We're going to talk about pitiful incidents,
pathophysiology, and associated conditions.
We're going to explore the indications,
risks,
and benefits for closure.
Just so that we're all on the same page.
It's important, we'll talk.
What exactly is a CFO?
We all know that embryologically
the foramen valley is
a normal component of fetal circulation.
And it provides the necessary shunt in
utero for blood to
get from the venous to the arterial system.
After, after you're born
that starts to close,
there's a little flap that goes across
the fossil Vallis by 12 months that
should be closed if there's
persistent patency of part
of some of that or all of that.
For fossa ovalis, you
have a PFOA and that is common.
It's common for this to occur.
Twenty-five percent of people probably have
a PFOA and most of them don't know
it and most of
them will never have a problem with it.
But it can be associated
with paradoxical EMBL I
from the venous directly
through the heart to the left side,
bypassing the lungs and causing
embolic phenomena in any major organ,
most worrisome, the brain.
So we'll start with a case
that I want you to think about because
it's illustrative and sets
the framework for our discussion here.
Patient to 46 year-old comes in
with a history of stroke, recent stroke,
cardiac exam, an ECG,
our normal neurologic evaluation
done by a neurologist.
Cardiologist doesn't anymore tooth
that but demonstrates a cortical stroke,
which I assume is a is an important finding.
So in that patient,
current guidelines would recommend want,
which of these things
I want you to just think
about this pick out in your mind an option.
Would you give anti-platelet therapy,
anticoagulation device closure?
Device closure only if there's
another event proving that there's
a problem or would you
refer to a neurologist and colleagues?
Just think about that.
And at least currently
the guidelines would suggest that
PFOA closure is in fact
recommended for that
for that particular patient.
And we'll talk about why these are
the devices that are available
to us to close PFOA.
There are two FDA approved devices.
The implants are occluder.
That's as you see, it's
got a nitinol mesh with
a polyester infill that
provide the left atrial portion
of the device is
smaller than the right atrial,
so there's less material in the left atrium.
You can actually recapture this
and move it around if you
need to, which is convenient.
But there is some potential,
especially in certain patients subgroups and
certain anatomical variants
for increased erosion.
Although this has not been seen in
the randomized trials of PFOA closure.
The Gore device is a nitinol,
a frame that sort of pillow
we PTFE material can expand and contract.
Both sides of this device
are are conformable and independent.
It's very soft law erosion profile.
It rapidly endothelial eyes
is due the material,
but there is more atrial fibrillation
associated with this device.
And the closure has not always
been seemed to be as robust
as with some other devices,
but they're both approved, both used widely.
So there are some of you
may have chosen to wait or not
do any PFOA closure
in the patient that we talked about earlier.
And a lot of that is due to
a fairly recent but negative trials.
There was a series of three trials.
Closure one PC and respect,
all showing insignificant benefit
to closure over medical therapy,
whether the endpoint was
a composite of neurologic or cardiac events.
All of them showed some
point estimate benefit to closure,
but not statistically significant benefit.
Subsequent trials published much
more recently in the literature
did show some benefit.
So the longer-term outcome of respect,
which again at, at seven years or six years,
had a p-value of 0 at
the longer-term follow-up actually
showed that there was some benefit to
PFOA closure in the very late stages.
You can see that crypt
agentic ischemic stroke population
there were 1000 patients
with a mean age of 46.
Just like our patient at
that at the beginning of the presentation,
mean follow up with six
years out to 10 years.
And the recurrent stroke
relative risk reduction
was 62 percent.
A dramatic improvement in
a reduction of stroke.
Closure was more effective in
some subgroups of patients
and this will come into play later.
So people with atrial septal aneurisms,
So not just failure of closure of that flap,
but a big floppy atrial septum
that allows a material
to come can be
thrombogenic and itself but
also allows more material to cross.
Large. Existing shunts all
showed more risk or
more potential benefit to closure.
Interestingly, there was there
was more DVT and
PE demonstrated
in the closure population as well.
Allowing you to think that perhaps
those events that were
pulmonary in nature may have
actually been neurologic in nature,
had it not had there not
been closure in those groups.
But that's that's just of interest.
Importantly, no difference in
serious adverse events or bleeding or
atrial fibrillation in the group
who got closure compared to medical therapy.
The close trial looked at
PFM closure with anti-platelet therapy
versus anti-platelet therapy alone.
This highlighted patients with
those high-risk features of atrial
septal aneurism or large shunt.
Again, mean age above 43
with a good follow-up.
Recurrent strokes were 0% versus
6% in this population up to about five years.
And atrial fibrillation, however,
was increased with with
placement of a device.
The Gore reduce trial
had a similar strategy here,
just of the overall
population of crypt agentic show
stroke a fairly large sample size,
81% had large shunts.
So this was
the high-risk feature in this group.
Large shunts.
Again, good follow-up and
a statistically significant benefit.
Well, you're while whether you're looking at
24 month symptomatic stroke or a combination
of symptomatic and silent imaging
identified stroke.
All of those things were beneficial.
Again, more atrial fibrillation.
In the people who got closure.
There was a large random
network meta-analysis of
the randomized trials from
2012 to 2018 published
in the BMJ Open Journal.
And you see that the lowest event rate was
for people who had PFOA closure
plus anti-platelet therapy.
Antiplatelet therapy alone,
which we'll talk about is actually
the medical therapy of choice had
had the worst outcome at
about 10 percent event rate over,
over eight to 10 years.
So quite a splay,
quite a spread in this meta-analysis.
There'd been a lot of
meta-analyses and a lot of work.
