G.'s invite speak on this topic.

Jason.

It's up is the director of biomedical
engineering or the company that you know

why the special on this is not a national
system or the beginning of the company to

do it doesn't want Jesus or less and you
have been resistant and method element.

You also know that it's nonsense if he
just looked at the manifold and biological

and Roy and functional and global
leaders senior sensor and design program

that's your great six minutes of making
the last rock of him from his previous no

less a new product development engineer
for my last R. and last year after this.

And sends it carcasses out
Johnson announced on ninety seven

year olds and he is seen by Bill and
the news from Give us a peek and

endless engineering mountain
from Florida and I must

order my stock we are positive
the House and the state the system

operation that he's already set up because
of the all of this being the piece leads.

So that we can see very clearly and
clearly and for

that I should suck more than
they need this far from.

Hello everyone.

I'd like to thank Dr Joseph and
all the organizers for

having me here today and I'm joined by
some other members from our company who

are going to help with the demonstration
of change in ways on my team and

also part it every year
as a summer intern.

So the approach we're taking with this
presentation is slightly different than

what you might have seen so far we're
going to focus as much on the method

particular method that's been used to
bring the technology that started as R.

and D. effort within academia
to commercial years and

there are several important factors
along the road that I think we're

driving with this excess that
we've seen so far today.

And I'd like to cover those and
they may seem obvious to you but.

They're very critical to
making the progress from

a research idea to your
commercial use particularly

the first one is that the idea needs to
be driven by an MET medical needs and

in this case in pressure sensing
companies organized around that idea and

then maintaining a clear idea for the
concept and philosophy for the technology

from start to finish it helps to keep
the path clear along the way and

then as far as how to tackle the challenge
you need to stay on top of the many

different technical challenges that
exist in bringing the concept to life.

It's not just a man's nanotechnology
a problem to get the device to work

involves other areas such as biomedical
and our IF engine airing which have

equally daunting and
difficult challenges to overcome and

finally if we have time at the end all
talk a little bit more about what our R.

and D. team and the rest the company
is mostly focused on today which

is the the last stage of the work for
our fairly application

which involves our clinical pivotal little
clinical study for our P.M.A. approval.

So pressure monitoring is a political to
many different therapeutic areas within

the medical field and when I talk about
pressure I mean invasive pressure at

the location of interest and with pressure
information within the hospital setting.

Doctors are able to make decisions
based on this information and are able

to know very quickly and accurately what
the status is of a particular organ or

any other area of interest and normally
this sort of information is not available

nine basically So
there is a constant dilemma on whether

it's worth it to go in with a catheter to
measure the pressure in that area in order

to know what it is versus just working
with whatever other symptoms exist.

Within these areas two particular
areas stood out at the beginning as

ones that were major issues in
the health care field as we

heard earlier in the last presentation
heart failure is a major problem which

we'll get into a little more and then also
aortic aneurism is both of these areas

are very linked to pressure and knowing
what the pressure is is very helpful and

the management of these diseases.

As we heard in the previous presentation
the trend over the last twenty years has

been a reduction in the rate of deaths
due to Q coronary higher cardio fortune

due to improve care or an angioplasty and
other treatments like that but

then these patients go on to live with in
peri heart function and heart failure.

So the rate of heart failure is growing
at a rapid pace of people living with

compromised heart function.

Are becoming more and
more common every day and

though the rate of survival over time for
patients with heart failure is

worse for
five years than any other disease.

Other than one cancer.

So here we're talking about
a wide range of diseases and

you see down at the bottom.

The ones with the worst survival rates
are on heart failure and lung cancer but

different from lung cancer
the progression over time is for

heart failure is a very gradual
decrease in function and

coupled with very sudden unexpected
balance of the compensation where

the management of the young
heart failure is us optimal

which results in a crisis moment where
the patient is rushed to the hospital and

typically goes to the I.C.U.
and gets I.V. dire.

It's or other other drugs to nurse them
back to a normal enough function to

be able to allow them to
return to their home.

This is this is a very
difficult challenge for

a cardiologist to to manage because there
are so many factors that can affect there

are their status such as their diet for
that day.

If they have a if the patient has a lot
of salt for that day they can now factor

balance of all their other medications
a whole host of other issues also can

exacerbate the symptoms of heart failure
and lead to these these urgent I.C.U.

visit and with each visit there is
a progressive decline as well as

often during the visits as one of
the patients all to many ladyhood die so

that it's very stressful on
the patient to have these episodes and

not to mention it's also the number one
cost in the health care system because

of the high cost of these on Persian
hospitalizations each day of a stay for

this sort of level care is
about ten thousand dollars so

we want to shift the paradigm for managing
heart failure from a reactive to more of

a proactive state such as
we have here with diabetes

measurement of glucose levels drives
the administration of insulin and

likewise we would like to be able to
track the heart pressure when I say

heart pressure me into cardiac in truck
cardiac pressure which is a key indicator

of the congestion level
within the heart which

is when I say that I mean the feeling
pressure for the left side of the heart

particularly the left atrium is indicative
of the the preload on the heart as well

as the young the workload that the left
ventricle and pulse of the right ventricle

is seeing as a function of congestion you
want to try to keep that into the normal

range so that you're not taxing or
overloading the heart and

keeping in mind his heart is already have
a heart function is already compromised to

begin with this concept of.

