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Review Article
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
Journal of Integrative Cardiology
ISSN: 2058-3702
An integrative approach to the Marfan aortic root between
the patient, the physician and basic scientists: A case study
in personalised external aortic root support (PEARS)
Tal Golesworthy1, Peter Verbrugghe2, Cemil Izgi3, Shelly Singh4 and Tom Treasure5*
1Exstent Ltd, Tewkesbury, UK
2Department of Cardiac Surgery, UZ Leuven, Herestraat 49, 3000 Leuven, Belgium
3Cardiovascular Magnetic Resonance Unit , Royal Brompton Hospital , London, UK
4Department of Chemical Engineering , Imperial College, London, UK
5Clinical Operational Research Unit, University College London, London, UK
Abstract
Aortic root aneurysm is a characteristic feature of Marfan syndrome and is the commonest cause of death in the natural history of this condition. Aortic root
replacement, introduced in the 1960s and iteratively developed over the subsequent thirty years dramatically improved the prognosis for people with Marfan syndrome.
In 2004 a fundamentally dierent approach was introduced. Rather than surgical resection of the brillin decient aorta, and its replacement with a fabric tube graft,
an external support, custom made to the shape and size of the individual’s aortic root, was manufactured in preparation for surgery. At operation this is positioned
around the aorta extending proximally to the aorto-ventricular junction and distally to beyond the origin of the brachiocephalic artery. is operation has now been
done in over 65 patients, mostly with Marfan syndrome, with 270 patient/years of follow-up. e mesh is soft, pliable and macroporous. Histologically the mesh can
be seen to become incorporated in the aortic adventitia with collagen bres passing through its interstices to form a strong composite neo-aorta without sacricing
the natural blood/endothelial interface and maintaining the natural support of the aortic valve within the sinuses of Valsalva. In this article we concentrate on the
collaborations between disciplines which have allowed the development and further investigation of this method. All conclusions at this stage are tentative because
the follow-up is not long enough to be fully condant of the results. At present the best indication for PEARS is early in the progression of the root aneurysm when
it oers conservation of the aortic valve and the blood/endothelial interface with the hope of indenitely minimising the hazards of the aortic root.
e clinical problem
‘e signature manifestation of cardiovascular pathology in MFS
is a grossly dilated aortic root, which commonly results in aneurysm,
aortic valve regurgitation, and an increased risk of dissection, rupture,
and death; hence, the root is the source of all evil aecting patients with
MFS’ [1].
is stark summary from one of the USA’s leading surgeons
specialising in aortic disease is a fair introduction to the problem.
e ‘natural history’
e expectation of life for people with Marfan people is severely
reduced by the prospect of aortic dissection. e landmark study
came from Johns Hopkins in Baltimore, USA and it remains our best
estimate of the natural history of the disease. In their dataset were 257
patients with Marfan syndrome. Half of the men had died by their late
thirties and the average age of death for women was about ten years
later. e average age at death was 32 years and where the cause was
known it was overwhelmingly the result of aortic root dissection [2].
A more sophisticated study of natural history will never be possible
because now, at the rst suspicion of Marfan syndrome, the aortic
root can be measured non-invasively by echocardiography. is was
undreamt of at the time the Johns Hopkins authors were accumulating
their data. However, there is no reason to revisit it: the main thrust of
their evidence in incontrovertible (Figure 1).
People with Marfan syndrome still die of aortic dissection and many
of these deaths should now be avoidable (Figure 1 and 2). e underlying
problem is deciency of brillin-1 which is both a structural protein and a
regulator of the transforming growth factor β (TGF-β) signalling pathway.
