High-density Map Research Articles

Characterization of conduction recovery and atrial electrophysiological properties after pulmonary vein isolation using pulsed field ablation

Abstract Background Pulsed field ablation (PFA) is a relatively new technology for isolation of pulmonary veins in patients with atrial fibrillation (AF). Data addressing reasons for recurrent atrial fibrillation despite primarily successful pulmonary vein isolation (PVI) using PFA are scarce, due to an up to date limited number of patients treated this way. Objective The aim of this study was to analyze electrophysiological characteristics of reconduction and / or left atrial substrate of patients referred to our center for Re-Do procedures for recurrent AF after an initial PVI using PFA. Methods 90 patients (mean age 66±9 years, 69 male (77%)) had been treated in our center from November 2021 to July 2023 with PVI using PFA. 9 (10%) of these patients were referred for Re-Do procedures. These were performed by radiofrequency ablation (RFA) using Carto system including high density mapping and high power / short duration (HPSD) ablation. We analyzed location of PV reconnection and low voltage areas (LVA) in the left atria. Results 7 out of 9 patients (77%) presented with reconnections of pulmonary veins. In one patient a single vein showed reconduction (RSPV), in 5 patients 2 veins were conducting (1x LSPV, 3x LIPV, 1 left sided common os (LCo), 1x RSPV, 3x RIPV). None of the patients showed 3 or 4 reconnected veins. Areas of reconduction in each vein were: LSPV 1x ridge, 1x posterior; LIPV 1x posterior, 1x anterior and posterior; LCo 1x posterior, RSPV 1x anterior, 2x carina, 1x anterior and posterior; RIPV 1x complete, 2x carina. In 7 patients a fibrotic atrial cardiomyopathy (FACM) was diagnosed via high density mapping of LVA’s. In 2 of these patients all 4 pulmonary veins were chronically isolated after the initial PVI. All patients except one (very small anterior LVA) with FACM ≥1 were treated with additional linear or encircling lesions according to the individual extent of the fibrotic areas. 2 patients had no LVA’s detectable. In one of those 2 patients 2 veins had reconnected. The other patient had chronically isolated veins (no proof of dormant conduction with adenosine) and no detectable non-PV-triggers under isoprenaline. Conclusion In the population of patients undergoing PVI using PFA in our center, only 10% had clinically relevant recurrences leading to the necessity of a Re-Do procedure. Most patients (77%) in this setting had reconnections of pulmonary veins. There is a tendency of posterior reconnections of the left pulmonary veins and reconnections of the carina of the right pulmonary veins, but the number of patients is too small to clearly define predilection sites that have to be paid attention to when using PFA. Additionally, left atrial substrate is an important problem in patients with recurrent AF despite primarily successful PVI and has to be considered and thoroughly addressed in Re-Do procedures.Reconnection of LSPV and anterior LVAAblation of RSPV and LSPV (posterior)

Clinical and electrophysiological characteristics and long term outcomes of catheter ablation for right and left atrial tachycardias

Abstract Background Atrial tachycardias (AT) are complex supraventricular tachycardias which are refractory to antiarrhythmic drugs that require catheter ablation. Purpose In this trial, we aimed to evaulate the outcomes of catheter ablation in patients with symptomatic atrial tachycardia, define the acute procedural success and the recurrence rates in long-term follow-up and determine the clinical and electrophysiological features that affect these outcomes. Methods A total of 666 [mean age: 55 ±16, gender: 344 (51.7%) female] symptomatic patients with AT were enrolled. Prior catheter or surgical ablation history for ATa was present in 199 (29.9%) and 18 (2.7%) of these patients, respectively. Activation mapping was performed during tachycardia in all patients as well as entrainment mapping when needed. Voltage mapping were performed in sinus rhythm in both atriums, late potential mapping was also performed in some patients. Low voltage areas and signals with continuous-fragmented morphology were tagged. Results Macroreentry was the primary mechanism in right and left atrium (70.2% and 52.8%, respectively). Cavotricuspid isthmus (CTI) dependent macroreentry was the most frequent mechanism in right ATs and perimitral reentry and roof-dependent macroreentry were the most common mechanisms in left ATs. A total of 59 (7.5%) complications were observed in 780 procedures.(2.1% major and 5.5% minor) Acute procedural success was 95.9%. Freedom from ATa was 72.8 % during a mean follow-up of 39±23 months. Freedom from ATa after index procedure was 82.3% at 12 months and 75.9 % at 24 months. After multiple procedures, freedom from ATa was 90% at 12 months and 86% at 24 months during the follow-up. In multivariate Cox regression analysis, atrial fibrillation (AF) [(HR) 2.43, 95% c(CI) 1.78-3.30; p<0.001] , history of cardiac surgery [(HR) 1.68, 95% c(CI) 1.22-2.30; p=0.001] and moderate to severe tricuspid regurgitation [(HR) 1.47, 95% c(CI) 1.08-2.01; p=0.014] were significant predictors of ATa recurrence. Conclusion Our findings demonstrated that tailored catheter ablation of ATs especially guided by high density mapping has a high acute success rate and favourable long-term outcomes in patients with symptomatic AT episodes.

