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Objective The study objective was to determine whether mini-invasive transthoracoscopic atrial fibrillation ablation can delay the progression of atrial fibrillation from paroxysmal to persistent. Methods Patients aged 18 to 80 years with paroxysmal nonvalvular atrial fibrillation and a history of stroke or systemic thromboembolism were consecutively enrolled from September 2014 to June 2019. In the treatment group, patients underwent transthoracoscopic atrial fibrillation ablation plus left atrial appendage excision (atrial fibrillation ablation plus left atrial appendage excision group). Patients unwilling to receive surgical intervention were treated with antiarrhythmic drugs and oral anticoagulants and recruited as a control group (atrial fibrillation plus antiarrhythmic drugs group). The primary end point was the progression of atrial fibrillation from paroxysmal to persistent. Results This study included 49 patients in the atrial fibrillation plus antiarrhythmic drugs group (29 men) and 77 patients in the atrial fibrillation ablation plus left atrial appendage excision group (48 men). In the atrial fibrillation ablation plus left atrial appendage excision group, after a median follow-up of 951 days (interquartile range, 529-1366 days), 8 patients (10.4%) progressed to persistent atrial fibrillation. In the atrial fibrillation plus antiarrhythmic drugs group, after a median follow-up of 835 days (interquartile range, 548-1214 days), 14 patients (28.6%) progressed to persistent atrial fibrillation. The atrial fibrillation ablation plus left atrial appendage excision group had a significantly lower incidence of atrial fibrillation progression than the atrial fibrillation plus antiarrhythmic drugs group during follow-up (3.9 vs 12.3 per 100 person-years, log-rank 8.6, P = .003). Conclusions Patients with paroxysmal nonvalvular atrial fibrillation who chose to undergo transthoracoscopic atrial fibrillation ablation had a lower incidence of progression to persistent atrial fibrillation than patients who chose conservative therapy. This strategy might be especially suitable for patients with paroxysmal nonvalvular atrial fibrillation at high risk of stroke and high risk of bleeding.

Although the autonomic nervous system has an evident impact on cardiac electrophysiology and radiofrequency ablation (RFA) is the conventional technique for treating persistent atrial fibrillation, the specific effects of RFA have been insufficiently studied to date. Here, we investigated whether RFA affects neurohumoral transmitter levels and myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake. To perform this task, we compared two groups of patients with acquired valvular heart disease: patients who had undergone surgical AF ablation and patients with sinus rhythm. The decrease in norepinephrine (NE) level in the coronary sinus had a direct association with the heart-to-mediastinum ratio (p = 0.02) and a negative correlation with 123I-MIBG uptake defects (p = 0.01). The NE level decreased significantly after the main surgery, both in patients with AF (p = 0.0098) and sinus rhythm (p = 0.0039). Furthermore, the intraoperative difference between the norepinephrine levels in the ascending aorta and coronary sinus (ΔNE) of –400 pg/mL was determined as a cut-off value to evaluate RFA efficacy, as denervation failed in all patients with ΔNE < –400 pg/mL. Hence, ΔNE can be utilized to predict the efficacy of the “MAZE-IV” procedure and to assess the risk of AF recurrence after RFA.

A 74-year-old woman with medical history of coronary artery disease with stent to right coronary artery (RCA) 1 year ago, hypertension, hyperlipidaemia and persistent atrial fibrillation was electively admitted for pulmonary vein isolation (PVI). Limited transoesophageal echocardiogram (TEE)

A 54-year-old man with early repolarization syndrome (ERS) implanted with an implantable cardioverter-defibrillator (ICD) developed persistent atrial fibrillation (AF) three years after the implantation. Similarly, the remote monitoring system begun frequently detecting ventricular fibrillation (VF) and polymorphic ventricular tachycardia (PVT). Longer RR intervals were repeatedly observed just before the initiation of PVT/VF. Catheter ablation for AF successfully diminished both the PVT and VF events.

It has been observed that the fourth-generation cryoballoon (CB4) ablation catheter increased the rate of acute real-time recordings of pulmonary vein isolation (PVI) during the ablation for the treatment of atrial fibrillation (AF). The aim of this analysis was to compare the long-term outcome results between patients treated with the CB4 and second-generation cryoballoon (CB2).In total, 492 patients suffering from AF, underwent PVI ablation with either the CB2 or CB4 catheter within this examination of the 1STOP real-world Italian project and were included in the analysis. Specifically, 246 consecutive patients treated by CB4 were compared to 246 propensity-matched control patients who underwent PVI using CB2.When comparing the patient cohorts treated with CB2 versus CB4, acute success rate (99.6 ± 4.7% vs. 99.7 ± 3.6%, p = .949) and peri-procedural complications (3.7% vs.1.2%, p = .080) were similar in both groups, respectively. However, procedure time (100 vs.75 min, p .001) and fluoroscopy duration (21 vs.17 min, p .001) were all significantly lower in the CB4 treated patient cohort. At the 12-month follow-up, the freedom from AF recurrence after a 90-day blanking period was significant higher in the CB4 as compared with the CB2 group (93.3% vs.81.3%, p .001).In summary, usage of the CB4 ablation catheter increased the rate of acute PVI recording capability and resulted in a higher rate of long-term PVI success, as demonstrated by the reduced rate of AF recurrence in comparison to the CB2 cohort at the 12-month follow-up period.

Introduction: Left atrial posterior wall isolation (LAPWI) is often performed in addition to pulmonary vein isolation (PVI) to improve outcome in patients with persistent atrial fibrillation (AF). In this setting, LAPWI + PVI using cryoballoon ablation had comparable results with radiofrequency ablation (RFA). The aim of the study is to evaluate the feasibility and safety of a new cryoballoon ablation system in PVI + LAPWI isolation, comparing it with the historical platform. Methods: The study was a prospective, non-randomized, single center study. Forty consecutive patients, undergoing PVI + LAPWI with the novel POLARx™, were compared to 40 consecutive patients who underwent the same procedure with the established Arctic Front Advance PRO™. Results: Acute isolation was achieved in all PVs in both groups and LAPWI was achieved in 38 patients (95%) in the POLARx group and in 36 patients (90%) in Arctic Front group. Procedural outcomes were similar between the two groups, except for lower temperatures during cryoapplications in the POLARx group, for both PVI and LAPWI. The complication rate was low and similar between groups. Conclusion: LAPWI+PVI with the novel POLARx™ Cryoballoon is feasible and safe; the results are comparable with the Arctic Front Advance PRO™ system.

BACKGROUND Additional benefit of cryoballoon left atrial roof line ablation (CB-RA) beyond cryoballoon pulmonary vein isolation (CB-PVI) is suggested in patients with persistent atrial fibrillation (PsAF). We sought to investigate the feasibility of CB-RA for PsAF and to determine the ablation area. METHODS AND RESULTS Fifty-three PsAF patients (67[58.5-75.5] years, 36 men, 11 longstanding PsAF) underwent CB-PVI. Subsequently, 44(83.0%) out of 53 patients underwent additional CB-RA. Voltage maps were created in all patients with a high-resolution mapping system. The total number and duration of CB-RAs were 3.9±0.7 and 468±84 seconds. LA roof areas were complete low voltage areas (LVAs) /scar in 37/44(84.1%) patients ("complete roof modification"). The normal LA posterior wall (LAPW) voltage area was 6.1(4.1-8.4)cm2, and the %LAPW isolation area was 61.0(47.2-71.7)%. The %LAPW isolation area was significantly greater in CB-RA patients than those without (64.0[54.2-73.2] vs. 45.0[39.5-50.5]%, p = 0.041) despite significantly larger LAs in the former group. The %LAPW isolation area was significantly greater in patients with transverse LA diameters

