CLASSICS IN THORACIC SURGERY
Ross’ First Homograft Replacement of the
Aortic Valve
Richard A. Hopkins, MD, James St. Louis, BS, and Philip C. Corcoran, MD
Department of Surgery, Georgetown University Medical Center, Washington, DC
Ross’ first homograft replacement of the aortic valve was
reported in 1962. The homograft has been in continuous
use around the world ever since. Much has been learned
about how to handle homografts, both before and during
their implantation. Homografts have special advantages,
which make them an appropriate choice in a number of
V iable cardiovascular allografts were first clinically
used by Gross in 1948, and then in 1952, DuBost
established aortic continuity with a homograft aorta after
resecting an abdominal aortic aneurysm. Direct cardiac
applications were conceived in the laboratory prepara-
tions of Lam and associates [l]. Valved aortic homografts
were first used when placed in the descending aorta to
ameliorate native aortic valve insufficiency by Gordon
Murray in 1956 [2], but the first orthotopic use of a
homograft for replacement of an aortic valve occurred in
July 1962 and was reported 6 weeks later in The Lancet by
Donald Ross [3]. This operation preceded by about 1 week
a similar procedure by Barrett-Boyes in New Zealand [4].
To understand the importance of this 1962 contribution,
it must be placed in context with the evolution of cardiac
surgery. The cardiopulmonary bypass machine had only
been available since 1954. The mechanical cardiac valve of
Starr (1960) had been reported but was not yet available in
the United Kingdom. There were many patients requiring
treatment for valvular heart disease, and the limitations of
valvuloplastic methods were increasingly appreciated.
The current resurgence of interest in homografts makes
another look at this initial contribution by Donald Ross
more pertinent.
Ross Operation-The Real Story
A fair amount of folklore has arisen about this first case
and somewhat apocryphal stories are in circulation. As it
turns out, Ross was quite cognizant of Lam‘s work on
dogs in the 1950s and of Duran and Gunning’s technical
advances placing a homograft aortic valve in the “subcor-
onary position.” In fact, their preliminary communication
[5] was reported in the same issue of The Lancet on the
page next to the publishing of Ross’ clinical experience.
Ross and his laboratory colleagues had been working on
freeze-drying aortic valves and had been collecting valved
aortic roots, evaluating them in their pulse duplicators
both before and after freeze-drying. At the time of the
reported operation, Ross had a small bank of freeze-dried
Address reprint requests to Dr Hopkins, Department of Surgery 4PHC,
Georgetown University Medical Center, 3800 Reservoir Rd, NW, Wash-
ington, DC 20007-2197.
0 1991 by The Society of Thoracic Surgeons
settings. This first successful case by Donald Ross set the
stage for the growth in homograft valve use and the
subsequent development of many ways of using al-
lograft cardiovascular tissue for optimal cardiac recon-
structions.
(Ann Thoruc Surg 1991;52:1190-3)
valves and was prepared to use one in the orthotopic
position, even though he had not yet sewn one in a dog
(Donald Ross: personal communication). Initially Mr Ross
attempted a decalcification of the native valve leaflets,
which resulted in total destruction during the operation.
The freeze-dried homograft was reconstituted and su-
tured into position with six separate mattress sutures and
a distal suture line consisting of continuous 3-0 silk. The
patient’s atrial septa1 defect was also closed. He survived
approximately 3 years without evident aortic valve dys-
function, and apparently, no autopsy was performed
(Donald Ross; personal communication, 1991). The pa-
tient’s death was due to cardiac failure, consistent with
the stage at which aortic valve operation was undertaken
in those early days.
As previously demonstrated in this series, ”chance
favors the prepared mind”; it is clear that this operation
was not due to simple, quick thinking. Ross was prepared
and had been performing relevant laboratory experiments
well before the clinical application. This early surgical
success with freeze-dried material later led to the wide-
spread use of this relatively harsh preservation method,
which was ultimately associated with poor long-term
material durability. Nevertheless, this initial clinical tri-
umph indicated the value of placing a well-functioning
aortic valve in the orthotopic position and underscored
many of the advantages of the homograft over the early
mechanical prostheses (vide infru). Two additional advan-
tages specific to this early era were availability and low
cost. Once manufactured valves became available in large
numbers, the logistics of homograft retrieval and process-
ing made them less attractive. The cost of homografts
continued to be favorable in the United Kingdom, Aus-
tralia, and New Zealand, and economics was one of the
reasons for continued use.