Peak frequency mapping usefulness and utilization for typical AVNRT ablation

Abstract Background Accurate identification of slow pathway for the AVNRT ablation is important to achieve successful result and avoid complications mainly AV nodal block. There were some developments to produce precise image to locate this such as identify low voltage bridge (LVB) using electro-anatomical mapping and visualization of direct slow pathway capture (DCSP). The peak frequency (PF) associated with bipolar EGMs is a novel parameter which may serve to distinguish near filed (NF) from far field (FF) electrocardiogram (EGM) components. This technique can be used to differentiate sub-components derived from high density mapping. Previous study suggested this mapping appears to assist in substrate differentiation, pathway localization, and contact assessment. However, this approach has been never evaluated clinically in AVNRT ablation Objective This study conducted to evaluate the usefulness and utilization of the peak frequency mapping to identify the slow pathway location. Method The study conducted in November to December 2023 where twenty consecutive patients with common AVNRT were included in the study. Regular bipolar voltage and activation maps were generated with a regular 4 mm tip catheter. Following this, peak frequency maps (PF) were computed online prior ablation and displayed on the activation map with shadowed areas where PF was <200 Hz (figure, left panel). Focal radiofrequency application (RFa) was directed to the areas of late activation (figure, left panel) and low frequency (figure, right panel) (LA-LF). Successful ablation reached if junctional rhythm was recorded during RFa and AVNRT was no longer inducible afterwards. Results Twenty patients (48 ±15 years, 75% female) were enrolled in the study. A late activation low frequency area of 0.92±0.48 cm2 was found in 18 of them. This study revealed that there was a difference between PF in the slow pathway area compared to the adjacent area where the mean PF at the slow pathway area was 175.5 ± 37.1 Hz (analysis per patient) and 170.1 ± 48.10 Hz (analysis per recording site) which was lower and differed significantly than the PF recorded at the adjacent atrial area (279.71 ± 28.11 Hz per patient, 279.91 ± 69.47 Hz per recording site) (P<0.0001). Following the mapping, RFa were successfully applied at these late activation low-frequency (LA-LF) area induced junctional rhythm in 17 patients. AVNRT was no longer inducible after the ablation in all 17 patients. Additional RFa were often given to reinforce the result (11 ± 9 RFa, 4.03 ± 3.35 min RFa time). Conclusion The peak frequency mapping could be performed to map the slow nodal pathway which is often located in an area of late activation and low frequency.

Presence and predictors of atrial low voltage zones in patients with non cardiovertable atrial fibrillation

Abstract Background Interventional treatment of persistent atrial fibrillation (pAF) presents a challenge due to the lack of clear evidence on adjunctive strategies beyond pulmonary vein isolation (PVI). One promising approach is ablation of left atrial low voltage zones, which has been shown to improve outcomes in patients with pAF. However, reliable assessment of left atrial endocardial voltage requires sinus rhythm (SR). In a significant proportion of patients with persistent atrial fibrillation (pAF) however, restoration of sinus rhythm (SR) cannot be achieved. These may lead to extensive ablations such as defragmentation or empirical isolation of the posterior wall of the left atrium. This study aims to investigate the potential of unsuccessful cardioversion prior ablation as a predictor for the presence of low voltage zones (LVZ) in the left atrium. Methods This retrospective, single-centre study was conducted on 264 patients (31,8% female; age: 67±10 years; mean AF duration: 1-2 years) diagnosed with pAF who underwent catheter ablation for pAF between 01/2017 and 01/2020. All patients underwent electrical cardioversion (CV) before ablation. If restoration of SR was achieved, high-density contact mapping was performed in sinus rhythm before pulmonary vein isolation (PVI), in case of unsuccessful initial cardioversion, high-density contact mapping was performed after repeated CV followed the PVI, respectively. Results Initial cardioversion was unsuccessful in 53 out of 264 (19.7%) patients. Subsequent to pulmonary vein isolation, cardioversion was successful in 47 out of 53 (81%) patients initially considered non-cardiovertible. In 32 out of 53 (60.4%) patients who had an initial unsuccessful cardioversion, no left atrial low voltage was identified. Amongst patients who underwent a successful initial cardioversion, left atrial low voltage zones were apparent in 77 out of 211 patients (36.5%). There is no significant difference in the the presence of left atrial low voltage between patients who had initially successful and unsuccessful CV (χ²(1) = 0.178, p = 0.673, φ = 0.026). According to the ROC analysis, the success of CV does not have any predictive value for LVZ (AUC 0.511). Conclusion Cardioversion failure before pulmonary vein isolation does not predict left atrial low-voltage zones (LVZ). PVI alone may be adequate even in patient with clinically "end stage" non-cardiovertible atrial fibrillation. Ablation beyond pulmonary vein isolation have the potential to overtreat this specific patient group, resulting in an increase in secondary arrhythmias. These findings indicate that even single-shot devices such as balloon-based techniques may be a considerable ablation strategy in these patient cohort.

Pulsed field ablation of atrial fibrillation using a large area focal catheter with a novel contact detection algorithm. A first-in-human experience using the QuickShot catheter

Abstract Background/Introduction Pulsed field ablation (PFA) is emerging as a safe and effective alternative energy modality for cardiac ablation. Data have shown that while tissue contact is critical for PFA, the amount of contact force is less important. Single-shot catheters have shown comparable results to current thermal methods for pulmonary vein isolation (PVI), however, are limited to anatomical-based ablation strategies and have limited ability to detect tissue contact. The investigational QuickShot™ large-area focal catheter (Galvanize Therapeutics, Redwood City, CA) combines high-density mapping with large-area focal ablation guided by contact detection. Purpose The QuickShot PEF-AF study was a prospective, single-arm, first-in-human study performed at a single European center to evaluate the safety and performance of the QuickShot catheter (see Figure 1, panel A) combined with the CE-marked CENTAURI™ System (Galvanize Therapeutics, Figure 1, panel B) for catheter ablation of atrial fibrillation (AF). Methods Subjects with paroxysmal or persistent AF underwent a PVI procedure under deep sedation (fentanyl, midazolam, propofol) guided by Rhythmia™ HDx (Boston Scientific, Marlborough, MA, Figure 1, panel D). Irrigation was set to a constant 6 mL/min during the procedure. Focal, monopolar, biphasic PFA lesions were delivered asynchronously at 33 Amps and a 10 mm inter-lesion spacing (center to center with 10 mm lesion tag size). Catheter-tissue contact was confirmed by ICE/fluoroscopy and a novel impedance-based contact detection system (Figure 1, panel C). The acute performance endpoint was PVI, assessed by entrance and exit block using high-density mapping. Procedural safety assessments included microbubble detection via ICE, induction of VT/VF, muscle stimulation, phrenic nerve function, and NIHSS post-procedure. Results Twenty (20) subjects (60% PAF, 60 ± 12 years, 75% male, 4.3 ± 0.52 cm LA AP diameter) were enrolled and treated. Acute PVI was achieved in 100% of patients and targeted PVs (82/82), with first-pass isolation in 88% of targeted PVs. The PVI time was 31 ± 10 min with 46.7 ± 11.4 PFA applications. There were no device- or procedure-related adverse events, and no documented incidence of microbubble formation, arrhythmia induction, muscle stimulation, phrenic nerve dysfunction, esophageal injury, or change in NIHSS post-procedure. Conclusion The QuickShot catheter enables safe and effective large-area focal PFA for subjects requiring PVI. The catheter design enables efficient and flexible focal lesion placement with the ability to ensure adequate apposition to targeted tissues using its novel contact detection algorithm. Future studies will investigate the use of this novel catheter for PFA strategies beyond PVI.

