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Ann Thorac Surg 2000;69:1327-1331
© 2000 The Society of Thoracic Surgeons

Original articles: Cardiovascular

Aortic valve replacement: comparison of late survival between autografts and homografts

Christopher J. Knott-Craig, MDa, Ronald C. Elkins, MDa, KathyLee Santangelo, MDa, Carolyn McCue, RNa, Mary M. Lane, PhDa

a Section of Thoracic and Cardiovascular Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

Address reprint requests to Dr Knott-Craig, Section of Thoracic and Cardiovascular Surgery, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190
e-mail: ckc{at}ouhsc.edu

Presented at the Forty-sixth Annual Meeting of the Southern Thoracic Surgical Association, San Juan, Puerto Rico, Nov 3–7, 1999.


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. Autografts (AG) and homografts (HG) are currently considered the best choices for replacement of the diseased aortic valve in young adults, although few data exist comparing their late outcome. Nonhomogeneous populations and evolving operative techniques confound existing comparisons.

Methods. To help clarify these issues, we reviewed our results with 238 hospital survivors (aged 17 to 82 years) undergoing operation between 1986 and 1999. All operations were done as root replacements, and patients needing concomitant valve replacement were excluded.

Results. Mean age of the 145 AGs and 93 HGs was 35 ± 13 years and 49 ± 17 years, respectively (p < 0.001). Previous aortic valve replacement was done in 12 (8%) AG and 32 (34%) HG patients (p = 0.001), and active endocarditis was present at time of current operation in 10 (7%) AG and 25 (27%) HG patients (p = 0.001). Maximum follow-up was 12.2 years for AGs and 12.8 years for HGs. Late survival at 10 years was 77% ± 11% for AGs and 67& ± 9% for HGs (p = 0.13). Freedom from AG or HG degeneration at 10 years was 97% ± 2% and 79% ± 10% (p = 0.63). Freedom from valve-related complications at 10 years was 73% ± 10% and 64% ± 10% (p = 0.93), respectively. Freedom from all reoperations at 10 years was 88% ± 5% for AG and 72% ± 11% for HG (p = 0.67).

Conclusions. Autografts and HGs have comparable late survival. The incidence of valve degeneration is low for both AG and HG up to about 8 years at which point there may be a trend toward an advantage for AG over the HG, suggesting benefit for the younger patient.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 References
 
Autografts (AG) or cryopreserved homografts (HG) are currently considered excellent choices for replacement of the diseased aortic valve in adults [1–5]. Both obviate the need for anticoagulation, have excellent hemodynamics, are resistant to infection, and have a negligible incidence of acute failure. The HG is especially useful in patients with extensive endocarditis [6–9]. It is a relatively simple, easily reproducible operation when used as a root replacement, but deteriorates over time at a variable rate depending on the age of the patient, and may need to be replaced within 10 to 20 years [10, 11]. On the other hand, AGs are particularly suitable for children and young adults where the patient has the potential to grow [12, 13], and the grafts do not usually deteriorate over time. Autografts may, however, develop dilatation with associated regurgitation [14, 15], although current modifications in technique are aimed at minimizing this risk [16–18]. Autograft procedures are technically more demanding, and places both the neopulmonary valve (HG) and the AG at risk of reoperation in the future.

Because of these differences and the natural bias toward using HGs for higher risk patients with significant comorbidity, older patients, and those with extensive endocarditis, or those needing multiple valve replacements, there exists little relevant data comparing the late outcome between HGs and AGs. These concerns prompted our review of hospital survivors of HG and AG procedures done (1) during the same time frame, (2) using similar surgical technique (root replacement), (3) age more than 16 years, and (4) excluding patients with multiple valve replacements.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 References
 
Between 1986 and 1999, 514 patients underwent either AG (n = 345) or HG (n = 169) replacement of the diseased aortic valve at the Oklahoma University Health Sciences Center. From these patients a group was identified that satisfied the following inclusion criteria: (1) patients older than 16 years; (2) root replacement technique was used for AG or HG replacement of the aortic valve; and (3) no patient underwent concomitant mitral or tricuspid valve replacement. Two hundred sixty-nine patients fulfilled these criteria; early mortality was 6% for AG (9 of 148) and 19% for HG (22 of 102).

The hospital survivors composed the study group of 238 patients. There were 173 men and 65 women. The Ross operation (AG) was done on 145 patients, and cryopreserved aortic HGs (CryoLife Inc, Atlanta, GA) were used in 93 patients. Despite the selection criteria, some differences between the AG and HG groups remain: (1) HG patients were older, (2) HG patients more often needed concomitant coronary artery bypass grafting, (3) HG patients more frequently had active endocarditis, and (4) HG patients included more patients with Marfan’s syndrome (Table 1).


