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Original Articles: Adult Cardiac

Minimally Invasive Pulmonary Vein Isolation and Partial Autonomic Denervation for Surgical Treatment of Atrial Fibrillation

Cardiopulmonary Research Science and Technology Institute, Dallas, Texas

Accepted for publication March 28, 2008.

^_* Address correspondence to Dr J. R. Edgerton, 4708 Alliance Blvd, Suite 700, Plano, TX 75093 (Email: edgertonjr{at}aol.com).

Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.

Dr James R. Edgerton discloses that he has a financial relationship with Atricure.

 

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Background: We seek to demonstrate the rationale and efficacy of a minimally invasive surgical approach to the treatment of atrial fibrillation (AF) that combines pulmonary vein antral isolation with targeted partial autonomic denervation.

Methods: The literature supporting the rationale of this approach is reviewed. Seventy-four patients underwent video-assisted bilateral pulmonary vein antral isolation with confirmation of block and partial autonomic denervation with follow-up of 6 months or greater and have a long-term rhythm monitor at 6 months.

Results: Success was defined as no episodes greater than 15 seconds of AF on long-term monitoring. Treatment was successful in 83.7% of patients with paroxysmal AF and 56.5% of patients with persistent/long-standing persistent AF.

Conclusions: There are evidence-based data that support both pulmonary vein electrical isolation and targeted partial autonomic denervation in the treatment of AF. These techniques can be combined in a minimally invasive surgical approach. Early data suggest this is a safe and efficacious approach for the treatment of paroxysmal AF. Techniques are being developed for the minimally invasive surgical treatment of persistent AF from an epicardial approach.

The pathophysiology of atrial fibrillation (AF) involves the interplay between triggers and a changing left atrial substrate. A complex network of interconnecting nerves (the intrinsic cardiac autonomic nervous system) joins the left atrium to the pulmonary veins (PVs). The neurons join in clusters of autonomic ganglia in fat pads overlying the junction of the PVs and the left atrium [1, 2]. These clusters are referred to as ganglionated plexi (GP) by Armour and colleagues [2]. In 1987, Fee and coworkers [3] found that blocking the atrial fat pad ganglia produced chronotropic, inotropic, and dromotropic changes in the atria. Pappone and associates [4] showed that long-term success in maintaining sinus rhythm was correlated with the presence of a vagal response during radiofrequency ablation and attenuation of heart rate variability during subsequent follow-up.

Elimination of the GPs in the canine model prevents inducibility of AF [5]. Additionally, there is clinical evidence for successful elimination of AF by ablating in areas of the autonomic ganglia, suggesting that ganglia play a critical role in the initiation and maintenance of AF [4, 6–9]. Scherlag and colleagues [6] have shown increased efficacy in the elimination of AF by adding GP ablation to PV isolation in humans. Additionally, they have begun to study the elimination of AF by ablation of GPs alone without PV electrical isolation.

Based on the above findings, we began performing a standardized procedure for the minimally invasive surgical treatment of AF consisting of bilateral PV antral electrical isolation and targeted autonomic denervation of the left atrium with selective left atrial appendectomy. The feasibility of minimally invasive PV isolation has been previously described [10].

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
The study was approved by the Institutional Review Board, and individual consents were obtained. Seventy-four patients (46 paroxysmal, 14 persistent, 14 long-standing persistent) underwent bilateral PV antral electrical isolation using a bipolar radiofrequency clamp. Groups were defined as follows: paroxysmal was recurrent AF that terminates spontaneously within 7 days; persistent AF was defined as AF sustained beyond 7 days, or lasting less than 7 days but requiring either pharmacologic or electrical cardioversion; long-standing persistent AF was continuous AF of greater than 1-year duration.

Of the the 74 patients, 13 had undergone one prior ablation, 6 had two prior ablations, and 1 patient had three prior ablations. Fifteen of the 74 had permanent pacemakers in place. All patients underwent transesophageal echocardiography on the table before the procedure, and those who had undergone a prior catheter ablation had a left atrial magnetic resonance imaging scan or left atrial computed tomography scan. The procedure was accomplished in two stages. With the patient in a left lateral decubitus position, the right-sided PVs were approached through a small thoracotomy in the right chest; the patient was then repositioned and redraped in the right lateral decubitus position to approach the left PVs through a limited left thoracotomy. This thoracotomy was a 5.0 cm to 6.0 cm incision in the third or fourth intercostal space without rib spreading. Visualization was accomplished with a 5.0 mm 30-degree endoscope placed in the middle to posterior axillary line in the sixth or seventh intercostal space.