Clinical trials of medical treatment intended to stabilise the brillin-
decient aorta of Marfan syndrome have so far failed to show the clinical
benet which was hoped for based on experiments in mice [3]. ere can
be little room for doubt that surgery to prevent dissection of the aortic root
remains for now the single biggest contribution to the greatly increased
expectation of life for people with Marfan syndrome who can now
expect to live on average into their seventies. Until the central problem
of genetically determined brillin deciency can be solved, prophylactic
surgery is the mainstay for treatment and more than doubles their average
life expectancy from fewer than four decades to more than seven decades
(Figure 2).
e rst x
Bentall’s case report from 1968 is universally accepted as the ‘rst
Correspondence to: Tom Treasure, Clinical Operational Research Unit,
University College London, London UK, E-mail: tom.treasure@gmail.com
Key words: aortic root aneurysm, Marfan syndrome, external support
Received: May 02, 2016; Accepted: May 21, 2016; Published: May 24, 2016
Golesworthy T (2016) An integrative approach to the Marfan aortic root between the patient, the physician and basic scientists: A case study in personalised external
aortic root support (PEARS)
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
composite replacement of the ascending aorta and the aortic valve
[4]. Surgical replacement of the ascending aorta for aneurysm was
a considerable challenge at the time and when it had been done, the
proximal anastomosis was made distal to the coronary orices [5].
ere had been cases of replacement of the aneurysmal aorta and the
valve but that le the sinuses of Valsalva, the most vulnerable part of
the aorta, still there to present a hazard. Replacement of the aorta
and valve together and reattaching the coronary arteries was Bentall’s
breakthrough.
e iterative improvements to reach ‘the modern
Bentall’
Aer Bentall’s publication, root replacement slowly became
established it but remained a challenging operation. It was unmentioned
in the Johns Hopkins paper four years later in 1972 and until the 1980s
it was an operation only performed in relatively few centres and then
only when the aorta was at threatening size. e rst PEARS operation
was in 2004 and while there have been more than 60 operations
performed it too has passed unremarked twelve years later in the most
recent publication from Johns Hopkins [6] while valve sparing root
replacement has become the more frequently performed operation
rather than the modern Bentall. Surgeons are understandable reluctant
to embark on new and potentially hazardous operations but we know
that there is a risk for the patient if surgeons are prevented from taking
risks in a risk averse society [7].
In the present article we reect in the integrative research work
undertaken to reach the point where aortic root surgery is now [8]. e
undesirable aspects of the original Bentall operation were overcome
stepwise. e original tube gras had to be preclotted; successive
introduction of collagen and gelatine sealed gras overcame that
problem. Surgeons initially had to hand sew the valve into the tube
but later manufacturers provided surgeons with factory made valved
conduits. e coronary anastomoses were for a time the Achilles’ heel
of the operation. e ostia were originally sutured en face into the tube
gra and the aorta wrapped around the gra but perigra leaks and
pseudoaneurysm formation were a familiar problem. With surgical skill
and practice a button technique, in which the coronaries were directly
anastomosed to the tube gra, largely overcame those problems.
Valve sparing root replacement
e next great step was valve sparing root replacement. Some
surgeons were concerned that the valve leaets would also prove to be
involved with the degenerative disease. Valve sparing versions of the
operation were separately developed by Yacoub [9] and David [10] and
the valve leaets proved to be durable. When they failed it was not
leaet tissue failure that was the problem. More oen it was continued
dilatation of the root or other factors related to the architecture of the
root and the support of the aortic valve. Time has shown that of the
two, David’s approach has been less prone to this mode of failure and
is now generally preferred.
e opportunity to conserve the patient’s aortic valve and avoid
life-long anticoagulation encouraged intervention earlier in the
progression of aortic root aneurysm formation, while the valve could
be more predictably and successfully conserved. e risk of dissection
is related to the size of the aorta and to its rate of change in size. In
recommending surgery other factors are taken into account such as
aortic valve regurgitation or an ominous family history which would
prompt earlier intervention. As root replacement could be performed
with progressively lower risk, there was progressive reduction in the
threshold size at which a patient`s risk of dying with even a relative
small aneurysm exceeded the risks of surgery [11]. In 1993 the suggested
threshold for recommending root replacement in Marfan syndrome
was 5.5 cm [12]. By 2000 it was 5.0 cm and consensus guidelines in
Europe and America now recommend 4.5 cm [13,14]. However this
is still major surgery and there are perioperative and ongoing risks.
e biggest concern with valve sparing surgery is later onset and
progression of aortic valve regurgitation resulting in further surgery at
a rate of about 13% per decade. On the other hand, root replacement
with a mechanical valve is associated with 7% thromboembolic risk per
decade [15].
