Latest / European Society for Vascular Surgery / Genetic Aortopathies: Navigating Complex Decisions in Practice with R. Afifi & S. Shalhub

Transcript

Genetic Aortopathies: Navigating Complex Decisions in Practice with R. Afifi & S. Shalhub · European Society for Vascular Surgery

0:14
Welcome to the ESVS podcast. I'm Rosalinda D 'Amico.
0:18
Today we will discuss a challenging and often
0:21
controversial area in aortic surgery, decision
0:24
-making in genetic aortic diseases. These are
0:28
inherited conditions that affect the structure
0:30
of the aortic wall and often lead to aneurysm
0:34
and dissection at a younger age. While guidelines
0:37
provide an important framework, their application
0:40
in genetic orthopathies is often complex. And
0:44
in real life, we frequently face challenging
0:47
decisions regarding time of intervention, treatment
0:50
strategy, and long -term management in often
0:54
young patients. I'm delighted to be joined today
0:57
by Professor Shalhoub, Professor of Surgery and
1:02
Division Head of Endovascular Surgery at Oregon
1:05
Health and Science University, an internationally
1:09
recognized expert in complex aortic disease with
1:14
a special focus on genetic orthopathies. and
1:17
by Professor Afifi from McGovernment Medical
1:20
School at UT Health Houston, an internationally
1:24
recognized expert in complex aortic treatment.
1:27
We recently met at the International Society
1:30
of Women Vascular Surgeons meeting in Atlanta.
1:35
Thank you, Rosalinda, for having us. It's a pleasure
1:38
to join you and having this discussion today.
1:43
And thank you as well for the invitation. I'm
1:45
honored to be here, and I appreciate doing this
1:48
with my colleague, Dr. Afifi. So let's start
1:52
with genetic testing. Professor Shalhoub, in
1:55
these patients, identifying an underlying mutation
1:58
can influence not only surveillance, but also
2:02
timing of intervention. Testing can be costly
2:06
and may generate anxiety in patients who often
2:09
have already experienced a major aortic event.
2:13
In your practice, how broadly do you apply genetic
2:17
testing and what really drives your decision
2:20
to test or not? I believe that knowledge is power.
2:25
And this is what I tell the patients, that knowing
2:27
the variant that they have, if we can diagnose
2:31
it, can not only change their management, as
2:34
you mentioned, but also gives them information
2:36
of what we know of that particular variant today.
2:40
And I appreciate what you're saying about the
2:42
anxiety. That is true. But in reality, the major
2:45
aortic event is quite traumatic already. So I
2:48
think... One of the ways people can cope is by
2:51
trying to understand why this happened to them.
2:53
Certainly, the other component of anxiety can
2:55
be related to the patients who may have not experienced
2:57
an aortic event yet, but potentially are at risk
3:00
because they have a family history. But again,
3:03
I think knowing this information is quite powerful.
3:05
There are a lot of barriers to testing. We actually
3:08
surveyed the vascular surgeons in 2023 and published
3:12
a paper in 2024 at Annals of Vascular Surgery
3:14
looking at these barriers. And as you mentioned,
3:18
cost. was shown as a barrier. But in reality,
3:20
I think this is important for the listeners to
3:22
understand that today genetic testing is cheaper
3:25
than a CT scan or an echocardiogram or a stent.
3:29
So the cost should not be a barrier at this point.
3:32
The bigger barrier is implementation, meaning
3:35
access to genetic expertise, workflows, as well
3:38
as having people who are experts in interpreting
3:41
the findings that we're seeing, particularly
3:42
when we see variants of unknown significance,
3:45
and then also integrating the results into routine.
3:48
clinical care. So we do see that, again, there's
3:51
not as much referrals as we would like. And also
3:54
from an implementation perspective, that is still
3:56
a barrier. Building on that, we have some evidence,
4:01
for example, from studies in vascular Ehlers
4:05
-Danlos, suggesting that early medical therapy
4:08
with seroliprolol or beta blockers can slow disease
4:11
progression. Do you think that early detection
4:14
through broader testing could meaningfully change
4:17
outcomes, or are we overestimating its impact?
4:22
No, I do think it does, actually, because the
4:24
value of earlier diagnosis is time, right? You
4:27
give people time to start the medical therapy,
4:30
to optimize their blood pressure, to lifestyle
4:32
modifying factors like quitting smoking and moderate
4:35
exercise, and then knowledge about what they
4:37
should watch for. We recently looked at 200 people
4:41
with Marfan syndrome, and the outcomes were correlated
4:45
with the timing of the diagnosis. So the earlier
4:49
they're diagnosed, the better the outcomes. that's
4:52
a surrogate marker that they have now entered
4:54
the system, whether they received more education
4:56
or had more medical therapy, that that makes
4:58
a difference. I think it's harder to sort that
5:00
out yet in vascular EDS, but we have enough.
5:02
large of a cohort to also investigate that study.
5:06
The study that you have from Europe that's important
5:08
to mention is by Frank and colleagues where they
5:10
looked at the B -BEST trial and they looked at
5:13
the outcomes decades later after starting therapy.
