Transcript BIOLOGICAL HEART VALVES - Mike Poullis

BIOLOGICAL HEART VALVES
Mr. S. V. GHOTKAR
HISTORICAL ASPECT
1952- The first artificial heart valve to be implanted in
humans was a mechanical one implanted by Hufnagel &
his attempts heralded the era of cardiac valve prostheses.
1955- While most workers were working on mechanical
devices, it was Murray, who considered replacing a
diseased valve with a valve taken from a donor animal.
Encouraged by results of his experiments with dogs he
implanted a valve harvested from a human cadaver into
descending thoracic aorta of a 22 Yr. man who had severe
AR. This man was a manual worker & was asymptomatic
when seen 6 Yrs later
1956- By this time pump oxygenater became
available & Lillehei performed the first aortic
valvotomy & repair using retrograde coronary sinus
perfusion.
These early operations by Hufnagel, Murray & Lillehei
had a great significance as they showed that body can
tolerate natural & mechanical prostheses as well as
native valves were amenable to repair.
Here began the competition between these three
modalities of treatment.
DEVELOPMENT OF AORTIC
HOMOGRAFTS

Subsequently as most researchers were
working on mechanical prostheses Murray’s
group in Toronto persisted with notion of
aortic homograft substitution in orthotopic
position.

In 1962 Alfred
Gunning & coworkers in Oxford
worked out a reliable
method for aortic
homograft harvest &
preparation.
Knowledge of Gunning’s work allowed Ross to perform the
first landmark sub-coronary homograft implantation in 1962.
This success was soon followed by Barrat-Boyce in New
Zealand, Mattias Paneth & Mark O’Brien at Brompton
hospital.
These were the people who adopted & pioneered homograft
aortic replacement at a time when most surgeons preferred the
durability & simplicity of Starr Edward valve insertion with a
single row of sutures.
The homograft insertion was technically more demanding in an
era when myocardial preservation was primitive.
To simplify homograft implantation Weldon from
John Hopkins hospital published results of laboratory
experiments with aortic homograft mounted on a
frame.
Angell adopted stent mounted homografts for aortic,
mitral & tricuspid replacement. Stent mounting
increased easiness of implantation & significantly
decreased incidence of early post operative
regurgitation in comparison to free hand sewn
homografts. However, medium term results showed
limited durability of stent mounted homograft tissue.
The stent thus caused accelerated tissue failure.
Ross flexible homograft
support
Shumway- Angell –
Cutter graft support
DEVELOPMENT OF
PERICARDIAL PROSTHESES

Availability of human cadaveric material
was always limited & led to search for
alternative materials.
In Zurich Senning used autologus fascia lata
to construct a trileaflet valve, but this turned
out to be disappointing.

Marion Ionescu in
Leeds mounted
heteregounus
pericardium on a
frame with a sewing
ring
DEVELOPMENT OF PORCINE
BIOPROSTHESIS

In 1964 after their succes with homografts,
Gunning & Duran diverted their attention to
preservation of heteregenous valves.
In the same year they performed first
human stent mounted porcine valve
implantation.
In 1965 Duran & Carpentier presented their
experience of mercurochrome preserved frame
mounted heterografts. This was soon followed
by reports by Mark O’Brien about his
experience with formalin preserved pig & calf
aortic heterografts.
However, long term results were poor because
of primitive preservation methods.
In 1966 Ionescu developed a
stent for mounting aortic
heterograts.
It had Titanium support, 3
legs covered with dacron
velour & dacron felt ring
was used as a sewing ring.
The porcine aortic valve
was sutured within the
frame.
Carpentier next produced a stent made of stainless
steel coated with Teflon to minimise
thromboembolism & he used mercurial salt for tissue
preservation. This stent is the precursor of stent used
in modern Carpentier- Edward valve
Within 5 yrs of use of stented valves it was realised
that stent mounting caused excessive stress on the
biological tissue which resulted in accelerated
degeneration. This setback caused practice of stent
mounting to disappear.

1968 -Preservation of
tissues with formaldehyde
or mercurochrome was
proving disappointing, this
problem was soon
resolved by Carpentier
who employed
gluteraldehyde
preservation for the first
time.
The chemical treatment of
tissues prevents collagen
denaturation & reduces
antegenicity of foreign
tissues.
Carpentier considered the stent mounted, chemically
treated porcine xenograft as a hybrid of biological &
mechanical structures & hence named them as
Bioprostheses.
Central laminar flow was a remarkable positive
aspect of these bioprostheses but still presence of the
stent was partly obstructive.
With efforts of Carpentier, Hancock & Angell
gluteraldehyde preserved, stented porcine valves
became commercially available & were soon in great
demand
DEVELOMPENT OF
PULMONARY AUTOGRAFTS
In 1967 Ross performed the first pulmonary
autograft operation for aortic valve replacement.
Initially autogenous pulmonary valve was used as
a sub- coronary implant & later as a full aortic root
replacement.
Ross anticipated that autologus pulmonary valve will
remain viable & maintain potential for growth in
children. Experience have shown this to be true.
Whilst Ross persisted with his operation
others were reluctant to perform a complex
double root replacement for isolated aortic
disease which otherwise could be treated with
very low morbidity & mortality with a stented
valve.
DEVELOPMENTS IN
REPLACEMENT OF MITRAL VALVE