A new way of thinking
One of the present authors (TG) and engineer in research
and development faced having a composite aortic root gra and
consequent life-long warfarin anti-coagulation. It was actually the fear
of permanent anti-coagulation that drove him to think of another way
[16]. He was reconciled to the need for surgery but could not see why
his aorta and working valve had to be removed. His question was why
Figure 1. Computed tomography images and explanatory surgeon’s drawing of a Type A
aortic dissection in a patient with typical Marfan syndrome from a family with numerous
affected members. The dissection has halted ow to the left kidney which is not functioning.
The dissection proved fatal.
Figure 2. Cardiac magnetic resonance image of a typical Type A dissection.
Golesworthy T (2016) An integrative approach to the Marfan aortic root between the patient, the physician and basic scientists: A case study in personalised external
aortic root support (PEARS)
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
not used modern methods of design and prototype manufacture to
create an external support?
Research before “the rst in man”operation CAD
modelling and making a rapid prototype
For each patient, measurements derived from MRI or CT images
are processed using a dedicated computer aided design (CAD) routine,
specically designed to model the ascending aorta, to produce a 3D
reconstruction of the individual patient’s aorta [17]. Initially MRI
was used particularly because we anticipated the need to do repeated
imaging of the aortic root to monitor the shape and size of the root.
Later we have increasingly used CT (Figure 3).
One important lesson learned in the context of integrative medical
research was the revelation that medicine had fundamentally broken
the convention in displaying images. Plans and architects’ drawings
are always set up so that the view point is above. at is true even
for roofers. e earliest images of the heart were its silhouette on
chest radiographs. ese are viewed as if facing the patient with the
right side of the patient’s image to the doctor’s le, matching the view
of the patient in front of her. When cross sectional images became
available for reasons of the convention of the ‘anatomical position’
the spine was downward and this was appropriate as the images were
made with the patient is lying supine. A convention emerged that they
too would be viewed with the patient’s right to the doctor’s le. is
has the result the cross-sectional images are viewed as if from below
opposite to other plan views. e rst reconstructions were brought to
a clinician to review (TT). e aorta was seen as a 3-D reconstruction
on a computer screen. Of particular importance to the engineer
was conrmation of the correct siting of the coronary attachments.
Rotating the image clockwise and anticlockwise the image on the
screen did not make sense. Suddenly the explanation dawned. e
engineer had reconstructed the images in the convention of plan
views intended to be looked at as if from above and had thus created
a vertical mirror image of the aorta [18]. is led to an important and
generalizable lesson. In integrative research it is vital to take nothing
for granted and to ensure that we take time to explain and listen to
each other with particular respect to discipline-specic nomenclature,
measurement and embedded conventions. It was said to be a failure to
recognise dierent measurement conventions that led to the crash of
NASA’s $125-million Mars Climate Orbiter in 1999.
e chemical properties and biological interface issues
Vascular gras have been made for well over y years
from a polymer PolyEthylene Terephthalate (PET). It has good
biocompatibility. It is made into fabrics/textiles of various kinds for
use in surgery. e familiar vascular gras are made in a low porosity
weave so that the interstices will quickly seal as coagulability is restored
when heparin is reversed. It is also useful if they have some wall stiness
so that they will follow a curve with a low tendency to kink. However
this produces sti material with abrasive edges. Surgeons who devised
means of ‘wrapping’ the aorta used the material to hand and it was
these vascular gra textiles that were used [19-21] (Figure 4).
