 Good afternoon my name is Abdi Rasag and I was asked to talk about left atrial appendage occluded devices as an alternative to anticoagulation therapy in patients with atrial fibrillation. I don't have any conflict of interest regarding this talk. As you know most common arrhythmia in clinical practice is atrial fibrillation which accounts for one-third of hospitalization for cardiac rhythm disturbances. It has caused a 66% increase in atrial fibrillation hospitalization and it's due to aging population and increased chronic heart disease. Its prevalence is about 2.2 million in U.S. and more than 4 million in European Union and the cost is significant it's estimated to be 16 billion in Europe. One out of six stroke is due to AFib and the prevalence of it and the incidence in octogenarian is about one of three strokes. Further more the strokes that happens because of AFib are larger strokes that can cause more of incapacity in patients. This shows how the atrial fibrillation is an aging population problem as you can see in two decades of life the risk of atrial fibrillation increases from 4% to 12% in octogenarians. The devices that I'm going to talk about they're all FDA approved. One was the first device that was approved in U.S. and subsequently the second generation of watchman flakes was approved in U.S. and then subsequently I will talk about ACP amylet which is a new kid in the block it was just approved a few weeks ago. ACP amylet is a left atrial appendage occluder which is second generation of amplizer and it's constructed from a nitinol mesh. It has a lobe and a disc and the lobe part of it can go anywhere from 16 to 34 mm and the disc would range from 22 to 41 mm and I will go over it in more details and the clinical trials that has been done. But let's first start talking about the first generation of the device which was watchman the first study which was done was protect AF study which was a prospective randomized trial of non-inferiority design with 5-year follow-up. As you can see there was no difference when you follow up to 5 years in ischemic stroke however when you look at the primary efficacy of stroke cardiovascular death and systemic embolism beyond 3 years there is a mortality benefit of the device over warframe and this was at the era that we didn't have any of these new oral anti-coagulation therapy. All cause mortality also showed a benefit of the device and the convergence between the two arm around two and a half, three years cardiovascular mortality was less in device arm too. However if you look at the safety data you can see that initially there was benefit to warframe but when you're following up to 5 years there was no significant difference and this was due to initial procedural complications and major bleeding initially that brought up the issue of the safety events in the arm of the watchman. What were concerns with protect AF and why it was not approved by AFD at that point? The issues were high initial rate of procedural complications failure to implant the device in some patients and low chats to score. At the time we were not using chat's VASC score which essentially gives you an indication of the risk of a thrombotic event. Prevail was the second study that was requested by FDA and was also a randomized study comparing watchman and warframe to confirm protect AF results and answers the concerns. As you can see even with operators that were not as seasoned and there were a certain number of the operators who were initial operators with the experience that operators gained the implant success rate increased from 90.9% to 95.1% and the risk of tympanod and cardiac perforation went from 1.6% to 0.4%. In fact there was only one patient who had cardiac perforation requiring repair. The study showed also non-inferiority although in this study the patients who were on control group did amazingly well because of the vigorous control of their anticoagulation therapy. If you are looking at the secondary efficacy endpoint which was stroke or any adverse event after seven days or systemic embolization post-randomization there was no difference. Update from this watchman clinical trials at five-year follow-up of protect there was superior efficacy, reduced mortality and similar overall safety as warframe. When you add protect AF and prevail meta-analysis there were similar all-cause stroke but less cardiovascular death compared with warframe. There was significant reduction in bleeding related costs in watchmen group compared to oral anticoagulation eligible patients. You can see that the primary efficacy and hemorrhagic stroke showed a benefit of using these devices. However, the schemic stroke did not show any benefit and all-cause mortality after two, after two and a half, three years it showed a divergence in favor of the device. What about the amulet? The initial studies were all done in Europe. There was a study group with 22 participating centers all over Europe. Enrollment was from December 2008 to November of 2013 with more than 1,000 patients and 1,345 patients follow-up years. As you can see there was a significant decrease in stroke reduction versus estimated based on Chad's VASC score and it decreased by 59%. Effectiveness in bleeding reduction was also more than 61% and in this patient dual antiplatelet therapy was used. The next generation of the watchmen was watchmen flex and watchmen flex had the advantage of being more of a closed system so you can push it inside of the left atrial appendage. There are not any sharp prones as you can see the difference between the two devices that increases the risk of bleeding and as you can see there was 72% relative risk reduction in bleeding compared to warfarin and 27% reduction in all cause mortality compared to warfarin. This study was a pinnacle flex IDE study. It was a single arm non-run device study and in this study only the DOAC was used 400 patients in 29 US sites and the patients were on DOAC plus aspirin for 45 days followed by clopidicrile and aspirin up to 6 months and then aspirin. The TE was done at 45 days and 12 months but they were followed up at 45 days 6 months 12 months 18 months and 24 months. In this study they also looked at all cause death, ischemic stroke, systemic embolization. Primary efficacy end point was the rate of effectiveness of closing the left atrial appendage with a peri device of leak of less than 5 millimeter demonstrated by TE at 12 months and they looked at ischemic stroke or systemic embolization at 24 months from the time of enrollment. And as you can see in this study the success rate was more than any of the previous studies that used watchmen or watchmen flex and the success to