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Ann Thorac Surg 2011;91:97-102. doi:10.1016/j.athoracsur.2010.08.037
© 2011 The Society of Thoracic Surgeons
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Right arrow Electrophysiology - arrhythmias

Original Articles: Adult Cardiac

Left Atrial Ganglion Ablation as an Adjunct to Atrial Fibrillation Surgery in Valvular Heart Disease

Adam L. Ware, MDb, Rakesh M. Suri, MD, DPhila,*, John M. Stulak, MDa, Thoralf M. Sundt, III, MDa, Hartzell V. Schaff, MDa

a Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota
b Mayo Medical School, College of Medicine, Mayo Clinic, Rochester, Minnesota

Accepted for publication August 19, 2010.

* Address correspondence to Dr Suri, Division of Cardiovascular Surgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (Email: suri.rakesh{at}mayo.edu).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: Our aim was to evaluate early results of ganglionic plexus (GP) ablation with modified Cox maze lesion sets for concomitant atrial fibrillation (AF) during corrective valve surgery.

Methods: Between December 2006 and April 2008, 20 patients (7 men; median age, 65 years; range, 52 to 82 years) with valvular heart disease and AF (intermittent in 12 [60%]) underwent corrective valve surgery with maze and GP ablation. Patients were then compared with a case-matched control cohort who underwent radiofrequency ablation maze alone.

Results: Procedures included mitral valve repair in 7 patients (35%), multivalve procedures in 5 (25%), mitral valve replacement in 4 (20%), aortic valve replacement in 3 (15%), and valve-sparing aortic root replacement in 1 (5%). All patients underwent concomitant AF ablation procedures (biatrial maze in 11 [55%], left-sided maze in 9 [45%]). Ganglionic plexus stimulation was performed in all patients. Sites at which the R-R interval doubled were considered active and were ablated. There were no early deaths. Freedom from AF at 1 year was significantly higher (90% versus 50%; p = 0.01) and mean New York Heart Association functional class was better (1 versus 1.7; p < 0.001) in the group that underwent maze and GP ablation compared with maze alone.

Conclusions: Active left atrial GP are frequently present in patients with AF and valvular heart disease, and GP ablation can be safely performed as an adjunct to AF ablation during valve surgery. Early results are promising and may yield higher freedom from AF compared with radiofrequency ablation maze alone.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
A trial fibrillation (AF) is a common finding in patients with valvular heart disease, and estimates indicate that as many as 50% of patients with mitral valve disease also have concomitant AF [1]. Aronow and colleagues [2] found that in patients with AF, compared with patients without AF, prevalence increased for concomitant mitral stenosis (17x), aortic stenosis (2.4x), mitral regurgitation (2.2x), and aortic regurgitation (2.1x). Similarly, other studies have found that nearly 40% of patients who undergo mitral valve repair have preoperative persistent AF [3, 4]. Importantly, AF is associated with adverse outcomes such as cerebrovascular accidents and increased mortality [5]. Currently, AF is commonly treated with alternative energy sources such as radiofrequency ablation (RFA) to create variations of the original Cox maze lesion set at the time of valve surgery [5–7].

More recently, ectopic impulses originating from the autonomic ganglionic plexus (GP) adjacent to the pulmonary veins have been implicated in the initiation of AF [8]. Cardiac GP are typically found in fatty epicardial tissue, consisting of efferent autonomic fibers and afferent neurons capable of exerting autonomic influence on the heart [9–11]. Further, isolated mapping and ablation of GP have been shown to reduce the recurrence of medically refractory AF [12]. In an attempt to investigate the value of this adjunctive procedure, we describe a technique and report early patient outcomes for a modified maze procedure in combination with mapping and ablation of GP to treat AF during cardiac valve repair or replacement.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
Patients
The Mayo Clinic Institutional Review Board approved this study, including waiver for informed consent owing to a lack of relevant patient identifiers. We retrospectively reviewed the medical records of 20 patients (7 men) who underwent concomitant ganglion ablation (GA) and maze procedure during corrective valve surgery between December 2006 and April 2008. Patients were selected for the procedure if they had echocardiographically confirmed valve disease and a history of AF. Median age at the time of operation was 65 years (range, 52 to 82 years). Twelve patients (60%) had preoperative intermittent AF and 8 patients (40%) had persistent AF. Preoperatively, 13 patients (65%) were in New York Heart Association (NYHA) functional class III or IV, and the median preoperative AF duration was 22 months (range, 8 days to 37 years).