5:16
And again, people who are in medical management
5:18
did better. And you saw a similar study out of
5:21
the Sheffield group looking at vascular EDS and
5:23
again showed that people who are on medical management
5:26
did better. So these natural history studies
5:28
suggest this as well. And moving to intervention,
5:32
we know that a new reason rupture can occur even
5:35
below standard threshold in these patients. Yet
5:39
guidelines are still largely based on diameter.
5:42
But in genetic aortopathy, is diameter really
5:46
enough? Or does the dynamic behavior of the aort
5:50
over time matter more? So I do think that, unfortunately,
5:54
what we still have is the diameter as a metric.
5:58
Specifically in genetic erythropathies, we do
6:01
have something that's a little bit more important
6:03
that matters here is family history. The specific
6:06
genetic mutation, the specific genes that are
6:09
there, and those things kind of express different
6:12
fragility, have different expressions as far
6:15
as their clinical behaviors. And so I think specifically
6:18
in the genetic erythropathies, we have a little
6:20
bit better data to help us actually make more
6:23
personalized information. We have a little bit
6:26
more problems doing that with the general population
6:29
where we lack information about family history.
6:31
So maybe in my opinion, we need a little bit
6:34
more data to try to find other information about
6:37
how does the aortic tissue behaves and what other
6:40
metrics can predict rupture and aneurysm growth
6:45
better than just diameter. And I think there
6:47
are more and more advanced imaging modalities
6:50
and other modalities that are trying to show
6:52
us that. So I'm hoping in the future we'll have
6:54
other metrics. than just diameter. And I agree
6:56
100 % with what you said. I think this is a very
6:59
practical approach. I tell the family we use
7:01
something, the idea of this is biological twinning,
7:04
where we look at the family members because that
7:06
is useful information. There's the closest genetically
7:08
to the family member, whether or not they have
7:11
a known genetic diagnosis or not. So that's one
7:14
methodology. The other one is we are trying to
7:16
understand this idea of arterial and aortic vulnerability
7:19
and understanding that a four and a half centimeter
7:22
aorta is not the same as a four and a half centimeter.
7:24
a half centimeter aorta on somebody else, particularly
7:26
if the body size is different or the native arteries
7:29
are substantially smaller. So the proportionality
7:32
of the aneurysm to the native aorta, I think
7:34
matters in my opinion as well. So I look at all
7:37
of that to better understand. And I look at the
7:39
growth rate, of course, over time. That is another
7:41
objective measure that we can see over time.
7:44
The other component, if somebody ruptured an
7:45
artery in the past at a smaller size, then that
7:49
is useful to guide us for the next artery. So
7:51
if you have one iliac artery that ruptured, at
7:53
one and a half centimeters, then it is fair to
7:56
expect that the other iliac artery is not going
7:57
to wait to become four centimeters before you
8:00
treat it. So you can also individualize that
8:02
to the person. And a related question, Professor
8:06
Afifi, concerns women. Do you think current threshold
8:11
adequately reflect sex -specific risk, or are
8:14
we underestimating risk in female patients with
8:17
genetic orthopathies? And does age, particularly
8:21
in women of childbearing age, influence the threshold
8:24
for intervention? So in general, unrelated just
8:30
to the genetic erotopathy on sex differences
8:32
in erotopathies and how they behave, we don't
8:35
have a lot of data. Most of the data that we
8:37
have historically in any of the aortic aneurysm
8:40
studies and guidelines are based on studies that
8:43
had majority of participants are men. And I do
8:45
believe there are multiple aspects. So women
8:47
at baseline have smaller aortic size if they're
8:50
aortic. And so many people have sometimes compared
8:52
to body surface area, not just the aortic diameter.
8:57
take that into account, but also the impact of
9:00
hormonal exposure over life and the protection
9:02
of estrogen versus estrogen. And there's very
9:05
little data on that and how much does that impact
9:08
your risk of developing an aortic aneurysm in
9:13
the future. And those differences also... are
9:18
relevant in women with genetic aortopathies as
9:22
well. And now I think the biggest risk factor
9:24
when we're talking about this is that pregnancy
9:27
by itself is a risk factor. And then add to it
9:29
a component of having a genetically triggered
9:32
disease, then you're adding another component
9:34
to the game. And so some of the things that I
9:37
do talk to my young patients who are in childbearing
9:40
age that have an aortopathy or a family history
9:43
of aortopathy or developed a dissection is having
9:45
that discussion with them about family. planning
9:47
because it definitely increases the risk of having
9:50
an aortic event during the pregnancy. If age
9:54
by itself is something that has a limit as far
9:57
as that discussion, I don't think so. No one
10:00
has really proven that there is a specific difference
10:02
between at what age does a woman get pregnant.
10:05
That's not something that we do correlate with,
10:07
but just any pregnancy, you do have that discussion
10:10
with them. Now, let's move to treatment strategy.
10:14
European guidelines still suggest open repair
10:18
in most patients with genetic orthopathies. However,
10:22
in real life, many of these patients present
10:24
with complex disease progression and prior surgery,
10:28
creating challenging redo situations. Do you
10:31
think we are still too restrictive regarding
10:33
endovascular repair in these patients? Or is
10:36
caution still justified? I think caution is absolutely
10:41
justified. But I also think that conversation
10:44
has become more nuanced. It's not just simple
10:47
open versus endovascular dichotomy. So historically,
10:51
the caution has come from well -founded reasons
10:53
where we know that these patients have abnormal
10:56
vessel wall biologies. They have vulnerable aortic
10:58
walls that are at risk for these retrograde aortic
11:01
dissections, for example, or senes or endoleaks.