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  		Table 1. Differences in Demographics Between Autograft and Homograft Groups

 
The diagnosis was predominantly aortic regurgitation in 56 AG patients (39%) and 44 HG patients (47%), and was predominantly aortic stenosis or mixed in 87 AG patients (60%) and 44 HG patients (47%). The aortic annulus was tailored (reduced in diameter) in 61 AG patients (42%) and 4 HG patients (4%), and the proximal suture line was reinforced with a cuff of pericardium or synthetic material in 113 AGs (78%) and 30 HGs (32%).

The analyses were done retrospectively from the Oklahoma University Health Sciences Center tissue valve follow-up database, which is updated continuously from echocardiographic reports, clinic notes, operative reports, and records of telephone contacts with patients and their physicians. Follow-up was achieved within 1 year of the close of this study (March 1999) in 97% of patients with AGs and 94% of patients with HG AVR. Median follow-up for AGs was 2.5 years and for HGs was 3.5 years. Maximum follow-up was 12.2 years for AGs and 12.8 years for HGs.

All analyses were performed using SAS System software, version 6.12 (SAS Institute, Cary, NC). Between-group differences of continuous variables were tested using a Wilcoxon two-sample test and {chi}2 or Fisher’s exact methods were used to test differences between proportions. Survival analysis and estimates of freedom from postoperative events were accomplished using Kaplan-Meier methods, with differences assessed using log-rank tests. Probability values of less than 0.05 were considered significant, and all p values are reported.

Definitions of end points
Valve degeneration was defined according to criteria published by Yacoub and colleagues [19] and includes severe regurgitation or stenosis of the AG or aortic HG, assessed by echocardiographic, clinical, operative, or postmortem evidence and reoperations on the AG or aortic HG. This excludes endocarditis-related valve failure and reoperations, and excludes complications related to the pulmonary HG.

Late survival represents survival from hospital discharge and includes all late deaths from all causes; early mortality is excluded.

Valve-related morbidity and mortality includes valve degeneration plus all valve-related deaths and sudden deaths, all reoperations on both the AG and aortic HG as well as the pulmonary HG (including those relating to endocarditis), and all other valve-related complications as published in The Annals of Thoracic Surgery guidelines [20].

Freedom from reoperation includes all reoperations on the AG or HG or pulmonary HG.


   Results
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 Abstract
 Introduction
 Patients and methods
 Results
Comment
 References
 
Late survival
Among AG patients, there were 6 late deaths, of which 3 were valve related. Among the HG patients, there were 13 late deaths, of which six were valve related. Causes of death are as follows: 10 cardiac deaths of which seven were valve related (endocarditis, 2; after reoperation, 1; sudden unexplained, 4) and three deaths were classified as other cardiac (congestive heart failure, 2; acute myocardial infarction, 1). Nine deaths were noncardiac (cancer, 4; automobile accident, 2; lupus erythematosus, 1; pulmonary embolus, 1; stroke, 1). Overall late survival at 5 and 10 years was 97% ± 2% and 77% ± 11% for AGs and 92% ± 3% and 67% ± 9% for HGs (p = 0.13) (Fig 1).



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  		Fig 1. Kaplan-Meier graph depicting late survival after homograft or autograft replacement of the aortic valve. Mean ± 67% confidence limit for three time intervals are indicated.

 
Valve degeneration
Among the AG group, there were 3 patients with severe AG regurgitation or who required reoperation on the AG. In 2 individuals the AG could be repaired, although 1 patient subsequently had the AG explanted and replaced with an HG. Five additional patients have moderate AG regurgitation, which appears to be stable, and they are being followed conservatively. Freedom from AG valve degeneration at both 5 and 10 years is 97% ± 2%. Among the HG group, 5 patients had the HG explanted for primary valve degeneration (4 for regurgitation and 1 for stenosis). Freedom from valve degeneration at 5 and 10 years was 97% ± 3% and 79% ± 10% (Fig 2).



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  		Fig 2. Kaplan-Meier graph depicting valve degeneration of the homograft or autograft after replacement of the aortic valve. Mean ± 67% confidence limit for three time intervals are indicated.

 
Valve-related morbidity and mortality
In the AG group, valve degeneration occurred in 3 patients, and valve-related mortality occurred in another 3 patients, as indicated in the above sections. One additional patient developed endocarditis. Five patients have had the pulmonary HG valve replaced, and 3 additional patients either have moderate stenosis or severe regurgitation of the pulmonary HG but have not yet had them replaced. Freedom from valve-related morbidity and mortality at 5 and 10 years was 91% ± 3% and 73% ± 10% (Fig 3). Three patients have required a permanent pacemaker.



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  		Fig 3. Kaplan-Meier graph depicting freedom from all valve-related morbidity and mortality after homograft or autograft replacement of the aortic valve. Mean ± 67% confidence limit for three time intervals are indicated.

 
Among the HG group, valve degeneration occurred in 5 patients and valve-related death occurred in 6 patients. Four patients developed endocarditis, 3 of which represented remote recurrent endocarditis in known drug abusers. No embolic strokes or bleeding occurred. Freedom from valve-related morbidity and mortality at 5 and 10 years was 94% ± 4% and 64% ± 10% (Fig 3). Three patients required a permanent pacemaker.

