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Original Articles: Adult Cardiac

Minimally Invasive Surgical Pulmonary Vein Isolation Alone for Persistent Atrial Fibrillation: Preliminary Results of Epicardial Atrial Electrogram Analysis

Beijing Anzhen Hospital, Capital Medical University, Beijing, Peoples Republic of China

Accepted for publication April 23, 2008.

^_* Address correspondence to Dr Meng, Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, Peoples Republic of China (Email: mxu{at}263.net).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Background: Minimally invasive surgical pulmonary vein isolation has become an alterative therapy for lone atrial fibrillation. This study evaluated the effect of the procedure on persistent atrial fibrillation by epicardial atrial electrography.

Methods: Five consecutive patients with lone persistent atrial fibrillation were enrolled. Intraoperative electrophysiology tests were performed before and after minimally invasive surgical pulmonary vein isolation. Morphology of the recordings and atrial fibrillation cycle length were analyzed.

Results: Sixty sites were recorded in 5 patients. Three types of bipolar electrogram were recorded at these sites. After ablation, all electrograms changed into type I in pulmonary veins and proximal antra, and remained unchanged in all proximal left atria. Atrial fibrillation cycle length at the proximal left atrium was shorter than that at the pulmonary veins. Atrial fibrillation cycle length recorded at proximal left atrium sites correlated with atrial diameter. The atrial fibrillation cycle length of the left atrium increased from 143 ± 11 to 170 ± 12 ms after pulmonary vein isolation. All 5 patients had atrial fibrillation immediately after the procedure and were treated with direct-current cardioversion and received amiodarone postoperatively. Freedom from atrial fibrillation was 100% at discharge and 60% at 6 months' follow-up.

Conclusions: Ectopic foci outside the pulmonary veins play an important role in persistent atrial fibrillation. Minimally invasive surgical pulmonary vein isolation might not be sufficient for persistent atrial fibrillation termination. The pulmonary vein isolation procedure, however, slows atrial fibrillation and makes supplemental pharmacologic cardioversion effective.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Atrial fibrillation (AF) is the most common atrial arrhythmia. Approximately 2.3 million people have AF in North America and 4.5 million in Europe [1]. In China the standardized rate of prevalence of AF is 0.61% and is increasing with age [2]. During the past three decades, surgical treatment for AF has been evolving with increasing understanding of the mechanism of AF. Nowadays, the traditional cut-and-sew techniques have been replaced by variable sources of energy ablation because of their complexity and complications. The application of alternative energy sources makes our approaches to cure AF easier.

Recently, another advance concerning treatment of lone AF has been minimally invasive surgical isolation of pulmonary veins (PVs) with new surgical tools, which is attributed to a landmark electrophysiologic study by Haïssaguerre and colleagues [3]. Minimally invasive surgical pulmonary vein isolation (PVI) has become an alterative therapy for lone paroxysmal AF and some cases of persistent AF, especially in patients who have thrombi in the left atrial appendage, and who are contraindicated for catheter ablation [4, 5]. This procedure, however, involves no linear ablation, such as a line connecting both sides of the pulmonary veins and the isthmus line. Previous clinical and laboratory studies have indicated that the mechanism of persistent/permanent AF initiation and maintenance is more complex than that of paroxysmal AF [6–10]. Also, prior studies have demonstrated a lower success rate in persistent AF than in paroxysmal AF patients [4, 5, 11]. Questions about minimally invasive surgical PVI include:

1 What is the mechanism of persistent AF termination after this procedure?

2 Is PVI alone sufficient for persistent or permanent AF?

3 What is the best target for persistent and permanent AF ablation?

The aim of this research was to analyze epicardial electrophysiologic characteristics of PVs, proximal antrum, and proximal left atrium (LA) before and after PVI, which may be useful for elucidating the mechanism of AF.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Patient Population
From June 21 to 27, 2007, 5 consecutive patients with lone persistent AF were enrolled into this study. The definition of persistent AF was taken from the 2006 guidelines for the management of patients with AF [1]. Exclusion criteria included left ventricular ejection fraction (LVEF) of less than 0.40, atrial thrombus, past thoracic operation, or severe lung dysfunction. All patients gave written informed consent for this study, which was approved by the Beijing Anzhen Hospital Ethical Committee. Preoperative data are summarized in Tables 1 and 2.

