Mar 7, 2022
This week, join author Marco Valgimigli and Associate Editor Mark Link as they discuss the original research article "Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: Primary Results of the SWISS-APERO Randomized Clinical Trial."
Dr. Carolyn Lam:
Welcome to Circulation on the Run, your weekly podcast summary and backstage fast as a journal and editors. We're your co-host, I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.
Dr. Greg Hundley:
I'm Dr. Greg Hundley, Associate Editor, Director of Poly Heart Center at VCU Health in Richmond, Virginia.
Dr. Carolyn Lam:
Greg, I've got a personal interest in this feature paper that's coming up. I've always been very intrigued with the left atrial appendant closure. Well guess what? This is the results of the Swiss-Apero Randomized Clinical Trial, comparing the Amulet with the Watchman device for percutaneous left atrial appendage closure, really interesting stuff coming right up, but let's hold everyone in suspense. As we go through some of the other favorite papers in today's issue. Would you like to go first?
Dr. Greg Hundley:
You bet Carolyn, this first paper really pertains to driving restrictions and earlier arrhythmia is in patients receiving a secondary prevention, implantable cardioverter defibrillator, and it comes to us from Dr. Christian Steinberg. So Carolyn, regulatory authorities of most industrialized countries recommend six months of private driving restriction after implantation of a secondary prevention ICD and these driving restrictions result in significant inconvenience in social implications. And so Carolyn, the purpose of this study was to assess the instance rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD using a retrospective across three Canadian tertiary care centers enrolling 721 consecutive patients with new secondary prevention ICD implants between the years of 2016 and 2020. And they were followed for a median of 760 days.
Dr. Carolyn Lam:
Nice. An important question. So what did they find Greg?
Dr. Greg Hundley:
Right Carolyn. So they found that the cumulative incidents of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days, and subsequently dropped to 0.4% between 91 and 180 days after ICD insertion. So Carolyn the incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and significantly declines after the first three months, lowering driving restrictions to months after the index cardiac event seems safe and revision of the existing guidelines should be considered in countries still adhering to a six month period.
Dr. Carolyn Lam:
Oh, love it Greg. Elegant study with clinically impactful results as with the next paper, I'm going to talk about a post talk analysis of the Danish trial in which authors led by Dr. Boas from Denmark and Dr. Bower from Austria and their colleagues. And what they did is they tested whether periodic repolarization dynamics or P R D, which is a marker of repolarization instability associated with increased sympathetic activity. Could indeed identify patients with non-ischemic cardiomyopathy that may benefit from prophylactic ICD implantation. So, 748 patients were included in this P R D sub-study. And they were included if they had a 24 hour whole term monitor recording at baseline with technically acceptable ECG signals during the night hours. P R D as a reminder of periodic repolarization dynamics was assessed using wavelet analysis according to previously validated models.
Dr. Greg Hundley:
Very interesting, Carolyn. So what did they find?
Dr. Carolyn Lam:
Periodic repolarization dynamics was independently associated with mortality. More over P R D was significantly associated with mortality in the control group, but not in the ICD group in this Danish trial. There was a significant interaction between P R D and effect of ICD implantation on mortality, such that patients with higher P R D had greater benefit in terms of mortality reduction with the ICD. Based on P R D the investigators could identify a new group of patients where prophylactic ICD implantation was associated with a significant absolute mortality reduction of 17.5% after eight years corresponding to a number needed to treat of only six. So this is the first sub-study of Danish to identify a marker on top of age, that can predict the treatment effect of prophylactic ICD implantation in patients with nonischemic cardiomyopathy.
Dr. Greg Hundley:
Very nice Carolyn. Well, my next paper comes to us from Dr. Kory Levine from the Washington University School of Medicine. And Carolyn recent studies have established that cc chemokine receptor type two are CCR2 marks the pro inflammatory subsets of monocytes, macrophages and dendritic cells that contribute to adverse left ventricular remodeling and heart failure progression. Now elucidation of the effector mechanisms that mediate adverse effects of CCR2 plus monocytes, macrophages and dendritic cells could yield important insights into therapeutic strategies to suppress myocardial inflammation.
