Download Homograft Aortic Valve Replacement—The Experience

ORIGINAL ARTICLE
Original Article
Homograft Aortic Valve Replacement—The
Experience of One Unit
Gautam Ganguly, MS, Zakir A. Akhunji, FRCS(I), William M.L. Neethling,
PhD(Cardiothoracic)1 and Andrew J. Hodge, FRACS(Cardiothoracic)∗
Department of Cardiothoracic Surgery, Fremantle Heart Institute, Fremantle Hospital, P.O. Box 480, Fremantle, WA 6959, Australia
Background. Homograft valves offer advantages including avoidance of anticoagulation and less susceptibility to infection especially in the setting of endocarditis. However, there is concern about their durability and possible accelerated
degeneration particularly in cases of second time replacement with homografts.
Aim. This study aimed to evaluate the pattern of homograft failure and the quality of life in patients after homograft
implantation.
Methods. Between 1990 and 1998, 58 patients underwent aortic valve replacement with a homograft (aortic homograft
= 47, pulmonary homograft = 11). Evaluation was based on clinical and echocardiographic examination, patient questionnaires and explanted valve pathology. Survival and freedom from cardiac related death were expressed by actuarial
methods.
Results. Follow up ranged from 1 to 10 years (mean 5.5 years). Analysis of questionnaires revealed 60% of respondents
to be in good performance status and 20% in moderate and 20% in poor performance status groups. Eleven patients
(18.9%) required subsequent redo valve replacement after initial homograft insertion (pulmonary = 6, aortic = 5) due to
either valve dehiscence (n = 4) or valve degeneration (n = 7). The mean interval of re-replacement was 5.4 years.
Conclusions. Pulmonary homografts have a high failure rate in the aortic position. Overall subjective and clinical improvement after surgery is less than expected for a “physiological” device. In the setting of low availability of homografts
the use of off-the-shelf devices such as stentless xenografts may be preferable in most cardiac surgical units in the current
era.
(Heart Lung and Circulation 2004;13:161–167)
© 2004 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New
Zealand. Published by Elsevier Inc. All rights reserved.
Keywords. Homograft; Valve replacement; Quality of life
Introduction
A
ortic valve replacement (AVR) with cryopreserved human aortic or pulmonary valves (homografts) is an
attractive alternative to the implantation of mechanical or
bioprosthetic valves as anticoagulation can be avoided and
durability is said to be at least as good as, or better than,
xenograft bioprostheses.1–4,30
The first orthotopic insertion of a homograft was
performed by Donald Ross in 1962. Brian Barrett-Boyes
performed a similar procedure in London the same year,
reported in 1964.5
At first the homografts were harvested aseptically and
implanted within a few days. This was soon replaced by
unsterile collection with subsequent sterilisation by ethylene oxide, betapropiolactone or irradiation. The homograft was then stored in Hank’s solution at 4 ◦ C or by
freeze drying. This technique had a high incidence of cusp
∗ Corresponding author. Present address: Cardiothoracic Surgical
Unit, Ward B8N, Fremantle Hospital, Alma Street, Fremantle, WA
6160, Australia. Tel.: +61-8-9431-3337; fax: +61-8-9431-2915.
E-mail address: [email protected] (A.J. Hodge).
# 1 Co-corresponding author.
rupture.6 In 1968 antibiotic sterilisation was introduced
at Green Lane Hospital, New Zealand by Barratt-Boyes.7
Cryopreservation was introduced in 1975 by O’Brien.8 The
use of the homograft was expanded by Yacoub and by
Ross for use in combined aortic valve and ascending aortic
replacement.5 Donald Ross performed the first AVR using
the autograft pulmonary valve in 1967.5,9,10
This study aimed to evaluate the pattern of homograft
failure and the quality of life in patients after homograft implantation in a small Unit largely typical of the
Units in Australasia. Evaluation was based on clinical and
echocardiographic examination, analysis of data from patient questionnaires and explanted valve histopathology.
Materials and Methods
Patients
Between 1990 and 1998, 58 patients underwent aortic valve
replacement with a homograft largely by one surgeon
(A.J.H.). Patients were selected on the basis of general
suitability for bioprosthetic replacement and none were
excluded on the grounds of risk or co-morbidity. A fre-
© 2004 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of
Australia and New Zealand. Published by Elsevier Inc. All rights reserved.
1443-9506/04/$30.00
doi:10.1016/j.hlc.2004.02.004
ORIGINAL ARTICLE
162
Ganguly et al.
