- Email: [email protected]
The stentless xenograft aortic valve: The wheel turns around
The Stentless Xenograft Aortic Valve: The Wheel Turns Around Mark F. O’Brien, FRACS, Michael A. H. Gardner, FRACS, Bruce Garlick, FRACS, Homayoun Jalali, MD, Susan Harrocks, RN, Lorraine McLoughlin, RN The Prince Charles Hospital and St Andrew’s War Memorial Hospital, Brisbane, Queensland, Australia
Background: A brief overview of the historical pathways of both stented and stentless porcine xenografts is presented in order to understand the return to and continuing clinical use of stentless devices. In addition, 7–11 years of durability with various models of stentless porcine valves has now accumulated and is beginning to be of relevance in determining the future place of this xenograft. Stentlessness and anticalcium agents, coupled with the poor results of stented xenografts in certain patient groups, have led to a resurgence of the clinical use of stentless xenograft valves for aortic valve replacement. An overview of the present state and future of stentless valves is given. Methods: At both The Prince Charles Hospital and St Andrew’s War Memorial Hospital, Queensland, Australia, 307 patients have received the Model 300 CryoLife-O’Brien stentless composite aortic xenograft from December 1992 to February 2000. Associated procedures were required in 56% of patients (mostly coronary artery bypass, mean 2.4 grafts, in 144 patients (47%) and left ventricular myomectomy in 34 patients (11%)). Results: The hospital mortality (four early deaths) has been 1.3 ± 1% (CL 95%) and the follow-up 100% for this analysis. The mean patient age was 73 years (range 57–89 years with 16% being 80 years and over). Morbid events have included six perivalvar leaks: four trivial and identified only on echo Doppler (no clinical murmurs) and two patients requiring reoperation at 10 days and 12 weeks with simple successful repair verified on subsequent echocardiograms. Of the 307 patients over the 7 year period, three valves only have been explanted, two for endocarditis at 1.5 and 3.5 years and one for possible technically induced structural failure at 15 months (probable needle damage). With this exception, there has been as yet no other intrinsic leaflet failure. Four early thromboembolic events (4 days–5 weeks) in patients with atrial fibrillation (no anticoagulants used postoperatively with the first 80 patients) constituted the important early morbid events. Late mortality of this elderly patient cohort has occurred in 27 patients over 7 years of maximum follow-up. One death (endocarditis) has been valve related at 5 years. Serial echocardiography (some 700 echoes in the study of this valve) has demonstrated a mean gradient of 7–9 mmHg with a very low incidence of trivial incompetence (96%) on Doppler examination with implant valve sizes ranging from 21 to 29 mm. One patient had significant regurgitation requiring reoperation. There has been no progression of either incompetence or stenosis of the remaining patients in this follow-up, now into the eighth postoperative year. Conclusion: The early and intermediate results appear excellent in this elderly patient cohort. Nevertheless, important surveillance is obviously required to determine the durability at 10–12 years, a crucial time when stented porcine xenografts began to show an obvious failure rate from structural deterioration, in the middle and elderly aged patient cohort. An attempt is made to outline the future of this type of stentless xenograft and to justify that its cautious use should probably be extended down to the over 50 year age patient cohort. (Heart, Lung and Circulation 2000; 9: 61–73) Key words: aortic valve replacement, CryoLife-O’Brien® xenograft, stentless. Correspondence: Mark F. O’Brien, Department of Cardiac Surgery, The Prince Charles Hospital, Rode Road, Chermside, Queensland 4032, Australia. Email: [email protected]
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he first xenografts used for clinical aortic valve replacement in 1965–1969 were stentless1–4 and most valves were non-glutaraldehyde preserved. This aortic valve, with and without excision of its right coronary leaflet muscle base, was preserved in a variety of unfavourable ways. The understanding of tissue preservation at that time was very much in its infancy. Consequently, poor clinical results with valve dysfunction within the first several years led to a high reoperation rate and the discontinuance of stentless xenografts by the end of 1969.5 In addition to inadequate tissue preservation, technical problems of implantation were encountered; first, with the asymmetry of some congenital bicuspid valves and aortic roots, and second, with the suturing around the xenograft’s muscle-based right coronary leaflet. Both factors increased the likelihood of leaflet deformation and the early appearance of progressive valve incompetence. At The Prince Charles Hospital in 1967, the technical problems were substantially solved with the first use of a composite valve assembled by matching three separate non-coronary cusps.5 The right and left coronary leaflets were removed and there was no need therefore to use any external dacron support as is currently used with most stentless valves. Clinical implants of this specifically designed composite valve began in September 1967. In addition, the excellent leaflet coaption of this composite valve substantially minimised the errors of host–graft matching and sizing within the host root at a time when experience of freehand subcoronary tissue valve implantation in the late 1960s was still in its infancy. Nevertheless this formaldehyde preserved valve, implanted 1967–1969 and composite that it was, became equally the victim of its poor preservation method. 6–8 The actuarial freedom from structural deterioration requiring reoperation fell to the unacceptable level of 50% at 5 years. However, at these many reoperations, some very relevant and important observations were made, the significance of which unfortunately was not realised for almost two decades. First, there was a complete absence of leaflet dehiscence of the tri-leaflet composite valve at the sutured commissures and second, no perivalvar separation occurred with the single continuous suture implantation technique. The concept of a composite valve appeared sound. It was ethically justified to recommence the clinical use of the valve but with glutaraldehyde preservation of the xenograft. In 1968–1969, Carpentier et al. introduced glutaraldehyde and stent mounting of the porcine valve.9 The problems of that era seemed to be ‘solved’. Glutaraldehyde preservation was far superior to formaldehyde and the stented valve was not only usable for atrioventricular valve replacement but also was a ready solu-
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tion to all technical difficulties of freehand aortic valve implantations especially into asymmetrical and large aortic roots. But two changes were made concurrently. The surgical principle of introducing one ‘advance’ at a time was not observed. Within less than one to two decades, the limitations of the stented valve were being clearly documented.10–20 Tissue degeneration, calcification, leaflet tears, perforations and simple ‘wearing out — like an old pair of shoes’ was seen by all surgeons implanting such stented bioprostheses. With multivariate analyses, the results in children and young adults (under 50 years) became most disappointing.14,15,18 In retrospect, an important logical omission obviously occurred in not trialling a glutaraldehyde composite stentless valve, even in a small series of patients in the early 1970s. We were in the situation to use these valves as they were all prepared and ready to implant, but the need to explant so many of the formaldehyde valves made us too wary. Consequently, the opportunity to provide answers regarding durability of the stentless valves, so eagerly awaited today, was lost. The long-term data on stentless valves has been required for some years for the younger patient and for the many for whom homografts and mechanical valves are not options (because of inadequate supply of tissue valve, lack of surgical experience, poor anticoagulant compliance, young age of recipient patient, young female and geographical situations). Consequently, the stentless valves already marketed as many models must still be considered valves under trial or study. The search for the best array of valves, both biological and mechanical, continues because for any one individual patient, a specific valve may be superior to many other valve types. The aim is to find and continually reevaluate which valve is the best for any one particular patient. The stented homograft valve was less durable than the stentless homograft and the same applied to formaldehyde preserved stented and stentless xenografts.21 Therefore, on sound theoretical grounds, it seems reasonable to forecast that the stentless xenograft valve will at least equal and more likely be superior in durability to the stented valve for AVR. In addition, superior haemodynamics, improved left ventricular regression22 and the growing evidence of superior longterm patient survival are now becoming evident.23 From 1967–1969, at The Prince Charles Hospital, 129 patients received the aortic composite valves.5,6,8 Except for non-commercial professional valve assembly and formaldehyde preservation, this valve was virtually the same as that of the present era. Specifically, low pressure (2–3 mm) glutaraldehyde fixation of the whole porcine valve and root precedes the extraction of the non-
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coronary leaflets for subsequent matching and trileaflet assembly (Fig. 1). The aim of this paper is to debate the current status and justification for continued use of the stentless valve, outline the clinical results of the Model 300 CryoLifeO’Brien® Composite Porcine Stentless Aortic Xenograft (CLOB; CryoLife® Inc., GA, USA; formerly the Bravo Cardiovascular Model 300, O’Brien-Angell valve), attempt to look to the future with variations and refinements of stentless valves and lastly to offer comments on the training of ‘tissue valve surgeons’ in the use of such devices.
coronary artery bypass grafts, present as most suitable candidates, particularly as most of their aortic roots are symmetrical and trileaflet. Second, a supra-annular implantation position affords good exposure especially in the small aortic root and provides a most effective central flow and a less obstructive orifice with low transvalvar gradients, almost mimicking the homograft valve. Third, with supra-annular implantation, the native annulus virtually dictates the effective orifice. In addition, some degree of restoration of annular movements results (see later).
Design of the Composite Valve
Brief Overview of Variations of Stentless Valves
The design of the composite Model 300 has distinct features that dictate a simple and precise implantation technique.24,26 First, with no tissue cuff on the ventricular aspect proximal to the leaflet hinge only a single superior suture line is required. As with continuous suturing, implantation can be reasonably rapid. Hence, elderly patients, almost half of whom have required associated
Figure 1. The CryoLife-O’Brien ® composite stentless porcine aortic xenograft valve. Assembled from three non-coronary leaflets.
Several valve companies have produced and marketed over these last 5–10 years a variety of stentless valves which, while possibly advancing the technology of tissue engineering, have presented an array that now demands accurate and difficult evaluation. Recent publications present excellent summaries of the available valves.27–30 It is unknown what influence these variations in design will have on durability just as it basically is still unknown statistically whether stentlessness will improve tissue durability. Most stentless valves using the whole valve have external dacron support varying from complete external covering (Baxter/Prima; Baxter Healthcare Corporation, CA, USA; and Toronto SPVTM; St Jude Medical Inc., MI, USA) to support of the muscle-based right coronary leaflet (Medtronic FreestyleTM; Medtronic Inc., MN, USA). The CryoLife-O’Brien® valve (CryoLife Inc., GA, USA), in being composite without a right coronary leaflet, is truly stentless and requires no dacron support. The major differences between models relate not only to the amount of this external dacron support when the whole porcine valve is used but also to the amount of xenograft tissue (both muscle and aortic wall) that is retained as proximal and distal cuffs. The CLOB valve has very minimal xenograft aortic wall superiorly and virtually no cuff proximally. Therefore, this valve requires only a single continuous suture line for implantation.24–26 The anatomical construction of these other stentless valves demands differing implantation techniques ranging from subcoronary, intra-aortic cylinder or full free root replacement, all with double proximal and distal suture lines. Although some valves can be trimmed to accommodate any of these three techniques (Medtronic Freestyle), it is debatable if this is advantageous as probably the better surgical results may be obtained by a more frequent use of a familiar constantly used technique.
