Efficacy and safety of hybrid epicardial and endocardial ablation versus endocardial ablation in patients with persistent and longstanding persistent atrial fibrillation: a randomised, controlled trial.

Background: Endocardial catheter ablation (CA) has limited long-term benefit for persistent and longstanding persistent atrial fibrillation (PersAF/LSPAF). We hypothesized hybrid epicardial-endocardial ablation (HA) would have superior effectiveness compared to CA, including repeat (rCA), in PersAF/LSPAF. Methods: CEASE-AF (NCT02695277) is a prospective, multi-center, randomized controlled trial. Nine hospitals in Poland, Czech Republic, Germany, United Kingdom, and the Netherlands enrolled eligible participants with symptomatic, drug refractory PersAF and left atrial diameter (LAD) > 4.0 cm or LSPAF. Randomization was 2:1 to HA or CA by an independent statistician and stratified by site. Treatment assignments were masked to the core rhythm monitoring laboratory. For HA, pulmonary veins (PV) and left posterior atrial wall were isolated with thoracoscopic epicardial ablation including left atrial appendage exclusion. Endocardial touch-up ablation was performed 91-180 days post-index procedure. For CA, endocardial PV isolation and optional substrate ablation were performed. rCA was permitted between days 91-180. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia >30-s through 12-months absent class I/III anti-arrhythmic drugs except those not exceeding previously failed doses. It was assessed in the modified intention-to-treat (mITT) population who had the index procedure and follow-up data. Major complications were assessed in the ITT population who had the index procedure. Thirty-six month follow-up continues. Findings: Enrollment began November 20, 2015 and ended May 22, 2020. In 154 ITT patients (102 HA; 52 CA), 75% were male, mean age was 60.7 ± 7.9 years, mean LAD was 4.7 ± 0.4 cm, and 81% had PersAF. Primary effectiveness was 71.6% (68/95) in HA versus 39.2% (20/51) in CA (absolute benefit increase: 32.4% [95% CI 14.3%-48.0%], p < 0.001). Major complications through 30-days after index procedures plus 30-days after second stage/rCA were similar (HA: 7.8% [8/102] versus CA: 5.8% [3/52], p = 0.75). Interpretation: HA had superior effectiveness compared to CA/rCA in PersAF/LSPAF without significant procedural risk increase. Funding: AtriCure, Inc.

Selection of patients for hybrid ablation procedure.

Catheter ablation for treatment of symptomatic non-paroxysmal atrial fibrillation remains challenging. Clinical failure and need for continued medical therapy or repeat ablation is common, especially in more advanced forms of atrial fibrillation. Hybrid ablation has emerged as a more effective and safe therapy than endocardial-only ablation particularly for longstanding persistent atrial fibrillation as demonstrated by the randomized controlled CONVERGE trial. Hybrid ablation requires collaboration of electrophysiologists and cardiac surgeons to develop specific workflows. This review describes the Hybrid Convergent approach in the context of available ablation options and offers guidance for workflow development and patient selection.

Efficacy of the stand-alone Cox-Maze IV procedure in patients with longstanding persistent atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat. METHODS AND RESULTS: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0-12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence. CONCLUSION: Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation.

Multi-catheter cryotherapy compared with radiofrequency ablation in long-standing persistent atrial fibrillation: a randomized clinical trial.

AIMS: Restoring sinus rhythm (SR) by ablation alone is an endpoint used in radiofrequency (RF) ablation for long-standing persistent atrial fibrillation (AF) but not with cryotherapy. The simultaneous use of two cryotherapy catheters can improve ablation efficiency; we compared this with RF ablation in chronic persistent AF aiming for termination to SR by ablation alone. METHODS AND RESULTS: Consecutive patients undergoing their first ablation for persistent AF of >6 months duration were screened. A total of 100 participants were randomized 1:1 to multi-catheter cryotherapy or RF. For cryotherapy, a 28-mm Arctic Front Advance was used in tandem with focal cryoablation catheters. Open-irrigated, non-force sensing catheters were used in the RF group with a 3D mapping system. Pulmonary vein (PV) isolation and non-PV triggers were targeted. Participants were followed up at 6 and 12 months, then yearly. Acute PVI was achieved in all cases. More patients in the multi-catheter cryotherapy group were restored to SR by ablation alone, with a shorter procedure duration. Sinus rhythm continued to the last available follow-up in 16/49 patients (33%) in the multi-catheter at 3.0 ± 1.6 years post-ablation and in 12/50 patients (24%) in the RF group at 4.0 ± 1.2 years post-ablation. The yearly rate of arrhythmia recurrence was similar. CONCLUSION: Multi-catheter cryotherapy can restore SR by ablation alone in more cases and more quickly than RF ablation. Long-term success is difficult to achieve by either methods and is similar with both.

