Chapter 34. Stentless Aortic Valve Replacement: Autograft/Homograft

Unique among the many options now available for aortic valve surgery are the very old, but still useful "human" valve options, including the aortic homograft and the pulmonary autograft (Ross procedure) alternatives. Having reviewed the subject more than 20 years ago,1 it is interesting to note how some things have changed but much has remained the same. Table 34-1 summarizes advantages and disadvantages of current replacement options.

The first choice for aortic valve replacement was the homograft aortic valve. Gordon Murray created an animal model to implant an aortic homograft valve in the descending aorta2 and was the first to apply the concept in the human demonstrating function for up to 4 years.3

Duran and Gunning at Oxford described a method for orthotopic (subcoronary) implantation of an aortic homograft valve in 1962,4 and in 1962 both Donald Ross in London5 and Sir Brian Barratt-Boyes in Auckland6 did this successfully in humans.

Initially, homograft aortic valves were implanted shortly after collection.7 This impractical method was rapidly supplanted by techniques to sterilize and preserve the valve for later use. Early methods employed beta-propiolactone6,8 or 0.02% chlorhexidine,9 followed by ethylene oxide9 or radiation exposure.10 Some were preserved by freeze-drying.6,11 Recognizing that the incidence of valve rupture was high in chemically treated valves, Barratt-Boyes introduced antibiotic sterilization of homografts in 1968.12 Cryopreservation of homografts was introduced in 1975 by O'Brien and continues to be the predominant method.13,15 Experimental use of autologous valve transplantation began in 1961 when Lower and colleagues at Stanford transposed the autologous pulmonic valve to the mitral position in dogs14 and shortly thereafter to the aortic position.15 Donald Ross applied this to humans, reporting in 1967 clinical experience replacing either the aortic or mitral valve with a pulmonary autograft.16 Nearly 20 years later the autograft was finally done in America by Elkins and Stelzer.17 The operation came to be known as the Ross procedure. After an initial surge of interest in the 1990s (more than 240 surgeons worldwide reported their experience to the Ross Procedure International Registry18), its use diminished in the next decade.

Procurement and Preservation

Homograft valves can be obtained from donors whose beating hearts are not suitable for transplantation but the larger source is tissue from nonbeating heart donors. This has been poorly understood and underappreciated by both medical professionals and the lay public.19 Regional transplant organizations now participate in procurement of both solid organs and tissues. Specialized homograft processing centers receive hearts in sterile, refrigerated containers. Donor history is reviewed and serology tested for transmissible disease. The great vessels with their valves are separated from the heart under sterile conditions, carefully inspected for defects, measured, cultured, and immersed in antibiotic solution before being sealed in multiple-layer packaging containing dimethylsulfoxide, which prevents cellular rupture during the carefully controlled freezing process.20 The homografts are then placed in vapor phase liquid nitrogen storage (about−195°C) until used.

Cellular and Immunologic Aspects of Homografts

The normal living valve contains multiple viable cell types, including endothelial cells, fibroblasts, and smooth muscle cells incorporated in a complex extracellular matrix. The cells and matrix elements are in a constant state of remodeling under the influence of regulatory systems that optimize the structure and function of the valve mechanism. It is understandable, therefore, that efforts to preserve homograft structure and function were translated into efforts to maintain homograft cellular viability. Radiation and chemical treatment led to very early failure and were quickly abandoned.6,8,10,12,21 Antibiotic sterilization of homografts and storage at 4°C does not maintain cellular viability beyond a few days.22,23 Cryopreservation became the gold standard when donor fibroblast viability was shown after implantation.13 Although antigenicity of the fibroblast is low and other cell types do not survive the freezing process, panel reactive antibody (PRA) and donor-specific HLA I and II antibody testing is positive in 60 to 80% of homograft recipients.24–26 The potential advantages of viability may be defeated by the detrimental effects of this on immune system reponse.26 Animal studies have confirmed an immune mechanism by demonstrating that deterioration in homograft valve function is prevented by immunosuppression27 and does not occur in T-cell–deficient rats.28 Clinical use of immunosuppression, however, could not be justified for homograft patients.

Tissue engineering concepts led to decellularization, which lyses cells and "rinses" out antigenic proteins, leaving an inert matrix and intact structural framework. Preserved mechanical properties and structural integrity were demonstrated in a sheep model of such a scaffold. In addition, the empty matrix seemed to attract circulating recipient stem cells, which repopulated the framework and differentiated into appropriate cell lines capable of maintaining the matrix.29 Initial use of the decellularized aortic homograft in humans demonstrated that structural integrity could be maintained with low, stable gradients and minimal regurgitation similar to standard cryopreserved homografts.30 The same concept has been applied to the pulmonary homograft used in the Ross operation.31,32 A decellularized xenograft valved conduit has also been used successfully for the right ventricular outflow (RVOT) reconstruction with the Ross.33 Long-term studies are needed to determine if native cell ingrowth occurs reliably.

In summary, despite intensive investigation over decades, the relative contribution of the immune response, preservation techniques, and warm ischemia time to ultimate valve degeneration is not clear. More importantly, after consideration of the structural benefits and the immune-reaction risks, the net advantage of maintaining cellular (particularly fibroblast) viability in the homograft is not well defined.34

Indications for Aortic Homografts

Aortic valve replacement (AVR) with an aortic homograft has a number of advantages, including excellent hemodynamic profile with low transvalvular gradients and possibly enhanced regression of left ventricular mass,35 low risk of thromboembolism without the need for systemic anticoagulation, and low risk of prosthetic valve infection. However, homografts are subject to structural deterioration which is inversely related to recipient age. Older donor age may also increase rates of degeneration. Furthermore, the availability of homografts is still limited, especially the larger sizes.