11:04
And they're also young. So we think about the
11:07
device durability over a lifetime. And again,
11:10
you see this need for repeated secondary interventions
11:13
over a lifetime as well. So these concerns are
11:15
real and should not be minimized. We even shown
11:18
that the risk of retrograde dissection is elevated
11:21
among people with family history without a known
11:23
diagnosis. We published this data in 2021 showing
11:25
that rate of retrograde aortic dissection was
11:28
about 13 % in people with familial aortic disease.
11:32
But at the same time, all the patients that we
11:34
see in practice a lot of times are more complex
11:37
than the patients that are in... in these guideline
11:39
statements. Many have had prior aortic operations
11:42
or hostile reoperative anatomy or progressive
11:45
distal disease, or maybe present in an emergency
11:48
or high -risk setting where purely an open strategy
11:50
is not feasible or maybe carries substantial
11:54
morbidity. So for me, the question is not whether
11:57
endo should replace open. It should not. But
12:00
how do we incorporate endovascular repair in
12:03
a thoughtful, selective, and safely approach
12:05
in these patient populations? Sometimes it can
12:09
be abridged as a temporizing strategy. Sometimes
12:11
it can modify your operative intervention to
12:13
make it less of an invasive operative intervention
12:16
if you need to. I'm curious to see what Dr. Afif
12:20
thinks. I completely agree with that. And there
12:22
has been publications also from a large group
12:27
of endovascular. And when you looked at the cohorts,
12:30
I think the ARC group, when they had a low...
12:33
complication rates. It's basically exactly what
12:35
Dr. Shahub just said, that most of their endovascular
12:38
interventions has been in patients who had prior
12:40
interventions. So their proximal or distal landing
12:42
zones were in grafts. And so it shows that when
12:45
you have those interventions done in the selected
12:48
patients where you can combine them, so you avoid
12:51
the redo because those are higher, more complex
12:54
cases where higher morbidity and mortality. So
12:57
if you kind of choose those patients and you
12:59
select When do you do that? And you have a surgical
13:03
landing zone, you lower the risk of the complications
13:05
from endo. I think you can give patients kind
13:08
of like the best of both worlds if you want.
13:12
And as we've said, many of the patients present
13:15
acutely not diagnosed. And much of the patients
13:18
who, for example, present with acute type B are
13:20
getting stent grafts immediately. So a lot of
13:23
the patients with genetic... disease or getting
13:25
T -bars not knowing that they have genetic disease,
13:28
right? And so a lot of times you can also see
13:30
how they're behaving. And so if they behaved
13:32
once okay with it, that sometimes can be a hint.
13:35
And I think also, if I'm not mistaken, Dr. Shalhoub
13:37
have presented a case or two from some of her
13:41
patients where they've had an endo and if they've
13:44
behaved well with it, she kind of learned from
13:46
it for another family member, whether they would
13:48
behave well with it or not. My hope that maybe
13:50
in the future innovations where endo will be
13:52
a solution, When we think a little bit outside
13:56
of the box and not just use the same kind of
14:00
technology, but think a little bit differently
14:03
in a way as far as the material or the mechanism
14:07
of how the stent works. Very interesting. And
14:11
if you opt for endovascular treatment in the
14:15
setting of dissection, where the goal is to adequately
14:18
cover the entry tear, How do you minimize the
14:21
risk of complications such as CNEs? So I would
14:27
say patient selection matters, obviously. And
14:30
when you look at these patients, a couple of
14:32
components. One, you know, what is the goal of
14:35
the TVAR? Are we doing this as a life -saving
14:37
intervention? Are we doing this to treat malperfusion?
14:39
Is there rupture? So that matters in terms of
14:42
how much I want to cover and where I'm going
14:45
to land. So from a technical standpoint, I really,
14:49
my goal is to minimize the mechanical stress
14:51
on the fragile aortic wall. And that is driven
14:54
primarily by sizing. where I avoid aggressive
14:57
oversizing. So less than 10 % oversizing or even
15:01
one -to -one ratio. And then paying attention
15:03
to the landing zone anatomy and how much tortuosity
15:06
and angulation there is, because I'm trying to
15:08
avoid the excessive radial force and angulation
15:11
forces on the aorta, which is where the new entry
15:14
tears are going to form. And more importantly,
15:17
of course, this is not a treat once and forget
15:18
procedure. You definitely have to follow them
15:20
closely. And I have spoken about this before,
15:23
where I think the aortic arch is an unstable
15:25
landing zone, particularly in people with TGF
15:27
beta and Marfan syndrome. And so those folks,
15:30
I think, ultimately will require an arch repair
15:33
in the future. So I would not just leave a T
15:35
-bar in there alone. I have used the strategy
15:38
of using bare metal stents as well across the
15:40
arch in select patients who I felt had excessively
15:44
fragile arteries. And I was concerned about this
15:47
retrograde dissection. And we're just about to
15:49
actually submit this to JVSCIT as a technique,
15:51
as a temporizing measure adjunct. And what about
15:56
you, Professor Afifi? Yeah, I completely agree.
