(Circulation. 1999;100:II-42.)
© 1999 American Heart Association, Inc.
Surgery for Valvular Heart Disease |
Patient Outcome and Valve Performance Following a Second Aortic Valve Homograft Replacement
From the Academic Department of Cardiac Surgery, Royal Brompton and Harefield NHS Trust, London, United Kingdom.
Correspondence to Sir Magdi Yacoub, FRS, Professor of Cardiothoracic Surgery, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, United Kingdom.
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Abstract |
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Background—Homograft valves offer many advantages; however, there is concern about their use in second aortic valve replacement because of the complexity of the procedure and the possibility of accelerated degeneration.
Methods and Results—One hundred and forty-four patients underwent a second aortic homograft replacement between 1973 and 1997 (mean follow-up 6.5±5 years, range 1 to 20 years). Eighty-three were male, and 61 were female, aged 17 to 77 years, mean 49.0 years. All patients had undergone previous aortic valve replacement with a homograft. The indication for reoperation was aortic regurgitation in 75 patients (52.1%), aortic stenosis in 28 (19.4%), and mixed aortic valve disease in 41 (28.5%). Root replacement was performed in 54 patients (38%) and subcoronary in 90 (62.5%). Early mortality was 3.4%. The actuarial survival rate was 93% and 82% at 5 and 10 years, respectively. Freedom from tissue degeneration was 96% and 80% at 5 and 10 years, respectively, and freedom from reoperation was 97% and 82% at 5 and 10 years, respectively.
Conclusions—This study shows that a second aortic valve homograft replacement results in good early and long-term survival. Accelerated degeneration does not occur. Left ventricular performance is improved, and earlier surgery could further improve outcome, indicating that an aortic homograft is a safe, durable option for patients requiring a second aortic valve replacement.
Key Words: : valves • aorta • regurgitation
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Introduction |
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Aortic homografts offer superior hemodynamics (with the potential to restore normal flow in the aortic root, sinuses, and coronary orifices), freedom from thromboembolism, and resistance to infection. This has resulted in a continued increase in the use of aortic homografts for aortic valve replacement. However, their use has been limited due to lack of availability, complexity of insertion, and limited durability. Many of the patients who had homograft replacement of the aortic valve will subsequently require re-replacement at some point in the future.1 2 3 4 5
There is no consensus about the choice of a valve substitute at the second operation. Although homografts may offer many advantages, there is concern about their use in this setting. The concern stems from the fact that at the second operation, advanced age, deterioration of ventricular function, and complexity of operation may add to the operative risks. We and others have shown that these valves express both class I and class II major histocompatibility antigens,6 and a strong donor-specific humoral immune response after homograft insertion can occur, particularly in patients who receive homovital homografts7 ; thus, at least in theory, the phenomenon of sensitization may cause accelerated degeneration of the second homograft.
To clarify these issues, we investigated early and late survival, homograft valve performance, changes in left ventricular function, and determinants of outcome after a second homograft aortic valve replacement.
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Methods |
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Between January 1973 and December 1997, 144 patients underwent aortic valve reoperation with a homograft by 1 surgeon (M.H.Y.). Eighty-three patients were male, and 61 were female. They ranged in age from 17 to 77 years, mean 49.0 years. The indication for reoperation was aortic regurgitation in 75 patients (52.1%), aortic stenosis in 28 (19.4%), and mixed aortic stenosis and regurgitation in 41 (28.5%). Postendocarditis tissue valve failure occurred in 14 (9.7%). All patients had undergone previous aortic valve replacement with a homograft, and the mean interval between the first and second operation was 11.5±5.2 years. Aortic valve root replacement was performed in 54 patients (38%), and the homograft was inserted freehand in the subcoronary position in 90 patients (62.5%). Homovital homografts were used in 121 patients (84%). Concomitant procedures were performed in 38 patients (26%) as shown in Table 1
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Preoperative left ventricular function was assessed by left ventricular angiography and echocardiography. In 102 patients (71%), left ventricular end-diastolic diameter (LVEDD) was >60 mm. Of these, 32 had fractional shortening (FS) of <25%.