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Yet the option is provided not only as a choice for the surgeon but also and perhaps more importantly to accommodate the varieties of host valve and root pathology. However, the subsequent fate of large amounts of xenograft aortic wall with the free root replacements in terms of the degree of subsequent calcification would suggest that in some patients the xenograft aortic wall has become extensively calcified. This was also found in the experimental Model 3.31 The eventual findings may vary when the results of the present and future methods of calcium mitigation become available. Will xenograft aortic wall calcification render a stentless valve stented? In addition to porcine valves, stentless pericardial valves have now become available, requiring comparative evaluation. There are several determinants that may affect durability to varying degrees. 1. Various methods of zero to 2–3 mmHg glutaraldehyde pressure fixation have given variable clinical results. The clinical advantages of zero-pressure fixation are still not clearly evident as both in the Intact (stented) valve and in the Medtronic Freestyle, zero-pressure fixation has been coupled with different calcium mitigating agents. Christie34 and others32,33 have clearly outlined the advantages of zero pressure leaflet fixation in retaining the more normal collagen crimp32–34 although this may gradually be lost in vivo. 2. Varying percentages of glutaraldehyde concentration (0.2–3.0%) are used. Reduction of the ischaemic time from animal death to retrieval, glutaraldehyde exposure, the importance of its concentration, length of storage and the effects of residual free aldehydes in inducing or reducing post-implant leaflet calcification and subsequent dysfunction are the foci of much recent experimental and clinical research. One aspect of this new direction is to pursue vigorously non-glutaraldhyde preservation processes.35 3. The precise amount of retained xenograft aortic wall probably will dictate the extent of future calcification. Although this may be modified by some calcium mitigating agents, patient factors especially younger age, may be more powerful determinants. The Toronto SPV and the CLOB stentless valves do not have any calcium mitigating agents, while the Medtronic freestyle xenograft has the alpha-oleic-amino agent which is reported to significantly minimise leaflet calcification but not necessarily aortic xenograft wall calcification.31 The effects of xenograft aortic wall calcification, as may occur with a root implant, on leaflet durability are unknown and may be impossible to determine. The normal dynamic extensibility of the aortic wall, annulus and leaflet may be substantially lost.
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4. The range of implant techniques from subcoronary to intraluminal cylinder replacement to full root replacement increases the operative complexity with implantation of more xenograft aortic wall. Simple techniques may be of advantage and safer for some or all of our patients. A number of surgeons need to validate the advantages of both implant techniques and valve devices or models in a range of patient cohorts. Multicentre studies may begin to achieve this.36,37 5. The presence of dacron over a large amount of xenograft wall may be an important factor that influences excessive fibrotic fixation of tissue, pannus ingrowth or calcification, rendering the bioprosthesis semi-stented or semi-rigid. Pannus ingrowth, seen with all valve types, both mechanical and bioprosthetic, has been reported infrequently with the porcine stentless valves. However, Luciani et al. did report one patient, receiving a CLOB valve who required reoperation because of pannus in-growth and valve leaflet obstruction.38 A commentary was made by O’Brien on this report.39 In this respect, it shares the same quality as the homograft valve. 6. With the supra-annular implantation of the CLOB valve (minimal xenograft aortic wall) an interesting observation is that late echocardiographic studies have demonstrated during phases of the cardiac cycle, annular and sinotubular systolic–diastolic expansion. This restoration of the ‘normal’ extensibility (diastolic and systolic motion) of the native resected and decalcified aortic valve annulus may indicate that this stentless xenograft has the least rigidity of all stentless valves. Dissipation to surrounding tissues of the stress forces of leaflet closure are achieved. 7. Already, ‘new advances’, new stentless valves, have been announced in 1999. The Toronto II SPV (glutaraldehyde and anticalcium agent), the CryoLife SynergraftTM valve (non-glutaraldehyde and decellularised for in vivo autologous cellular repopulation) and others were spoken of at the May 1999, Third International Bioprosthesis Meeting.35,37 All these changes await 10 years or more of clinical evaluation.
Implantation Technique Although a range of valve sizes enables routine ‘off the shelf’ use, some preoperative estimation of the measurements and configuration of the aortic root can be obtained from echocardiography. Angiography appears unnecessary and provides no more information. Echocardiography assists the surgeons in the overall understanding of the variation of the human aortic root and the building of knowledge desirable and even essential for stentless tissue valve use. Direct intraoperative verifi-
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cation of these measurements, with or without intraoperative transoesophageal echocardiography, is required prior to valve size selection and standard routine washing of the xenograft. If washing can be carried out prior to cardiopulmonary bypass, perfusion times are lessened by some 5–10 min. After complete excision of the diseased aortic valve leaving no annular ridge nor any loose calcium, three equidistant 3/0 polypropylene (No. 8936 on a small taper cut half circle V5 needle) sutures are placed through the supra-annular aortic sinus wall above the mid-point level of the nadir of each sinus–annulus (Fig. 2). Sutures are, therefore, passed immediately above the valve annulus. Many surgeons are initially hesitant that all sutures are to be actually passed into supra-annular aortic wall tissue. Re-checking of the equidistant nature of these three sutures is essential for subsequent symmetrical implantation. The three sutures are then passed vertically up through most of the CLOB xenograft aortic wall from outside inferiorly to inside superiorly leaving virtually no subvalvar xenograft wall ridge (Fig. 3). The three sutures are then tied. Careful supra-annular implantation produces the better haemodynamic result in our hands (Fig. 4). There are no internal knot ends which may perforate leaflet tissue and care is essential so as to not damage leaflet tissue which is never touched by surgical forceps. For the continuous suturing, it is safer to pass the needle through xenograft wall and then through host tissue in order to minimise risks of needle damage to leaflet tissue which might occur if the suture was passed from host through the xenograft. Nevertheless, one of our patients and the only one with ‘structural degeneration’ may well have had such needle damage. This can still occur as the needle is passed through the host annulus; the point of the needle can impinge on the belly of the xenograft leaflet as it is drawn out of the aortic root. A transverse aortotomy has eliminated the need for pericardial patching of the aorta. With an oblique aortotomy such a patch was often necessary to avoid approximating the right anterior and the posterior commissures. Nevertheless, even within the transverse aortotomy, the commissural posts after fixation must be equidistant from one another. Occasionally, when the transverse aortotomy is made too low or proximal, the top of the xenograft commissure projects above the aortotomy edge. After partial aortic closure, the commissure needs then to be attached to and within the distal aorta with additional through-and-through sutures tied outside the aorta. This presents no problem but is rarely necessary. With a subcoronary implant, the sinotubular diameter as well as the annular diameter should be measured. If the former is dilated more than some 10% of the annular
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measurement, the sinotubular aorta may require reduction aortoplasty, otherwise commissural splaying will produce central incompetence and, as strongly proposed by Petracek et al.,40 will influence and reduce durability. This is considered an important contribution. Alternatively, with the CLOB valve, in particular, a larger valve can be implanted (e.g. for an annulus measurement of 25 mm and a sinotubular diameter of 27–29 mm, a CLOB valve of 29 mm should be implanted well out in the supra-annular position). The haemodynamic result has been shown to be excellent in such a situation. Overall, the implantation technique is very simple, the valve easy to implant,24–26 but if the recommended steps are not followed, malalignment and leaflet deformation can occur and the consequent results are far from optimal. The common mistakes are twofold; first, too
Figure 2. In the supra-annular position near the central midpoint of each sinus, three equidistant 3.0 polypropylene sutures are placed.
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small a bite of the xenograft wall (Figs 5a–c) leaves a ledge, a space or a tissue protuberance into the left ventricular cavity, and second, intra-annular rather than supra-annular implantation produces suboptimal haemodynamics (Fig. 6). Left ventricular subvalvar muscle is occasionally an additional obstruction secondary to the valve stenosis, particularly in elderly females with concentric hypertrophic left ventricular (LV) muscle and a small LV cavity. Experience has revealed that a much smoother immediate postoperative cardiac performance and clinical progress has been obtained in those patients who have received associated LV subvalvar longitudinal myomectomy. For this reason 11% of this series have
received this additional procedure. The surgical indications have been the subjective observation of a very prominent LV subvalvar muscle often with the inability to visualise the lower half or free edge of the anterior leaflet of the mitral valve. It has also been clinically noted that myomectomy when indicated and performed has led to a smoother immediate postoperative course after both stented bioprosthetic and mechanical valve implants. Although it is stressed that the calcified valve should be excised leaving no tissue at annulus level, dehiscence of the aorta from the annulus needs to be avoided, or if present, repaired separately with interrupted polypropylene sutures. Knots need to be carefully kept away from the leaflet which will rest supra-annularly. Mediratta et al.41 and the reply by Hvass42 outline their experience of posterior aorto-annular dehiscence and the
Figure 3. The suture takes a broad bite of the xenograft wall and a similar broad bite of the supra-annular sinus aortic wall.
Figure 4. The single layer continuous suture technique with external aortic termination knot.
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suggestions of surgical correction with returning to full bypass, re-cardioplegia and intra-aortic closure of the dehiscence and reattachment of the stentless xenograft. If calcification does extend onto the aortic wall of the aortic sinus this should not be removed as it weakens the aortic wall and may produce significant haemorrhage. This calcification is a contraindication to CLOB valve supraannular implantation. Occasionally, periaortic haematoma occurs post-bypass, especially anteriorly. This resolves after Protamine neutralisation of the heparin and has never required specific surgery in the author’s hands. It is due to peri-aortic suture line bleeding from the supra-annular aortic sinus suture line. It has never led to coronary right artery obstruction.
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Clinical Results From December 1992 to February 2000, 307 patients have received Cryolife-O’Brien Model 300 stentless porcine xenograft for aortic valve replacement at The Prince Charles Hospital and at St Andrew’s War Memorial Hospital, Queensland, Australia. The hospitals’ Ethics Committee approval and Therapeutic Goods Administration (TGA) Australia and registration as a Certified Trial Notification (CTN) valve were obtained in 1992. Detailed informed patient consent was mandatory. The follow-up has been 100% complete. The mean age was 73 years (range 59–89 years), 49 patients (16%) being 80 years or older at the time of operation. Concomitant procedures
Figure 5. (a) Incorrect implantation with too small a bite in the xenograft wall. This error produces a space behind the xenograft and may be inadequate to fix the xenograft wall securely against the host wall. (b) Incorrect implantation technique with intra-annular fixation: It should be supra-annular. (c) Correct supra-annular alignment.
