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.
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.
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).
Preoperative imaging of the aorta. (A, B) Computed tomographic angiography. (C) Cardiac magnetic resonance.
Evaluation of pulmonic valve by CMR. (A) Longitudinal view. (B) Cross-sectional view showing three distinct leaflets and sinuses.
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.
Pulmonary autograft harvest. A right-angle clamp can be passed through the right ventricular outflow tract muscle below the anterior commissure to assure safe beginning of the harvest incision.
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.
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.
Proximal autograft suture line. The continuous suture technique is facilitated by leaving the sutures loose enough to easily see the leaflets to optimize depth and spacing and minimize tearing of this delicate muscle cuff. A measured strip of felt is incorporated in this suture line. Note that the noncoronary sinus tissue and the "pillar" of tissue between the coronary buttons has been preserved for later inclusion around the autograft root.
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.
Fabric support of autograft wall. (A) The arterial wall of the autograft is supported by segments of vascular graft material especially when native aortic wall is intrinsically poor. The entire autograft is enclosed with a combination of native aortic wall and vascular graft material and attached to the ascending aortic graft incorporating another strip of felt. (B) Completed Ross with external fabric support and ascending aortic replacement as well.
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.
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.
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.
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).
Dilated Ross procedure at 10 years. (A) CTA appearance. (B) Echocardiogram showing minimal central AR.
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.
Calcified pulmonary homograft. The inflow anastomosis of this pulmonary homograft is markedly narrowed and calcified 16 years after a Ross procedure. Gradient was only 28 at rest but 75 mm Hg with exercise. (A) Appearance on CT scan. (B) Gross specimen at explant. (C) Microscopic showing acellular scar.
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