The 2nd International Symposium on Left Atrial Appendage: Insights from the World of Left Atrial Appendage

The second edition of the International Symposium on Left Atrial Appendage (ISLAA) was held in Orlando, Florida on March 14-16, 2014. This was the second annual symposium dedicated to the science of the left atrial appendage (LAA); the first annual conference was held in March 2013 in Kansas City, Missouri. Course directors for this year’s conference included Dr. Dhanunjaya Lakkireddy from the University of Kansas Hospital, Dr. Andrea Natale from the Texas Cardiac Arrhythmia Institute, Dr. David Holmes from the Mayo Clinic, Dr. Saibal Kar from Cedars-Sinai Medical Center, and Dr. Vivek Reddy from Mount Sinai Hospital. 

In the last several years, the LAA has been the focus of extensive clinical studies, largely due to the development of several tools and techniques for LAA exclusion, which is becoming increasingly relevant because of the obvious limitations with oral anticoagulant agents. Therefore, the ISLAA course structure was designed to accommodate healthcare providers of all levels in an effort to increase their awareness of the pathophysiological role of the left atrial appendage as well as the various techniques and tools for LAA exclusion.

ISLAA represents a true collaborative effort from all stakeholders in the science of atrial fibrillation (AF), stroke and LAA. There was equal contribution and great participation from the electrophysiologists, interventional cardiologists, cardiovascular surgeons, imaging cardiac specialists, trialists, stroke neurologists and industry involved in addressing this particular group of patients. With the risk of AF-related stroke steadily increasing, ISLAA became very relevant frontier science that evoked significant interest in the medical circles. There was a perfect balance between LAA interventions and pharmacotherapy, including the novel oral agents. It evolved into a true breeding ground for a great science where much needs to be studied. ISLAA inspired a few cardiovascular educators around the country to follow suit.

The anatomy of the LAA was explained in detail by Dr. Samuel Asirvatham of the Mayo Clinic. The various anatomical landmarks and relationships of the major blood vessels and coronary arteries in relation to the LAA were thoroughly explained. Dr. Madhu Reddy from the University of Kansas Hospital delivered the next talk, presenting on the pathophysiological role of the LAA in systemic thromboembolism. He described the LAA as “the most lethal attachment in the human body.” Further, Dr. Andrea Natale explained how the LAA serves as both a trigger and substrate for the maintenance of AF, and presented the various studies in which isolation of the appendage was done for the treatment of AF recurrences. In spite of the widely perceived pathological role of LAA, its physiological role cannot be ignored. Dr. Lakkireddy, then laid out the physiological role of AF during his presentation, “Impact of LAA Exclusion on Cardiovascular Physiology and Systemic Homeostasis.” He highlighted the neurohormonal role of LAA, which is mediated by means of atrial natriuretic peptide and also the reservoir function of the LAA. He then presented the data on how various electrolytes, glucose, fatty acids, weight and blood pressure are affected following the LAA exclusion by means of the LARIAT (SentreHEART, Inc.) procedure.

Dr. Loren Berenbom from the University of Kansas Hospital then presented the utility of various stroke risk assessment tools such as CHADS₂, CHA₂DS₂-VASc and R₂CHADS₂ scores. He further emphasized the importance of considering various bleeding risk scores before starting patients on oral anticoagulation. He also highlighted the correlation of stroke risk and morphological shape of the LAA. He strongly stressed on the “need for oral anticoagulation except in those patients with an exceptionally low risk for stroke.” Following this, another speaker from the University of Kansas Hospital, Dr. Peter Tadros, presented the challenges in the management of patients who are on concurrent antiplatelet therapy and oral anticoagulants for coronary artery disease and AF. He advised to exercise due caution given the increased risk of bleeding from antiplatelet and oral anticoagulant agents; however, he cautioned against undertreatment in these patients. This was followed by the high-octane debate, “Everyone with a CHADS₂ Score of 2 or More Should be Considered for LAA Closure/Ligation.” Playing the protagonist was Dr. Kar; the antagonist role was played by Dr. Moussa Mansour from Massachusetts General Hospital. Dr. Kar presented the data from the PROTECT AF, PREVAIL and ASAP studies to make the case of LAA exclusion. Battling against this evidence, Dr. Mansour cited the data from these studies was too small to be extrapolated to the general population. As a countermeasure, he presented the safety and efficacy data from various clinical trials using newer oral anticoagulant agents involving thousands of patients, and therefore, argued that not all patients with a CHADS₂ score of 2 or more needed to undergo an LAA exclusion procedure. 