Procedural characteristics, details on epicardial mapping-based lesion transmurality, and long-term success of posterior wall isolation with a pentaspline pulsed field ablation device

Abstract Background Achieving durable posterior wall isolation (PWI) with thermal-based energies is challenging, as reconnection rates have been reported to be up to 60%. Additionally, PWI can significantly increase the risk of collateral thermal damage to the esophagus. Pulsed field ablation (PFA) is a non-thermal energy source with a remarkable safety profile due to its selectivity to cardiac tissue. Additionally, PWI durability was reported to be 100% in a recent phase-3 study enrolling persistent AF patients undergoing PFA via the FarapulseTM system. Purpose To report procedural details, acute lesion transmurality, and long-term success of PWI via the FarapulseTMsystem. Methods Consecutive persistent AF patients undergoing first-time ablation with the FarapulseTM system at four different centres were prospectively enrolled. All patients received first-time pulmonary vein isolation (PVI) and PWI. PFA was performed with either a 31mm or a 35mm device and an energy output of 2.0kV. At least 2 applications per position were delivered. Primary efficacy endpoint was freedom from any atrial tachyarrhythmia >30s after a 3month blanking period. PW lesion transmurality was assessed in a subpopulation of patients with an indication for hybrid AF ablation and left atrial appendage (LAA) clipping. The procedure was performed according to the following steps: 1) endocardial PVI plus PWI via the FarapulseTM system; 2) endocardial high-density mapping with RhythmiaTM plus Intellanav OrionTM; 3) thoracoscopy-assisted epicardial high-density mapping with Intellanav OrionTM 4) left atrial appendage clipping. Results 157 persistent AF patients (mean age: 62±11years; 75.5% males) were included. First-pass PVI was achieved in 100% of patients. On average, pulsed electric field applications for PWI were 16.3±2.4. Mean procedural time was 66±17min; left atrial dwelling and fluoroscopy times were 46±12min and 14±6min, respectively. SR restoration during PWI was observed in 8 (5.1%) cases. Minor and major periprocedural complications occurred in 2.5% (groin hematoma: 4pts) and 0.6% (diplopia with negative cerebral MRI) patients, respectively. During a mean follow-up of 353±58 days, arrhythmia-free survival was 78.3% (n=123). A redo ablation was performed in 23 patients, showing reconnection of 22.8% of PVs. Durable PWI was observed in 82.6% of patients. In the subpopulation of patients (n=3) undergoing hybrid ablation plus LAA clipping, thoracoscopy-guided epicardial mapping of the PW was performed between 57 and 72 minutes after the last endocardial PFA application. All patients showed transmural PWI (Figure1). Conclusions In a real-world multicenter registry, PWI by means of the FarapulseTM system was safe and feasible, contributing to approximately 80% success rate after 1 year. Endocardial PFA-based PWI led to 100% transmural lesions acutely, with a rate of reconnection <20% at redo procedures.

Functional substrate mapping characteristics during sinus rhythm predicts critical isthmus of scar related atrial tachycardia

Abstract Background Atrial tachycardia (AT) is a common rhythm disorder in patients with underlying atrial scar due to previous atrial surgery or valvular heart disease. Data is scarce about the role of functional characteristics or conduction properties during sinus rhythm that may have role in the critical isthmus (CI) of re-entry. Purpose We aimed to evaluate the relationship between the functional substrate mapping (FSM) characteristics of right and left atrium and the CI of re-entrant ATs in patients with atrial low-voltage areas. Methods A total of 95 [mean age: 57 ± 13, gender: 57 (60%) female] symptomatic patients with history of left and right AT who underwent catheter ablation with 3-D high-density mapping were enrolled. Isochronal late activation mapping were created during sinus/paced rhythm to detect deceleration zones (DZ). After induction of AT, activation mapping was performed in all patients. Results In 95 patients, 96 left-ATs [49 (51%) ATs were macroreentry and 47 (49%) ATs were localized reentry] and 40 right-ATs [24 (60%) ATs were macroreentry and 16 (40%) ATs were localized reentry] were mapped. Atrial low voltage zones comprised 23.3 ± 13.0 % of total right atrium and 33.3 ± 21.2 % of total left atrium. The mean value of bipolar voltage, EGM duration, and conduction velocity during sinus rhythm corresponding to CI of ATs were 0.17 ± 0.10 mV, 121 ± 39 ms, and 0.09 ± 0.06 m/s, respectively. Total number of DZs were 125 and all CIs of reentry were colocalized with DZs detected during FSM. The positive predictive value of DZs to detect CI of inducible ATs is 87.2%. Freedom from ATa was 76.8% at 12 months follow-up. Conclusion Our findings demonstrated the utility of FSM during sinus rhythm to predict the successful termination sites for ATs. These areas displayed continuous-fragmented signal morphology in correlation with the CI of AT detected during activation mapping.