Background The efficacy of pulmonary vein isolation (PVI) alone is not guaranteed for persistent atrial fibrillation (PeAF), and it is unclear which type of ablation approach should be applied in addition to PVI. This study aimed to compare outcomes and prognosis between empirical linear ablation and low-voltage area (LVA) ablation after PVI for PeAF. Methods We enrolled 128 patients with PeAF who were assigned to the linear ablation group (n = 64) and the LVA ablation group (n = 64) using a propensity score-matched model. After PVI and cardioversion, the patients underwent either empirical linear ablation or LVA ablation during sinus rhythm. All patients in the linear ablation group underwent both roof line and mitral valve isthmus (MVI) ablations. An electrical-guided ablation targeting LVA ( Results The baseline characteristics were well-balanced between the two groups. Fifty patients had LVA (22 and 28 patients in the linear and LVA groups). The roof and MVI lines were completed in 100% and 96.9% of the patients. During the mean follow-up of 279.5 ± 161.3 days, the LVA group had significantly lower recurrence than the linear group (15 patients [23%] vs. 29 patients [45%], p = 0.014). Thirty-five patients were prescribed antiarrhythmic drugs during the follow-up period (linear group, n = 17; LVA group, n = 18); amiodarone and bepridil were administered to most of the patients (15 and 17 patients, respectively). The difference in the prognosis was relevant among the patients with LVA, while this trend was not observed in those without LVA. The LVA ablation group demonstrated significantly lower radiofrequency energy and shorter procedural time compared to the linear ablation group. The recurrence of atrial flutter was more likely to occur in the linear group than in the LVA group (14 [22%] vs. 6 [9.4%], p = 0.052). Conclusion The electrophysiological-guided LVA ablation is more effective than empirical linear ablation in PeAF patients with LVA. Unnecessary empirical linear ablation might have a risk of iatrogenic gap and atrial flutter recurrence.

Background Despite studies using localized high density contact mapping and lower resolution panoramic approaches, the mechanisms that sustain human persistent atrial fibrillation (AF) remain unresolved. Voltage mapping is commonly employed as a surrogate of atrial substrate to guide ablation procedures. Objective To study the distribution and temporal stability of activation during persistent AF using a global non‐contact charge density approach and compare the findings with bipolar contact mapping. Methods Patients undergoing either redo or de novo ablation for persistent AF underwent charge density and voltage mapping to guide the ablation procedure. Offline analysis was performed to measure the temporal stability of three specific charge density activation (CDA) patterns, and the degree of spatial overlap between CDA patterns and low voltage regions. Results CDA was observed in patient‐specific locations that partially overlapped, comprising local rotational activity (18% of LA), local irregular activity (41% of LA), and focal activity (39% of LA). Local irregular activity had the highest temporal stability. LA voltage was similar in regions with and without CDA. Conclusion In persistent AF, CDA patterns appear unrelated to low voltage areas but occur in varying locations with high temporal stability.

Late-onset atrial fibrillation (LOAF) after valve surgery for degenerative mitral valve disease often with underlying mitral valve prolapse is a known phenomenon. However, there is no similar data for postoperative rheumatic heart disease (RHD) patients. We sought to assess the incidence and predictors of LOAF during postoperative follow-up in RHD patients. This single-center retrospective case–control study included a total of 384 RHD patients with normal sinus rhythm (NSR) who underwent rheumatic valve surgery between 1st July 2008 and 30th June 2013. Patients detected with de novo persistent atrial fibrillation (AF) after 2 months of valve surgery were diagnosed as having LOAF. Presurgical demographic and echocardiographic parameters were compared between the LOAF and NSR groups to identify risk factors for LOAF. The incidence of de novo LOAF after rheumatic valve surgery was 9.63% at an average of 2.67 ± 1.32 years follow-up. Age ≥ 32 years [OR 2.4 (95% CI 1.2–5.1); P = 0.01] and left atrial (LA) size ≥ 51 mm [OR 5.9 (95% CI 2.8–12.4); P

In a patient with long-standing persistent atrial fibrillation, elimination of an epicardial connection between the right-sided pulmonary venous carina and the right atrium during catheter ablation resulted in intra-atrial conduction injuries in the presence of advanced atrial remodeling. (Level of Difficulty: Advanced.), Central Illustration

Background: For patients with persistent atrial fibrillation (AF), whether linear ablation should be performed remains controversial, and the efficacy and safety for ablation index (AI)-guided high-energy linear ablation of mitral isthmus (MI) and left atrial (LA) posterior box isolation is still unclear. The aims of this study were to assess the feasibility and clinical success rate of pulmonary veins isolation (PVI) combined with linear ablation of LA roof and posterior inferior (posterior wall isolation) and MI compare with the PVI-alone method in patients of persistent AF. Methods and results: 362 consecutive persistent AF patients were enrolled from two electrophysiology centers. A total of 200 cases were in PVI-plus group and 162 cases were in PVI-alone group. The PVI-alone group received wide circumferential isolation of both ipsilateral pulmonary veins. PVI combined with linear ablation of left atrial posterior wall isolation (LAPWI)and MI were performed in the PVI-plus group. The primary study end point was the first recurrence of an atrial arrhythmia. After 24 months, freedom from the primary endpoint was achieved in 73.5% of the patients in the PVI-plus group and 62.5% in the PVI-alone group (hazard ratio = 0.62, 95% confidence interval: 0.43–0.91, log rank p = 0.012). The procedure-related complication rates were 2.5% in PVI-plus group and 1.9% in PVI-alone group (p = 0.808). Conclusion: In this study, the ablation strategy of ablation (PVI plus linear ablation of mitral isthmus and posterior box isolation) was feasible and safe for persistent AF patients. Compared with the PVI-alone method, it improved outcomes in patients with persistent AF.

Aims Pulmonary vein (PV) antrum isolation proved to be effective for treating persistent atrial fibrillation (PeAF). We sought to investigate the results of a personalized approach aimed at adapting the ablation index (AI) to the local left atrial wall thickness (LAWT) in a cohort of consecutive patients with PeAF. Methods and results Consecutive patients referred for PeAF first ablation were prospectively enrolled. The LAWT three-dimensional maps were obtained from pre-procedure multidetector computed tomography and integrated into the navigation system. Ablation index was titrated according to the local LAWT, and the ablation line was personalized to avoid the thickest regions while encircling the PV antrum. A total of 121 patients (69.4% male, age 64.5 ± 9.5 years) were included. Procedure time was 57 min (IQR 50–67), fluoroscopy time was 43 s (IQR 20–71), and radiofrequency (RF) time was 16.5 min (IQR 14.3–18.4). The median AI tailored to the local LAWT was 387 (IQR 360–410) for the anterior wall and 335 (IQR 300–375) for the posterior wall. First-pass PV antrum isolation was obtained in 103 (85%) of the right PVs and 103 (85%) of the left PVs. Median LAWT values were higher for PVs without first-pass isolation as compared to the whole cohort (P = 0.02 for left PVs and P = 0.03 for right PVs). Recurrence-free survival was 79% at 12 month follow-up. Conclusion In this prospective study, LAWT-guided PV antrum isolation for PeAF was effective and efficient, requiring low procedure, fluoroscopy, and RF time. A randomized trial comparing the LAWT-guided ablation with the standard of practice is in progress (ClinicalTrials.gov, NCT05396534).