The pericardium was opened widely, 2.0 cm anterior to the phrenic nerve. Pericardial retraction sutures were brought out through the posterior chest wall to aid in visualization. The PVs were mapped by first sensing in the PV to determine baseline electrical activity. Then ganglionated plexi were located by high-frequency stimulation of 12 volts at a cycle length of 50 ms and a pulse width of 1 to 10 ms [6]. A GP was confirmed if a vagal response with an increase in the R-to-R interval of 50% or greater occurred. After dissecting around the PVs, a bipolar radiofrequency device was introduced and placed around the PV antrum well up onto the left atrium as far as possible away from the PV bifurcation. Three to five ablation lines were placed in slightly different positions to ensure electrical isolation. After this, sensing was repeated on the PVs to confirm entrance block from the left atrium indicating a transmural lesion and electrical isolation. The ablation was repeated as necessary until block was demonstrated. High-frequency burst pacing was again done in areas where GP were initially identified. If any vagal responses remained, these areas were further locally ablated until the response to high-frequency stimulation was considered negative as defined by no significant increase in the R-to-R interval during stimulation.

A 19F silicone elastomer drain was placed through the scope site, the working port incisions were closed, the wounds dressed, and the patient was then positioned in the right lateral decubitus position to approach the left sided PVs.

Similar exposure was obtained on the left side. On this side, the pericardium was opened posterior to the phrenic nerve, thus aiding in visualization of the PVs, the ligament of Marshall, and the base of the left atrial appendage. Again, baseline mapping was done on the PVs as well as high-frequency stimulation for localization of GP. Electrical isolation of the left PV antrum was accomplished again with a bipolar radiofrequency clamp after identifying and dividing the ligament of Marshall. Electrical block was again confirmed by sensing for entrance block in the PVs. High-frequency stimulation was repeated to ensure that there were no remaining GP as measured by a vagal response during high-frequency stimulation. The trabeculated portion of the left atrial appendage was then excised using a stapling device, the pericardium closed, drain placed, and the wounds were closed and dressed. The patient was then awakened, extubated in the operating room, and transferred to the intensive care unit for observational care.

Rhythm was monitored by office electrocardiogram (ECG) at 1, 3, and 6 months. At 6 months, the burden of AF was assessed by a 14- to 21-day autotriggered event monitor. When patient circumstances dictated, a 24-hour Holter monitor was substituted for the 21-day event monitor. The long-term monitors used sample the rhythm at 15-s intervals. When AF was detected by irregular rhythm, a single 15-s rhythm strip was recorded. Another rhythm strip was not recorded during that episode. Accordingly, we counted the number of episodes of AF but were unable to determine the duration of episodes more than 15 seconds or the true burden of AF. Patients with pacemakers underwent pacemaker interrogation for episodes of AF.

	Results

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
Morbidity and Mortality
Four patients suffered complications. There was one clotted hemothorax, which required thorascopic drainage. One patient had renal insufficiency without the need for dialysis, and 1 patient had transient brachial plexopathy, likely related to positioning on the operating table. Early in our experience, there was 1 death related to tearing of the base of the left atrial appendage.

Location of Positive Ganglionated Plexi
Data related to positive GP were collected for 34 patients. The GP most frequently found to be positive were those closest to Waterston's groove for the right pulmonary vein approach, and for the left, the area closest to the atrioventricular groove.

Rhythm
Rhythm documentation was complete in 70 of 74 of patients (94.6%) at 6 months by ECG; 66 of 74 (89.2%) had longer term monitors. This consisted of 24-hour Holter monitors in 24 patients (36.4%), 14- to 21-day event monitors in 31 patients (46.9%), and pacemaker interrogations in 11 patients (16.7%).

Success was defined as no AF episodes of greater than 15 seconds on monitoring at 6 months postoperative. For the entire group of patients, 65 of 70 (92.9%) had only sinus rhythm on ECG at 6 months, whereas 49 of 66 (74.2%) who had longer-term monitors had no detectable AF (>15 seconds).

Patients with paroxysmal AF fared better. By ECG, 43 of 43 (100%) were in sinus rhythm at 6 months and by longer term monitoring, 36 of 43 (83.7%) had successful treatment. In patients with persistent or long-standing persistent AF, 22 of 27 (81.5%) had sinus rhythm by 6-month ECG, and 13 of 23 (56.5%) had sinus rhythm by longer term monitoring (Table 1). The percentage of patients off antiarrhythmic drugs is listed in Table 1. However, it should be noted that very often the decision to discontinue antiarrhythmic drugs was not made until after the 6-month office visit.

