Ann Thorac Surg 2001;71:S306-S310
© 2001 The Society of Thoracic Surgeons
Bioprosthetic valves and conduits: new developments
Long-term results after aortic valve replacement with the Biocor PSB stentless xenograft in the elderly
Giovanni Battista Luciani, MDa,
Francesco Santini, MDa,
Stefano Auriemma, MDa,
Luca Barozzi, MDa,
Paolo Bertolini, MDa,
Alessandro Mazzucco, MDa
a Division of Cardiac Surgery, University of Verona, Verona, Italy
Address reprint requests to Dr Luciani, Division of Cardiac Surgery, University of Verona, O.C.M. Piazzale Stefani 1, Verona, 37126, Italy
e-mail: luciani{at}netbusiness.it
Presented at the VIII International Symposium on Cardiac Bioprostheses, Cancun, Mexico, Nov 3–5, 2000.
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Abstract
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Background. This study seeks to define the long-term results after Biocor PSB stentless aortic valve replacement (AVR) in elderly patients, including the effects of No-React treatment.
Methods. We reviewed the outcomes of 106 consecutive patients, aged 70 ± 6 years, having Biocor PSB (93 standard, 13 No-React) AVR between October 1992 and October 1996.
Results. There were three early deaths (3%) and 15 late deaths (15%), during a mean follow-up of 5.8 ± 1.6 years. At 8 years, survival was 82% ± 4% and freedom from cardiac death was 94% ± 3%. Freedom from valve failure was 92% ± 4% at 8 years (No-React: 92% ± 8% at 4 years). Replacement of the xenograft was required in 5 patients. Freedom from reoperation was 91% ± 4% at 8 years (No-React: 92% ± 8% at 4 years). Four bleeding and two embolic events were recorded: overall valve-related event-free survival was 81% ± 7% at 8 years (No-React: 76% ± 12% at 4 years). Age of long-term survivors averaged 77 ± 5 years and their New York Heart Association status was 1.3 ± 0.6 (versus 2.9 ± 0.6 preoperatively, p = 0.01).
Conclusions. Satisfactory freedom from cardiac events and from valve deterioration added to uniform improvement in functional status despite advanced age and high prevalence of comorbid conditions make AVR with the Biocor PSB xenograft a valid long-term therapy for the elderly. No-React treatment does not influence xenograft durability.
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Introduction
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Aortic valve replacement with stentless aortic xenografts has increased in popularity during the past decade [1]. The ability to reproduce the normal physiology of the aortic valve and to enhance prompt regression of left ventricular hypertrophy has proved to be a selective advantage of stentless valves over stented [2]. It has been hypothesized that this advantage may, in turn, explain the lower prevalence of cardiac adverse events late after operation [3]. However, the expectation of longer durability when compared with standard aortic bioprostheses has not been satisfied. Indeed, preliminary observations on long-term outcome after stentless aortic valve replacement suggest that the rate of primary tissue failure may be similar to stented xenografts [4].
The Biocor PSB stentless valve (Biocor Industria e Pesquisa Ltda, Belo Horizonte, MG, Brazil) was introduced into clinical practice in the early 1990s. Reports published thus far have focused on valve performance in the young [5, 6]. In addition, most of the clinical series have been collected in developing countries [5, 6]. Midterm results after implant of the Biocor PSB valve in an older patient population have been described by our group [7]. Durability similar to other available stentless xenografts has been demonstrated [7]. In an attempt to define the long-term behavior of the Biocor PSB valve, including the impact of a new anticalcification treatment, review of an 8-year experience has been undertaken.
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Material and methods
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Patients
One hundred six patients underwent aortic valve replacement using the Biocor PSB stentless valve at the University of Verona between October 1992 and October 1996. Ninety-three had standard valves and 13 had the Biocor No-React process. Thereafter, due to changes inherent, initially, with the distribution in Italy and, subsequently, with the production worldwide, the stentless xenograft was no longer used at our institution. Since 1992, two other stentless valves have been used besides the Biocor PSB in a total of 376 patients. Selection criteria for implant of an aortic xenograft were age older than 65 years; contraindications to oral anticoagulation therapy; and deliberate request of a biological valve by the patient. The choice between a stented and a stentless bioprosthesis and the choice among the three different stentless xenografts was ultimately made by the surgeon in a nonrandom fashion. Associated valvular or vascular lesions requiring concomitant intervention or reoperation and severity of left ventricular dysfunction, when present, were never considered contraindications to the use of stentless valves. Demographic profile of the patient population is summarized in Table 1.
