Highlights From the International Symposium on Left Atrial Appendage (ISLAA 2013)

On March 1-2, 2013, the 1st International Symposium on Left Atrial Appendage (ISLAA) took place at the InterContinental Hotel in Kansas City, Missouri. Leading the event were course co-directors Dhanunjaya Lakkireddy, MD, Andrea Natale, MD, Saibal Kar, MD, and David Holmes Jr., MD.

This two-day symposium was a curtain raiser to the new science of appendageology. With increasing focus on atrial fibrillation and stroke pathophysiology, this symposium was a perfect beginning to the new frontier in cardiovascular medicine: the left atrial appendage (LAA). This was the first-of-its-kind symposium on this side of the Atlantic organized by the thought leaders of this evolving field. A detailed yet focused approach to highlighting various pathophysiologic and anatomic aspects of the LAA along with pharmacologic and interventional methods of stroke prevention has been taken. This was the most comprehensive course on the LAA that has the potential to attract a much wider audience, including neurologists and neurosurgeons. This was also the first course that successfully brought together electrophysiologists, interventional cardiologists, and cardiothoracic surgeons in understanding more about the LAA. 

ISLAA course co-director Dr. Lakkireddy highlighted the role of the LAA. He remarked, “LAA not only contributes to systemic homeostasis through its endocrine function, but also plays an important role in thromboembolism and maintenance of atrial arrhythmias.”

The eminent cardiologists from premier institutes such as the Mayo Clinic, University of Kansas, Cedars Sinai Hospital, and Texas Cardiac Arrhythmia Institute (TCAI) came together to organize this conference and provide an opportunity for participants to update their knowledge on the various research studies and recent technological developments related to the LAA. Dr. Natale from TCAI described ISLAA as “the only conference I am aware of that focuses solely on the LAA, the impact of LAA ligation/occlusion, the evolution of LAA ligation/occlusion technology, and the future direction of this technology. This conference provides an opportunity for the participants to enhance their knowledge on the LAA.” The participants for ISLAA included physicians, nurses, and allied health professionals in the fields of electrophysiology, family medicine, and internal medicine. 

ISLAA featured comprehensive CME agenda, detailed presentations of different LAA closure techniques, live case demonstrations, debates, and panel discussions, all involving world-class faculty. 

The first day of the symposium began with opening remarks by ISLAA course co-director Dr. Lakkireddy from the University of Kansas. This set the stage for the symposium’s principal focus areas. 

ISLAA presenter Dr. Samuel Asirvatham from the Mayo Clinic spoke about embryology, anatomy, and histopathology, and discussed the development of LAA from the embryologic remnant of the left atrium. He highlighted that the main axis of LAA, with respect to the main axis of the pulmonary artery, may vary — in 25% of cases the main axis of LAA is oriented perpendicularly to the main axis of the pulmonary artery. He emphasized that the ridge separating the LAA and the pulmonary vein is an anatomically important landmark for delineating LAA. In pulmonary vein isolation this ridge is ablated; therefore, combining pulmonary vein isolation and LAA closure procedures would increase the difficulty of the procedure. 

This was followed by a presentation by ISLAA course co-director Dr. Lakkireddy about physiologic contributions of the LAA on systemic homeostasis. He explained that LAA is a major source of atrial natriuretic peptide, which is in turn related to glucose and lipid metabolism. Dr. Lakkireddy further elaborated the role of atrial natriuretic peptide in regulating sodium and water excretion, and the impact of atrial appendectomy on urine output and sodium excretion. He discussed an ongoing feasibility study at the University of Kansas Medical Center to assess the impact of left atrial appendage exclusion on atrial physiology and systemic homeostasis (LAA-EXPOSIS). 

ISLAA presenter Dr. Miguel Valderrábano from the Methodist DeBakey Cardiology Associates discussed different epidemiological risk factors and mechanistic factors to predict stroke risk. He touched on different anticoagulant medications that are currently available to decrease the risk of stroke. He also spoke about different scores to predict bleeding risk, such as the HAS-BLED and HEMORRR₂HAGES scores. 

This was followed by an interesting presentation by ISLAA course co-director Dr. Natale about the role of LAA as a source of AF and the importance of isolating the LAA to decrease AF recurrence. He presented an outline of the BELIEF trial. He further explained that the decision regarding discontinuation of warfarin should be based on six-month follow-up echo assessing LAA contractility. He reiterated that in longstanding persistent atrial fibrillation, the relative contribution of LAA, non-pulmonary vein triggers to arrhythmias increases progressively. 

Dr. Loren Berenbom from the University of Kansas Medical Center elaborated on stroke risk prediction instruments such as CHADS₂ and CHA₂DS₂VASc. He emphasized the importance of using the CHA₂DS₂VASc score in low-risk AF patients. He explained the utility of the R₂ CHADS₂ (creatinine clearance less than 60 ml/min) score and the bleeding risk scores HEMORR₂HAGES, HAS-BLED, and ATRIA. 