Strategies for recurrent atrial fibrillation in patients despite durable pulmonary vein isolation

Abstract Background Pulmonary vein isolation (PVI) is the cornerstone in treatment of atrial fibrillation (AF). Despite initially successful PVI patients experience recurrence of AF mostly due to reconnection of pulmonary veins (PVs). However, a certain number of patients presents with recurrent AF despite durable PVI. The optimal ablation strategy for these patients has yet to be discerned. Aim The aim of this study was to compare outcomes for different ablation strategies for recurrent AF despite persistent PVI. Methods All redo procedures for recurrence of AF from 01/2016 – 6/2022 at our center were analyzed. Only patients with proven durable PVI (entrance/exit block and high density (HD) mapping) were included. Patients were excluded, if re-PVI or right atrial ablation was necessary. In all procedures (HD) 3-D mapping and radiofrequency ablation were performed. Ablation strategy was at operators’ discretion. A 12-month follow up (FU) was obtained. Results A total of 405 left-atrial procedures for the recurrence of AF were analyzed. In 85 (21.0%) procedures all PVs were still isolated. Of these 30 patients (35.3 %) were female and 70 patients (82.4 %) suffered from persistent AF. In 49 patients (57.6 %) LA scar was detectable (85.7 % persAF). The ablation strategies consisted of: roof line (n=9; 10.6 %), left atrial anterior line (n=8, 9.4 %), roof line and left atrial anterior line (n=8, 9.4%), roof line and left atrial inferior line (n=18, 21.2 %), box lesion (n=6, 7.1 %), other left atrial ablation lines (n=20, 23.5 %) and substrate modification (CFAE and substrate encirclement) (n=16, 18.8 %). In patients with PAF (n=15), 3 patients received a roof line (20.0 %), 3 patients received the latter and left atrial inferior line (20.0 %), 5 patients received other left atrial ablation lines (33.3 %) and 4 patients received substrate modification (CFAE and substrate encirclement) (26.7 %). After a mean follow up of 401 +/- 125 days 55.3 % (n=47) of patients were free from any atrial arrhythmia (roof line 77.8 +/- 15 %, left atrial anterior line 87.5 +/- 13 %, roof line and left atrial anterior line 37.5 +/- 18 %, roof line and left atrial inferior line 50 +/- 12 %, box lesion 83.3 +/- 17 %, other left atrial ablation lines 45.0 +/- 11 %, substrate modification (CFAE and substrate encirclement) 43.8 +/- 13 %, p=0.122), 35.3 % (n=30) showed recurrence of AF (p=0.287) and 9.4 % (n=8) showed atrial tachycardia (AT) (p=0.693). None of the ablation strategies led to a significantly superior outcome. Conclusion In patients suffering from recurrence of AF despite durable pulmonary vein isolation different substrate modification strategies did not show any superiority for one or the other. Despite the necessity of additional ablation beyond PVI the optimal ablation strategy needs to be yet determined to improve outcome for redo procedures.

The evaluation of the efficacy of automated peak frequency annotation algorithm for the identification of critical isthmus of ventricular tachycardia and deceleration zones

Abstract Background Substrate modification techniques have widely been adopted due to hemodynamic instability and non-inducibility of clinical ventricular tachycardia (VT). Accurate annotation of local near field EGMs is paramount to better evaluate the ventricular substrate. Furthermore, annotation of late potentials (LP) necessitates substantial manual input and isochronal late activation mapping (ILAM) involves constant sensitivity adjustments, potentially affecting the accuracy of local ventricular signal representation. Objective This study aims to assess the utility of novel automated peak frequency (PF), which aims to determine near field local activity in low voltage regions in the prediction of the CI of scar related reentrant VTs. Furthermore, the effectiveness of automated PF annotation of near field EGMs to identify deceleration zone (DZ) during ILAM was also evaluated. Methods A total of 18 patients with scar-related VT were analyzed. In all patients, VT isthmuses were identified based on activation maps and acute termination achieved during radiofrequency ablation. Automated PF annotation using Ensite X system (Abbott) was retrospectively performed in all cases specifically in areas of low voltage with fractioned signals. The accuracy of applying the PF value and automated ILAM map for detecting VT isthmus was also assessed. Results Among the study group, 12 (66.7%) had ischemic cardiomyopathy, while 6 (33.3%) had nonischemic cardiomyopathy [3 (16.7%) with arrhythmogenic right ventricular cardiomyopathy, 2 (11.1%) with idiopathic dilated cardiomyopathy, and 1 (5.6%) with hypertrophic cardiomyopathy]. All identified isthmuses were located in areas exhibiting bipolar voltage below 0.5 mV and a PF of 250 Hz with fractionated EGMs Automated NF DZ annotation predicted the VT isthmus in 16/18 (88.9%) of the cases similar to the conventional ILAM with manual adjustment (88.9%). Conclusion Using high-density electroanatomical mapping with near field algorithm, a PF cutoff of 250 Hz accurately identified the low voltage regions to predict the CI of VT. In addition, automated annotation of EGMs during ILAM similarly identified the DZs compared with conventional last deflection algorithm with manual adjustments, which were colocalized with CI of VTs.

Identification of deceleration zones during sinus rhythm for locating critical isthmuses in left atrial macroreentrant tachycardias

Abstract Introduction Ablation of left atrial (LA) macroreentrant tachycardias (LAMT) poses considerable challenges, with issues such as tachycardia cycle length variations, multiple reentrant circuits, and tachycardia termination during entrainment maneuvers. Evaluating deceleration zones (DZ) through atrial pacing during sinus rhythm, and their correlation with potential critical conduction isthmuses (CI) in LAMT, remains unexplored. This approach may facilitate LAMT ablation. Objective To investigate the presence of DZ through atrial pacing during sinus rhythm and their association with LAMT critical conduction isthmuses (CI). Methods Patients who underwent LAMT high-density activation mapping with a 16-pole grid catheter were included. Conventional mapping (activation, voltage and entrainment mapping during tachycardia) was performed to localize the CI. Atrial pacing with three atrial extrastimuli (S2/S3/S4 with 500/500/300 ms coupling interval) was performed during sinus rhythm from the distal coronary sinus (CS). Isochronal late activation mapping (ILAM) of the S3 and S4 cycles was compared. Deceleration zones (DZ) were defined as an offset in the color scale of the activation map in an area with at least a radius of 10 mm. ILAMs were evaluated blindly, and DZs were compared with CIs defined by conventional mapping during tachycardia and validated by radiofrequency application termination. Results 18 p (60.50 ± 11.63 yo, 11 male) and 21 procedures were included. LAMT termination was successful in 18 out of 21 procedures (85.71%) and failed in 3 due to the epicardial component of the reentrant circuit. ILAM during CS pacing was achieved in 13 patients and was not possible in 5 p due to multiple LAMTs leading to empiric linear ablation in 1 and to recurrent induction of LAMT or AF during the pacing protocol. A DZ was identified in 13 out of 16 maps (81.25%) in the S3 map, which was more pronounced in the S4 map. In all these 13 maps, the final ablation site was within the DZ in the S4 map, terminating the tachycardia with focal RF applications in 11 and with extended in 2. Conclusions Deceleration zones identified through atrial pacing during sinus rhythm are prevalent in LAMT patients. These zones generally correspond to the critical conduction isthmus and offer a valuable method for mapping the reentrant circuit when mapping during stable LAMT is not feasible.