Materials
The Biocor PSB valve is a composite valve made of selected individual porcine cusps, tanned with glutaraldehyde at zero pressure, and sutured to a strip of bovine pericardium, which is shaped in the form of a conduit and scalloped, above and below the insertion of the valve leaflets. The No-React anticalcification formula (Shelhigh Inc, Millburn, NJ) involves aldehyde cross-linkage to achieve high resistance to biodegradation, an aldehyde detoxification process, and surface modification with a surfactant [8].
Operative technique
Sizing of the valve was based on the diameter of the sinotubular junction. Grafting was performed either with the use of interrupted 4-0 multifilament polyester sutures (aortic annulus 23 mm or smaller) or with three running 4-0 polypropylene sutures (aortic annulus 25 mm or larger), for the inflow sutureline, and three running 4-0 polypropylene sutures, for the outflow sutureline. The operative variables of the patient population are reported in Table 1.
Anticoagulation therapy
Warfarin therapy was not used routinely except for patients with chronic atrial fibrillation.
Follow-up methods
Cross-sectional patient follow-up was completed between September and October 2000 by an in-hospital clinical assessment or telephone interview. Two (2%) patients were lost to follow-up investigation.
Statistical analysis
Continuous variables were expressed as means ± SD. Categorical variables were expressed as percentages. Continuous variables were compared using the two-tailed Student’s t test for paired data. Time-related events were described using the Kaplan–Meier method. Significance was inferred at a p value less than 0.05. End points of the study were survival, cardiac death-free survival, freedom from valve-related events, freedom from valve deterioration, freedom from structural valve deterioration, or freedom from reoperation.
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Results
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Survival
Hospital mortality was 3% (3 of 106) and late mortality was 15% (15 of 103). Cause of early death was cardiac in 2 patients and neurologic in 1. Average follow-up of survivors was 5.8 ± 1.6 years (range 4.5 to 8 years). Late deaths were due to cardiac-related events in 6 patients, malignancy in 3, pneumonia in 2, trauma in 2, cerebrovascular accident in 1, and digestive hemorrhage in 1. Overall survival was 94% ± 2%, 89% ± 3%, and 82% ± 4% (Fig 1, solid line) and freedom from cardiac-related death 98% ± 1%, 95% ± 2%, and 94% ± 3% (Fig 1, dotted line), at 1, 4, and 8 years.
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Fig 1. Actuarial survival (solid line) and freedom from cardiac death (dotted line) of 106 patients undergoing aortic valve replacement with the Biocor PSB stentless xenograft. Error bars represent ± SEM values.
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Valve-related complications
Adverse events related to the stentless valve were recorded in 12 (12%) patients, including 3 with No-React valves, during the study period: 6 patients had xenograft valve deterioration, requiring replacement in 5, as reported below (4 from hemorrhagic and 2 from embolic complications). Survival free from valve-related complications was 99% ± 1%, 92% ± 3%, and 81% ± 7% at 1, 4, and 8 years (Fig 2, dotted line). Valve-related event-free survival for patients with Biocor No-React xenografts was 100% and 76% ± 12% at 1 and 4 years.
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Fig 2. Actuarial freedom from valve-related adverse events (dotted line), structural valve failure (solid line), and reoperation on the xenograft valve (broken line) in 106 patients undergoing aortic valve replacement with the Biocor PSB stentless xenograft. Error bars represent ± SEM values.
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Valve deterioration
Stentless valve failure was identified in 6 (6%) patients, including 1 with a No-React valve. Deterioration was due to structural cause in 4 patients and nonstructural causes in 2. All patients with structural and 1 with nonstructural failure resulting from endocarditis presented with moderate to severe prosthetic valve regurgitation, acute in 2. The other patient with nonstructural deterioration presented with critical (peak pressure gradient of 50 mm Hg) transprosthetic obstruction, which appeared within 1 year of implant. Freedom from structural valve deterioration was 100%, 98% ± 2%, and 92% ± 4% at 1, 4, and 8 years (Fig 2, solid line). Freedom from structural deterioration for the Biocor No-React was 100% and 92% ± 8% at 1 and 4 years.
