Until now mechanical eyeball

and no wall from the future of Sabah

by Dr. Patrick Perino,

right here from New Orleans.

Good afternoon.

This originally was supposed to be

Tom Gleason's talk, but

one of his partners is ill.

And so Tom was sorry,

but unable to attend.

But these are his slides.

And so if you're willing to take a

journey with me into the mind of Tom

Gleason, we'll kind of see

what happens.

Those are Tom's disclosures

rather than mine.

So the question is, is,

is there still a role for mechanical

aortic valve in

the era of transcatheter valves and

suture loss valves and all these

other options?

And I think it's important that

while the speed issues and things

like that that we just heard are

important to consider, durability

remains a significant issue.

And I think we would all recognize

that we can't place an infinite

number of transcatheter valves

inside one another.

They're not like those Russian

dolls.

And so Tom suggested that perhaps

the mechanical valves might be

a better option, in particular

for younger patients.

And in the notion trial,

they looked at Bioprosthetic valve

failure and

found a significant

early failure rate for both

transcatheter valves and for

surgical tissue valves.

And one thing that's interesting

about the notion trial is if you

look at the surgical valves that

were implanted, a significant

percentage of the 19 millimeter

valves were trifecta valves.

And Mike gave and that group

had the paper that showed that the

trifecta has a relatively

high early failure rate in the

smaller diameters.

In addition, some of the smaller

valves are used in the notion trial

or the mitral valve valves,

which also have been reported to

have an earlier failure rate.

And so this data, which shows

the failure rate of some of the TAVI

valves, might also be

a not good representation

of surgical valve failure rate.

Here are some early images.

Two and a half years after

transcatheter valve

demonstrating, in fact, there is an

early failure rate in early

calcification for these

tiny valves. They're they're not

somehow magically protected from

failure as opposed to the surgical

valves.

When you look at a survival

advantage for patients under 60

years old looking at

valve replacement, whether it's

aortic valve or mitral, there seems

to be in some studies a survival

advantage for mitral or mechanical

replacement of these valves.

If you look at mechanical versus

biological mitral matched

cohorts, patients under 65,

the patients who got mechanical

valves had improved overall

survival.

And with aortic valve, there was an

overall survival advantage as well

with mechanical valves.

The biggest issue, I think, though,

is, of course, the risk of bleeding

complications and strokes related to

mechanical valves.

There's clearly an increased risk of

major bleeding.

In this study, the stroke risk was

similar and the overall

survival was similar.

But the reoperation rate

consistently, of course, is higher

with the tissue valves and the

bleeding and stroke complication

rate is higher with

the mechanicals

for overall survival for young

patients.

There doesn't seem to be a higher

risk of death over the short term

or intermediate term for patients

with mechanical valves.

And there is an age dependent hazard

of death. And in this study out of

Stanford,

it looked like for patients

who are getting a mechanical valve,

there's a survival benefit up to

about age 70.

And for patients getting a

mechanical valve, there's probably a

survival benefit up to age about 55.

But again, the issues remain

bleeding complications and stroke

with free operation.

The predominant issue for the

biological prostheses,

the patients that got biological

valves had lower

survival due to valve related

complications versus

mechanical valves.

And whether this was valve failures

or other related problems,

it may be that the

patients, you know, obviously

there's a risk with Reoperation for

these patients, that's not zero.

Another important consideration is

the durability of the orifice area

with mechanical valves.

There is some diminishing over time,

but the bioprosthetic valves

obviously as they age, the orifice

area is going to go down.

The notion that we can just put a

tissue valve in these patients and

then put it to have evolved and then

just re operate on whenever the time

is right is a little bit

put to bed. But this study which

demonstrates that re operation in

octogenarians

is a is is and is

known to be a high risk procedure

for those patients and to delay

them and kick that can down

the road by sticking multiple

transcatheter valves into a worn out

tissue valve may just

create a higher risk down the road.

Question is, is what can we do if we

know the valves themselves are

better and then the problem tends to

be the anticoagulation, or are there

some opportunities there?

And in this study in which patients

manage their own high and or with

the home testing kit, which it's

worth pointing out, there's nobody

coming by to calibrate that.

And so the reliability of those

measurements isn't is

predictable as it is when it's done

in a laboratory. But patients who

managed their own INR

and had a lower target didn't have

adverse complications,

but were able to control

their own INR and avoid, as we can

see here, both bleeding risk and

stroke risk with maintenance of a

lower INR at home.

They didn't have valve related

complications and they didn't seem

to have as many anti coagulant

related problems for the Prozac

trial. A similar thing that

demonstrated the lower INR

was safe and didn't result in

an increased risk of stroke.

Obviously the coagulation pathway,

there's multiple sites for

intervention. Coumadin,

the oldest tool in the toolbox,

relatively speaking.

Thanks for playing ablation pathway

in multiple sites, whereas some of

the newer direct thrombin

inhibitors or the Today inhibitors

have a different role and may offer

opportunities that we haven't had in

the past.

Here's a study from the British

Medical Journal.

Looking at frail patients with

atrial fibrillation.

They're going to look at the subset

of older, frail patients.

As you all know, the Today

inhibitors did very well in trials

versus Coumadin for atrial

fibrillation, but it remains an

issue for older patients in regard

to their bleeding risk.

And this study is about to start

to look at that. For A-fib, there

have been animal studies in which

mechanical valves were implanted in

the animals were treated with some

of the novel ethical arguments.

But the problem is that the animal

valuation pathways are not always

the same as human.

The dose response is not always the

same. But even in spite of that,

the results have generally been

encouraging.

This trial is going to start

soon to look at

a another

today inhibitor for mechanical

valves.

The Re-align study is the only

study to date that's been done

with alternate anticoagulants,

and this study was halted

due to adverse outcomes, but the

adverse outcomes were in Population

A and those were patients that had

this drug started immediately after

the operation. And Group B

listed here is population B.

The drug was started more than three

months after the operation, and

they had relatively fewer events.

And this is another study

out of Switzerland.

This enrolled only a few patients.

They had to close it because they

had limited enrollment, but they

didn't have any valve related

complications or any

or bleeding or stroke events.

This is a group of patients.

To which it's hypothesized

that the noacs may be advantageous

versus Coumadin.

If you wait more than three months

after surgery, probably your

position is safer than mitral.

You've got to have the right valve

in place, good LV function

and limited other risks.

The proactive trial follows in

the Neil the Pro Act trial, which

looked at low INR for the Onyx

valve.

This study is going to look at tiny

inhibitors, specifically Eliquis for

this study, and that study should

start enrolling next month.

There's going to be another low INR

trial.

The NOACS versus warfarin trials

are underway.

There's other drugs in the pipeline.

And if we can avoid the

drug related complications of

mechanical valves.

In the face of the durability and

reliability and predictability of

mechanical belts.

The mechanical valves may emerge

as the best choice for younger

patients, in particular those under

55 for aortic valve and

under 74 mechanical mitral.

Thank.