Paroxysmal Atrial Fibrillation Patients Research Articles

First comparison of single-tip versus single-shot pulsed field ablation for pulmonary vein isolation in paroxysmal atrial fibrillation: interim analysis of a randomized trial

Abstract Background Non-thermal pulsed field ablation (PFA) is an emerging technology to perform pulmonary vein isolation (PVI) for atrial fibrillation (AF). Different PFA systems are available, but no comparative data exist. Purpose Randomized trial to compare single-tip versus single-shot PFA for initial PVI in paroxysmal AF patients. Methods In this single-center trial, paroxysmal AF patients are prospectively enrolled and 1:1 randomized in the single-tip or single-shot PFA group. Single-tip PVI is performed using a PFA generator and a 3.5mm contact-force enabled ablation catheter guided by 3D mapping system. The pulsed electric field dosing is 25 Ampere (A) (anterior) and 22 A (posterior), respectively. In the single-shot PVI group, a 31 or 35mm pentaspline PFA catheter is used for fluoroscopy-guided PVI. Eight PFA applications (2.0 kV) are applied per PV. In this interim analysis, acute efficacy, safety and short term clinical outcome within the 3 months blanking period were assessed. A subset of patients underwent cerebral MRI to detect silent lesions. Results To date, 50 patients were enrolled and underwent PVI in conscious sedation (25 single-tip, 25 single-shot, 63 ± 5 years, 42% female, CHA2DS2-VASc 2 [1-3]). There were no differences in baseline characteristics. Acute PVI was achieved in 100%. In the single-tip group, total procedure time was significantly longer (125 ± 31 min vs. 44 ± 12 min, p <0.001) and fluoroscopy time was significantly shorter (4 ± 2 min vs. 15 ± 6 min, p <0.001) as compared to the single-shot group. One groin hematoma was noted in the single-shot group. In the single-tip group, 1 aneurysm spurium was detected and 1 pericardial tamponade requiring drainage resulted from coughing during single-tip PFA while no real-time visualization of the catheter was available. No permanent sequelae occurred. There were no PFA specific complications and no cerebral embolisms were detected in all 14 MRI scans. At 3 months, 92% (single-shot group) and 80% in the single-tip group were free from arrhythmia (p=0.42). AF recurrences in the blanking period occurred in 2 patients in the single-shot group and in 5 patients in the single-tip group after a median of 2 [1-5] days following the procedure. Conclusions In this interim analysis of a randomized trial, single-shot or single-tip PFA for PVI both demonstrated high acute efficacy and a favourable 3 months clinical outcome. Procedural time was significantly longer in the single-tip PFA group. No silent lesions were detected in cerebral MRI. Non-availability of real-time visualization and contact-force information of the single-tip ablation catheter during energy application is a current technical limitation that could be associated with complications.

Multicenter retrospective evaluation of a patient-tailored electrogram-based ablation strategy using an artificial intelligence software in repeat atrial fibrillation ablation procedures

Abstract Background While pulmonary vein isolation (PVI) is the gold standard approach of treatment of atrial fibrillation (AF), the optimal strategy in case of AF recurrences for redo patients is not well established. Several studies described the usefulness of ablating in atrial regions exhibiting abnormal electrograms, i.e. spatio-temporal dispersion, during AF and an artificial intelligence (AI) electrograms (EGMs)-based software solution has been developed and validated to obtain real-time adjudications of multipolar electrograms in de novo patients. Purpose This study sought to evaluate the novel AI-EGMs-based software approach for redo-AF ablation procedures. Methods This study was a retrospective, multicentric, nonrandomized study. Patients with recurrent symptomatic AF were enrolled in 7 European centers. Redo ablation procedures were performed using the AI software and acute and long-term outcomes after ablation were evaluated. Results A total of 117 patients with refractory symptomatic AF admitted for redo procedure were included with 30% paroxysmal, 42% short-standing persistent and 28% long-standing persistent AF at the time of the redo procedure. During the index procedures, a previous PVI ablation was performed in all patients while additional ablation such as lines and EGM-based ablation was performed in 64 patients (55%). Out of 117 patients, 30 (26%) presented with structural heart disease, 61 (52%) with hypertension, 31 (26%) with a BMI >30, 16 (14%) a sleep apnea syndrome and 24 (20%) had an antiarrhythmic treatment at the time of the procedure. The average AF history was 6.54 ± 4.15 years with an average sustained duration equal to 25 ± 62 months. AI-EGMs-based AF ablation was performed in all patients and easily integrated in the physicians’ workflow during redo procedures. AF termination, i.e. AF regularization or sinus rhythm conversion, occurred in 82/117 patients (71%) with sinus rhythm conversion by ablation in 79/117 patients (68%). After a mean follow-up of 11 ± 5 months, 81% of patients were free from documented AF, with or without antiarrhythmic drugs (AADs) after one redo procedure and 60% of patients were free from any documented atrial arrhythmia, with or without AADs, after one redo procedure per patient. Furthermore, we observed that 77%, 84% and 82% of patients were free from documented AF with or without AADs in paroxysmal, short-standing and long-standing persistent AF patients respectively, and that 71%, 59% and 49% of patients were free from any documented atrial arrhythmia with or without AADs in paroxysmal, short-standing and long-standing persistent AF patients respectively. Conclusions This retrospective study reports that patient-tailored spatiotemporal dispersion ablation is a relevant and standardized approach for repeat AF ablation. This was obtained with an AI-EGMs-based software solution, which may be added to the operative workflow of redo AF procedures.

