials.gov (NCT05005143).

Reliable pace termination of postoperative atrial fibrillation in the canine sterile pericarditis model: Implications for atypical atrial flutter.

BackgroundWe have identified a reentrant circuit in the pulmonary vein region, which drives the atria, producing fibrillatory conduction, as one mechanism of postoperative atrial fibrillation (POAF) in the canine sterile pericarditis model.ObjectiveIn this model, we tested the hypothesis that overdrive pacing from a site at or near such a reentrant circuit would interrupt it and thereby terminate POAF.MethodsWe studied 11 sterile pericarditis dogs on postoperative days 1–4. Atrial electrograms (AEGs) were recorded during POAF, overdrive pacing, and pace termination from 3 sites simultaneously: Bachmann's bundle, posterior left atrium, and right atrial appendage. When recorded AEGs demonstrated regular activation, pace termination was attempted at that site by delivering a drive train starting with 4 consecutive beats at a cycle length (CL) of 2–5 ms shorter than that of the intrinsic CL.ResultsSixteen episodes of sustained POAF (>5 minutes) diagnosed by electrocardiogram were induced. During all episodes of POAF, AEGs recorded from the left atrium exhibited regular activation, ie, constant AEG morphology and CL. When capture of the reentrant circuit by overdrive pacing occurred (mean 13 ± 5, range 5–23 beats), all 16 POAF episodes were successfully terminated. In all termination episodes, at the end of pacing but prior to the return of sinus rhythm, there was disorganized atrial activation in the previously organized sites (mean 2 seconds, range 0.1–8 seconds). However, these beats did not sustain POAF in the absence of a reentrant circuit (“driver”).ConclusionOverdrive pacing from a site demonstrating regular activation during sustained POAF terminated the POAF by interrupting the reentrant circuit.

Visualization of thermal damage using 68\xa0Ga-FAPI-PET/CT after pulmonary vein isolation

Purpose68 Ga-fibroblast-activation protein inhibitor (FAPI) positron emission tomography (PET) is a novel technique targeting FAP-alpha. This protein is expressed by activated fibroblasts which are the main contributors to tissue remodeling. The aim of this proof-of-concept study was to assess 68 Ga-FAPI uptake in the pulmonary vein (PV) region of the left atrium after pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) and radiofrequency (RFA) as a surrogate for thermal damage.MethodsTwelve PVI patients (5 RFA, 7 CBA) underwent 68 Ga-FAPI-PET 20.5 ± 12.8 days after PVI. Five patients without atrial fibrillation or previous ablation served as controls. Standardized uptake values of localized tracer uptake were calculated.ResultsFocal FAPI uptake around the PVs was observed in 10/12 (83.3%) PVI patients, no uptake was observed in 2 PVI patients and all controls. Patients after PVI had higher FAPI uptake in PVs compared to controls (SUVmax: 4.3 ± 2.2 vs. 1.6 ± 0.2, p < 0.01; SUVpeak: 2.9 ± 1.4 vs. 1.3 ± 0.2, p < 0.01). All CBA patients had an intense uptake, while in the RFA, group 2 (40%), 1 (20%), and 2 (40%) patients had an intense, moderate, and no uptake, respectively. We observed higher uptake values (SUVpeak) in CBA compared to RFA patients (4.4 ± 1.5 vs. 2.5 ± 0.8, p = 0.02).ConclusionWe demonstrate in-vivo visualization of 68 Ga-FAPI uptake as a surrogate for fibroblast activation after PVI. CBA seems to cause more pronounced fibroblast activation following tissue injury than RFA. Future studies are warranted to assess if this modality can contribute to a better understanding of the mechanisms of AF recurrence after PVI by lesion creation and gap assessment.

Imaging of subendocardial adipose tissue and fiber orientation distributions in the human left atrium using optical coherence tomography.