Surgical Technique
Patients were cooled to a temperature of 28°C under total
cardiopulmonary bypass. Myocardial preservation was achieved by
using crystalloid cardioplegia at 4°C (St. Thomas Hospital, No
1), infused through the aortic root or directly into the
coronary ostia. The myocardial temperature (measured by a
myocardial temperature probe placed in the ventricular
septum) was reduced to <10°C. Cardioplegia infusions were repeated
every 20 minutes. The left ventricle was vented through the apex in all
cases.
The aortic valve was exposed through a curved aortotomy beginning anteriorly and extending into the middle of the noncoronary sinus. This allowed excellent exposure of the valve and possible enlargement of the root by extending the incision across the annulus into the subaortic curtain for 2 to 3 mm. The valves were inserted either as free homografts in the subcoronary position by means of the 2-suture line technique with a lower interrupted and upper continuous suture line or as an aortic root replacement with reimplantation of the coronary arteries. The decision as to whether to perform root replacement depended on the size of the root, distortion, size of the aortic sinuses, and the need to exteriorize abscess cavities in case of endocarditis. The techniques used for freehand and root replacement have been described in detail elsewhere.1 4
Homograft Details
Homograft valves were harvested under sterile conditions from
heart transplant recipients in 121 cases and from brain-dead multiorgan
donors in 23 cases. Donors were aged 15 to 60 years (mean 41±12
years). The valves were harvested under sterile conditions from
transplant recipients, categorized as homovital, stored at 4°C (Table 2), and cryopreserved if not implanted
within 12 days. Antibiotic sterilized valves were obtained from a
routine postmortem examination within 48 hours of death, sterilized in
antibiotic solution (Table 3) for 24
hours, placed in tissue culture medium (Table 2) at 4°C, and
classified as homografts. These valves were not cryopreserved and
were implanted within 4 weeks of sterilization. Cryopreservation
was used in 12 (8.3%) of the valves. The interval between harvesting
and insertion varied from 1 hour to 65 days (mean 11±13 days). All
donors were HIV and hepatitis-B surface antigen seronegative.
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Follow-Up
At follow-up, functional status and physical examination were
assessed, and a chest roentgenogram, an ECG, and an echocardiogram
obtained in 141 patients (97.9%). Three patients (2.1%) lived abroad,
and follow-up information was incomplete after 1 year. Definition and
mode of defining morbidity and mortality were in accordance with the
guidelines recommended by the Ad Hoc Liaison Committee for
Standardizing Definitions of Prosthetic Heart Valve
Morbidity.8 Early mortality was defined as death within 30
days of the operation and degenerative valve failure as moderate or
severe valve malfunction discovered at reoperation or postmortem
examination, as well as moderate or severe
regurgitation or stenosis (with a peak gradient
of >30 mm Hg) diagnosed by routine
echocardiographic Doppler imaging in the absence of
previous or current endocarditis.
Statistical Methods
The 
2 test was used to compare
frequencies of the different variables, and a P value of
<0.05 was considered significant. Probability of survival, freedom
from valve degeneration, and reoperation was calculated by use of the
Kaplan-Meier method.9 The Cox proportional hazards
model10 was used to analyze the time of follow-up
after reoperation and time until death or a second reoperation among
those patients who did not die early after the operation.
According to the Cox model, the hazard function at time t for a patient
with covariates 1,
2· · ·, kis
given by the following equation:
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Results |
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Mortality
There were 5 early deaths (3.4%). One patient could not be weaned off cardiopulmonary bypass and died on the operating table. One was weaned from bypass with the help of a biventricular assist device but later died of multiorgan failure. Three patients died in the intensive care unit because of persistent low cardiac output syndrome leading to multiorgan failure.
Overall actuarial survival was 93% at 5 years and 82% at 10 years
(Figure 1). During a period of follow-up
that ranged from 30 to 7300 days (mean 2373 days), there were 21 late
deaths. In 2 patients, aortic regurgitation resulted in
left ventricular failure. In 1 patient, left
ventricular function continued to deteriorate; despite a
functioning homograft and maximum medical therapy, further
complications of ventricular arrhythmias occurred.
In another patient, left ventricular failure developed
secondary to acute mitral insufficiency with a normally functioning
homograft. In 3 patients, the cause of failure could not be confirmed,
so it was attributed to aortic homograft failure for the purposes of
analysis. One patient died after mitral-valve replacement at
another institution.