Initial experience with the convergent procedure for longstanding persistent atrial fibrillation: A 5 year dataset.

In patients with longstanding persistent atrial fibrillation (AF), outcomes from catheter ablation remain suboptimal. The convergent procedure combines minimally invasive surgical ablation with subsequent catheter ablation, and may contribute towards maintenance of sinus rhythm in this patient group. We performed the convergent procedure on 43 patients with longstanding persistent AF from 2013-2018. Patients underwent clinical review at 3, 6, and 12 months and thereafter as necessitated by their symptoms. Our dataset describes patients' baseline characteristics and rhythm control protocols, as well as outcomes including arrhythmia recurrence, the need for antiarrhythmic drugs, requirement for repeat rhythm control procedures, and complications. These data provide a real world insight into the risks and benefits of the convergent procedure in patients with longstanding persistent AF.

European multicentre experience of staged hybrid atrial fibrillation ablation for the treatment of persistent and longstanding persistent atrial fibrillation.

The management of non-paroxysmal atrial fibrillation (AF) remains controversial. We examined the efficacy and safety of the 2 stage Hybrid AF ablation approach by analysing the largest series of this technique reported so far. METHODS: The approach aims to electrically isolate the left atrial posterior wall incorporating the pulmonary veins ('box-set'pattern). An initial video-assisted thoracoscopic (VATS) epicardial ablation is followed after a minimum of 8 weeks by endocardial radiofrequency catheter ablation. RESULTS: Of 175 patients from 4 European cardiothoracic centers, who underwent the surgical (COBRA Fusion, AtriCure Inc) 1st stage ablation, 166 went on to complete 2nd stage catheter ablation. At median follow up of 18 months post 2nd stage procedure 93/166 (56%) had remained free of AF or atrial tachycardia (AT) recurrence off antiarrhythmic drugs. 110/175 62.9% were in sinus rhythm off all antiarrhythmic drugs at last clinic follow-up (132/175 75.4% including those on antiarrhythmic drugs). 18 patients (10.8%) underwent a further re-do ablation (mean of 1.1 ablations per patient) 105/166 (63%) remained free of AF/AT recurrence off antiarrhythmic drugs following last ablation procedure.Latterly, ILRs have been implanted in patients (n = 56); 60% have remained fully arrhythmia free and 80% have shown AF burden < 5% at a median 14 months follow-up [IQR: 13.5 (8-21.5)]. Only 10.9% have reverted to persistent AF. 5 patients (2.9%) had a perioperative stroke and 4 patients (2.3%) exhibited persistent weakness of the right hemidiaphragm following stage 1 VATS epicardial ablation. One patient died following stroke (overall mortality 0.6%). CONCLUSIONS: In patients with non-paroxysmal AF with unfavourable characteristics for catheter ablation, the staged hybrid approach results in acceptable levels of freedom from recurrent atrial arrhythmia, however, complication rates are higher than with catheter ablation alone.

Optimal endpoint for catheter ablation of longstanding persistent atrial fibrillation: A randomized clinical trial.