Surgical Procedure
The bilateral PVI procedure is conducted after induction of general anesthesia administered with a double-lumen endotracheal tube. PVI is performed first on the right side if the patient does not have a thrombus in the left atrial appendage. The surgical procedure is performed as described previously by Wolf and colleagues [4]. A small modification is that we provided direct visualization through incision at the fourth intercostal space in the anterior axillary line for better exposure.

After pericardial suspension, electrophysiology tests were performed. Then, the right PV was dissected bluntly with an articulated lighted dissector (AtriCure, OH). The bipolar radiofrequency (RF) clamp (Isolator; AtriCure), guided by an 18F red rubber catheter, was positioned with its two jaws encircling the antrum. Bipolar RF energy was applied to electrically isolate the PVs with the generator system (Isolator).

The end point of PVI is elimination of the PVs and antrum potentials, which are confirmed by epicardial mapping. After ablation, the electrophysiology test procedure was performed again. Left-side PVI and electrophysiology tests were performed as for the right side. The left-side procedure included additional techniques, such as division of the Marshall ligament and excision of the left atrial appendage with an EZ45 stapler (Ethicon Endo-Surgery, Cincinnati, OH).

Electrophysiology Tests
Surface electrocardiogram and bipolar epicardial electrograms filtered at 30 to 500 Hz were recorded simultaneously with a digital amplifier and recording system (Jin Jiang Electronic Technology, ChengDu, China). Before and after PVI, a quadripolar mapping catheter (Biosense Webster, Diamond Bar, CA) was positioned along the long axis of the PVs, with its distal end on the left atrium (Figs 1 and 2). Such a position was adapted to simultaneously record epicardial electrograms of the PV, proximal antrum, and proximal left atrium. PV, proximal antrum, and proximal left atrium potentials were recorded before and after RF ablation.

View larger version (23K): [in this window] [in a new window]   Fig 1. Position of quadripolar mapping catheter before ablation. (A) The catheter was positioned along the right superior pulmonary vein (RSPV) with its distal end at the proximal left atrium (LA). (B) The catheter was positioned along the left superior pulmonary vein (LSPV) with its distal end at the proximal LA. (C) The catheter was positioned along the right inferior PV with its distal end at the proximal LA. (D) The catheter was positioned along the left inferior PV (LIPV) with its distal end at the proximal LA.

View larger version (26K): [in this window] [in a new window]   Fig 2. Position of quadripolar mapping catheter after ablation. (A) The catheter was positioned along the right superior pulmonary vein (RSPV) with its distal end at the proximal LA. (B) The catheter was positioned along the left superior pulmonary vein (LSPV) with its distal end at the proximal left atrium (LA). (C) The catheter was positioned along the right inferior PV with its distal end at the proximal LA. (D) The catheter was positioned along the left inferior PV (LIPV) with its distal end at the proximal LA.

1 Morphology of the recordings, which was classified into three types (Fig 3): type I, no activation; type II, stable baseline between two activation complexes; and type III, complex fractionated atrial electrograms (CFAEs). According to the description of Nademanee and colleagues [12], CFAEs were defined as multicomponent atrial electrograms including (a) atrial electrograms with two or more deflections and/or perturbation of the base line, and/or continuous electrical activity over a 10-second period, or (b) atrial electrograms with a very short cycle length of 120 ms during a 10-second period.

2 AF cycle length (AFCL) was determined by averaging the interval of 30 consecutive cycles before and after ablation. Electrogram intervals of less than 100 ms and continuous electrical activity were counted as a single interval.

View larger version (13K): [in this window] [in a new window]   Fig 3. Epicardial electrograms after ablation, which comprised three types of bipolar electrogram. Arrows point to three segments of electrograms encircled by rectangular frames. The morphology of the electrogram at the antrum was type I, for no activation was recorded at the proximal antrum. The morphology of electrogram recorded at the proximal left atrium (LA) was a mixture of types II and III. Stable baseline between two activation complexes was seen in the type II electrogram. Type III electrogram was a complex fractionated atrial electrogram, according to the description of Nademanee and colleagues [12]. (PV = pulmonary vein.)

Direct-current cardioversion (DCC) was performed immediately after operation if AF still remained and was performed again before discharge if AF was recurrent. All patients were monitored with continuous ECG recordings for the first 3 postoperative days. Daily 12-lead ECGs were performed on admission.