Homograft aortic valve replacement—the experience of one unit
Table 1. Pre-operative Valvular Pathology in Patients
(n = 44) for Primary Replacement
Valvular Pathology
Calcified aortic stenosis (AS)
Aortic regurgitation (AR)
AS + AR
Endocarditis
Number (% of total)
24 (41.3)
5 (8.6)
11 (18.9)
4 (6.8)
Table 2. Valvular Pathology in Patients (n = 14) for Redo
AVR with Homograft (Previous Bioprosthesis)
Prosthetic Pathology
Endocarditis
Calcific degeneration
Valve dehiscence with
transprosthetic or
periprosthetic leak
Number (% of total)
4 (6.8)
6 (10.3)
5 (8.6)
quent cause of exclusion was unavailability of a suitably
sized homograft. Forty were male and 18 were female.
They ranged in age from 22 to 88 years with a mean of
63 years. Twenty-seven patients (46.5%) were older than
65 years at the time of surgery. Forty-four patients underwent primary homograft replacement (75.8%). The indication for this replacement is shown in Table 1. Fourteen
patients (24.1%) underwent redo AVR with a homograft
after a previous AVR with a tissue valve. The indication
for redo AVR is shown in Table 2. Forty-seven patients
received an aortic homograft and 11 patients received a
pulmonary homograft into the aortic position. Eleven patients (18.9%) in this series required subsequent redo AVR
after homograft insertion due to either valve dehiscence
(4 cases) or valve degeneration (7 cases). Of these 11 patients, 6 had received a pulmonary homograft and 5 had
received an aortic homograft at the initial operation. The
mean interval of re-replacement after the first homograft
replacement was 5.4 years and the types of valve used during this re-replacement are shown in Table 3.
Homografts were inserted free hand in the sub-coronary
position in 48 patients (82.7%) and aortic root replacement was done in 10 patients (17.3%). Concomitant procedures were performed in 14 patients (24.1%), 12 undergoing coronary artery bypass procedures and 2 undergoing mitral valve annuloplasty. Pre-operative left ventricular function was assessed by echocardiography and/or
LV angiogram. Fifteen (25.8%) patients had mild to moderate impairment of left ventricular function and 3 (5.2%)
patients had severe systolic dysfunction. The remainder
(69%) had normal LV function.
Table 3. Types of Valves (n = 11) Used for Re-replacement
After Homograft AVR
Types of Valve
Mechanical (St Jude)
Stented pericardial
Stentless porcine (Toronto)
Homograft (aortic)
Heart Lung and Circulation
2004;13:161–167
Surgical Technique
All patients were operated on using cardiopulmonary
bypass (CPB) with core cooling to 28–32 ◦ C. Myocardial
preservation was achieved by using intermittent cold
blood cardioplegia at 4 ◦ C infused antegrade through
the aortic root, retrograde through the coronary sinus,
or directly into the coronary ostia because of aortic
regurgitation or when the root was open. The myocardial
temperature was reduced to less than 12 ◦ C in all coronary territories. Cardioplegic infusion was repeated every
20–30 min. The left ventricle was vented through the right
superior pulmonary vein and across the mitral valve in all
cases.
For sub-coronary implantation, the native aortic valve
was exposed through a curved aortotomy beginning just
above the shoulder of the right ventricle, extended transversely to the left, and towards the centre of the noncoronary sinus without transgressing the sino-tubular
junction, on the right. This gave good exposure of the aortic
valve to allow thorough excision/explantation of the valve
and annular debridement without disturbing the integrity
of the aortic root. The homograft valves were inserted either in the sub-coronary position or as an aortic root replacement with re-implantation of the coronary buttons.
The decision as to whether to perform root replacement
depended on the configuration of the root, size of the aortic sinuses, donor/recipient configuration mismatch, and
the need to debride abscess cavities in patients with endocarditis.
Homograft Preparation
Homografts were collected, antibiotic sterilised, cryopreserved and thawed according to the protocol initiated by
O’Brien and co-workers.26,27
Follow Up
The duration of follow up ranged from 1 to 10 years with a
mean of 5.5 years and a cumulative follow up time of 442
patient years. All patients were followed up at 1 month, 3
months, 6 months and then annually. At follow-up apart
from clinical examination, a chest X-ray, ECG and echocardiogram were done for all patients. A questionnaire concerning physical status and life style was sent in April 2000
and resulted in a 93% response rate (40 of 43 survivors).
The study was censored in May 2000. Evaluation of the
quality of life and physical activity was made on the basis
of clinical examination and data from the questionnaire.
The questionnaires were prepared in accordance to the SF36 Health Survey Scoring Manual of Medical Outcomes
Trust, Boston.11 The questionnaire, apart from personal
data, also contained questions concerning quality of life
before and after surgery and level of exercise tolerance.