Monitoring pressure to be able to predict

enough coming hospitalization has
been studied already in this case.

Medtronic looking at the pattern
of increase in interest cardiac

pressure in this case ph and diastolic
pulmonary artery and I felt pressure.

There's an increase in pressure
typically as much as a week and

over a period of days prior to all
to minute urgent hospitalization.

So the concept is that if you can reduce
this increase using medications or

in your back into the target range you can
prevent this sort of hospitalization using

Home Care a sort of model so
that the drugs that are available

to respond to these pressure
trends are that are exists.

However the information is lacking in
terms of knowing how to adjust these these

drugs to optimally treat the patient.

And so in their study they did show
a relevant decrease in the rate of

hospitalization events for their off study
group however their target was a thirty

percent reduction which they did mean and

the reason for this after the fact was it
was shown to be due to the inclusion of

this group of patients which is more far
along in heart failure class for patients.

They're typically bedridden and
their function has already been severely

affected by heart failure and they may be
less helped by these sort of treatment

methods but in that subgroup of class
three patients there was a major

reduction in the hostile rehospitalization
rate which is a very aggressive number.

So let's talk a little bit also about

the aneurism application with
this was our first product and

in this application abdominally order
to any reasons are a dilatation of

the the order at the bifurcation between
the order and the only act arteries and

it's the thirteenth leading cause of
death in the US the original procedure

to repair and I'm Donnelly ordered
aneurism is a is a surgery which Reese.

It's the any order in this location
replaces it with a synthetic craft

more recently and a woman all approach
has been developed where a stent graft is

the ploy from within the artery to route
the blood through the diseased section and

depressurize this region of course if
the pressure exist without being created.

Eventually it will rupture at some point
leading to a pretty pretty immediate that.

So one of the problems with
this approach though although

preferred by patients because there's
more minimally invasive is that there can

be a reoccurrence of of the leakage
between any of the SEALs whether here or

here or in between the the joints
between the components or

Also there is collateral vessel
possibility for these so it's very hard to

know if you've maintained a seal
over time of the current method for

follow up on these patients who receive
this repair is to do continuous follow up.

C.T.'s that upon tracks
tomography exams where

the lead passes are looked for using Doc.

Now this procedure has issues and
that at some of the patients being

exposed to high doses of
radiation continuously for

the remainder her life others contacts
Casas toxicity on the kidneys as well.

Also accuracy and ultimately
the doctors looking at leat pass as

opposed to pressure and
the existence of elite

does not necessarily mean that there's
a problem in terms of pressure.

And then there's the cost of the exam as
well as the inconvenience to the patient

so we saw a wireless sensor in
place outside of the bank routing

is a good way to monitor the pressure
in the graft after repair and

potentially allow you to not
have to do the C.T. follow ups.

The company was founded in two thousand
and one so you've been at this for

a while and one of the co-founders
is Dr Allan from Georgia to.

The concept originally
started with a project for

DARPA which was a passive wireless sensor

much like the current one that went into
the combustion chamber of a jet engine and

measured the pressure inside the hostile
environment eliminating the need for

a direct wired connection from outside
the combustion chamber to inside and

improve the reliability that of measuring
that pressure from this project which is

a joint project between Georgia Tech and
MIT and then made its way into of medical

arena through cardiograms and the core IP
was license from those two universities.

So the presentation I'm giving here is
the end result of the work of many people

sixty five employees of the company as I
mentioned earlier the first product which

is the area in or
is in sensor has been cleared for

use and over seven thousand have
been sold and implemented the US and

then we're currently focus on the heart
failure sensor which we have for

which we have implanted five
hundred fifty patients in the U.S.

as well as over six hundred worldwide and
our company to date is the only

permanently implant a wireless sensor
which has been approved for years.

So let's talk about the fundamental
philosophy and concept for

the technology on the left
you see a typical

medical device a cardiac
resynchronize ation pacemaker.

And if it later has multiple leads which
are fed into different areas within

the heart and has many connections many
components and recent news has shown that

the there are quite a few reliability
issues with these devices and over time.

There can be fatigue issues as well as
problems that require the removal and

also these devices are powered using using
a battery which eventually will wear

out and so
that means that the they can get.

And it will need to be
replaced at the very least.

So as a cardiologist
the other co-founder Dr J.

out of who had experienced all these
issues wanted to come up with something

that was simple elegant and
reliable that would could be implanted and

never have these sort of issues and could
be used for diagnostic information but

he also knew that if it's a diagnostic
purpose from an implant there would be

a very low tolerance for any sort of
safety risk associated with the device.

So the approach we took with the R.
and D. effort.