BackgroundOptical coherence tomography (OCT) has the potential to provide real‐time imaging guidance for atrial fibrillation ablation, with promising results for lesion monitoring. OCT can also offer high‐resolution imaging of tissue composition, but there is insufficient cardiac OCT data to inform the use of OCT to reveal important tissue architecture of the human left atrium. Thus, the objective of this study was to define OCT imaging data throughout the human left atrium, focusing on the distribution of adipose tissue and fiber orientation as seen from the endocardium.Methods and ResultsHuman hearts (n = 7) were acquired for imaging the left atrium with OCT. A spectral‐domain OCT system with 1325 nm center wavelength, 6.5 μm axial resolution, 15 μm lateral resolution, and a maximum imaging depth of 2.51 mm in the air was used. Large‐scale OCT image maps of human left atrial tissue were developed, with adipose thickness and fiber orientation extracted from the imaging data. OCT imaging showed scattered distributions of adipose tissue around the septal and pulmonary vein regions, up to a depth of about 0.43 mm from the endocardial surface. The total volume of adipose tissue detected by OCT over one left atrium ranged from 1.42 to 28.74 mm3. Limited fiber orientation information primarily around the pulmonary veins and the septum could be identified.ConclusionOCT imaging could provide adjunctive information on the distribution of subendocardial adipose tissue, particularly around thin areas around the pulmonary veins and septal regions. Variations in OCT‐detected tissue composition could potentially assist ablation guidance.

Evaluation of Multiscale Frequency Approach for Visualizing Rotors in Patients with Atrial Fibrillation.

Atrial Fibrillation (AF) is most common cardiac arrhythmia. It is associated with increased risk of stroke, heart failure and sudden cardiac death. Catheter ablation is a treatment used to control AF and has had suboptimal success for patients with persistent AF, which is primarily maintained by rotors outside of the pulmonary veins (PV) region. The pivot point (core) of the rotor is considered an efficient target for ablation. Currently available electro-anatomical mapping systems cannot accurately predict the exact location of the pivot point of rotors outside of the PV region, so there is a need for novel approaches to accurately identify and distinguish sites for ablation. Recently, a multiscale frequency (MSF) technique was developed for accurate identification of the pivot point of rotors and validated using optical mapping experiments in exvivo rabbit hearts, where electrical activity can be directly visualized. However, the nature of optical signals and its spatial resolution are very different from clinical intracardiac electrograms (iEGM). Here we extend the MSF approach to 3D iEGM and compare its prediction with the traditional dominant frequency (DF) approach, using Pearson's correlation and earth mover's distance methods. Our results demonstrate that the similarity between MSF and DF are high in some regions, but very low in other spatial regions of the human atria. This indicates the inconsistency in the traditional DF approach in identifying pivot points and identifying such low similarity regions can be used to find sites for successful ablation.

Electrophysiological effects of nicotinic and electrical stimulation of intrinsic cardiac ganglia in the absence of extrinsic autonomic nerves in the rabbit heart

BackgroundThe intrinsic cardiac nervous system is a rich network of cardiac nerves that converge to form distinct ganglia and extend across the heart and is capable of influencing cardiac function.ObjectiveThe goals of this study were to provide a complete picture of the neurotransmitter/neuromodulator profile of the rabbit intrinsic cardiac nervous system and to determine the influence of spatially divergent ganglia on cardiac electrophysiology.MethodsNicotinic or electrical stimulation was applied at discrete sites of the intrinsic cardiac nerve plexus in the Langendorff-perfused rabbit heart. Functional effects on sinus rate and atrioventricular conduction were measured. Immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase, and/or neuronal nitric oxide synthase (nNOS) was performed using whole mount preparations.ResultsStimulation within all ganglia produced either bradycardia, tachycardia, or a biphasic brady-tachycardia. Electrical stimulation of the right atrial and right neuronal cluster regions produced the largest chronotropic responses. Significant prolongation of atrioventricular conduction was predominant at the pulmonary vein-caudal vein region. Neurons immunoreactive (IR) only for ChAT, tyrosine hydroxylase, or nNOS were consistently located within the limits of the hilum and at the roots of the right cranial and right pulmonary veins. ChAT-IR neurons were most abundant (1946 ± 668 neurons). Neurons IR only for nNOS were distributed within ganglia.ConclusionStimulation of intrinsic ganglia, shown to be of phenotypic complexity but predominantly of cholinergic nature, indicates that clusters of neurons are capable of independent selective effects on cardiac electrophysiology, therefore providing a potential therapeutic target for the prevention and treatment of cardiac disease.