15:59
I think the biggest thing is trying to avoid
16:01
oversizing. Again, you want to try to minimize
16:03
any radial force on the tissue. You want to really
16:07
respect the tissue. And I think one of the things
16:08
when you think about endo is like when you've
16:10
done enough open with those tissues, you kind
16:12
of respect the tissue. You know how fragile it
16:14
is. So if you're going to land distally, you
16:15
want to try to make sure that you're landing
16:17
in a straight segment of the aorta rather than
16:19
right at the torturosity segment. And again,
16:22
the indication. If you're doing it for a rupture
16:24
and an aneurysm, you're going to have to make
16:26
sure that you're covering more. If it's just
16:28
for the malperfusion, then less is better. So
16:31
I don't have to cover as much, just as long as
16:33
I cover enough to make sure that the malperfusion
16:35
resolves. And related to that, in a neurismal
16:39
disease, how do you balance the need for adequate
16:43
oversizing to achieve a durable seal with the
16:47
risk of intraprocedural rupture in a fragile
16:49
aorta? So again, endo is not going to be my first
16:54
choice unless I have a surgical landing zone.
16:58
If I have a surgical landing zone, then you don't
17:00
really much worry about the oversized because
17:02
you're landing in a graft. But if I am landing
17:05
in a natural tissue, then yes, you're going to
17:07
be very cautious about landing, about ballooning.
17:10
And I would add to this to avoid ballooning these
17:13
landing zones too. We didn't talk about that,
17:15
but I think we have to be very cautious because
17:17
exactly we're talking about a fragile aortic
17:19
tissue. So ballooning definitely increases your
17:22
risk of rupture interoperatively. And it's worth
17:24
mentioning complex aortic repair here for stent
17:27
grafts that require branch grafts, if you will,
17:30
specifically or fenestrated EVARs with stenting
17:32
of the branch vessels. We do know, for example,
17:35
in Loewy's -Dietz syndrome and in vascular EDS,
17:38
the medium -sized arteries are at risk for dissection.
17:40
So that population specifically, I'm very cautious
17:44
when we talk about doing a complex repair with
17:48
stenting into the renals or SMA or celiac. In
17:51
contrast, for example, Marfan syndrome, the FBN1
17:55
variants, even though the aorta is fragile, I
17:57
think they can tolerate branches into the grafts.
18:00
So I know that several studies are looking at
18:03
that specifically for the complex repair, but
18:05
I would say that should be tailored to the known
18:07
variant that you are dealing with. So TGF -beta
18:10
and COL3A1 are particularly red flags, and I
18:13
just don't think they'll tolerate branch. vessel
18:15
interventions as well as somebody with Marfan
18:18
syndrome, for example. I personally would still
18:21
be very cautious with doing things that are complex
18:24
and we're not knowing, but I'm also knowing that
18:26
a lot of the places and other people are doing
18:28
it. So I think that in the coming few years,
18:30
we'll get more and more data that's being published
18:33
about this, and we might have more information
18:35
to kind of guide some of those questions. And
18:38
given the complexity and risk of these procedures,
18:41
both in a neurismal disease and dissection, Do
18:45
you anticipate specific bailout strategies already
18:48
at the planning stage? And what are your go -to
18:51
options? Of course, any of those patients, if
18:55
you're going to think about having to do any
18:57
endo, you're always going to have to make sure
18:59
that you're able to do the open bailout. So if
19:02
you're going to do an endovascular approach and
19:04
the patient has a retrograde type A, you need
19:06
to make sure that you have a backup with a cardiac
19:09
surgery available. And so you have to make sure
19:12
that you're doing these procedures in a place
19:13
where you have on a multidisciplinary team. You
19:15
need to be able to convert to open if you need
19:18
to. Of course, needless to say that the minute
19:20
it converts to open, especially emergent, it's
19:24
never an easy or simple procedure If it's ruptured,
19:27
it's even more complicated. I agree with what
19:29
Dr. Afifi said. I can think of a patient who
19:32
I took care of who has Marfan syndrome, and we
19:35
really needed to do a TAMBI on him rather than
19:38
open repair because he just was not going to
19:39
tolerate an open repair. And we did biologically
19:42
informed decision -making with this, and it was
19:44
a shared decision -making with him saying that
19:46
he would likely have retrograde dissection. It's
19:49
just a matter of when, and he sure did. A week
19:50
later, we had to extend the T -bar to zone two
19:54
that ultimately... he underwent an arch repair,
19:56
which he recovered well from. So we know it's
19:59
a high -risk operation. The other thing, not
20:01
in the bailout per se, but in terms of the secondary
20:03
intervention, it is my observation that they
20:07
are at high risk for type 2 endoleaks from the
20:10
intercostal arteries. And I think the frequency
20:12
is higher than the general population. And I've
20:15
had several people with these genetic conditions
20:17
that we've had to do endovascular repairs on.