Past medical history included coronary artery disease in 3 patients (15%), pulmonary hypertension in 3 patients (15%), transient ischemic attack in 2 patients (10%), myocardial infarction in 1 patient (5%), scleroderma in 1 patient (5%), and stroke in 1 patient (5%). Prior cardiovascular procedures included catheter-based AF therapy in 4 patients (20%), electrical cardioversion in 3 patients (15%), angioplasty with stenting in 1 patient (5%), and percutaneous valvuloplasty in 1 patient (5%). The mean left atrial size was 65.4 ± 2.1 mm, and the mean left atrial volume index was 62.8 ± 4.4 mL/m2.

Indications for surgery included severe mitral valve regurgitation in 10 patients (50%), combined mitral valve stenosis and regurgitation in 4 patients (20%), aortic valve stenosis in 3 patients (15%), combined aortic and mitral valve stenosis and regurgitation in 1 patient (5%), mitral valve stenosis in 1 patient (5%), and ascending aortic and aortic root aneurysm in 1 patient (5%). Concomitant procedures performed included tricuspid valve repair in 4 patients (20%), closure of patent foramen ovale in 2 patients (10%), and coronary artery bypass grafting in 1 patient (5%).

Surgical Procedure
After median sternotomy and initiation of cardiopulmonary bypass, active GP were mapped with 12 V of high-frequency stimulation at a cycle length of 50 ms and a pulse width of 1.5 ms [13]. Standard locations of active GP sites have been previously described [14]. Stimulation that resulted in a doubling of the R-R interval was designated as an active GP [14]. All active sites were immediately ablated with an RFA pen (AtriCure, Inc, West Chester, OH) (Fig 1).


Figure 1
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  		Fig 1. Mapping and ablation of left atrial ganglionic plexus. Mapping was performed with 12 V of high-frequency stimulation (cycle length, 50 ms; pulse width, 1.5 ms). Ganglionic plexuses were considered active if stimulation resulted in a doubling of the R-R interval. All active sites were immediately ablated with a radiofrequency ablation pen.

 
After GP mapping and ablation, the aorta was cross-clamped and the heart was arrested with cold-blood cardioplegia. The indicated valve procedure with concomitant maze procedure was then completed. Intermittent AF was treated with a modified left atrial maze procedure, and persistent AF was treated with a modified biatrial maze procedure [15]. A biatrial maze was also performed in patients who had a previously failed catheter ablation procedure or severe arrhythmia-related symptoms. The modified left atrial maze consisted of right and left pulmonary vein isolation with a dry bipolar RFA clamp (AtriCure, Inc; Fig 2A). The RFA clamp was used to place a bridging lesion between the right and left pulmonary veins, along the inferior aspect of the left atrium. Cryoablation (CryoCath Technologies Inc, Montreal, Quebec, Canada) was used to create two more lesions; a lesion to the base of the excised or excluded left atrial appendage and a connecting lesion to the medial annulus of the mitral valve (Fig 2B). For the biatrial maze procedure, an RFA clamp was also applied to the medial and lateral portions of the right atrial appendage and along the intercaval groove. Two cryolesions were created at the right atrial isthmus and at the atriotomy toward the tricuspid annulus. When the surgical procedure was complete, exit block was confirmed by test-pacing the right and left pulmonary veins distal to the vein isolation lesion. Failure to demonstrate exit block resulted in subsequent pulmonary vein isolation and retesting as described elsewhere [14].


Figure 2
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  		Fig 2. Modified left atrial maze lesion set. (A) Right and left pulmonary veins were isolated with a dry bipolar radiofrequency ablation clamp. (B) Linear cryolesions were created from the left inferior pulmonary vein to both the left atrial appendage and the posteromedial mitral annulus. Exit block was confirmed after weaning from cardiopulmonary bypass to confirm the integrity of the left-sided lesions.