Relevance to Current Surgical Practice
The surgical method for aortic valve replacement with a
homograft has evolved since the initial Ross operation, to
a great part due to Ross himself and the people he has
trained. Other major early contributors include Barrett-
Boyes, Kirklin, Duran, Angell, O’Brien, Wallace, and
0003-4975/91/$3.50
Ann Thorac Surg
1991;52:1190-3
Yacoub [5-91. More extensive reconstructions of the aortic
outflow involve a spectrum of techniques that capitalize
on the material properties of the homograft [lo, 111.
Advantages of Homografts
1. Optimal hydraulic function with central nonobstruc-
tive flow results in excellent hemodynamic perfor-
mance, even in small sizes, and thus optimal hemody-
namics for both right and left ventricular outflow valve
replacement, especially for children and in the adult
small aortic root.
2. Thromboembolism and hemolysis rates are extremely
low, requiring no major anticoagulation.
3. Surgical implantation is relatively simple: right-sided
conduit operations are easier with homografts than
with rigid Dacron conduits, and left-sided reconstruc-
tions are facilitated by the greater flexibility in the way
aortic homografts can be used in either "freehand"
implantation or variations of aortic root reconstruc-
tions.
4. Calcification rarely affects the leaflets; thus, ultimate
homograft failure usually results in gradual valvular
insufficiency, rather than obstructive physiology.
5. Rapid "rejection" with disappearance of the leaflets of
the homograft has been reported but is extremely rare
(specific immunosuppressive therapy is almost never
used).
6. The viable allograft appears to have the greatest resis-
tance to prosthetic endocarditis, and therefore it is the
valve of choice in the infected heart.
Indications for Use
Current practice by most congenital cardiac surgeons is to
always use homografts (when available) for right ventric-
ular outflow tract reconstructions [12]. Homografts can be
used even in the smallest of infants. Once a child has
reached the 15-kg weight range, adult-sized right ventric-
ular outflow tract reconstructions can be accomplished.
The long-term results with wet stored (ie, not cryopre-
served) homograft right-sided reconstructions have been
excellent when prosthetic extensions have been avoided,
and thus the expectation is reasonable that cryopreserved
tissues will also perform well in this position.
For left-sided reconstructions, acceptable options in-
clude mechanical and xenograft prostheses, each with
specific characteristics, advantages, and disadvantages.
One clear indication for the use of the homograft in the
aortic root is for acute active bacterial endocarditis, either
prosthetic or native [6, 131. Another is in children requir-
ing left ventricular outflow tract reconstruction either as
an aortic valve or an aortic root replacement with or
without annulus enlargement procedures (eg, Konno).
The special qualities of the homograft serve to simplify the
technical aspects of complex left ventricular outflow tract
reconstructions in both adults and children. In such
reconstructions, homografts would be preferred, even if
durability were no greater than xenografts, because the
other advantages of technical simplicity, hydraulic supe-
riority, and infection resistance are so favorable. The small
CLASSICS HOPKINS ET AL 1191
HOMOGRAFT VALVE REPLACEMENT
aortic annulus and the congenital aortic stenosis spectrum
can often be repaired more completely and easily with a
homograft, encouraging an approach to the left ventricu-
lar outflow tract using reconstruction techniques of annu-
loplasty, aortoplasty, and various grades of root replace-
ment (eg, mini-root, "full" root replacement with
coronary ostial transplantation). Many of the difficulties of
implanting rigid prostheses into complicated geometric
situations are easily resolved with a homograft [lo, 111.
The role of freehand homograft aortic valve replace-
ment for routine aortic valve replacements is more con-
troversial. The limitation of the resource counsels against
use in elderly patients in whom xenograft valves perform
well without anticoagulation. Women of child-bearing age
and other patients aged less than 50 years are attractive
candidates for the homografts because of the lack of
requirement for anticoagulation and the possibility of
increased durability (beyond that expected of a xenograft
and approaching the expected mechanical prosthetic per-
formance) from the new generation of cryopreserved
valves [14]. Patients without contraindications to antico-
agulation between age 50 and 65 years are usually well
managed with mechanical prostheses.