Freedom from reoperation
Freedom from reoperation for AGs was 88% ± 5% at 10 years and for HGs it was 72% ± 11% (Fig 4).



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  		Fig 4. Kaplan-Meier graph depicting freedom from all valve-related reoperations after homograft or autograft replacement of the aortic valve. Mean ± 67% confidence limit for three time intervals are indicated.

 

   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
References
 
Homografts have been used experimentally and clinically as aortic valve substitutes for more than 30 years [10, 19, 21]. Many of the reasons for its enthusiastic embrace in the 1960s and 1970s are equally relevant today: resistance to infection, excellent hemodynamics, and paucity of valve-related complications. Limitations to its universal acceptance, such as limited availability and failure due to technical error, have largely been overcome by improved methods of harvesting and preservation in HG banks [22, 23], and by improved surgical technique, recognizing that the HG is best inserted as a functional unit (eg, root replacement) [1, 5, 6, 10, 19, 24, 25]. Although numerous surgeons have contributed to the understanding and current acceptance of the HG as an aortic valve substitute, the perseverance and innovation of pioneers such as Ross, Barratt-Boyes, Yacoub, and O’Brien cannot be overstated.

The pulmonary AG (Ross operation) experience started as another innovative solution to the problem of left ventricular outflow obstruction in children in whom the HG was thought to be less than ideal [12, 26]. During the past decade it has become widely accepted as an excellent choice for aortic valve replacement in children and young adults [2, 27, 28]. In addition to the advantages of HGs, AGs have the potential to regenerate and grow, may be even more resistant to infection [8], and may have superior durability over the long term [11, 29]. Recently, a cautionary note has been expressed over the development of progressive neoaortic regurgitation due to AG dilatation [14, 15, 17]. We have sought to minimize this risk with newer innovations aimed at reducing and fixing the diameter of the aortic root annulus at the time of the initial Ross operation [17, 18, 30].

In the analysis of this retrospective review, which was designed to evaluate the long-term results of HG and AG in a homogenous adult population, it is clear that the review has important limitations: the subgroups AG and HG are not comparable. Table 1 indicates that the HG group has significantly higher comorbidity risks, which although obviated by the exclusion of early mortality in the study design, still translate into inferior long-term outcomes. As an example, the high incidence of patients with active endocarditis among HG patients (27% versus 7%), many of whom have ongoing predisposition to recurrent endocarditis, negatively impacts late survival, freedom from reoperation, and freedom from valve-related complications [8]. The higher median age of the HG patients compared to the AG patients has also been shown to negatively impact late survival and valve-related complications [31]. The only accurate way to compare long-term outcome between AGs and HGs is in a prospective randomized trial [4, 11]. Initial analysis indicates that the AG had better durability and hemodynamics than the cryopreserved HG [11]. Yacoub is currently analyzing his results with exactly such a prospective trial (personal communication).

Late survival at 10 years was 77% and 67% for AG and HG, respectively (Fig 1). These include noncardiac deaths and are very similar to results from other comparable HG series [5, 10, 32], and better than comparable series of mechanical or bioprosthetic valves [33, 34], which have 10-year survival of 50% to 60%. According to data from the Ross Procedure International Registry, survival for AG at 7 years was about 92% [29].

Freedom from valve degeneration or primary valve failure may represent the most accurate way to assess the long-term durability of valves, and in this context both AG and HG performed very well (Fig 2). Freedom from valve degeneration at 5 year and 10-year follow-up was 97% and 97% for AGs, and 97% and 79% for HGs (p = not significant). There appears to be a trend starting about 10 years postoperatively suggesting that the AG may perform better than HG over the longer term. This is supported by other recent data [4, 10, 11].

Freedom from reoperation on the aortic HG, or AG and pulmonary HG for AG patients, at 8 and 10 years was 92% and 88% for AGs and 96% and 72% for HGs (p = NS) (Fig 4), comparable to HG data from Yacoub showing 82% freedom from reoperation at 10 years [5]. When one examines estimated freedom from all valve-related morbidity and mortality (including reoperations), the data again is not statistically different over the follow-up period (Fig 3)—73% for AGs and 64% for HGs at 10 years. These data are significantly better than many comparable series of mechanical or bioprosthetic valves [33–36] and the HG data are very similar to that of the newer stentless bioprostheses, with the exception of a higher incidence of thromboembolism in the latter [37–39].

In summary, both HGs and AGs perform well over a 10-year follow-up period, with low incidence of primary tissue failure and low incidence of valve-related complications. Thromboembolic phenomena are rare, the incidence of recurrent endocarditis is low, and the hemodynamics of the valves are excellent. In this regard AG do not offer significant advantage over HG for the patient older than about 60 years. For the younger adult with little comorbidity, the AG may offer benefit over the longer run. With the newer innovations in operative technique currently used, this may become more evident over the next 5 to 10 years of follow-up.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

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