Hybrid Convergent Procedure Combined With Endocardial Cryoablation: Evolution of Approach and Future Directions

A prevailing strategy to manage non-paroxysmal atrial fibrillation (AF) that balances procedural risk and efficacy remains elusive. Despite technological advancements and refinements in our understanding of fibrillatory mechanisms, sustainable clinical success in managing non-paroxysmal atrial fibrillation has actually declined since the first mainstream surgical ablation trials were conducted in the 1980s. Despite its superiority when managing patients with persistent AF as compared to catheter ablation, surgical ablation is largely confined to concomitant surgical procedures involving coronary bypass and valve repair/replacement.

In 2020, the management of non-paroxysmal AF can be categorized as surgical, catheter based, or hybrid (which utilizes the technical efficiencies of both approaches).

Hybrid approaches can be further stratified according to the surgical method of entering the thorax: ablation via thoracoscopy versus a novel pericardioscopic approach. In this article, we discuss the evolution of the hybrid convergent ablation procedure, which utilizes a single subxiphoid incision in conjunction with a conventional catheter-based ablation to dovetail the epicardial surgical lesions. Further, we discuss our recently published outcome data utilizing endocardial cryoablation with the convergent approach. Finally, we discuss future directions that entail integrating epicardial left atrial appendage management with the hybrid AF convergent procedure, thereby providing comprehensive management to the patient with non-paroxysmal AF. 

Introduction

Rhythm control for paroxysmal AF has a high clinical success rate with an acceptable procedural risk. Recent trials have shown that catheter ablation as a first-line strategy bests pharmacologic management.^1-4 Catheter ablation trials involving non-paroxysmal AF have shown impressive short-term success; however, long-term sustainability has been difficult to demonstrate,^5,6 and as a result, it continues to bear either a Class IIa or IIb indication within nonsurgical consensus guidelines to manage non-paroxysmal AF.⁷ The resultant gap in treatment has prompted clinicians and industry to consider novel treatment strategies, including hybrid approaches. Although the idea to align surgical and non-surgical disciplines to manage cardiac disease is in no way novel, the treatment of non-paroxysmal atrial fibrillation has historically been siloed to either substrate modification via comprehensive surgical approaches or attempts to manage triggers using catheter ablation. More recently, the left atrial posterior wall has been the focus of contemporary catheter-based ablation trials,⁸ although long-term efficacy and safety are yet to be determined.

Hybrid Convergent Ablation

The hybrid convergent approach was originally developed in the early 2000s.⁹ The approach was novel as it allowed for ablation to be performed through a novel cannula placed in the pericardial space, allowing for unrestricted ablation of the posterior wall. The ablation catheter utilizes a closed irrigated design using an impedance-based generator varying unipolar RF output.¹⁰ Over the past 2 decades, the procedure has evolved and become safer. The cannula, once inserted through the diaphragm via an insufflated abdomen, has been moved to a single incision in the subxiphoid space similar to a surgical pericardial window. The ablation catheter is now outfitted with proximal and distal electrodes providing the surgeon the ability to map and pace, thereby adjudicating the effectiveness of the lesion set in real time (Figure 1). The lesion set, originally termed the ex-Maze to describe its utilization of intersecting lines similar to the Cox-Maze lesion set, was modified by Dr. Andy Kiser and our group to preferentially utilize complete substrate ablation, thereby eliminating the potential for gaps¹¹ (Figure 2, Video 1). Finally, the convergent approach has been selectively performed with an epicardial nitinol clip placed at the base of the left atrial appendage via a thoracoscopic cannula¹² (Figure 3, Video 2). Following the epicardial ablation, patients either proceed with the catheter-based endocardial ablation or return at a prespecified time following discharge to have the second portion of the procedure (Figure 4).

Epi/Endo Dissociation

Mechanisms to explain atrial fibrillatory conduction have evolved considerably since the original mechanistic theories were first described. Gaining considerable popularity is the concept of dual-layer conduction that suggests that fibrillatory conduction occurs both along the endocardial and epicardial “layers” of the atrial wall.^13,14 Asynchronous conduction between these layers may promote and sustain fibrillatory conduction. In this model, non-transmural ablation has the potential of increasing atrial fibrillation. Further, epicardial attachments between the right and left atrium as well as discrete areas within the left atrium have the ability to maintain fibrillation despite endocardial-only ablation. The failure of single-layer ablation has been shown in clinical studies documenting a silent endocardial posterior wall with persistent epicardial posterior wall conduction. The convergent procedure is unique in design as it ablates both the epicardium and endocardium. Although a randomized controlled trial (RCT) comparing catheter-based posterior wall silencing and convergent ablation at the time of writing does not exist, the convergent approach has been investigated against catheter-based ablation with linear lesions¹⁵ as well as utilization of cryotherapy as the endocardial ablation energy.¹⁶

