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Ann Thorac Surg 1996;61:565-569
© 1996 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Thoracoscopic Obliteration of the Left Atrial Appendage: Potential for Stroke Reduction?

Division of Cardiovascular Surgery and Departments of Surgery and Anatomic Pathology, Mayo Clinic, Rochester, Minnesota; and Cardiovascular Diseases, Mayo Clinic, Jacksonville, Florida

Accepted for publication September 1, 1995.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. In a review of all relevant articles describing the site of left atrial thrombus in patients with atrial fibrillation, the thrombus was localized to the left atrial appendage in 43% of patients with rheumatic heart disease and in 91% of patients with nonrheumatic atrial fibrillation. This study was designed to test the feasibility of thoracoscopic obliteration of the left atrial appendage as a means of reducing thromboembolic stroke.

Methods. Thoracoscopic obliteration of the left atrial appendage was undertaken in 10 dogs, 5 with staples and 5 with an endoloop. Obliteration also was attempted in 8 fresh human cadavers.

Results. In all dogs, the appendage was rapidly oblit-erated (21.3 ± 7.6 minutes) and confirmed at euthanasia at 11 weeks. In 3 cadavers, anatomic and disease factors prevented visualization of the left atrial appendage; in 1 the appendage tore, and in the remainder the appendage was obliterated.

Conclusions. Obliteration of the left atrial appendage is feasible and may be considered as an additional surgical procedure to reduce stroke. The group of patients in whom it offers the greatest potential are those with atrial fibrillation deemed ineligible for warfarin, those without atrial thrombus and with a free pericardial and pleural space.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also 515 and 755.

There are substantial data, particularly since the advent of transesophageal echocardiography (TEE), to support the assumption that the great majority of thromboemboli in nonrheumatic and rheumatic atrial fibrillation (AF) originate in the left atrial appendage. In a review of articles [1] in which the incidence and site of atrial appendage thrombi within the left atrium were documented, 62% of atrial thrombi in patients with

rheumatic mitral valve disease (predominantly stenosis) were appendiceal, whereas 91% of left atrial thrombi in nonrheumatic AF were appendiceal.

We hypothesize that if the atrial appendage can be safely obliterated, then the incidence of embolic stroke may be lessened. If the appendage can be obliterated using a thoracoscopic technique, a procedure of lesser magnitude than thoracotomy, then it may offer an alternative form of management for patients ineligible for warfarin therapy. To determine the feasibility of atrial appendage obliteration done using the thoracoscope, we performed the procedure in mongrel dogs and in human cadavers.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Surgical procedures, subsequent care, and conduct of experiments were performed after approval and according to criteria set forth by the Institutional Animal Care and Use Committee of the Mayo Foundation, in accordance with guidelines of the National Institutes of Health and the Public Service Policy on humane care and use of laboratory animals.

Ten mongrel dogs, weighing 30.6 ± 2.9 kg, were anesthetized with methohexital 12.5 mg/kg intravenously (Brevital; Eli Lilly and Co, Indianapolis, IN). Anesthesia was maintained with halothane delivered by a volume-cycled ventilator. The electrocardiogram and oxygen saturation were monitored. Transesophageal echocardiography with emphasis on visualization of the left atrial appendage was performed pre-, intra-, and postoperatively. In 5 dogs, the atrial appendage was obliterated with staples, and in 5 the appendage was obliterated with an endoloop of 0 Vicryl (Ethicon, Cincinnati, OH). Procedures were documented on videotape.

Three ports were made: one in approximately the seventh interspace approximately 5 cm from the midsternum (port 1), a second inserted anteriorly in the fourth interspace (port 2), and a third more posteriorly in the fourth interspace (port 3). Carbon dioxide was instilled to a pressure of 4 to 10 mm to collapse the lung. In all animals, the pericardium was opened anterior and parallel to the phrenic nerve. Through the first port, the camera was inserted; through port 2, the pericardium was grasped with an instrument; and, using scissors inserted through port 3, the pericardium was opened. The technique then varied depending upon whether the appendage was obliterated with staples or with the endoloop. In those having the appendage stapled, the camera was withdrawn from port 1 and inserted in port 3. Through port 1, a 35 endo GIA stapler (Ethicon Endosurgery, Cincinnati, OH) with the knife blade removed was inserted, positioned across the base of the atrial appendage, and fired. In dogs having the appendage obliterated with the endoloop (Ethicon), the camera position was not changed. The endoloop was introduced through port 3 and the appendage was grasped through the loop of the suture. The loop was positioned across the base of the appendage and then tightened. The pericardium was left open, and the pleura was not drained.