Ten patients with persistent/long-standing persistent AF were considered treatment failures. Two of these patients were persistent after surgical ablation. The 8 patients who were converted to paroxysmal AF averaged 20 AF episodes each during long-term monitoring.

	Comment

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
It has been shown previously [11] that there is as much as a 40% difference in detection rates of AF when comparing implanted devices to random ECGs. Our data would confirm that the true burden of AF is not accurately assessed by random samplings of rhythm monitoring such as random ECGs. Nevertheless, most published literature today does use interval random ECGs or short rhythm strips to determine the outcomes of treatment for AF. In that context, our success rate for patients with paroxysmal AF compares very favorably. However, success rates for persistent and long-standing persistent AF of 81.5% by ECG and 56.5% by longer term monitoring leave room for improvement.

One might expect that PV antral isolation and partial autonomic denervation would not be adequate treatment for a patient in persistent and long-standing persistent AF because of the associated changes in the left atrial substrate that occur in these conditions [12]. This electrical remodeling of the left atrium results in a fixed shortened refractory period and a shortened fibrillatory interval [13]. Passive mechanical stretch of the left atrium that occurs in this chronic condition can in itself be arrhythmogenic [14, 15]. Atrial fibrosis has also been associated with AF [16, 17]. Therefore, it is likely that isolating the PV triggers alone is insufficient treatment for persistent and long-standing persistent AF. Hence, a more extensive lesion set similar to the left sided Cox Maze III is necessary.

To accomplish the left-sided Cox Maze III lesion set, a connecting lesion would need to be added between the left- and right-sided PVs, a connecting lesion to the base of the atrial appendage, and a connecting lesion to the mitral valve annulus. Traditionally, these connecting lesions are placed endocardially between the left and right inferior PVs, and from the right inferior PV down to the mitral valve annulus crossing the left atrial isthmus. However, when the epicardium is approached in a minimally invasive fashion, there are three inhibitors to placing the lesions in these locations. First, with currently available techniques, there is little to no visualization affordable posteriorly behind the left atrium. Second, as the circumflex coronary artery frequently overlies the mitral valve annulus, there is significant risk for collateral damage to this vital structure. Finally, the epicardial landmark for the mitral annulus is the coronary sinus. However, it has been shown [18] that the coronary sinus can be as much as 13 mm away from the mitral valve annulus, thus risking an incomplete connection, which may result in left atrial flutter.

In the minimally invasive approach, however, we can obtain excellent visualization through the transverse sinus behind the aorta and the pulmonary artery. Therefore, we have begun placing all of our connecting lesions here on the dome of the atrium (Fig 1). By working behind the superior vena cava and through the transverse sinus, we can place a transverse connecting lesion across the dome of the left atrium connecting the right superior PV with the left superior PV. It is then only a short extension of this line on the left side that connects it to the base of the left atrial appendage. The connecting lesion to the mitral valve annulus can also be accomplished on the dome of the left atrium within the transverse sinus. The left fibrous trigone touches the mitral valve annulus and connects it to the aorta at the aortic root. The left fibrous trigone meets the aortic valve at a point where the left coronary cusp and the noncoronary cusp join. Therefore, with good visualization, we can place this connecting lesion from the left fibrous trigone at the anterior mitral valve annulus, across the anterior dome of the atrium and touching transverse dome line. This, then, completes all of the left atrial lesions of the classic Cox Maze III operation. We have early studies under way to confirm transmurality of these lesions with conduction block.

View larger version (40K): [in this window] [in a new window]   Fig 1. The minimally invasive approach provides excellent visualization through the transverse sinus behind the aorta and the pulmonary artery. Connecting lesions on the dome of the atrium are shown.

In conclusion, there are evidence-based data that support both PV electrical isolation and targeted partial autonomic denervation in the treatment of AF. These techniques can be combined in a minimally invasive surgical approach. Early data suggest this is a safe and efficacious approach to the treatment of paroxysmal AF. Techniques are being developed for the minimally invasive surgical treatment of long-standing persistent AF from an epicardial approach.

	Discussion

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 
DR MARC MOON (St. Louis, MO): Jim, those are outstanding results with a less invasive procedure. I found with open pulmonary vein isolation similar results but maybe not quite as good in the persistent group like you have shown. The real question is, does that treat them forever, and have you followed any patients? You must have some up to a year out. Do you notice any tapering off of the success rate at that point?