Reoperation
Reintervention on the stentless xenograft was required in 5 (5%) patients, including 1 with a No-React valve. Four patients with structural valve failure and 1 with nonstructural valve failure underwent reoperation: 2 on an urgent basis because of acute aortic insufficiency and active endocarditis with hemodynamic compromise. Reoperation consisted in stentless valve replacement with a stented bioprosthesis in 4 patients and aortic root replacement with an aortic homograft in 1. There was 1 death at reintervention, in a patient presenting with acute aortic insufficiency who had been operated on elsewhere. Xenograft valves explanted for structural deterioration uniformly showed cusp tear at the insertion onto the pericardial wall. Chemical analysis demonstrated minimal calcification at the level of the leaflets (calcium content less than 1.5 mg/g dry tissue). Freedom from reoperation on the valve was 100%, 98% ± 2%, and 91% ± 4% at 1, 4, and 8 years (Fig 2, broken line). For No-React valves, freedom from reoperation was 100% and 92% ± 8% at 1 and 4 years. Ten more patients required reinterventions during follow-up, unrelated to the stentless xenograft, including permanent pacemaker implant in 7 (7%), coronary bypass grafting in 1, percutaneous transluminal coronary angioplasty in 1, and percutaneous mitral valvuloplasty in 1.
Functional status
Mean patient age at follow-up was 77 ± 5 years. Significant improvement in New York Heart Association functional class was observed in long-term survivors (1.3 ± 0.6 versus 2.9 ± 0.6, p = 0.01). Seventy-seven (87%) survivors were free from chronic oral anticoagulation therapy.
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Comment
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Survival
Long-term observations of the clinical outcome after aortic valve replacement with the Biocor PSB stentless xenograft in an elderly population have confirmed the early and midterm findings [7]. The operation was followed by satisfactory survival and excellent freedom from cardiac untoward events. Up to 8 years after implant, the prosthesis has proved to be dependable and has allowed satisfactory freedom from complications related to the valve itself.
Studies of long-term survival using the Biocor PSB stentless xenograft are not available. Vrandecic and associates [5] reported an operative mortality of 5% and a raw late mortality of 4% in a mostly young patient population (mean age 36 years) at a mean follow-up of 2 years. More recent work by Von Oppell and colleagues [6] using the Biocor No-React valve has confirmed similar operative and late mortality (6% and 2%, respectively) in a slightly older patient population (mean age 44 years) at a comparable follow-up period. Comparison with survival after aortic valve replacement with the Toronto SPV xenograft appears sound as the latter is the one stentless valve with the longest available follow-up and with a design similar to the Biocor PSB valve. In a recent review, David and coworkers [4] described a 9-year survival of 89% in a series of 242 patients aged 62 years receiving the Toronto SPV valve. Given the older mean age (70 versus 62 years) and the higher prevalence of associated disease conditions (half versus one-third of patients) in the present study, the 8-year survival of 82% well matches the results of David and associates [4]. This finding is in line with the comparative analysis of 4-year outcomes after aortic valve replacement using the Biocor PSB and the Toronto SPV stentless xenografts performed at our own institution [7]. Consequently, superior survival compared with the standard stented xenografts can be anticipated with the Biocor PSB valve, as previously observed with the Toronto SPV valve [3]. Similar considerations apply to survival free from cardiac death. In the latter case, the 8-year estimate for the Toronto SPV valve is nearly identical to the one found herein (95% versus 94%) [3]. If the hypothesis correlating extent of left ventricular hypertrophy with prevalence of cardiac mortality proves true [3], it follows that the Biocor PSB valve is as effective as the Toronto SPV valve in enhancing ventricular mass regression.
Valve performance
As for survival, data regarding the prevalence of valve-related complications, including deterioration, late after implant of the Biocor PSB valve are lacking. Four reoperations due to nonstructural deterioration (prosthetic valve endocarditis and paravalvular leak, each in 2 patients) have been reported in 110 midterm survivors by Vrandecic and associates [5]. Four (8%) of 49 operative survivors have presented with critical transprosthetic obstruction (ie, nonstructural valve failure) and 9 (18%) with greater than mild aortic regurgitation (ie, structural valve failure) in the 4-year experience of Von Oppell and associates [6]. Thus, the 4-year freedom from valve-related adverse events was 71%, albeit estimated on an incomplete number of observations (follow-up 77% complete) [6]. It appears a rather forbidding task to reconcile the above findings with the gratifying 8-year results in our series. However, important discrepancies exist between the present work and the ones published previously [5, 6]. The latter series have both been collected in developing countries (Brazil, South Africa), on mostly young patients with a high prevalence of rheumatic and infective aortic valve disease [5, 6]. Translation of those observations to western world countries, where porcine xenografts are commonly used in aged patients with senile aortic valve disease, appears unjustified. Indeed, in an elderly population, such as the one herein, use of the Biocor PSB valve is associated with long-term freedom from complications identical to the Toronto SPV valve (81% at 8 years) [3]. Furthermore, freedom from structural valve deterioration (92% versus 85%) and from reoperation (91% versus 82%) prove superior to those reported with the Toronto SPV valve [3]. Given the older mean age of our patient cohort, in fact, the untoward effect of competing risks (ie, death from nonvalve-related cause and valve-related complications) leads to overestimations of the real prevalence of adverse events. Thus the actual freedom from valve-related complications is definitely greater than the actuarial estimate reported herein. However, available follow-up is too limited to conclude on longer durability of the Biocor PSB stentless valve compared with stented bioprostheses. It has been observed that the attrition rate of stented xenografts increases steeply 10 years after implant. Preliminary findings with the Toronto SPV valve, the only stentless valve to have reached the 10-year landmark, suggest that durability is similar to commonly used stented bioprostheses [3, 4].