20:19
And ultimately, we get in the setting of rupture,
20:21
for example, or malperfusion, and ultimately
20:23
had to work with our IR colleagues on embolizing
20:26
these lumbars or even direct sac embolization,
20:30
trans -thoracic sac embolization. I don't have
20:33
stats in terms of how frequently we see that,
20:35
but it is my impression that they're higher risk.
20:37
They just, for some reason, do not seal those
20:39
endoleaks, these type 2 endoleaks. Now, looking
20:43
at the topic more broadly, these are often young
20:47
patients and we are essentially committing them
20:50
to lifelong aortic management. Do you think we
20:53
still focus too much on single interventions
20:56
rather than on overall lifetime strategy? And
21:01
eventually, what are the cornerstones of a lifetime
21:04
strategy in this patient given the cumulative
21:06
risk of progression and re -intervention over
21:09
decades? I mean, I think this is important to
21:14
remind them that this is a lifetime strategy.
21:17
The entire aorta is diseased. These are young
21:20
folks who are at risk for subsequent disease.
21:23
There's a risk for secondary interventions, number
21:25
one. Number two, in the people with endovascular
21:29
repair, it has been shown that there is for secondary
21:31
interventions. And one point that's worth mentioning
21:35
is that we are changing ultimately the hemodynamics
21:37
of the aorta. We're taking a fragile, very pliable
21:40
aorta. You see these people, they have wide pulse.
21:42
pressures, for example, at baseline, very malleable
21:45
aorta, and we're putting a stiff endovascular
21:47
device in, and now you're transmitting the forces
21:49
distally. And we've seen this in even aortic
21:51
dissections, just even without a genetic diagnosis,
21:54
that there's progression of the distal disease.
21:57
And I do think that happens. The other component
21:59
that you have to also think about is risk of
22:01
heart failure in the long term. That population,
22:03
for example, Marfan syndrome and Loewy's deeds
22:05
are at risk for heart failure, generally speaking,
22:08
as part of their syndrome. And then the question
22:10
is, are we accelerating this? When we replace
22:12
the entire aorta. So not only do I talk about
22:15
saying that it is aortic care in the long term,
22:17
but also we have to think about their heart function
22:19
in the long term as well. It's not just a single
22:24
procedure. It's a lifelong kind of follow -up,
22:27
and it's adjustment to them, right? It's how
22:30
do they navigate their life. And so it's taking
22:33
young people living their life, wanting to go
22:35
to the gym, wanting to do sports. So you're limiting
22:39
them in multiple aspects of their life. They
22:41
want to have family. What's the meaning of that
22:43
for children? And sometimes they do have children
22:45
who have the disease. So it's something that
22:48
takes them through their life. And so it's a
22:50
follow -up through that. And as Dr. Schultz mentioned,
22:53
it's impact on their heart, cardiac disease as
22:56
well. I think the approach has to be more than
23:02
just a procedure. It's kind of like a patient
23:04
-centered and it's a lifelong follow -up. And
23:07
many of the patients stay with us for a long
23:09
time, follow up. You can see them, you see their
23:11
families. There are aspects of this that we didn't
23:14
even touch on or talk about, but the mental health
23:17
aspects of this, the burden of this, right? Every
23:20
event that we talk about has 30 % of patients
23:23
with aortic dissection develop PTSD. What's the
23:26
impact of that? I have patients who have dissections
23:30
that are related to pregnancy. They are afraid
23:32
to stay alone with their baby afterwards because
23:34
what if something happens when they're alone
23:35
with the baby? So there are aspects of things
23:37
that we don't talk about. We are not the experts
23:40
on. As a team who takes care of those patients,
23:42
we'll have to address every aspect of this as
23:45
a lifelong. So it's not just the aorta and it's
23:48
not their one surgery. Aortic centers that care
23:51
for these patients, you will see often that there
23:54
are multiple members of the team that have multiple
23:56
specialties, and we see them along multiple years,
23:59
and we know them and many members of their family.
24:03
I was going to add to what Rana was mentioning,
24:06
is that we, in the aortic dissection collaborative,
24:09
when we work with the patient population living
24:11
with dissections, they identified mental health
24:14
as a core research priority. The John Ritter
24:17
Foundation worked with a group to come up with
24:20
a guide for mental health that can be given to
24:24
the survivors of aortic dissection. So that resource
24:26
is freely available, can be downloaded as a PDF,
24:28
and can be given to the patients. So I think
24:31
that is a valuable resource. resource. Yeah,
24:34
definitely. And our team, and our clinic, for
24:36
example, we have our own, one of our, Dr. Sandhu,
24:41
one of our team members, she just finishes her
24:43
thesis in psychiatry, which focuses on mental
24:46
health and cardiovascular, especially neurotic
24:48
disease. She had developed our own quality of
24:51
life focused aortic. Every aortic patient that
24:55
comes to our clinic gets surveyed every visit
24:59
to make sure that we screen them for any signs
25:02
of anxiety, depression. And if red flags come
25:04
up, we make sure that we refer them for the right
25:07
treatment. Speaking of follow -up, how do you
25:11
structure follow -up after repair, particularly
25:14
after endovascular treatment? I'm aggressive
25:19
in terms of imaging, whether it's open or endovascular.