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The potential risk factors investigated as predictors of early death are shown in Appendix 1. Poor left ventricular function (FS <25%) and concomitant procedures, particularly coronary artery revascularization, significantly increased risk of early death.
Table 4 summarizes the causes of late
deaths. The possible risk factors analyzed for late death
included those used for analysis of early mortality, plus age,
sex of the donor, and dissection and storage time of the homografts
(Appendix 2). Multivariate analysis identified
poor left ventricular function (LVEDD >6) as a significant
risk factor for late death (hazard ratio 4.008, P=0.02).
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In this series, long-term survival (93% at 5 years and 82% at 10 years) after a second homograft aortic valve replacement was similar to that after the first homograft aortic valve replacement reported from our institution,4 with a survival rate approaching 92% and 85% at 5 and 10 years, respectively.
Degenerative Valve Failure
With the criteria of presumed degenerative valve failure defined
above, freedom from valve degeneration at 5 and 10 years was 96% and
80%, respectively (Figure 2). The linear
incidence rate for the total follow-up period of 20 years was 2.88%
(95% CI, 2.37% to 3.48%) per patient year. We analyzed the
possible influence of all patient- and valve-related covariates (in a
multivariate Cox model) in an attempt to define the
factors that could affect degeneration. Although none of the factors
reach statistical significance, antibiotic- sterilized homograft valves
compared with homovital valves and a left ventricular
end-diastolic diameter >6 cm tended to increase the risk.
The hazard ratios were 2.05 (P=0.061) and 2.01
(P=0.093), respectively.
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To define the relative risk of degeneration after the second operation in comparison with that after the first operation, we compared reoperation rates after both operations. Freedom from reoperation after the first homograft was 90% (SE=0.024), 64% (SE=0.04), and 26% (SE=0.03) at 5, 10, and 15 years, respectively (mean=11.5 years), compared with 96% and 80% at 5 and 10 years after the second homograft.
Reoperation
Sixteen patients required further reoperation, all with
another homograft. The interval between the second and third operations
ranged from 6 months to 20 years (mean 8.6±1.5 years). The cause of
valve dysfunction was endocarditis in 5 (3.4%) and degeneration in 11
(7.6%). Freedom from reoperation from any cause was 97% at 5
years and 82% at 10 years (Figure 3).
Freedom from endocarditis was 97% at 5 years (SE=0.016) and 94.5% at
10 years (SE=0.024) (Figure 4). This is
comparable to freedom from endocarditis rates of 98% and 94% at 5 and
10 years, respectively, reported previously in our series of first-time
aortic valve replacement with a homograft.4 The linearized
incidence rate of endocarditis for the total follow-up period was
0.52% (95% CI, 0.33% to 0.82%) per patient year. Moreover,
reoperation for endocarditis-related valve failure was lower after the
second homograft in this series (see Methods).
Multivariate analysis showed that operation for
endocarditis was a risk factor for reoperation (hazard ratio 2.80,
P=0.03).
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Morbidity
Thirty-three patients had other postoperative complications as
outlined in Table 5. Eight patients
(5.5%) required support with intra-aortic balloon counterpulsation
initially after surgery; the patients were later successfully weaned.
Five patients (3.5%) required an exploratory sternotomy for bleeding.
A permanent pacemaker was implanted in 1 patient who developed complete
heart block due to an abscess cavity involving the
interventricular septum. Three of 4 patients with
neurological events recovered completely before leaving the
hospital.
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Echocardiography
Follow-up echocardiography was performed
on 141 patients (97.9%). Patients underwent
echocardiography during follow-up every 1 to 2
years. The interval between the second operation and last
echocardiogram ranged from 1 to 20 years (mean 7±5 years). Overall,
there was no significant change in FS from the preoperative value, but
in patients with a preoperative FS of <25% (n=32), there was an
improvement in FS of 23±24% (Figure 5).