I think is one of the main reasons for
our successful development today

the sensor obviously needed to be
developed using a man's approach and

that was a unique feature but
then there were other large challenges on

the biomedical side that's our team and
then also the R.F. the hardware and

software external system and then these
each of these areas had overlapping

requirements which for which we had
to work together very very closely to

accomplish all those meet
all those those challenges.

So the basic concept for the function the
sensor involved in L C resident circuit.

Like I said earlier there is
no internal power supply and

the capacitor part of the circuit
is a pressure sensitive.

So the pressure outside changes
the distance between the plates

changes as a function of
the pressure change and

therefore that also the resonant frequency
shifts as a function of pressure changes.

This is analogous to a tuning fork where
the the the tune of the pitch of the of

the ringing is a function of the size and
shape the geometry of the of or the tuning

fork in the same sort of way the sensor is
excited by an external energy impulse and

then the external transmitter turns off
and listens for a response from the sensor

and the particular frequency of the
response is correlated to the pressure.

In that location.

The concept is not too new for medical
applications it's been around for a while

this this paper from one nine hundred
sixty seven is one of the first examples

where devices similar to ours were
implanted inside the hide to measure and

draw killer pressure but at the time
in that paper the authors noted that

significant challenges still exist and
existed in need of further development and

some of these challenges is as we've
come to learn are issues such as long

term stability after the device has been
a planet significant innovation had to be

done by a by party managed to tackle
that issue detection distance being

able to achieve a large enough detection
range with a small enough size sensor was

also a very big challenge the ability
to miniaturize the pressure

sensitive aspect of the device especially
for minimally invasive implant

required man's expertise as well as
on coming up with a way that we could

practically make it also required some of
the innovations in the area of madness.

So let's talk a little bit about the
the fundamental operation of the sensor

this slide comes from our first employee
Dr Michael fine Segador of attack

who worked in Dr Allen's group.

He put these together as part of his Ph D.
work and as we all work on this we

realize that there are a lot of different
capacitance is involved in the sensor and.

One of the biggest ones that we did we had
to work with is the one from the xterm

environment so once the sensor is
implanted into the body the dielectric

media of the surrounding environment
changes from air to blood which is a major

change in dielectric So you need to
somehow account for that to not have too

much of a shift in the resonant frequency
of the center as a result of that change.

Used approaches such as insulation as
well as limiting the electromagnetic

field which extends outward into the media
so that this effect is minimized.

Also there is the parallel paths through
the substrate which are very important

especially as it relates to the quality
factor of the circuit in order for

the sensor to work as opinion Listen sort
of advice it has to have a high enough

quality factor so

it's passive running is long enough to be
able to detect by the external system.

So the quality factor typically
needs to be high enough and

not affected by the surrounding media or

the substrate which limits your options
in terms of material selection.

So as you can see there are very many many
parameters that needed to be optimized

in order to get the correct frequency
as well as the quality factors

in the right sort of range.

The of course the sensitivity
the sensors the pattern on the memory

of the width of the membrane as well
as the material type but also this

pressure inside of the air cavity is
a critical parameter in order for

the membrane to consistently deflect the
right amount as a function of pressure.

You need to have a consistent
reference pressure inside

this this means that there cannot be
a leak rate between the inside and

the outside such that the inside
pressure will change over time so

that means in translation that
the package must be her magic.

And hermetic to a level that you don't
have minuscule changes of the flexion

as a function of the loss of molecules
from the inside to the outside.

So at the end of the development effort.

We the result were two main platforms for

source sensors the one on
the top is one that uses purely

memes sort of processing techniques
the inductor coil is a player a spiral

which is played with copper and
the two court two opposing coils.

Spaced apart by a very small gap
giving the capacitance so it's really

two coils separated by the gap and that
the hub changes as a function of pressure.

We like this this design the most is
in terms of ability to manufacture and

reliability It doesn't have
any connections at all.

However.

When you have a planar spiral coil the
total size of the device is larger than if

you have a are three dimensional
dimensional quality.

So eventually for the heart failure
application which requires another level

of miniature ization.

The result was the same concept however
with a three dimensional coil and as

I mentioned earlier both are hermetically
sealed with the Hermetic sort of package.

No internal power supply.

They both example exhibit stable
performance over long time frames

of course they're both compatible and
have batch fabrication capability.

So what makes this a nano device.

I needed to include the slide in
order to be able to present today.

But the gap between the capacitor is the
starting position is only one micron and

this is important in order to minimize
the amount of total deflection and

of the membrane as well as we want to have

the stiffness of the membrane behind
off such that anything that grows

on top of the membrane such as the tissue
response from from the body is is not

significant to the overall stiffness of
the membrane and the amount of deflection.

So in terms of its sensitivity.

We we then have on
the order of one nano meter

per millimeter of mercury change
once once the device is completed.

So it's sensitive down to
an animator level across the way for

their very tight process controls in order
to achieve a consistent in yield and

that we control the height
of the electrodes

down to twelve near meters as well as
the trenches that they're plated with then

are controlled within one hundred
nanometers another point.