Transseptal puncture is one of the common procedures done by electrophysiologists and interventional cardiologists for accessing the left atrium. Accurate knowledge of the anatomy as well as the various tools used to perform this procedure are of paramount importance in LAA exclusion procedures. Dr. Reda Ibrahim from the University of Montreal gave a detailed presentation on this topic. He laid emphasis on the right area and position for transseptal puncture, which is the inferior and posterior part of the interatrial septum in order to have direct access to the LAA. He also presented clips to demonstrate the difficulty in performing the transseptal puncture in flail interatrial septum, and shared his tips and tricks for performing this procedure. Pericardial access is one of the key requirements for performing the LARIAT procedure in order to place the epicardial magnetic guide wire and then later for ensnaring the LAA with a suture. Dr. Randall Lee from the UCSF Medical Center enlightened the audience with various techniques for performing the dry pericardial access. He first described the orientation of the needle, which should be directed posterior-superiorly at an angle of 30-45º. Next, he described the contrast dye technique and telescoping needle technique to perform the dry pericardial tap. Lastly, he described the use of a 90º fluoroscopic view to visualize the needle entering the pericardial sac. Further, Dr. Rodney Horton from the Texas Cardiac Arrhythmia Institute shared with the audience his expertise on selecting the right candidate for LAA exclusion. He gave an insightful review of the size and anatomical limitations of the various LAA exclusion devices, and thus highlighted the need for a customized approach to individual patients. Dr. Steven Hoff, who practices cardiothoracic surgery at Vanderbilt University, then discussed the thoracic anatomy for performing the minimally invasive LAA surgical ligation procedure.

Dr. Holmes provided a thoughtful lecture on the evolution of various percutaneous techniques in LAA exclusion. This was followed by a talk on the past, present and future of surgical LAA exclusion by Dr. James Edgerton of the Texas Heart Hospital. Dr. Edgerton emphasized the checkered past of LAA exclusion by the stapler and suture technique, resulting in incomplete exclusion of the LAA. He then highlighted newer surgical exclusion equipment such as the TigerPaw System (MAQUET) and the AtriClip (AtriCure, Inc.), which are minimally invasive and result in better LAA exclusion. Following this was a debate on the pros and cons of discontinuing oral anticoagulation after LAA exclusion, during which various studies were cited and examples of leaks and thrombus formation, as well as the extremely low risk of stroke with very small leaks, were presented. 

These talks were followed by case demonstrations of LAA exclusion using various devices. Dr. Hoff demonstrated the technique of LAA exclusion using the AtriClip device, emphasizing how it can be implanted using a minimally invasive thoracoscopic approach. He called for a collaborative approach among electrophysiologists and surgeons for selecting the appropriate candidates for this procedure. Dr. Lee demonstrated the LAA exclusion using the LARIAT device; this is an endo-epicardial LAA ligation technique using endo and epicardial magnetic guide wires. He shared the tips and tricks that they commonly use in their lab while performing the LARIAT procedure, especially the “telescoping needle approach” for performing dry pericardial access. Dr. Kar then demonstrated the technique of WATCHMAN device (Boston Scientific) implantation, and discussed the various complications that can occur while implanting this device. He stressed several times about how to deploy the device while withdrawing the sheath and not the other way around. He also emphasized the release criteria for the device once it has been deployed. Following this, Dr. Natale explained in detail the deployment technique of the Coherex WaveCrest device (Coherex Medical, Inc.). He presented step-by-step instructions on deployment of this device. Additionally, he presented the results from the WAVECREST I trial, which showed a high rate of procedural success and low risk of adverse events. Dr. Ibrahim then talked about implantation of the AMPLATZER Cardiac Plug (ACP; St. Jude Medical); he shared the protocol of this device deployment as practiced by his institution, and demonstrated a video showing step-by-step approach. 