Dr. Carolyn Lam:
Hmm, indeed. And so what did these author determine regarding the suppression of myocardial inflammation?
Dr. Greg Hundley:
So Carolyn this team utilized mouse models of re perfused myocardial infarction, and angiotensin two and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation to investigate cc chemokine ligand 17. They found that cc chemokine ligand 17 serves as a pro-inflammatory mediator of CCR2 macrophages and dendritic cells, and their results suggest that inhibition of cc chemokine ligand 17 may serve as an effective strategy to promote T-cell regulation recruitment, and thereby suppress myocardial inflammation.
Dr. Carolyn Lam:
Wow, thanks, Greg. That was beautifully summarized great stuff. Well, there are other exciting articles in today's issue. There's an exchange of letters between Doctors Nagareddy and Spear on “Interleukin One Alpha as a Central Regulator of Leukocyte Endothelial Adhesion in Myocardial Infarction and Chronic Kidney Disease. There's an ECG challenge by Dr. Yang entitled, “A Fatal Case of Y QRS tachycardia following Sintilimab treatment for lung cancer. It can happen.” There's an On My Mind paper by Dr. Faed on “CYP2C19 Genotyping in Anticoagulated Patients Post PCI: Should it be Routine?”
Dr. Greg Hundley:
Great, Carolyn and I've got a Research Letter from Professor Poo entitled “Efficient in Vivo Hemology- Directed Repair within Cardiomyocytes.” Well, how about we get onto that feature, discuss and learn more about Watchman devices and left atrial appendage closure.
Dr. Carolyn Lam:
Ooh, let's go.
Dr. Greg Hundley:
Well, listeners. Now we are onto the feature discussion today, and we're so privileged to have with us, Dr. Marco Valgimigli from Bern, Switzerland and our own Associate Editor, Dr. Mark Link from UT Southwestern. Welcome gentlemen. Well, Marco, we will start with you. Can you describe for us a little bit of the background material as to why you wanted to perform this study and what was the hypothesis that you wanted to address?
Dr. Marco Valgimigli:
But thank you so much for having me left atrial appendage closure is a therapeutic option for a patient who have formal indication to oral anti-population because of atrial fibrillation yet have some relative or absolutely contraindication to the treatment because mainly of high bleeding risk features, mainly because of previous bleeding complications. The two most frequently use device to accomplish that procedure are from one side Watchman, which is FDA approved. And on the other hand, the Amulet, which has been historically the device, which has been most frequently used in Europe, these two devices have been formally compared in one head to head study, which is Amulet IDE and also reported in the journal some month ago. However, it was important also to compare the new Watchman iteration, which the Watchman Flex, which was not part of the original Amulet IED, which only compared Amulet with Watchman 2.5.
Dr. Marco Valgimigli:
Before we set up this multicenter study, which recruited patients across eight centers and four European countries, we roughly screened 450 patients. And we ended up randomizing 222 to either of these two device being Amulet or Watchman. We set up this study to answer a superiority hypothesis, actually, of Amulet versus Watchman and we assume that Amulet would be superior compared to Watchman with the respect to the need for crossover to a known randomly allocated device or LA Patency at 45 day SCCTA.
Dr. Greg Hundley:
Very nice Marco. And so now describe for us your study design. And then what was your study population?
Dr. Marco Valgimigli:
That was an investigate initiated and conducted multicenter study, which took place across eight centers in four European countries. We screened roughly 450 patients to be able to randomize. Finally, 222 were evenly allocated to either of these two device. We selected patients with either fibrillation and form lead for oral anti-regulation to with relatively high chat box score on average four and very high has bled at least three or greater. In fact, 95% of our patient had prior bleeding before being considered for the study.
Dr. Greg Hundley:
Very good. And describe for us your results.
Dr. Marco Valgimigli:
So the superiority that we assumed was actually not met. The primary point, which was again, crossover to a known allocated device or patency rate at 45 day SCCTA was pretty much similar with rates being 68% in the Watchman group and 70% in the Amulet group. So basically no real difference. We did see though some interesting differences with respect to some key secondary endpoints.