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Figure 6. Maximising the effective orifice by supra-annular implantation compared to the reduced orifice with an incorrect intra-annular implantation. were required in 173 patients (56%), most of which (n = 144) were coronary artery bypasses (2.4 grafts/ patient). All but four patients survived (30 day/hospital mortality = 1.3 ± 1%, 95% confidence limits). Follow-up has now entered its eighth year. Early mortality occurred in four patients and was all valve unrelated (retroperitoneal haemorrhage from intraaortic balloon insertion first day postoperative; aortic dissection at cardioplegic site (second day); ruptured spleen (patient fell out of bed, third day); and sudden death at home (arrhythmia 29th day). Late mortality occurred in 28 patients (5 months–5.7 years). Valve related aetiology of death occurred only in the two un-reoperated late endocarditis patients. All other causes could be explained very readily on natural causes in this elderly patient cohort (e.g. cancer (n = 7), CVA (n = 6), etc). There were perioperative cerebrovascular events in two patients, both of whom had previous strokes. Both recovered well but subsequently died in the second postoperative year from further strokes. Three early systemic thromboemboli occurred in unanticoagulated patients who had troublesome early atrial arrhythmia. In the first 80 patients in this series, no anticoagulants were given. Now this medication is recommended for 2 months and no further early thromboembolic episode has since occurred. In spite of the presence of a stentless valve, it is realised that this elderly patient cohort is more likely to develop such postoperative arrhythmia, unlike the younger homograft aortic valve patients who are less likely to develop arrhythmias and who receive no anticoagulant medication postoperatively. Over the seven
complete years of follow-up, seven elderly patients had cerebrovascular events leading to death in five patients. Additional morbid events include six paravalvar leaks, four of which were only echocardiographically detected with no clinical murmurs. In two patients, one patient with a suture that was too loose (10 days postoperative) and in another patient with a broken suture (15 weeks), both having 4/0 polypropylene continuous suturing, reoperation was required. A successful longterm outcome with valve repair has been verified in both patients by late echocardiography. For the last 240 patients, a stronger 3/0 polypropylene suture has been used without further major problem. Endocarditis has occurred in five patients, 1.5–5 years after operation. Two patients died without reoperation. Three received reoperation: two valves were replaced and in the third patient a competent non-infected valve was left in situ and the healed VSD caused by endocarditis voces successfully closed. Reoperation (six patients) was required for structural deterioration in one patient only at 15 months, who had a discrete perforation in leaflet tissue, the surrounds of which looked normal. In being so unlike the usual xenograft leaflet perforation, where surrounding leaflet tissue is thin and almost transparent, it was considered that this patient may have had an inadvertent suture needle injury. The event has nevertheless been ascribed to one of structural deterioration. This patient had moderate incompetence immediately after the initial operation and this progressed, therefore it was unlikely to be due solely to structural degeneration or ‘intrinsic’ leaflet failure. The other five reoperations have been for endo-
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carditis (three patients) and perivalvar leak (two patients). Clinical and echocardiographic assessment of valve incompetence has revealed excellent results. Initially in the series, intraoperative transoesophageal echocardiographic examination was carried out. Now transthoracic examination is performed at the pre-hospital or preoperation phase, postoperation at fifth–sixth day, at 6 months, 1 year and 1–2 yearly thereafter. In many patients, a trace of non-progressive incompetence is present. Transvalvar gradients, effective orifice area and degree of incompetence according to both the host annular size and the implanted valve size (21–29 mm) across time have shown only in one patient, a mean gradient of 7–9 mmHg with progression of incompetence43 requiring reoperation. One patient has a persisting high transvalvar gradient with a mean of 24 mmHg and a peak of 44 mmHg at 2 years after operation. It is unlikely that this patient has pannus in-growth producing leaflet obstruction and a decreased orifice area. The gradient is more likely due to residual LV hypertrophy particularly as it has been present since operation. No other patient had a haemodynamic pressure gradient abnormality. The details of serial echocardiography have been clearly documented,43 have not changed in the 1999 analysis and are not repeated in any detail in the present study. In that analysis overall, 96% of patients have either nil, or a trivial degree of incompetence on echocaradiography across time to greater than 4 years after operation. A valuable instructive comparison of haemodynamic and LV mass regression between the CLOB valve and the supra-annular Carpentier-Edwards stented porcine valve has been reported in detail.22,43 Briefly, at 6 months the mean gradients were lower (P ≤ 0.001), the effective orifice was greater (P ≤ 0.05) and the dimensionless performance index higher (P = 0.01) in the stentless CLOB group versus the Carpentier-Edwards stented group.22 There was important LV reduction and regression at 6 months postoperatively in both groups, but the reduction was greater in the stentless valves than the stented valves (P = 0.04). Other studies using alternative stentless valves have also confirmed similar major LV hypertrophic regression.30
Statistical Analysis Statistical analysis comprising Kaplan–Meier actuarial analyses of patient survival, freedom from thromboembolism, endocarditis, reoperation for structural deterioration and reoperation from all causes are outlined in Table 1. Only to the fourth–fifth year follow-up period are sufficient patient numbers available to provide meaningful statistics. Comparison of echocardio-
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graphic results was made using analysis of variance contingency tables.
Discussion The long-term durability of a stentless xenograft in general is still unknown in spite of the 10 years follow-up of a small series with the Toronto (SPV) valve.27 This review of the CLOB valve has outlined a follow-up in the eighth year. To the present time only one structural failure has occurred. The use of this xenograft is primarily in elderly patients in whom death is the competing risk, modifying the analysis of both durability and survival accordingly. Nevertheless, stentless valves appear to offer excellent immediate results auguring well for the long-term future. Many clinical questions will arise over the next several years. Which is the best stentless valve? Will it be necessary to have two or three different models at our disposal for use in various clinical situations? What will be the easiest (for the surgeon) and best (for the patient) implantation techniques? What is the fate of glutaraldehyde aortic wall when a root replacement is used? Will the dacron-supported valves have excessive fibrosis and calcification rendering the valve in time, essentially like a stented one? Will explantation at reoperation be difficult? Will non-glutaraldehyde preservation and better calcium mitigation agents produce yet a newer generation of durable valves applicable for all patient age groups?35 Lastly, is stentlessness a surgical gimmick or is it good theory gradually being translated to a successful clinical application? Table 1. events
Patient survival and actuarial freedom from morbid 4 Years 7 Years AVR>4 years ago AVR>7 years ago n = 119 n=5
Patient survival (n = 307, 1st op 31.12.1992) • 4 early hospital/ 86% ± 3% 30 day deaths • 27 late deaths (276 survivors) Freedom from • thromboembolism 93% ± 2% • endocarditis (5) 95% ± 3% • reoperation for (i) structural 99% ± 1% deterioration (1) (ii) all causes 96% ± 2% (perivalvar leak (2) endocarditis (3) structural deterioration (1))
68% ± 7%
93% ± 2% 95% ±3%* 99% ± 1% 96% ± 2%
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The Possible Advantages of Stentlessness Stentless xenografts have some of the attributes of the aortic homograft valve. Perhaps the most striking quality compared to the stented xenograft is the favourable haemodynamics, particularly in the small aortic root. No stent should imply no obstruction. The effective orifice within a given host aortic root is much greater compared to other prostheses and bioprostheses. This applies particularly with the CLOB valve where, for example, a 27 mm valve is inserted supra-annually into a 25 mm host annulus. Although the xenograft leaflets are a little stiff, they still produce low mean transvalvar gradients almost but not quite as good as those with a homograft valve or a Synergraft® xenograft. Evidence has accumulated that stentless valves enhance LV hypertrophic regression faster and more completely than do stented valves.22 Jin et al. compared the haemodynamic data of homografts, stentless (Toronto SPVTM) and stented valves.30 Both types of stentless valves caused less resistance to LV ejection and produced greater early improvement in LV function and consequently more complete resolution of LV hypertrophy. These important findings were verified by Del Rizzo et al.44 with the Toronto SPV valve and by Thomson et al.22 analysing this series of CLOB implants. The theoretical advantage and probably the primary reason for renewed interest and clinical use of the stentless xenograft is the high probability of improved durability due to the better distribution of physical forces during leaflet movements. The leaflets of a stented valve have to be perfectly assembled to minimise the unnatural forces of physical closure. Most stented valves are not perfectly assembled. Nevertheless, even if leaflet coaption does evenly distribute the physical stress without any excessive forces on the leaflet commissures, the dissipation of forces, as occurs through the flexible normal aortic wall, is absent in the stented structure.32–34 The evidence for stress mitigation with the stentless valve rests on the available data of the durability of stented and unstented homografts and on the differences of stented and stentless xenografts that were formaldehyde preserved in the late 1960s.21 In both instances, the stentless tissue was far more durable. There is also some experimental evidence that stentless porcine aortic valves are less likely to calcify.31 However, any improved durability of a stentless xenograft will not be evident statistically until another 5 years have elapsed.
The Limitations, The Teaching to Junior Surgeons and the Contraindications of Stentless Xenografts The implantation of a stentless structure is technically more demanding and exacting than the insertion of a
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framed bioprosthesis or mechanical valve. Implantation techniques are more difficult to learn and more difficult to teach. The operative procedures are less frequent and available only in a small number of interested surgical centres. Consequently, the opportunities for cardiac surgical trainees to learn are reduced. Repeated practice on animal hearts is mandatory in order to overcome these problems and to produce a high standard of clinical practice. In the 2000s, the learning curve can be reduced to a minimum with animal heart practice. Nowadays, at many conferences, tissue valve workshops on animal hearts are conducted by several companies to encompass the implantation techniques of pulmonary autograft, homograft and stentless xenograft valves. However, attendance at one of these workshops may not be sufficient in itself and additional laboratory bench practice is required. In using a stentless xenograft, unlike using a stented valve, the surgeon must take much more notice of the host anatomy and pathology. Both annular and sinotubular diameters, the symmetry of the annulus (bicuspid or tricuspid), the orientation of the outflow tract and aortic root, the presence and degree of calcification of the aortic sinus and the degree of destruction of the root with endocarditis become of major importance. The subsequent surgical technique requires to be planned around these variables and new surgical decisions may need to be made at the operating table. In the 1967–1969 stentless valve series, no perivalvar leak was seen at reoperation or autopsy. The same single continuous suture line was used except that the suture in this early series was a braided 3/0 Merselene and the valve at that time was formaldehyde preserved. The current experience is with a 3/0 polypropylene and it is possible that this suture has too much stretch and is not reliable to suture a glutaraldehyde preserved tissue to a living tissue. The few reoperations that have been necessary (three endocarditis, one structural failure, two perivalvar leaks) have indicated that the plane between the glutaraldehyde xenograft aortic wall and host is very easily separated. Nevertheless, perivalvar leak has not been a problem in the last 240 patients in this series of CLOB implants. There are three significant but rare contraindications to the subcoronary implantation of this composite valve. First, excessive aortic root calcification may preclude suturing in the supra-annular and peri-commissural aortic tissue. This probably applies as well to other models of stentless valves using xenograft subcoronary implantation. Such calcification is not common, but if present, an alternative stented bioprosthesis (e.g. pericardial valve) should be chosen. In this series, no stentless valve implantation has had to be abandoned in the middle of
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implantation because of aortic wall calcification. This decision has always been made on inspection of the aortic root, prior to selection of the particular valve. Second, the larger aortic annulus (≥30 mm) is a contraindication for this valve, the largest size of which is a 29 mm CLOB valve. Last, for the subcoronary implant of a stentless xenograft, gross asymmetry of the aortic root, although rare in the elderly, may produce a less desirable result than that obtainable with a stented pericardial valve. With refinement of surgical pathways, the next 5 years will provide the solutions to current problems. In the meantime, it is imperative that the more senior surgeons maintain open doors for our juniors to be exposed, to learn, to practise and to take over the analyses of the patients in order that all may have first hand information of stentless valve durability as it unfolds.