About the materials used for the substrate
is that they must be incredibly

dimensionally stable over time because
as I said earlier the sensitivity

is a function of the animators changes and
deflection so

the material itself can change on
that order over a period of time and

our specification first ability over
time is two millimeters per year so

that says that the dimensional stability
has to be within two nanometers per year.

So this slide we showed earlier is just to
remind us of the operation of the device

as we get into talking about
the external measurement system.

We've got so on the top you see

the profile of the external
measurement system transmit poles.

To microsecond burst is transmitted
at about one watt power level and

then it has to be shut off almost
instantaneously in order to then be able

to detect a very small signal from
from the sensor which dies down

fairly quickly to have the next light how
quickly it is but it's very quick and

then it is sample somewhere around this
point in time to be able to determine what

is the the resonant frequency of the
sounds are and the the two the external

antenna and the internal sensor
are loosely coupled magnetic transformer.

So here are some of the numbers on the
external measurement system to convey some

of the complexity of how that operates

the sensor signal completely
decays within two microseconds.

And as an order of magnitude
the transmit power is point nine watts.

But the receive power is only
one hundred people Watts.

So some of these features of the externals
measurement system would not have been

possible no matter how good the innovation
was a decade or two ago some of some of

the capabilities that exist today
are a lot due to the innovation.

As the area of the cell phone industry and
other ships outside exist as a result

of those so in order to get
adequate power from the sensor

the signal must be sampled within thirty
five nanoseconds of the transmitter

burst otherwise the sensors say holistic
aid to a point where it's not detectable.

And then the sensors signal a sample
rate a hundred kilo herds in order to be

able to average over time and
get the most accurate result.

So now I'm going to show
the implant procedure animation and

how the product is used.

So the sheet is introduced
in the family vein

as one dance blue catheter which
is the typical catheter used for

right heart catheterization procedure to
measure pressure in the home area artery

in the invasive manner is used to
advance into the home an artery.

So what we show here is the Senate is this
one dance balloon advancing with blood

flow through the I.V. see up into
the left home enter a branch and

then this balloon will stop at a certain
point where the vessel diameter is equal

to the dime or balloon and pressure
can be measured through this catheter.

So this procedure is very common even
residents will learn how to do it so

it was important to find
something that was and

he procedure that everyone can do
as a starting point for implant

many to start over with us.

So once it's on Dan's balloon
is in position a guide.

Wire is advanced through it and

this one dance catheter is removed
leaving the guide work place once a guy

wires in place a catheter with the center
loaded on top of it is in advance and.

Position and wires pole to release the
sensor loops on the sensor prevent it from

going further than the desired location
and blood flow helps to lodge a position

then the patient can lie on
a pillow to measure the sensor and

the patient does this on a daily basis.

Typically and then the data and
summary numbers are transmitted to

a website which the health care
providers can look at any time.

So you get a trench art which looks
a lot like a stock market chart and

their goal is to have the the pressures
over time remain in the target range and

if they aren't then the health
care providers can think

about what to do differently to
operate the back to the ranch.

So let's talk about why did we choose to
place the sensor in the home an artery.

There are there other places we could have
done a place that such as in the left

atrium the left atrium would be
the best choice as far as measuring

the thing that we care about which is
the preload on the left and trickle.

However in the left atrium
to in order to access it.

You have to cross the the angel
septum from the Venus side and

the more risky and difficult
procedure as well as you're leaving

a hole in the in the septum
that the knees are heal.

In addition any devices placed on
the arterial side has the risk

inherent risk that it could dislodge and
belies to the brain on top of that

the big concern is that any device might
have some sort of thrombus sort of growth

over it which thing could become dislodged
that could also then go to the brain.

So there's just a whole list of risks and
concerns associated with placement in

a left atrium the other the other
location which is the pulmonary artery

the pressure to transit particularly the
diastolic pressure in the pulmonary artery

changes mostly as a function
of the left atrium.

So it's possible to look for
the same sort of information from the P.A.

pressure and so based on all those
factors we chose to the place.

It in the palm of Ari and also because of

the blood flow carrying the sensor
in any any object into the lawn.

You don't have the the migration
rays that have on the arterial side.

So as far as the implant procedure the
particular target location is typically

the left lower lobe of the of the lung and
we like to place it here.

Also because it's within four inches of
the back which ensures that we're going

to get a strong signal as we acquire the
sensor from the at the back of the patient

and then we place the sensor another
vessel which is between seven and

fifty millimeters in diameter and
this ensures that there is sufficient

flow around the sensor once
the center has been positioned.

Finally the centers of aligned
with the long axis of the body so

that no matter how the center
is oriented within the vassal

the the extra magic that
system can couple to it.

The open area of the coil or the delivery

system which is what our team worked
on primarily is an over the wire

delivery catheter which is a standard type
of catheter he used to deliver stance or

to inflate obstructions with
a balloon which has been

modified to to hold the sensor
The There are three lumens one is for

the guide wire the two
sided Lumens are for

the tether wires which extend from this
cap all the way through the shaft and

coming out of not just on the side of
the shaft the threads through loops and

over the sensor retaining the sensor until
it's released by when we tell the wires

the catheter is loaded in a hoop like this
and sterilized and then is ready for here.