One disadvantage of using vascular gras in this way, and one
repeatedly brought to our attention, is that there are reported instances
of wraps ‘migrating’ [22]. As the material shis its abrasive edge can
injure delicate structures and particularly the nearby coronary arteries.
e macro physical properties required of an external support textile
for the aorta are signicantly dierent from the conventional sti,
woven gras then available.
e fabric used for external support, (ExoVasc® PEARS implant,
Exstent Ltd, Tewkesbury, UK) while being the same polymer and
similar biocompatability is knitted and much less dense. It is very so
and presents no edge. It is also porous with interstices of 0.7 mm. is
would be fatal if used to replace an arterial wall because the patient
would bleed to death in minutes but haemostasis is not required of
the fabric in the PEARS operation. e blood is still contained within
the patient’s own aortic wall with its healthy and normal endothelium
providing a kindly interface with the blood (Figure 5-8).
First in man
On 24th May 2004 the rst operation was performed and the rst
recipient was the inventor himself [23]. e operation was carefully
worked out and there has been not revision of the essential features of
Figure 3. A computer aided design (CAD) model viewed on the screen. The orices of the
pulmonary artery are marked. Viewed as if from the patients left the right coronary arises at
the front of the aorta and the left coronary orice to the rear. The ‘left’ in this nomenclature
is because the artery supplies predominately the ‘left’ ventricle which is in turn is named
more for reasons of physiological right/left heart conventions than that it is leftward. Figure 4. A completed ascending aortic replacement. 1985.
Golesworthy T (2016) An integrative approach to the Marfan aortic root between the patient, the physician and basic scientists: A case study in personalised external
aortic root support (PEARS)
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
the method although there have been renements with experience. e
external support was brought to the operating table on its former which
is an exact model of the patient’s own aorta and the orientation can be
visually conrmed (Figure 5). Fine right angle forceps are useful for
dissecting “under” the coronary arteries (Figure 6). Control of arterial
pressure is vital especially when dissecting between the aorta and right
ventricular outow tract. Aer careful conrmation of the orientation,
the openings for the coronary arteries are made in the support mesh
(Figure 7). ese are made in the form of asterisks so that no one edge
impinges in the coronary artery but the tongues can extend onto its
external surface oering an opportunity to be tethered there by the
healing process. e longitudinal seam, which is anterior and runs
down the non-coronary sinus, is opened. e transverse extensions
from the axial seam to the coronary openings are made. e tongues of
mesh material which are thus created are passed proximal to (beneath)
the coronary arteries and the incisions in the mesh extending to the
coronary orices are then sutured. e lower margin of the support is
secured to the aorta-ventricular junction. e anterior seam is sutured.
With the arterial pressure low, the mesh is loose around the aorta but
as the pressure is allowed to normalise the aorta expands and puts the
supporting mesh under tension (Figure 8).
Research aer 1st in man
e rst operation was in the inventor. Why not an animal? It
is in fact unusual for operations to be rehearsed in animals before
being applied in man, even though that might be a public perception.
More oen the rst attempts are made, as here, in humans and if the
operation looks as though it is worth pursuing, this prompts animal
experiments to resolve biological questions. at may be surprising
but is has very oen been the case
Biological incorporation
ere had been prior experience with this PET fabric but it had
appeared with the word ‘girdling’ in the title [24]. is defeated our
searches. We are at fault too for putting ‘jacket’ in our original title
[23] and other subsequent reports have has used the words ‘sleeve’[25]
and ‘corset’[26]. We now think that tricky and enigmatic titles are best
avoided; they may defeat indexing and searching to no one’s advantage.
e ‘girdling’ paper by Cohen et al should have been known to us in the
development phase but it was not and we had to discover the potential
for incorporation for ourselves. Cohen et al present a histological image
in their paper showing the mesh incorporated in the aortic adventitia
with ingrowth of collagen (Figure 9).