The strongest indication for a homograft is for treatment of active aortic valve endocarditis, particularly in patients with root abscess, fistula formation, or prosthetic valve infection.36 The pliable handling characteristics, ease of coronary reimplantation, the potential for using the attached donor mitral anterior leaflet, and the ability to reconstruct the debrided root with all biological material to minimize risk of persistent infection, all make the homograft exceptionally well suited to this challenging task. The homograft's very low early hazard rate for endocarditis sets it apart from other valve alternatives.37

Aortic homograft is also a reasonable option in the older patient (>60) with a small aortic root. The hemodynamic advantages of the homograft translate into better relief of outflow obstruction and improved exercise tolerance. Given its resistance to thromboembolic complications the aortic homograft can also be considered for younger patients requiring composite aortic valve or root replacement who cannot be anticoagulated. However, recent data from a prospective randomized trial would argue that most of the advantages of the homograft can be duplicated by the stentless porcine root replacement which has a significantly lower rate of calcification and valve dysfunction in this study.38

Preoperative Evaluation

Preoperative transthoracic echocardiography (TTE) is an invaluable diagnostic tool for evaluation of the AV and associated anatomic structures. Echo measurement of the left ventricular outflow tract (LVOT) can accurately predict aortic annulus diameter and thus the size of the homograft required.39–41

Computed tomographic angiography (CTA) or cardiac magnetic resonance (CMR) imaging can also be very useful in the evaluation of potential homograft patients, particularly those with aortic root abscess (Fig. 34-1). Coronary angiography should be employed with the standard indications but may be hazardous in patients with mobile vegetations on the aortic leaflets. Standard chest computed tomography with and without contrast should be considered in any reoperative setting to assess proximity of vital structures to the sternum and extent of ascending aortic or arch calcification or aneurysm. Heavy calcification around the coronary ostia may preclude safe reimplantation of coronary "buttons" or even a distal subcoronary suture line.

Transesophageal echocardiography (TEE) is often necessary to establish the presence of a root abscess, but its major role is for intraoperative confirmation of the anatomy and assessment of both valve and ventricular function.

Operative Technique

General Preparation

Routine cardiac surgical monitoring including TEE is considered the standard of care. An antifibrinolytic agent such as epsilon-aminocaproic acid is helpful. A standard midline sternotomy incision provides full exposure of the heart, ease in cannulation, and access for optimal myocardial protection. Routine distal aortic cannulation and a dual-stage venous cannula usually can be employed.

Unless circulatory arrest is needed, minimal systemic cooling (32°C) is adequate if the heart is maintained at 10 to 15°C using a standard insulating pad and directly monitoring the myocardial septal temperature. A combination of antegrade and retrograde cold blood cardioplegia can be used with the bulk of the protection coming from the retrograde. The open aortic root reveals coronary return from both ostia to confirm effective retrograde.

A transverse aortotomy high above (1.5 to 2 cm) the commissures is usually best. The diseased aortic valve is excised and the annulus is measured with cylindrical sizers. The sinotubular junction should also be evaluated for the subcoronary technique. The homograft is trimmed appropriately. In general, 2 to 3 mm of tissue, proximal to the nadir of each cusp, is advised for security in suture placement, leaving even more for full root replacements.

Techniques of Homograft Placement

Subcoronary Implant Technique

The subcoronary method involves two suture lines within the native root. The homograft is usually oriented anatomically to properly align the commissures and the coronaries. The proximal end of the homograft is sewn to the native annulus in a circular plane at the level of the nadir of each sinus curving upward slightly in the membranous septum to avoid injury to the conduction system. This anastomosis can be done with either interrupted or continuous sutures (Fig. 34-2).

The top of each commissure is tacked to the aortic wall. The right and left sinus walls are then scalloped out to a point 3 to 5 mm from the leaflets. The noncoronary sinus can also be removed but is usually left intact. A 4-0 or 5-0 polypropylene suture is started at the lowest point under each coronary ostium and a continuous suture line constructed from there up to the top of the commissure on either side. On the top of the noncoronary sinus, excess homograft tissue is trimmed down and tacked to the top of the aortotomy. The aortotomy is then closed with continuous 4-0 polypropylene suture incorporating the top of the homograft noncoronary sinus with the native aortic wall (Fig. 34-3). The ascending aorta is vented as the aortic clamp is removed. TEE can quickly assess any regurgitation at this point. Distention of the ventricle should be avoided by prompt defibrillation (if necessary) and pacing if required.

Because even slight malalignment of the commissures can result in regurgitation, the subcoronary implant technique is considered more demanding than the other homograft techniques and may have poorer long-term results than the other methods.42–46 It is a good technique for patients with small, symmetric aortic roots and sinotubular junctions, whereas it is a poor choice for those with dilated, asymmetric, or severely diseased roots.

Homograft Cylinder–Inclusion Root Technique

The cylinder modification of the subcoronary technique was developed in an attempt to preserve the native geometry of the homograft inside the recipient aortic root. The proximal suture line is identical to the subcoronary method but the sinuses are not scalloped out. Instead, a buttonhole is made in the right and left sinuses in such a way as to allow the homograft wall to be sewn to the native sinus wall around the coronary ostia. After the coronaries are secure, the distal end of the homograft is attached at the commissures and then incorporated circumferentially into the aortotomy closure. This method is the most difficult technically and is seldom used.

Homograft Root Replacement

The root replacement technique can be used in any root and is particularly useful in small roots or those destroyed by endocarditis. The root replacement allows size flexibility, which allows thawing an appropriate homograft without wasting clamp time. Very large roots may require commissural plication as described by Northrup.47

The aorta is opened transversely well above the commissures of the valve. The diseased valve is excised and annulus debrided. The aorta is transected and the coronary ostial buttons are mobilized in standard fashion. Antegrade cardioplegia should be avoided after this point to avoid injury to the mobilized ostia.

The homograft root is usually oriented anatomically, which makes matching the two roots easiest. The proximal suture line can be constructed with either continuous or interrupted technique. Interrupted is best in difficult reoperations, especially for prosthetic valve endocarditis because it allows for very accurate, deep placement of individual stitches. A strip of autologous (or bovine) pericardium is used to reinforce this crucial anastomosis. Polypropylene sutures of 3-0 or 4-0 are used and organization scrupulously maintained on suture guides. The homograft parachutes down as the sutures are carefully tightened (Fig. 34-4).