Does a higher body mass index influence additional presence of low voltage areas in the left atrium in patients with persistent atrial fibrillation?

Abstract Introduction Pulmonary vein isolation (PVI) is recommended during all atrial fibrillation (AF) catheter ablation procedures. In nearly half of patients with persistent AF, low voltage areas (LVAs), commonly defined as areas in left atrium (LA) with a bipolar electrogram amplitude of < 0.5 mV, could be documented during electrophysiological study (EP). The remaining presence of these areas in LA after a PVI-only catheter ablation procedure is identified as a risk factor for recurrence of AF. Targeting and ablating (substrate modification) these areas reduces recurrency of AF. Pre-procedural identification of patients with additional LVAs is thus very important, until date very challenging and not established. Many markers are evaluated but it remains elusive. Extensive adipose tissue in obese patients leads to LA enlargement and remodeling via different mechanisms, leading to higher incidence of AF. The link between obesity and presence of LVAs in LA other than of pulmonary veins (PV) is to our knowledge not yet evaluated. Aim of the study Is to evaluate role of body mass index (BMI) in the presence of low voltage areas in left atrium besides pulmonary vein by comparing the BMI in patients with persistent AF with and without LVAs in LA, thus eventually identifying BMI as a possible pre-procedural marker of the presence of these areas. Methodology We analyzed data from 91 consecutive patients with persistent AF undergoing first time LA catheter ablation from 09/2021 until 10/2023 inside of the Jen-PACE study. In all patients a high-density 3D endocardial voltage mapping was carried out using EnSite Precision™/ Ensite X™ and the Advisor™ HD-Grid Mapping Catheter. Results The mean BMI was 29.6 ± 4.8, mean LV-EF was 53,4% ± 9.7, 24 patients (27%) were females, average age was 67 years. Depending on the presence of low voltage areas, the patients underwent either PVI only when no such areas were documented (61 patients, 67%) or PVI and substrate modification (30 patients, 33%) with documentation of LVAs. There was no statistical difference in the BMI between the two groups (29.9 ± 4.9 in patients with PVI only vs 29.0 ± 4.8 in patients with PVI + substrate modification; p=0.37). Furthermore, in a subgroup analysis of only adipose patients with a BMI higher than 30 (44 patients; 48%; mean BMI 33.8 ± 3.0), there was no significant difference in BMI between the two groups (34.2 ± 3.3 in PVI only vs 33.2 ± 2.4 in patients with PVI and substrate modification; p=0.2) Discussion and conclusion Even though a high BMI is generally related to a higher incidence of AF, a higher BMI was not observed in patients having additional low-voltage areas in LA compared to patients in whom such areas could not be identified. Electric remodeling caused by obesity could be rather diffuse than localized in specific areas in LA. BMI is not a pre-procedural marker for the presence of additional low voltage areas in LA.

Direct epicardial validation of posterior wall isolation in persistent atrial fibrillation: pulsed field versus radiofrequency ablation

Abstract Background Lesion transmurality is an important determinant of durable effectiveness of catheter ablation (CA) for atrial fibrillation (AF). The impact of different energy sources on the achievement of transmural left atrial (LA) ablation has not been explored so far. Purpose We sought to compare the transmurality associated with pulsed field ablation (PFA) and radiofrequency (RF) ablation of LA posterior wall (PW) among patients with persistent AF. Methods Eight patients (mean age, 70±7 years; 88% male) undergoing CA for persistent AF with PW ablation and adjunctive high-density epicardial mapping were included in a multicenter international registry. In four patients, PW ablation was performed using PFA, while in the remaining four, RF energy was used with high/very-high-power short-duration settings. The primary study outcome was transmural PW isolation (PWI) with endocardial-only ablation. Results A trend towards shorter times required to complete endocardial PW ablation was observed with PFA compared to RF (9±1 vs 11±2min, p=0.065). At endocardial mapping, apparent PWI was observed in all cases. However, transmural PWI after endocardial-only ablation was demonstrated in each patient in the PFA group, but only in one RF case, in whom 50 Watt/≥10 sec settings were used (100% vs 25%, p=0.143). Interestingly, in three patients in the RF group, endocardial ablation resulted in conversion of AF into atypical flutter, which could be successfully terminated by epicardial ablation. Conclusions We observed a trend towards greater transmurality with PFA compared to high/very-high power RF ablation in the region of septopulmonary bundle. This observation may have potential implications on clinical outcomes after endocardial AF CA.

Quantitative and qualitative assessment of left atrial cardiomyopathy as well as prediction of atrial fibrillation recurrences upon PVI using machine learning

Abstract Introduction Atrial fibrillation (AF) is one of the most common heart pathologies in daily clinical practice and confers significant mortality and morbidity. However, AF ablation often proves ineffective - even after successful pulmonary vein isolation (PVI). The prediction of PVI failure for the long-term treatment of AF as well as the improved assessment of the underlying substrate appears pivotal. We hypothesize, that ML can be applied to better characterize the substrate and recurrence in AF patients upon PVI. Methods & Results We retrospectively evaluated data from 205 patients that underwent AF ablation between 2019 and 2023, including high-density 3D electroanatomic maps (sinus rhythm), LA rotational angiography, invasive LA hemodynamic measurements (after transseptal passage), echocardiography, 12-lead ECG and laboratory testing. A neuronal net was trained on selected features extracted from those datasets using supervised learning and employed to predict measures of atrial cardiomyopathy and AF recurrence. Patients were 66±1 years old and received first or second pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation with 18% documented recurrences upon a mean follow-up of 23±1months. First, we extensively refined or developed tools for automated P-wave analysis from 12-lead ECGs as well as local LA voltage and volume quantification. Next, LA hemodynamics and volumes were assessed: Mean LA volume as derived from rotational angiography significantly correlated with LA volume index as obtained using echocardiography. Interestingly, LA size showed no correlation with NT-proBNP, LA low voltage or LA hemodynamics. In addition, global (25±2% of total LA area) and local (i.e. anterior, posterior, roof) LA voltage was determined and shown to be an independent predictor of AF recurrence. In our first unselected subset of 136 patients with 2nd PVI for atrial fibrillation, our ML models predicted LA fibrosis (i.e. low voltage regions; Utah stage) from 12-lead ECGs with an accuracy of 90%. Accuracy was 87% for the prediction of AF recurrences from LA pressure and low-voltage regions. In addition, the algorithm predicted AF recurrences from 12-lead SR ECGs obtained before PVI with an accuracy of 91%. Conclusion Artificial neural networks allow to quantitatively and qualitatively predict measures of atrial cardiomyopathy and atrial fibrillation recurrence probability upon complete PVI with high accuracy.Figures