25:22
So I do scan people. After endovascular repair,
25:25
I scan them before they discharge from the hospital.
25:28
After open repair, I will scan them at one month
25:31
because I'm similarly looking to see if there's
25:33
any new entry tears that had formed. And then
25:36
after that, if everything looks great, for endo,
25:39
I would do three months, six months, one year.
25:41
For open repair, I would do it annually, one
25:45
year after. And then if that looks great, then
25:47
I'm done with it. surveillance for the open repair.
25:50
Dr. Rafifi, what do you do? Yeah, it's similar.
25:53
I think it also for me depends on what I fixed
25:55
and what's still there in the patient. So for
25:58
example, even if we did open If we did it just
26:00
partial or just the thoracic portion, there is
26:02
still an ascending portion or there is still
26:05
an abdominal portion, then there will still be
26:07
a follow -up mostly annually or biannually, depending
26:10
on what residual disease there is. As far as
26:13
endo, I agree with Dr. Shalhoub, the same protocol.
26:17
Having said that, some patients progress faster.
26:19
I have to adjust the protocol according to that.
26:22
Before we conclude, I would like to bring this
26:25
discussion into real -life decision -making with
26:29
a couple of clinical scenarios that reflect situations
26:32
we commonly face in practice. Let's consider,
26:36
Professor Fifi, a case of a 50 -year -old man
26:39
with Marfan syndrome, previous ascending repair
26:42
for a type A dissection, now presenting with
26:46
a growing post -dissection aneurysm involving
26:48
the arch and the proximal descending aorta. but
26:51
not the abdominal part. How would you approach
26:54
this and how do you balance open versus hybrid
26:58
or total endovascular repair in this case? So
27:04
if we're saying that it's a larger size, sometimes
27:06
the patients require first to have a redo repair
27:09
of that arch first in order for me to do an open
27:12
repair of the descending because otherwise...
27:14
it is more difficult to just suture to a five
27:17
centimeter. So if the arch is a five centimeter,
27:19
there is no point of you going, doing open and
27:22
estimosing to that. If you're talking about a
27:24
two or if it's about three centimeters and you
27:26
do fix the descending first and you leave the
27:30
arch for if he dilates in the future. He's 50
27:33
and he's fit. I still would approach first and
27:36
do open and repair first the descending. Again,
27:39
the risks in open and the risks for paraplegia
27:43
and everything else increases with the extent
27:45
that you repair. So if it's just thoracic, the
27:47
risks are lower. So if I don't have to do a complete
27:51
extent to repair, then I wouldn't just do it
27:54
just to do it because we're going there, right?
27:56
So it depends on how does my area of... anastomosis
28:02
looks like to make that final decision whether
28:04
first I go for a descending. Now, if I'm doing
28:07
it first descending and I decided that the arch
28:10
is not big enough to be repaired first, I will
28:12
do what we call a reversed elephant trunk, where
28:14
is the technique where I kind of invert all the
28:16
graft from the proximal portion so that if they
28:20
do need something in the future and they do need
28:23
the repair, redo arch, it's easier to kind of
28:25
just pull that graft up and kind of make it a
28:27
little bit easier from the proximal repair. I
28:31
would add a different approach in the sense that
28:33
if the arch is big enough to repair, the conversations
28:36
we'll have with our cardiac surgeons is to redo
28:39
the arch. Basically, it's a redo sternotomy,
28:41
fix the arch. Sometimes to make it easier, I'll
28:44
go ahead and debranch the left subclavian. So
28:46
they only have to deal with the innominate and
28:48
the left carotid. And then we also do the frozen
28:51
elephant trunk technique during that operation.
28:53
So that's sewn into the arch and it's really
28:55
stable. And again, the discussion is how long
28:58
is the piece in the frozen elephant? and trunk,
29:00
I think 10 centimeters while the risk of the...
29:05
spinal cord ischemia is lower than 15 centimeters.
29:08
So 10 centimeters is better, but we also have
29:11
to be mindful that 10 centimeters may end you
29:13
in the proximal descending aorta. So the angulation
29:16
is not favorable. So that's the other part of
29:18
the discussion. And we balance then a 10 centimeter
29:21
piece with a plan for secondary intervention
29:23
of extending it distally after they've recovered
29:26
from the first operation, understanding that
29:28
we're also transmitting the forces distally,
29:30
and that may be additional work that needs to
29:32
be done on the rest of the aorta over time. But
29:35
that is an alternative approach to open repair,
29:37
for example, in some patients. Open repair in
29:39
the sense that it is not the descending open
29:41
repair, but fixing the arch and making your way
29:44
now that the aorta is replaced from the root
29:46
all the way downwards in a sequential manner.