Dr. Vijay Swarup from the Arizona Heart Rhythm Center delivered a wonderful talk on setting up an LAA exclusion program. During his talk, he demonstrated why LAA exclusion is not just a procedure but rather a program due to its complexity and the need for collaboration between echocardiographers, electrophysiologists, interventionists, anesthetists, surgeons and the nursing team. He also stressed the importance of engaging the hospital administration as well as establishing outcomes research and marketing, which will lead to not only help AF patients, but also help grow the practice and advance the field of appendagealogy. Next was a talk on the optimal use of transesophageal echocardiogram (TEE) during LAA exclusion, delivered by Dr. Swaminatha Gurudevan of the Cedars-Sinai Heart Institute. He emphasized the importance of multi-plane TEE while implanting various endocardial LAA exclusion devices. He also presented the application of 3D echo for selecting the right size of the exclusion device as well as for defining the anatomy of the LAA. Continuing with imaging, Dr. Douglas Gibson explained the role of CT imaging in LAA exclusion and how it is useful in pre-operative evaluation for the WATCHMAN and LARIAT devices. The CT scan can be used to determine the size, shape, orientation and depth of the LAA in addition to structural chest wall abnormalities such as pectus excavatum. The CT scan can also help plan the approach for the LAA exclusion procedure. 

LAA exclusion is associated with potential complications such as pericardial effusion, tamponade rupture of the myocardium, air embolism, stroke and embolization of the LAA exclusion device. Dr. Horton shared with the audience several important tips and tricks to minimize these complications. He also demonstrated the importance of the pigtail catheter for LAA cannulation to avoid perforation and proper sheath management to prevent the introduction of air into the system. Regarding the epicardial approach for the LARIAT procedure, he emphasized the importance of selecting the appropriate angle for pericardial access. Dr. Holmes further emphasized the management of complications, such as thrombus, perforation and device embolization, in LAA exclusion procedures. He also cited data from the CAP Registry and PREVAIL to show the decreasing incidence of complications with increase in operator experience and evolution of the procedural technique. Dr. Natale then talked about leaks into the LAA following LAA exclusion. He demonstrated the different leak patterns in endovascular exclusion techniques, wherein the leaks are eccentric. This is different from the central leaks seen in the case of the LARIAT procedure due to the “gunny sack effect.” He also showed evidence of the implications of these residual leaks and management of these leaks. Dr. Matthew Earnest from the University of Kansas Hospital presented next on the topic of post-procedural anticoagulation after LAA exclusion. This is an interesting topic given the limited evidence on post-procedural anticoagulation after LAA exclusion. He cited the reports of thrombus formation after WATCHMAN and LARIAT procedures, and argued the need for further studies on this intriguing clinical conundrum. 

Next, two eminent surgeons debated on the need for routine LAA ligation during open-heart surgery. Dr. Richard Whitlock from McMaster University argued for routine ligation of the LAA, citing the high rates of discontinuation of oral anticoagulation in AF patients and the safety of LAA exclusion devices and surgery. He explained the role of AF in cryptogenic stroke, and the subsequent need for LAA exclusion during open-heart surgery as a prevention strategy for stroke. Opposing the case for routine LAA ligation, Dr. Edgerton presented the importance of the LAA in homeostatic integrity mediated by the atrial natriuretic peptide present in the LAA, as well as its functional role in volume regulation. He also cited the lack of complete LAA exclusion during surgical exclusion. The conclusion to this argument is likely to be answered by the LAAOS III trial, which is currently enrolling patients. The study design was explained in detail by Dr. Whitlock, who is the principal investigator for this study. Further thoughtful review of the impact of surgical ablation or exclusion of the LAA and its implications for rhythm control was provided by Dr. A. Marc Gillinov from the Cleveland Clinic. 