A straightforward assessment of anterior mitral isthmus lines block

Abstract Background Complex atrial fibrillation (AF) and left atrial flutter (LAFL) ablation procedures often involve creating lines on the anterior wall of the left atrium, such as the anterior septal and lateral mitral isthmus lines. Purpose This study aims to evaluate the role of a simplified criteria to demonstrate the achievement of conduction block across the anterior wall of the left atrium ("anterior mitral isthmus") after linear ablation (LA). Methods Patients scheduled for persistent AF or LAFT ablation were prospectively recruited. The procedure employed a homogeneous LA strategy that included the anteromedial, anterolateral and roof lines. The following intervals were measured before and after LA, placing a multipolar catheter in the left atrial appendage (LAA) in order to register the earliest egm in a reproducible position: 1) P-LAA: conduction time from the sinus P wave onset to the LAA, 2) IASp-LAA: conduction time pacing at CL 500 ms from the interatrial septum to the LAA, 3) CSp-LAA: conduction time pacing at CL 500 ms from the distal CS to the LAA, 4) LAA-QRS onset. Patients with linear ablation were further divided according to the presence or block (BG) or non-block group (NBG) in the anterior at the end of the procedure, demonstrated with a high-density activation map. A parallel control group (CG) of patients with paroxysmal AF without LA was also included for comparison. Statistical analysis involved the Kruskal-Wallis and Mann-Whitney test with Bonferroni correction. Results 21 patients were enrolled in the study: mean age 66.67 years (± 8.48), 80% male sex. Among them, 16 had AF and AFL and underwent LA, while the remaining 5 constitute the CG. Baseline measures before LA did not exhibit significant differences compared to the CG with mean values for P-LAA at 93±20 ms (P=2.35), IASs-LAA at 82±27 ms (P=1.94), CSs-LAA at 52±17 ms (P=0.91), and LAA-QRS at 80±27 ms (P=1.82). However, upon comparing the BG and NBG, significant differences emerged in P-LAA (82±10 ms vs. 11±5 ms (P=0.002) and IAS-LAA (83±17 ms vs. 27±24 ms (P=0.004), while no significant differences were observed in the remaining intervals. In comparisons between the BG and the CG, significant differences were noted in P-LAA (82±10 ms vs. 16±10 ms (P=0.01) and IAS-LAA (83±17 ms vs. 1.2±17 ms (P=0.01), without differences in the other intervals. Conversely, when comparing NB to the CG, no significant differences were observed in any of the intervals. Finally, P-LAA >70 ms and the IASp-LAA >55 ms showed a sensitivity of 100 % and specifitity of 100 vs. 87% respectively to discriminate anterior wall block. Conclusion The simple measurement of the P-LAA and IAS-LAA interval proves highly valuable in evaluating anterior mitral isthmus lines block, serving as a complementary approach to conventional maneuvers. P-LAA >70 ms and IASp-LAA > 55 ms could be usefull to discriminate anterior wall block.Anterior linear ablation with block

Changes in local endocardial electrograms immediately after PFA show dose-dependent variations

Abstract Background/Introduction Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation. The behaviour of local electrograms after PFA has been poorly characterized and it remains unknown if it is possible to differentiate between different electroporation levels based on local electrogram analysis. Purpose The objective of this study was to characterize the alterations in bipolar and unipolar endocardial electrograms after performing PFA at different doses. Methods Five anesthetized pigs were submitted to PFA treatments. Endovascular access to the right atrium was gained through the femoral vein to create a line of ablation between the superior and inferior vena cava using a focal monopolar catheter. The catheter was switched between a conventional cardiac navigation system (CARTO system) and a custom PFA generator. Two different PFA doses were used: a high dose (HD-1600V) at top and bottom of the line and a low dose (LD-1000V) in the central part of the ablation line. Bipolar and unipolar electrograms were recorded with the ablation catheter before and immediately after each ablation. Additionally, high-density electroanatomical maps were acquired with a multielectrode catheter before and immediately after the procedures. Four weeks later, the animals were remapped again and subsequently euthanized. Atrial tissue was removed and processed to identify the presence of fibrosis in the previously ablated lesions. Results We performed 106 ablations (84 high dose vs. 22 low dose). Four weeks later, histological staining of chronic lesions revealed that the HD lesions were larger and more fibrotic than the LD (Figure 1). Immediately after each ablation R/S-wave amplitudes and their corresponding |dV/dt|max decreased for the bipolar and unipolar electrograms. The percentages of bipolar electrogram reduction HD vs. LD were: R wave 73% vs. 39%, S wave 68% vs. 37% and |dV/dt|max 81% vs. 38%; 1 way-ANOVA p<0.05 for all, Figure 2). The R-wave amplitude in M1-M2 was significantly lower in HD compared to LD (HD vs. LD: 0.3 ± 0.2 mV vs. 0.7 ± 0.6 mV; 1 way-ANOVA p<0.01). S-wave and |dV/dt|max of unipolar electrograms presented a similar behaviour (M2 |dV/dt|max HD vs. LD: -116 ± 118 mV/s vs. -260 ± 267 mV; 1 way-ANOVA p<0.01). Conclusion Local electrograms display PFA dose-dependent variations. This information could result useful to create new metrics to assess in real time the performance of PFA systems.Figure 1.EAM maps and histology studyFigure 2.EGM signals and statistics