Routine cases can be expedited with a continuous suture technique with 4-0 polypropylene begun at the right-left commissure. The fibrous trigones and commissures of the native and homograft roots serve as anatomical landmarks and should match up as one proceeds around. The initially loose suture line is tightened carefully with nerve hooks and tied securely.

The coronary buttons are attached with continuous 5-0 or 6-0 polypropylene after excising the homograft coronary stumps. The distal end of the homograft and the native aorta are trimmed and sewn together with continuous 4-0 polypropylene incorporating another strip of pericardium for support. The native aorta is vented anteriorly and systemic flow rate lowered as the cross-clamp is removed.

Care is taken to avoid systemic hypertension or vigorous traction on the reconstructed root to avoid bleeding. Topical hemostatic agents and biological glues can be used, but they should not be routinely necessary. Blood and blood products are not routinely required unless the patient is coagulopathic.

Postreplacement Assessment

Ventricular function, regional wall motion abnormalities, and valve function may all be accurately determined with TEE. With appropriate loading conditions, moderate to severe AR warrants inspection and revision of the homograft. Mild AR is usually tolerated well and does not warrant reexploration.

Postoperative Management

Even mild hypertension should be avoided to prevent disruption of crucial aortic suture lines. Coagulopathic bleeding is best addressed with products targeted to specific abnormalities defined by laboratory studies.

Adequate volume replacement is required to keep the stiff ventricle of aortic stenosis filled and alpha adrenergic support is often required for the patient who is vasodilated. Atrial rhythm disturbances should be treated aggressively. Elderly patients, particularly females, with aortic stenosis and diastolic dysfunction are at increased risk of morbidity and even mortality from postoperative atrial fibrillation. The increased volume loading needed to overcome the loss of atrial transport often leads to pulmonary congestion requiring reintubation and prolonged support. Forward cardiac output is impaired and renal function deteriorates. Cardioversion should be considered early in these patients and loading with intravenous amiodarone is usually indicated. Preoperatively loading with amiodarone may minimize the incidence and consequences of this arrhythmia.48

Temporary pacing, preferably atrial as well as ventricular, should be enabled. Permanent pacing is indicated if epicardial wires become unreliable, heart block was present preoperatively, or the underlying rhythm fails to return within a week after surgery.

Stroke risk can be minimized by careful intraoperative epiaortic ultrasound to guide or avoid cannulation and clamping. TEE-guided evacuation of air is essential and flooding the field with carbon dioxide may be helpful.

Myocardial dysfunction is best prevented by careful temperature-monitored myocardial protection but long operations may still require temporary inotropic support. Caution must be used in the hyperdynamic ventricle with diastolic dysfunction. The combination of a hyperdynamic left ventricle and a dysfunctional right heart is very challenging. These patients may benefit from atrial pacing (if pacing is required), phosphodiesterase inhibitors, adequate volume replacement, and alpha agonists.

Renal insufficiency is a risk minimized by maintenance of adequate flows and pressure during bypass and generous volume administration in the early postoperative period. A thirsty patient with dry mucous membranes is a good clue that intravascular volume is still depleted. Later, diuretics are needed to encourage mobilization and excretion of this extra fluid. Hypotension should be avoided but vasopressors can have direct negative effects on renal blood flow.

Low-dose aspirin is often recommended for homograft patients, but is not necessary and formal anticoagulation with warfarin is not required at all unless dictated by other conditions. A routine predischarge echo should be done to confirm valve function, ventricular function, and freedom from pericardial effusion.

Results

Perioperative Complications

In patients without active endocarditis at the time of surgery, operative mortality in the current era is 1 to 5%.44,49,50 The risk in experienced hands is comparable to using a stented bioprosthetic or mechanical valve. Ischemic time for a root replacement with either stentless porcine or aortic homograft is approximately 90 minutes.51 A contemporary series of 100 consecutive aortic homografts (virtually all root replacements including 13 reoperations) demonstrated no hospital mortality with 100% survival at 1 year and 98% at 5 years.52

In contrast, patients with active endocarditis have a higher early mortality ranging from 8 to 16%.44,53–56 Prosthetic valve endocarditis (17.9 to 18.8%) is worse than native (2.6 to 10%).53,57

Hemorrhage, heart block, stroke, myocardial infarction, and wound complications occur with similar frequency to those of other AVRs, but early risk of endocarditis is lower with homografts than any other replacement valve.37

Hemodynamics and Exercise Capacity

Hemodynamic characteristics of homografts are excellent at short- and medium-term follow-up, both at rest and during exercise.58,59 A study of 31 patients demonstrated increases in peak and mean gradients of 6.6 and 3.0 mm Hg, respectively, without a significant change in effective orifice area (EOA).58 Importantly, the EOA of even the 17- to 19-mm homografts was 1.7 cm2 and larger valves approximated the normal aortic valve areas as high as 2.7 cm2 for 24- to 27-mm homografts.

The typical subcoronary homograft implant demonstrates a 1- to 2-mm Hg drop in mean transvalvular gradient over the first 6 months but with full root replacement, the hemodynamic benefit is fully realized immediately. In the randomized trial of homograft versus stentless porcine root replacement the mean gradients were only 6 ± 1 mm Hg in the stentless and 5 ± 2 mm Hg in the homografts. Only one patient in each group had mild regurgitation after 5 years.51 These authors concluded that stentless and homograft root replacements are hemodynamically equivalent in the mid-term.

Long-Term Outcomes

Long-term outcome has been shown to be technique dependent in a meta-analysis of more than 3000 patients (37% full root, 63% subcoronary) from 18 studies with a mean follow-up of 12.5 years. Reoperation was significantly lower in the root replacement group.60 There may have been some bias against reoperation in failing roots, in which failing subcoronary implants were more readily subjected to reoperation.