Impact of pulmonary vein variant anatomy during cryo-ablation in paroxysmal and persistent AF patients: 1-year outcome from a nationwide multicenter clinical setting

Abstract Background Complete electrical pulmonary vein isolation (PVI) by cryo-balloon approach is a well-established ablation strategy of atrial fibrillation (AF). While contrast findings exist regarding the influence of variant pulmonary vein (PV) anatomy on predicting AF recurrence, limited data are currently available specifically for cases involving the POLARx cryoablation system during PVI. Purpose We report the real-world experience of POLARx in the context of de novo AF ablation in a multicenter Italian registry. Methods Consecutive patients undergoing AF ablation from the CHARISMA registry at 10 Italian centres were included. Protocol-directed cryoablation was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred >60 sec or when time to isolation was not available. The ablation endpoint was PVI as assessed by entrance and exit block. All patients were followed-up for at least 12 months after the procedure. Results Four-hundred twenty-nine patients were included (n=358, 83.4% paroxysmal AF, n=71, 16.6% persistent AF, mean age 60.7±10 years, 28.3% female, mean LVEF 58±8%). PVI was achieved in all pts using only cryoablation. Twenty-eight (6.6%) patients exhibited an anatomical variant: 17 (4.0%) a common ostium and 11 (2.6%) an adjunctive PV. The mean number of freeze applications per patient was 5.1 (1.2 for LSPV, 1.3 for LIPV, 1.2 for RSPV and 1.3 for RIPV). Over a median of 398[370-461] days of follow-up, 14 (3.2%) patients experienced an early recurrence of AF during the 90-day blanking period. Overall, 63 patients (14.7%) suffered an AF recurrence after the 90-day blanking period (median time to recurrence 342[171-381] days). The proportion of patients exhibiting AF/AT recurrences was higher in the persistent AF group (17 out 71, 23.9%) than in the paroxysmal AF group (46 out 358, 12.8%, p=0.026), with a hazard ratio of 2.02 (95%CI: 1.2 to 3.5, p=0.0137) whereas patients with anatomy variant showed a similar AF/AT recurrence rate (5 out 28, 17.9%) than in the standard anatomy group (58 out of 401, 14.5%) with a hazard ratio of 1.43 (0.6 to 3.6, p=0.441). Four (0.9%) transient phrenic nerve palsy were observed, both with full recovery in the 48-h post procedure; no major procedure-related adverse events were reported. Conclusion In this multicenter study, the cryo-balloon system demonstrated safety and efficacy in treating both paroxysmal and persistent AF patients, yielding a low incidence of AF/AT recurrence during follow-up, regardless of the presence of variant PV anatomy.

Pulmonary vein isolation using pulsed field ablation versus high-power-short-duration radiofrequency ablation for paroxysmal atrial fibrillation: efficacy, safety, and long-term follow-up

Abstract Background Pulsed field ablation (PFA) is a novel, nonthermal, cardiac tissue selective ablation modality. To date, radio-frequency (RF) guided high-power-short-duration (HPSD) ablation represents the gold standard for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). This study investigated the efficacy of PFA-PVI versus HPSD-PVI in terms of single-procedure arrhythmia-free outcome and safety. Methods Consecutive, paroxysmal AF patients who underwent PVI using PFA or HPSD were enrolled. In group PFA, PVI was performed using a 31/35-mm pentaspline PFA catheter. The ablation procedure in group HPSD was performed with HPSD-RF energy (45 watts), using Ablation Index (AI) and the CLOSE protocol. The CLOSE protocol combines AI and ≤6 mm interlesion distance using a 4-mm surround flow catheter. Results A total of 420 patients (group PFA: 211; group HPSD: 209) were included (55% men; age 67 ± 10 years). There was no difference between both groups with regard to age, gender and CHA2DS2-VASc-Score. Complete isolation of all PVs was achieved in 100% of patients. Procedure time was significantly shorter in group PFA (74 ± 41 min vs. 127 ± 34 min; p < 0.001); fluoroscopy time and dose area product were significantly longer in group PFA (18 ± 7 min vs. 4 ± 3 min; p < 0.01 and 555 ± 460 uGym2 vs. 213 ± 273 uGym2; p <0.01). Overall procedural complications were 1,4% in group PFA and 5,2 % in group HPSD (p < 0.01), driven by a higher tamponade rate in group HPSD. During a mean follow-up of 12 months after a single procedure, 170 (81%) patients of group PFA were free of arrhythmia recurrence versus 160 (76%) patients in group HPSD (p = 0.798) (Figure 1). Conclusions PVI using PFA compared to PVI using HPSD shows a similar acute efficacy but a significantly reduced complication rate and a shorter procedure time. One-year clinical success rates are favorable, but not different between groups.Figure 1

Stroke risk assessment in different atrial fibrillation subtypes: CHA2DS2-VASc score and beyond