Spatiotemporal stability of digital twin-guided atrial fibrillation dominant frequency sites and the clinical outcome of catheter ablation

Abstract Background Although the dominant frequency (DF) may localize the reentrant drivers of atrial fibrillation (AF), its meandering nature makes it difficult to localize as an extra-pulmonary vein (extra-PV) target. Purpose We explored and quantified the spatiotemporal stability of DF by sophisticated digital-twin maps and the association with the rhythm outcome of clinical AF catheter ablation (AFCA). Methods We retrospectively examined the DF sites in the digital twin integrated by high-density electroanatomical maps (EAM) of 170 patients previously included in the CUVIA-AF2 trial (male 70.6%, 59.2±11.3 years old, 100% persistent AF). We monitored 34 seconds of virtual AF and analyzed DF sites in 10 different left atrial (LA) regions at 3 consecutive periods (6 seconds each after 16sec induction and blanking periods). The spatiotemporal stability index (STSI) was calculated to quantify mean DF's spatial and temporal variability. During protocol-based rhythm follow-up, we assessed the atrial arrhythmia recurrence rate by dividing patients into two groups based on STSI 0.75. Results During the simulation, 108 out of 170 (63.5%) patients obtained mean DF values in all three consecutive periods. There were 26 (24.1%) patients in the stable DF group (STSI ≥0.75, Stable group) and 82 (75.9%) patients in the unstable DF group (STSI <0.75, Unstable group). Although the proportion of patients with hypertension (73.1 vs. 47.6%, p=0.041) was higher and left ventricular end-diastole diameter (51.3±3.9 vs. 49.0±4.4 mm, p=0.020) was larger in the stable DF group than in the unstable DF group, other parameters, including LA size, LA voltage, or AF ablation targets, did not differ between two groups. During the median 19 [15-22] months follow-up, the atrial arrhythmia recurrence rate of the Stable group is higher than that of the Unstable group (log-rank p=0.031, HR = 2.06, CI [1.06-4.01]) Conclusions We found that the temporally stable DF in EAM-integrated virtual AF, the potential extra-PV AF drivers, is a surrogate marker of the adverse rhythm outcome of AFCA. A prospective clinical trial targeting the spatiotemporally stable DF will be warranted.

Transbaffle or retrograde aortic approach for atrial arrhythmias ablation in patients with D-TGA treated with atrial switch surgery

Abstract Introduction Patients with D- transposition of the great arteries (TGA) treated with Senning or Mustard surgeries have high incidence of supraventricular tachycardias (SVTs). Accessing to the pulmonary venous atrium (PVAt) is frequently required to perform the ablation, however it can be challenging. Aim To investigate the differences between a retrograde aortic approach (Re-Aa) and transbaffle approach (TBa) for PVAt ablation in this set of patients. Methods Prospective observational study in a third level hospital since April 2018 until October 2022, with a medium-term follow-up. All consecutive patients (pt) with history of SVT and atrial switch surgery that underwent electrophysiologic study (EP) and electroanatomic mapping using a high-density Grid mapping catheter and a contact-force ablation catheter were included. Results A total of 25 EPs were performed in 20 pt (13 (52%) Female, median age 37 y.o [IQR 34-41], median follow-up time 13 month [IQR 10-37]). In 14 pt the PVAt was mapped and ablated via Re-Aa, and in 11 with TBa. Table 1 shows basal patients characteristics, note that no significant differences between groups were found. In 19 pt (76%) a CTI-dependent flutter was documented (10 (71%) in Re-Aa group and 9 (82%) in TBa, p=0.6). Furthermore, in 7 pt other tachycardia circuits were found. Accurate mapping of all the CTI walls were achieved with both strategies, however, the posterior PVAt wall and the pulmonary veins were suboptimal mapped with Re-Aa due to a lack of catheter contact. Acute ablation success was 83% in Re-Aa and 100% in TBa (p=0.5). Despite a higher recurrence rate in the Re-Aa in the first months (20% vs 0%), no significant differences in recurrences were found between groups within 1 year of follow-up (HR 1.3 [95%CI: 0,2-7], p=0.8) (FIGURE). Complication rate was 20% in Re-Aa and 0% in TBa. All complications were directly related to the arterial vascular access (1 femoral pseudoaneurysm, 1 iliac dissection, 1 mediastinal hematoma), and were successfully treated. Conclusion In D-TGA treated with atrial switch surgery, PVAt mapping and ablation is feasible with both strategies with a high acute success rate and without significant differences in recurrences at mid-term follow up. However, TBa is associated with a lower complications rate and also with a better catheter contact and accurate mapping in the PVAt posterior wall.

Patient-tailored low-voltage-guided ablation of atrial fibrillation: initial experience using a novel ultra-low-temperature cryoablation system

Abstract Introduction The ideal ablation strategy for patients (pts) with persistent atrial fibrillation (PersAF) is still debated. In recent randomized studies, strategies of ablating electrically abnormal atrial regions in addition to pulmonary vein isolation (PVI) have shown promise, and a novel ultra-low-temperature cryoablation (ULTC) system might overcome the limitations of radiofrequency (RF) energy to create transmural lesions in diseased tissue. Purpose Aim of this study is to report procedural aspects, acute efficacy, and safety of our initial experience in treating AF pts with this novel ULTC system. Methods Patients scheduled for catheter ablation who had a high likelihood of having left atrial (LA) low voltage zones (LVZ) underwent ablation with the ULTC system. A detailed high-density LA 3D-electronatomical map was created in sinus rhythm using a multi-electrode catheter. Bipolar LVZs were defined as at least 1cm2 surface of bipolar voltage <0.5mV. The ablation strategy consisted of PVI and linear ablation of the LVZs, transecting (if narrow) or isolating (if broad) the areas of abnormal signals and anchoring these lines to electrically silent structures (PVs or mitral valve ring). Electrical isolation and block across linear ablations were tested as universally accepted. Continuous variables are expressed as median (and interquartile ranges). Results From April to September 2023, 25 pts (10 female) were included (see table for patients´ and procedural characteristics). Procedure duration was 210 (135-270) min, and diminished over time from initially (in the first 12 pts) 260 (203.75-302.50) min to 190 (135-235) min (p=0.047). PVI was achieved in 15/18 pts (83%) using the ULTC, in the remaining 3 pts RF energy touch-up was needed. Linear ablation and isolation of LVZs were always (41/41 in 22pts, 100%) successfully achieved with the ULTC (see figure for an example). Except for 1 right phrenic nerve palsy, no major acute complications were observed. Post-procedural chest pain was not reported by any patient, in 1 patient mild pericardial effusion was detected and treated conservatively. During the 48h post-procedural ECG-monitoring, no sustained atrial arrhythmias occurred. Conclusions This is the first report of patient-tailored low-voltage-guided AF-ablation using a novel ULTC system. Despite representing our initial clinical experience, acute efficacy was very good (95% of acute bidirectional block across lines). Procedure-duration decreased over time, indicating an initial learning curve. Acute safety was reassuring but particular attention should be paid for phrenic nerve function during ablation of the right PVs. The absence of post-procedural pain, pericardial effusion, or acute post-procedural arrhythmias indicates limited ablation-induced inflammation.Result of ULTC ablation in a diseased LA