Outcome Data

More than a decade’s worth of outcome data has been published on the convergent procedure, although the great majority of published literature had been retrospective.¹¹ The CONVERGE IDE trial sought to study the convergent procedure in a RCT design¹⁵ (Figure 5). The trial enrolled 153 patients at 27 locations (25 in the United States and 2 in the United Kingdom). Patients were randomized 2:1 to either the hybrid convergent procedure or endocardial catheter ablation alone. The trial’s primary effectiveness endpoint was freedom from AF, atrial tachycardia (AT), and atrial flutter (AFL), absent class I and III anti-arrhythmic drugs (AADs) except for previously failed or demonstrated intolerance to class I or III AADs, with no increase in dosage following the 3-month blanking period through the 12-month post-procedure follow-up visit (Figures 6 and 7). The primary safety endpoint was the incidence of protocol-defined major adverse events (MAEs) for subjects undergoing the convergent procedure from the time of the intervention through 30 days post intervention. There were no deaths, cardiac perforations, or atrioesophageal fistulas reported in the trial, with an overall MAE rate of 7.8% in the treatment arm. Although the trial was a much needed addition to validate the procedure’s efficacy, questions remained. The endocardial energy used in the trial was radiofrequency (RF). Endocardial cryoablation has been long thought to provide additional efficacy to epicardial ablation given the complimentary lesion profile afforded by the balloon. Further, the method of endpoint surveillance, as with most contemporary catheter ablation trials, used discrete interrogations using 24-hour Holters at 12 months as opposed to continuous monitoring. Both issues were addressed in a 2-center, prospectively and consecutively collected single-arm study involving 226 patients investigating endocardial cryoablation with epicardial convergent RF.¹⁶ Patients were followed between 2011 and 2018, with more than half followed using continuous loop recorders or previously implanted devices allowing for AF burden analysis. The results showed an impressive AF burden reduction to <5% in 94% of patients within 3- to 12-month follow-up and in 88% of patients within 12- to 24-month follow-up.¹⁶ Of particular significance was the disease severity of the patient population. Ninety-nine percent of studied patients had non-paroxysmal AF, and of this group, more than 60% had long-standing persistent AF. The study provides encouraging results in a historically difficult patient population largely underrepresented in AF ablation trials using a novel combination of ablation technologies. 

Future Directions

Despite the proliferation of studies investigating ablation in non-paroxysmal AF patients, many issues and unanswered questions remain. 

1. The nomenclature used to describe non-paroxysmal AF has obfuscated the interpretation of ablation trials and application of those results to clinical practice. For instance, ablation trials now limit study populations to either early persistent (a category identifying patients with AF less than 3 months), persistent, or rarely long-standing persistent. While the intent of the investigators is to appropriately study ablation within discrete AF subtypes, clinicians in practice have extrapolated those results beyond the intended scope of investigation. The likely effect is a mismatch between study results and the results observed in clinical practice. It will be important to design trials investigating true persistent and long-standing persistent AF patients, as these patients represent an increasingly growing proportion of patients in clinical practice.

2. Markers of disease severity vary widely among catheter ablation trials. Left atrial size, AF duration prior to index ablation, co-morbid conditions, and amiodarone usage prior to ablation are some examples of potential confounding variables that have the effect of improving or diminishing trial results within a particular AF subtype. Here again, the non-standardization of these clinical variables complicate comparisons between AF ablation trials. Registries such as the TRAC-AF database employed in our study of hybrid AF convergent cryo have the advantage of sampling actual patient populations managed in clinical practice instead of curated study populations. This allows clinicians to extrapolate registry results to clinical practice more exactly.

3. The left atrial appendage is increasingly becoming recognized as an arrhythmogenic structure along with the vein of Marshall. As AF disease severity increases, questions arise as to the importance of electrically silencing these structures for optimal long-term freedom from recurrent AF. Although trials studying endocardial electrical isolation of the left atrial appendage exist, the addition of mechanical electrical isolation using epicardial appendage ligation/exclusion will be an important addition to this body of literature. 

4. AF burden, previously an esoteric parameter of unknown clinical significance, has increasingly been recognized as an important clinical endpoint in AF rhythm control trials. CASTLE-AF has improved our understanding in following AF burden to impact hard clinical endpoints in patients with non-paroxsymal AF.¹⁷ It will be important to include this endpoint in future ablation trials, as the historical 30-second AF definition marking failure might not be clinically relevant in patients with non-paroxysmal disease. Further sophistication in AF detection algorithms by continuous monitoring devices, device-specific AF interval detection limits, and timing of implant may affect the interpretation of AF burden analysis and will also require some degree of standardization to make comparisons across trials. 

5. The trial follow-up period in non-paroxysmal AF investigations is a critical parameter when comparing ablation technologies. Scherr et al have effectively shown the hazards of drawing conclusions of clinical efficacy in persistent AF trials in their seminal publication following stepwise ablation patients to 5 years showing progressive decline in AF freedom with each passing year following the index ablation year.⁵ Tilz et al confirmed this observation in their well-designed trial also looking at long-term follow-up following index ablation in persistent AF patients.⁶ The ablation space is rapidly expanding with either devices modifying the delivery of RF in balloon and single-shot technologies, cryothermal energy, and non-thermal energies including pulsed field electroporation and laser. It will be important to follow these clinical observations beyond the usual 12-month trial designs to ensure lesion durability.

Conclusion

In summary, the hybrid convergent procedure combined with endocardial cryoablation has the potential to effectively manage patients with persistent and long-standing persistent AF. The addition of epicardial ligation at the time of the procedure might serve to improve AF-free survival, although the incremental benefit and the impact on stroke reduction remains to be shown. As the number of technologies to manage non-paroxysmal AF expand, careful attention to the patient populations studied will help to match the optimal AF subtype and the ablation technology used for that subtype. 

Find more information on Twitter at:

@kevinjmakati, @tampacardiac

Disclosures: Dr. Makati reports relationships with AtriCure, Boston Scientific, Medtronic, and Abbott. Dr. Sherman reports a relationship with AtriCure. Dr. Gerogiannis reports a past relationship with AtriCure. Dr. Sood reports relationships with AtriCure, Abbott, and Medtronic.

Video 1: Convergent hybrid ablation procedure animation.

Video 2: 2D/3D transesophageal echocardiogram before and after left atrial appendage ligation using AtriClip device.

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