Abstract Background Patients with atrial fibrillation (AF) have been known to have an inhomogeneous risk of stroke, with several well-documented risk factors including hypertension, history of stroke, and diabetes mellitus that have been incorporated into the CHA2DS2–VASc score to stratify risk levels. Accumulating evidence has suggested that AF subtype, namely persistent AF and paroxysmal AF, also have an impact on stroke development. Purpose This study focused on the impact of AF subtype on stroke risk in a large, long-term follow-up cohort as to provide insight of the impact on ischemic stroke risks. Such findings may play a role in future ischemic stroke risk stratification in selected patients. Methods A total of 7346 AF patients were followed up for 10 years from January 2010 to December 2020 (mean follow-up time 2.74 years). Among these patients, 2460 (33.5%) had persistent or permanent AF (PerAF) and 4886 (66.5%) had paroxysmal AF (PAF). The study evaluated the risk of ischemic stroke between the two groups using Cox models adjusting for all components of the CHA2DS2–VASc score. Analyses were further stratified into the usage of oral anticoagulation (OAC) or no OAC. Results Comparing AF patients based on subtype, it was found that PerAF patients were older, had a higher prevalence of previous stroke, congestive heart failure, PAD, DM, and were more often prescribed anticoagulants. Univariate analysis found patients with PerAF at a higher risk for ischemic stroke (HR 1.262, p<0.001). The results remained significant after multivariate analysis with factors of the CHA2DS2–VASc score (HR 1.234, p<0.001). After stratifying patients according to anticoagulation prescription, PerAF and PAF patients were found to have similar rates of developing ischemic stroke in patients under DOAC. Conclusions Patients with PerAF have a higher risk of stroke during follow-up independent of components of the CHA2DS2VASc score. In patients with OAC use, there was no difference in stroke risk between AF subtypes.Stroke Risk in OAC-naive patientsStroke Risk in OAC-experienced patients

Acute and one-year procedural effects with proactive esophageal cooling during radiofrequency ablation with proactive esophageal cooling - comparison of paroxysmal and persistent atrial fibrillation

Abstract Background/Introduction Proactive esophageal cooling is FDA cleared to reduce the likelihood of ablation-related esophageal injury from radiofrequency (RF) cardiac ablation, and is becoming more prevalent as an alternative to luminal esophageal temperature (LET) monitoring. Data also suggest shorter procedure times and improved freedom from arrhythmia with esophageal cooling due to the lower continuity index achieved with esophageal cooling. Purpose To determine acute and long-term procedural outcomes of PVI for paroxysmal and persistent atrial fibrillation (AF) using active esophageal cooling. Methods Procedure times and one-year follow-up rhythm status of all patients treated with PVI for paroxysmal and persistent AF by a single operator were reviewed. Patients were treated over the time span February 2020 through July 2022. Procedure times and freedom from atrial arrhythmia were then compared between paroxysmal and persistent AF. Results A total of 317 patients with paroxysmal or persistent atrial fibrillation were treated over the course of the study timeframe. Of these patients, 167 (52.7%) had paroxysmal atrial fibrillation, and 150 had persistent AF. Mean age was 70.6±11.0 years (paroxysmal AF: 68.2±10.4 years and 43% female, persistent AF: 73.4±11.0 years and 37% female), with 40% female overall. Mean procedure time was 68.8±28.1 minutes (61.4 minutes for paroxysmal, 77.3 minutes for persistent). Most patients (224, or 71%) received no fluoroscopy, while the remainder received 1.28±4.0 minutes of fluoroscopy use. The KM estimate for freedom from atrial arrhythmia at one-year for paroxysmal patients was 81.4±3.9%. For persistent patients, the KM estimate for freedom from atrial arrhythmia at one-year was 70.4±4.4% (Figure 1). Conclusions Proactive esophageal cooling is associated with a high rate of long-term freedom from arrhythmia for both paroxysmal and persistent AF patients, as well as short procedure times, and the ability to achieve low or zero fluoroscopy use.Figure 1

Ultra-high density mapping for the evaluation of the antral scar extension after ablation with a radiofrequency balloon catheter in atrial fibrillation patients

Abstract Background The Heliostar radiofrequency (RF) balloon ablation catheter enables one-shot pulmonary veins isolation (PVI). The RF balloon by occluding the PV ostia creates an antral scar. Purpose We sought to investigate the extension of the antral scar by mean of ultra-high density mapping. Methods Paroxysmal and persistent atrial fibrillation (AF) patients undergoing first PVI ablation with the Heliostar catheter across 4 European centers were enrolled. Ultra-high density mapping of left atrium was performed with the Octaray catheter, a octa-spline mapping catheter before and after the ablation. All maps were acquired in sinus rhythm, patients in AF underwent electrical cardioversion before mapping. The bipolar voltage maps from each patients were analysed: the left atrial area < 0.2 mV was considered scar and was calculated before and after the ablation and the distance between left and right antral lesions at upper and inferior posterior wall were also calculated. Results Overall, 49 patients were enrolled, 82% were male, the mean age was 60±9 years, 66% had paroxysmal AF. PVI was achieved in 100% patients. The mean left atrial area was 209±44 cm2, the scar after the ablation was 9±4.6 %, with 49±11% of the posterior wall still viable (bipolar voltage > 0.5mV). The distance between left and right antral lesions at the upper posterior wall was 26.57 mm whereas at the inferior aspect was 29.59 mm. Conclusions The RF balloon catheter creates a wide antral scar during AF ablation although without compromising the integrity of the posterior wall.