Clinical validation of a novel digital twin framework for ventricular functional substrate simulation in post-infarction patients

Abstract Background Catheter ablation is a cornerstone treatment for scar related post-infarction ventricular arrhythmias. Functional substrate driven ablation strategies guided by local activation time (LAT) mapping have been proven as efficient and effective approaches, especially when dealing with large scar areas. In-silico electrophysiological modeling is emerging as a potential tool for procedural planning and guidance. Purpose To clinically validate the feasibility, diagnostic performance, and accuracy of a novel late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) based digital twin framework for simulated LAT map generation in post-infarction patients and their integration with CARTO3 EAM suite. Methods Five ischemic subjects who underwent CMR-aided scar-related ventricular tachycardia ablation at our referral center were retrospectively enrolled. Their CMR derived 3D pixel-signal-intensity (PSI) maps generated with ADAS3D were processed with novel in-house software to obtain patient-specific ventricular geometry, tissue characterization, and to generate a model of Purkinje system and myocyte fiber orientation. According to local normalized pixel intensity (NPI) values, myocardial regions were marked as healthy, scar, or border-zone. Electrophysiological properties of border-zone (BZ) were modulated according to local NPI. Continuous and 8-steps isochronal endo-epicardial LAT maps were generated and imported in CARTO3 system, aligned with electroanatomical mapping (EAM), and compared at an ASE 17-segments level, in terms of sensitivity, specificity, predictive values, and accuracy to actual high-density LAT maps obtained with a multipolar catheter. Deceleration Zones (DZ) were defined as previously described (>3 isochrones within 1 cm radius). Results A total of 85 ASE segments (34 epicardial) were analyzed. 24 EAM segments (28%) held DZs, 40 (47%) segments harbored bipolar scar or BZ. Thirty-seven (44%) CMR segments held scar core/BZ. Thirty (35%) digital model segments harbored DZs. Generated LAT maps were successfully imported and aligned with CARTO3 EAM suite for validation. In terms of DZ localization prediction, our LAT model showed 83% sensitivity (95% CI 63%-95%), 90% specificity (95% CI 80%-96%), 77% positive predictive value (PPV) (95% CI 56%-91%), 93% negative predictive value (NPV) (95% CI 83%-98%), 88% accuracy (95% CI 79%-94%). Conclusion Our newly developed framework for LGE-CMR derived functional substrate simulation in post-infarction patients holds high sensitivity, specificity, predictive values, and accuracy for DZ localization. Further validation, with a larger sample size, is required for evaluating potential implications in clinical practice.

Increased left atrial pressure is associated with fibrosis, elevated mechanical load and ventricular diastolic dysfunction in patients undergoing AF catheter ablation

Abstract Background Increased left atrial filling pressures might be a hallmark feature of atrial cardiomyopathy which has been associated with an increased incidence of atrial fibrillation (AF) recurrence even after successful pulmonary vein isolation (PVI). The interplay between left atrial pressure, measured during the ablation procedure, and other parameters characterising atrial and ventricular remodelling in patients with AF remains elusive. Methods and Results Between 2018 and 2022, 182 patients undergoing PVI for paroxysmal or persistent AF were included in the study. Mean left atrial pressure (mLAP) was measured invasively during the ablation procedure after transseptal puncture. A mLAP higher than 15 mmHg was considered the cut-off value for LA hypertension. Bipolar high-density 3D electro-anatomical maps (Carto) obtained during the procedure were used to manually quantify low-voltage (<0.5 mV) and normal voltage areas of the LA surface and a global low-voltage/normal voltage ratio index was derived. Contemporary transthoracic echocardiography data were included to evaluate LV systolic and diastolic function and blood samples were obtained post-procedurally from all patients. In bivariate linear regression analysis, mLAP reached only modest correlation with E/e’ as an imaging marker of diastolic dysfunction (R=0.31, p=0.005) (Figure 1A), with particular differences in mLAP values between patients with marked diastolic impairment (E/e’ > 15) vs. subgroups with mild dysfunction ( 8 < E/e’ ≤ 15) or normal diastolic function (E/e’ ≤ 8 ) (Figure 1B), log NT proBNP (R=0.34, p<0.001) (Figure 1C) and low-voltage/normal voltage ratio index (R=0.21, p=0.014) (Figure 1D). For a total of 158 patients, data about 1 year recurrence of AF were available, of these 22 (13.9%) had a recurrence after two procedures using cryo-energy for the index PVI and radiofrequency ablation for the re-PVI (second procedure). A Kaplan-Meier analysis and log-rank test showed a trend but no statistical significance regarding an increased AF recurrence rate between patients with and without LA hypertension (χ2 = 2.63, p= 0.09) (Figure 2). Conclusion Direct intra-procedural invasive measurement of LA pressures can offer an important and convenient novel piece of information for patients undergoing catheter ablation procedures for AF, with potential implication for post-procedural recurrence risk stratification. Atrial hypertension is only partially related to LV diastolic impairment, atrial fibrosis and myocardial mechanical load burden.