One-year outcomes of pulmonary vein isolation with a novel cryoballoon: Primary results of the FROZEN AF trial.

INTRODUCTION: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open-label, prospective, single-arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. METHODS AND RESULTS: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow-up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re-initiated in 26.8% of patients after the 3-month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. CONCLUSIONS: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF.

Hybrid Convergent ablation for atrial fibrillation: A systematic review and meta-analysis.

Background: Hybrid Convergent ablation for atrial fibrillation (AF) combines minimally invasive surgical (epicardial) and catheter (endocardial) ablation. The procedural goal is to achieve more extensive, enduring ablation of AF substrate around the pulmonary veins, posterior wall, and vestibule of the posterior wall left atrium. Objective: To perform a systematic review and meta-analysis on safety and effectiveness of contemporary Hybrid Convergent procedures. Methods: PubMed, Embase, and manual searches identified primary research articles on Hybrid Convergent. Inclusion criteria focused on contemporary practices (epicardial ablation device and lesions). Clinical outcomes at 1 year or later follow-up, patient population, procedural details, and major adverse events (MAE) were recorded. Results: Of 249 records, 6 studies (5 observational, 1 randomized controlled trial) including 551 patients were included. Endocardial energy sources included radiofrequency and cryoballoon. Hybrid Convergent ablation was mostly performed in patients with drug-refractory persistent and longstanding persistent AF. Mean preprocedural AF duration ranged between 2 and 5.1 years. Most patients (∼92%) underwent Hybrid Convergent in a single hospitalization. At 1 year follow-up or later, 69% (95% confidence interval [CI]: 61%-78%, n = 523) were free from atrial arrhythmias and 50% (95% CI: 42%-58%, n = 343) were free from atrial arrhythmias off antiarrhythmic drugs. Thirty-day MAE rate was 6% (95% CI: 3%-8%, n = 551). Conclusion: Hybrid Convergent ablation is an effective ablation strategy for persistent and longstanding persistent AF. Contemporary procedural approaches and published strategies aim to mitigate complications reported in early experience and address delayed inflammatory effusions.

Quality of life after the initial treatment of atrial fibrillation with cryoablation versus drug therapy.

BACKGROUND: The STOP AF First trial recently demonstrated that initial treatment with cryoballoon ablation (CBA) is safe and superior to antiarrhythmic drug (AAD) therapy for preventing atrial arrhythmia recurrence in patients with symptomatic atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the change in quality of life (QoL) and symptoms after first-line CBA vs AAD therapy. METHODS: Patients with symptomatic AF not previously receiving rhythm control therapy were randomized to AAD (class I or III) or CBA (Arctic Front Advance, Medtronic, Mounds View, MN). QoL was evaluated at baseline and at 6 and 12 months by using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Quality of Life-5 Dimensions questionnaires. A review of AF-associated symptoms was conducted at baseline and at 1, 3, 6, and 12 months. RESULTS: In total, 203 subjects received either CBA (n = 104 [51.2%]) or AAD therapy (n = 99 [48.8%]). Improvements in the AFEQT summary and subscale scores were significantly larger with CBA than with AAD therapy at 6 and 12 months (P < .02 for all). Clinically meaningful improvement (>5 points) in the AFEQT summary score from baseline to 12 months was observed in 96.0% (100) of patients in the CBA arm vs 72.2% (71) of patients in the AAD arm (P < .001). No significant between-group differences were observed in the change in the European Quality of Life-5 Dimensions index or visual analog scale scores. Overall, 54.4% (57) of the CBA group vs 29.7% (29) of the AAD group reported no AF-specific symptom recurrence after a 90-day blanking period (P = .0005). CONCLUSION: First-line CBA vs AAD therapy is associated with larger improvements in AF-specific QoL and a higher rate of symptom resolution.

Left atrial posterior wall isolation in conjunction with pulmonary vein isolation using cryoballoon for treatment of persistent atrial fibrillation (PIVoTAL): study rationale and design.

