Hello, my name is Paul Freedman.
I'm Chair of
the Department of Cardiovascular Medicine
at Mayo Clinic and the Midwest.
And today had the pleasure of speaking with
my colleague, Dr. Graceland,
Vice Chair for the division
of circulatory failure,
expert in the management
of heart failure patients.
Dr. Lynn, thank you for joining me.
Thanks so much for having me.
So today I want to talk about
matrix management of mitral regurgitation
to help people with heart failure.
So first of all, what
is functional mitral regurgitation?
It's a great question.
So functional mitral regurgitation is
that it's a pretty common problem
that we see in our clinic.
We distinguish functional
mitral regurgitation
from what might be termed
primary organic
mitral regurgitation because there are
differences in how we approach
patients and how we approach management.
So we typically think of
functional mitral regurgitation
as something that's
that secondary that happens to
the mitral valve because
of what's happening in the rest of the heart.
So in heart failure we expect
that the ventricle where we model.
So if patient has ischemic cardiomyopathy,
there may be regional wall
motion abnormalities.
Patient has dilated cardiomyopathy,
the venture will be enlarged and that'll have
effects on the mitral valve structured.
So instead
of thinking of mitral regurgitation,
that's because of a direct problem
to the mitral valve like a flail leaflet.
In this case, we have
changes to the mitral valve architectures.
So the annulus will change,
become dilated and patients with
dilated cardiomyopathy
it'll become a little bit flatter.
That results in some tethering
of the leaflets.
If the patient has
regional wall motion abnormalities,
for example, because
they had a prior infarct.
We might expect that
to pull down or to change
position or the papillary muscles and
that can affect the mitral valve.
So basically what we're saying
is that it's it's a problem with
the ventricle that then
causes a secondary problem
with the mitral valve and it leads
to problems with co-optation.
And that's what results
in mitral regurgitation.
So fundamentally, when you're
looking at it with an echocardiogram,
you can clearly see the difference between
organic and functional mitral regurgitation.
I would say cerumen
when I approach one of these patients and
they ACA lab because
in addition to seeing patients in
heart failure clinic will also be
reading their echoes and interpreting
the echos is I'm seeing a patient
that I always look at
the mitral valve and I see a patient with
severe mitral regurgitation and
think what's the mechanism?
Because that's immediately how
I split my mind,
how I think about treating this patient.
So I can see that there's a problem with
the mitral valve itself is prolapsed.
It was a flail segment Or I could see that,
but it's really a tricky problem.
Ventricular problem relating to
changes in mitral valve architecture.
And then maybe hemodynamic
changes increase preload.
Other factors that lead
me to think that the mitral regurgitation,
it's secondary to other
things that are happening with the heart.
So heart failure clinic,
you see a patient and you notice that they
have functional mitral regurgitation.
How do you treat that?
How does that fit into
the overall treatment paradigm?
So in contrast to a patient that has
primary organic mitral valve disease,
where I think that the problem is
that the mitral valve is abnormal.
It's flail or it's
prolapsed and I need to fix
that mitral valve because
that's called mitral regurgitation.
And the mitral regurgitation
cause the heart failure.
Here I'm thinking that that it's more
of a structural problem
with the heart ventricular problem,
even dynamic problem that's lead
to functional mitral regurgitation.
So I think more about
how can I change the structure of the heart?
How can I change the heme dynamics?
So what can I do to
improve
this patient's heart failure that will
hopefully help heart to remodel
the way that
the mitral regurgitation gets better.
So I think first,
is this a patient who's falling reloaded?
Can I tell that from
the physical exam or do I
see increased filling pressure on the ACO?
That tells me what I need to do
as offload this patient by
decreasing preload and putting
the patient on higher doses of diuretics.
And also look to see whether this is
a patient that can be
optimized with medical therapy.
So we know that guideline directed
medical therapy aimed
at improving hemodynamics,
neurohormonal blockade,
that, that can help to
improve function hemodynamics of the heart,
then that might lead to improvement
in mitral regurgitation.
Which is another important point
about functional mitral regurgitation,
is that it's dynamic
and it really changes depending
on what a patient's
particular presentation is like that day.
So for example, someone comes
into the hospital very,
very volume overloaded.
We might expect to see
more much regurgitation.
Then at a later time when we had
a chance to optimize them,
put them on medical therapy
and diaries from them.
Maybe the mitral regurgitation
is a little less prominent.