Aims Although mobile health tools using photoplethysmography (PPG) technology have been validated for the detection of atrial fibrillation (AF), their utility for heart rate assessment during AF remains unclear. Therefore, we aimed to evaluate the accuracy of continuous PPG-based 1 min mean heart rate assessment during AF. Methods and results Persistent AF patients were provided with Holter electrocardiography (ECG) (for ≥24 h) simultaneously with a PPG-equipped smartwatch. Both the PPG-based smartwatch and Holter ECG automatically and continuously monitored patients’ heart rate/rhythm. ECG and PPG recordings were synchronized and divided into 1 min segments, from which a PPG-based and an ECG-based average heart rate estimation were extracted. In total, 47 661 simultaneous ECG and PPG 1 min heart rate segments were analysed in 50 patients (34% women, age 73 ± 8 years). The agreement between ECG-determined and PPG-determined 1 min mean heart rate was high [root mean squared error (RMSE): 4.7 bpm]. The 1 min mean heart rate estimated using PPG was accurate within ±10% in 93.7% of the corresponding ECG-derived 1 min mean heart rate segments. PPG-based 1 min mean heart rate estimation was more often accurate during night-time (97%) than day-time (91%, P < 0.001) and during low levels (96%) compared to high levels of motion (92%, P < 0.001). A neural network with a 10 min history of the recording did not further improve the PPG-based 1 min mean heart rate assessment [RMSE: 4.4 (95% confidence interval: 3.5–5.2 bpm)]. Only chronic heart failure was associated with a lower agreement between ECG-derived and PPG-derived 1 min mean heart rates (P = 0.040). Conclusion During persistent AF, continuous PPG-based 1 min mean heart rate assessment is feasible in 60% of the analysed period and shows high accuracy compared with Holter ECG for heart rates

Although a left atrial posterior wall isolation (LAPWI) in addition to a pulmonary vein isolation is a well-accepted option for persistent atrial fibrillation (AF), a complete isolation can be challenging. This study aimed to evaluate the performance of a modified ablation index (AI) (AI/bipolar voltage along the ablation line) for predicting a durable LAPWI. The study included 55 consecutive patients, aged 65 ± 11 years, who underwent an electroanatomic mapping-guided LAPWI of AF. The association between the gaps (first-pass LAPWI failure and/or acute LAPW reconnections), voltage amplitude along the roof and floor lines, and thickness of the LAPW was investigated. Gaps occurred in 22 patients (40%) and in 26 (8%) of the 330 line segments. Gaps were associated with a relatively high bipolar voltage (3.38 ± 1.83 vs. 1.70 ± 1.12 mV, P

Focal activation is believed to be an atrial fibrillation (AF) driver; however, little is known about whether all focal activations are necessary for AF persistence. The purpose of this study was to assess the electrical nature of focal activation and identify high-priority focal activations using a novel mapping system (CARTOFINDER). Thirty-five patients with persistent AF who underwent catheter ablation were assessed. Cycle length (CL) and CL standard deviation (CLSD) on unipolar recordings and voltage amplitude and electrogram morphologies on bipolar recordings were evaluated at all points of interest. The most frequent CL at each mapping site was defined as the dominant CL. We identified dominant focal activations (DFAs) that had a shorter dominant CL on the integrated CARTOFINDER map. The effect of elimination of DFAs on AF maintenance was assessed by the composite endpoint (termination to sinus rhythm, organization of the rhythm to atrial tachycardia, and AF CL slowing). In all, 450 focal activations were identified among 10,868 points, and 50.4% of focal activations were DFAs. Focal activations showed relatively long CL and regularity with short CLSD. Most focal activations showed an isoelectric baseline and were located outside of the fractionated electrogram area. Both DFAs and non-DFAs were typically observed in the normal voltage range. Elimination of DFAs was achieved in 19 (54.3%) patients, with a remarkable impact on AF maintenance (68.4% vs. 25.0%, p = 0.018). In conclusion, DFAs may play an important role in AF maintenance and could be an attractive therapeutic target for AF.

Aim. To assess the effectiveness and safety of refralon based cardioversion on the experience of the cardiology department of Orenburg Regional Clinical Hospital.Methods. The archival medical histories of 14 patients with persistent atrial fibrillation (AF) and 2 patients with persistent atrial flutter (AFL) (overall 16 patients), who underwent an attempt to restore sinus rhythm with refralon, were analyzed. The mean age of the patients was 51.7±10.4 years. The mean duration of AF/AFL since its last detection was 8.0±6.5 weeks (from 8 days to 8 months). Fifteen patients had hypertension, 3 of them had coronary artery disease (CAD), and 1 patient had CAD with type 2 diabetes mellitus. One of the patients had lone AF. Before cardioversion, all patients underwent the following examination: clinical and biochemical blood tests, clinical urine tests, electrocardiography (ECG), echocardiography (Echo), transesophageal Echo, Holter ECG, the determination of the level of thyroid-stimulating hormone, thyroxine, electrolytes, including potassium and magnesium.Results. According to Echo, initially, the transverse size of the left atrium in patients was 4.3±0.3 cm. Its increase was noted in 68.7% of patients (from 4.3 to 5.0 cm). Restoration of sinus rhythm after the first step of refralon administration at a dose of 10 μg/kg was achieved in 8 patients, after the second step of administration (total dose 20 μg/kg) - in 5 patients and after the third step (total dose 30 μg/kg) - in 2 patients. In 1 patient, restoration of sinus rhythm was not achieved after the administration of the third bolus. Out of 15 patients with restored sinus rhythm, AF recurrence occurred in three. In one of the patients with successful cardioversion, the sinus rhythm was restored the next day. The duration of the last episode of AF and the size of the left atrium did not significantly affect the effectiveness of cardioversion and amounted to 62±54 days and 4.3±0.35 cm, respectively, in patients with successful cardioversion, and with a recurrence of AF - 34.3±28 days and 4.2±0.35 cm (p=0.2; р=0.6). The efficacy of cardioversion with refralon was 71.4% in patients with AF, and 100% in patients with AFL. No adverse events of refralon were found in patients.Conclusion. At the time of discharge, sinus rhythm was recorded in 12 out of 16 patients (75%). The ineffectiveness of cardioversion with refralon was noted only in patients with AF; in all patients with AFL the sinus rhythm was restored.

We present two cases of successful pharmacological cardioversion using antiarrhythmic drug refralon in patients with persistent atrial fibrillation after pulmonary vein cryoablation and ineffective electrical cardioversion. These clinical cases represent the first experience of successful use of refralon in patients who underwent cryoablation.

Aims This study evaluates the efficacy and safety of first-line single-stage hybrid ablation of (long-standing) persistent atrial fibrillation (AF), over a follow-up period of 2 years, and provides additional information on arrhythmia recurrences and electrophysiological findings at repeat ablation. Methods and results This is a prospective cohort study that included 49 patients (65% persistent AF; 35% long-standing persistent AF) who underwent hybrid ablation as first-line ablation treatment (no previous endocardial ablation). Patients were relatively young (57.0 ± 8.5 years) and predominantly male (89.8%). Median CHA2DS2-VASc score was 1.0 (0.5; 2.0) and mean left atrium volume index was 43.7 ± 10.9 mL/m2. Efficacy was assessed by 12-lead electrocardiography and 72-h Holter monitoring after 3, 6, 12, and 24 months. Recurrence was defined as AF/atrial flutter (AFL)/tachycardia (AT) recorded by electrocardiography or Holter monitoring lasting >30 s during 2-year follow-up. At 2-year follow-up, single and multiple procedure success rates were 67% and 82%, respectively. Two (4%) patients experienced a major complication (bleeding) requiring intervention following hybrid ablation. Among the 16 (33%) patients who experienced an AF/AFL/AT recurrence, 13 (81%) were ATs/AFLs and only 3 (19%) were AF. Repeat ablation was performed in 10 (20%) patients and resulted in sinus rhythm in 7 (70%) at 2-year follow-up. Conclusion First-line single-stage hybrid AF ablation is an effective treatment strategy for patients with persistent and long-standing persistent AF with an acceptable rate of major complications. Recurrences are predominantly AFL/AT that can be successfully ablated percutaneously. Hybrid ablation seems a feasible approach for first-line ablation of (long-standing) persistent AF.