Based on their score the patients were divided into three
groups: poor, moderate and good performance status.
Number of Patients
5
2
2
2
Statistical Methods
The estimated probability of survival and freedom
from cardiac related death were expressed by actuarial
methods.12 Outcome after surgery was calculated accord-
Ganguly et al.
Homograft aortic valve replacement—the experience of one unit
163
ing to a standard exponential model based on the average
complication rate and survival time.
Table 4. Causes of Late Deaths in Homograft AVR Recipients
Results
Non cardiac
1. Seizure
2. Brain tumour
3. Carcinoma colon
4. Cerebrovascular accident
5. Brain tumour
6. Carcinoma prostate
Mortality
There were a total of nine (15.5%) cardiac deaths and six
(10.3%) non-cardiac deaths over the study period of 10
years. Of the cardiac related deaths, five (8.6% of the total group) were early (within 60 days). Two patients could
not be weaned from CPB and died on the table. Another
patient was weaned off CPB with the help of a right ventricular assist device (RVAD) but died in ICU after 2 days
on RVAD support. The fourth patient died after 12 days in
the ward following ventricular arrhythmia. The fifth patient died after 4 weeks due to continuing endocarditis
and interstitial pneumonia. The risk factors found to be
predictors of early death are shown in Table 6. Risk stratification analysis was done on the basis of the Parsonnet
scoring system.13 The average Parsonnet score in this patient group was 14 resulting in a predicted operative mortality of approximately 14%. The operative mortality in this
series was 8.6% at 60 days.
During the period of follow up there were 10 late deaths.
The causes of these late deaths are shown in Table 4. Overall actuarial survival was 70% at 2 years, 55% at 5 years and
50% at 10 years (Fig. 1).
Homograft Failure
Homograft failure was defined as need for re-operation
due to either degenerative valve failure, valve dehiscence
or endocarditis. Degenerative valve failure was defined
as moderate or severe valve malfunction due to calcification or cusp perforation diagnosed at echocardiography.
Valve dehiscence was defined as actual anatomical sep-
Cause of Death
Cardiac
1. Valve dysfunction and
congestive heart failure
2. Congestive heart failure
3. Congestive heart failure
and arrhythmia
4. Unknown
Interval After
AVR (Years)
9
6
5
5
4
3
6
2
2
5
aration of the homograft tissue from the native annulus
or native aortic wall causing periprosthetic leak. Eleven
patients (18.9%) required reoperation due to homograft
failure. The linearised failure rate for homograft valves
in this series was 2.48% per year. Expressed as an actuarial curve (Fig. 2), at 10 years no valve had escaped a
valve-related complication. The interval between initial
homograft AVR and re-operation ranged from 1 to 9 years
with a mean of 5.4 years. Valve degeneration occurred in
7 of the 53 patients discharged from hospital (13.2%) and
valve dehiscence occurred in 4 of the 53 patients (7.5%).
Six pulmonary homografts needed re-operation for degeneration (n = 4) or dehiscence (n = 2) and five aortic
homografts needed re-operation for degeneration (n = 3)
or dehiscence (n = 2). There were no reoperations for endocarditis. One patient required heart transplantation 8
years after homograft replacement. In this case when examined histologically after explant, both the homograft
Figure 1. Postoperative survival for cardiac related (䉭) and all (䉱) deaths, represented as an actuarial curve.
ORIGINAL ARTICLE
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2004;13:161–167
ORIGINAL ARTICLE
164
Ganguly et al.
Homograft aortic valve replacement—the experience of one unit
Heart Lung and Circulation
2004;13:161–167
Figure 2. Ten year prosthetic failure free rate (includes all cardiac-related deaths and complications), expressed as a percentage and represented as
an actuarial curve after homograft aortic valve replacement.
aortic wall (Fig. 3) and the valve leaflets (Fig. 4) had extensive areas of acellular non-viable tissue. The results of histology on the remaining explanted valves were not readily
available.
Morbidity
Fourteen patients (24.1%) had various post-operative complications including low cardiac output, resternotomy for
bleeding, permanent neurological deficit, renal failure,
etc. as shown in Table 5. The patient who required RVAD
also required intra-aortic balloon counter-pulsation and
dialysis.
Quality of Life
Analysis of questionnaires revealed 60% (24 patients) to be
in good performance status and 20% (8 patients) in moderate and 20% in poor performance status groups. Three patients in the moderate performance group and one patient
in the poor performance group attributed their physical
limitations to causes other than cardiac-knee replacement
(2 patients), rheumatoid arthritis (1 patient) and dementia (1 patient). Clinical assessment of NYHA functional
class preoperatively and at the longest postoperative review recorded NYHA I 6.6% versus 30%, NYHA II 33.3%
versus 45%, NYHA III 50% versus 25% and NYHA IV 10%
versus 0%.