29:50
Now a second case, a young pregnant woman with
29:53
a vascular LSD and a small dissecting aneurysm
29:57
of the superior mesenteric artery. Professor
30:00
Shalhoub, how would you approach management in
30:03
such a delicate situation? This is a difficult
30:06
situation. So you're giving me a combination
30:08
of vascular ADS and pregnancy. My impression
30:11
is that the superior mesenteric artery dissections
30:14
and vascular ADS, the majority of them can be
30:16
managed medically. This particular person is
30:20
at significant high risk for peripartum complications,
30:25
whether it's in the SMA specifically or the rest
30:28
of the vasculature, because she is already now
30:30
demonstrating instability that is related to
30:32
these hormonal changes. So I would definitely
30:35
make sure that we have multidisciplinary care
30:38
around her. I don't think she needs an intervention
30:40
directly, but what she needs is aggressive medical
30:43
management and surveillance throughout the pregnancy
30:46
with the understanding that she is carrying a
30:49
high -risk pregnancy now, particularly because
30:51
she has both diagnoses. If the superior mesenteric
30:55
artery dissection is now leading to malperfusion,
30:58
then that is a very different scenario. I've
31:00
not encountered that specifically, but you would
31:03
need to address that in that context of emergency.
31:06
Similarly, with rupture, that would create a
31:09
problem where you just have to go to the operating
31:11
room and ligate the vessel. You can try, depending
31:14
on where the dissection is, if there's rupture
31:17
and where the rupture is located, you can also
31:19
try endovascular approaches. These are, of course,
31:22
heroic, life -saving measures. in the context
31:24
of rupture and somebody who is pregnant, but
31:27
you have to save the mother first. So you just
31:30
need to do what you need to do to save her and
31:31
get her out of trouble if she is ruptured. Thoughts,
31:35
Dr. Arfifi? Yeah, and that's exactly the thing.
31:38
Again, it depends also, I think things that we
31:41
think about our age of pregnancy when you make
31:46
these decisions. So first of all, when the patient
31:48
comes in as pregnant with some kind of either
31:50
aortic or vascular abnormality findings, dissection,
31:54
and they're referred with kind of like, oh, we
31:58
need to terminate so that, you know, there is
31:59
no risk. And the patient says, but what if I
32:02
don't want to, right? And so you're at that dilemma.
32:04
As Dr. Shalhoub said, I think at that point,
32:06
we discuss the risks and make the decisions.
32:08
And we do close follow -up. If there is no event
32:12
of life -threatening event, the treatment is
32:14
medical, very close follow -up. We can repeat
32:17
imaging. during pregnancy can do an MRI. Now,
32:21
having said that, if anything is life -threatening
32:23
in emergency, you can do a CT angio during pregnancy.
32:25
The level of radiation in CT angio is still tolerated
32:31
and it doesn't cause any damage for the fetus,
32:33
not a one CT angio. So routine follow -up and
32:38
planning it for the trimester. Usually, if we
32:41
find it out in the early trimester, we just make
32:43
sure at least that We have follow -up at least
32:46
in each trimester with new imaging. And then
32:48
we also plan electively for when do we want to
32:50
deliver. Do we want to take the pregnant patient
32:53
to full term or not? Because usually the majority
32:55
of the volume overload and everything else that
32:58
happens, happens towards the end of the third
33:00
trimester. We have that discussion, whether we
33:04
want it to come to full term or do we want to
33:06
deliver at week 34, trying to minimize the risks
33:09
around that time. And then we plan the discussion
33:12
around where do we have that delivery? What kind
33:15
of monitoring do we do it? What kind of delivery
33:17
do we do? So we kind of have all that discussion
33:19
with the multidisciplinary team. And in case
33:22
of an emergency, as Dr. Shahub had mentioned,
33:24
your goal is to kind of, of course, try to save
33:29
the mother. Having said that. If this happens
33:31
or occurs at a viable age of the baby, usually
33:36
the cut based on guidelines and everything else
33:39
is week 28. If that happens over age 28, a lot
33:43
of the recommendations will be a C -section and
33:46
hoping for the survival of the fetus. But anything
33:48
below that, you just go ahead and do first the
33:51
life -saving procedure for the mother and with
33:57
30 -40 % mortality, a fetus with with any anesthesia
34:03
and procedure that you're performing. To wrap
34:06
up, if you had to identify one priority for improving
34:10
current clinical practice in these patients,
34:14
what would it be? If I had to choose one priority,
34:19
it would be earlier integrated multidisciplinary
34:22
care for these patients, whether they're known
34:24
to have genetic erythropathies or suspected to
34:26
have genetic erythropathies. So actually, when
34:30
you look at the families with genetic erythropathy,
34:32
somebody who has a family history technically
34:34
has a genetic erythropathy, but the genetic testing
34:37
will only pick up 30 % of that population. So
34:40
70 % of the families have something, but we don't
34:43
know what they have. So I think this multidisciplinary
34:46
care is really important. We have the Northwest
34:48
Genetic Aortopathy and Arteryopathy Program Clinic.
34:51
This is a once a month. We're staffed by myself
34:53
and adult and pediatric cardiology and genetics
34:57
and genetic counseling, because I think it's
34:59
important to integrate the genetics, the imaging,
35:03
the medical management, our cardiac and vascular
35:05
surgery expertise, longitudinal surveillance
35:07
and family screening as all of that. And then
35:10
like Dr. Rafi, you mentioned mental health. assessment
35:12
and support to these patients and their family
35:14
members is very important. So I would say multidisciplinary
35:17
care. Yeah, I agree. Multidisciplinary care,
35:21
but I think also is the awareness. One of the
35:23
things that I do hear a lot from the patients
35:25
is the frustration that it's not much is known
35:28
in the general population. In the medical field,
35:32
a lot of that, they kind of encounter lack of
35:35
knowledge when they get to the emergency departments
35:37
or when they encounter care in their primary
35:41
care, family physicians or outside of the experts.