Background Atrioventricular (AV)-synchronous single-chamber leadless pacing using a mechanical atrial sensing algorithm produced high AV synchrony in clinical trials, but clinical practice experience with these devices has not yet been described. Objective To describe pacing outcomes and programming changes with AV-synchronous leadless pacemakers in clinical practice. Methods Consecutive patients without persistent atrial fibrillation who received an AV-synchronous leadless pacemaker and completed follow-up between February 2020 and April 2021 were included. We evaluated tracking index (atrial mechanical sense followed by ventricular pace [AM-VP] divided by total VP), total AV synchrony (sum of AM-ventricular sense [AM-VS], AM-VP, and AV conduction mode switch), use of programming optimization, and improvement in AV synchrony after optimization. Results Fifty patients met the inclusion criteria. Mean age was 69 ± 16.8 years, 24 (48%) were women, 24 (48%) had complete heart block, and 17 (34%) required ≥50% pacing. Mean tracking index was 41% ± 34%. Thirty-five patients (70%) received ≥1 programming change. In 36 patients with 2 follow-up visits, tracking improved by +9% ± 28% (P value for improvement = .09) and +18% ± 19% (P = .02) among 15 patients with complete heart block. Average total AV synchrony increased from 89% [67%, 99%] to 93% [78%, 100%] in all patients (P = .22), from 86% [52%, 98%] to 97% [82%, 99%] in those with complete heart block (P = .04), and from 73% [52%, 80%] to 78% [70%, 85%] in those with ≥50% pacing (P = .09). Conclusion In patients with AV-synchronous leadless pacemakers, programming changes are frequent and are associated with increased atrial tracking and increased AV synchrony in patients with complete heart block., Graphical abstract

Recent advances have been made in AF treatment, including the role of early rhythm control and landmark clinical trials using ablation therapy. However, some treatment gaps remain, including the creation of durable lesions outside the pulmonary veins and effective treatment of longstanding persistent AF. A novel epicardial-endocardial ablation approach – the hybrid convergent procedure – was developed to combine surgical and catheter ablation techniques into a collaborative, multidisciplinary approach to managing AF. In this review, the authors discuss recently published data on hybrid convergent ablation, including results of the CONVERGE clinical trial, in the context of current challenges to treatment of persistent and long-standing persistent AF. The review also aims to provide perspective on outstanding questions and future directions in this area.

Background Left atrial (LA) posterior wall isolation (PWI) is commonly used with persistent atrial fibrillation (AF) ablation. However, potentials are often still recorded in the posterior wall after pulmonary vein isolation (PVI), roof linear ablation, and bottom linear ablation in clinical practice. We aimed to explore the methodological approach and electrophysiological characteristics of PWI. Methods Thirty-six patients who attended our center with long-standing persistent AF were retrospectively analyzed. After routine PVI and roof and bottom linear ablation, complete PWI was confirmed in sinus rhythm by voltage mapping and high-output pacing. Otherwise, activation mapping and voltage mapping were used to guide ablation on the line or inside the posterior wall until bidirectional block was achieved. Results The first-pass success rate of PWI was 39%. In the remaining 61% of patients with posterior wall electrograms, activation mapping in sinus rhythm showed that the earliest activation point was not on the ablation line but in a relatively dispersed focal area, possibly related to epicardial muscular sleeve insertion. Voltage mapping revealed a focal high-voltage area in the posterior wall matching the relatively dispersed earliest activation site, in which an average of five points of ablation achieved complete PWI without serious esophageal injury. The middle zone contained 80% of the additional posterior wall ablation points. Conclusions PWI was performed safely and effectively with an average of five additional ablation points in the posterior wall in 61% of patients under the guidance of voltage mapping. This article is protected by copyright. All rights reserved.

Purpose. The aim of this study was to reveal the effect of the duration and characteristics of anticoagulant therapy on the clot dissolution in the left atrial appendage (LAA) in patients with persistent atrial fibrillation (AF).Material and methods. The repeat transesophageal echocardiography was performed in 68 patients with persistent AF, because the thrombus was detected in the LAA during the first examination. Of these, 37 (54.4%) patients started or continued to receive warfarin and 31 (45.6%) patients continued to receive the direct oral anticoagulants. Transesophageal echocardiography was repeated after 3-5 weeks. One follow-up examination was for 53 patients, two follow-up examination was for 11 patients and three follow-up examination was for 4 patients. Cox regression analysis was performed to identify factors affecting the likelihood of clot dissolution and Kaplan-Meier survival analyses with log-rank tests were used to compare the clot dissolution time.Results. The chance of the LAA thrombus lysis is 50% after 35.0 ± 3.7 days of receiving anticoagulants. This time is reduced to 30.0 ± 1.4 days for small thrombus (no more than 18 mm), and it increases to 45.0 ± 7.4 days (p = 0.038) for large thrombus. The dissolution time of small thrombus depends on the characteristics of the treatment: the median of the dissolution curve is 24.0 ± 3.7 days when the patients received the direct oral anticoagulants, and the median of the dissolution curve is 40.0 ± 7.2 days (p = 0.009), if the patients received warfarin. The dependence of the dissolution time of large thrombus on the characteristics of treatment did not found.Conclusion. The LAA thrombus dissolution time in patients with atrial fibrillation depends on their size, and the dissolution time of small thrombi depends on the characteristics of anticoagulant therapy.

Purpose Left atrial (LA) rapid AF activity has been shown to co-localise with areas of successful atrial fibrillation termination by catheter ablation. We describe a technique that identifies rapid and regular activity. Methods Eight-second AF electrograms were recorded from LA regions during ablation for psAF. Local activation was annotated manually on bipolar signals and where these were of poor quality, we inspected unipolar signals. Dominant cycle length (DCL) was calculated from annotation pairs representing a single activation interval, using a probability density function (PDF) with kernel density estimation. Cumulative annotation duration compared to total segment length defined electrogram quality. DCL results were compared to dominant frequency (DF) and averaging. Results In total 507 8 s AF segments were analysed from 7 patients. Spearman’s correlation coefficient was 0.758 between independent annotators (P P P P Conclusion DCL identifies rapid atrial activity that may represent psAF drivers. This study uses DCL as a tool to evaluate the dynamic, patient specific properties of psAF by identifying rapid and regular activity. If automated, this technique could rapidly identify areas for ablation in psAF.

Complex ablation for persistent atrial fibrillation (AF) aims to modify the arrhythmogenic substrates to become incapable to perpetuate the arrhythmia. Ablation-associated determinants of atrial tachycardia (AT) rather than AF recurrences are unknown. The aim of the study was to evaluate the association between the type of arrhythmia recurrence and electrophysiological findings during redo procedures. A total number of 384 consecutive patients with persistent AF underwent complex ablation consisting of PV isolation (PVI), biatrial electrogram-guided ablation, and linear ablation with the desired procedural endpoint of AF termination. Electrophysiological findings during redo procedures and its relation to AR type are the subject of this study. Overall, 177 (46%) patients underwent a second procedure. Patients with AT recurrences had significantly more often persistent PVI (47 vs. 25%; P = 0.002). Moreover, a higher number of recovered PVs were associated with AF recurrence (3 PVs recovered, AF = 16.1% vs. AT = 5.2%; P = 0.02; 4 PVs recovered, AF = 18.5% vs. AT = 6.3%; P = 0.01), regardless of the extent of substrate ablation during the first procedure. Durable PV isolation but not the extent of atrial substrate ablation determines the type of arrhythmia recurrence. Thus, the PVs may represent dominant perpetuators (and not only triggers) of persistent AF even in the presence of a significantly modified atrial substrate.