Ross then attempted to replace mitral valve with a
mitral homograft. Though early post-operative
hemodynamics were excellent, most patients
sustained rupture of chordae tendeniae within a
few months of operation. In addition proper
placement of papillary muscles inside LV required
considerable judgment & skills. Because of these
reasons MV homografts replacement has never
regained wide spread acceptance.
RESSURECTION OF
STENTLESS VALVES

It was being increasingly realised that
presence of stent is a disadvantage as it
accelerates tissue degeneration. It also tends
to obstruct the flow through the valve albeit
to much lesser extent than mechanical
valves.

In 1988 Tyrone David reexplored the use of
stentless gluteraldehyde
fixed aortic xenograft.
Hemodynamic evaluation
showed very small
gradients & minimal
regurgitation in early
implants.
David then went on to develop a low pressure
fixed stentless, cloth covered porcine valve.
This device is now known as Toronto
SPVmarketed by SJM Inc. This device lacks
sewing ring & this allows insertion of a larger
valve in individual annulus. This valve
provided an alternative to aortic homografts
which are always in limited supply inspite of
development of cryopreservation techniques.
St. Jude Toronto SPV
Along the same lines Medtronic Inc.
introduced their stentless ‘ Freestyle’ valve
in the form of porcine aortic root with
Dacron covering of inflow portion. This is a
gluteraldehyde preserved, zero pressure
fixed valve treated with alpha-amino- oleic
acid which acts as a anti-mineralising
agent.
Medtronic Freestyle Stentless Valve
SPECTRUM OF BIOLOGICAL
VALVES AVAILABLE FOR CLINICAL
USE TODAY
Stented porcine valves– e.g. C. E., Hancock
 Stentless porcine valves – e.g. Toronto SPV
 Pericardial xenografts
 Aortic or pulmonary allografts
 Pulmonary autografts

STENTED PROSTHESES

Stents used in modern valves are made-up
of Elgiloy, Delrin, Acetylco-polymer resin.

Advantages of a stentStent provides framework for supporting the
leaflets, it also makes implantation easier as
compared to valves without a stent.
Disadvantages of the stent
They increase stress on leaflets causing
accelerated degeneration.
 They are obstructive to flow & hence
increase the gradients across the valve.
 In mitral position they can cause LVOT
obstruction or even rupture of LV especially
when a large valve is used in presence of
small LV cavity.

Comparison between orifice area
in stented and stentless valves
Stentless
Stented
PRESERVATION/ FIXATION OF
TISSUES IN BIOLOGICAL VALVES




Currently gluteraldehyde is the preferred agent.
It cross links the collagen & increases the strength
of tissues
It also acts as a sterilizing agent.
Preservation with gluteraldehyde can be done at
High pressure ( 60 - 80 mm Hg)
Low pressure ( Less than 2 mm Hg )
No pressure ( 0 mm Hg )
Modern prostheses are fixed with either low
pressure or zero pressure, this is believed to
maintain collagen crimp frame work which will in
turn maintain physical properties of biological
tissues.
ANTI-MINERALIZATION
TRATMENT



Dystrophic calcification is an important factor
which contributes to delayed failure of biological
valves. This problem is more severe in patients
who are young or who have chronic renal failure.
Pathogenesis of bioprosthetic calcification is
incompletely understood.
Calcification occurs initially in areas of maximal
mechanical stress e.g. commissures. But there are
both host related & bioprosthesis related factors.
Gluteraldehyde in itself is a promoter of calcification
as it can chelate calcium.
There are various agents which are currently being
used as decalcification agents v.i.z. Alpha- oleic acid,
Polysorbate 80, Sodium decadecyl sulphate, Toludin
blue etc.
Cells & cellular antigens are also believed to promote
calcification. They can be removed by enzymatic
detergents leaving only acellular matrix. This process
is presently used in SJM-X-CELL investigational
prosthesis.
CURRENT RESEARCH IN
BIOPROSTHETIC PRESERVATION

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Use of gluteraldehyde can be detrimental. There is
extensive research going on to find an alternative.
Epoxy compound Denacol has been found to be useful,
however high concentrations can be cytotoxic.
Diphosphonates, acyclazide, carbodimide are other
agents are under investigation.
Photo-oxidation of bioprostheses promotes collagen
cross linking & is being experimented.
Seeding of viable endothelial cell on biological tissues
with the aim of endothelization of bioprosthesis is also
under investigation.
PROCESSING OF
ALLOGRAFTS
Presently three types of allografts are
available



Cryopreserved
Antibiotic preserved- with cryopreservation they
are obsolete now.
Fresh allografts- They are available increasingly
due to increased no. of heart transplants.
ALLOGRAFT PROCURMENT
Nondiseased valves are removed from
hearts of heart transplant recipients ( Age
6month- 55 years).
 Sterile technique is observed during
harvesting.
 Ascending aorta with aortic valve in situ is
removed, origin of innominate artery marks
the distal extension & LV base with AML
marks the proximal extent of the block.