Lessons Learned From Homograft Aortic Valve Implantation Without doubt the 28 year experience at The Prince Charles Hospital with homograft techniques from subcoronary implantation to root replacement in 1022 patients45 has provided experience with the handling of valve tissue and familiarity of the diseased aortic root with its many variations of symmetry. But still the learning curve with newer staff surgical members exists even though it may now be somewhat flatter! A homograft root replacement for aortic valve disease alone would not be indicated in the elderly (over 70 years). This is because of the limited homograft valve supply and because results with other valve types are good and shorter operation times are more appropriate in this older age group, many of whom require associated coronary artery bypass grafting. Much is known about the fate of the homograft but the same cannot be said about the stentless porcine aortic xenograft. Some caution is required with the general use of stentless xenografts across the recipient age spectrum. Because stented xenografts have given a poor record in young and middle aged patients up to 50–60 years old,46 it would seem wise not to use the stentless valve in this younger age group unless homografts are not available or anticoagulants are to be avoided. In such circumstances, the stentless valve could then be used instead of the stented bioprosthesis in the hope that improved durability will be the advantage. This latter scenario of use in younger patients is more likely to occur in the countries where rheumatic valve disease predominates, and in countries where anticoagulants are best avoided. The optimal age range of the recipient receiving a stentless valve has not yet been determined. Already there have been many stentless valves implanted into younger patients. However, collation of results involves signifi-
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cant co-operation from surgeons, hospitals and valve companies to provide relevant accurate data. To date, this has not been forthcoming. Although stented xenografts give excellent results in the elderly,47–49 this same group of patients are ideal recipients of the stentless valve. They provide at least immediate clinically comparable results. At our hospitals, the results with the CryoLife-O’Brien valve have been excellent with only four 30 day/hospital postoperative deaths (1.3%) in 307 elderly patients since its inception in 1992. As the durability of stentless valves becomes more apparent and providing the results become superior to the stented variety, then the valve can in the future ethically be used in younger adults. This, however, is not the present recommendation. The advantages of rapid implantation in this patient group, 56% requiring a combined procedure, is evident in this series. In this patient group, unlike that of the younger homograft valve recipients, the valve pathology is more likely to be a trileaflet, acquired degenerative calcific aortic valve stenosis. Such symmetry is most favourable for this composite valve with its minimal xenograft tissue and its single continuous suture technique in the supra-annular position. At present, it may be close to the ideal valve for the elderly.
Acknowledgements Acknowledgment is given to the several echocardiologists, in particular Dr Daryl Burstow, Malcolm Davison and Helen Thompson, who have assisted in our study of the stentless valve; to Susan Smith for her help in the statistical analyses; Jacci Green for her data collection in the earlier years of this study and to Helen Gay for her secretarial services and to the many faithful patients, particularly early in our experience, who were much aware that the CLOB valve was a trial valve under close surveillance.
References 1. Binet JP, Duran CG, Carpentier A, Langlois J. Heterologous aortic valve transplantation. Lancet 1965; 2: 1275. 2. O’Brien MF, Clareborough JK. Heterograft aortic valve transplantation for human valve disease. Med. J. Aust. 1966; 2: 228–30. 3. O’Brien MF. Heterograft aortic valves for human use: Valve bank, techniques of measurement and implantation. J. Thorac. Cardiovasc. Surg. 1967; 53: 392–7. 4. Carpentier A, Lemaigre G, Robert L, Carpentier S, Dubost C. Biological factors affecting long-term
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results of valvular heterografts. J. Thorac. Cardiovasc. Surg. 1969; 58: 467–83. O’Brien MF, Neilson GH, Galea EG, Molphy R, Power W, Stephens BJ. Heterograft valves: An analysis of clinical results of valve replacement. Circulation 1970; 41 (Suppl II): 5–11. O’Brien MF. Heterologous replacement of the aortic valve. In: Ionescu MI, Ross DN, Wooler GH (eds). Biological Tissue in Heart Valve Replacement. Butterworths, London, 1972; 445–66. Stephens BJ, O’Brien MF. Pathology of xenografts in aortic valve replacements. Pathology 1972; 4: 167–73. O’Brien MF. Proceedings of the First International Workshop on Tissue Valves. Ann. Surg. 1969; 172: 12–13. Carpentier A, Deloche A, Relland J et al. Six year follow-up of glutaraldehyde-preserved heterografts with particular reference to the treatment of congenital valve malformations. J. Thorac. Cardiovasc. Surg. 1974; 68: 771–82. Jamieson WR, Burr LH, Munro AI, Miyagishima RT, Gerein AN. Cardiac valve replacement in the elderly: Clinical performance of biological prostheses. Ann. Thorac. Surg. 1989; 48: 173–85. Jamieson WR. Modern cardiac valve devices: Bioprostheses and mechanical prostheses: State of the art. J. Card. Surg. 1993; 8: 89–98. Burdon TA, Miller DC, Oyer PE et al. Durability of porcine valves at fifteen years in a representative North American patient population. J. Thorac. Cardiovasc. Surg. 1992; 103: 238–52. Magilligan DJ Jr, Lewis JW Jr, Tilley B, Peterson E. The porcine bioprosthetic valve. Twelve years later. J. Thorac. Cardiovasc. Surg. 1985; 89: 499–507. Williams DB, Danielson GK, McGoon DC, Puga FJ, Mair DD, Edwards WD. Porcine heterograft valve replacement in children. J. Thorac. Cardiovasc. Surg. 1982; 84: 446–50. Dunn JM. Porcine valve durability in children. Ann. Thorac. Surg. 1981; 32: 357–68. Hammond GL, Geha AS, Kopf GS, Hashim SW. Biological versus mechanical valves. Analysis of 1,116 valves inserted in 1,012 adult patients with a 4,818 patient-year and a 5,327 valve-year follow-up. J. Thorac. Cardiovasc. Surg. 1987; 93: 182–98. Thubrikar MJ, Deck JD, Aouad J, Nolan SP. Role of mechanical stress in calcification of aortic bioprosthetic valves. J. Thorac. Cardiovasc. Surg. 1983; 86: 115–25. Pupello DF, Bessone LN, Hiro SP, Lopez-Cuerca E, Glaterer MS, Ebra G. The Carpentier-Edwards bioprosthesis: A comparative study analysing failure rates by age. J. Cardiac Surg. 1988; 3 (Suppl.): 369–74.
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19. Ferrans VJ, Boyce SW, Billingham ME, Jones M, Ishihara T, Roberts WC. Calcific deposits in porcine bioprostheses: Structure and pathogenesis. Am. J. Cardiol. 1980; 46: 721–34. 20. Jamieson WR. Stented porcine bioprostheses: Durability and outcomes, 1975–1993. In: Piwnica A, Westaby S (eds). Stentless Bioprostheses. Isis Medical Media, Oxford, 1995; 24–35. 21. Angell WW, Pupello DF, Bessone LN, Hiro SP, Brock JC. Effect of stent mounting on tissue valves for aortic valve replacement. J. Cardiac Surg. 1991; 6 (Suppl. 4): 595–9. 22. Thomson HL, O’Brien MF, Almeida AA, Tesar, PJ, Davison MB, Burstow DJ. Haemodynamics and left ventricular mass regression: A comparison of the stentless, stented and mechanical aortic valve replacement. Eur. J. Cardiothorac. Surg. 1998; 13: 572–5. 23. David TE, Puschmann R, Ivanov J et al. Aortic valve replacement with stentless and stented porcine valves. A case-match study. J. Thorac. Cardiovasc. Surg. 1998; 116: 236–41. 24. O’Brien MF. The CryoLife-O’Brien composite aortic stentless xenograft: Surgical technique of implantation. Ann. Thorac. Surg. 1995; 60: S410–413. 25. Implantation brochure, 1999. Available from CryoLife International Inc, 1655 Roberts Boulevard, NW Kennesaw GA 30144, USA or Advanced Biomedical Pty Ltd, 5 Vista Court, Ringwood East, Victoria 3135, Australia. 26. O’Brien MF. Implantation technique of the CryoLifeO’Brien® stentless xenograft aortic valve: The simple, rapid, and correct way to implant and the errors to avoid. Seminars Thoracic Cardiovasc. Surg. 1999; 11 (Suppl. 1): 121–125. 27. David TE, Feindel CM, Scully HE, Bos J, Rakowski H. Aortic valve replacement with stentless porcine aortic valves: A ten year experience. J. Heart Valve Disease 1998; 7: 250–4. 28. Westaby S. Why stentless valves? In: Piwnica A, Westaby S (eds). Stentless Bioprostheses. Isis Medical Media, London, 1995; 3–16. 29. Piwnica A, Westerby S. Stentless Bioprostheses. Iris Medical Media, Oxford, 1995. 30. Jin XY, Zhang Z-M, Gibson DG, Yacoub MH, Pepper JR. Effect of valve substitute on changes in left ventricular function and hypertrophy after aortic valve replacement. Ann. Thorac. Surg. 1996; 62: 683–90. 31. Hazekamp MG, Goffin YA, Huysmans HA. The value of the stentless biovalve prosthesis. An experimental study. Eur. J. Cardiothorac. Surg. 1993; 7: 514–19.
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32. Thubrikar M, Deck JD, Aouad J, Nolan SP. Role of mechanical stress in calcification of aortic bioprosthetic valves. J. Thorac. Cardiovasc. Surg. 1983; 86: 115–25. 33. Sabah HN, Hamid MS, Steni PD. Mechanical stress on closed cusp porcine bioprosthetic valves: Correlation with sites of calcification. Ann. Thorac. Surg. 1986; 42: 93–6. 34. Christie GW, Barratt-Boyes B. On stress reduction in bioprosthetic heart valve leaflets by the use of a flexible stent. J. Cardiac Surg. 1991; 6: 476–81. 35. O’Brien MF, Goldstein S, Walsh S, Black KS, Elkins R, Clarke D. The Synergraft® valve: A new acellular (non-glutaraldehyde fixed) tissue heart valve for autologous recellularization. Seminars Thoracic Cardiovasc. Surg. 1999; 11 (Suppl. 1) 194–200. 36. Hvass U, Palatianos G, Frassani R, Puricelli C, O’Brien M. Multicenter study of stentless valve replacement in the small aortic root. J. Thorac. Cardiovasc. Surg. 1999; 117: 267–72. 37. Third International Bioprosthesis Symposium, May 1999, Grand Cayman: Peer review manuscripts published in Seminars of Thoracic and Cardiovascular Surgery. October 1999. 38. Luciani GP, Bertolini P, Mazzacco A. Early failure of freehand aortic stentless xenograft valves. J. Thoracic Cardiovasc. Surg. 1997; 113: 1109–10. 39. O’Brien MF. Early failure of freehand aortic stentless xenograft valves. J. Thoracic Cardiovasc. Surg. 1998; 115: 961–63. 40. Petracek MR, Shuman TA, Pirolo JS, Tedder M, Ball SK, Graves D. Use of Toronto stentless porcine valve in patients with aortic dilatation. Seminars Thoracic Cardiovasc. Surg. 1999; 11 (Suppl. 1): 74–8.