So this is what the cath in the center

looks like once it's in visitation
ready for deployment after deployment.

Here is an angiogram performed with
the sensor in place you can see plenty

of blood flow around the sides or.

And over time.

This is this is a history the thousand G.
done on animal study.

You can see there is
a the response from the wall is

a is primarily in the theory all
coded which is what we want to see in

that we want to show that hope
after a while the center becomes

invisible to the blood flow in terms
of surface from biscuit here to there.

So let's talk a little bit about
the particulars of the data.

This is actually an example patient
from the study that has been

the identified is pretty typical with
these patients when they come in for

the implant that they're home an artery
pressures are fairly elevated and so

prior to the implant the the pressure
the doctors might have thought that

they were optimally managed
based on the other symptoms but

as soon after the fact they see that
they're elevated and then are able to act

with some change in medication so that
you see here the first change resulted in

the desired response but then
something else cause it to go back up.

So then there was another change and
since then the pressures have lowered and

remained stable in the target range
over time and one of the common problems

with just managing based on symptoms is
that the doctors are hesitant to do these

sort of increases without more information
because there can be harmful side effects.

If you overdo it such as a kidney
failure and other things.

So once they know the pressures
are elevated They know that it's warranted

to increase the medication levels and
then you can see this patient has now

been hospitalized since that time so

far the pressure away form information
we did a very high quality way form

in that there is no artifact we're
measuring the pressure right directly

at the site there is no transmission
artifact from the side of the measurement.

Such as you would get through an invasive
catheter measurement and from that we were

able to extract other information because
we can determine accurately things like

the opening and closing of the monitor
valve and from that we can use stablished

methods as to make cardiac output which
is another very important grammar and

then once you have estimated a cardiac
output based on the pressure way for

you can also calculate the estimated
total momentary resistance.

So these top trends are added
based on calculations and

this bottom areas that actually
the measured pressure over time for

an it an example patient this patient is
a particularly interesting example because

this patient was moving on to class
four type stage heart failure

more severe and this was already known
the patient was on the transplant list and

eventually received a heart
transplant at this point in time

with with these hospitals
ation events occurring.

Prior to that as you can see also is
in terms of the pressure trend there is

an increasing pressure trend that could
not be addressed by medication also

normal your cardiac output again is an
estimated parameter but this makes sense.

What's happening here.

Normally cardiac output remains
stable as a function of the heart's

response to the needs of the body but when
the heart is failing till the point where

it cannot do that you can see here
there is a steady decrease and

that's to made a cardiac output
over a period of one hundred days.

Meanwhile there is also a major
increase in the resistance

to flow through the lungs as
a function of the increase congestion.

We believe so.

Then after the heart transplant was
performed you see a gradual decrease

in the pressure trend.

It's interesting to me that it
doesn't happen instantaneously.

You see here one hundred fifty date
sort of timeframe after the new heart

is received for
the pressures to normalize the same way

a Likewise with the cardiac
output in the resistance trance.

But then after that period time.

And you see you stable
pressure trans as well as

stabilization of the other parameters.

So if we have time I'd like to go
through the clinical study structure and

the results to we have
time to talk about that.

OK All right.

So today we're very excited about having
reached this milestone we finished

all the enrollment in our our clinical
study in the last patients follow up is

now completed.

We're at this stage of compiling the data
for our failure study the I wanted

to include this summary because it's
another key thing to imagine in terms

of the development of a concept to
commercial use when something such

as an implant is being developed which
is a totally new concept such as this.

There are strict requirements and
there's a high bar for

proving that it works so conceptually
it seems like it should work but

we need to prove it through
a randomized study in order to

prove what we're trying to prove which is
a reduction in the hospitalization rate we

had a large sample size which included
five hundred fifty patients and we

did it over seventy five different sites
in the U.S. and with the expectations

of what the hospitalization rates would be
ahead of time we were able to determine

that we should be able to achieve a ninety
percent statistical power with this sort

of structure for the study and then again
the primary endpoint we've already talked

about other things that we're looking at
is the ability to change the moment or

are the pressure as a function of the
the knowledge of the the information and

result in medication changes a portion
of the subjects hospitalized and

then the number of days alive outside of
hospital and then also the quality of life

improvement as a function of improved
medication was also evaluated

separately also we wanted to evaluate
the the effect on the total cost of care.

Because that's that's another thing that's
going to be a compelling argument for

this device if we can show that there is
a reduction in hospitalization it's clear

that we can also show that there's
a reduction in cost in health care.

So we're hoping to complete our P.M.A.
process either at the end of the year or

early next year and we have a panel review
ever hoping to do at the end of this year.

So some of the other facts
about the trial to mention.

Their regional clinical
implant the first clinical

implant was back in two thousand and
five the last one was in two thousand and

nine and we implanted over six
hundred six hundred two worldwide.