Harvesred Aortic Allograft Block
Harvested sterile graft is then preserved in
culture medium ( RPMI 1640) + Antibiotics
e.g. Lincomycin + Cefoxitin +Vanco +
polymixin B
 Stored at 4* C
 This graft can then be used directly as a
homovital graft or can be cryopreserved
(- 40 *C) for future use.

During allograft preservation viability of
cellular & mechanical components is very
important.
 Fresh allografts do have clearly viable cells
( endothelial & fibroblasts ) at the time of
implantation.
 However, preservation of cellular viability
has disadvantage of inducing
immunological response

HEMODYNAMICS OF
BIOPROSTHETIC VALVE



Bioprostheses have superior hemodynamic
performance as compared to any mechanical prosthesis
currently available.
Central laminar flow is the the biggest advantage, this
minimizes turbulence & also decreases
gradients.However, presence of stent does impede flow.
The hemodynamic performance of free hand allograft is
excellent & is more or less similar to native valve.
MECHANICAL Vs TISSUE VALVES

OVER THE PAST 20 YEARS MECHANICAL &
TISSUE VALVES HAVE CONTINUED TO
IMPROVE THOUGH DEBATE OVER THEIR
RELATIVE MERITS CONTINUES.
Tissue
Mechanical
Life span
Finite
Infinite
Str. Failure
Higher chances
Minimal chances
Hemodynamics
Excellent
Acceptable
Long term anticoagulatio
Event free survival
Not required
Must
Technical skill
Better despite the need
of reoperation
More with stentless
INDICATIONS FOR USE OF
BIOLOGICAL VALVES
 Biological
valves are preferred when -
There is contraindication to use of
anticoagulation
 Women in reproductive age group who wish
to conceive
 Patients over 65 year of age


STS database reveals that Mechanical valves were used in 56-62%,
Xenograft in 32-38% &
Allograft or autografts in 6%

For AVR, generally
65 yrs & above – Bioprosthesis preferred
40 – 65yrs - Mechanical or allografts
16 – 65yrs – Mechanical, allografts or
autografts
Paediatric group – Mechanical or autograft

Stentless porcine bioprostheses are currently
recommended for elderly with small annuli.
It is also proposed as an alternative to allografts.
Limited supply of allografts restricts its use to
selected patients, particularly those with native
valve or prosthetic valve endocarditis complicated
by annular abscess or ventriculo- aortic
discontinuity.
They are also preferred in young & middle aged
patients.
CONTRAINDICATIONS TO
BIOLOGICAL PROSTHESES

Mechanical valves are preferred than biological
in patients who have –
- Hypercalcemic syndrome
-CRF
Bioprostheses are usually avoided in young
patients as degeneration & calcification occurs
early.
CLINICAL PERFORMANCE
OF BIOLOGICAL VALVES
Clinical performance of a valvular prosthesis is
judged according to the ‘Guidelines for reporting
morbidity after cardiac valvular operations’
( Edmunds etal, ATS, 1988)
Literature provides extensive documentation of
individual prostheses, combination of prostheses
& comparisons between mechanical & biological
prostheses. Only few randomised studies are
available which include Veterans Administrative
trial (VA) study on valvular heart disease &
Edinburgh heart valve trial.

PERFORMANCE OF STENTED
XENOGRAFT PROSTHESES
Current C-E pericardial prosthesis- Pellerin
& co-authors in 64 yr old population report
10 yr freedom of structural failure of 93.5%.
At 12 yrs no patient had reoperation for
structural failure.
Cosgrove & co-authors have come out with
similar results.
CLINICAL PERFORMANCE
OF ALLOGRAFTS

There are no randomised trials comparing
allografts to mechanical or bioprosthetic valves.
Thromboembolism essentially does not occur with
allografts.
The method of allograft preservation determines
the rate of structural valve degeneration.
O’Brien reports 91% freedom from structural at
12 yrs for patients between 20-60 yrs.
CLINICAL PERFORMANCE
OF AUTOGRAFTS

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
Ross has reported 85 % freedom from reoperation
at 20 yrs for his procedure of pulmonary autograft
for aortic root replacement.
Elkins report that pulmonary autografts in children
grow with somatic growth.
The complexity of this operation & related
morbidity & mortality affect the eventual place of
this operation for aortic valve replacement surgery.
PERFORMANCE OFBIOPROSTHESES IN
MITRAL POSITION
Jamieson etal have reported that durability of
bioprostheses is less in mitral position than
in aortic position.
This more rapid deterioration may be due to
higher pressure sustained by cusps during
ventricular systole than pressure sustained
during diastole.
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