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41. Mediratta N, Sosnowski AW, Galinanes M. Posterior aortoventricular bleeding after supra-annular stentless aortic valve replacement. J. Thoracic Cardiovasc. Surg. 1999; 117: 1031–32. 42. Hvass U. Posterior aortoventricular bleeding after aortic valve replacement with the stentless CryoLifeO’Brien valve. J. Thorac. Cardiovasc. Surg. 2000; 119: 857–58. 43. O’Brien MF, Gardner MAH, Garlick RB et al. The CryoLife-O’Brien stentless aortic porcine xenograft valve. J. Cardiac Surg. 1998; 13: 376–85. 44. Del Rizzo DF, Goldman DS, Christakis GT, David TE. Hemodynamic benefits of the Toronto stentless valve. J. Thorac. Cardiovasc. Surg. 1996; 112: 1431–46. 45. O’Brien MF, Harrocks S, Stafford EG et al. The homograft aortic valve. A 29 year, 99.3% follow-up of 1022 valve replacements. J. Heart Valve Disease 2000 (in press). 46. McGiffin D, Galbriath AJ, O’Brien MF et al. An analysis of valve re-replacement following aortic valve replacement with biological devices. J. Thoracic Cardiovasc. Surg. 1997; 113: 311–18. 47. Barratt-Boyes BG, Jaffe WM, Whitlock RM. The Medtronic intact porcine valve: Ten-year clinical review. J. Thorac. Cardiovasc. Surg. 1998; 116: 1005–14. 48. Jamieson WR, Lemieux MD, Sullivan JA, Munro AI, Metras J, Cartier PC. Medtronic intact porcine bioprosthesis: 10 years’ experience. Ann. Thorac. Surg. 1998; 66: S118–21. 49. Banbury MK, Cosgrove III DM, Lytle BW, Smedira NG, Sabik JF, Saunders CR. Long-term results of the carpentier-edwards pericardial aortic valve: A 12year follow-up. Ann. Thorac. Surg. 1998; 66: S73–6.
Background: A brief overview of the historical pathways of both stented and stentless porcine xenografts is presented in order to understand the return to and continuing clinical use of stentless devices. In addition, 7–11 years of durability with various models of stentless porcine valves has now accumulated and is beginning to be of relevance in determining the future place of this xenograft. Stentlessness and anticalcium agents, coupled with the poor results of stented xenografts in certain patient groups, have led to a resurgence of the clinical use of stentless xenograft valves for aortic valve replacement. An overview of the present state and future of stentless valves is given. Methods: At both The Prince Charles Hospital and St Andrew’s War Memorial Hospital, Queensland, Australia, 307 patients have received the Model 300 CryoLife-O’Brien stentless composite aortic xenograft from December 1992 to February 2000. Associated procedures were required in 56% of patients (mostly coronary artery bypass, mean 2.4 grafts, in 144 patients (47%) and left ventricular myomectomy in 34 patients (11%)). Results: The hospital mortality (four early deaths) has been 1.3 ± 1% (CL 95%) and the follow-up 100% for this analysis. The mean patient age was 73 years (range 57–89 years with 16% being 80 years and over). Morbid events have included six perivalvar leaks: four trivial and identified only on echo Doppler (no clinical murmurs) and two patients requiring reoperation at 10 days and 12 weeks with simple successful repair verified on subsequent echocardiograms. Of the 307 patients over the 7 year period, three valves only have been explanted, two for endocarditis at 1.5 and 3.5 years and one for possible technically induced structural failure at 15 months (probable needle damage). With this exception, there has been as yet no other intrinsic leaflet failure. Four early thromboembolic events (4 days–5 weeks) in patients with atrial fibrillation (no anticoagulants used postoperatively with the first 80 patients) constituted the important early morbid events. Late mortality of this elderly patient cohort has occurred in 27 patients over 7 years of maximum follow-up. One death (endocarditis) has been valve related at 5 years. Serial echocardiography (some 700 echoes in the study of this valve) has demonstrated a mean gradient of 7–9 mmHg with a very low incidence of trivial incompetence (96%) on Doppler examination with implant valve sizes ranging from 21 to 29 mm. One patient had significant regurgitation requiring reoperation. There has been no progression of either incompetence or stenosis of the remaining patients in this follow-up, now into the eighth postoperative year. Conclusion: The early and intermediate results appear excellent in this elderly patient cohort. Nevertheless, important surveillance is obviously required to determine the durability at 10–12 years, a crucial time when stented porcine xenografts began to show an obvious failure rate from structural deterioration, in the middle and elderly aged patient cohort. An attempt is made to outline the future of this type of stentless xenograft and to justify that its cautious use should probably be extended down to the over 50 year age patient cohort. (Heart, Lung and Circulation 2000; 9: 61–73) Key words: aortic valve replacement, CryoLife-O’Brien® xenograft, stentless. Correspondence: Mark F. O’Brien, Department of Cardiac Surgery, The Prince Charles Hospital, Rode Road, Chermside, Queensland 4032, Australia. Email: [email protected]
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T
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he first xenografts used for clinical aortic valve replacement in 1965–1969 were stentless1–4 and most valves were non-glutaraldehyde preserved. This aortic valve, with and without excision of its right coronary leaflet muscle base, was preserved in a variety of unfavourable ways. The understanding of tissue preservation at that time was very much in its infancy. Consequently, poor clinical results with valve dysfunction within the first several years led to a high reoperation rate and the discontinuance of stentless xenografts by the end of 1969.5 In addition to inadequate tissue preservation, technical problems of implantation were encountered; first, with the asymmetry of some congenital bicuspid valves and aortic roots, and second, with the suturing around the xenograft’s muscle-based right coronary leaflet. Both factors increased the likelihood of leaflet deformation and the early appearance of progressive valve incompetence. At The Prince Charles Hospital in 1967, the technical problems were substantially solved with the first use of a composite valve assembled by matching three separate non-coronary cusps.5 The right and left coronary leaflets were removed and there was no need therefore to use any external dacron support as is currently used with most stentless valves. Clinical implants of this specifically designed composite valve began in September 1967. In addition, the excellent leaflet coaption of this composite valve substantially minimised the errors of host–graft matching and sizing within the host root at a time when experience of freehand subcoronary tissue valve implantation in the late 1960s was still in its infancy. Nevertheless this formaldehyde preserved valve, implanted 1967–1969 and composite that it was, became equally the victim of its poor preservation method. 6–8 The actuarial freedom from structural deterioration requiring reoperation fell to the unacceptable level of 50% at 5 years. However, at these many reoperations, some very relevant and important observations were made, the significance of which unfortunately was not realised for almost two decades. First, there was a complete absence of leaflet dehiscence of the tri-leaflet composite valve at the sutured commissures and second, no perivalvar separation occurred with the single continuous suture implantation technique. The concept of a composite valve appeared sound. It was ethically justified to recommence the clinical use of the valve but with glutaraldehyde preservation of the xenograft. In 1968–1969, Carpentier et al. introduced glutaraldehyde and stent mounting of the porcine valve.9 The problems of that era seemed to be ‘solved’. Glutaraldehyde preservation was far superior to formaldehyde and the stented valve was not only usable for atrioventricular valve replacement but also was a ready solu-
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tion to all technical difficulties of freehand aortic valve implantations especially into asymmetrical and large aortic roots. But two changes were made concurrently. The surgical principle of introducing one ‘advance’ at a time was not observed. Within less than one to two decades, the limitations of the stented valve were being clearly documented.10–20 Tissue degeneration, calcification, leaflet tears, perforations and simple ‘wearing out — like an old pair of shoes’ was seen by all surgeons implanting such stented bioprostheses. With multivariate analyses, the results in children and young adults (under 50 years) became most disappointing.14,15,18 In retrospect, an important logical omission obviously occurred in not trialling a glutaraldehyde composite stentless valve, even in a small series of patients in the early 1970s. We were in the situation to use these valves as they were all prepared and ready to implant, but the need to explant so many of the formaldehyde valves made us too wary. Consequently, the opportunity to provide answers regarding durability of the stentless valves, so eagerly awaited today, was lost. The long-term data on stentless valves has been required for some years for the younger patient and for the many for whom homografts and mechanical valves are not options (because of inadequate supply of tissue valve, lack of surgical experience, poor anticoagulant compliance, young age of recipient patient, young female and geographical situations). Consequently, the stentless valves already marketed as many models must still be considered valves under trial or study. The search for the best array of valves, both biological and mechanical, continues because for any one individual patient, a specific valve may be superior to many other valve types. The aim is to find and continually reevaluate which valve is the best for any one particular patient. The stented homograft valve was less durable than the stentless homograft and the same applied to formaldehyde preserved stented and stentless xenografts.21 Therefore, on sound theoretical grounds, it seems reasonable to forecast that the stentless xenograft valve will at least equal and more likely be superior in durability to the stented valve for AVR. In addition, superior haemodynamics, improved left ventricular regression22 and the growing evidence of superior longterm patient survival are now becoming evident.23 From 1967–1969, at The Prince Charles Hospital, 129 patients received the aortic composite valves.5,6,8 Except for non-commercial professional valve assembly and formaldehyde preservation, this valve was virtually the same as that of the present era. Specifically, low pressure (2–3 mm) glutaraldehyde fixation of the whole porcine valve and root precedes the extraction of the non-
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coronary leaflets for subsequent matching and trileaflet assembly (Fig. 1). The aim of this paper is to debate the current status and justification for continued use of the stentless valve, outline the clinical results of the Model 300 CryoLifeO’Brien® Composite Porcine Stentless Aortic Xenograft (CLOB; CryoLife® Inc., GA, USA; formerly the Bravo Cardiovascular Model 300, O’Brien-Angell valve), attempt to look to the future with variations and refinements of stentless valves and lastly to offer comments on the training of ‘tissue valve surgeons’ in the use of such devices.
coronary artery bypass grafts, present as most suitable candidates, particularly as most of their aortic roots are symmetrical and trileaflet. Second, a supra-annular implantation position affords good exposure especially in the small aortic root and provides a most effective central flow and a less obstructive orifice with low transvalvar gradients, almost mimicking the homograft valve. Third, with supra-annular implantation, the native annulus virtually dictates the effective orifice. In addition, some degree of restoration of annular movements results (see later).