The average time frame for
having the sensor was three and

sixty five days with
a maximum of over four years.

I think this is the implant
procedure is important for

this to be a simple easy and
problem free as I mentioned earlier and

we did demonstrate that the average time
or typical time frame plan was thirty.

Excuse me the whole procedure
was thirty minutes the implant

of the sensor itself was only
seven minutes typically.

And then ninety nine percent technical
success with the implant procedure ninety

four percent technical compliance
with the patients taking readings and

then we're planning to present
the results fairly shortly.

There will at least be
a presentation about the trial at

this meeting on May
thirty first very soon.

We don't know yet

if the result will be ready present at
that point but they will be ready shortly.

The key thing to mention though which we
know already today is that there were no

on interest paid to that
first device events related

to the system throughout the whole study.

So that's an impressive statistic
already that we can cite.

So with that I would like to
talk about the conclusions or

my conclusions from the effort today.

Some of the things that have driven
the success aside from the technical

innovations have been that
the technology efforts.

Driven along by a real and
that clinical need.

We didn't just choose to use memes
because it was a cool way to do it.

We we did it because there was really
not another good way to do it and

there was a solution that was uniquely
provided by man's capabilities all on

the way we've maintained this design
philosophy that focuses on reliability and

safety and it's worked so far and
then this multidisciplinary R. and B.

approach I think has been it
seems like common sense but

it's been something that if
we hadn't done it that way.

I don't think we would have succeeded.

So with that I'd like to call can
can up here and we can we can do

a demonstration after which will
answer questions we have of years.

Astley mile here and what we're looking at
now is the point in the procedure where

the guide wire has been reduced
by way of a slime dance Hatter.

And it is introduced through
being as she had more of

a access point and wires cracking
through if you're against it.

Well you're right.

Better call on Mary already has a laugh
on our every implacable patient.

So just a second look at this.

I'm serious about it all
happened as we said earlier this

answer is rather happier perhaps using
a wire that there is enough isn't

over the loose end of
the sensor releases or for

my own the capital sort of the second one

I think I was in place then he
added if you would over watch.

This part of the process
is very common for

a half dozen years right here in
the states that are presented here for

this and now the senator is
introduced to the seat allergies.

She function is the arena for the leaders
from the asshole to the outside hand

maintains he stays to see her
house steps or comes out there in

the street at this point you just have to
use the ball on horoscope as a hood and

through the U.C. Davis through our

good.

All right.

I don't know you say there you
are just like all right so

are you worried you'll see it right we're
going to advance a past the place where we

normally where are we with the boy in this
location priceless and no mayor in or

OK show us a better chance
outside now to avoid it.

Let's recap all the wires which allows
us to Bill Lloyd out of the loose

maintain its position prevent you
from going for just a little of

what I was doing the Floyd is in our
location within the patient's own area and

they've been lying down to deal with
things the camera and the sensors and

the Master so various that we have
here we have a sensor in a jar

which can be pressurized using all.

You mean that

this is what you mean this use

you get to this now actually.

So this is the xterm system which
we were showing today and for

our first demo purposes we have our newest
thing which is a wireless connection

between the time the the external system
and because of battery power I think is

the reason for the issue also that if then
you could also just use another external

measurement system let's say there was
some problem with the system itself.

I did.

You could use another
one like this it would

also it.

The center itself has ultra
reliable track record.

So we haven't have or

had an instance where the sensor
itself has stopped working.

If something like this occurs with
their external measurement system.

You could replace it with a fix or
something else you were there wouldn't be

in there hasn't been a situation where
you need to put one out of one or

remove the one that's already there who

will work legally.

What was the one.

Yeah there's a whole there's a line.

Yes it was randomized there's a whole
list of inclusion next clue the criteria

primary one for inclusion then they
have class three heart failure

as determined by primary care are for
other or.

Ologist And then there are exclusionary
criteria such as they could not have

a primary phone or hypertension which was
irreversible by medication so they had to

have heart failure which was the type that
was reversible to some extent by treatment

with medication and then the groups
were randomized fifty fifty and

two control control groups in
the study groups in the study group

the the information from the pressure
sensor was available to the health care

providers in the code control group
it was not so good to use today.

It was a randomized though
selection process so.

So each and every sensor received
there existed be every patient receive

the sensor and then after that there
is a transition process which to

determine whether they were the treatment
group or the control group.

So all of these activists.

These are all the patients that
own their own people and now.

Now all patients have class three hard
to read exactly these patients yet

and so they control patients were
managed per the standard of care for

heart failure and
there are established requirements for

that as well including
also the effect of a phone

call to the patient which would occur
as a result of pressure measurements.

There was some established evidence that

increased communication with these
patients actually helped them do better.

So we had to call the control group

an equal number of times to
tell anybody just patients.

If it was well that they were

at a point where they'd already are also
shown a track record of more than three or

at least one hundred schools ation I
believe within the last six months.

There were some criteria like that.