At 11 weeks, the dogs were again anesthetized with sodium pentobarbital (30 mg/kg intravenously) and a midline sternotomy was made. The heart was examined using epicardial echocardiography. The dogs were euthanized, the hearts were removed, and the left atrium was inspected.

The procedure also was attempted in 8 human cadavers. In the cadavers, three ports were used for access. The most appropriate sites appeared to be the second interspace anteriorly in the midclavicular line (for grasping the pericardium and the atrial appendage), the sixth interspace in the midclavicular line (for the camera or stapling instrument), and the fifth interspace in the anterior axillary line (usually for the scissors to open the pericardium, but also for the camera or for the stapling instrument). The procedure as performed in the dog and human experiments is illustrated in Figures 1 and 2.

View larger version (38K): [in this window] [in a new window]   Fig 1. . Technique used to open the pericardium.

View larger version (40K): [in this window] [in a new window]   Fig 2. . Two techniques used for thoracoscopic obliteration of the left atrial appendage. When the endoloop is used, the camera will be positioned as shown in Figure 1.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

Echocardiographic results showed that in all animals, the atrial appendage was easily visualized pre- and postoperatively, but, possibly for anatomic reasons, it was poorly visualized during CO₂ instillation. The duration of the procedure from the time of skin incision to closure was 21.3 ± 7.6 minutes (range, 13 to 36 minutes). There was no difference in time between the two techniques.

Using echocardiography, we confirmed obliteration of the left atrial appendage in all dogs both at the time of the procedure and at euthanasia. No recesses were visualized. In some dogs, particularly those having obliteration with staples, a dense echogenic area was noted at the site of the appendage. In 1 animal, the echocardiographic density projected into the lumen of the left atrium. However, no thrombus was noted within the left atrium in any dog. At postmortem examination of dogs having obliteration with an endoloop, the left atrial appendage appeared as a small fibrous nubbin; in those obliterated with staples, the appendage was of normal size and was firm, containing organizing thrombus. In dogs having the appendage obliterated with an endoloop, there were small crevices corresponding to the pectinate muscles; in the stapled group these crevices were less obvious. In 2 dogs with stapled appendages, there was a small recess up to 5 mm in depth near the superior pulmonary vein. We believe that this was due to the angle of placement of the linear stapler and may be prevented by retraction of the appendage superiorly. The appearance of a normal and an obliterated canine left atrial appendage is shown in Figures 3 and 4.

View larger version (120K): [in this window] [in a new window]   Fig 3. . Internal aspect of the canine left atrial appendage.

View larger version (158K): [in this window] [in a new window]   Fig 4. . Appearance of the obliterated canine left atrial appendage at sacrifice. The arrow demarcates the line of staple closure.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The stimulus for investigating the possibility of left atrial appendage obliteration as a thoracoscopic procedure was twofold: (1) Thrombus associated with nonrheumatic AF occurs predominantly within the left atrial appendage in 91% of patients [1]; and (2) there is a large number of patients in whom the anticoagulant drug warfarin is not suitable as therapy to reduce embolic stroke. Alternative methods of treatment must be considered to reduce the risk of thromboembolic stroke. The arguments for considering obliteration of the left atrial appendage are detailed in the current review; those relevant to this article will be summarized.

With the advent of TEE, the left atrium, which abuts the underlying esophagus, is extremely well visualized. Atrial thrombus is easily seen within the left atrium and left atrial appendage. In patients with AF undergoing cardiac operations in which the left atrium was opened, TEE was 100% sensitive and 99% specific, and had a positive predictive value of 91% and a negative predictive value of 100% for the presence of thrombus [2]. Left atrial spontaneous echo contrast or ``smoke'' is thought to represent a precursor of thrombus formation; its presence is associated with increased thrombus formation within the atrial appendage and thromboembolic risk [3]. In a multicenter study evaluating TEE in patients with unexplained cerebral ischemia, left atrial thrombus and spontaneous echo contrast were present in 18% and 52% of patients, respectively [4].