There is strong evidence in support of pulmonary vein isolation (PVI) with concomitant left atrial (LA) posterior wall (PW) isolation (PWI) for the treatment of patients with persistent atrial fibrillation (persAF). While this may be achieved using surgical and catheter-based strategies, there is growing interest in performing this approach using the cryoballoon. There are several potential advantages to this strategy. First, lesions created using the current-generation cryoballoons are typically large and durable. Second, cryoballoon ablation offers a simple technique to directly ablate and debulk the LAPW. Moreover, some consider cryoenergy a safer modality specifically with regard to collateral structures (ie, the esophagus). Based on the available data, cryoballoon PVI + PWI is associated with greater intraprocedural AF terminations and reductions in long-term AF recurrence (typically by ~20%), as compared to PVI alone in patients with persAF, but with similar rates of adverse events. As such, PVI + PWI has emerged as a significant predictor of freedom from recurrent AF (odds ratio: 3.67, 95% confidence interval: 1.44-9.34; p = 0.006) as well as all atrial arrhythmias (hazard ratio: 2.04, 95% confidence interval: 1.15-3.61; p = 0.015). Adjunct radiofrequency ablation to complete PWI is required in at least one-third of the patients, and this need is highly predicted by the LA size (significantly increased with an LA diameter > 48 mm). LAPW reconnection also seems to be associated with LA dimension, particularly an LA diameter greater than 48 mm (negative predictive value: 89.7%). Nevertheless, based on the analysis of patients who underwent repeat electrophysiology study for arrhythmia recurrences, cryoballoon PVI + PWI yields acceptable long-term durability (> 80%).

Catheter ablation (CA) is a commonly used treatment for persistent atrial fibrillation (AF). Since its medium/long-term success rate remains limited, preoperative prediction of its outcome is gaining clinical interest to optimally select candidates for the procedure. Among predictors based on the surface electrocardiogram, the dominant frequency (DF) and harmonic exponential decay (γ) of the fibrillatory waves (f-waves) have reported promising but clinically insufficient results. Hence, the main goal of this work was to conduct a broader analysis of the f-wave harmonic spectral structure to improve CA outcome prediction through several entropy-based measures computed on different frequency bands. On a database of 151 persistent AF patients under radio-frequency CA and a follow-up of 9 months, the newly introduced parameters discriminated between patients who relapsed to AF and those who maintained SR at about 70%, which was statistically superior to the DF and approximately similar to γ. They also provided complementary information to γ through different combinations in multivariate models based on lineal discriminant analysis and report classification performance improvement of about 5%. These results suggest that the presence of larger harmonics and a proportionally smaller DF peak is associated with a decreased probability of AF recurrence after CA.

Background: Phase analysis has been used to identify and localize atrial fibrillation (AF) sources for targeted ablation. We previously demonstrated that repetitive wannabe reentry (incomplete reentry) often generated an apparent stable rotor using phase analysis. The misinterpretation caused by phase analysis using atrial electrograms (AEGs) may result from detecting inaccurate time points at phase inversion (π to −π) in the instantaneous phase waveform converted from AEG. The purpose of this study was to evaluate the accuracy of phase analysis to detect atrial activations recorded from the high-density mapping of AF in patients with persistent and long-standing persistent (LSP) AF. Methods and Results: During open heart surgery, we recorded activation from both atria simultaneously using 512 electrodes in 7 patients with persistent and LSP AF. The phase analysis was compared to manual measurements during 4 s of data. For the accuracy of activation sequence maps, a successful recording site was defined as having ≤4 mismatched activation times during the 4 s. In all AF episodes, the accuracy of the phase analysis was only 82% of the total number of activation times due to either activation time differences (14.7%), under-sensing (2.7%), or over-sensing (0.6%). Only 67.9% of the total recording sites met the requirement of a successful recording site by phase analysis. In unsuccessful recording sites, AEG characteristics were relatively irregular cycle length (CL), complex AEG, and double potential AEG. Conclusion: The phase analysis was less accurate in recording sites with a relatively irregular CL, complex AEG, or double potential AEG. As a result, phase analysis may lead to the misinterpretation of atrial activation patterns during AF. A visual review of the original AEG is needed to confirm the detected AF sources of phase analysis before performing targeted ablation.

Purpose Catheter ablation has become a mainstay therapy for atrial fibrillation (AF) with rapid innovation over the past decade. Variability in ablation techniques may impact efficiency, safety, and efficacy; and the ideal strategy is unknown. Real-world evidence assessing the impact of procedural variations across multiple operators may provide insight into these questions. The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (PAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that will enroll patients at high volume centers, including academic institutions and private practices, with operators performing ablations primarily with low fluoroscopy when possible. The study will also evaluate the contribution of advent in technologies and workflows to real-world clinical outcomes. Methods Patients presenting at participating centers are screened for enrollment. Data are collected at the time of procedure, 10–12 weeks, and 12 months post procedure and include patient and detailed procedural characteristics, with short and long-term outcomes. Arrhythmia recurrences are monitored through standard of care practice which includes continuous rhythm monitoring at 6 and 12 months, event monitors as needed for routine care or symptoms suggestive of recurrence, EKG performed at every visit, and interrogation of implanted device or ILR when applicable. Results Enrollment began in January 2018 with a single site. Additional sites began enrollment in October 2019. Through May 2021, 1,243 patients underwent 1,269 procedures at 13 institutions. Our goal is to enroll 4000 patients. Discussion Real-AF’s multiple data sources and detailed procedural information, emphasis on high volume operators, inclusion of low fluoroscopy operators, and use of rigorous standardized follow-up methodology allow systematic documentation of clinical outcomes associated with changes in ablation workflow and technologies over time. Timely data sharing may enable real-time quality improvements in patient care and delivery. Trial registration Clinicaltrials.gov: NCT04088071 (registration date: September 12, 2019) Supplementary Information The online version contains supplementary material available at 10.1007/s10840-021-01031-w.

Background The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial demonstrated that adding vein of Marshall (VOM) ethanol infusion to catheter ablation (CA) improves ablation outcomes in persistent atrial fibrillation (AF). There was significant heterogeneity in the impact of VOM ethanol infusion on rhythm control. Objective The purpose of this study was to assess the association between outcomes and (1) achievement of bidirectional perimitral conduction block and (2) procedural volume. Methods The VENUS trial randomized patients with persistent AF (N = 343) to CA combined with VOM ethanol or CA alone. The primary outcome (freedom from AF or atrial tachycardia [AT] lasting longer than 30 seconds after a single procedure) was analyzed by 2 categories: (1) successful vs no perimitral block and (2) high- (>20 patients enrolled) vs low-volume centers. Results In patients with perimitral block, the primary outcome was reached 54.3% after VOM-CA and 37% after CA alone (P = .01). Among patients without perimitral block, freedom from AF/AT was 34.0% after VOM-CA and 37.0% after CA (P = .583). In high-volume centers, the primary outcome was reached in 56.4% after VOM-CA and 40.2% after CA (P = .01). In low-volume centers, freedom from AF/AT was 30.77% after VOM-CA and 32.61% after CA (P = .84). In patients with successful perimitral block from high-volume centers, the primary outcome was reached in 59% after VOM-CA and 39.1% after CA (P = .01). Tests for interaction were significant (P = .002 for perimitral block and P = .04 for center volume). Conclusion Adding VOM ethanol infusion to CA has a greater impact on outcomes when associated with perimitral block and performed in high-volume centers. Perimitral block should be part of the VOM procedure.