Design of the Composite Valve
Brief Overview of Variations of Stentless Valves
The design of the composite Model 300 has distinct features that dictate a simple and precise implantation technique.24,26 First, with no tissue cuff on the ventricular aspect proximal to the leaflet hinge only a single superior suture line is required. As with continuous suturing, implantation can be reasonably rapid. Hence, elderly patients, almost half of whom have required associated
Figure 1. The CryoLife-O’Brien ® composite stentless porcine aortic xenograft valve. Assembled from three non-coronary leaflets.
Several valve companies have produced and marketed over these last 5–10 years a variety of stentless valves which, while possibly advancing the technology of tissue engineering, have presented an array that now demands accurate and difficult evaluation. Recent publications present excellent summaries of the available valves.27–30 It is unknown what influence these variations in design will have on durability just as it basically is still unknown statistically whether stentlessness will improve tissue durability. Most stentless valves using the whole valve have external dacron support varying from complete external covering (Baxter/Prima; Baxter Healthcare Corporation, CA, USA; and Toronto SPVTM; St Jude Medical Inc., MI, USA) to support of the muscle-based right coronary leaflet (Medtronic FreestyleTM; Medtronic Inc., MN, USA). The CryoLife-O’Brien® valve (CryoLife Inc., GA, USA), in being composite without a right coronary leaflet, is truly stentless and requires no dacron support. The major differences between models relate not only to the amount of this external dacron support when the whole porcine valve is used but also to the amount of xenograft tissue (both muscle and aortic wall) that is retained as proximal and distal cuffs. The CLOB valve has very minimal xenograft aortic wall superiorly and virtually no cuff proximally. Therefore, this valve requires only a single continuous suture line for implantation.24–26 The anatomical construction of these other stentless valves demands differing implantation techniques ranging from subcoronary, intra-aortic cylinder or full free root replacement, all with double proximal and distal suture lines. Although some valves can be trimmed to accommodate any of these three techniques (Medtronic Freestyle), it is debatable if this is advantageous as probably the better surgical results may be obtained by a more frequent use of a familiar constantly used technique.
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Yet the option is provided not only as a choice for the surgeon but also and perhaps more importantly to accommodate the varieties of host valve and root pathology. However, the subsequent fate of large amounts of xenograft aortic wall with the free root replacements in terms of the degree of subsequent calcification would suggest that in some patients the xenograft aortic wall has become extensively calcified. This was also found in the experimental Model 3.31 The eventual findings may vary when the results of the present and future methods of calcium mitigation become available. Will xenograft aortic wall calcification render a stentless valve stented? In addition to porcine valves, stentless pericardial valves have now become available, requiring comparative evaluation. There are several determinants that may affect durability to varying degrees. 1. Various methods of zero to 2–3 mmHg glutaraldehyde pressure fixation have given variable clinical results. The clinical advantages of zero-pressure fixation are still not clearly evident as both in the Intact (stented) valve and in the Medtronic Freestyle, zero-pressure fixation has been coupled with different calcium mitigating agents. Christie34 and others32,33 have clearly outlined the advantages of zero pressure leaflet fixation in retaining the more normal collagen crimp32–34 although this may gradually be lost in vivo. 2. Varying percentages of glutaraldehyde concentration (0.2–3.0%) are used. Reduction of the ischaemic time from animal death to retrieval, glutaraldehyde exposure, the importance of its concentration, length of storage and the effects of residual free aldehydes in inducing or reducing post-implant leaflet calcification and subsequent dysfunction are the foci of much recent experimental and clinical research. One aspect of this new direction is to pursue vigorously non-glutaraldhyde preservation processes.35 3. The precise amount of retained xenograft aortic wall probably will dictate the extent of future calcification. Although this may be modified by some calcium mitigating agents, patient factors especially younger age, may be more powerful determinants. The Toronto SPV and the CLOB stentless valves do not have any calcium mitigating agents, while the Medtronic freestyle xenograft has the alpha-oleic-amino agent which is reported to significantly minimise leaflet calcification but not necessarily aortic xenograft wall calcification.31 The effects of xenograft aortic wall calcification, as may occur with a root implant, on leaflet durability are unknown and may be impossible to determine. The normal dynamic extensibility of the aortic wall, annulus and leaflet may be substantially lost.
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4. The range of implant techniques from subcoronary to intraluminal cylinder replacement to full root replacement increases the operative complexity with implantation of more xenograft aortic wall. Simple techniques may be of advantage and safer for some or all of our patients. A number of surgeons need to validate the advantages of both implant techniques and valve devices or models in a range of patient cohorts. Multicentre studies may begin to achieve this.36,37 5. The presence of dacron over a large amount of xenograft wall may be an important factor that influences excessive fibrotic fixation of tissue, pannus ingrowth or calcification, rendering the bioprosthesis semi-stented or semi-rigid. Pannus ingrowth, seen with all valve types, both mechanical and bioprosthetic, has been reported infrequently with the porcine stentless valves. However, Luciani et al. did report one patient, receiving a CLOB valve who required reoperation because of pannus in-growth and valve leaflet obstruction.38 A commentary was made by O’Brien on this report.39 In this respect, it shares the same quality as the homograft valve. 6. With the supra-annular implantation of the CLOB valve (minimal xenograft aortic wall) an interesting observation is that late echocardiographic studies have demonstrated during phases of the cardiac cycle, annular and sinotubular systolic–diastolic expansion. This restoration of the ‘normal’ extensibility (diastolic and systolic motion) of the native resected and decalcified aortic valve annulus may indicate that this stentless xenograft has the least rigidity of all stentless valves. Dissipation to surrounding tissues of the stress forces of leaflet closure are achieved. 7. Already, ‘new advances’, new stentless valves, have been announced in 1999. The Toronto II SPV (glutaraldehyde and anticalcium agent), the CryoLife SynergraftTM valve (non-glutaraldehyde and decellularised for in vivo autologous cellular repopulation) and others were spoken of at the May 1999, Third International Bioprosthesis Meeting.35,37 All these changes await 10 years or more of clinical evaluation.
Implantation Technique Although a range of valve sizes enables routine ‘off the shelf’ use, some preoperative estimation of the measurements and configuration of the aortic root can be obtained from echocardiography. Angiography appears unnecessary and provides no more information. Echocardiography assists the surgeons in the overall understanding of the variation of the human aortic root and the building of knowledge desirable and even essential for stentless tissue valve use. Direct intraoperative verifi-
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cation of these measurements, with or without intraoperative transoesophageal echocardiography, is required prior to valve size selection and standard routine washing of the xenograft. If washing can be carried out prior to cardiopulmonary bypass, perfusion times are lessened by some 5–10 min. After complete excision of the diseased aortic valve leaving no annular ridge nor any loose calcium, three equidistant 3/0 polypropylene (No. 8936 on a small taper cut half circle V5 needle) sutures are placed through the supra-annular aortic sinus wall above the mid-point level of the nadir of each sinus–annulus (Fig. 2). Sutures are, therefore, passed immediately above the valve annulus. Many surgeons are initially hesitant that all sutures are to be actually passed into supra-annular aortic wall tissue. Re-checking of the equidistant nature of these three sutures is essential for subsequent symmetrical implantation. The three sutures are then passed vertically up through most of the CLOB xenograft aortic wall from outside inferiorly to inside superiorly leaving virtually no subvalvar xenograft wall ridge (Fig. 3). The three sutures are then tied. Careful supra-annular implantation produces the better haemodynamic result in our hands (Fig. 4). There are no internal knot ends which may perforate leaflet tissue and care is essential so as to not damage leaflet tissue which is never touched by surgical forceps. For the continuous suturing, it is safer to pass the needle through xenograft wall and then through host tissue in order to minimise risks of needle damage to leaflet tissue which might occur if the suture was passed from host through the xenograft. Nevertheless, one of our patients and the only one with ‘structural degeneration’ may well have had such needle damage. This can still occur as the needle is passed through the host annulus; the point of the needle can impinge on the belly of the xenograft leaflet as it is drawn out of the aortic root. A transverse aortotomy has eliminated the need for pericardial patching of the aorta. With an oblique aortotomy such a patch was often necessary to avoid approximating the right anterior and the posterior commissures. Nevertheless, even within the transverse aortotomy, the commissural posts after fixation must be equidistant from one another. Occasionally, when the transverse aortotomy is made too low or proximal, the top of the xenograft commissure projects above the aortotomy edge. After partial aortic closure, the commissure needs then to be attached to and within the distal aorta with additional through-and-through sutures tied outside the aorta. This presents no problem but is rarely necessary. With a subcoronary implant, the sinotubular diameter as well as the annular diameter should be measured. If the former is dilated more than some 10% of the annular
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measurement, the sinotubular aorta may require reduction aortoplasty, otherwise commissural splaying will produce central incompetence and, as strongly proposed by Petracek et al.,40 will influence and reduce durability. This is considered an important contribution. Alternatively, with the CLOB valve, in particular, a larger valve can be implanted (e.g. for an annulus measurement of 25 mm and a sinotubular diameter of 27–29 mm, a CLOB valve of 29 mm should be implanted well out in the supra-annular position). The haemodynamic result has been shown to be excellent in such a situation. Overall, the implantation technique is very simple, the valve easy to implant,24–26 but if the recommended steps are not followed, malalignment and leaflet deformation can occur and the consequent results are far from optimal. The common mistakes are twofold; first, too
Figure 2. In the supra-annular position near the central midpoint of each sinus, three equidistant 3.0 polypropylene sutures are placed.
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small a bite of the xenograft wall (Figs 5a–c) leaves a ledge, a space or a tissue protuberance into the left ventricular cavity, and second, intra-annular rather than supra-annular implantation produces suboptimal haemodynamics (Fig. 6). Left ventricular subvalvar muscle is occasionally an additional obstruction secondary to the valve stenosis, particularly in elderly females with concentric hypertrophic left ventricular (LV) muscle and a small LV cavity. Experience has revealed that a much smoother immediate postoperative cardiac performance and clinical progress has been obtained in those patients who have received associated LV subvalvar longitudinal myomectomy. For this reason 11% of this series have
received this additional procedure. The surgical indications have been the subjective observation of a very prominent LV subvalvar muscle often with the inability to visualise the lower half or free edge of the anterior leaflet of the mitral valve. It has also been clinically noted that myomectomy when indicated and performed has led to a smoother immediate postoperative course after both stented bioprosthetic and mechanical valve implants. Although it is stressed that the calcified valve should be excised leaving no tissue at annulus level, dehiscence of the aorta from the annulus needs to be avoided, or if present, repaired separately with interrupted polypropylene sutures. Knots need to be carefully kept away from the leaflet which will rest supra-annularly. Mediratta et al.41 and the reply by Hvass42 outline their experience of posterior aorto-annular dehiscence and the
Figure 3. The suture takes a broad bite of the xenograft wall and a similar broad bite of the supra-annular sinus aortic wall.