DR EDGERTON: I have stayed away from reporting our 12-month results because the numbers in that group are still small. Within a couple of months, we will have almost 50 patients who are out a year, go to data lock on those, and be able to report the results. At this time I know the data on only 27 of those patients. And I will tell you that, without applying statistical analysis, our results at 12 months are very similar to what I reported at 6 months. Interestingly, we have a couple of patients who crossed over from a failure at 6 months to a success at 12 months, and several who crossed over from a success at 6 months to a failure at 12. Those patients have our intense scrutiny.

DR MOON: Do you have any insight into how you are going to decide in the future which patients with persistent you are going to do a full maze on as opposed to this procedure? You alluded to it in your conclusions, but any way to differentiate it at this point?

DR EDGERTON: We think that our results in the persistent and long-standing persistent population are inadequate, and therefore we have spent time trying to develop a minimally invasive approach to perform the full Cox Maze III left atrial lesion set in a minimally invasive manner. We now have 20 patients in that series with a more extensive lesion set who have 6-month follow-up, and those are being subjected to analysis at this time.

DR FARZIN FOTOUHI (Lima, OH): The big question is, we all have been doing concomitant procedures in combination with other procedures, and as we are embarking on trying minimally invasive procedures, the question is, where do we stand? For paroxysmal atrial fibrillation, it is clear that we can offer our patients a high degree of success rate. The big question is in the other category of the patients, where do we stand and what do we tell our patients? I have been quite confused over the last 3 or 4 days. A number of articles are being presented and a lot of authors are suggesting that they have excellent results in all comers, and I have been just not convinced offering this procedure to the patients who are in a category other than just paroxysmal atrial fibrillation. I think your paper clearly supports using it for paroxysmal atrial fibrillation, but where do we stand with the nonparoxsymal group?

DR EDGERTON: I think you are wise to be skeptical and tread cautiously into that arena, and we are doing so under a research protocol, but only because we have altered the lesion set. I think it has been shown by our paper here and by several others that have been published very recently that pulmonary vein electrical isolation alone is inadequate for the patients with persistent and long-standing persistent atrial fibrillation. We have embarked on a more extensive lesion set and are doing that under a research protocol and hope to be able to tell you something about that next year. But I would not advise pulmonary vein isolation alone for that patient group at this time.

DR EVGENIJ POTAPOV (Berlin, Germany): Do you think that the ablation of the ganglionated plexus adds some effect to this procedure? You have two groups, with ablation of ganglionated plexus and without. Do you think it is an additional effect?

DR EDGERTON: You say we have two groups?

DR POTAPOV: You have two groups. At the beginning you did not ablate the ganglionated plexus and in the last 82 patients you did. So do you think there is a statistical significance between the two groups?

DR EDGERTON: It is an intriguing point to bring up and I will go back and look at those, but I will tell you the number of patients in whom we did not do ganglionated plexus ablation is very small, too small for any valid comparison. Now the evidence for doing ganglionated plexus ablationis not found in the surgical literature. It is all presumptive evidence that we have taken out of the catheter-based literature. Time and space constraints will prevent me from summarizing all that literature, but there is strong suggestive evidence that ablation of the ganglionated plexus contributes to the success of this procedure.

DR MOON: The success rates you presented in the paroxysmal group are excellent. Do you still feel the need to ligate the left atrial appendage in this group? Why not just forget it? It is pretty dangerous, I think.

DR EDGERTON: That is an excellent question and one that we ask ourselves all the time within our group. The left atrial appendage is an important organ. It serves an important endocrine function, and serves as a compliance chamber for the left atrium, and removal of it is not without some risk, as you have noted.

It is important to remember that we are reporting only 6-month follow-up in a relatively small number of patients. If we were certain that this procedure results in long-term elimination of atrial fibrillation in a high percentage of our patients, then clearly we should leave the atrial appendage alone. And we ask ourselves now at this point in time, when do we stop? Is 80% success adequate? Is 6 months follow-up adequate? Should we leave the left atrial appendage alone? I acknowledge the question and also acknowledge I don't know the answer.

DR ANDREA J. CARPENTER (San Antonio, TX): I congratulate you on being the first I have seen to have the courage to present both the intermittent success rate, which is substantially better than outcomes for persistent long-term atrial fibrillation. I am heartened and certainly hope all future publications will do the same. Thank you, Dr Edgerton.

DR EDGERTON: Thank you.

	References

Top Abstract Introduction Patients and Methods Results Comment Discussion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): James R. Edgerton Syma Prince Michael J. Mack Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Edgerton, J. R. Articles by Mack, M. J. Search for Related Content PubMed PubMed Citation Articles by Edgerton, J. R. Articles by Mack, M. J. Related Collections Electrophysiology - arrhythmias