Pulsed electric field, cryoballoon, and radiofrequency for paroxysmal atrial fibrillation ablation: a propensity score-matched comparison

Abstract Background and Aims Pulmonary vein isolation (PVI) is the most effective rhythm control strategy in paroxysmal atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel, non-thermal energy source to selectively ablate cardiac tissue. We report the first multicenter experience on PVI via the pentaspline FarapulseTM PFA system versus thermal-based technologies in a propensity score-matched population of paroxysmal AF patients. Methods Propensity score matching was adopted to compare PVI-only ablation outcomes via the FarawaveTM PFA system (Group PFA), cryoballoon ablation (Group CRYO), or focal radiofrequency (Group RF) (PFA:CRYO:RF Ratio=1:2:2). Results Among 1572 (mean age: 62.4±11.3 years; 42.5% females) PAF patients undergoing their first time PVI with either PFA (n=174), CRYO (n=655), or RF (n=743), propensity score matching yielded 174 PFA, 348 CRYO, and 348 RF patients. First-pass isolation was achieved in 98.8% of pulmonary veins (PVs) with PFA, 81.5% with CRYO, and 73.1% with RF (p<0.001). Procedural and dwell times were significantly shorter with PFA. Overall complication rates were 3.4% (n=6) with PFA, 8.6% (n=30) with CRYO, and 5.5% (n=19) with RF (p=0.052). The 1-year Kaplan-Meier estimated freedom from any atrial tachyarrhythmia was 79.3% with PFA, 74.7% with CRYO, and 72.4% with RF (log-rank p-value: 0.24). Among 145 repeat ablation procedures, PV reconnection rate was 19.1% after PFA, 27.5% after CRYO, and 34.8% after RF (p=0.01). Conclusion PFA contributed to significantly shorter procedural times. Follow-up data showed a similar arrhythmia freedom among groups, although a higher rate of PV reconnection was documented in post-CRYO and post-RF redo procedures.RecurrencePVs

Charge-density mapping to evaluate non-pulmonary vein substrate in patients with paroxysmal atrial fibrillation: the ACUPRED study

Abstract Background/introduction Pulmonary veins (PV) electrical isolation (PVI) is the main ablation strategy for the treatment of paroxysmal atrial fibrillation (AF), since the description of PV triggers. However, non-PV substrate and triggers in AF are not a negligible clinical issue. Indeed, in up to 22% of patients with AF recurrence after PVI, all PV are found isolated. Non-PV triggers can be demonstrated in up to 10-15% of non-selected patients at first AF ablation and non-PV substrate has been related to functional slow conduction and fibrosis also in paroxysmal AF. Purpose The aim of this study is to evaluate non-PV substrate (slow conduction) and triggers with charge-density (CD) mapping in patients with paroxysmal AF. Methods All patients, were prospectively enrolled in 2023. Inclusion criteria for the study were: 1) paroxysmal AF patients undergoing PVI procedure with a single-shot device and 2) CD mapping pre- and post- PVI. CD mapping was performed during CS proximal pacing at cycle length (CL) 600 ms and CS proximal pacing at CL 300 ms, pre- and post- PVI. Conduction velocity (CV) magnitude (in cm/s) and vector (direction and sense) were calculated offline for each CD map for all anatomical vertices. Reduction map was defined as the map of CV magnitude difference between CL 600 ms and CL 300 ms, Figure 1. Refraction map was defined as the map of CV direction difference between CL 600 ms and CL 300 ms, Figure 1. Non-PV substrate was defined at pre-PVI maps as: 1) slow conduction (<30 cm/s) at CL 600 ms or CL 300 ms, or 2) difference in CV magnitude (>25 cm/s) at reduction map, a marker of functional slow conduction (induced by fast pacing), or 3) difference in CV direction more than 90° between two neighboring vertices at refraction map, a marker of anisotropy, Figure 1. Non-PV triggers were defined as non-PV premature atrial contractions >10/min or inducing AF. Results A total of 43 patients (60.6 ± 11.2 years, 74.4% males) with paroxysmal AF undergoing first procedure PVI were analyzed. Non-PV substrate was found in 13 patients (30.2%). Non-PV triggers were found in 3 patients (6.9%), including one patient on the posterior wall near right PV antra and two patients on the posterior wall near the left PV antra. At a mean follow-up of 5.6 months, a total of 5 patients (11.6%) experienced a recurrence. Patients experiencing a recurrence had more frequently non-PV substrate (80.0% vs 23.7%, p=0.024) and lower CV magnitude at CL 600 ms pre-PVI (72.3 cm/s vs 83.1 cm/s, p=0.04). At survival analysis for 34 patients (79.1%) out of the 2 months blanking period, patients with non-PV substrate had lower freedom from AF recurrence (56% vs 90%, p=0.0028), Figure 2. Conclusion In patients with paroxysmal AF undergoing index PVI, non-PV substrate or triggers can be found in up to 37.1% of cases. Non-PV substrate is associated with worse arrhythmic prognosis.Figure 1Figure 2