Complexity and Distribution of Drivers in Relation to Duration of Persistent Atrial Fibrillation

BackgroundThe underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood. ObjectivesThis study sought to investigate the complexity and distribution of AF drivers in PsAF of varying durations. MethodsOf 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAF <12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms. ResultsIn this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (p < 0.05), number of re-entrant rotations and focal events (p < 0.05), and number of regions harboring re-entrant (p < 0.01) and focal (p < 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (p < 0.01), superior right atrium (p < 0.05), and inferior right atrium (p < 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration. ConclusionsThe complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention.

Kurtosis as a statistical approach to identify the pivot point of the rotor.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that causes stroke affecting more than 2.3 million people in the US. Catheter ablation to terminate AF is successful for paroxysmal AF but suffers limitations with persistent AF patients as current mapping methods cannot identify AF active substrates outside of pulmonary vein region. In this work, we developed a novel Kurtosis based mapping technique that can accurately identify pivot points of the rotors that were induced in ex-vivo isolated rabbit heart. The results indicate that the chaotic nature of rotor pivot point results in higher Kurtosis compared to the periphery thereby enabling its accurate identification. Our results suggest that Kurtosis technique can be further applied to intra-atrial electrograms from AF patients with rotors to accurately identify the rotor pivot point by generating 3-dimensional (3D) patient-specific Kurtosis maps. Validation of this new Kurtosis based mapping technology is required through clinical studies with both paroxysmal and persistent AF patient data.

PM190 Safety and Efficacy of Robotic Pulmonary Vein Isolation With a New Remote Catheter System

Pulmonary vein isolation (PVI) as a cornerstone for catheter ablation of atrial fibrillation (AF) remains a complex and time-consuming procedure.To assess feasibility, safety, and acute efficacy of a novel irrigated multielectrode ablation catheter guided by an electroanatomic mapping system for PVI in patients with paroxysmal AF.Twenty-five consecutive patients (60 ± 10 years) with paroxysmal AF underwent PVI by using a novel decapolar mapping and ablation catheter (nMARQ catheter, Biosense Webster Inc, Diamond Bar, CA). Ablation was guided by electroanatomic mapping allowing radiofrequency (RF) energy delivery in the antral region of pulmonary veins (PVs) from 10 irrigated electrodes simultaneously. The day after ablation, cardiac magnetic resonance imaging was performed routinely in order to assess for potential acute PV stenosis.Overall, 97 of 97 (100%) targeted PVs could be isolated with a mean of 27 ± 11 RF applications and a mean total burning time of 15 ± 6 minutes per patient. The total procedure time from femoral vein access to catheter withdrawal was 110 ± 31 minutes, including a mean total fluoroscopy time of 23 ± 9 minutes. On average, 6 ± 3 RF impulses with a maximum of 25 W were applied per vein. After a short learning curve, procedure, fluoroscopy, and total burning times decreased to 94 ± 16, 16 ± 3, and 9 ± 2 minutes, respectively (P < .05). Entrance and exit blocks could be verified by placing the ablation catheter into 90 of 97 (93%) PVs in 18 of 25 (72%) patients. No procedure-related complications were observed, especially no acute PV stenosis could be detected.The use of a novel irrigated multielectrode ablation system for PVI is feasible and safe, resulting in acute isolation of all targeted PVs with no complications and short procedure times. Sustainability of these initial results has to be confirmed in long-term efficacy and follow-up trials.

What Currents Underlie Pulmonary Vein Automaticity?

What Currents Underlie Pulmonary Vein Automaticity?