BACKGROUND: There is growing evidence in support of pulmonary vein isolation (PVI) with concomitant posterior wall isolation (PWI) for the treatment of patients with symptomatic persistent atrial fibrillation (persAF). However, there is limited data on the safety and efficacy of this approach using the cryoballoon. OBJECTIVE: The aim of this multicenter, investigational device exemption trial (G190171) is to prospectively evaluate the acute and long-term outcomes of PVI versus PVI+PWI using the cryoballoon in patients with symptomatic persAF. METHODS: The PIVoTAL is a prospective, randomized controlled study ( ClinicalTrials.gov : NCT04505163) in which patients with symptomatic persAF refractory/intolerant to ≥ 1 class I-IV antiarrhythmic drug, undergoing first-time catheter ablation, will be randomized to PVI (n = 183) versus PVI+PWI (n = 183) using the cryoballoon in a 1:1 fashion. The design will be double-blind until randomization immediately after PVI, beyond which the design will transform into a single-blind. PVI using cryoballoon will be standardized using a pre-specified dosing algorithm. Other empiric ablations aside from documented arrhythmias/arrhythmias spontaneously induced during the procedure will not be permitted. The primary efficacy endpoint is defined as AF recurrence at 12 months, after a single procedure and a 90-day blanking period. Arrhythmia outcomes will be assessed by routine electrocardiograms and 7-14 day ambulatory electrocardiographic monitoring at 3, 6, and 12 months post-ablation. CONCLUSION: The PIVoTAL is a prospective, randomized controlled trial designed to evaluate the outcomes of PVI alone versus PVI+PWI using the cryoballoon, in patients with symptomatic persAF. We hypothesize that PVI+PWI will prove to be superior to PVI alone for prevention of AF recurrence.

Combined epicardial and endocardial ablation for atrial fibrillation: Best practices and guide to hybrid convergent procedures.

The absence of strategies to consistently and effectively address nonparoxysmal atrial fibrillation by nonpharmacological interventions has represented a long-standing treatment gap. A combined epicardial/endocardial ablation strategy, the hybrid Convergent procedure, was developed in response to this clinical need. A subxiphoid incision is used to access the pericardial space facilitating an epicardial ablation directed at isolation of the posterior wall of the left atrium. This is followed by an endocardial ablation to complete isolation of the pulmonary veins and for additional ablation as needed. Experience gained with the hybrid Convergent procedure during the last decade has led to the development and adoption of strategies to optimize the technique and mitigate risks. Additionally, a surgical and electrophysiology "team" approach including comprehensive training is believed critical to successfully develop the hybrid Convergent program. A recently completed randomized clinical trial indicated that this ablation strategy is superior to an endocardial-only approach for patients with persistent atrial fibrillation. In this review, we propose and describe best practice guidelines for hybrid Convergent ablation on the basis of a combination of published data, author consensus, and expert opinion. A summary of clinical outcomes, emerging evidence, and future perspectives is also given.

Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.

BACKGROUND: In patients with symptomatic paroxysmal atrial fibrillation that has not responded to medication, catheter ablation is more effective than antiarrhythmic drug therapy for maintaining sinus rhythm. However, the safety and efficacy of cryoballoon ablation as initial first-line therapy have not been established. METHODS: We performed a multicenter trial in which patients 18 to 80 years of age who had paroxysmal atrial fibrillation for which they had not previously received rhythm-control therapy were randomly assigned (1:1) to receive treatment with antiarrhythmic drugs (class I or III agents) or pulmonary vein isolation with a cryoballoon. Arrhythmia monitoring included 12-lead electrocardiography conducted at baseline and at 1, 3, 6, and 12 months; patient-activated telephone monitoring conducted weekly and when symptoms were present during months 3 through 12; and 24-hour ambulatory monitoring conducted at 6 and 12 months. The primary efficacy end point was treatment success (defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day blanking period to allow recovery from the procedure or drug dose adjustment, evaluated in a Kaplan-Meier analysis). The primary safety end point was assessed in the ablation group only and was a composite of several procedure-related and cryoballoon system-related serious adverse events. RESULTS: Of the 203 participants who underwent randomization and received treatment, 104 underwent ablation, and 99 initially received drug therapy. In the ablation group, initial success of the procedure was achieved in 97% of patients. The Kaplan-Meier estimate of the percentage of patients with treatment success at 12 months was 74.6% (95% confidence interval [CI], 65.0 to 82.0) in the ablation group and 45.0% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan-Meier estimate of the percentage of patients with an event within 12 months, 1.9%; 95% CI, 0.5 to 7.5). CONCLUSIONS: Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon. (Supported by Medtronic; STOP AF First ClinicalTrials.gov number, NCT03118518.).