All patients were followed up in the outpatient clinic at 1, 3, and 6 months after the operation, and 12-lead ECG and echocardiography were performed in all patients during each follow-up visit. Symptoms suggestive of arrhythmia were evaluated by ECG or 24-hour ECG. The electrograms were mailed or faxed to a referring physician who was blinded to the surgical procedure.

Statistical Analysis
Continuous variables are expressed as means ± standard deviation and categoric data as proportions. Comparisons of continuous variables were made with the Student unpaired t test. One-way analysis of variance was used for more than two group comparisons. Correlation between the cycle length and preoperative patient characteristics was analyzed by linear correlation. A value of p < 0.05 was considered statistically significant.

	Results

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Clinical Outcome
PVI was achieved in all 5 five patients. The mean total procedure time was 161 ± 19 minutes (range, 130 to 180 minutes). There were no major procedurally related complications, including death, bleeding, respiratory failure, stroke, or pacemaker implantation. DCC was performed in all 5 patients. One patient was electrically cardioverted again before discharge. The average hospital stay was 10.8 ± 1.6 days (range, 9 to 13 days). All 5 patients had 6 months' follow-up postoperatively. The perioperative outcomes are reported in Table 3.

Electrophysiology Outcome
Twelve sites were recorded per patient including four PVs, proximal antra, and proximal left atria. Sixty sites were recorded altogether in the 5 patients.

Morphology of Electrograms
Before ablation, three types of bipolar electrogram were recording at these sites. All electrograms in the PVs were type II (20 of 20 sites, 100%); some electrograms in the proximal antra were type II (8 of 20 sites, 40%); and were a mixture of types II and III (12 of 20 sites, 60%). All electrograms in the proximal left atria were a mixture of types II and III (20 of 20 sites, 100%). After ablation, all electrograms in PVs and proximal antra were type I. Morphology of electrograms in the proximal left atria were still a mixture of types II and III (20 of 20 sites, 100%). In all 5 patients, activation time of the left atrium was before that of the antrum and the PVs (Fig 4).

View larger version (16K): [in this window] [in a new window]   Fig 4. According to time reference line, the vertical line, the activation time of the left atrium (LA) was before that of the antrum and pulmonary vein (PV). Arrows show the direction of activation conduction.

	Comment

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
At present, minimally invasive surgical PVI is a new option in addition to drug therapy and catheter ablation for the treatment of patients with lone AF. However, the success rate is lower in patients with persistent or permanent AF than in those with paroxysmal AF [4, 5]. Our electrogram data provided some information that was useful for elucidating the mechanism of persistent AF termination after minimally invasive surgical PVI.

Sources of Ectopic Foci Perpetuating AF
Previously, the prevailing theory showed that chronic AF is maintained by coexisting multiple random wavelets [13, 14]. In recent studies, the notion that focal activation occurs with fibrillatory conduction has been demonstrated [3, 15, 16]. However, according to data from epicardial and endocardial mapping, spatial distribution of these sites in persistent/permanent AF differs from that in paroxysmal AF. Wu and colleagues [17], using computerized epicardial mappings of the right atrial free wall and left atrial posterior wall, studied 6 patients with permanent AF and organic heart diseases undergoing operations and rapid repetitive activities were consistently observed in the LA posterior wall, at or near the PVs. With a 256-channel, three-dimensional dynamic mapping system, Nitta and colleagues [18] have performed intraoperative mapping of the entire atrial epicardium in 21 patients with permanent AF and mitral valve disease. Concurrent multiple repetitive activation arising from the posterior left atrium adjacent to the PVs or the left atrial appendage was recorded in all patients [18]. Sahadevan and colleagues [19] performed epicardial mapping of chronic AF in 9 patients and demonstrated that drivers from the left atrium that cause fibrillatory conduction is a mechanism of AF.