Figure 3. Representative electron micrograph of an aortic wall section of an explanted aortic homograft, showing non-viable acellular material
(black arrows) in the media (magnification 6000×).
Ganguly et al.
Homograft aortic valve replacement—the experience of one unit
165
Figure 4. Representative electron micrograph of the aortic valve leaflet of an explanted aortic homograft, showing damaged collagen fibers (black
arrows) in the spongiosa. The tissue is acellular (magnification 6000×).
Table 5. Post-operative Complications Following Homograft
AVR
Complication
IABP
RVAD
Dialysis
Resternotomy
Septicaemia
Stroke
Complete heart block
Number (% of total)
3 (5)
1 (1.6)
2 (3.3)
3 (5)
2 (3.3)
2 (3.3)
1 (1.6)
Discussion
Aortic valve replacement with cryopreserved homografts
has well established advantages in avoiding anticoagulation and has less susceptibility to infection.1 Various authors in the past have indicated good surgical outcome
and good early and long term survival.14–16 Podolec et
al. compared quality of life after homograft and mechanical prosthetic valve implantation and did not find any
significant difference in outcome.17 Analysis of the patient questionnaire in our series suggests only 74% of
patients improved their quality of life and only 70% of
patients actually had improvement in NYHA class after
surgery.
The findings of 18.9% incidence of homograft failure
within a mean interval of 5.4 years remains a matter of concern regarding the durability of these prostheses. The difference in re-operation rate for aortic and pulmonary homografts was statistically significant as 5 out of 47 (10.6%)
patients with aortic homograft and 6 out of 11 (54.5%) patients with pulmonary homograft needed subsequent reoperation (P = 0.002, estimated at 95% confidence limits)
and we would agree with previous work18–22 that the pulmonary homograft is not a suitable replacement in the
aortic position Poor alignment of the prosthetic inflow
and of the spatial separation of the commissural posts
has been cited as a reason for early prosthetic failure. Although there is of necessity a learning curve for the correct
insertion of these prostheses, immediate post-operative
echocardiography in this series did not detect any functional problem.
It is attractive to think that once inside a patient, the
purpose-designed collagen/elastin matrix of the homograft, if devitalised prior to insertion by the processes of
collection, preservation and storage, would repopulate itself with autologous cells, resulting in a completely viable
structure. It is very disappointing that this had not occurred in our removed degenerate homografts, but has
been reported previously.28,29
The 8.6% incidence of early mortality was considered
higher than other published results from high volume
Units.23–25,30 The operative group was moderately high
risk according to the Parsonnet score and in concert with
the usual patient population that we see (average Parsonnet score for all patients in our Unit having a procedure which includes aortic valve replacement is 17).
Comparison of results between groups is difficult without appropriate risk stratification, although available risk
stratification scores for coronary artery surgery (e.g. Parsonnet, Tu, Higgins, Tremblay) are no more than 70%
predictive.
Analysis of risk factors for early death indicates that age
beyond 70 years, female gender, endocarditis and associated procedures increase the risk of death significantly
(Table 6).
The overall mortality of 15.5% over 10 years is high, but
comparable with other published series,25 and is what we
have come to expect from these prostheses. Seven years
ago on abandoning the homograft as the prosthesis of
choice, our group moved to the use of commercially available stentless porcine bioprostheses and have found the
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Ganguly et al.
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Heart Lung and Circulation
2004;13:161–167
Table 6. Risk Factors Examined for Early Death
Factor
Age
Sex
LV dysfunction
Re operation
Endocarditis
Risk
Odds Ratio
≥70 years:<70 years
Female:male
Moderate:severe
3:1
8:1
1:2
1:1
10:1
0.147
0.019
0.024
0.949
0.002
1:1
1:1
9:1
0.865
0.503
0.002
Type of procedure
Root replacement
Subcoronary
Associated procedures
clinical outcomes to be at least as good and with lower
mortality and morbidity rates. There is the added benefit
of easy procurement and storage.
In conclusion it can be said that:
(i) Pulmonary homografts have a high failure rate in the
aortic position.
(ii) The performance of aortic homografts in the aortic
position is disappointing in our hands.
(iii) Overall subjective and clinical improvement after
surgery is less than expected for a “physiological” device.
The authors would like to thank Drs. Peter Bissaker, Mark Newman and Ian Gilfillan for their contribution to this study, and
Sharyn Baker for her collection and collation of the patient data.
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Heart Lung and Circulation
2004;13:161–167