 
To further evaluate the effect of GP ablation, we compared outcome with a control population who underwent valvular surgery with concomitant AF ablation with radiofrequency, but without GP ablation. Patients were case matched 1:1 according to age at operation and type of preoperative AF. Median age of both groups was 65 years; the control and preoperative AF was intermittent in 12 patients in each group. Important clinical characteristics that were present in each group after matching was performed are shown in Table 1.


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  		Table 1 Clinical Characteristics for Study Group (Ganglion Ablation + Maze) and Control Group (Maze Alone) a
 
Statistical Analysis
Demographic information and other patient-related data were obtained from Mayo Clinic medical records. Follow-up information was harvested from subsequent clinic visits and correspondence with patients and their physicians. After a blanking period of 3 months, rhythm was evaluated by electrocardiography or 24-hour Holter monitor testing during hospitalization and outpatient follow-up. Data were expressed as median with a range or as mean ± standard error of the mean. Early death was defined as death occurring within 30 days of operation or at any time during the index hospitalization.


   Results
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 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Ganglion mapping demonstrated active GP in all patients; all had active GP on the left side, but 3 patients (15%) had no identifiable active GP on the right. Eighteen patients (90%) had at least one active GP in the ligament of Marshall. On average, patients had four active GP on the right and five active GP on the left. There were no intraoperative complications that were directly attributed to the use of ganglionic mapping, and the addition of this adjunct added roughly 10 to 15 minutes of total operative time. The mean aortic cross-clamp time was 69 ± 9.6 minutes and mean cardiopulmonary bypass time was 108 ± 14.1 minutes.

Postoperative Rhythm
There were no early deaths. As expected, early atrial arrhythmias were common postoperatively. At dismissal, 10 patients (50%) were in normal sinus rhythm, 3 patients (15%) were in rate-controlled atrial flutter, 3 patients (15%) were in AF, 1 patient (5%) was in a junctional rhythm with stable blood pressure, and 1 patient (5%) was in a stable ectopic atrial rhythm. Two patients (10%) required a permanent pacemaker for sick sinus syndrome. Arrhythmias that developed during the postoperative period were aggressively treated with amiodarone and β-blockers; 12 patients (60%) were dismissed on amiodarone. After dismissal, antiarrhythmic medications were managed by the patients' cardiologist.

Follow-Up
Follow-up was obtained for all 20 patients, with a median of 25 months (range, 12 to 37 months). During follow-up, 1 patient died suddenly of unknown causes 3 months after dismissal; a request for postmortem examination was refused. This patient had an uncomplicated postoperative course and was dismissed in normal sinus rhythm. At last contact, this patient was still in normal sinus rhythm and was in NYHA functional class I. Notable aspects of the patient's past medical history were hyperlipidemia, coronary artery disease with prior stent placement, two prior myocardial infarctions, carotid endarterectomy, renal artery stenosis with stent placement, and cerebrovascular accident resulting in left hemiparesis.

Atrial fibrillation within the first 3 months postoperatively (typical blanking period) was common among the 19 late survivors; only 2 patients (11%) had no documented recurrence of AF, 10 patients (53%) had one recurrence, 3 patients (16%) had two recurrences, and 2 patients (11%) had three recurrences. Two patients remained in rate-controlled AF throughout the follow-up period. Electrical cardioversion was attempted in 4 patients (successful in 2 patients), and the remainder were either treated medically or spontaneously converted to sinus rhythm. At last follow-up, 17 of 19 patients (89%) were free of AF, 15 patients (79%) were in normal sinus rhythm, and 2 patients (11%) were in a paced rhythm. Rhythm analysis was obtained from 24-hour Holter monitoring in 4 patients (21%), and 15 patients (79%) had 12-lead electrocardiography. Seventeen patients (89%) were in NYHA class I, and 2 patients (11%) were in NYHA class II. At last follow-up, 10 patients (53%) were taking β-blockers, 9 patients (47%) warfarin, 2 patients (11%) sotalol, 2 patients (11%) digoxin, and 1 patient (5%) amiodarone; importantly, 14 of the 19 patients (74%) were free of AF and off antiarrhythmic medications.