BACKGROUND: In longstanding persistent atrial fibrillation (LPeAF), the ideal endpoint of ablation remains to be determined. This study was to explore the value of pursuing AF termination or no with the same strategy during ablation on the long-term outcomes in patients with LPeAF. METHODS: Utilized "CCL" strategy is a fixed ablation approach consisting of circumferential pulmonary vein antrum isolation, ablation of complex fractionated atrial electrogram, and linear ablation between two anatomical structures (the mitral isthmus, left atrial roof). Note that 400 patients were randomized to group A (technical endpoint) and group B (pursuing AF termination). RESULTS: A group with technical endpoint had lower rate of acute AF termination (AF→sinus rhythm, 3.5% vs 18.1%; AF→atrial tachycardia, 23.7% vs 44.7%; P < 0.01) and shorter duration of ablation (164.9 ± 20.8 vs 223.4 ± 24.9, P < 0.01), radiofrequency delivery time (69.8 ± 18.1 vs 102.2 ± 26.3, P < 0.01), and x-ray exposure time (18.2 ± 8.8 vs 27.9 ± 12.4, P < 0.01) than those in B group (pursuing AF termination). During follow-up, freedom from atrial arrhythmias did not differ between the two groups after a single ablation procedure (46.5% vs 54.3%, P=0.12) and the final ablation procedure (60.1% vs 65.8%, P  =  0.24). CONCLUSION: In patients of LPeAF, pursuing AF termination during ablation was associated with similar long-term clinical outcome compared to that with technical endpoint. Ablation to termination is not the best strategy during ablation.

Prognostic Value of Inferior Shift of P wave Axis after Catheter Ablation for Longstanding Persistent Atrial Fibrillation based on Dallas Lesion Set Including Anterior Line

BACKGROUND AND OBJECTIVES: Although an anterior linear ablation is an effective lesion set in radiofrequency catheter ablation (RFCA) for longstanding persistent atrial fibrillation (L-PeAF), its durability for bidirectional block (BDB) is only about 60% at repeat procedure. We hypothesized that changes in electrocardiogram (ECG) may predict an anterior line block state and the clinical outcome of L-PeAF ablation. SUBJECTS AND METHODS: We studied 304 L-PeAF patients (77% male, 60±10yrs), who consistently underwent RFCA Dallas lesion set (circumferential pulmonary vein isolation, posterior box lesion, and anterior line) protocol with subsequent comparison of pre-procedural and post-procedural P wave axes, and one year follow-up (n=205) sinus rhythm (SR) ECGs. RESULTS: 1. P wave axis shifted inferiorly at immediate post-procedure (p<0.001), and was independently correlated with BDB of anterior line (β=10.4, 95% confidence interval [CI] 2.79-17.94, p=0.008). 2. The degree of post-procedural inferior shift of P wave axis did not reflect clinical recurrence within one-year (n=205, p=0.923), potentially due to conduction recovery of an anterior line. However, among 160 patients without clinical recurrence within one-year, P wave axis at one-year ECG was independently associated with very late recurrence of AF after one-year (n=160, hazard ratio [HR] 0.98; 95% CI 0.97-0.99, p=0.001), during 45.6±16.7 months of follow-up. 3. Among 22 patients who underwent repeat procedures, P wave axis shift was more significant in patients with maintained BDB of an anterior line than in those without (p=0.015). CONCLUSION: An inferior shift of P wave axis reflects the achievement and the maintenance of an anterior line BDB, and is associated with better long-term clinical outcome after catheter ablation for L-PeAF based on Dallas lesion set.

Hybrid Procedure (Endo/Epicardial) versus Standard Manual Ablation in Patients Undergoing Ablation of Longstanding Persistent Atrial Fibrillation: Results from a Single Center.