Dr. Greg Hundley:
And describe those.
Dr. Marco Valgimigli:
So for example, the type of leaks that was recorded was actually different with respect to the two devices with intra device leaks, being much more frequent with Amulet and peri device leak, being much more frequent with Watchman. Also the rate of any or major procedure complications were slightly yet significantly higher in the Amulet group. And interestingly as well, we had some minor differences with respect to the device related thrombosis, which was numerically slightly higher in Watchman as compared to Amulet also, we performed at 45 day TEE, Transesophageal Echo and with that respect, we did see a slightly, yet numerically and significantly higher rate of peri device leak, detected at Transesophageal Echo with Watchman as compared to Amulet, which is in a way reflecting our SCCTA findings.
Dr. Greg Hundley:
Very nice. And so lots of results comparing these two devices for a left atrial appendage closure. So Mark, you see many papers come across your desk. What attracted you to this particular paper?
Dr. Mark Link:
Yeah, this is a very important clinical paper. The left atrial occlusion devices are going to continue to be used and with increasing frequency and there can be very beneficial. The Amulet is not approved in the United States. And so comparison between Watchmen and the Amulet are very important, both for the US and for Europe and the rest of the world. And that's why we were attracted to this paper, it's a nice randomized paper comparing the two most commonly use devices.
Dr. Greg Hundley:
Help us put the results of this study into the context in really how we might manage patients and how we're considering these devices, both from the European perspective and then also here in the US.
Dr. Mark Link:
I think what this study shows is that they're more or less equivalent and there may be theoretical reasons why one may be better than the other, but in this trial it didn't really come out. So I think the Amulet used more in Europe. The Watchman is used exclusively here, but I think this opens a window for the Amulet to come to America also and be approved by the FDA.
Dr. Greg Hundley:
Very good, well, coming back to you, Marco, where do you see is the next study that needs to be performed in this arena of research?
Dr. Marco Valgimigli:
I think now we have relatively effective device in accomplishing what we would like to accomplish. Namely sitting the LAA for preventing subsequent thromboembolic events. However, the procedure despite operators have been growing in terms of interest and experience is still associated with some degree of complications. Some of them are minor, but some of them are not. I think the next future, we should try to minimize those complication to the lowest possible event so that this procedure can potentially be also offered to a broader patient population, perhaps not just as a replacement of oral anticoagulation, but perhaps in association with oral anticoagulation to further minimize the stroke and other thrombotic events.
Dr. Greg Hundley:
And Mark, do you have anything to add here?
Dr. Mark Link:
Yes. I think what we need more information on is two things. One is procedural complications, procedural complications were higher with the Amulet device. And is that because it was a newer device and people are just learning how to use it, or is there something there that's really important? So that's one and then the really important one is long term clinical outcomes. This was a relatively short term trial when you're talking about strokes and anticoagulation. And so what I'd like to see is longer term follow up with both devices in the future.
Dr. Greg Hundley:
Well, thank you Mark. So now Marco, do you have any additional studies that you're performing really on this same dataset?
Dr. Marco Valgimigli:
Well, I actually fully agree with Mark, very long term follow up is absolutely mandatory in this patient population. And I'm very glad to announce that this Swiss Apero study that we have been discussing will actually continue. Continuing patients follow up five years so that we will have much more clinical information, at least comparative effectiveness, clinical information between two devices. And also we'll be performing at 13 months, a second SCCTA to better understand the dynamic nature of these peri device or inter device list, whether they actually do see over time and which of them may or not play a clinical role.
Dr. Greg Hundley:
Very nice well listeners, we want to thank Dr. Marco Valgimigli from Bern, Switzerland and our own associate editor, Dr. Mark Link from UT Southwestern for really bringing us this very important paper that compared the results of the Watchman, which is for primarily used in the US versus the Amulet, primarily used in Europe, a left atrial appendage closure device. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run.
Speaker 5:
This program is copied right of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.