Comparison With Control Group
Preoperative clinical characteristics were similar between groups (Table 1). In addition, the type and length of operation were also similar. Median follow-up was 25 months in the GA plus maze group and 41 months in the RFA maze alone group (p = 0.01). Freedom from AF in the GA plus maze group was 90% at 6 months and 1 year, whereas freedom from AF in the maze alone group was 81% at 6 months and 50% at 1 year (p = 0.01). Mean NYHA functional class was 1 ± 0.1 in the GA plus maze group compared with 1.7 ± 0.6 in the maze alone group (p < 0.001).


   Comment
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 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
Atrial fibrillation is a serious comorbidity commonly present in patients with valvular heart disease. Surgical ablation of AF during valve surgery offers patients the potential to regain normal activity, prevents the development of heart failure [16], and can also reverse cardiac dysfunction caused by tachycardia-induced cardiomyopathy [17]. In addition, elimination of AF offers freedom from the complications of long-term anticoagulation, particularly in patients undergoing valve repair or biologic valve replacement. Thus, the goal of increasing the efficacy of surgical arrhythmia procedures is worthy of pursuit. In this preliminary series, we indeed found that when GA was added to a RFA maze procedure, patients had a higher freedom from AF at 1 year of follow-up and significant improvement in functional status.

The traditional cut and sew biatrial maze procedure is the gold standard for the surgical treatment of AF, with long-term cure rates reported as high as 90% [18, 19]. The addition of the maze procedure to mitral valve repair has been shown to decrease the incidence of late AF, stroke, and anticoagulant-associated bleeding compared with treatment consisting of valve repair alone [7]. The initial cut-and-sew procedure was deemed lengthy and technically difficult by some, and subsequently it did not gain widespread acceptance despite excellent outcomes [16]. Recently, the use of alternative energy sources to create all or part of the standard Cox maze lesions simplified the original operation, leading to a decrease in both bypass and cross-clamp times [20]. Advances in RFA technology have allowed the maze procedure to be used more frequently as an adjunct during valve repair or replacement surgery in patients with concomitant AF. The use of RFA technology has decreased the technical complexity of the operation; however, concern persists that the results obtained using alternative energy sources do not match those observed with the cut-and-sew maze procedure [21]. Recent studies of patients undergoing the radiofrequency maze at the time of valve surgery demonstrated an overall 73% long-term freedom from AF [22] compared with 79% among patients undergoing the cut-and-sew technique [23]. Regardless of lesion type, the addition of a surgical antiarrhythmia procedure during valve surgery has decreased recurrence of late AF, diminishing the incidence of postoperative stroke and cardiovascular-related death [24].

The issue of the ideal lesion set is controversial, and multiple ablation procedures exist, ranging from simple pulmonary vein isolation to full maze protocols [25, 26]. In studies comparing the effectiveness of various lesion sets, full and limited maze procedures have produced similar results, but pulmonary vein isolation alone has varied in reported effectiveness [15, 25]. Recent data suggest that both biatrial lesion patterns and left atrial lesion sets are efficacious in eliminating AF as part of an operation addressing concomitant cardiac disease [26, 27]. Gillinov and colleagues [26] proposed that the ideal lesion pattern should include wide pulmonary vein isolation along with a bridging lesion between left and right pulmonary veins and a second to the mitral annulus. These lesion sets are thought to both control the propagation of macroreentrant circuits [28], and prevent their initiation.