Figure 4. The single layer continuous suture technique with external aortic termination knot.
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suggestions of surgical correction with returning to full bypass, re-cardioplegia and intra-aortic closure of the dehiscence and reattachment of the stentless xenograft. If calcification does extend onto the aortic wall of the aortic sinus this should not be removed as it weakens the aortic wall and may produce significant haemorrhage. This calcification is a contraindication to CLOB valve supraannular implantation. Occasionally, periaortic haematoma occurs post-bypass, especially anteriorly. This resolves after Protamine neutralisation of the heparin and has never required specific surgery in the author’s hands. It is due to peri-aortic suture line bleeding from the supra-annular aortic sinus suture line. It has never led to coronary right artery obstruction.
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Clinical Results From December 1992 to February 2000, 307 patients have received Cryolife-O’Brien Model 300 stentless porcine xenograft for aortic valve replacement at The Prince Charles Hospital and at St Andrew’s War Memorial Hospital, Queensland, Australia. The hospitals’ Ethics Committee approval and Therapeutic Goods Administration (TGA) Australia and registration as a Certified Trial Notification (CTN) valve were obtained in 1992. Detailed informed patient consent was mandatory. The follow-up has been 100% complete. The mean age was 73 years (range 59–89 years), 49 patients (16%) being 80 years or older at the time of operation. Concomitant procedures
Figure 5. (a) Incorrect implantation with too small a bite in the xenograft wall. This error produces a space behind the xenograft and may be inadequate to fix the xenograft wall securely against the host wall. (b) Incorrect implantation technique with intra-annular fixation: It should be supra-annular. (c) Correct supra-annular alignment.
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Figure 6. Maximising the effective orifice by supra-annular implantation compared to the reduced orifice with an incorrect intra-annular implantation. were required in 173 patients (56%), most of which (n = 144) were coronary artery bypasses (2.4 grafts/ patient). All but four patients survived (30 day/hospital mortality = 1.3 ± 1%, 95% confidence limits). Follow-up has now entered its eighth year. Early mortality occurred in four patients and was all valve unrelated (retroperitoneal haemorrhage from intraaortic balloon insertion first day postoperative; aortic dissection at cardioplegic site (second day); ruptured spleen (patient fell out of bed, third day); and sudden death at home (arrhythmia 29th day). Late mortality occurred in 28 patients (5 months–5.7 years). Valve related aetiology of death occurred only in the two un-reoperated late endocarditis patients. All other causes could be explained very readily on natural causes in this elderly patient cohort (e.g. cancer (n = 7), CVA (n = 6), etc). There were perioperative cerebrovascular events in two patients, both of whom had previous strokes. Both recovered well but subsequently died in the second postoperative year from further strokes. Three early systemic thromboemboli occurred in unanticoagulated patients who had troublesome early atrial arrhythmia. In the first 80 patients in this series, no anticoagulants were given. Now this medication is recommended for 2 months and no further early thromboembolic episode has since occurred. In spite of the presence of a stentless valve, it is realised that this elderly patient cohort is more likely to develop such postoperative arrhythmia, unlike the younger homograft aortic valve patients who are less likely to develop arrhythmias and who receive no anticoagulant medication postoperatively. Over the seven
complete years of follow-up, seven elderly patients had cerebrovascular events leading to death in five patients. Additional morbid events include six paravalvar leaks, four of which were only echocardiographically detected with no clinical murmurs. In two patients, one patient with a suture that was too loose (10 days postoperative) and in another patient with a broken suture (15 weeks), both having 4/0 polypropylene continuous suturing, reoperation was required. A successful longterm outcome with valve repair has been verified in both patients by late echocardiography. For the last 240 patients, a stronger 3/0 polypropylene suture has been used without further major problem. Endocarditis has occurred in five patients, 1.5–5 years after operation. Two patients died without reoperation. Three received reoperation: two valves were replaced and in the third patient a competent non-infected valve was left in situ and the healed VSD caused by endocarditis voces successfully closed. Reoperation (six patients) was required for structural deterioration in one patient only at 15 months, who had a discrete perforation in leaflet tissue, the surrounds of which looked normal. In being so unlike the usual xenograft leaflet perforation, where surrounding leaflet tissue is thin and almost transparent, it was considered that this patient may have had an inadvertent suture needle injury. The event has nevertheless been ascribed to one of structural deterioration. This patient had moderate incompetence immediately after the initial operation and this progressed, therefore it was unlikely to be due solely to structural degeneration or ‘intrinsic’ leaflet failure. The other five reoperations have been for endo-
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carditis (three patients) and perivalvar leak (two patients). Clinical and echocardiographic assessment of valve incompetence has revealed excellent results. Initially in the series, intraoperative transoesophageal echocardiographic examination was carried out. Now transthoracic examination is performed at the pre-hospital or preoperation phase, postoperation at fifth–sixth day, at 6 months, 1 year and 1–2 yearly thereafter. In many patients, a trace of non-progressive incompetence is present. Transvalvar gradients, effective orifice area and degree of incompetence according to both the host annular size and the implanted valve size (21–29 mm) across time have shown only in one patient, a mean gradient of 7–9 mmHg with progression of incompetence43 requiring reoperation. One patient has a persisting high transvalvar gradient with a mean of 24 mmHg and a peak of 44 mmHg at 2 years after operation. It is unlikely that this patient has pannus in-growth producing leaflet obstruction and a decreased orifice area. The gradient is more likely due to residual LV hypertrophy particularly as it has been present since operation. No other patient had a haemodynamic pressure gradient abnormality. The details of serial echocardiography have been clearly documented,43 have not changed in the 1999 analysis and are not repeated in any detail in the present study. In that analysis overall, 96% of patients have either nil, or a trivial degree of incompetence on echocaradiography across time to greater than 4 years after operation. A valuable instructive comparison of haemodynamic and LV mass regression between the CLOB valve and the supra-annular Carpentier-Edwards stented porcine valve has been reported in detail.22,43 Briefly, at 6 months the mean gradients were lower (P ≤ 0.001), the effective orifice was greater (P ≤ 0.05) and the dimensionless performance index higher (P = 0.01) in the stentless CLOB group versus the Carpentier-Edwards stented group.22 There was important LV reduction and regression at 6 months postoperatively in both groups, but the reduction was greater in the stentless valves than the stented valves (P = 0.04). Other studies using alternative stentless valves have also confirmed similar major LV hypertrophic regression.30
Statistical Analysis Statistical analysis comprising Kaplan–Meier actuarial analyses of patient survival, freedom from thromboembolism, endocarditis, reoperation for structural deterioration and reoperation from all causes are outlined in Table 1. Only to the fourth–fifth year follow-up period are sufficient patient numbers available to provide meaningful statistics. Comparison of echocardio-
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graphic results was made using analysis of variance contingency tables.
Discussion The long-term durability of a stentless xenograft in general is still unknown in spite of the 10 years follow-up of a small series with the Toronto (SPV) valve.27 This review of the CLOB valve has outlined a follow-up in the eighth year. To the present time only one structural failure has occurred. The use of this xenograft is primarily in elderly patients in whom death is the competing risk, modifying the analysis of both durability and survival accordingly. Nevertheless, stentless valves appear to offer excellent immediate results auguring well for the long-term future. Many clinical questions will arise over the next several years. Which is the best stentless valve? Will it be necessary to have two or three different models at our disposal for use in various clinical situations? What will be the easiest (for the surgeon) and best (for the patient) implantation techniques? What is the fate of glutaraldehyde aortic wall when a root replacement is used? Will the dacron-supported valves have excessive fibrosis and calcification rendering the valve in time, essentially like a stented one? Will explantation at reoperation be difficult? Will non-glutaraldehyde preservation and better calcium mitigation agents produce yet a newer generation of durable valves applicable for all patient age groups?35 Lastly, is stentlessness a surgical gimmick or is it good theory gradually being translated to a successful clinical application? Table 1. events
Patient survival and actuarial freedom from morbid 4 Years 7 Years AVR>4 years ago AVR>7 years ago n = 119 n=5
Patient survival (n = 307, 1st op 31.12.1992) • 4 early hospital/ 86% ± 3% 30 day deaths • 27 late deaths (276 survivors) Freedom from • thromboembolism 93% ± 2% • endocarditis (5) 95% ± 3% • reoperation for (i) structural 99% ± 1% deterioration (1) (ii) all causes 96% ± 2% (perivalvar leak (2) endocarditis (3) structural deterioration (1))
68% ± 7%
93% ± 2% 95% ±3%* 99% ± 1% 96% ± 2%
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The Possible Advantages of Stentlessness Stentless xenografts have some of the attributes of the aortic homograft valve. Perhaps the most striking quality compared to the stented xenograft is the favourable haemodynamics, particularly in the small aortic root. No stent should imply no obstruction. The effective orifice within a given host aortic root is much greater compared to other prostheses and bioprostheses. This applies particularly with the CLOB valve where, for example, a 27 mm valve is inserted supra-annually into a 25 mm host annulus. Although the xenograft leaflets are a little stiff, they still produce low mean transvalvar gradients almost but not quite as good as those with a homograft valve or a Synergraft® xenograft. Evidence has accumulated that stentless valves enhance LV hypertrophic regression faster and more completely than do stented valves.22 Jin et al. compared the haemodynamic data of homografts, stentless (Toronto SPVTM) and stented valves.30 Both types of stentless valves caused less resistance to LV ejection and produced greater early improvement in LV function and consequently more complete resolution of LV hypertrophy. These important findings were verified by Del Rizzo et al.44 with the Toronto SPV valve and by Thomson et al.22 analysing this series of CLOB implants. The theoretical advantage and probably the primary reason for renewed interest and clinical use of the stentless xenograft is the high probability of improved durability due to the better distribution of physical forces during leaflet movements. The leaflets of a stented valve have to be perfectly assembled to minimise the unnatural forces of physical closure. Most stented valves are not perfectly assembled. Nevertheless, even if leaflet coaption does evenly distribute the physical stress without any excessive forces on the leaflet commissures, the dissipation of forces, as occurs through the flexible normal aortic wall, is absent in the stented structure.32–34 The evidence for stress mitigation with the stentless valve rests on the available data of the durability of stented and unstented homografts and on the differences of stented and stentless xenografts that were formaldehyde preserved in the late 1960s.21 In both instances, the stentless tissue was far more durable. There is also some experimental evidence that stentless porcine aortic valves are less likely to calcify.31 However, any improved durability of a stentless xenograft will not be evident statistically until another 5 years have elapsed.