The left ventricular end-diastolic and
end-systolic diameters significantly decreased by 12%±13%
and 8%±18%, respectively (Figures 6 and 7). Left ventricular mass
index decreased by 16±31% (Figure 8).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1Appendix 2References |
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This paper has served to define the rate of survival and valve function after a second homograft aortic valve replacement. Survival appears to be good and is similar to that of a first-time homograft,4 5 11 and it compares favorably with our and other series of re-replacement with tissue valves.12 13 It also compares favorably with re-replacement with other forms of valve substitute14 15 16 17 18 19 which may be due to the achievement of near-normal flow characteristics in the aortic root. We have previously shown 13 that in aortic homograft re-replacement, patients with a homograft for the 10 years before re-replacement have a better survival after the second operation in comparison with those with a prior mechanical valve.
In the current study, multivariate analysis showed that preoperative left ventricular function strongly affected late survival, suggesting earlier surgery may give better results. In this study, multivariate analysis of other patient- and valve-related factors did not show any to affect late survival. In a large series of first-time homografts,5 we found that patient age, sex, donor age, and allograft viability also affected survival, and it is likely that some of these factors would also affect outcome in second homograft replacement if this series were larger.
Freedom from degeneration and reoperation in this series also compared favorably with that of first-time homografts. In the absence of endocarditis, there were no early failures, suggesting no accelerated degeneration.20 The interval to reoperation, even in the younger age group, did not affect degeneration after the second homograft, suggesting that previous accelerated degeneration does not predict further degeneration.
We have previously found4 that a recipient age of <30 increased the rate of degeneration after a first-time homograft, and it may be that by the second operation patients are older, so that degeneration is less likely. In our large series of first-time homografts, we found that other factors such as donor minus patient age, a donor age >65 years, and diabetes affected degeneration.5 Although the current study has a long period of follow-up, the number of degeneration events may not be great enough to predict all the factors affecting degeneration, and some of these factors may also affect degeneration. Concerns over the immunogenicity of fresh homografts that express class I and II major histocompatibility antigens, which could lead to early valve degeneration21 because of sensitization to the previous allograft20 22 were not supported by our data.
In conclusion, this study has shown that a second homograft aortic valve replacement offers good early and long-term survival, like the first operation. There is no evidence of accelerated degeneration. Left ventricular function improves postoperatively, particularly in patients with poor function before reoperation. Poor preoperative left ventricular function and associated procedures impair survival, suggesting earlier reoperation may further improve outcome.
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Appendix 1 |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1Appendix 2References |
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Risk Factors Examined for Early Death
Age Sex Left ventricular function (LVEDD, left ventricular end-systolic diameter, FS<25%) Indication of second operation Associated procedures Type of valve used (homograft/homovital) Type of procedure (root/subcoronary) Type of first operation Reoperation interval
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Appendix 2 |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1Appendix 2References |
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Risk Factors Examined for Late Death and Valve Degeneration
Age Sex Left ventricular function (LVEDD, left ventricular end-systolic diameter, FS<25%) Indication of second operation Associated procedures Type of valve used (homograft/homovital) Type of procedure (root/subcoronary) Type of first operation Reoperation interval Age of donor Sex of donor Dissection time of homograft Storage time of homograft
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References |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1Appendix 2References |
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1. Ross DN, Yacoub MH. Homograft replacement of the aortic valve: a critical review. Prog Cardiovasc Dis. 1969;11:275–293.[Medline] [Order article via Infotrieve]
2.
Barratt-Boyes BG, Roche AH, Subramanyan R, Pemberton
JR, Whitlock RM. Long- term follow-up of patients with the
antibiotic-sterilized aortic homograft valve inserted freehand in the
aortic position. Circulation. 1987;75:768–777.
3. O’Brien MF, McGiffin DC, Stafford EG. Allograft aortic valve replacement long term comparative clinical analysis of the viable cryopreserved and antibiotic 4c stored valves. J Cardiac Surgery. 1991;6:534–563.[Medline] [Order article via Infotrieve]
4.
Yacoub M, Rasmi NR, Sundt TM, Lund O, Boyland E,
Radley-Smith R, Khaghani A, Mitchell A. Fourteen-year experience with
homovital homografts for aortic valve replacement. J Thorac
Cardiovasc Surg. 1995;110:186–193.