But here as we talked about,
absolute increase of 2% with
h of atrial fibrillation,
about a nine or 10 percent absolute
decrease in stroke with
closure in
the setting of anti-platelet therapy.
So solid evidence in this population.
So actually there's been
a flurry of statements
now updating people about
PFOS and secondary stroke prevention.
This one endorsed by
the Academy of American Academy of Neurology
is appropriate for this audience.
There is a statement by sky,
the interventional
cardiology group coming out.
It's not yet published
and can't be commented on,
but that will be coming out
shortly and has some added insight as well.
But in this most recent recommendation,
PFOA closure is recommended for
embolic infarct if no
other stroke causes identified,
this has to be a true crypt
agentic stroke because otherwise you're
putting people at risk
without potential benefit.
We'll go through some of the risk profiles
and some of the ways you can tease out
whether it is a true crypt agentic stroke or
not and the best age population.
But this is important for shared
decision-making because the absolute benefit
for placement of a device
is about a 3.4% absolute risk reduction.
While there are peri-operative events
and about 4% of patients and
atrial fibrillation is present
with a increase annually.
Again, a younger people
with a true crypt agentic stroke,
large shunt and
other high-risk features tend to do
better and have a better risk reduction
with closure.
And if patient the first closure by choice,
you can consider antiplatelet
or anticoagulation therapy.
So how do we exclude and
non PFA cause mechanism of stroke?
You asked your neurologist of course.
So having a heart brain team
is he has
helpful imaging of course is essential,
ruling out identifying stroke
and location of stroke,
making sure it's a cortical stroke.
As a higher likelihood
extracranial imaging is,
is, is important obviously,
Venus thrombophilia testing,
as we've talked about both
yesterday and earlier today,
with a variety of factors really ruling out
a prothrombotic evaluation as a
which would be a primary treatment source
rather than necessarily device closure.
Tce or TE, as we saw in our original case,
is important with that bubble study
that shows bubbles
flying across the septum
and dysrhythmia monitoring,
monitoring is also important to
exclude silent atrial fibrillation,
paroxysmal atrial fibrillation,
which could be a notice
for stroke and would
be important to identify.
So long-term monitoring can be helpful,
especially in people at increased risk,
those people age older than 60 who
might have a higher incidence
of paroxysmal atrial fibrillation.
Long-term monitoring up to a year with
an implantable device is
sometimes encouraged.
Another way to do this is we
saw some of the MD Calc.
Scores earlier this morning.
And in fact, there's the rope score
is a score where you can a grade.
It's just a, a six components score
that includes age and the other
factors that you see on the slide.
It gives you a score and
a percent chance that
the stroke is likely due to a PFOA.
This can be somewhat helpful.
It's got all of the,
basically what you're doing is you're
including or excluding
typical stroke risk factors
and then adding in an age component.
So it quantifies what you, your gestalt.
Unfortunately, the specific score,
while easy and readily available,
cannot be replicated
always in previous trial.
So you can't retrospectively find
a clear association with
outcome in all trials.
And so prospectively it needs to be
tested a little bit more, but it is a,
a means to help select patients for
PFOA closure who do
have truly criminogenic stroke.
So summarizing this in a way.
So who are candidates for closure?
Again, careful patient selection
with neurology input is helpful.
People who do qualify for
PFOA closure would be
those patients who are younger,
high anatomic risk including
that atrial septal aneurism,
large right to left shunt,
long PFOA, no other stroke,
wrists, high bleeding risk,
or patient preference.
People you might have second thoughts
about would be
the older patients small shunts,
other stroke risk factors, low bleeding risk,
and they could tolerate anti-platelet therapy
or patient preference.
Again,
going through that
shared decision-making which
is mandated by guidelines.
Pfoa closure complications
include atrial fibrillation,
as we said, about 3%.
With up to 15 percent
occurring late air embolus.
Rarely during the procedure,
device symbolization does happen,
erosion can happen,
and tampon out is very rare.
Those all of those events are quite rare.
And from an invasive proceduralists,
probably tolerable,
but, but it's something
to discuss with the patient.
Most device related AF occurs
early and resolves spontaneously
to end, does not cause a stroke.
The, the so anti-platelet therapy is
indicated after closure for
at least three months.
There's some there's some discussion
about the role of
anti-platelet therapy or anticoagulation
therapy with or without the device.
And I think that if people have noted
atrial fibrillation or if
they're high risk or
they have
other indication for anticoagulation,
it would be reasonable to
treat them with with
anticoagulant even with a device in place,
especially if they have
persistent atrial fibrillation.
In conclusion, the amplitude
and gore devices are FDA
approved and utilized for
PFOS closure in the appropriate patient,
which is guideline recommended
for carefully selected patients who
have no other identifiable cause
for the stroke apart from
paradoxical embolus.
And our anti-platelet therapy
or anticoagulation is indicated if
there's no PFOA closure
performed and the selection
is really not clear.
We don't have great data about it.
Most of the most recent trials compared
anti-platelet therapy to PO4
with anti platelet therapy.
And so that is the primary selection,
but anticoagulation is indicated
especially if there's
another reason for anticoagulation
such as atrial fibrillation,
thrombophilia or
thrombotic burden, et cetera.
Other patient populations
who could benefit from
PFOA closure include orthodoxy,
which is people who
get shorter breath when they're
sitting up and feel
better when they're laying down.
That's bunch.
It's a rare condition
but can be improved with PFOA closure.
Other populations have shown
benefit decompression illness for
divers, pacemaker lead thrombus.
Those populations are being
studied, no clear indication.