In clinical trials, warfarin has been shown to be effective in preventing stroke associated with AF; however, these patients were highly selected (in three of the North American warfarin-placebo trials, only approximately 10% were ultimately randomized). Further, this group was not representative of the true population at risk (older patients were not included). In those assigned to warfarin therapy, withdrawals occurred at rates of 4% to 20% per year [5]. In warfarin-treated patients in whom strokes developed, approximately half occurred in patients who required temporary cessation of therapy or who had inadvertent therapeutic lapses [5, 6]. The single placebo-controlled study involving AF patients with a mean age of 75 years reported an overall withdrawal rate from anticoagulation therapy of 38% after 1 year [7]. In a community practice, 21.8% of patients had contraindications or refused warfarin therapy [8]. Thus, although warfarin is effective in reducing the incidence of stroke, in practice it is often difficult to treat patients continuously and effectively in the recommended manner.

Patients considered ineligible for warfarin are currently managed either with no therapy, accepting the risks of thromboembolism; with anticoagulant therapy, accepting the risk of bleeding complications and, if anticoagulation therapy is used at a lower intensity, of possible lesser efficacy of thromboembolism prevention; or with aspirin alone. An alternative form of management for these patients is to consider obliterating the major source of thromboemboli—the left atrial appendage. If the procedure can be done using the thoracoscope, it offers the potential of a relatively minor procedure with an important benefit (stroke prevention). Our study was designed to explore this possibility.

We are not aware of the technique being done elsewhere. However, pericardiectomy, drainage of pericardial effusions, and resection of pericardial cysts have been done with ease and with low morbidity rates [9]. The previous work by DiSesa and colleagues [10] in the open-chest model has confirmed the ability to obliterate the left atrial appendage with staples, which are used commonly in video-assisted thoracic surgery.

As shown in this study, the procedure is feasible, and experimentally was done rapidly and without complications. We envisage that in the clinical situation, with some minor modifications, it may be as effective as in dogs. The significance of the small recesses (up to 1 mm in depth) of the pectinate muscles remaining after the obliteration procedure in relation to thrombus formation and embolization is unknown.

Until a clinical trial is completed, our further comments concerning the clinical situation must be considered conjecture. A clinical trial is necessary to determine whether this procedure should be extended generally and whether the procedure has benefit. A double-lumen tube would result in collapse of the lung and better visualization of the pericardial sac. We advocate CO₂ instillation so that if an inadvertent tear in the atrial appendage is produced, the possible embolic effects of air will be eliminated or reduced [11]. A hemodynamic study on the effects of carbon dioxide instillation in the chest in humans has shown no deleterious effects if the intrapleural pressure remains less than 10 mm Hg and the flow is less than 2 L/min [12]. It is recommended that the knife blade within the stapling device be removed so that any remote likelihood of bleeding is reduced. There have been instances when the endostapling device has cut a vessel and failed to staple it, resulting in massive hemorrhage [13]. This also occurred in one of our cadaver experiments. Obliteration of the appendage in the human may be more difficult than in the canine model because of the presence of extrapericardial fat, making visualization of the phrenic nerve difficult, and because of the more posterior position of the left atrial appendage in humans. It is not certain, until attempted in the clinical situation, whether collapse of the lung will result in rotation of the mediastinum toward the collapsed side, exaggerating difficulties with left atrial appendage visualization; or whether positioning of the patient in a limited left anterior thoracotomy position will actually improve visualization. The circumflex coronary artery lies within fat close to the base of the left atrial appendage. In our experiments, the stapler and endoloop, which are designed for structures that can be encircled, did not include cardiac tissue other than the appendage. We believe therefore that damage to the circumflex coronary artery, because it lies deep within the atrioventricular groove, is unlikely. Care should be taken if the circumflex coronary artery is large and appears to project onto the surface of the atrioventricular groove.