The Convergent Atrial Fibrillation Ablation Procedure: Evolution of a Multidisciplinary Approach to Atrial Fibrillation Management.

The treatment of AF has evolved over the past decade with increasing use of catheter ablation in patients refractory to medical therapy. While pulmonary vein isolation using endocardial catheter ablation has been successful in paroxysmal AF, the results have been more controversial in patients with long-standing persistent AF where extrapulmonary venous foci are increasingly recognised in the initiation and maintenance of AF. Hybrid ablation is the integration of minimally invasive epicardial ablation with endocardial catheter ablation, and has been increasingly used in this population with better results. The aim of this article was to analyse and discuss the evidence for the integration of catheter and minimally invasive surgical approaches to treat AF with specific focus on convergent ablation and exclusion of the left atrial appendage using a surgically applied clip.

Predictors of early mortality in patients age 80 and older receiving implantable defibrillators.

BACKGROUND: There are no upper age restrictions for implantable defibrillators (ICDs) but their benefit may be limited in patients > or = 80 years with strong competing risks of early mortality. Risk factors for early (1-year) mortality in ICD recipients > or = 80 years of age have not been established. METHODS: Two-center retrospective cohort study to assess predictors of one-year mortality in ICD recipients > or = 80 years of age. RESULTS: Of 2,967 ICDs implanted in the two centers from 1990-2006, 225 (7.6%) patients were > or =80 years of age and followed-up at one of the two centers. Mean age was 83.3 +/- 3.1 years and follow-up time 3.3 +/- 2.6 years. Median survival was 3.6 years (95% confidence interval 2.3-4.9). Multivariate predictors of 1-year mortality included ejection fraction (EF) < or = 20% and the absence of beta-blocker use. Actuarial 1-year mortality of ICD recipients > or = 80 with an EF < or = 20% was 38.2% versus 13.1% in patients 80+ years with an EF > 20% and 10.6% for patients < 80 years with an EF < or = 20% (P < 0.001 for both). There was no significant difference in the risk of appropriate ICD therapy between those patients 80+ years with EF above and below 20%. CONCLUSION: In general, patients > or = 80 years of age who meet current indications for ICD implantation live sufficiently long to warrant device implantation based on anticipated survival alone. However, those with an EF < or = 20% have a markedly elevated 1-year mortality with no observed increase in appropriate ICD therapy, thus reducing the benefit of device implantation in this population.

Wide complex tachycardia in a healthy young man.

We describe a case of a young man referred with a broad complex tachycardia for evaluation and ablation. Electrophysiological study was performed and revealed a left lateral accessory pathway with antegrade decremental conduction causing antidromic reciprocating re-entrant tachycardia. Ablation was successfully performed. Left lateral accessory pathways with decremental conduction are rarely encountered.

Left atrial linear lesions are required for successful treatment of persistent atrial fibrillation.