Colleagues in Leuven undertook a series of survival experiments
in sheep to address the uncertainties we had about the security of the
external support and its eect on the histology of the blood vessel wall.
Figure 5. The shape is provided by the rigid former. The mesh itself is soft, pliable and with
no stiffness or hard edges as can be seen beyond the extent of the former. The seam up the
front is released and re-sutured once the mesh is positioned around the aorta.
Figure 6. A tense moment as the dissector is passed proximal to the left coronary artery.
Figure 7. An incision will be made from the longitudinal seam but the opening for the
coronary artery itself is an asterisk conguration so that no edge is presented directly to
the coronary artery.
Figure 8. A schematic to show the eventual position of the mesh with respect to the
brachiocephalic artery (BCA) and the left and right coronary arteries (RCA, LCA) and
the tethering stitches to aortoventricular junction. The tethering is a temporary measure
because the ask shaped nature of the mesh and the root will cause it to retain its position
and it becomes adherent and eventually incorporated.
Golesworthy T (2016) An integrative approach to the Marfan aortic root between the patient, the physician and basic scientists: A case study in personalised external
aortic root support (PEARS)
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
e carotid arteries of growing sheep were enclosed in a sleeve of our
support mesh. Aer 4-6 months the arteries were excised. ere
was an increase in the overall thickness of the arterial wall (Figure 9)
[27]. is in contrast to the report of Neri et al in which the aortic
wall underlying the reinforcement of a conventional woven gra was
extremely thin with atrophy of the aorta [28]. Histological evaluation
of the supported carotid arteries showed densely incorporation of the
mesh in the adventitia, associated with a strong brotic reaction. is
was reected in a signicant increase in maximum tensile strength of
the supported segments compared to normal arterial tissue [27].is in
itself would prevent aortic rupture, as this occurs when the wall stress
exceeds the tensile strength of the aortic wall. is overall increasing in
thickness of the aortic wall is discernible on the MRI images in the rst
patients aer ten years (2004 to 2014) (Figures 10 and 11).
Autopsy ndings
Only one patient has died with a mesh in place providing our only
opportunity to see how the mesh behaves in the human Marfan aorta.
is conrmed the previous observations that collagen bres had grown
through the interstices of the mesh (and between bres in the threads/
yarns) and outside it making a tight integrated neo-aortic wall [29]. is
was just as we had seen in the sheep and was as we hoped and perhaps
expected. Not expected and remarkable was that there appeared to be
Figure 9. Sirius red staining of a carotid artery ve months after being sleeved with mesh.
It shows an intact vascular architecture with densely incorporated mesh material with a
brotic reaction around it.
Figure 10. The cardiac magnetic resonance (CMR) images of the rst patient (TG) before
and then years after undergoing the rst PEARS operation.
Figure 11. The cardiac magnetic resonance (CMR) images of the rst patient (TG) before
and then years after undergoing the rst PEARS operation.
Figure 12. Longitudinal stress distributions in nite element models (with and without
aortic root motion) of a Marfan patient before and after PEARS implantation
healing of the media. Histological sections of the aorta from the arch,
beyond the support, showed the characteristic appearance of medial
degeneration. More proximally, where one would have expected the
histology to be worse, with more degenerative changes, it was in fact
normal with respect to the histological appearance. e most likely
explanation is that the degeneration of the aortic media had healed.
While we were surprised to see it, on reection a standard tried and
tested means of getting collagen to heal elsewhere is to splint it. at is
how torn tendons are treated. Were we witnessing for the rst time a
benecial eect on splinting on the aorta? (Figure 11).
Proof of principle in terms of holding the sinuses and
valve
We studied the eect of external support in a rigorously conducted
prospective study in the rst ten patients operated on from 2004 to
2007. All patients had surgery as planned without complications and
had completed at least one year of follow-up. MRI images before and
aer PEARS were presented for measurement amongst duplicate
images of 37 unoperated Marfan patients to permit assessment of intra-
observer measurement reproducibility. All 94 images were presented
in random sequence to a radiologist unaware of the research question.