The pioneering work of Mark O'Brien in Brisbane, Australia, produced a huge series of homograft patients over nearly three decades with 99.3% follow-up.50 This series demonstrated that rates of reoperation were lower in the full root patients (n = 3, 0.85%) than the subcoronary (n = 18, 3.3%). Of note, operative mortality was only 1.13% in 352 root patients.

Long-term durability was compromised by young age of recipient to the point that those less than 20 years of age had a 47% rate of reoperation for structural valve degeneration at 10 years. Conversely, those more than 60 had a 94% freedom from reoperation at 15 years, and those between 21 and 60 had 81 to 85% freedom at 15 years. This series confirmed the very low incidence of thromboembolic phenomena (without anticoagulation) and a low but not insignificant rate of endocarditis.

Lund reported crude survival at 10 and 20 years to be 67 and 35%, respectively,44 whereas Langley and O'Brien reported actuarial survival at 10, 20, and 25 years to be 81,49 58,49 and 19%, respectively.50

Structural valve failure of homografts increases with time, and approximates 19 to 38% at 10 years and 69 to 82% at 20 years.44,49 Freedom from repeat AVR, for any reason, parallels structural valve failure and is 86.5 and 38.8% at 10 and 20 years, respectively.49 As heterograft tissue technology has progressed, the difference between homograft and heterograft durability has narrowed to the point of near equivalency, with both showing a dramatic age-dependent relationship with youngest patients failing most rapidly.61

Freedom from endocarditis at 10 years is 93 to 98%,49,50 and at 20 years 89 to 95%.44,49,50 Freedom from thromboembolism at 15 and 20 years is 92 and 83%, respectively.50 Thrombosis of a homograft has been reported, but in the setting of lupus anticardiolipin antibody syndrome.62

In patients with active endocarditis requiring AVR, results may be poorer, with survival ranging from 58% at 5 years53 to 91% at 10 years,56 and is significantly lower in patients with prosthetic valve endocarditis (PVE).54 Of note, however, the risk of recurrent endocarditis is less than 4% up to 4 years postoperatively.43,53,54,56 These results still compare favorably with alternatives; therefore, aortic homograft is considered by many to be the valve of choice for aortic valve or root replacement in patients with active endocarditis.

Homograft Reoperation

Because of extensive calcification after many years the risk at reoperation after homograft replacement can be as high as 20%.63 The subcoronary implants may be easier in this regard because the native aortic root is preserved. The full root replacement is more of a problem. Up to about 10 years, calcification is limited and it is theoretically possible to place a new valve inside the homograft annulus after removing the leaflets.64 Ultimately, however, the conduit becomes so rigid as to preclude such an alternative and complete re-replacement of the root is required (Fig. 34-5). The most hazardous part of this operation is related to the coronary ostial buttons, which must be protected and available for use again.

Reoperation can be made easier by anticipating the need for this at the original operation. Keeping the coronary buttons large at the initial operation is one way to avoid problems with dissecting them again. The homograft root should be kept as short as possible to minimize the extent of ultimately calcified wall and maximize the amount of normal aorta available for subsequent cannulation and clamping. Closing the pericardium or using a pericardial substitute can make sternal re-entry safer. Careful assessment of the aorta and mediastinum on CT preoperatively can alert one to the need for early peripheral cannulation and even sternotomy under circulatory arrest.

Clamping the aorta distal to the main pulmonary artery is very useful in these cases and avoids the hazards of entering a great vessel while dissecting between them before the clamp is on. Complete excision of the calcified wall is often the best policy, but leaving a little margin around each coronary ostium may make reconstruction easier. Another homograft is often an excellent solution because it is easier to reimplant the coronary ostia, but even a Ross operation can be done in this setting, as was done for the 40-year-old man shown in Fig. 34-5.

An increasingly attractive option in the future for older patients is transcatheter valve replacement, which should be well-suited to the calcified homograft root as reported from Milan65 (Fig. 34-6).

Conclusions

Between the lack of availability of homografts and the improvements in readily available alternatives such as stentless porcine devices, homograft replacement of the aortic valve is less common than it was 20 years ago. However, it remains a versatile, highly effective tool with potential advantages in small aortic roots greater than age 60 and in settings of severe aortic root endocarditis. The homograft can be placed with a low operative mortality risk and provide excellent hemodynamic function immediately without the need for any anticoagulation. Its major downside is the inexorable deterioration of its structure over time, which makes it a poor choice in very young patients. Those patients may well be best served by the autograft operation.

Theoretical Considerations

The pulmonary autograft shares the hemodynamic advantages and anti-thrombotic features of the homograft but is the only valve which has the benefit of being a fully viable autologous tissue. Pulmonary leaflets have been found to have equivalent breaking strain compared to aortic leaflets and even higher tensile strength.66 The living pulmonary valve demonstrates the adaptability of human biology to change in response to changing physiologic conditions. The histologic features of this adaptation have been elegantly described and illustrated.67 The initial response is to lay down a collagen-rich support on the ventricular aspect of the leaflets. This thins out later but remains slightly thicker than normal aortic leaflets. All three layers of the leaflets, fibrosa, spongiosa, and ventricularis contain viable cells which maintain a rich extracellular matrix to support the leaflet function. Endothelial cells are transformed to become capable of smooth muscle actin production becoming more like the aortic than the pulmonary phenotype. The autograft (pulmonary artery) walls are a different story. There is rapid loss of elastin with fragmentation and loss of cellularity and increasing collagen deposition. This may reflect the need to sacrifice elasticity for strength to withstand systemic pressure.

Patient Selection

The cardinal principle in selecting patients for the Ross procedure is that they must have a life expectancy of at least 20 to 25 years. Other simpler alternatives can be expected to give 10 to 15 years, even in young patients, although durability of tissue valves in patients less than 35 years of age can be very limited. Active lifestyle, potential for childbearing, and contraindications to anticoagulation favor the Ross procedure. Many young people seek out this option specifically to avoid the issues of anticoagulation and even to allow extreme athletic activity, such as mountain biking and triathlons. Practically speaking, the ideal patient is under 50 years of age but special circumstances can extend this to 65 or even slightly higher.