Presenting an interventional cardiologist’s perspective on balancing anticoagulation and bleeding in high-risk percutaneous intervention (PCI) patients, Dr. Peter Tadros from the University of Kansas Medical Center explained that 10–15% of patients undergoing percutaneous intervention require oral anticoagulation. He emphasized that peri-procedural bleeding related to percutaneous interventions is a major predictor of mortality. He spoke about different bleeding avoidance strategies: best combination of anticoagulant and antiplatelet drugs, choosing the right stent, gastric acid suppression, avoiding glycoprotein IIb/IIIa inhibitors, use of bivalirudin, and LAA closure. 

This was followed by an interesting debate on whether patients should routinely be considered for LAA closure/ligation. Dr. Brian Whisenant from Intermountain Medical Center’s Structural Heart Disease Program argued in favor of LAA exclusion, stating that current data shows only 50–60% of patients receive warfarin. He explained that discontinuation rates with dabigatran were similar to warfarin, and bleeding risk with other newer anticoagulant medications was similar. He then presented data regarding the WATCHMAN device from different trials (PROTECT, ASAP), which demonstrated the benefit of LAA closure compared to warfarin therapy. Dr. Mathew Price from Scripps Clinic Torrey Pines argued that there was a difference in the median CHADS₂ score in the PROTECT AF trial compared to other trials involving newer anticoagulants. He spoke about the low-risk patient cohorts in the PROTECT AF trial and the low event rates in both WATCHMAN and oral anticoagulation arms. He also stated there is a significant number of complications with LAA occlusion devices. He reiterated that the benefits with LAA occlusion devices have been overestimated, and these benefits can be mitigated with newer anticoagulants. 

ISLAA presenter Dr. David Burkhardt from TCAI spoke about different imaging modalities to assess heart anatomy. He talked about the utility of transesophageal and intracardiac echocardiography in assessing the valves and left atrium, and also its limitations in ruling out LAA thrombus. This was followed by a succinct presentation by Dr. Randall Lee from the University of California-San Francisco, who explained the technique of dry pericardial access using a subxiphoid approach. He showed the value of a 90-degree left lateral fluoroscopic view in addition to other views to obtain more accurate information about the location of the needle. He also emphasized the importance of cardiac CT for planning the pericardial access. 

In his presentation, Dr. Price reiterated that patients at high risk for stroke and bleeding should be considered for LAA exclusion. He outlined the inherent limitations to each of the available technologies in LAA exclusion. He talked about features of the LAA that are predictors of failure, such as LAA >40 mm, bilobed appendage, superiorly oriented with LAA apex and posteriorly oriented heart. 

During lunch, Dr. Asirvatham spoke about different anticoagulation trials, including the RELY/ROCKET/ ARISTOTLE trials. He elaborated on the mechanism of action of different anticoagulant drugs. He spoke about the newer anticoagulants such as betrixaban and edoxaban. In conclusion, he stated that compliant young patients with good renal function are appropriate candidates for anticoagulation. 

This was followed by live case demonstrations of LAA occlusion using the AMPLATZER cardiac plug and ligation with the LARIAT device. Dr. Rodney Horton from TCAI showed a recorded case of the WATCHMAN LAA exclusion device.

Later, Dr. James Edgerton from HeartPlace Dallas described the technique of LAA ligation using the AtriClip; this was followed by Dr. Christopher Phillips from Trinity Health Heart & Lung Center describing LAA ligation using the AtriClip from a posterior approach. He also stated the advantages of the posterior approach, which include shorter hospital stay, preservation of muscles in chest wall, and visualization of the base of LAA.

Dr. Zoltan Turi from the Cooper Structural Heart Disease Program spoke about the evolution of percutaneous techniques in LAA occlusion or exclusion, as well as discussed the PLAATO study and the feasibility study of first-generation LAA occluders. He also spoke about the PROTECT AF trial, the AMPLATZER cardiac plug registry, and LAA closure using the LARIAT procedure.

ISLAA presenter Dr. Marc Gillinov from the Cleveland Clinic spoke about the indications of surgical LAA exclusion. He then presented data from past studies, which showed a high rate of incomplete LAA exclusion. Dr. Gillinov described LAA exclusion using the TigerPaw and AtriClip devices. He presented a study demonstrating routine LAA ligation during cardiac surgery that may prevent postoperative AF-related cerebrovascular accidents. 