Heart rate dynamics after pulmonary vein isolation: pulsed-field vs. radiofrequency ablation

Abstract Background The autonomic nervous system (ANS) plays a pivotal role in the onset and maintenance of atrial fibrillation (AF). During thermal ablation, the epicardial ganglionated plexi (GP) can inadvertently be affected, as indicated by a post-ablation increase in heart rate (HR), potentially impacting post-procedural outcomes. Pulsed-field ablation (PFA) offers a safer and potentially more effective alternative, as lesion transmurality is not inversely related to safety as in thermal ablation. However, PFA's tissue selectivity may limit its effectiveness in ablating potential AF triggers like GP. Purpose We aimed to assess the impact of PF and RF energy on GP ablation by examining HR changes following PVI procedures. Methods We examined consecutive paroxysmal AF patients undergoing PVI at a single center, using either a variable-loop circular PFA catheter, as part of the inspIRE trial, or a conventional point-by-point RF catheter (1:2 ratio). ECGs were collected before and after ablation at multiple time points, including 1-hour, 1-day, 1-month, and 3-month intervals, with a 24-hour Holter ECG at 3 months. Patients without obtainable sinus rhythm ECGs at these time points were excluded. We also gathered data on post-ablation antiarrhythmic drug and beta-blocker usage. Data are reported as mean±SD, and analysis employed Student’s t-tests, paired t-tests, chi-squared tests, and multiple linear regression analysis to identify influencing factors. Results A total of 105 patients were included (PF = 35, RF = 70). Baseline demographics were similar (Table A). In the RF group, HR significantly increased at all measured time-points. In contrast, this trend was not observed in the PF group (Figure A and B). Following the procedure, the RF cohort exhibited a significantly higher HR compared to PF (7.3±10.3 vs. 0.8±11 at 1-day, p=0.018), and this difference persisted after 3 months (8.5±10.1 vs. 0.9±9, p<0.001, Figure C). These findings remained consistent when HR was assessed using Holter ECG data (HR at 3 months: mean 72.1±8.8 vs 65.8±9.4, min 55.2 vs 48.9; p=0.002, p=0.001, Figure D). The use of RF energy was the only predictor of HR increase after the ablation procedure (β = 7.687, p < 0.001, Table B). Conclusion Our findings indicates that PFA does not increase resting HR as seen with thermal RF ablation, suggesting limited effect on ANS modulation. The role of adjunctive GP ablation during PVI procedures remains a topic of debate.While PFA shows promising improvement in lesion durability, current evidence does not conclusively establish its advantage over RF. This invites contemplation about whether the addition of GP ablation in RF procedures could be a contributing factor. The absence of HR acceleration may pose issues for patients with sick sinus syndrome or pure vagally mediated AF. Further research is essential to confirm these findings and their clinical implications.Central illustrationTables

Preventing vagal response during pulmonary vein isolation with pulsed field ablation: impact of the order of the targeted pulmonary veins

Abstract Background Vagal responses are frequently observed during pulmonary vein isolation (PVI). Radiofrequency ablation of the anterior right ganglionated plexus (ARGP) before PVI has been demonstrated to effectively prevent VR occurrence. Pulsed-field ablation (PFA) has emerged as an alternative energy source for PVI. Despite PFA being selective for the myocardium, intraprocedural VRs and reversible effects on ganglionated plexi (GP) have been documented during PVI. Purpose We aimed to investigate whether initiating PVI from the right superior pulmonary vein (RSPV) before any other pulmonary veins (PVs) could prevent VR occurrence via concomitant transient ARGP modulation. Methods 60 consecutive paroxysmal atrial fibrillation patients undergoing PVI with the pentaspline PFA ablation catheter were prospectively included. In the first 30 patients, PVI was started from the left superior pulmonary vein (LSPV-first group). In the last 30 patients, the RSPV was targeted first, followed by the left PVs, and finally the right inferior PV (RSPV-first group). VR was defined as sinus bradycardia (<40 beats/min), asystole, or atrioventricular block (AVB). Heart rate (HR) was evaluated at baseline, during PVI, and post-ablation to assess GP modulation. Results Baseline characteristics were similar between the two study groups. VR during PVI occurred in 22 (73%) patients in the LSPV-first group and 3 (10%) in the RSPV-first group (Figure1, p<0.001). A higher rate of VRs was observed in patients in the LSPV-first group compared to patients in the RSPV-first group during ablation of the LSPV and LIPV (73% vs. 7%, p<0.001 and 27% vs. 0%, p=0.005, respectively), while no differences were found during ablation of the right PVs. Temporary pacing was employed in 10 (33%) patients in the LSPV-first group and 3 (10%) in the RSPV-first group (p=0.028). RSPV isolation induced similar acute HR increase in the two groups (13±9 bpm vs 13±10 bpm, p=0.9). However, no significant HR variation was documented in both groups at the end of the procedure compared to baseline (all p>0.05). Conclusion PVI with PFA is frequently associated with intraprocedural VRs when ablation is initiated from the LSPV. However, an RSPV-first approach determined transient HR increase and reduced VR occurrence.Figure 1