Since the discovery that ectopic impulses originating in the pulmonary vasculature can initiate AF [8], there has been a surge of research within the field of GA physiology. The role of GP in the initiation of AF was further implicated when Scherlag and colleagues [13] discovered that simultaneous stimulation of both the GP and the pulmonary veins led to the initiation of AF at lower thresholds and amplitudes when compared with stimulation of the pulmonary veins alone. Furthermore, it was subsequently discovered that the ablation of GP resulted in 96% of those treated becoming resistant to previously inducible AF [29]. A potential role for GP ablation assumed even greater importance after recent reports that both pulmonary vein isolation and certain less complete iterations of the maze procedure may only partially denervate the atrium. Lall and colleagues [30] compared cardiac responses to sympathetic and parasympathetic stimulation before and after either a maze procedure or pulmonary vein isolation in a canine model and found that neither procedure resulted in complete atrial denervation. This finding may partially explain why studies consistently demonstrate that pulmonary vein isolation alone results in cure rates ranging between only 59% and 83% [25, 31]. It has been speculated that this wide variation in efficacy (when compared with that of the full biatrial maze procedure) might occur because several areas of active GP, particularly along the ligament of Marshall and the right-sided interatrial groove, are not eliminated by pulmonary vein isolation alone [14]. This has led to the hypothesis that the combination of a maze procedure with GA may more completely denervate the left atrium and better prevent future episodes of AF.

There are very few clinical studies investigating the utility and efficacy of GA. Early clinical data were generated from procedures that used a bilateral thoracotomy to access the pulmonary vasculature [12, 14]. In these reports, the GP were mapped or ablated along with pulmonary vein isolation, resulting in 75% (15 of 20 patients) [12] and 93% (14 of 15 patients) [14] freedom from AF at 6 months postoperatively. Similar to the findings in the current series, a recent study compared a concomitant maze procedure with and without GA to treat AF in conjunction with a mitral valve procedure; freedom from AF without antiarrhythmic medications at 6 months was significantly higher in the patients undergoing maze with GA (93%) compared with the patients undergoing maze alone (62%) [32].

Our present study examined the role of combined GA and RFA procedures in patients undergoing surgery for valvular heart disease. We have detailed a protocol for GA ablation in conjunction with left atrial or biatrial RFA lesions for concomitant AF. Our series indicates that combining GA and an RFA-modified maze procedure is technically feasible, safe, and does not significantly prolong operative times. Furthermore, we demonstrate that compared with a matched control population undergoing similar operative procedures and RFA maze alone, higher freedom from AF and improved NYHA functional class are associated with the maze procedure plus GA. The establishment of firm conclusions will await the results of longer-term follow-up in accordance with current Heart Rhythm Society guidelines [33].

Limitations
Evaluation of cardiac rhythm was performed routinely during hospitalization and in the early perioperative period. Subsequent follow-up data were collected by the referring physician or cardiologist. The lack of homogeneity in 24-hour Holter monitoring among patients may have led to an underestimation of AF recurrence by missing asymptomatic episodes of paroxysmal AF [34]. Our rate of freedom from AF is based on the latest clinical follow-up and interval contact, which may overestimate success as reported recently [35]. Different lesion sets for the treatment of lone AF continue to be studied at our institution and elsewhere. The results of this study may not be directly translatable to the treatment of lone AF because each of the patients in the current series had valvular heart disease as the primary indication for operation. However, it is in these patients that this adjunctive procedure may have its greatest benefit as it may ensure a more complete denervation of the posterior left atrium.

Our more recent use of the robotic platform for mitral valve repair plus concomitant maze has led to the diminished use of GA in order to decrease the need for contralateral left-sided working ports. As further long-term data accrues and technical refinements to GA equipment evolve, we may revisit the addition of bilateral GA to these operations. The effectiveness of the traditional cut and sew maze is likely better than historic RF maze controls presented in this study. We utilized the latter as a control group in this study to match the energy source employed during combined RFA/GA procedures.

Conclusions
Our study demonstrates that active GP in patients with AF associated with valvular heart disease frequently exist and may explain recurrent AF after the maze procedure. We detailed a protocol for the performance of concomitant GA as an adjunct to RFA for AF during valve surgery and have found that it is safe, expedient, and associated with satisfactory early outcomes. In addition, when compared with a matched population undergoing valve surgery and maze alone, the addition of GA was associated with better freedom from AF at 1 year and improved functional status. Long-term follow-up, which is currently underway, is essential to determine both the incremental value and efficacy of this approach.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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