The generally accepted contraindications are significant pulmonary valve disease, congenitally abnormal pulmonary valves (eg, bicuspid or quadricuspid), Marfan's syndrome, other connective tissue disorders, complex coronary anomalies, and probably severe coexisting autoimmune disease, particularly if it is the cause of the aortic valve disease. Active rheumatic disease is a relative contraindication because the autograft can be attacked early by the acute rheumatic process and lead to early failure.68 Bacterial endocarditis is not a contraindication for the Ross procedure, although it is best used when only leaflet destruction is present or root involvement can be reconstructed without distortion.69

Comorbid conditions should also be considered before offering this operation to any given patient. These conditions often limit life expectancy and also influence the ability of the patient to withstand this longer procedure. Poor left ventricular function, multivessel coronary disease, and need for complex mitral repair are examples. Ascending aortic dilatation or aneurysm have been considered contraindications by some, but these can be and should be easily addressed. Previous AVR or other open cardiac operations are not a contraindication to the Ross procedure, but all the standard considerations of reoperative surgery apply including appropriate imaging to allow safe sternal re-entry.

Bicuspid aortic valves (BAV) are the most common etiology of severe aortic stenosis or regurgitation in patients less than 65 years of age. Some have felt this group should not undergo the Ross procedure because of potential complications of intrinsic aortopathy, which is common in BAV patients.70 Because this is the largest group of patients potentially to benefit from the operation, it has been the quest of Ross surgeons to find ways to make the operation safe and durable in this situation. Controversy still exists as to whether primary aortic regurgitation (AR) is less favorable than primary aortic stenosis.71,72 The patient with aortic stenosis (AS) is more likely to have a smaller annulus, which is resistant to dilatation, as opposed to the AR patient, whose annulus is often dilated and continues to dilate if not supported. There is also more of a tendency to distal aortic dilatation in the setting of AR as opposed to AS. These issues are addressable by technical modifications, which is discussed later in detail.

Preoperative Evaluation

Because most candidates for the Ross procedure are less than 50 years of age, it is not usually necessary to subject them to cardiac catheterization. CTA is an excellent tool to evaluate the entire ascending aorta and arch as well as the proximal coronary arteries. Cardiac magnetic resonance (CMR) can be used as well but does not give as much resolution as CTA for the coronaries. Both give excellent imaging of the entire aorta (Fig. 34-7). Transthoracic echocardiography gives excellent assessment of the aortic valve, ventricular function, and aortic root. Approximately 1% of patients are found to have a bicuspid pulmonary valve at surgery. Unfortunately, echo, CTA, and CMR have all been limited in their ability to define the morphology of the pulmonary valve. With proper gating, timing of contrast, and attention to the pulmonary trunk, however, this can be determined fairly reliably (Fig. 34-8).

Technique

The original description by Donald Ross involved a fully scalloped subcoronary implant of the pulmonary autograft using essentially the same technique he had used for a subcoronary homograft implant. Modifications were adopted to decrease the immediate incidence of regurgitation by maintaining the cylindrical geometry of the autograft either within the aortic root or as a complete replacement thereof. The root replacement has become the most commonly employed technique.

Full median sternotomy is usually the best incision. Aortic cannulation should be kept high and bicaval cannulation is preferable because the open RVOT is a constant source of air. Initial antegrade and then generous retrograde cold blood cardioplegia is employed insulating the heart from surrounding structures and monitoring the effectiveness of myocardial cooling with a septal temperature probe. Traditional venting via the right superior pulmonary vein is not necessary because the open pulmonary artery serves that purpose.

Extensive dissection between the great vessels allows retraction of the aorta with an umbilical tape and keeps the cross-clamp off the right pulmonary artery. After clamping the aorta, the space between the aortic and pulmonary roots is dissected until the roots are completely separated. Final separation is often safest after the aorta is opened and coronary locations can be readily identified.

A rather high transverse aortotomy incision keeps all technique options open, but if a subcoronary implant is planned, extending an oblique incision into the noncoronary sinus can be employed. The aortic valve pathology is inspected as well as coronary ostial positions. A stenotic valve can be excised at this point and the annulus debrided and measured.

Common to any of the techniques is the need to harvest the pulmonary autograft from the right ventricular outflow tract (RVOT). The close proximity of the left coronary system and general constraints of this maneuver are obvious from the elegant anatomical casts published by Muresian.73 The main pulmonary artery is incised transversely just distal to the valve and the opening extended to either side taking care to avoid the left coronary. A flexible sucker can be placed in the distal PA as a vent. The pulmonic valve is inspected to make sure it is a healthy, three-leaflet valve with minimal fenestrations. The remainder of the PA is divided. The adipose tissue between the back of the PA and the left main is gently dissected down to the muscle in the back of the RVOT with the cautery.

The RVOT is opened with a no. 15 blade well below the anterior commissure as determined by palpation or by passing a suture or clamp through the muscle about 5- to 6-mm below the valve from inside out (Fig. 34-9). The initial incision is cautiously extended until the leaflet can be clearly seen. The dissection then continues around each side leaving 3 to 4 mm of muscle cuff. Posteriorly, a natural plane can be appreciated between the right and left ventricular septal components. The septal perforators are always in the left side and can be avoided by taking only the right ventricular part of the septum. Most often they are not seen. Small branches of the coronary sinus posteriorly can be the source of annoying venous bleeding at the end, so gentle administration of retrograde can identify these and allow control at this point.

The autograft is trimmed by following the curvilinear course of the leaflets on the inflow end leaving a smooth 3- to 4-mm cuff of muscle. The inflow end is measured by gently inserting cylindrical sizers. The RVOT opening can also be measured at this time. An appropriate pulmonary homograft can then be thawed.