Day 1 concluded with an interesting debate on the topic, “Is LAA Occlusion/Exclusion Good Enough to Allow for Discontinuation of Coumadin?” Dr. Ted Feldman from NorthShore University Health System presented the data from the PROTECT AF trial, which demonstrated decreased stroke risk after successful implantation of the device. He highlighted that there was significant improvement in quality of life in the WATCHMAN arm. He reiterated that even though there were residual peri-device leaks at one year, this was not associated with increased risk of thromboembolism. He stressed that bleeding risk would continue to be present with newer anticoagulants. In response, Dr. Asirvatham argued that only a minority of patients with stroke in AF has recognized thrombus in LAA, and there are other potential intracardiac sources of thrombus apart from LAA in patients with AF. He presented the data from the ASSERT trial, which showed that there was no temporal relationship between AF episode and embolic event. He highlighted the complication rate with device placement. He concluded by stating that neo-endothelialization can be a source of thrombi and appendage ligation may be insufficient to decrease the risk of stroke. 

Day 2 started with a presentation by Dr. Vijay Swarup from the Arizona Heart Rhythm Institute, sharing his experience of setting up the LAA exclusion program in Arizona. He spoke about the role of different components of the LAA exclusion program: AF program, physicians, marketing, hospital administration, echocardiographers, anesthesia, electrophysiology and cardiac catheterization laboratory nursing staff, and data research program. He described the steps in setting up the program: organizing a multispecialty team, adoption and implementation of AF protocols, devising the structure for the AF clinic, measuring quality outcomes, and creation of a marketing strategy. 

Dr. Swaminatha Gurudevan from Cedars-Sinai Heart Institute spoke about the role of multiplane transesophageal echocardiography (TEE) for assessing the size, function and morphology of LAA. He highlighted the utility of TEE to rule out thrombus and identification of sludge. He elaborated the advantages of 3D TEE for evaluating the dimensions of elliptically shaped LAA orifices and obtaining simultaneous biplane TEE. He then spoke about the role of computed tomography (CT) in assessment of LAA morphology as well as dimensions of LAA orifice. He highlighted the utility of CT to detect LAA thrombus and leaks around the device.

This was followed by a presentation by Dr. Horton on the challenges during WATCHMAN device placement. He stressed that ideal transseptal puncture site is inferior and posterior as superior puncture causes difficulty in obtaining correct sheath orientation relative to LAA ostium. He spoke about the utility of the pigtail catheter for gentle cannulation of the LAA. He spoke about sheath management to avoid aspiration of the WATCHMAN device. He then touched upon the challenges during epicardial non-surgical LAA exclusion. He stressed on identifying LAA with suitable anatomy. He spoke about the safe technique to obtain epicardial access, emphasizing on the angle and position of the needle. 

Speaking about complications in LAA exclusion procedures, course co-director, Dr. David Holmes from the Mayo Clinic highlighted the importance of prevention of complications by anticipating potential complications, selecting the appropriate patients, acquiring simulator experience, and training the team. He spoke about potential factors that increase the risk of device embolization and steps to be followed for device extraction. He stressed on the importance of fulfilling all device release criteria to prevent device embolization. 

This was followed by a presentation by Dr. Moussa Mansour from Massachusetts General Hospital about mechanism of incomplete closure with different procedures. He described the mechanism of incomplete closure with closure devices and surgical techniques. He highlighted that in the PROTECT AF trial, there was no association between stroke and exclusion leak. He stressed the importance of choosing LAA with suitable anatomy and avoiding the use of steroids after epicardial closure to prevent leaks. He also touched on issues related to management of the leak such as closing the leak, prevention, and decision of discontinuation of oral anticoagulant medication. 

ISLAA presenter Dr. Feldman presented the most recent data from the ASAP and PROTECT AF trials, which showed reduction in ischemic stroke event rate after device placement. He concluded by stating that all methods for LAA exclusion may leave a nidus for thrombus formation and anticoagulant or antiplatelet therapy should be given for a certain duration of time after the procedure. However, it may be possible to discontinue antithrombotic therapy at some point in the future after LAA exclusion. 

This was followed by an interesting debate on the topic “Should LAA be Ligated Routinely During an Open Heart Surgery?” Dr. Michael Mack from The Heart Hospital advocated for LAA ligation in AF patients undergoing mitral valve surgery and isolated AF patients, as well as those undergoing mitral valve surgery alone. He stated that post-operative AF occurred in 25% of cardiac surgery patients, which is in turn associated with increased incidence of stroke. In response, Dr. Gregory Muehlebach with Mid-America Thoracic and Cardiovascular Surgeons listed ten reasons not to perform routine LAA ligation during open heart surgery. He spoke about the cost of procedure and risks associated with the placement of devices as well as surgical closure. He highlighted the contribution of contractile and endocrine function of LAA to hemodynamics and systemic homeostasis. 