5. Lund O, Chadrasekeran V, Grocott-Mason R, Elwida H, Mahzhar R, Khaghani A, Mitchell A, Ilsley C, Yacoub MH. Primary aortic valve replacement with allografts over twenty-five years: valve-related and procedure-related determinants of outcome. J Thorac Cardiovasc Surg.. 1999;117:77–90.
6. Yacoub MH, Suitters A, Khaghani A, Rose ML. Localisation of major histocompatibility complex antigens in aortic homografts. In Biologic and Bioprosthetic Valves: Proceedings of the Third International Symposium. New York, NY: York Medical Books; 1986:63–72.
7. Smith JD, Ogino H, Hunt D, Laylor RM, Rose ML, Yacoub MH. Humoral immune response to human aortic valve homografts. Ann Thorac Surg. 1995;60:S127–S130.
8. Edmunds LH Jr, Clark RE, Cohn LH, Miller G. Guidelines for reporting morbidity and mortality after cardiac valve operations. Ann Thorac Surg. 1988;46:257–259.[Medline] [Order article via Infotrieve]
9. Kaplan EL, Meier P. Nonparametric estimation from incomplete information. J Am Stat Assoc. 1958;53:457–481.
10. Cox DR, Oakes D. Multivariate analysis. In: Cox DR, Oakes D, eds. Analysis of Survival Data. London, England: Chapman and Hall. 1984:64.
11. Kirklin JW, Barratt-Boyes BG. Aortic valve disease. In: Kirklin JW, Barratt-Boyes BG, eds. Cardiac Surgery, 2nd ed. New York, NY: Churchill-Livingstone; 1992:491-557.
12. McGiffin DC, O’Brien MF, Stafford EG, Gardner MA, Pohlner PG. Long-term results of the viable cryopreserved allograft aortic valve: continuing evidence for superior valve durability. J Card Surg. 1988;3:289–296.[Medline] [Order article via Infotrieve]
13.
Albertucci M, Wong K, Petrou M, Mitchell A,
Somerville J, Theodoropolous S, Yacoub M. The use of unstented
homograft valves for aortic valve reoperations. J Thorac
Cardiovasc Surg. 1994;107:152–161.
14. Cohn LH, Aranki SF, Rizzo RJ, Adams DH, Cogswell KA, Kinchla NM, Couper GS, Collins JJ Jr. Decrease in operative risk of reoperative valve surgery. Ann Thorac Surg. 1993;56:15–20.[Abstract]
15.
Morishita K, Mawatari T, Baba T, Fukada J, Abe T.
Re-replacement for prosthetic valve dysfunction:
analysis of long-term results and risk factors. Ann
Thorac Surg. 1998;65:696–699.
16. Parr GV, Kirklin JW, Blackstone EH. The early risk of re-replacement of aortic valves. Ann Thorac Surg. 1977;23:319–322.[Abstract]
17. Wideman FE, Blackstone EH, Kirklin JW, Karp RB, Kouchoukos NT, Pacifico AD. Hospital mortality of re-replacement of the aortic valve: incremental risk factors. J Thorac Cardiovasc Surg. 1981;82:692–698.[Abstract]
18. Kawachi Y, Matuzaki K, Tominaga R, Yasui H, Tokunuga K. The risks of reoperation for prosthetic valve dysfunction. Surg Today. 1994;24:415–419.[Medline] [Order article via Infotrieve]
19. Bosch X, Pomar JL, Pelletier LC. Early and late prognosis after reoperation for prosthetic valve replacement. J Thorac Cardiovasc Surg. 1984;88:567–572.[Abstract]
20. Yankah AC, Wottge HU, Muller-Ruchholtz W. Prognostic importance of viability and a study of a second set allograft valve: an experimental study. J Card Surg. 1988;3:263–270.[Medline] [Order article via Infotrieve]
21. Yacoub MH. Applications and limitations of histocompatibility in clinical cardiac valve allograft surgery. Cardiac Valve Allograft, 1962–1987. New York, NY: Springer-Verlag; 1988:95.
22. Smith JD, Hornick PI, Rasmi N, Rose ML, Yacoub MM. Effect of HLA mismatching and antibody status on "homovital" aortic valve homograft performance. Ann Thorac Surg. 1998;66(6 suppl):5212–5215.
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