implant was 98.5%. It has to be noted that 6.6% of all patients in the Pinnacle study were not able to receive watchmen devices and 97% of these subjects were successfully implanted with the new generation watchmen flex and as you can see this device goes anywhere between 20 millimeter and 35 millimeter and essentially the size of this left atrial appendage was all over the place but they were successful in implanting more than 98% of these cases. If you look at the primary safety end point the performance goal was 4.2% but really the complication was only 0.5% there was no all cause death, there was an ischemic stroke but there was no systemic embolization and no device procedure related events which required surgery. Essentially in this study it showed the great safety of watchmen flex and then watchmen flex was approved by FDA to be used when they looked at the primary safety end point which showed only 0.5% of complication and primary efficacy end point was great and there was no leak of less than 0.5%. They were hoping for 97% but they had 100% without any major leak and when you're looking at use of oral anticoagulation post implant majority of the patients were on essentially a pixiban or a river oxaban and oral anticoagulation discontinued at 45 days in about 96% of this population. So you can see that oral anticoagulation discontinuation at 45 days was 96% which was superior at all of the previous study using watchmen which was anywhere between 87 to 93%. Furthermore device related thrombus and embolic event happened only in 2 out of 395 patients after 12 months of follow-up. All of all patients were on dual anti-plated therapy or aspirin at the time of device related thrombus detection. Two subject experience ischemic stroke or systemic embolization and one of the bleeding that has happened was in a patient who had essentially appellation which was not related to the device. In the European limited market release also the technical success was 100% and precordial effusion was 0.6% with 1.2% access site complication. So the good news is there are different device designs which will provide solution to different patient needs and survival benefit data with watchmen is encouraging and essentially left atrial appendage closure is associated with lower risk of stroke in patient with contraindication to oral anticoagulation and whenever even the stroke happens these strokes are less devastating. So there are several points. Number one patient definitely benefits from less intracranial hemorrhage. Point number two is the risk of implanting of this device significantly decreased by decreasing the access complication, precordial effusion, stroke and device leak or thrombus. Finally we had significant reduce in complication of the device itself. The risk factors for device related thrombus are things like prior TIA or stroke, larger left atrial appendage diameter, lower ejection fraction, permanent AFib and device position especially if you have a leak and the question of how much leak is acceptable leak is still subject to debate. What are the unanswered question? The target population is not still well defined should this procedure be for all or limited to patients intolerant to oral anticoagulation therapy. How relevant are the findings of these studies in the era of these duax and are all of the devices equivalent do we need comparative studies? Are they particular anatomy that have one or different kind of device works better? The next study is champion AF which is ahead to comparing the safety and efficacy of watchmen flex to duax in patients with non-valvular atrial fibrillation with lower risk. We are going to talk quickly about the amplizer amulet IDE randomized trial. This is the trial that looked at the amulet and initiated in 2016 to establish safety and efficacy of amplizer amulet. It is the dual seal mechanism that we talked about and there was no need for oral anticoagulation but just dual antiplatelet therapy. Essentially it was in patient with paroxysmal persistent or permanent atrial fibrillation with chance vascular more than three or chance score of more than two which were suitable for short term warfarin therapy but then unable to take long term oral anticoagulation therapy and essentially they had a TE at 45 days and 12 months and all of these patients were on dual antiplatelet therapy or aspirin plus oral anticoagulation therapy. It was a randomized study that compared amulet to watchmen and primary endpoint was safety at 12 months and effectiveness at 18 months and we looked at mechanism of action at 45 days and primary safety endpoint at 12 months. As you can see it was one to one randomization between watchmen and amulet it was watchmen and not watchmen flex because at the time of the study watchmen flex was not out. These are some baseline characteristics of the patients with a chance mask of more than four in this population and this shows at the time of the discharge majority of the patient on amulet were on dual antiplatelet therapy but still one fifth were on oral anticoagulation therapy. On watchmen majority were on oral anticoagulation therapy. As you can see residual jet of more than 5mm was only 1% in the amulet arm. Again it was non inferiority of the amulet compared to the watchmen in this study procedure complication was higher initially and then it went down as you can see the pericardial effusion was 2.4% amulet but it went down significantly when the operators gained experience with this new device. Schemic stroke or systemic embolism in 18 months were similar with watchmen also secondary in point of stroke systemic embolism and cardiovascular death was similar and major bleeding was similar despite low oral anticoagulation usage again major bleeding rates were comparable between the groups and if you look at the device related thrombus to watchmen patient experience Schemic stroke whereas none of the amulet patient did. In the interest of time I'm going to go to conclusion of this study that the dual seal amulet left atrial appendage occluder was superior with respect to left atrial appendage occlusion and non inferior with respect of safety and efficacy in patients with non valvular atrial fibrillation compared to the watchmen again there was no comparison to watchmen flex and all three primary end points which was closure at 45 days safety at 12 months and effectiveness and 18 months was met and as a result in August 14, 2021 amulet was approved. What is next is catalyst randomized clinical trial is a multi center trial which is a randomization between amulet versus NOAC and it's going to look at a 2500 patient in 150 centers and the study was just started thank you.