Objectives This study was to test the hypotheses that: 1) when using phase analysis, repetitive Wannabe re-entry produces a phase singularity point (i.e., a rotor); and 2) the location of the stable rotor is close to the focal source. Background Recent contact mapping studies in patients with persistent atrial fibrillation (AF) demonstrated that phase analysis produced a different mechanistic result than classical activation sequence analysis. Our studies in patients with persistent AF showed that focal sources sometimes produced repetitive Wannabe re-entry, that is, incomplete re-entry. Methods During open heart surgery, we recorded activation from both atria simultaneously using 510 to 512 electrodes in 12 patients with persistent AF. We performed activation sequence mapping and phase analyses on 4 s of mapped data. For each detected stable rotor (>2 full rotations [720°] recurring at the same site), the corresponding activation patterns were examined from the activation sequence maps. Results During AF, phase singularity points (rotors) were identified in both atria in all patients. However, stable phase singularity points were only present in 6 of 12 patients. The range of stable phase singularity points per patient was 0 to 6 (total 14). Stable phase singularity points were produced due to repetitive Wannabe re-entry generated from a focal source or by passive activation. A conduction block sometimes created a stable phase singularity point (n = 2). The average distance between a focal source and a stable rotor was 0.9 ± 0.3 cm. Conclusions Repetitive Wannabe re-entry generated stable rotors adjacent to a focal source. No true re-entry occurred.

Background Many studies have reported the predictors of atrial fibrillation (AF) recurrence after persistent AF (peAF) ablation. However, the correlation between the atrial defibrillation threshold (DFT) for internal cardioversion (IC) and AF recurrence rate is unknown. Here we investigated the relationship between the DFT prior to catheter ablation for peAF and AF recurrence. Hypothesis DFT prior to ablation was the predictive factor for AF recurrence after peAF ablation. Methods From June 2016 to May 2019, we enrolled 82 consecutive patients (mean age, 65.0 ± 12.4 years), including 45 with peAF and 37 with long‐standing peAF, at Hamamatsu Medical Center. To assess the DFT, we performed IC with gradually increasing energy prior to radiofrequency application. Results Forty‐nine and 33 patients showed DFT values less than or equal to 10 J (group A) and greater than 10 J or unsuccessful defibrillation (group B). During the mean follow‐up duration of 20.5 ± 13.1 months, patients in group B showed significantly higher AF recurrence rates than those in group A after the ablation procedure (p = .017). Multivariate analysis revealed that DFT was the only predictive factor for AF recurrence (odds ratio, 1.07; 95% CI, 1.00–1.13, p = .047). Conclusions The DFT for IC was among the strongest prognostic factors in the peAF ablation procedure.

Aims: Electrographic flow (EGF) mapping is a method to detect action potential sources within the atria. In a double-blinded retrospective study we evaluated whether sources detected by EGF are related to procedural outcome. Methods: EGF maps were retrospectively generated using the Ablamap® software from unipolar data recorded with a 64-pole basket catheter from patients who previously underwent focal impulse and rotor modulation-guided ablation. We analyzed patient outcomes based on source activity (SAC) and variability. Freedom from atrial fibrillation (AF) was defined as no recurrence of AF, atypical flutter or atrial tachycardia at the follow-up visits. Results: EGF maps were from 123 atria in 64 patients with persistent or long-standing persistent AF. Procedural outcome correlation with SAC peaked at >26%. S-type EGF signature (source-dependent AF) is characterized by stable sources with SAC > 26% and C-type (source-independent AF) is characterized by sources with SAC ≤ 26%. Cases with AF recurrence at 3-, 6-, or 12-month follow-up showed a median final SAC 34%; while AF-free patients had sources with significantly lower median final SAC 21% (p =.0006). Patients with final SAC and Variability above both thresholds had 94% recurrence, while recurrence was only 36% for patients with leading source SAC and variability below threshold (p =.0001). S-type EGF signature post-ablation was associated with an AF recurrence rate 88.5% versus 38.1% with C-type EGF signature. Conclusions: EGF mapping enables the visualization of active AF sources. Sources with SAC > 26% appear relevant and their presence post-ablation correlates with high rates of AF recurrence.

Atrial fibrillation (AF) mostly originates from the pulmonary vein (PV). As a result, 70%−90% of AF patients can be successfully treated with extensive PV isolation. However, the precise identification of the site of trigger in the remaining 10%–30% with non-PV foci1, 2, 3 is often difficult. Especially in cases that require multiple electrical cardioversions because of immediate recurrence of AF after cardioversion, the mapping of origins becomes more difficult. In this case, a prominent Eustachian ridge was demonstrated as a source of AF trigger by high-density grid mapping catheter (Advisor™ HD Grid Catheter; Abbott Medical, Minneapolis, MN).

Background Achieving long-term successful outcomes with catheter ablation (CA) of persistent atrial fibrillation (PsAF) remains a challenge. Multiple attempts to determine effective ablation strategies besides the pulmonary veins (PV) were made but, so far, there is no agreed standard approach and no clear consensus as to which is the best one. Among the most frequently used techniques was ablation of complex atrial fractionated electrograms (CFAE) but studies showed contradictory results. The optimal procedural endpoint also needs further refinement. Objectives We sought to evaluate outcomes in regard to patient characteristics and procedural termination. We also aimed to assess whether continuation of antiarrythmic therapy in the blanking period (1 to 3 months after the procedure) influences long term results. Methods We enrolled consecutive patients with persistent and long-standing PsAF (LS-PsAF) who underwent one or more radiofrequency catheter ablations (RF CA) - pulmonary vein antral isolation (PVAI), followed by CFAE or resultant atrial tachycardia/flutter elimination, were retrospectively analyzed. Procedural objective was tachyarrhythmia (AF or resultant atrial flutters/tachycardias) termination (TT) to sinus rhythm (SR) during RF delivery. If after extensive substrate based or activation guided ablation sinus rhyhtm was not restored, conversion was performed with antiarrhythmic drugs (AAD), overdrive pacing or electrical shock. Screening for arrhythmia recurrence was performed via clinical interview and 48 hours Holter monitoring at 1,3 and 6 months and then every 6 months. Results The cohort included 94 patients (age 54.5±11.4, 67 (71%) males, CHADSVASc 2.3±2, 11 (12%) LS-PsAF) Acute restoration of sinus rhythm (SR) was achieved in 93.4% of the cases, 43% by ablation of CFAE or resultant atrial tachycardia/flutter(AT/AFL), 36.2% by electric cardioversion, 7.4% by chemical conversion, 3.1 % overdrive pacing, 3.7 % spontaneuous/mechanical. The long term success rate after a mean of 1.7±0.8 procedures was 59% at a mean follow-up period of 80±28 months. Freedom from AF was significantly higher when arrhythmia termination was obtained during RF delivery (p – 0.003). Short-term use of AAD in the blanking period did not lead to improved long term outcomes. Conclusions In patients with PsAF and LS-PsAF restoration of sinus rhyhtm during RF delivery for pulmonary vein isolation, ablation of CFAE or resultant atrial tachyarrhythmia predicts long term procedural success. Further research to determine the best strategy to achieve this outcome is necessary.