Golesworthy T (2016) An integrative approach to the Marfan aortic root between the patient, the physician and basic scientists: A case study in personalised external
aortic root support (PEARS)
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
Measurements were made of the ascending aorta at the level of closure
of the aortic valve cusps from magnetic resonance imaging studies taken
preoperatively and at xed intervals thereaer. e largest dierence
between the preoperative measurement and that made at least one year
aer surgery was determined. In eight of the ten patients, the largest
observed change was a marked reduction in aortic root diameter. e
primary objective of this surgery was achieved in each case, reinforcing
the ascending aorta whilst leaving the native aortic valve intact and
conserving the blood/endothelium interface (Figure 11).
e conguration of the aorta was unchanged and there were no
instances of valve deterioration. e aortic root dimensions were
generally smaller. is is because under operative conditions the
aorta is under less tension and closure of the mesh holds it at a slightly
smaller size which was an inadvertent but welcome eect.
Means of comparison before it is possible to have a
randomised trial
We were prepared to subject PEARS to a randomised controlled
trial and proposed this in journal articles and in meetings [30,31]. is
was going to take time so rst we started by doing a matching study
using available data. Our hypothesis was that PEARS reduced the
burden of care compared with aortic root replacement.
A matched comparison group, of similar age, aortic size and aortic
valve function to those having the novel intervention, was constructed,
by minimization [32] from among patients who had aortic root
replacement during the same time frame. e rst 20 patients, aged
16-58 years with aortic root diameters of 40-54 mm, having external
support surgery were compared with 20 patients, aged 18-63 years and
aortic root diameters of 38-58 mm, who had conventional aortic root
replacement, between May 2004 and December 2009.
Comparing total root replacement and customised aortic root
support surgery, cardiopulmonary bypass (CPB) was used in only the
rst PEARS patient for 20 minutes compared with 134 minutes (range
52-316 minutes) for root replacement. ere was no myocardial
ischaemia for PEARS but a median of 114 minutes (41-250 minutes)
for root replacement. ere were similar large dierences for blood
loss and blood product usage which was rarely required for PEARS.
Opportunities for explicative research
Aortic wall stress by MRI
ere was much theorizing as to whether supporting the ascending
aorta might transfer the stress to other parts of the aorta. e critics
largely avoided the fact that tube gra replacement had been practiced
for y years and this was not a central problem. However we were
accumulating a good number of patients and had the opportunity to
study this question with magnetic resonance imaging. e aim of this
study was to assess the mechanical eects of PEARS on aortic root
systolic downward motion (an important determinant of aortic wall
stress), aortic root distension and on the le ventricle (LV).
e cohort of 27 Marfan patients who had prophylactic PEARS
surgery between 2004 and 2012 were included. Systolic downward
aortic root motion and aortic root distension before the operation and
in the latest follow-up were measured randomly and blindly aer a
median follow-up of 50 months (IQR 26-72) following implantation of
PEARS. Systolic downward motion of the aortic root was signicantly
decreased (12.6 ± 3.6 mm pre-operation vs. 7.9 ± 2.9 mm latest follow-
up, p<0.00001) [33] (Figures 12 and 13).
is work was taken a step further with engineering colleagues
at Imperial College London. e biomechanical implications and
haemodynamic changes associated with PEARS was investigated
using combined cardiovascular magnetic resonance (CMR) imaging,
nite element (FE) analyses and computational uid dynamics (CFD).