We believe that simultaneous TEE is essential during the procedure, but particularly before the first incision is made. Operations should be deferred if thrombus is identified in the left atrial appendage or possibly elsewhere in the left heart, or if present in the right heart in the setting of a patent foramen ovale. One should use TEE to monitor the presence or absence of spontaneous echocardiographic contrast within the left atrium or left atrial appendage, to check placement of the stapler, and to assess Doppler velocities before and after the procedure. A contraindication to the procedure would be an obliterated pleural or pericardial space.

The procedure should not be considered in patients with preexisting thrombus, demonstrated by TEE within the atrial appendage, as manipulation could result in embolism of the thrombus. How best to manage this particular patient will need to be established; if thoracoscopic obliteration is shown to be feasible in the clinical situation, it may be worthwhile to place the patient on an intensive anticoagulation regimen and to repeat the TEE. If thrombus has disappeared, the patient may be reconsidered for obliteration. Disappearance of thrombus has been described after 1 month of anticoagulation therapy [14]. Although TEE has been shown to have a high sensitivity (100%), high specificity (99%), and high negative predictive value (100%) [2], we cannot assure the patient that this is absolute. Manipulation of the atrial appendage, despite all efforts to exclude the presence of underlying thrombus within the appendage, may result in migration of thrombus within the bloodstream and possible stroke. Stroke may also be due to other causes.

The concept of a prophylactic procedure to prevent stroke or further stroke is not unique; examples are carotid endarterectomy and closure of a patent foramen ovale. We estimate that if obliteration of the left atrial appendage reduces the incidence of stroke by 50% to 75%, then the annual stroke rate will be reduced from 12% per year, in patients who have had a prior stroke and have contraindications to warfarin therapy (the placebo arm of the European Atrial Fibrillation Trial) [15], to 3% to 6% per year. This is similar to results recently published by the North American Symptomatic Carotid Endarterectomy Trial [16]. Prolonged hospital stay after video-assisted thoracic surgery is usually due to prolonged air leak, which should not occur after thoracoscopic obliteration of the left atrial appendage.

The maze procedure [17] is extremely effective in restoring sinus rhythm and is applicable to those patients who are symptomatic in terms of dyspnea, as atrial contraction and improvement in heart rate may be restored. Resection of both atrial appendages, however, is an essential part of the maze procedure. A reduction of thromboembolism solely due to restoration of sinus rhythm will be difficult to prove; it is just as likely to be due to obliteration of the atrial appendage. If benefit in terms of thromboembolism is shown with the lesser procedure of thoracoscopic atrial appendage obliteration, then this procedure may be appropriate for high-risk patients who are unsuitable for anticoagulation therapy and who are also unlikely to be candidates for the maze procedure.

In summary, we have shown that obliteration of the left atrial appendage is feasible and may possibly be extended to the clinical situation as an additional surgical procedure to reduce the incidence of stroke. The group of patients in whom we believe it offers the greatest potential are those deemed ineligible for warfarin, who have no thrombus within the atrium and who have a free pericardial and pleural space. A clinical trial, which we are establishing, is needed to determine whether our hypothesis is correct. The proposed trial offers a unique opportunity to randomize from the first patient. If benefit is demonstrated, then the procedure can be extended at the time of open heart operations to patients with established AF or at high risk of postoperative AF [18].

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We acknowledge the assistance of Steve Krage, Ron Lee, Gerald McGrath, and Marilyn Oeltjen with the care of the animals. The study was supported by a grant from the Mayo Foundation (A22994) and in part from a grant by Ethicon Endosurgery.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Odell, Mayo Clinic, 200 First St, Rochester, MN 55905.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Blackshear JL, Odell JA. Obliteration of the left atrial appendage to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755–9.[Abstract/Free Full Text]
2. Manning WJ, Waksmonski CA, Haering JM, et al. Sensitivity and specificity of transesophageal echo for left atrial thrombi: a prospective consecutive surgical study [Abstract]. Circulation 1994;90:I-224.
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7. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications of atrial fibrillation. Lancet 1989;28:175–9.
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This Article Abstract 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): John A. Odell William D. Edwards Thomas A. Orszulak Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Odell, J. A. Articles by Orszulak, T. A. Search for Related Content PubMed PubMed Citation Articles by Odell, J. A. Articles by Orszulak, T. A. Related Collections Related Articles