Extending the talk on rhythm control using LAA exclusion strategy was Dr. Lakkireddy, who presented the results from the LAALA-AF study. This study compared patients who had undergone AF ablation alone to patients who have undergone the LARIAT procedure and AF ablation. The recurrence rates of AF were lower in patients who had undergone AF ablation along with the LARIAT procedure. Dr. Lakkireddy attributed the lower rates of recurrence of AF in these patients due to the loss of triggers and substrate present in the LAA due to ischemic necrosis of the LAA. 

Next was a three-way debate on who should perform the LAA exclusion procedure, contested by Dr. Lakkireddy, Dr. Kar and Dr. Edgerton. First up, Dr. Lakkireddy justified his case for electrophysiologists performing these procedures due to their considerable knowledge, skills and the volume of cases they handle, making them experts in this field of appendage exclusion. Dr. Edgerton strongly disputed the evidence suggested by Dr. Lakkireddy; he cited the superior hands-on approach of the surgeons as a better approach to performing these procedures because they can see, feel and touch the heart during the procedure. He also showed the availability of the minimally invasive thoracoscopic approach for LAA exclusion as an alternative approach to endovascular devices. Dr. Kar then brought forth the case for the interventional cardiologists, noting their knowledge and expertise in the field of structural heart disease as well as their adeptness in handling catheters and guide wires makes them optimal for performing these procedures. It was a very entertaining and enlightening debate, and in the end, all three agreed that a team approach is the best strategy and that everyone on the team should serve as backup to provide the right care for these patients. 

Dr. Holmes then presented details from clinical trials evaluating the WATCHMAN device, namely the PROTECT AF, ASAP, CAP and PREVAIL studies. Dr. Abdi Rasekh from the Texas Heart Institute also presented data from the various clinical trials evaluating the LARIAT procedure, including the PLACE I, PLACE II, and other multicenter observational studies. In addition, Dr. Rasekh discussed how the burden of AF decreased in patients after the LARIAT procedure. Next, Dr. Ibrahim discussed the clinical trials on the AMPLATZER Cardiac Plug,  including several registries such as the European Union, Canadian and the Belgian registries. He also presented data from a trial comparing the WATCHMAN and ACP devices. Dr. Edgerton then presented data from clinical trials on surgical LAA occlusion devices.

Dr. Natale shared his group’s experience with Coherex’s WaveCrest endovascular LAA occlusion device. This device has retractable anchors and is enmeshed by a ePTFE membrane that is non-thrombogenic. Dr. Natale displayed the deployment of this device and presented the data from WAVECREST I and II trials, which showed an acute success of >92%. Dr. Earnest then re-emphasized the importance of developing a comprehensive program for LAA exclusion. He equated LAA exclusion to other cardiac procedures with a heart team approach, and called for this approach comprising the various physicians, nursing and other support staff to provide comprehensive medical care before, during and after LAA exclusion. Cost also needs to be a factor when considering patients for LAA exclusion. Discussing this aspect was Dr. Miguel Valderrábano from The Methodist Hospital, Houston. He presented data showing the cost effectiveness of LAA exclusion with the WATCHMAN device. The incremental cost-effectiveness ratio of the WATCHMAN device is lower than that of dabigatran, but the WATCHMAN device was more effective than dabigatran. Further, he argued that although the initial cost with these implantable devices is high, the long-term benefits of lower adverse events may make them more cost effective. A multimedia presentation of several challenging LAA exclusion cases was also offered by Dr. Lakkireddy, Dr. Holmes, Dr. Kar, Dr. Lee, Dr. Natale and Dr. Swarup; during this presentation they discussed the tricks they used to overcome challenges and complications encountered during these procedures. 

Dr. Daniel Singer from Massachusetts General Hospital gave a detailed presentation on the evolution of stroke prophylaxis in AF, recapping the various clinical studies that have shown a benefit in oral anticoagulation and discussing the evolution of various stroke predictor scoring systems. Dr. Michael Ezekowitz from Lankenau Medical Center presented the data from the RE-LY AF, ROCKET AF, ARISTOTLE and ENGAGE AF studies, which pertain to the safety and efficacy of novel oral anticoagulant agents in the management of AF. 