This original operation by Ross has stimulated other
surgeons' ingenuity to expand the applications of such
transplanted tissues. Cryopreserved cardiovascular tis-
sues are now used for a variety of nonvalved operations in
which their material properties are found to be superior.
The hypoplastic left heart operation includes the use of
homograft pulmonary artery tissue as a key component
for the reconstruction of the aortic arch. Nonvalved pul-
monary artery bifurcations and pulmonary artery tissue
simplify extensive reconstructions in complicated forms of
pulmonary atresia and acquired pulmonary artery steno-
ses. The Konno procedure has been combined with the
aortic root replacement as a total left ventricular outflow
reconstruction tunnel aortic stenosis using homograft for
all tissue repair.
The first Ross operation gave tremendous impetus to
the evolution of homograft surgery. And even more
important has been the continuing commitment by Ross
and his London colleagues to the further development
and refinement of the use of homografts [15]. Their
unabated interest has continued since 1962. As with any
replacement device, homograft cardiovascular tissue
transplants are not perfect and are not always the ideal
material.
Possible Disadvantages of Homografts
1. Potential transmission of disease
2. Lack of availability
3. Unknown durability beyond 15 years for currently
processed valves
4. Evolving preservation techniques
5. Imperfectly understood role of the immune response
6. Some variability in the performance of these valves
7. Surgical technical challenges
1192 CLASSICS HOPKINS ET AL
HOMOGRAFT VALVE REPLACEMENT
Cardiovascular Tissue Harvesting and Preparation
Methodology
Ross’ case is a pioneering event that classically illustrates
the enormous utility of the surgical case report. The
rapidly reported and widely disseminated success in this
patient led to life-enhancing operations in hundreds, if
not thousands, around the world in the 1960s and after.
However, this same case report also illustrates the limita-
tion of this type of communication if extended beyond
surgical method, as the preservation methodology was
similarly applied elsewhere. Unfortunately, durability
was adversely affected by the freeze-drying process (and
other harsh preservation methods); this fact was recog-
nized within 5 years [16]. Ross and Barratt-Boyes realized
this and settled on a gentle tissue culture-type cold
storage method, adopted worldwide during the 1970s.
The valves harvested from the donor shortly after death,
gently treated and maintained in nontoxic antibiotic-laced
tissue culture medium at 4°C (so-called antibiotic wet
stored), have been found to have durability matching or
slightly exceeding xenografts in the aortic position and
tremendously superior in the pulmonary outflow position
~71.
The application of cryopreservation to complex tissues
(derived from the cryobiology of individual cell preserva-
tion-eg, sperm, red blood cells) to capture the durability
advantage of the fresher tissue has been a natural and
logical progression. The initial work by Angel1 and
OBrien has led to the Brisbane series of aortic valve
replacements with durability approaching or exceeding
90% valve and patient survival at 15 years [14]. Given the
other advantages of homograft valves, this is a remarkable
achievement that has naturally led to a resurgence of
interest by physicians. (An analogous 15-year series for
cryopreserved valves in the right ventricular outflow
position is not yet available.) Great attention is now
focused on the lack of availability of cryopreserved valves,
which is the greatest restraint on their use.
The exact role of fibroblast cellular viability is also not
yet clear; it is not known how much quantitive cellular
viability is needed to confer increased durability. The role
of leaflet endothelium is not understood; it may stimulate
antibody response and actually decrease the long-term
survival, and thus should be specifically removed during
processing [18]. Optimal methods are still not strictly
defined for managing the intervals between donor demise
and processing, the limits of transport conditions, stor-
age, thawing, and insertion. However, certain features
are now being teased from the available data. Prolonged
warm ischemia (greater than 24 to 36 hours), harsh
harvesting, and thermally unstable transportation meth-
ods appear to be injurious. High concentrations of antibi-
otics or prolonged disinfection protocols are particularly
damaging to cell survival [19]. Prolonged cold, wet stor-
age before cryopreservation (5 to 7 days) and improper
freezing and thawing techniques lead to cell disruption.