Background It is expected that ablation procedures will be increasingly offered to a more aged population affected with persistent AF (persAF); however, the clinical outcomes of ablation in this specific population are not well described. We aimed to analyze the efficacy and safety of CB‐A in this group of patients compared with a younger cohort. Methods and results Eighty‐three patients with (persAF) aged ≥75 years (group 1; mean age 78.2 ± 3.1 years) and 166 patients also affected with persAF aged 30 seconds) atrial arrhythmias without anti‐arrhythmic medication after a blanking period of 3 months. At 2 years, clinical success was achieved in 108 out of 249 patients (43.4%). Median follow‐up was 24 months (IQR: 18.4‐25.5 months). Older patients suffered from more recurrences than those in the younger cohort ((53/83 patients, 63.9% vs 88/166 patients, 53.0%; P = .03). Thirty (12.0%) patients suffered a complication, but the incidence of complications was not different between both groups. The most frequent complication was transient phrenic nerve injury. Conclusions The global 2 years efficacy of CB‐A PVI in persAF is 43.4%. A lower success rate is achieved in the older patients (36.1%) compared to the younger age group (47.0%). However, the complication rate was not different between age groups., The mid‐term success rate of pulmonary vein isolation by means of second‐generation cryoballoon in persistent atrial fibrillation is significantly lower in older patients (>75 years) compared with the younger cohort. There is no difference in the complication rate of pulmonary vein isolation by means of second‐generation cryoballoon of between younger and older patients.

Noncontact charge-density mapping allows rapid real-time global mapping of atrial fibrillation (AF), offering the opportunity for a personalized ablation strategy.The purpose of this study was to compare the 2-year outcome of an individualized strategy consisting of pulmonary vein isolation (PVI) plus core-to-boundary ablation (targeting the conduction pattern core with an extension to the nearest nonconducting boundary) guided by charge-density mapping, with an empirical PVI plus posterior wall electrical isolation (PWI) strategy.Forty patients (age 62 ± 12 years; 29 male) with persistent AF (10 ± 5 months) prospectively underwent charge-density mapping-guided PVI, followed by core-to-boundary stepwise ablation until termination of AF or depletion of identified cores. Freedom from AF/atrial tachycardia (AT) at 24 months was compared with a propensity score-matched control group of 80 patients with empirical PVI + PWI guided by conventional contact mapping.Acute AF termination occurred in 8 of 40 patients after charge-density mapping-guided PVI alone and in 21 of the remaining 32 patients after core-to-boundary ablation in the study cohort, compared with 8 of 80 (10%) in the control cohort (P .001). On average, 2.2 ± 0.6 cores were ablated post-PVI before acute AF termination. At 24 months, freedom from AF/AT after a single procedure was 68% in the study group vs 46% in the control group (P = .043).An individualized ablation strategy consisting of PVI plus core-to-boundary ablation guided by noncontact charge-density mapping is a feasible and effective strategy for treating persistent AF, with a favorable 24-month outcome.

Learning objectives Atrial fibrillation (AF) is a multisystemic disorder that is associated with an excess risk of stroke, heart failure and mortality.1 It remains the most common sustained arrhythmia and its significance should not be underestimated. Research focused on unveiling the mechanisms of AF began over a century ago. During this period, several theories have been proposed. More recently, the notion of rotors and spiral waves propagating in the atria was used to address the flaws of prior concepts and enhance our understanding on the development of AF.2 3 Presently, it is believed that the initiation and maintenance of AF is linked to a complex interplay between two crucial components: ‘trigger’ and ‘substrate’. The former refers to one or more ectopic foci that initiate rapid electrical activity resulting in depolarisation of surrounding cardiac myocytes. Maintenance of AF is subsequently dependent on the presence of a suitable substrate in terms of electrophysiological, mechanical and anatomical properties.4 The biggest breakthrough in our understanding of AF occurred two decades ago when Haissaguerre et al demonstrated the role of pulmonary veins as the most common sites of triggers for the disease.5 This observation serves as the fundamental basis for ablation therapy for AF. In practice, AF is frequently diagnosed following an incidental finding of uncoordinated atrial activation on a timely surface ECG; subsequent classification of the disease is based on temporal rhythm-based patterns (table 1).6 The latter concept stems from the idea that many patients who develop AF initially suffer from paroxysmal episodes due to triggers that promote …

Atrial fibrillation (AF) is the most common cardiac arrhythmia. This study aimed to identify potential novel biomarkers for persistent AF (pAF) using integrated analyses and explore the immune cell infiltration in this pathological process. Three pAF datasets (GSE31821, GSE41177, and GSE79768) from the Gene Expression Omnibus (GEO) database were integrated with the elimination of batch effects. 264 differentially expressed genes (DEGs) were identified using Linear models for microarray data (LIMMA), 12 modules were screened out by weighted gene co-expression network analysis (WGCNA) in pAF compared with normal controls. Subsequently, common genes (CGs) were identified as the intersection of DEGs and genes in the most significant module. Functional enrichment analysis showed that CGs were mainly enriched in the "Calcineurin-NFAT (nuclear factor of activated T-cells)" signaling pathway, particularly regulator of calcineurin 1 (RCAN1), and protein phosphatase 3 regulatory subunit B, alpha (PPP3R1). Ulteriorly, the microRNA-transcription factor-mRNA network revealed that microRNA-34a-5p could target both RCAN1 and PPP3R1 in the pAF pathogenesis. Finally, immune infiltration analysis by CIBERSORT, a versatile computational method, displayed a higher level of monocytes, dendritic cells and neutrophils, as well as a lower level of CD8+ T cells and T cells regulatory (Tregs) in pAF compared with the control group. In conclusion, our present study revealed several novel pAF-associated genes, miRNAs, and pathways, including microRNA-34a-5p, which might target RCAN1 and PPP3R1 to regulate pAF through the calcineurin-NFAT signaling pathway. In addition, there was a difference in immune infiltration between patients with pAF and normal groups and immune cells might interact with specific genes in pAF.

Objectives This study aimed to assess the comparative efficacy of 4 ablation strategies on the incidence rates of freedom from atrial fibrillation (AF) or atrial tachycardia (AT) through a 3-year follow-up in patients with persistent AF. Background The optimal substrate modification strategies using catheter ablation for patients with persistent AF remain unclear. Methods Patients with persistent AF were enrolled consecutively to undergo each of 4 ablation strategies: (a) Group 1 (Gp 1, n=69), pulmonary vein isolation (PVI) plus rotor ablation assisted by similarity index and phase mapping; (b) Gp 2 (n=75), PVI plus linear ablations at the left atrium; (c) Gp 3 (n=42), PVI plus elimination of complex fractionated atrial electrograms; (d) Gp 4 (n=67), PVI only. Potential confounders were adjusted via a multivariate survival parametric model. Results Baseline characteristics were similar across the 4 groups. At a follow-up period of 34.9±38.6 months, patients in Gp 1 showed the highest rate of freedom from AF compared with the other 3 groups (p=0.002), while patients in Gp 3 and 4 showed lower rates of freedom from AT than those of the other two groups (p=0.006). Independent predictors of recurrence of AF were the ablation strategy (p=0.002) and left atrial diameter (LAD) (p=0.01). Conclusion In patients with persistent AF, a substrate modification strategy using rotor ablation assisted by similarity index and phase mapping provided a benefit for maintaining sinus rhythm compared to the other strategies. Both ablation strategy and baseline LAD predicted the 3-year outcomes of freedom from AT/AF This article is protected by copyright. All rights reserved.