ISLAA presenter Dr. Richard Whitlock from McMaster University spoke about the arrhythmogenic role of LAA in AF. He presented the outline of the LAAOS III study to assess the impact of LAA occlusion in AF patients undergoing coronary artery bypass surgery. He outlined the eligibility criteria for patients as well as the primary and secondary objectives of the LAAOS III study. 

This was followed by a presentation from Dr. Lakkireddy, describing the arrhythmogenic role of LAA. He spoke about change in LAA voltage and reduction in arrhythmia burden after LAA ligation. He described the outline of the Left Atrial Appendage Ligation and Ablation for Atrial Fibrillation (LAALA-AF) registry, which is a prospective registry to assess the additional benefit of adjunctive LAA ligation in patients undergoing AF ablation.

Next was a three-way debate about who should perform the LAA occlusion/exclusion procedure. With the advent of new techniques, electrophysiologists and interventionalists have to share the center stage of LAA exclusion surgeries alongside cardiothoracic surgeons. What was thought to be a great turf war debate ended up being a very cordial work as a team consensus. Dr. Mack, who debated for the surgeons, explained the heart team concept for managing the patients with coronary artery disease. This concept encourages collaboration between clinical cardiologist, interventional cardiologist, and cardiac surgeon. He described his personal experience of learning the MitraClip procedure with the aid of interventional cardiologists. Dr. Holmes, who represented the interventionalists, agreed with Dr. Mack about the heart team concept and suggested that multi-disciplinary team-based care is required to improve patient care. Dr. Horton, who led the electrophysiologists in the debate, also supported the view that a team approach is best for the patient. He reiterated that experience with transseptal catheterization is inversely related to the complication rate, and endovascular closure of LAA should be performed by only those well trained in performing this procedure. He concluded that the LAA exclusion/occlusion procedure can be performed by either the electrophysiologist or interventional cardiologist, provided he or she has acquired the mastery of requisite skills for the planned procedure.

A detailed discussion of difference trials of LAA occlusion/exclusion presented by Dr. Holmes outlined the design and statistical overview of the PROTECT AF trial. He presented the primary efficacy results of intention to treat analysis and other secondary statistical analyses (post-procedure, per-protocol and terminal therapy), all of which demonstrated that the WATCHMAN device was non-inferior to warfarin therapy. He spoke about the decrease in procedure- and device-related safety adverse events over time, with improvement in implant time, implant success rate and warfarin discontinuation rates. Dr. Lee outlined the objectives of the PLACE II study including safety and efficacy endpoints. He presented the outcomes of LAA ligation and spoke about the incidence and size of leaks, occurrence of stroke, and other adverse events in this patient cohort. ISLAA course co-director Dr. Saibal Kar from Cedars Sinai Hospital described the structure of the AMPLATZER cardiac plug and presented the outline of the trial comparing the safety (superiority) and effectiveness (non-inferiority) of this device to optimal medical therapy in non-valvular AF patients. He highlighted that this will be the largest randomized study comparing LAA occlusion with medical therapy. Dr. Mack described the design of the LAAOS II study, which demonstrated reduction of stroke risk after LAA occlusion. He explained the LAAOS III study was started in July 2012 with a goal of enrolling 4,700 patients. He then described the FAST II study, which compared the mini-invasive mini-maze with radiofrequency catheter ablation to achieve freedom from atrial fibrillation. 

ISLAA co-director Dr. Natale described the structure of the WATCHMAN, Occlutech, and Coherex Medical devices. He discussed LAA occlusion with AtriCure and Cardioblate. He spoke about the LARIAT device, highlighting the risk of tissue accumulation at the center of the LAA orifice. He described the structure of the Epitek device, which was studied in animals but was not experimented in humans since good device position was achieved in only 41%.

This was followed by a presentation by Dr. Matthew Earnest from the University of Kansas Medical Center about the heart team approach of cardiovascular care. He stressed the importance of a multi-disciplinary approach for patient selection and access, highlighting that each specialist brings his own skill set to the table. He also spoke about the disadvantage of this multi-disciplinary approach, which uses the services of two proceduralists and echocardiographers for the entire procedure duration. 

Speaking about systemic thromboembolization and the role of the LAA, Dr. Luigi Di Biase from TCAI and Montefiore Hospital stressed that prevention of thromboembolization is key in the management of AF. He spoke about the correlation between stroke risk and morphology of the LAA. He reiterated that the risk of embolic event with cactus, windsock, and cauliflower types of LAA is 4 times, 4.5 times and 8 times, respectively, when compared to chicken wing morphology. The day ended with a presentation of interesting cases by Dr. Kar and Dr. Lee.

The 1st International Symposium on Left Atrial Appendage was a huge success! Next year’s conference will be held March 14-15, 2014 in Kansas City, Missouri. 

Disclosure: The authors report receiving grants for the conference in regards to the submitted work; they have no other conflicts of interest to report.