The enhanced durability of cryopreserved or very fresh
valves has been attributed to putative fibroblast viability
at the time of implantation. The notion is that these cells
can participate in repair and remodeling of the leaflet,
Ann Thorac Surg
1991;52:1190-3
thus preserving the material properties, strength, and
elasticity of the leaflet matrix-perhaps functioning to
normalize it after the stresses of storage and transplanta-
tion, and maybe even repairing damage accruing with the
60 to 180 flexions per minute for the months and years
following surgical implantations. These attractive hy-
potheses are not yet proven [20]. It may be that cell
viability is simply a marker for well-maintained matrix
physical-chemical properties, or that fibroblast viability is
present only for the initial restoration of the matrix after
transplantation [21-261. Despite pending proof of mecha-
nism, it is hard to ignore the improving results and
increasing “durability” of the ”gently” treated homograft.
In essence, the homograft method for aortic valve replace-
ment has almost a continuous 30-year track record-
exceeded only by 2 years by the Starr valve. It is an
acceptable if not preferable ”prosthesis” for many indica-
tions and certainly does not qualify as an ”experimental”
device. The Engineer who designed this valve does not
require pulse duplicator experiments to validate His design.
The principles of preparation are well understood, and
worldwide variations generally fall well within the scope of
current tissue banking knowledge and understanding and
represent relatively minor modifications of an overall ap-
proach. The challenge facing regulatory groups, cryopreser-
vation facilities, cardiovascular scientists, and cardiac sur-
geons, who wish to establish aspects critical to the
enhancement of homograft performance while maintaining
the greatest possible safety for the recipient, is to avoid
doing worse than has been achieved by Ross and others for
the past 28 years.
Ross and the other early advocates of the homograft
valve have done a tremendous service by demonstrating
the usefulness and in some applications the superiority of
the homograft valve. Even the aseptic ”nonviable” ho-
mografts (fresh wet stored) have great utility and an
excellent record that would qualify or even mandate use
in patients when other advantages exceed the properties
of available mechanical and xenograft prostheses. The
homograft is an important therapeutic option. Its avail-
ability needs to be greatly amplified by increased dona-
tions, more extensive harvesting, and the creation of
realistic harvesting, processing, and allocation protocols
that maximize availability while achieving, as a minimum,
the performance of the ”gently treated” ”nonviable”
valve of the wet storage era. Ultimately, it will be possible
to identify and separately categorize valves for which the
potential durability exceeds that historical ”norm” and
thus select these valves for use in younger patients.
References
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Editor’s Note
W e a s k e d Mr Ross for his c o m m e n t s on Dr Hopkins’
interesting article.
Mr. Ross’ Commentay
It is interesting to recall that we h a d so little confidence i n
t h e first homograft that we regarded it a s a temporary
expedient until we could import a Starr valve a n d b u y
time while we d i d accelerated fatigue testing on o u r
freeze-dried valves. However, a s d a y s passed into weeks
and finally t o m o n t h s with maintained valve function a n d
w i t h a n increasing n u m b e r of valves i n patients, we forgot
a b o u t mechanical valves a n d concentrated on refining o u r
homograft insertion techniques. Also, after collateral
w o r k by o u r immunological colleagues a t Guy’s Hospital,
we accepted t h e decision that although there w a s a n
immunological reaction it d i d n o t justify t h e u s e of ste-
roids a n d t h e resulting d a n g e r of infection.
Different sterilization a n d stage m e t h o d s h a v e n o t elim-
CLASSICS HOPKINS ET AL 1193
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inated t h e problem of tissue failure a s far a s we are
concerned. This feature h a s been t h e main stimulus
responsible for our development of t h e pulmonary au-
tograft operation, which we consider t o offer a p e r m a n e n t
valve uniquely suited to children a n d young adults.
Encouraged b y t h e impressive function of t h e autoge-
n o u s pulmonary valve i n t h e aortic position, we h a v e
turned to t h e pulmonary homograft, which is readily
available a n d usually of better quality t h a n its aortic
counterpart. N o t only h a s it performed impeccably i n
right ventricular reconstruction, b u t we a n d others are
investigating its use as a n aortic valve replacement.
The most rewarding aspect of o u r homograft experience
after years i n the surgical wilderness is t o enjoy t h e
newfound enthusiasm of colleagues over t h e world.
Donald Ross, FRCS
25, Upper Wimpole St
London, WZM 7TA
England