Patient-specic aortic geometries were reconstructed from pre-
and post-PEARS CMR images of three Marfan patients. In the FE
models, the wall and PEARS materials were assumed to be isotropic,
incompressible and linear elastic, and a static load corresponding to
the patients’ pulse pressure was applied with a zero-displacement
constraint at all boundaries. Results revealed peak aortic stresses and
displacements before PEARS were located at the sinuses of Valsalva
Figure 13. Pre- and post-PEARS instantaneous velocity streamlines in a Marfan patient
at peak systole and mid-systolic deceleration obtained using combined CMR imaging and
CFD modelling.
Figure 14. A series of ‘copies’ of individual patients’ aortas showing the variation of shape
and dimensions.
Golesworthy T (2016) An integrative approach to the Marfan aortic root between the patient, the physician and basic scientists: A case study in personalised external
aortic root support (PEARS)
J Integr Cardiol, 2016, doi: 10.15761/JIC.1000163 Volume 2(3): 295-302
but following PEARS surgery, they were shied to the aortic arch, at the
interface between the supported and unsupported aorta. Nevertheless,
the peak stresses found in all these models were well below the tensile
strength for dilated ascending aortas. In a subsequent study, the zero-
displacement constraint at the aortic root was replaced with a systolic
downward aortic root motion which revealed the PEARS signicantly
reduced the maximum longitudinal stress in the ascending aorta
(Figure 12). e point of maximum stress and therefore greatest change
was in the rst few centimetres of the ascending aorta, the site at which
the intimal tear of aortic dissection was most likely to occur [33].
For the CFD models, upstream ow conditions were derived
from phase-contrast MR images. CFD results showed the qualitative
patterns of the haemodynamics were similar pre- and post-PEARS, as
seen in Figure 13, with variations in mean helicity ow indices of -10%,
35% and 20% in the post-PEARS aortas. It can be hypothesised that
morphological and functional alterations of the aortic wall in the post-
PEARS aorta resulted in the observed changes in the haemodynamic
parameters when compared with the pre-PEARS aorta. Interestingly,
all values were within the reported range for normal aortas [34-36].
Regulatory issues
Introducing a new technique in surgery is now quite tightly
regulated although it must be said that it is not as tightly regulated as
pharmaceuticals. PEARS was initially performed under the scrutiny of
Research Ethics Committee of the Royal Brompton Hospital and has
subsequently been through Health Technology Approval under the
British system of NICE approval [37]. It is now being considered for
commissioning outside the innovating centres through a mechanism
called Commissioning through Evaluation [38].
Cognitive cul-de-sacs
is experience of integrative research has been instructive in
considering how we rethink problems. e nobel prize winning scientist
Peter Medawar postulated that the dinosaurs were an ‘end product’
and might be seen as an evolutionary cul de sac. Mammals including
ourselves were not a product of further evolution from the dinosaur but
a step back to an earlier evolutionary branch. e eventual solution is
not always reached by relentlessly solving the problems of the previous
design. ere were many iterative changes to the Bentall operation but
the radical change was then to conserve rather than replace the aortic
valve. David’s operation is in its sixth version and while the operation
provides excellent clinical outcomes, there are occasional deaths and
problems, early and late.
An alternative is to reframe the question in the light of opportunities
oered by new technology. What matters to the Marfan patient is
maximising life and minimising risk and fear. e non-ablative tissue
sparing solution oered by PEARS may allow very early low-risk pre-
emptive surgery, safeguarding many Marfan patients at an earlier stage
in what were precarious lives. In the future, also patients with other
types of aortic disease might benet from this technique (Figure 14).
e radical idea that resulted in PEARS was not to remove but to
conserve the aortic wall. is straight away avoids all the problems
related to the blood/endovascular interface. It also greatly reduces the
magnitude of surgery. Added to these is the rather remarkable nding
that not only does it result in a very satisfactory neo-aorta but then
there is the observation that the supported aortic media is capable
of healing, albeit in its brillin decient state. And nally to be able
to customise, individualise or personalise (call it what you will) the
device to the patients is made possible by modern image acquisition,
manipulation and going from image to a three dimensional product.
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Copyright: ©2016 Golesworthy T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
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