Contrary to stented bioprostheses, the mode of failure of the Biocor PSB valve is subtle. Progressive transprosthetic obstruction due to restricted leaflet motion has not been recorded in the present study, but rather appearance, often abrupt, of severe valve regurgitation due to leaflet tear. Pathologic findings of explanted xenografts consist of cusp laceration with minimal calcification and closely resemble those found in the Toronto SPV valve [9]. The difference in type of structural alterations when compared with stented bioprostheses cannot be explained by shorter implant duration: average implant duration was 61 months for the Hancock II bioprosthesis in the series of Butany and associates [10] versus 58 months in the present study. More likely, the fact that the stentless valve is integral with the aortic root may expose the leaflet to increasing stress when the sinotubular junction dilates, as in normal aging [11]. Computer-generated models of the aortic root have demonstrated exponential rise in strain and stress on the aortic valve leaflets insertion sites even with moderate (ie, greater than 15%) dilation of the root [12]. Interestingly, cusp tear of explanted Biocor PSB valves has uniformly presented at the insertion sites of the commissures. A mode of structural deterioration unique to the stentless xenograft may thus exist, which depends on changes of the native aortic root rather than on the device itself. Accordingly, fixation of the sinotubular junction at the time of operation appears rational, although the consequences of progressive dilation of the sinus of Valsalva also deserve further investigation.
Reoperation on failed Biocor PSB valves has proved uneventful in our practice. The absence of any stentless valve wall calcification, a finding that often complicates replacement of freehand aortic homografts, may certainly explain the ease of reintervention. However, thorough experience with operations on the aortic root (including autografts, homografts, and xenografts) is the single most important factor in limiting the risk of reoperation [13]. Inadequate choice of timing or technique may otherwise significantly increase the morbidity of reintervention. It follows that referral of patients with degenerated stentless xenografts to centers with longstanding experience with aortic root operations is strongly advised.
No-React treatment
The No-React treatment has recently been proposed as an anticalcification method for biological tissues, including porcine xenografts, superior to the ones currently available [8]. Although experimental evidence in favor of the No-React treatment is still controversial [8, 14], clinical experience is limited. In a series of 52 Biocor No-React stentless aortic valve implants, Von Oppell and associates [6] observed a disappointing 71% freedom from reoperation or prosthetic valve regurgitation (ie, valve deterioration) at 4 years. The real estimate may have been even lower because of incomplete follow-up collection, as reported above. Interpretation of this result is complex, however, as the population at risk was young with a high prevalence of rheumatic valve disease. The present study has the theoretical advantage of looking at a patient cohort more representative of aortic valve disease in western countries. Unfortunately, the subgroup receiving Biocor No-React valves was too small to allow meaningful inferences on the durability of the xenograft. Apparently, the behavior of the Biocor No-React xenografts is similar the one of the standard Biocor PSB valve, as structural deterioration occurs at a comparable rate and with identical pathologic changes of the valve.
Study limitations
The present has inherent limitations. Patient and prosthesis selection has been nonrandom, which may have introduced bias in favor of stentless xenografts when compared with stented bioprostheses. In addition, the Biocor PSB valve is no longer used at our center. However, the data herein are meaningful as the xenograft is still in the market and is currently used elsewhere.
Conclusions
Aortic valve replacement with the Biocor PSB stentless xenograft is a satisfactory long-term treatment modality for the elderly patient in that it offers excellent freedom from untoward cardiac events, valve deterioration, and anticoagulant therapy. Moreover, it allows durable improvement of clinical conditions.
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References
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Abstract
Introduction