Superior vena cava isolation in paroxysmal atrial fibrillation - mind the phrenic

Abstract Background Pulmonary vein isolation (PVI) is the standard of care for patients with atrial fibrillation (AF), but medium-term success rates are far from ideal. Therefore, new methods are being developed, with emphasis on ectopic foci outside the pulmonary veins. Superior vena cava (SVC) is one of the most important non-pulmonary origins of AF and some studies suggested that empiric SVC isolation could improve outcomes in ablation of paroxysmal atrial fibrillation (PAF). Although complications have been reported in SVC ablation, most studies found complication rates of SVC ablation similar to conventional cryoballoon PVI. Aim This prospective, single-center study aimed to assess the complication rate and success rate of PVI followed by SVC isolation by cryoballoon application in comparison with conventional cryoballoon PVI. Methods We designed an unblinded, randomized clinical trial and recruited consecutive patients with PAF who were randomized to a conventional cryoballoon PVI or PVI and additional SVC cryoballoon isolation using single 180 s freeze. Results A total of 140 patients (61.4% male, mean age 62.1 years) with PAF were included and 67 (47.9%) were randomized to SVC isolation in addition to conventional ablation. Planned 180-s freeze in the SVC could be completed in 15 (22.4%) patients, while 27 (40.3%) patients received at least 120-s freeze. The mean time to SVC isolation was 40.2 ± 37.9 s. Real-time recording of SVC isolation was observed in 39 (58.2%) patients. Right phrenic nerve palsy (PNP), impending or transient, occurred in 6 (8.2%) patients in the PVI-only group and in 25 (37.3%) patients in the SVC-group (Chi-square test p < 0.001). There were no persistent PNP cases. Bradycardia or junctional rhythm was observed during a procedure in 15 (22.4%) patients who received SVC isolation. One patient eventually received a permanent AAI pacemaker due to a sinus node injury. Conclusion Our data suggest that SVC isolation can be successfully achieved in the majority of PAF patients using conventional cryoballoon. However, this significantly increases the rate of transient or impending PNP and sinus node injury in comparison to conventional cryoballoon PVI. Therefore, careful phrenic nerve function monitoring and attention to sinus bradycardia or junctional rhythm are important to mitigate this risk. Follow-up data are being collected to determine whether this risk could be outweighed by a lower rate of PAF recurrence.

Impact of residual induction number of non-pulmonary vein foci on the 2-year outcomes in patients with paroxysmal atrial fibrillation.

Residual non-pulmonary vein (PV) foci are significantly associated with atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). However, we previously reported among patients with non-PV foci induced only once, none experienced AF recurrence. Thus, we aimed to investigate the correlation between the residual induction number of non-PV foci and ablation outcome in paroxysmal AF patients. We investigated 55 paroxysmal AF patients with residual non-PV foci after PVI and ablation of non-PV-foci. Study patients were classified into the residual one-time induction of non-PV foci (residual OTI-nPVF) group (n = 23) and residual repeatedly induced non-PV foci (residual RI-nPVF) group (n = 32). Furthermore, the residual RI-nPVF group was divided into the low inducibility group (n = 10) and high inducibility group (n = 22) according to the presence or absence of non-PV foci provoked by two sets of drug induction tests (non-PV foci inducibility). In addition, the latter was divided into the ablation group (n = 14) or observation group (n = 8). The 2-year AF recurrence-free rate in the residual RI-nPVF group was significantly lower compared to the residual OTI-nPVF group (53% vs. 90%, p = 0.018). There was no significant difference of the 2-year AF recurrence-free rates in the inducibility of non-PV foci (p = 0.913) and the presence or absence of ablation (p = 0.812) in the residual RI-nPVF group. Among paroxysmal AF patients, the presence of residual RI-nPVF was associated with higher AF recurrence compared to residual OTI-nPVF. Furthermore, within residual RI-nPVF subgroup, non-PV foci inducibility or ablation of some residual RI-nPVF did not affect ablation outcome.

Impact of inter-lesion distance and first-pass isolation on outcomes of pulmonary venous isolation for paroxysmal atrial fibrillation.