Background Second-generation cryoballoon ablation is safe and effective in patients with paroxysmal (PAF) and persistent atrial fibrillation (AF). Objective This study aimed to assess the long-term clinical outcomes and freedom from AF in patients undergoing thermal-guided cryoablation without the use of an electrical mapping catheter. Methods All patients who had undergone thermal-guided second-generation cryoablation without electrical mapping between January 2015 and April 2018 at Eastbourne District General Hospital were retrospectively analysed. Success was defined as freedom from atrial arrhythmia lasting >30 s during the follow up period. Results The study included 234 patients with a mean age of 65.3 ± 10.6 years. There were 134 (57.0%) and 100 (42.7%) patients who had PAF and persistent AF respectively. Arrhythmia recurrence occurred in 38 of 134 (28.4%) PAF and 42 of 100 (42.0%) persistent AF patients after mean follow up of 40 ± 9.2 months. The patients with PAF had a significantly greater freedom from arrhythmia than patients with persistent AF (p = .040). The mean procedure time was 55.5 ± 12.2 min and the mean fluoroscopy time was 10.9 ± 4.8 min 73.5% of patients were discharged on the same day. Conclusion Thermal-guided cryoablation is feasible, safe and results in freedom from arrhythmia in the majority of paroxysmal and persistent AF patients in the long term. Randomised controlled trials are required to confirm the findings of this study.

Electrical isolation of the left atrial appendage (LAA) improves outcomes of patients with persistent atrial fibrillation (AF) but may increase the risk of thromboembolism.The purpose of this study was to describe a method to map and ablate appendage drivers without complete electrical isolation.One hundred thirteen patients underwent an ablation procedure for persistent AF. The procedure was performed during AF and consisted of pulmonary vein and posterior LA isolation as well as ablation of the LAA. The right atrium (RA) was targeted in patients with a right-to-left gradient in cycle length (CL). The end point of appendage ablation was CL slowing or AF termination but not complete isolation.Among the 113 patients (mean age 64.6 ± 8.6 years; ejection fraction 54% ± 13%; LA diameter 46 ± 6.5 mm), radiofrequency ablation terminated AF in 51 patients (45%). RA ablation was performed in 41 patients (36%) at the index or repeat procedure. The mean AF CL in the RA appendage (RAA) was shorter than that in the LAA (160 ± 32 ms vs 186 ± 29 ms; P.01) in these patients. The most frequent target in the RA was the RAA (CLs approaching 50-60 ms). Discontinuing radiofrequency ablation upon AF termination or conduction slowing prevented LAA isolation. After a mean follow-up of 24 ± 15 months, 89 patients (78%) remained arrhythmia-free without antiarrhythmic medications.An ablation strategy guided by the AF CL addresses LAA drivers without complete electrical isolation and also helps identify the RAA as a source of persistent AF.

Beyond pulmonary vein isolation, the two main additional strategies: Cox-Maze procedure or targeting of electrical signatures (focal bursts, rotational activities, meandering wavelets), remain controversial. High-density mapping of these arrhythmias has demonstrated firstly that a patchy lesion set is highly proarrhythmogenic, favoring macro-re-entry through conduction slowing and providing pivots for localized re-entry. Secondly, discrete anatomical structures such as the Vein or Ligament of Marshall (VOM/LOM) and the coronary sinus (CS) have epicardial muscular bundles that are more frequently involved in re-entry than previously thought. The Marshall Bundle can be ablated at any point along its course from the mid-to-distal coronary sinus to the left atrial appendage. If necessary, the VOM may be directly ablated using ethanol infusion to eliminate PV contributions and produce conduction block across the mistral isthmus. Ethanol ablation of the VOM, supplemented with RF ablation, may be more effective in producing conduction block at the mitral isthmus than repeat RF ablation alone.

BACKGROUND The second-generation cryoballoon (CB2) provides effective and durable pulmonary vein isolation (PVI) associated with encouraging clinical outcome. The novel fourth-generation cryoballoon (CB4) incorporates a 40% shorter distal tip. This design change may translate into an increased rate of PVI real-time signal recording, facilitating an individualized ablation strategy using the time to effect (TTE). METHODS AND RESULTS Three hundred consecutive patients with paroxysmal or persistent atrial fibrillation were prospectively enrolled. The first 150 consecutive patients underwent CB2 based PVI (CB2 group) and the last 150 consecutive patients were treated with the CB4 (CB4 group). A total of 594/594 (100%, CB4) and 589/594 (99.2%, CB2) pulmonary veins (PVs) were successfully isolated utilizing the CB4 and CB2, respectively (p = .283). The real-time PVI visualization rate was 47% (CB4) and 39% (CB2; p = .005) and the mean freeze cycle duration 200 ± 90 s (CB4) and 228 ± 110 s (CB2; p

Ablation treatment for persistent atrial fibrillation (persAF) remains challenging due to the absence of a 'ground truth' for atrial substrate characterization and the presence of multiple mechanisms driving the arrhythmia. We implemented an unsupervised classification to identify clusters of atrial electrograms (AEGs) with similar patterns, which were then validated by AEG-derived markers.956 bipolar AEGs were collected from 11 persAF patients. CARTO variables (Biosense Webster; ICL, ACI and SCI) were used to create a 3D space, and subsequently used to perform an unsupervised classification with k-means. The characteristics of the identified groups were investigated using nine AEG-derived markers: sample entropy (SampEn), dominant frequency, organization index (OI), determinism, laminarity, recurrence rate (RR), peak-to-peak (PP) amplitude, cycle length (CL), and wave similarity (WS).Five AEG classes with distinct characteristics were identified (F = 582, P0.0001). The presence of fractionation increased from class 1 to 5, as reflected by the nine markers. Class 1 (25%) included organized AEGs with high WS, determinism, laminarity, and RR, and low SampEn. Class 5 (20%) comprised fractionated AEGs with in low WS, OI, determinism, laminarity, and RR, and in high SampEn. Classes 2 (12%), 3 (13%) and 4 (30%) suggested different degrees of AEG organization.Our results expand and reinterpret the criteria used for automated AEG classification. The nine markers highlighted electrophysiological differences among the five classes found by the k-means, which could provide a more complete characterization of persAF substrate during ablation target identification in future clinical studies.

INTRODUCTION Non-pulmonary vein (PV) triggers are a major cause of atrial tachyarrhythmia (ATA) recurrence after catheter ablation. However, the effect of the diagnosis-to-ablation time (DAT) on non-PV triggers in persistent atrial fibrillation is unknown. METHODS AND RESULTS This observational study evaluated 502 consecutive persistent AF patients who underwent initial ablation. We compared 408 patients whose DAT was

Introduction Success rates of catheter ablation in persistent atrial fibrillation (AF) remain suboptimal. A better and more targeted ablation strategy is urgently needed to optimize outcomes of AF treatment. We sought to assess the safety and efficacy of targeting atrial fibrosis during ablation of persistent AF patients in improving procedural outcomes. Methods The DECAAF II trial (ClinicalTrials. gov identifier number NCT02529319) is a prospective, randomized, multicenter trial of patients with persistent AF. Patients with persistent AF undergoing a first-time ablation procedure were randomized in a 1:1 fashion to receive conventional pulmonary vein isolation (PVI) ablation (Group 1) or PVI + fibrosis-guided ablation (Group 2). Left atrial fibrosis and ablation induced scarring were defined by late gadolinium enhancement magnetic resonance imaging at baseline and at 3-12 months postablation, respectively. The primary endpoint is the recurrence of atrial arrhythmia postablation, including atrial fibrillation, atrial flutter, or atrial tachycardia after the 90-day postablation blanking period. Patients were followed for a period of 12-18 months with a smartphone ECG Device (ECG Check Device, Cardiac Designs Inc.). With an anticipated enrollment of 900 patients, this study has an 80% power to detect a 26% reduction in the hazard ratio of the primary endpoint. Results and conclusion The DECAAF II trial is the first prospective, randomized, multicenter trial of patients with persistent AF using imaging defined atrial fibrosis as a treatment target. The trial will help define an optimal approach to catheter ablation of persistent AF, further our understanding of influencers of ablation lesion formation, and refine selection criteria for ablation based on atrial myopathy burden.