Church. So the heart volume
becomes a little small or
the leaflets and get closer
together and you get
less leakage kind of thing.
Yeah. Yeah. Let's get into it.
So what does electric lipid, who's eligible?
How do you pick people for it?
To my chocolate, them.
It's really been
an interesting technology and
product game changer and how we
think about mitral regurgitation.
Because I think for a lot of
times where a lot of years that we
thought of
mitral regurgitation as something that
happened with the later stage
of ventricular remodeling.
So the patient has
progressive heart failure and
progressive LV remodeling and then they
end up with functional mitral regurgitation.
And that, that's a consequence of what's
happening to the heart and
what's happening with heart failure.
And we wouldn't necessarily think
to fix it because
the patient might be too high risk surgery
and they might not necessarily have.
A lot of mortality or
survival benefit from doing that.
And the mitral clip, the
two matriculate main trials
that much FOR the French trauma
us trial, court,
trial really change that and
made us think about functional
mitral regurgitation as a target.
It's something we can treat
that might potentially
improve heart failure and
outcomes for this particular patient.
Instead of something that we've thought of as
this is the end result of
heart failure that we
would just leave alone and
managed medically as best we could.
So I think of a patient as
being eligible for my chocolate.
This is someone who
has been treated with medical therapy,
is optimized on
guideline directed medical therapy,
which today in 2002 we know means quadruple
therapy with a RAS inhibitor
or a beta blocker,
an SGLT-2 inhibitor and
spironolactone or an MRA.
We know that those patients who
are maximally optimized with
medical therapy still have
severe mitral regurgitation are symptomatic,
but those are the patients that we can
probably help with mitral clip
or Tier I guess is
the preferred term out which
is the transcatheter edge,
edge repair of the mitral valve.
And that, that optimization
of medical therapy is really the key.
It's defined those patients
completely medically optimize that
and still have severe MR.
Those are the patients that are
most likely to bond with it.
So just at a very high level,
what is the procedure was done?
So the procedure is done in the cath lab.
So rather than thinking of
an open heart surgery
conventional much about repair surgically,
it's a procedure that we do in
the cath lab and it's just like it sounds,
it's an edge to edge repair.
We think of that old Alpha ARE stitches.
He could sometimes to see
those in the ACA lab
where you look at
the mitral valve and it looks
like it's kind of clipped in the middle.
The surgeons put a little stitch
in the middle of the bow.
And you can see the mitral valve opening,
but that middle part always stays together.
So that's what the clip does in effect,
is that in the cath lab,
we can use an interventional approach,
non-surgical approach to place
this clip on the mitral valve.
And if one clip is sufficient,
you can use that to reduce
the amount of mitral regurgitation.
Valve will probably still leak some,
but a lot less than before.
And in some cases, if one clip isn't enough,
you can put multiple clips on to get
a better result and
less residual mitral regurgitation.
So with one flip than if
the leaflets article up getting the middle,
they're stuck together, then you have
two smaller orifices on
either side of the clip.
Yeah, exactly. So again,
if if you think about
how this looks like from
a short axis image of
the mitral valve where you can see,
you could see that, that clip down.
But if you think of
the donut and then you see
that clip down section in the middle.
And then on either side, two
offices that open and close.
So what kind of outcomes were seen in
the COAP trial and
the maitre if our trial
what my patients expect.
Because my first question,
the second one will be the two trials didn't
show the same outcome in terms of benefit.
And I'd like you just to comment on
the impact on patient selection.
Yeah, there's really been a lot
written about that topic.
I think it was really a surprise to people
first when co-op was positive and second,
then the French trial wasn't.
And really to think about
how to reconcile those results.
But I think actually the two trials
are very complimentary because
I think a really important difference between
the two trials is how they
selected patients to call out,
for example, is a positive trial
because the main thing
was that they were able
to show this improvement in
survival at which the French trial is not.
But even though the two trials
enrolled similar patients with
advanced heart failure and
dilated hearts who
had significant much regurgitation.
They were subtle differences in
the two patient populations
that I think are really,
really important in
terms of patient selection.
And if you think about it when you
put the two trials together, it's,
it really tells a story about how we think
about managing heart failure
and overall fits with what we've,
we've thought about
functional mitral regurgitation
and Howard thoughts have
evolved over the years.
So looking at the
two patient population side-by-side,
both trials require that patients were
maximally optimized on medical therapy.