In the cardiology literature, sites of high-frequency activity and CFAE have been regarded as new targets for termination of AF [20, 21]. It has been demonstrated that these sites play important roles in the maintenance of AF. In paroxysmal AF, these sites are distributed mainly in PVs, while in persistent or permanent AF, in addition to PVs, these sites also exist in the left atrium, superior vena cava, and coronary sinus. In our study, we recorded rapid activation in all PVs, proximal antra, and proximal left atria before ablation. Compared with electrograms of PVs, higher frequency activation was recorded in the proximal left atria. Results of atrial electrogram morphology analysis showed that CFAEs were distributed in the proximal antra and proximal left atria. In all 5 patients, we found that the activation time of the left atria preceded that of the PVs and antra. After ablation, no potentials were recorded in the PVs and antra in any of the 5 patients, but high frequency activation and CFAEs could still be recorded in the left atrium, and the immediate heart rhythm was AF in all cases. These results proved that:

1 PVs, antra, and left atria are sources of ectopic foci that serve as drivers for perpetuating AF;

2 left atrial or non-PV ectopy may play an dominant role in perpetuating AF before and after ablation, despite the exact culprit sites in the left atrium being unknown; and

3 PVI alone might not be sufficient to achieve instant termination of AF and extensive ablation might be necessary.

Interestingly, we found that AFCLs recorded at proximal left atrial sites were correlated with left atrial diameter: the higher the AFCL, the larger the left atrial diameter. It is assumed that a bigger left atrium harbors more ectopic foci, which drive AF. Our results may explain the findings of Chen and colleagues [22], who showed that the preoperative left atrial size are is a primary predictors of sinus conversion by the RF Maze procedure.

Mechanism of Termination of AF After PVI
In our study, potential in PVs and antra in all 5 patients disappeared after ablation, which suggests that complete isolation of PVs and antra was achieved. However, rapid high-frequency activity was still recorded in the proximal left atrium and AF still existed, and prolongation of AFCL after PVI at the proximal left atrium site was observed. In addition, the rate change of the AFCL at the proximal left atrium was less in patients with recurrence of AF than in those who were free from AF. The mechanism of the prolongation of AFCL after PVI is unclear. It may be related to a reduction of the number of wavelets created by focal drivers in PVs.

Sanders and colleagues [20] have demonstrated that ablation of the PVs that harbor dominant frequency sites is associated with a significant increase in AFCL, whereas ablation at a PV without a dominant frequency site does not change AFCL. In a previous study by Haïssaguerre and colleagues [23], prolongation of AFCL within the coronary sinus was observed during PV ablation and increased gradually with the number of ablated PVs. In another study [24], they assessed AFCL as a marker during ablation of persistent AF. They observed that prolongation of AFCL preceded heart rhythm conversion. Patients without AF termination displayed shorter fibrillatory cycles at baseline and less prolongation of AFCL in the left atrium after ablation.

In our study, we used AFCL at the proximal atrium as a marker to evaluate the effect of PVI on persistent AF. Although PVI alone could not terminate persistent AF, prolongation of AFCL after PVI made pharmacologic cardioversion of AF achievable. In fact, all 5 patients with drug-refractory AF were free from AF before discharge with supplemental amiodarone and DCC, and 3 of the 5 patients did not have recurrence of AF with the use of amiodarone during the first 6 months.

Major Findings and Clinical Implications
With epicardial atrial electrogram analysis, we acquired limited information regarding persistent AF. We recorded higher frequency activation outside the PV and antrum before and after ablation. This suggests that non-PV foci might play a dominant role in maintenance of persistent AF. According to present research, the left atrium is more important than the PV and antrum in maintaining persistent AF. First, higher frequency activation is recorded at the left atrium and activation frequency correlates with left atrial size. Second, the rate of change of AFCL at the proximal left atrium may be a predictor for AF recurrence. This suggests that minimally invasive surgical PVI alone might not be sufficient for persistent AF, and extensive ablation of the left atrium is necessary. It is of interest that PVI alone is not useless. The procedure isolates ectopic foci from PVs, which results in prolongation of AFCL, which makes pharmacologic cardioversion easier. However, the high recurrence rate of AF in these patients is expected, because the culprit sites for maintaining AF are still outside the PVs.

Limitations
The number of patients was low, and the follow-up time was relatively short. Extensive epicardial mapping was not performed, for technical and time reasons, to locate epicardial culprit sites.

Conclusions
Ectopic foci outside the PVs play an important role in persistent AF. Minimally invasive surgical PVI alone might not be sufficient for persistent AF termination. However, it slows AF and makes supplemental pharmacologic cardioversion more effective.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
We would like to thank Shuping Ding and Yongqiang Cui for their assistance in data collection.

	References

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments 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): Xu Meng Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, H. Articles by Meng, X. Search for Related Content PubMed PubMed Citation Articles by Li, H. Articles by Meng, X. Related Collections Electrophysiology - arrhythmias