Subcoronary Technique

If the subcoronary or inclusion cylinder technique is chosen, the operation proceeds similarly to subcoronary homograft replacement. Proximal and distal suture lines are constructed as described. Of note, the aortic root must match the autograft at both the annulus and the sinotubular junction. Accordingly, tailoring of the root with annuloplasty and/or downsizing the sinotubular junction may be required.74 The potential advantage of this technique is to preserve the native root support around the autograft, which may prevent autograft dilatation and insufficiency. However, if the native aorta dilates, the autograft will do so as well.

Root Replacement Technique

In preparation for full root replacement the aortic transection is completed and the coronary ostial buttons are dissected out and mobilized appropriately. The native noncoronary sinus and the "pillar" of tissue between the right and the left buttons are preserved for later "re-inclusion" around the autograft root. The best orientation for the autograft is determined by placing it in the aortic root. Usually the bare area from the back of the PA is positioned in the left coronary sinus.

A strip of Teflon felt about 5- to 7-mm wide is cut to length around a size 2 mm larger than the inflow size of the autograft. The proximal autograft suture line is constructed incorporating the felt strip. This can be done with interrupted 3-0 or 4-0 simple sutures best organized on suture guides. Continuous 4-0 polypropylene can also be used beginning under the right-left commissure and working down the left sinus. The noncoronary and right sinuses follow. The sutures are left loose and slightly remote to facilitate visibility (Fig. 34-10). When completed, the suture line is carefully tightened with nerve hooks and tied securely.

The coronary buttons are then reimplanted with continuous 6-0 Prolene. The position of the right coronary is always higher than anticipated, usually just at the sinotubular junction of the autograft.

Excess pulmonary artery wall is trimmed from the autograft down to just above the commissures and very close to the tops of the coronary buttons. The native aortic wall elements that were preserved earlier are now brought up beside the autograft and shortened if necessary. If the native root was dilated or frankly aneurismal, artificial support can be employed using felt patches or vascular graft material.

The distal autograft is attached to the ascending aorta with continuous 4-0 polypropylene incorporating the natural and/or fabric support elements along with another strip of felt placing the sutures right at the tops of the commissures to establish a new sinotubular junction (Fig. 34-11). With the aorta closed, antegrade cardioplegia can be administered to give a test of valve competence and integrity of the coronary and distal suture lines.

The pulmonary homograft is now attached to the RVOT with continuous 4-0 polypropylene. Care is taken to take long and superficial bites posteriorly over the area of the septal perforator. The distal suture line is completed with continuous 4-0 or 5-0 polypropylene.

The ascending aorta is vented and the cross-clamp removed. Generous reperfusion time is recommended. Bleeding is certainly a risk with so many needle holes in delicate tissue submitted to aortic pressure. For this reason care must be taken to avoid vigorous retraction, which can cause more harm than good. Amicar is recommended, as is autologous blood removal at the beginning of the operation for return at the end. Biological glues can be helpful but their use is not a substitute for accurate suture line construction.

Concomitant Aortic Surgery

Because of the recognition that patients with bicuspid aortic valves are at risk for late dilatation and aneurysm of the ascending aorta, one should resect any aorta greater than 5 cm in diameter. Below 3.5 cm it is hard to justify any treatment. Between 3.5 and 5 cm it is reasonable to employ plication or lateral aortorrhaphy concepts to bring the aorta down to 3.5 or less.75,76 Because the vast majority of dissection in the BAV patient begins in the ascending aorta,77 complete resection of aneurysms up to the arch (hemi-arch replacement) should be considered. This actually adds very little time to the operation if planned appropriately. The proximal end of the aortic graft is attached to the (usually reinforced) autograft root to restore aortic continuity.

Operative Risk

According to the International Ross Registry, overall perioperative mortality (i.e., <30 days) was 4.1% (129 deaths in 3922 patients).18 Given the 1% risk of alternative operations, this may be unacceptably high. Like so many highly technical procedures, experience makes a big difference. The author's own experience demonstrated a "learning curve" with three deaths in the first 30, three more in the next 178 and no deaths in the next 260. Clearly the complexities of reoperative status, need for circulatory arrest, replacement of ascending aneurysm, and concomitant mitral repair should encourage referral to an experienced surgeon if a Ross procedure is to be considered. Individualized discussion with each patient should examine the options and consider the potential risks and benefits of each. Because a volume–outcome relationship may be apparent, the option of referral to regional "centers of excellence" should be included in this discussion.

Results

Pioneer Series Results

No discussion of the Ross operation could be complete without a careful look back at the pioneer series of patients treated by Donald Ross.78 The 1997 paper from this seminal source analyzed 131 hospital survivors followed for 9 to 26 years with a mean of 20 years. The technical problems that led to early reoperation with the subcoronary technique were recognized in that series and the cylinder modification adopted. Even the full root replacement method was employed as an alternative by Ross in 20 patients beginning as early as 1974.79 Survival at 10 and 20 years was a remarkable 85 and 61%, respectively. Freedom from autograft replacement was 88 and 75%, where freedom from homograft replacement was 89 and 80% each at 10 and 20 years. Of 53 late deaths, 46 were cardiac. Importantly, of the 30 autografts that were explanted, only three had evidence of degenerative change, which was patchy and did not involve all leaflets. The remainder had completely viable structure as long as 24 years after implantation. Clearly, the transplanted pulmonary autograft is and remains a fully living valve. Homograft stenosis accounted for all but 1 of 20 late reoperations on the right side. Thromboembolic phenomena were documented in 20 patients, but only one did not have another systemic risk factor for a source.