INTRODUCTION: Ablation of longstanding persistent atrial fibrillation (LSPAF) is the most challenging procedure in the treatment of AF, either by surgical or by percutaneous approach. OBJECTIVE: We investigated the difference in success and complication rates between combined surgical epicardial and endocardial catheter ablation procedure and our standard endocardial ablation procedure. METHODS AND RESULTS: Twenty-four consecutive patients (group 1) with LSPAF and enlarged left atrium (>4.5 cm) underwent a combined procedure, consisting of surgical, closed-chest, epicardial, radiofrequency ablation (nContact, NC, USA) via pericardial access, and concomitant endocardial ablation (hybrid procedure). Procedural complications and long-term outcomes were compared to those of 35 consecutive patients who refused the hybrid procedure and underwent standard endocardial only ablation (group 2). Baseline characteristics were comparable. In group 1, 1 patient (4.2%) developed post-procedural cardio-embolic stroke and 3 (12.5%) died (1 atrio-esophageal fistula, 1 fatal stroke, 1 of unknown cause in early follow-up), while no strokes or deaths occurred in group 2. Overall complication rates were higher for group 1 (P = 0.036). At 24-month follow-up, 4 (19%) patients in group 1 and 19 (54.3%) in group 2 were arrhythmia-free after a single procedure, on or off antiarrhythmic drugs (P<0.001). Total procedural time (276.9 ± 63.5 vs. 203.15 ± 67.3 minutes) and length of hospital stay (5 [IQR 3-8] vs. 1 [IQR 1-3] days were significantly shorter for group 2 (P <0.001). CONCLUSIONS: In patients with LSPAF and enlarged left atrium, a concomitant combined surgical/endocardial ablation approach increases complication rate and does not improve outcomes when compared to extensive endocardial ablation only.

Effect of periprocedural amiodarone on procedure outcome in patients with longstanding persistent atrial fibrillation undergoing extended pulmonary vein antrum isolation: results from a randomized study (SPECULATE).

BACKGROUND: The impact of amiodarone on ablation outcome in longstanding persistent atrial fibrillation (LSPAF) patients is not known yet. OBJECTIVE: The purpose of this study was to assess the effect of amiodarone on procedural-outcomes in LSPAF patients undergoing catheter ablation. METHODS: We enrolled 112 LSPAF patients on amiodarone and scheduled to undergo atrial fibrillation (AF) ablation. Patients were randomized to amiodarone discontinuation 4 months before ablation (group 1, n = 56) and a control group (group 2, n = 56) in which ablation was performed without amiodarone discontinuation. All patients underwent pulmonary vein (PV) antrum and posterior wall isolation, defragmentation and extra PV triggers ablation. Patients were followed up for recurrence for 32 ± 8 months post-ablation. Repeat procedures in all recurrent patients were performed off amiodarone. RESULTS: During ablation, AF termination was more frequent in group 2 compared to group 1 [44 (79%) vs 32 (57%), P = .015]. After high-dosage isoproterenol, more non-PV triggers were disclosed in group 1 compared to group 2 (42 [75%] vs 24 [43%] respectively, P <.001). Group 2 had lower procedure, radiofrequency and fluoroscopy times compared to group 1 (2.7 ± 1 vs 3.1 ± 1 h, 69 ± 13 min vs 87 ± 11 min and 64 ± 14 min vs 85 ± 18 min respectively, p < .05). At 32 ± 8 month follow-up, on or off antiarrhythmic drug success rate was 37 (66%) in group 1 and 27 (48%) in group 2 (P = .04). During redo, new non-PV trigger sites were identified in group 2 patients. CONCLUSION: Periprocedural continuous amiodarone was associated with higher organization rate and lower radiofrequency ablation rate. However, masking non-PV triggers increased the late recurrence rate.

The Convergent Procedure - A Standardised and Anatomic Approach Addresses the Clinical and Economic Unmet Needs of the Persistent Atrial Fibrillation Population.

A standardised treatment management approach is needed to address the escalating worldwide prevalence of atrial fibrillation (AF). The persistent and longstanding persistent AF patient population particularly needs this standardised treatment option to manage their AF. These patients have underlying structural heart disease that result in increased hospitalizations, long-term medical management that increases the cost burden of the healthcare system. Approximately 100 patients have undergone the Convergent Procedure at our center since its introduction 2 years ago, as a treatment option for AF patients. The epicardial and endocardial ablation procedures performed sequentially in a single setting has shown a single procedure success rate of 80%, similar to published success rates at other centers. The epicardial posterior wall isolation silences a majority of known substrates and the endocardial procedure completes the pulmonary vein isolation, creates the cavotricuspid line and provides diagnostic confirmation. The Convergent Procedure should be considered as a first line treatment option for the persistent and longstanding persistent AF patient population who have very limited or no treatment options for the long-term successful management of their AF.