Were they had to have shown a track record
of hospitalizations due to their heart

failure symptoms.

So there was a probable benefit
assuming the technology works and that.

If you could reduce the rate of occurrence
of out then they could possibly not have

as many heart failure hospitalization
future cases of medication.

Just to see if this is a dangerous.

This is you know no it's not.

I mean we have to convince before even
starting the study the F.D.A. and

the other physicians involved that there
was a great safety track record based on

better studies pretty want to
collapse studies on animals and

eventually initial human work which
of all those small subset not not

these five hundred fifty initially we did
a study with one of the patients where we

established safety and
the measurement function sensor hello to

the device rest understand what
the patients were suffering.

You may get a little randomized control.

All right well and that information would
not normally be available anyway without

the center so then the sanction
that knowing the the information

will help is actually the purpose of
the study so that does not prove that.

So we're doing the study in order to
demonstrate that knowing information

helps improve management.

So once we determine that.

Then the right solution for anything is

just this is the use of life is very

OK in the site.

OK this is better than mine.

It's very special to you.

So I can't really respond to that but I
think you will need to send happened this

and that more time with this
a few more questions there.

That's an interesting question.

I don't know whether those patients
are listed in the exclusion criteria so

far but you know the device
has a very smooth coating of

silicone it's actually smoother
than the typical coating for

other devices like a pacemaker lead
in that it's dipped coated and

we've shown a great response in
terms of tissue over growth so

within the period of one month or last
we did have the center totally covered

by a tissue and there was a point
there and this is this is equivalent

to the other vessel lining in terms
of the interface but I can't say for

sure what the issues Pacific effect
would be on sickle cell phone Asians.

But I would suspect that it
would be a different matter and

so it's coated

in a dip coating of silicone which creates
a surface kind of like a drop of water in

terms of its smoothness so that the
silicone itself the conforms by by surface

tension to the other one when it's on
here to the the object and then we care.

It makes it kind of like a little sort
of bubble shape around the sensor so

that helps.

Actually the glass itself with a few
silica might also give a nice response to

if we didn't put it on
that is what he meant.

And I'm sorry say that what

we also saw the resident

frequency itself varies as a function of
the pressure change outside of the sensor.

So as the pressure changes the men.

Brain which contains the capacitor
distance changes and

then that part of the resonant frequency
shifts as a function of pressure

on you.

I see what you mean so so

there is an increase in pressure which
is associated with congestion which

is because the left side primarily of
the heart is not pumping efficiently so

there is a back up like a large amount of
blood is coming back from the lungs to

the left side the heart is not
ejaculating blood it fast enough already.

And so there is this back up of pressure
which then backs up to the lines

at least a few of the fluid accumulation
which then leads to sort of a surprise

exacerbating the whole issue which already
exists within the right side of the heart

is having to pump with an increased
workload against this elevated pressure

in the laws so the whole heart is working
harder as a result of the ineffectiveness

of the left ventricle
to sustain the output.

If you think we need it

so well the sensor itself is passive So

it's the membrane is deflecting as
a function of the pressure all the time.

Only when the external
measurement system activates or

energize a circuit then will there be
a ring down response in the electro.

In the R.F. domain not mechanical and that

is detected by the external measurement
system and the particular frequency at

which the resonance occurs is that
related to a pressure not a channel or.

Right right right.

The way to power.

It was and if you like that.

OK Well the hold it has been done
both with copper in the gold.

Well that's a good question.

There with the goal is that you
should never have to do that and

we've so far demonstrated that that is not
necessary and we've done long term studies

to show that the drift rate is low
enough that you should not have to

recalibrate and that's that's the this
requirement that I mentioned earlier

that is that the drift rate requirement
is less than two millimeters per year.

So by that we mean the mean pressure

at a static pressure as measured by
the sensor does not deviate from the real

value by more than two
millimeters per year our life.

You mean for other technology itself was

lifespan what we had at the lifespan is
indefinite essentially due to the fact

that it doesn't have an internal power
supply our stated requirement is that

it must meet performance requirements for
a ten year period.

So we've tested to that level but there's
really no reason to imagine that it

would stop working at a time maybe
at some really long time frame.

You might want to recalibrate it
let's say the drift actually were two

millimeters per year.

If it's been twenty years maybe
there would be off by forty but

that's all theoretical but you can be

calibrated if you want to buy another task
of procedure but that's not desirable.

Well you know it's a good question
that there has not been and

then that comes up all the time because
with other devices such as pacemakers

there are situations where you do need to
remove the lead such as infection arc or

the pace of the lead fails or something
like that so far there hasn't been any

need to do that because there are some
important differences between this implant

and others like pacemakers or heart
valves primarily because it's catheter

delivered like a stent it's possible to
maintain a very high levels to realty

versus other procedures where you're
having to do some surgical staff where you

can possibly create a source for infection
back in then we need to the heart.

So the infection risk is much lower as
a function of how we're doing it and

we have not seen any infections yet.