AIMS: This study evaluates the clinical outcome and incidence of left atrial (LA) macro re-entrant atrial tachycardia (AT) in patients in whom persistent atrial fibrillation (AF) terminated during catheter ablation without the need of roof and mitral lines. METHODS AND RESULTS: Persistent AF was terminated by ablation in 154 of 180 consecutive patients. AF history was 60 months including 11 months of continuous AF. Patients were divided into two groups: those who had not required both LA linear lesions to terminate AF (group A, 85 patients), and those who had (group B, 69 patients). There was no difference in clinical and echocardiographic characteristics between both groups except for a shorter duration of continuous AF in group A (9 vs.12 months, respectively) (P = 0.03). After 28 months of follow-up, the incidence of LA macro re-entrant AT necessitating linear ablation was higher in group A (76%) compared with group B (33%) (P = 0.002). When complete linear block could not be achieved during the index procedure, the incidence of subsequent roof (P = 0.008) or mitral isthmus (P = 0.010) dependent macro re-entrant AT was higher. CONCLUSION: Although persistent AF can be terminated by catheter ablation without linear lesions, the majority will require linear lesions for macro re-entrant AT.

Advances in mechanisms of atrial fibrillation: structural remodeling, high-frequency fractionated electrograms, and reentrant AF drivers.

The mechanisms to explain atrial fibrillation (AF) have been widely debated. Although contemporary experimental techniques have provided more insight, hypotheses regarding AF propagation conceived in the early half of the century remain minimally altered and relevant today. Modern mapping technologies have implicated multiwavelet reentry as the electrophysiologic basis to explain AF propagation within the atrial myocardium; however, reentry has also been observed within pulmonary veins and may behave as a focal trigger. The ability to terminate AF by catheter ablation has provided additional clues to explain AF induction and sustenance. The presence of complex fractionated electrograms (CFAE) and subsequent successful CFAE-directed ablation suggest that diseased atrial myocardium is a necessary substrate for AF maintenance. Atrial remodeling creates differential areas of refractory periods and conduction velocity, which, in turn, creates a suitable environment for AF. This review addresses the complex relationship between remodeled atrial myocardium and reentry and explores the role of CFAEs in AF maintenance.

Equivalent arrhythmic risk in patients recently diagnosed with dilated cardiomyopathy compared with patients diagnosed for 9 months or more.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) recently expanded coverage for implantable cardioverter-defibrillators (ICDs) in patients with left ventricular ejection fraction < or =35% and nonischemic dilated cardiomyopathy for > or =9 months. To investigate the ramifications of these criteria, the ICD registry from Tufts-New England Medical Center was analyzed for arrhythmic events and death in patients with newly diagnosed (<9 months) vs late-diagnosed (> or =9 months) nonischemic dilated cardiomyopathy. OBJECTIVES: The purpose of this study was to analyze the arrhythmic risk in patients with recent vs late diagnosis of nonischemic dilated cardiomyopathy. METHODS: One hundred thirty-one patients with nonischemic dilated cardiomyopathy were divided into two cohorts (<9 or > or =9 months of symptoms) and analyzed for any occurrence of treated ventricular arrhythmia, potentially lethal arrhythmias defined as ventricular flutter rates > or =230 bpm, and ventricular fibrillation. Patients with documented sustained ventricular tachycardias (included in prior CMS coverage) were excluded. RESULTS: In the study group, the mean age was 58.1 +/- 15 years and ejection fraction 20.6% +/- 8%. In a follow-up period of 25.3 +/- 24 months, the 52 patients with a recent diagnosis (1.4 +/- 2 months) had no difference in the occurrence of ventricular arrhythmias (P = .49) and malignant ventricular arrhythmias (P = .16) compared with the 79 patients diagnosed > or =9 months (mean 58.1 +/- 39 months). CONCLUSION: Patients with nonischemic dilated cardiomyopathy experienced equivalent occurrences of treated and potentially lethal arrhythmias irrespective of diagnosis duration. These findings suggest that the 9-month time qualifier used in the CMS guidelines for ICD reimbursement may not reliably discriminate patients at high risk for sudden cardiac death in this selected population.