Exercise Hemodynamics of the Ross Operation

Multiple studies demonstrate the excellent hemodynamic profile offered by the autograft in the Ross operation. A comparison with normal age- and gender-matched controls showed peak gradients going from only 2 to 4 mm Hg in both groups with exercise.80 Effective orifice areas of 3.5 cm2 (EOAI 1.9 cm2/m2) did not change with exercise in either group. Full root Ross patients had better hemodynamics than subcoronary Ross patients, but the difference (1.98 ± 0.57 versus 1.64 ± 0.43 cm2/m2) was more important statistically than it was clinically.81 This study also documented the superiority of the Ross hemodynamics over stented and stentless valves and even over aortic homografts.

It is important to remember that the Ross operation includes RVOT reconstruction, and the hemodynamics of that structure can adversely affect exercise capacity. One study documented an average resting gradient of 14 ± 10 mm Hg rising to 25 ± 22 mm Hg for the pulmonary homografts of Ross patients compared with only 3 ± 1 mm Hg at rest and 5 ± 4 mm Hg with exercise in the normal native RVOT of aortic homograft recipients.82 The higher gradients in the RVOT may contribute to slightly lower maximal oxygen consumption compared with normal controls, even though Ross patients easily exceeded 100% of predicted consumption.

Contemporary Results

With operative mortality now approaching that of alternative valve replacements, the long-term results are the vital point in considering the Ross operation for any given patient. The comparative incidence of reoperation for structural valve deterioration with present-generation tissue valves and the continuing risks of thromboembolism and anticoagulant-related hemorrhage with modern mechanical devices must be fairly presented to patients along with the data for the Ross.

A thorough review of available series confirms that survival is extremely good after the Ross operation and approximates that of the normal age-matched population.83 Combined with its low incidence of thromboembolic complications and endocarditis as well as avoidance of anticoagulation with its risks of bleeding, the Ross is a very attractive option for young people. Some of these patients will undoubtedly require further surgery, but the outcomes of subsequent surgery have also been extremely good, which contributes to the long-term survival.

Elkins reported results in 487 patients operated on between 1986 and 2002.84 Hospital mortality was 19 to 3.9%. Of 15 late deaths, none were owing to reoperation but only 7 were not cardiac related. Actuarial freedom from all cause mortality was 92 ± 2% at 10 years and 82% ± 6% at 16 years. There was only one documented thromboembolic event. Actuarial freedom from endocarditis was 95 ± 6% at 16 years. Of 38 patients who needed further surgery, autograft reoperation was more common than homograft reoperation. Importantly, the vast majority of these patients had bicuspid or even unicuspid morphology, but their risk of reoperation was actually lower than the 9/78 three-leaflet valve patients. Patients with primary aortic regurgitation fared significantly worse until 1996 when the institution of routine annular reduction and fixation was initiated. Subsequent results in AR were then only slightly inferior to those in AS in whom the 15-year freedom from autograft valve failure was 82 ± 6%. Technique seemed important as only 21/389 full roots required reoperation where 17/79 intra-aortic implants did.

Pulmonary Autograft Dysfunction

Pulmonary autograft stenosis has never been reported but the incidence of regurgitation increases with time and seems to be due to autograft or native aortic dilatation or both. The recognition of early AR due to technical problems with intra-aortic implants led to widespread acceptance of the root replacement method when we reported this in 1989.85 Unfortunately, the totally unsupported autograft as a freestanding aortic root replacement proved to have potential for dilatation with root aneurysm and AR as a result. Annular dilatation was appreciated early and addressed with annuloplasty and external fixation with fixed pericardium or prosthetic material. Dilatation at the sinus and sinotubular junction levels was not appreciated and addressed until about a decade later. Incidence of this problem has been difficult to define and risk factors have been controversial. Autograft function can often remain excellent even with significant root dilatation (Fig. 34-12).

Brown found that preoperative ascending aortic dilatation, male gender, and postoperative systemic hypertension were significant in a Cox proportional hazard analysis for the development of moderate neo-aortic regurgitation.86 Hypertension, particularly early postoperatively, can cause acute dilatation and damage to the delicate autograft leaflets before they have time to adapt to the systemic pressure environment. The unsupported root technique having failed in 22 of 142 patients in Rotterdam over a 17-year period, the adult Ross procedure was abandoned at Erasmus.87 David expressed concern about the potential for dilatation at multiple levels particularly in bicuspid valve patients because of a higher incidence of aortic wall pathology.88

Multiple approaches have been developed to solve the dilatation problem. Sievers has demonstrated that a rigorously selected population of patients with frequent "tailoring" of the native aortic root can be treated with a subcoronary Ross implant with excellent results up to at least 10 years.74 Others including this author89 and Oswalt 90 stressed the need for multilevel fixation to support the autograft. Still others have suggested use of absorbable mesh,91 pericardial,92 or fabric93 wrapping to completely enclose the autograft. The restrictive nature of this approach may produce other problems by compressing the pliable, dynamic autograft into a rigid cylinder with decrease in potential for vascular ingrowth. Clearly the patient with root and ascending aneurysm cannot be treated by a simple inclusion cylinder implant, but the patient with normal root anatomy and good size match can be served quite well by this alternative. Individualization is required to make sure that the autograft whether inside the intact or "tailored" aortic root or implanted as a full root has appropriate supporting autologous tissue and/or prosthetic material of appropriate dimensions to allow normal valve function and prevent late dilatation. With this approach it is not unreasonable to anticipate autograft failure rates of less than or equal to 10% at ten years and less than or equal to 20% at twenty years.

Pulmonary Homograft Dysfunction

As part of the Ross operation, the single aortic valve operation becomes a double valve operation also leaving the RVOT substitute at risk for future problems. The pioneer series clearly demonstrated the homograft to be superior to other alternatives of that day, but controversy remains particularly over the advantages and disadvantages of homograft viability on the right side. Although the initial hemodynamics of the cryopreserved pulmonary homografts are excellent, consistent increase in transvalvular gradients occurs within 6 to 12 months. This early increase in gradient usually stabilizes by 2 years, but can be progressive in 1 to 2% of patients. An immune system response has been implicated, but the mechanisms are poorly understood.94

The pulmonary homograft can develop extensive calcification of the inflow end indicative of an intense scar response to the homograft muscle cuff (Fig. 34-13). Schmidtke and associates tried to minimize this with a unique trimming of the muscle and replacing it with a cuff of pericardium.95 This proved effective over the first two years but failed to make a long-term difference. An intense adventitial inflammatory reaction with diffuse thickening along the entire homograft was described with elegant MRI flow studies by Carr-White.96 This caused extrinsic compression of the conduit portion of the homograft.