Whereas in the same group if you had done
pacemakers you would have by this point in

time then also because there is no
finite battery life there really

isn't a reason to take it out at any point
and also with the reliability levels we've

demonstrated that should not fail
if it were to fail I imagine

the conclusion would be
not to try to take it out.

Leave it in place and either put in
another or don't do anything but

if it's if it's better not
to implant a second one.

But there really has not been a need
to do that and we we imagine that there

shouldn't be a need there.

Yes to some extent you know excuse me.

It does not affect the vast number.

Yes sir we can pass around some
samples for you to look at the effect

of the orientation is on the signal
strength with the coupling.

The ideal copper wiring is going to
be when the oil open area is facing.

But you know the antenna.

When it's this way you get the worst
case and the coupling is diminished.

However the value that is interpreted
it is not affected by that.

So that's an important thing is you don't
you don't want the value measured to be

affected by the orientation and.

Yes

yes

it

is

a that's a good question and I believe
you're talking I have this right.

Interacting vascular ultrasound those

techniques are typically used it's an
additional staff an additional expense and

Normally those that approach is used when
you want to understand better the three

dimensional shape of something
like a lesion which cannot be

appreciated sufficiently well by a two
dimensional for a scope image in this

case we're implant in that is typically
the uplift of all and coronary arteries or

peripheral artery disease word.
You're trying to

optimize the choice of stand
placement of the standard of living.

That's a most common use
of that type of technology

when the information you get from
the two D. image is insufficient.

However in this case we're
normally putting the sensor

in a relatively healthy vassals that they
don't have a prior disease state and

also due to the design of the loops
it's NOT be especially critical

where along the length of
the vessel you place the sensor.

If you were to place it more
proximal then the ideal location

the blood flow will carry it to the point
where the loops will eventually law.

So that's actually one of the features of
the loops that we we wanted to up have

because we didn't want there to be a real
high criticality with the placement with

a stent for instance you need to precisely
place it because of the specific size for

the stand relative to the vessel you don't
want to oversize or undersize it here.

The loops are able to tolerate
a pretty wide range of diameter.

So in practice we use imaging that
was performed through this one

man's catheter before the device
was introduced and from that image.

We're able to save it and look at
the size of us all and have it next to

the live image on a separate screen of the
catheter in the sensor being introduced.

Then we can align the sensor
position with the previous image and

know that we're in the right position and
then release the sensor.

But there are a lot of techniques to
get more in-depth in more detail such

as that which they could do but they don't
choose to because it's not necessary.

Every time.

So so

the external measurement system transmits
at around point nine watts of power.

So then

the power that is coupled into the sensor
varies as a function of the distance so

as you bring the sensor farther
away the power of this coupled.

And then this received back
was reduced and at some point

the power returned is not sufficient
to be able to measure the signal.

So we had to develop the sensor
in the external system such that

the the power received from the sensor at
the distance that it needs to be implanted

was sufficient.

And typically you can receive more energy
from the sensor the larger it gets so

there's a tradeoff there where you want
to make the sensor as small as possible.

Yet you also want to be detectable
at the given distance so

it's all a function of
the size of the inductor coil.

So the larger that it is the more the more
power can be captured by the sensor.

So I think I said in the presentation
that the return power

from the sensor typically is very small
What was it you can remember now but

it's on it's a billionth of a watt
sort of order of magnitude.

So that's kind of a major technical feat
for the external systems able to measure

that or
detect that we're there you can actually

hear that is this and
it is actually in the past year or so.

So the sensors are made from a few silica
away first and then there are medically

sealed as they're diced so and
then over that we encapsulate with with

silicone I think that helps with the you
know dimension of any faction Australia.

Yes that

is the pieces within the extra
measurement system hearing.

Yeah yeah there is this is the area
that I know the least about but there is

a coherent detection method where based on
the timing of the transmit poles by phase

the external measurement system is able to
distinguish the signal from the senator.

Apart from other R.F. noise as well
as we're operating in a range that

should not have as much competing
sort of R.F. noise artifact.

And then also we can do filtering
on a signal to look for.

Physiological relevant information as
opposed to other spurious sort of Russian

girl who starts out here.

OK we operate within the range of thirty
to thirty seven point five megahertz

So I mean we were part of
a special provable from the F.

sixteen or if you doubt yourself.

Well so the idea is that you
never have to remove it.

So it's more like a stand in that
situation if you connect in that

sense it's deployed once and
then still remains for

the life of the page you are going back.

This is the Oracle presentation problem
is a must and the last ten years or

so it is harder.

Acting because you know
that the center and

there are exhaustive presentation
on the night mission.

I think that is us.

You know they demonstrated on the set
of all or you know you've expect for

a living in this for profit of course
annually in fact really bond will still

need really my vision for
us a year or so in ice or

something there the second part was
you know I've seen this myself as

all that us it was just here
the rest of it you know I

mean there's this very movie director
just like as you see here so

you know he did all of this I'm sure

you're if you

put your mind up for
your kind of this just like for

us to live in this vision
of the city regulations.

It was our rule you had
a period it was sure exactly.