Circulation March 8, 2022 Issue

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.