That the COAP trial had
a fairly straight enrollment criteria where
the enrolling physician would
have to present the patient to
a central committee and
justify the type of
medical therapy that had been prescribed.
And having been someone
who enrolled in the trie can testify to
how strict criteria war it
so that it was important to
document if patients were not able to
reach a particular targeted medical therapy,
why that was so
that the committee could be very
satisfied that everything had
been done in Spanish was maximized.
My trough our trial also
require that patients we
intensified on medical theory,
the left to the treatment team,
to the local team.
So there wasn't that centralized committing.
Then when he looked at the outcomes
side-by-side and we'll GD&T arm,
the medical arm co-op.
Those patients had somewhat
better reduction and
functional mitral regurgitation
with medical therapy alone,
less heart failure event.
So it's suggested that maybe
the medical therapy was more
intense or at least more,
more uniform in that group
than it was in the mature R groups.
So that's really one important difference.
The second difference was that
the co-op trial put
a cap on how big the ventricles could be,
70 millimeters, which is
in the new heart failure guidelines.
Ventricles of less than 70 millimeters is
the criteria for being
eligible for my chocolate.
And that comes directly
from the co-op trials,
so they call it trial selected people with
smaller ventricles and more severe,
much regurgitation.
So you could say in a way.
It's disproportionate MR. for
the size of the ventricle,
whereas an FR the ventricles
tend to be bigger than
the IO or the way that
we we graded the severity of MR,
suggested that the MR was not as severe.
And then the third difference was
that the people on the call our trial
had on average a higher anti probably MP,
suggesting there may be sicker
and a little bit more decompensated.
So in, in, in a really high-level,
say in a co-op trial that they
really selected the patients
with the strictest and
most intensified medical therapy.
Where the ventricles for we're
not necessarily too big,
but they had the most severe MR.
So it's a really,
really highly selected group.
So that the way that I take away points from
that is that there may be
patients for the vegetables too big,
so it's kinda pass the point of no return.
And may be treating
the functional mitral regurgitation
isn't going to improve things.
But they are patients that I've
reached that point or
the sweet spot where
the ventricles remodel just enough.
You've given just enough
medical therapy and now's
the time to do the repair with my chocolate.
And maybe the patient will have benefits.
But it's a lot of sense
That's really clear and it
just underlines
the importance of patient selection.
To get that if you pointed
out that there's a reduction in mortality,
what other benefits my
patients see from undergoing
a procedure
if they're appropriately selected?
I would say that their optimal
outcome for me when
I'm setting a patient for my trick,
that procedure is that I want
to see the types of benefits that I
would say with any type
of therapy for heart failure.
That is, I'd like to see
an improvement in their hemodynamics.
So patients with decompensated
heart feather mitral regurgitation,
I expect the filling pressures were
quite high and then pulmonary hypertension,
which is secondary, would
be quite high or the
RV SP will be quite high.
These patients may have
more advanced renal function
as a consequence of having advanced hardware.
So I would expect to see symptoms improve.
I expect to see hemodynamics and credit
including secondary pulmonary hypertension.
And then in some cases,
as we treat these patients,
maybe that would be an improvement
in and other parameters as well,
such as renal function with IQ and
is as you look into
your crystal ball towards the future,
because it's really is a dramatic shift in
the way we treat patients with heart failure.
Do you see other dramatic changes
or what do you see as
the next big things to
help us care for people with Arthur?
To if we move beyond
the mitral valve and when we already
have transcatheter aortic valve replacements.
And now we have a pretty
clear way of thinking about
which patients are going to benefit
from transcatheter mitral valve repair.
Think the next frontier is
the tricuspid valve.
You know, we've, we've always talked about
this is the forgotten valve.
And in our patients
with advanced heart failure
eventually left heart failure
becomes by ventricular heart failure.
By
ventricular heart failure almost invariably
involves severe tricuspid regurgitation.
I think we've always struggled with
how to manage those patients.
So there's some really
exciting things happening in
the transcatheter realm for
interventions on the tricuspid valve.
And I'm hopeful that eventually
we'll find some type of a solution,
at least a pathway to managing
those patients in that percutaneous,
a non-surgical manner as well.
It really is striking
the new advances in
heart failure that it just
changing the field from drugs that
we never really thought
of as heart failure drugs,
but his diabetes drugs to trans
can therapies to more advanced therapies.
Dr. Grace Lin, thank you so
much for speaking with me today and
educating all of us and
new ways of taking care of our peg.
Thank you so much.
Thanks for having me.