35:45
And so I do think awareness and multidisciplinary
35:49
care is what's important because I think the
35:51
more we hear other people's opinion, we discuss
35:53
this, we learn more about it, we're aware more
35:56
of things, and we talk about it. And as Dr. Shalhoub
35:58
mentioned, it's not just the positive genetic
36:00
testing that matter. I think the family history
36:03
matters. We've confirmed that as well in one
36:06
of our studies where the highest risk factor
36:08
for dissection in pregnancy was not positive
36:11
genetic testing. It was positive family history.
36:13
And finally, looking ahead, what do you think
36:16
is the biggest unanswered question in genetic
36:19
orthopathies today and how? should we ideally
36:23
address it? I would say for me, the biggest unanswered
36:26
is how do we move from anatomy -based decision
36:28
-making to biologically informed decision -making?
36:32
I would like, Dr. Rafi, if you mentioned the
36:34
family history. So currently we have diameter
36:35
family history and syndrome level diagnosis,
36:38
which are all important factors, but they don't
36:41
explain the variation that we see even within
36:44
syndromic conditions, why somebody dissects and
36:46
ruptures at a small arterial diameter, why others
36:49
can grow a large aneurysm, for example. example.
36:52
I can give you two examples of people with vasculitis
36:54
with vastly different genotypes and phenotypes.
36:58
And so really the question is, how do we measure
37:01
vascular vulnerability in a way that is clinically
37:03
useful? One of the things that we're working
37:05
on now is looking at dermal or skin biopsies
37:08
and looking at the collagenopathy and elastinopathy.
37:12
Those are the terms that I'm using to think about
37:13
the collagen architecture or collagen fibril
37:16
diameter changes and heterogeneity and looking
37:19
at the elastic fiber. degradation in people.
37:22
And taking that in context with understanding,
37:26
combining that with the genotype and the clinical
37:28
phenotyping and their imaging and operative outcomes
37:30
and how this correlates to their arterial tissue
37:33
and looking at the outcome. So the question is
37:35
that I'm having now is, can we use the skin as
37:38
a surrogate into understanding what is happening
37:40
in the aorta and the arterial tissue, particularly
37:42
in the context of genetic testing that is negative?
37:45
So I do think the next era of genetic what is
37:50
the diameter only and what is the genetic type,
37:54
but also what is the trajectory of this biology
37:56
and what is the safest lifetime strategy for
37:59
this particular patient? So for me, the unanswered
38:03
question would be if there is a way for us to
38:06
have an early detection of the heritable thoracic
38:10
aortic diseases prior to an event, because many
38:14
of the patients are de novo. They are the first
38:16
ones in their family. So even if we don't have
38:17
a family member, history or until they have an
38:21
event. And unfortunately, we have many stories
38:23
of patients that get diagnosed only after that
38:26
first event and that mortality that we kind of
38:28
get from autopsies in the morgue. So is there
38:32
a way for us to try to diagnose them early and
38:34
have that early detection at multiple levels,
38:36
right? There are screenings in schools and there
38:39
are screenings at multiple levels of the PCP.
38:41
So are there any level that we can actually get
38:43
that early detection? There are ways that I'm
38:48
hopeful for. There are certain developments.
38:51
For example, they're developing an app where
38:53
just by taking a look at a picture based on them
38:57
analyzing with AI multiple pictures of patients
38:59
that had different heritable erythropathies,
39:02
they can predict with high predictability whether
39:05
that patient has a certain known mutation or
39:08
not. Now, again, it's very limited based on now
39:10
knowledge that we have, but I'm hoping that in
39:12
the future with all the technology that we're
39:14
developing. We might have ways by just taking
39:17
a look at a picture or a history or just a regular
39:20
lab. We can get some hints that can tell us that
39:23
this patient has an aortopathy and we can prevent
39:26
that first life -threatening event. I'd also
39:30
like to put in a quick plug for the Vascular
39:33
Genetic Consortium. So this is an effort that
39:35
we're doing here in the United States where we're
39:37
trying to get multiple centers aligned. We're
39:40
in the process of creating these IRBs and the
39:42
data sharing agreements. Dr. Afifi is one of
39:45
our collaborators as well. And so that is also
39:47
an opportunity to increase the number of patients
39:50
and have bigger cohorts of patients, particularly
39:53
in the setting of a fragmented healthcare delivery
39:55
system, which is perhaps different than what
39:58
is in Europe. but in the US that is one of our
40:01
challenges. But if we can come together and we're
40:04
in the steps of making this infrastructure happen,
40:06
that will also help us with this information
40:08
as we move forward too. These are very interesting
40:11
perspectives. So Professor Fifi, Professor Shalhoub,
40:15
thank you very much for joining us. This has
40:17
been really an insightful discussion. And thank
40:20
you to our listeners for turning into the ESVS
40:23
podcast. Please follow the ESVS socials to stay
40:27
updated on new releases. Talk to you soon. Bye!