The Limitations, The Teaching to Junior Surgeons and the Contraindications of Stentless Xenografts The implantation of a stentless structure is technically more demanding and exacting than the insertion of a
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framed bioprosthesis or mechanical valve. Implantation techniques are more difficult to learn and more difficult to teach. The operative procedures are less frequent and available only in a small number of interested surgical centres. Consequently, the opportunities for cardiac surgical trainees to learn are reduced. Repeated practice on animal hearts is mandatory in order to overcome these problems and to produce a high standard of clinical practice. In the 2000s, the learning curve can be reduced to a minimum with animal heart practice. Nowadays, at many conferences, tissue valve workshops on animal hearts are conducted by several companies to encompass the implantation techniques of pulmonary autograft, homograft and stentless xenograft valves. However, attendance at one of these workshops may not be sufficient in itself and additional laboratory bench practice is required. In using a stentless xenograft, unlike using a stented valve, the surgeon must take much more notice of the host anatomy and pathology. Both annular and sinotubular diameters, the symmetry of the annulus (bicuspid or tricuspid), the orientation of the outflow tract and aortic root, the presence and degree of calcification of the aortic sinus and the degree of destruction of the root with endocarditis become of major importance. The subsequent surgical technique requires to be planned around these variables and new surgical decisions may need to be made at the operating table. In the 1967–1969 stentless valve series, no perivalvar leak was seen at reoperation or autopsy. The same single continuous suture line was used except that the suture in this early series was a braided 3/0 Merselene and the valve at that time was formaldehyde preserved. The current experience is with a 3/0 polypropylene and it is possible that this suture has too much stretch and is not reliable to suture a glutaraldehyde preserved tissue to a living tissue. The few reoperations that have been necessary (three endocarditis, one structural failure, two perivalvar leaks) have indicated that the plane between the glutaraldehyde xenograft aortic wall and host is very easily separated. Nevertheless, perivalvar leak has not been a problem in the last 240 patients in this series of CLOB implants. There are three significant but rare contraindications to the subcoronary implantation of this composite valve. First, excessive aortic root calcification may preclude suturing in the supra-annular and peri-commissural aortic tissue. This probably applies as well to other models of stentless valves using xenograft subcoronary implantation. Such calcification is not common, but if present, an alternative stented bioprosthesis (e.g. pericardial valve) should be chosen. In this series, no stentless valve implantation has had to be abandoned in the middle of
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implantation because of aortic wall calcification. This decision has always been made on inspection of the aortic root, prior to selection of the particular valve. Second, the larger aortic annulus (≥30 mm) is a contraindication for this valve, the largest size of which is a 29 mm CLOB valve. Last, for the subcoronary implant of a stentless xenograft, gross asymmetry of the aortic root, although rare in the elderly, may produce a less desirable result than that obtainable with a stented pericardial valve. With refinement of surgical pathways, the next 5 years will provide the solutions to current problems. In the meantime, it is imperative that the more senior surgeons maintain open doors for our juniors to be exposed, to learn, to practise and to take over the analyses of the patients in order that all may have first hand information of stentless valve durability as it unfolds.
Lessons Learned From Homograft Aortic Valve Implantation Without doubt the 28 year experience at The Prince Charles Hospital with homograft techniques from subcoronary implantation to root replacement in 1022 patients45 has provided experience with the handling of valve tissue and familiarity of the diseased aortic root with its many variations of symmetry. But still the learning curve with newer staff surgical members exists even though it may now be somewhat flatter! A homograft root replacement for aortic valve disease alone would not be indicated in the elderly (over 70 years). This is because of the limited homograft valve supply and because results with other valve types are good and shorter operation times are more appropriate in this older age group, many of whom require associated coronary artery bypass grafting. Much is known about the fate of the homograft but the same cannot be said about the stentless porcine aortic xenograft. Some caution is required with the general use of stentless xenografts across the recipient age spectrum. Because stented xenografts have given a poor record in young and middle aged patients up to 50–60 years old,46 it would seem wise not to use the stentless valve in this younger age group unless homografts are not available or anticoagulants are to be avoided. In such circumstances, the stentless valve could then be used instead of the stented bioprosthesis in the hope that improved durability will be the advantage. This latter scenario of use in younger patients is more likely to occur in the countries where rheumatic valve disease predominates, and in countries where anticoagulants are best avoided. The optimal age range of the recipient receiving a stentless valve has not yet been determined. Already there have been many stentless valves implanted into younger patients. However, collation of results involves signifi-
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cant co-operation from surgeons, hospitals and valve companies to provide relevant accurate data. To date, this has not been forthcoming. Although stented xenografts give excellent results in the elderly,47–49 this same group of patients are ideal recipients of the stentless valve. They provide at least immediate clinically comparable results. At our hospitals, the results with the CryoLife-O’Brien valve have been excellent with only four 30 day/hospital postoperative deaths (1.3%) in 307 elderly patients since its inception in 1992. As the durability of stentless valves becomes more apparent and providing the results become superior to the stented variety, then the valve can in the future ethically be used in younger adults. This, however, is not the present recommendation. The advantages of rapid implantation in this patient group, 56% requiring a combined procedure, is evident in this series. In this patient group, unlike that of the younger homograft valve recipients, the valve pathology is more likely to be a trileaflet, acquired degenerative calcific aortic valve stenosis. Such symmetry is most favourable for this composite valve with its minimal xenograft tissue and its single continuous suture technique in the supra-annular position. At present, it may be close to the ideal valve for the elderly.
Acknowledgements Acknowledgment is given to the several echocardiologists, in particular Dr Daryl Burstow, Malcolm Davison and Helen Thompson, who have assisted in our study of the stentless valve; to Susan Smith for her help in the statistical analyses; Jacci Green for her data collection in the earlier years of this study and to Helen Gay for her secretarial services and to the many faithful patients, particularly early in our experience, who were much aware that the CLOB valve was a trial valve under close surveillance.
References 1. Binet JP, Duran CG, Carpentier A, Langlois J. Heterologous aortic valve transplantation. Lancet 1965; 2: 1275. 2. O’Brien MF, Clareborough JK. Heterograft aortic valve transplantation for human valve disease. Med. J. Aust. 1966; 2: 228–30. 3. O’Brien MF. Heterograft aortic valves for human use: Valve bank, techniques of measurement and implantation. J. Thorac. Cardiovasc. Surg. 1967; 53: 392–7. 4. Carpentier A, Lemaigre G, Robert L, Carpentier S, Dubost C. Biological factors affecting long-term
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19. Ferrans VJ, Boyce SW, Billingham ME, Jones M, Ishihara T, Roberts WC. Calcific deposits in porcine bioprostheses: Structure and pathogenesis. Am. J. Cardiol. 1980; 46: 721–34. 20. Jamieson WR. Stented porcine bioprostheses: Durability and outcomes, 1975–1993. In: Piwnica A, Westaby S (eds). Stentless Bioprostheses. Isis Medical Media, Oxford, 1995; 24–35. 21. Angell WW, Pupello DF, Bessone LN, Hiro SP, Brock JC. Effect of stent mounting on tissue valves for aortic valve replacement. J. Cardiac Surg. 1991; 6 (Suppl. 4): 595–9. 22. Thomson HL, O’Brien MF, Almeida AA, Tesar, PJ, Davison MB, Burstow DJ. Haemodynamics and left ventricular mass regression: A comparison of the stentless, stented and mechanical aortic valve replacement. Eur. J. Cardiothorac. Surg. 1998; 13: 572–5. 23. David TE, Puschmann R, Ivanov J et al. Aortic valve replacement with stentless and stented porcine valves. A case-match study. J. Thorac. Cardiovasc. Surg. 1998; 116: 236–41. 24. O’Brien MF. The CryoLife-O’Brien composite aortic stentless xenograft: Surgical technique of implantation. Ann. Thorac. Surg. 1995; 60: S410–413. 25. Implantation brochure, 1999. Available from CryoLife International Inc, 1655 Roberts Boulevard, NW Kennesaw GA 30144, USA or Advanced Biomedical Pty Ltd, 5 Vista Court, Ringwood East, Victoria 3135, Australia. 26. O’Brien MF. Implantation technique of the CryoLifeO’Brien® stentless xenograft aortic valve: The simple, rapid, and correct way to implant and the errors to avoid. Seminars Thoracic Cardiovasc. Surg. 1999; 11 (Suppl. 1): 121–125. 27. David TE, Feindel CM, Scully HE, Bos J, Rakowski H. Aortic valve replacement with stentless porcine aortic valves: A ten year experience. J. Heart Valve Disease 1998; 7: 250–4. 28. Westaby S. Why stentless valves? In: Piwnica A, Westaby S (eds). Stentless Bioprostheses. Isis Medical Media, London, 1995; 3–16. 29. Piwnica A, Westerby S. Stentless Bioprostheses. Iris Medical Media, Oxford, 1995. 30. Jin XY, Zhang Z-M, Gibson DG, Yacoub MH, Pepper JR. Effect of valve substitute on changes in left ventricular function and hypertrophy after aortic valve replacement. Ann. Thorac. Surg. 1996; 62: 683–90. 31. Hazekamp MG, Goffin YA, Huysmans HA. The value of the stentless biovalve prosthesis. An experimental study. Eur. J. Cardiothorac. Surg. 1993; 7: 514–19.
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32. Thubrikar M, Deck JD, Aouad J, Nolan SP. Role of mechanical stress in calcification of aortic bioprosthetic valves. J. Thorac. Cardiovasc. Surg. 1983; 86: 115–25. 33. Sabah HN, Hamid MS, Steni PD. Mechanical stress on closed cusp porcine bioprosthetic valves: Correlation with sites of calcification. Ann. Thorac. Surg. 1986; 42: 93–6. 34. Christie GW, Barratt-Boyes B. On stress reduction in bioprosthetic heart valve leaflets by the use of a flexible stent. J. Cardiac Surg. 1991; 6: 476–81. 35. O’Brien MF, Goldstein S, Walsh S, Black KS, Elkins R, Clarke D. The Synergraft® valve: A new acellular (non-glutaraldehyde fixed) tissue heart valve for autologous recellularization. Seminars Thoracic Cardiovasc. Surg. 1999; 11 (Suppl. 1) 194–200. 36. Hvass U, Palatianos G, Frassani R, Puricelli C, O’Brien M. Multicenter study of stentless valve replacement in the small aortic root. J. Thorac. Cardiovasc. Surg. 1999; 117: 267–72. 37. Third International Bioprosthesis Symposium, May 1999, Grand Cayman: Peer review manuscripts published in Seminars of Thoracic and Cardiovascular Surgery. October 1999. 38. Luciani GP, Bertolini P, Mazzacco A. Early failure of freehand aortic stentless xenograft valves. J. Thoracic Cardiovasc. Surg. 1997; 113: 1109–10. 39. O’Brien MF. Early failure of freehand aortic stentless xenograft valves. J. Thoracic Cardiovasc. Surg. 1998; 115: 961–63. 40. Petracek MR, Shuman TA, Pirolo JS, Tedder M, Ball SK, Graves D. Use of Toronto stentless porcine valve in patients with aortic dilatation. Seminars Thoracic Cardiovasc. Surg. 1999; 11 (Suppl. 1): 74–8.
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