Contiguity of ablation lesions is a critical determinant of success for paroxysmal atrial fibrillation (PAF) ablation. Evidence supports maintaining an inter-lesional distance (ILD) ≤ 6mm during pulmonary venous isolation (PVI). Meanwhile, first-pass isolation (FPI) on PVI outcome in follow-up was not deeply studied. The impact of ILD and FPI on PAF ablation outcomes was investigated. Consecutive PAF patients who underwent first-time antral PVI were recruited. Coordinates of ablation points were extracted from the electro-anatomical mapping system and analyzed using custom-developed software to determine the ILD. A gap is defined as ILD greater than 6mm. FPI was defined as the achievement of PVI by encircling the ipsilateral veins while simultaneously recording their electrical activity using a multipolar catheter. The primary endpoint was freedom from documented atrial arrhythmias including AF, atrial tachycardia (AT), or atrial flutter (AFL) lasting longer than 30s during follow-up. A total of 105 patients underwent first-time antral PVI. During 13.3 ± 0.6months of follow-up, atrial arrhythmias recurrence was noted in 22.9% of the patients. Atrial arrhythmia recurrence was significantly higher in patients with more gaps (> 2) (37.0% versus 11.9%, P < 0.01), and the number of gaps was an independent predictor of AF/AT/AFL recurrence. (Hazard ratio [HR] 1.20, 95% CI 1.03-1.40, P = 0.02). The group with FPI for at least one ipsilateral pair of PVs exhibited a decreased number of gaps (2.0 versus 7.0, P < 0.01) and demonstrated a significant correlation with a reduction of recurrence (HR 0.26, 95% CI 0.09-0.71, P = 0.01). Among 16 patients who underwent repeat ablation, the number of gaps during the index PVI was associated with PV reconnection (PVR) (P < 0.01). Gaps created during PVI are a modifiable determinant of AF/AT/AFL recurrence, and avoidance of gaps is crucial to improve clinical outcomes of PAF ablation. In addition, FPI exhibited a strong predictive capability for clinical success in patients with PAF.

Autonomic Effects of Pulsed Field vs Thermal Ablation for Treating Atrial Fibrillation: Subanalysis of ADVENT

BackgroundAutonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA’s relative myocardial selectivity may minimize autonomic effects. ObjectivesThis study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation. MethodsADVENT was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months. ResultsThis study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01). ConclusionsPFA’s effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study.

Ablation-induced left atrial mechanical dysfunction recovers in weeks after ablation.

The immediate impact of catheter ablation on left atrial mechanical function and the timeline for its recovery in patients undergoing ablation for atrial fibrillation (AF) remain uncertain. The mechanical function response to catheter ablation in patients with different AF types is poorly understood. A total of 113 AF patients were included in this retrospective study. Each patient had three magnetic resonance imaging (MRI) studies in sinus rhythm: one pre-ablation, one immediate post-ablation (within 2days after ablation), and one post-ablation follow-up MRI (≤ 3months). We used feature tracking in the MRI cine images to determine peak longitudinal atrial strain (PLAS). We evaluated the change in strain from pre-ablation, immediately after ablation to post-ablation follow-up in a short-term study (< 50days) and a 3-month study (3months after ablation). The PLAS exhibited a notable reduction immediately after ablation, compared to both pre-ablation levels and those observed in follow-up studies conducted at short-term (11.1 ± 9.0days) and 3-month (69.6 ± 39.6days) intervals. However, there was no difference between follow-up and pre-ablation PLAS. The PLAS returned to 95% pre-ablation level within 10days. Paroxysmal AF patients had significantly higher pre-ablation PLAS than persistent AF patients in pre-ablation MRIs. Both type AF patients had significantly lower immediate post-ablation PLAS compared with pre-ablation and post-ablation PLAS. The present study suggested a significant drop in PLAS immediately after ablation. Left atrial mechanical function recovered within 10days after ablation. The drop in PLAS did not show a substantial difference between paroxysmal and persistent AF patients.

Comparison of Postprocedural P-Wave Vector Magnitude on 12-Lead Electrocardiogram Between Cryoballoon and Radiofrequency Ablation

Pulmonary vein isolation (PVI) causes changes in P-wave parameters. However, the difference in changes in P-wave parameters including P-wave vector magnitude (Pvm) between radiofrequency catheter ablation (RFCA) and cryoballoon ablation (CBA) remains unknown. Paroxysmal atrial fibrillation (PAF) patients who underwent only PVI were enrolled. Pvm was calculated by the square root of the sum of the squared P-wave amplitude in leads II and V6 and one-half of the P-wave amplitude in V2. The patients were divided into two groups: RFCA and CBA. ΔPvm was calculated as ΔPvm (mV)=(Pvm at pre-PVI)-(Pvm at post-PVI).The following factors were evaluated: (1) differences in the ΔPvm between the two groups, (2) relationship between late arrhythmia recurrence and ΔPvm in both RFCA and CBA groups and (3) the impact of relevant factors on ΔPvm. The study population included a total of 426 PAF patients (RFCA, 167 patients; CBA, 259 patients). ΔPvm was significantly larger in CBA than RFCA (p<0.001). Kaplan-Meier analysis showed late arrhythmia recurrence was significantly higher in patients with low ΔPvm (<0.019mV) than high ΔPvm (≥0.019mV) in RFCA (Log-rank p<0.001), and low ΔPvm (<0.033mV) than high ΔPvm (≥0.033mV) in CBA (Log-rank p<0.001). Multiple regression analysis showed that CBA and heart rate change were independently and significantly associated with ΔPvm (p<0.001 and p<0.001, respectively). In conclusion, ΔPvm was significantly larger in CBA than RFCA during procedure. Low ΔPvm had a higher risk of late arrhythmia recurrence in both RFCA and CBA.