The incidence of homograft stenosis is probably 5 to 10% at 10 years. Risk factors proposed include younger donor age, shorter time of cryopreservation, and homograft size.97 Because small size is the most consistent risk factor, oversizing helps reduce the effect of shrinkage.

Most patients tolerate peak gradients up to 50 mm Hg without symptoms so the clinical significance is less than the incidence of stenosis. In the Oklahoma series, homograft failure (reoperation or percutaneous intervention) occurred in 33 of 487 patients giving actuarial freedom from failure of 90 ± 2% at 10 years and 82 ± 4% at 16 years.84 The advent of catheter-based valve replacement has made it possible to treat some of these patients percutaneously.98

Moderate or even severe homograft regurgitation may also be detected by echocardiography in as much as 10% of patients by 10 years but this lesion is well tolerated by the right ventricle in the absence of pulmonary hypertension. It is probable that most pulmonary homografts will ultimately suffer this mode of failure but the majority will last 20 to 25 years before they reach this point.

After four decades of use and research, the cryopreserved pulmonary homograft is the best RVOT substitute documented for use in the Ross procedure. Rarely, a stentless porcine bioprosthesis has been used. Tissue engineering concepts seem ideally suited to this low pressure area where a decellularized homograft or even heterograft matrix can perform nicely while providing an environment suitable for maturation of new cellular elements derived from circulating stem cells, adjacent ingrowth, or preoperative seeding. Initial clinical studies with both show promise but await long term follow up.33,99

The prospect of reoperation after a Ross procedure has been regarded as a complex and hazardous undertaking.87 Concern about dissection and rupture is largely unsupported. Rupture of the autograft has never been reported. Localized dissection of the autograft does occur but does not extend across circumferential suture lines that protect the distal aorta and the coronary ostia. The wall of the autograft, although thinner than native aorta, is encased in scar tissue from the original surgery, making leakage into a free pericardial space extremely unlikely.

If moderate autograft regurgitation has developed with root dilatation, a policy of waiting for symptoms or ventricular dysfunction/dilatation typically indicative for surgical intervention should be considered appropriate, not just treating a sinus dimension. If distal native aorta dilates to 5.0 cm or greater, it may be reasonable to intervene before it gets to 5.5 cm in the setting of original bicuspid aortic valve disease. If other valve disease or coronary disease dictates operative intervention, the dilated autograft should not be ignored. If the autograft has been supported at the inflow end with felt, the Yacoub valve–sparing approach may be appropriate because the annulus is already supported. If there is strictly a leaflet problem, such as prolapse or perforation, repair might be considered, but only if a durable repair can be anticipated. Complete redo root replacement should be considered if both the leaflets and the sinuses are problematic. The living, pliable autograft makes this much easier than a redo after a standard Bentall.

Safe reoperation begins with appropriate planning at the original operation where closure of the pericardium or coverage of the heart with pericardial substitute will allow safe sternal re-entry. Central cannulation is almost always possible, but peripheral cannulation should be considered in multiple reoperative settings or when preoperative imaging suggests perilous re-entry. Crucial to safe conduct of these operations is avoidance of the plane between the pulmonary homograft and the aorta. There is usually plenty of room distal to the pulmonary artery to clamp the aorta before this plane needs to be addressed. Coronary buttons are often very close to the distal autograft anastomosis, so aortotomy at reoperation should never be proximal to this suture line. The complete spectrum of replacement options is open at reoperation, including simple mechanical or stented tissue valves, subcoronary or full root stentless, aortic homograft, or Bentall operation with biologic or mechanical valved conduit. The RVOT homograft should be left alone unless grossly abnormal by preoperative evaluation. If reoperation is required for RVOT obstruction, this can be accomplished on the beating heart. The old conduit is opened longitudinally from normal right ventricular muscle to normal PA. The thick proximal scar is resected carefully and as much of the old conduit is removed as necessary to allow placement of a new homograft. The posterior wall and that facing the aorta can be left intact to avoid injury to the autograft and coronary tree.

Of all the substitutes for the diseased aortic valve, only the pulmonary autograft has all the biologic advantages of a truly living structure. It is delicate and demands precise implantation technique for immediate and long-term success. Appropriate aortic tailoring or support is needed in the majority of patients to prevent late autograft dilatation and dysfunction. Approximately 20% of patients will probably require additional surgery for either the neo-aortic or the neo-pulmonary aspects of this operation by 20 years, but they will not require anticoagulation and will not be limited in activity or lifestyle during that time. In appropriate hands, this operation can be done very safely and is a durable and excellent choice for young active people with aortic valve disease. Compared with the virtually 100% reoperation rate at 20 years for animal tissue valves, unavoidable and ongoing risks of thromboembolic and hemorrhagic complications with mechanical valves, and proven advantage of the Ross procedure over aortic homograft in randomized prospective trial,100 the Ross procedure is a very viable option. Long-term survival may actually be superior to any other aortic valve operation.

Appropriate imaging of patients after these patients is essential and should include a thorough echo evaluation at least every 2 years. CT or MRI evaluation of the aorta should probably be done at least every 10 years and more frequently if progressive aortic dilatation is observed. Reoperation when required can be done safely in experienced centers with preservation of the autograft possible in some cases. The Ross operation should be offered as an option for any patient under the age of 50 with aortic valve disease and a life expectancy in excess of 20 to 25 years. Under ideal circumstances, it can be considered in the 50- to 65-year-old population where the Ross procedure has the possibility of lasting to the end of a normal life span.