The final debate of the symposium was between Dr. Sanjeev Saksena from the Rutgers-Robert Wood Johnson Medical School and Dr. John Camm from St. George’s, University of London. Dr. Saksena debated that the new generation oral anticoagulants are better than warfarin in AF management, and cited data from various trials demonstrating the safety and efficacy of these agents. In addition, he noted these agents impose fewer limitations on patients’ lifestyles. Dr. Camm differed starkly in his opinion. He demonstrated the evidence that warfarin was an effective agent for diminishing stroke risk in AF. He also showed evidence that newer oral anticoagulant agents are associated with increased bleeding risk and hemorrhagic strokes compared to warfarin, and cited cost as a major limitation in the use of these agents. Dr. Luigi Di Biase from the Albert Einstein College of Medicine Montefiore shared his expertise on the periprocedural management of oral anticoagulants. 

Next, Dr. Gerald Naccarelli from the Penn State Hershey Medical Center delivered a talk on understanding the antidotes for oral and systemic anticoagulants. He proposed an acronym for the management called HASHTI (Hold, Antidote, Supportive measures, Hemostatic measures, Transfusion and Investigation). He explained in detail the various measures needed to achieve hemostasis, and expressed concern regarding the lack of reversal agents for the newer oral anticoagulant agents. He also talked about the development of reversal agents such as aDabi-Fab, which is an antibody to reverse the effect of dabigatran and also recombinant factor Xa inhibitor antidote. These agents are currently being evaluated.

The next talk by Dr. Camm was on why oral anticoagulants are still the best answer for stroke prophylaxis. He expressed concern at the rising global prevalence of AF. He demonstrated data from various studies that demonstrate the effectiveness of oral anticoagulation in mitigating the risk of stroke. He then showed evidence that oral anticoagulation with warfarin was still cost-effective compared to LAA exclusion devices, and that this factor becomes increasingly relevant in poorer countries. He advocated that oral anticoagulants, if used appropriately, were still a better option compared to LAA exclusion procedures on a global scale. Dr. Jonathan Piccini from Duke University Medical Center then spoke about selecting the appropriate oral anticoagulant. He also cited data from various studies demonstrating the safety and efficacy of each oral anticoagulant agent, and urged healthcare providers to consider the comorbidities and risk profile of the patient and custom select the oral anticoagulant based on this. Dr. Asirvatham then spoke on the optimization of stroke prophylaxis strategies in non-valvular AF. He explained in detail the merits and demerits of drugs and devices, and called for a balanced approach to custom deliver the right care for each individual patient. He also talked about how endovascular LAA occlusion devices could potentially interfere with AF ablation due to their mechanical properties. Dr. Ezekowitz then talked about the management of valvular AF, giving a detailed insight into the mechanisms of valvular AF and how clinical trials have excluded these patients. 

There were also several abstract presentations during the ISLAA 2014 conference. Dr. Jayasree Pillarisetti from the University of Kansas Hospital presented her study on differences in leak patterns among patients implanted with the WATCHMAN and LARIAT devices. Dr. Nagaraj Hosakote from the Nebraska Heart Institute presented his institution’s data on the periprocedural use of colchicine for decreasing pericarditis pain in patients undergoing the LARIAT procedure. Dr. Arun Kanmanthareddy from the University of Kansas Hospital presented on AF burden in patients with implanted cardiac devices following the LARIAT procedure. 

The audience got a fair amount of time to ask clinical questions to the keynote speakers. Additionally, several members of the audience shared their own thoughtful insights on the management of LAA exclusion devices. 

The 2nd ISLAA conference was a grand success, presenting healthcare providers with a full range of knowledge of the procedures and challenges in the science of appendagealogy. The growing popularity of this conference has attracted speakers from all over the world, and they were well received by an enthusiastic audience comprised of different levels of healthcare providers from across the world. The video sessions from this conference will be available soon, and can be viewed at www.islaasymposium.com. 

The third edition of the ISLAA conference has been slated for February 6-8, 2015 in Los Angeles, California. We look forward to receiving you at the next edition of this conference!