Circulating exosome long non-coding RNAs are associated with atrial structural remodeling by increasing systemic inflammation in atrial fibrillation patients.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with severe clinical sequelae, but its genetic characteristic implicated in pathogenesis has not been completely clarified. Accumulating evidence has indicated that circulating exosomes and their carried cargoes, such as long non-coding RNAs (lncRNAs), involve in the progress of multiple cardiovascular diseases. However, their potential role as clinical biomarkers in AF diagnosis and prognosis remains unknown. Herein, we conducted the sequence and bioinformatic analysis of circulating exosomes harvested from AF and sinus rhythm patients. A total of 53 differentially expressed lncRNAs were identified, and a total of 6 significantly changed lncRNAs (fold change > 2.0), including NR0046235, NR003045, NONHSAT167247.1, NONHSAT202361.1, NONHSAT205820.1 and NONHSAT200958.1, were verified by qRT-PCR in 215 participants. Moreover, these circulating exosome lncRNA levels were different between paroxysmal and persistent AF patients, which were dramatically associated with abnormal hemodynamics and atrial diameter. Furthermore, we observed that the area under ROC curve (AUC) of six lncRNAs combination for diagnosis of persistent AF was 80.34%. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analysis indicated these exosome lncRNAs mainly concerning response to chemokine-chemokine receptor interaction, which induced activated inflammation and structural remodeling. In addition, increased plasma levels of CXCR3 ligands, including CXCL4, CXCL9, CXCL10 and CXCL11, were accumulated in AF patient tissues. Our study provides the transcriptome profile revealing pattern of circulating exosome lncRNAs in atrial structural remodeling, which bring valuable insights into improving prognosis and therapeutic targets for AF.

Patterns of atrial fibrillation, relevant cardiac structural and functional changes predict functional and cognitive outcomes in patients with ischemic stroke and atrial fibrillation

BackgroundAtrial fibrillation (AF) pattern, relevant cardiac changes are important predictors of outcomes in AF, but their impact on patients with ischemic stroke and AF remained unclear. We aimed to explore the impact of AF patterns, cardiac structural and functional markers on long-term functional and cognitive outcomes in ischemic stroke patients with AF. MethodsIschemic stroke patients diagnosed with AF were enrolled in this retrospective cohort study. AF pattern was defined by both traditional and novel classification, in which patients were divided into AF diagnosed after stroke (AFDAS) and known before stroke (KAF). Left atrial (LA) diameter, left ventricular ejection fraction (LVEF), natriuretic peptide (BNP) and cardiac troponin (cTnI) were dichotomized according to the median value. Outcomes include poor functional outcome and cognitive impairment at the 1-year follow-up. Multivariable logistic regression was performed to validate the association between AF pattern, parameters of cardiac change and functional and cognitive outcome. ResultsA total of 377 patients were included. Non-paroxysmal AF patients had a higher risk of poor functional outcome (OR = 3.59, P < 0.0001) and cognitive impairment (OR = 2.38, P = 0.019) than paroxysmal AF patients, while there were no differences between AFDAS and KAF. Lower LVEF (OR = 1.83, P = 0.045) and higher BNP (OR = 2.66, P = 0.001) were associated with poor functional outcome. Lower LVEF (OR = 2.86, P = 0.004), higher LA diameter (OR = 2.72, P = 0.008) and BNP (OR = 2.31, P = 0.023) were associated with cognitive impairment. ConclusionsAF type and related cardiac markers can serve as predictors for poor functional and cognitive outcomes. Comprehensive cardiac assessment and monitoring should be strengthened after stroke.

Possible risk factors for atrial fibrillation in patients with heart failure with mildly reduced ejection fraction

Aim. To study possible risk factors (RFs) for the development of paroxysmal and persistent atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrHF).Material and methods. The study included 193 patients with chronic HFmrHF and non-valvular paroxysmal/persistent AF. Seventy-six comparable patients, but without AF, were studied as a control group. All patients underwent a detailed physical examination, including electrocardiography (ECG), echocardiography, ambulatory blood pressure monitoring, and Holter ECG monitoring. Levels of inflammatory markers, namely high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-a and fibrotic marker, transforming growth factor-b1 (TGF-b1) were measured using ELISA. The results obtained were analyzed using the method of binary logistic regression and odds ratio (OR), which allows us to assess the relationship of a specific outcome with possible risk factors and compare study groups according to the detection rate of risk factors.Results. A higher level of diastolic blood pressure (DBP) (OR=1,09, confidence interval (CI)=1,01-1,17, p=0,017) is a possible risk factor for paroxysmal AF in patients with CHF. Possible risk factors for paroxysmal and persistent AF in such patients are an increase in episodes of hypertensive crisis (OR=1,17, CI=1,071,43, p=0,001) and an increase in body mass index (BMI) (OR=1,13, CI=0,931,27, p=0,031). An increase in the OR index of left ventricular diastolic and systolic parameters was associated with significant atrial and ventricular remodeling, which contributes to AF progression from paroxysmal to persistent. Higher levels of inflammatory markers were observed in patients with AF compared with patients with HFmrHF without AF. The increase in the OR level of TGF-b1 (OR=3,84, CI=2,106,23, p=0,005) was significant in patients with persistent AF.Conclusion. Using the OR method, an increase in DBP, the prevalence of hypertensive crisis, BMI, left atrial and ventricular remodeling, an increase in markers of systemic inflammation and fibrosis are possible risk factors for AF in patients with HFmrHF.