CARDIAC SURGERY

THE CURRENT STATUS OF THE ROSS OPERATION :  DOES IT STILL HAVE A ROLE FOR THE YOUNG ADULT PATIENT WITH AORTIC VALVE DISEASE?

Gosta Pettersson ¹, M.D., Ph.D; Richard A. Grimm ², D.O., F.A.C.C. 
¹Department of Thoracic and Cardiovascular Surgery and ²Department of Cardiovascular Medicine,
The Cleveland Clinic Foundation, Cleveland, Ohio, USA

Introduction
Current Aortic Valve Surgery at the Cleveland Clinic
Aortic Valve Reoperations
The Ross operation, current position, results and issues
Cleveland Clinic and Copenhagen experience with the Ross operation
Cleveland Clinic and Copenhagen experience of reoperations after previous Ross 
Present approach to the Ross operation
   Patient selection
   Preoperative evaluation
   Operative technique
Specific intraoperative considerations and comments on technique
The Top Hat or Ross II procedure
Conclusion
References

Introduction

  In 1967 Mr. Ross invented and performed a conceptually innovative and technically challenging operation using the patient’s own normal pulmonary valve as an aortic valve substitute and taking into consideration the time and methods of myocardial protection (1).  Few surgeons besides Mr. Ross himself adopted the operation because of its difficulty and complexity.  As time went by, Mr. Ross’ series grew and good long-term results were reported (2).  Impressive long-term results triggered a new interest in Mr. Ross’ operation.  Steltzer and Elkins started implanting the autograft as a freestanding root and soon recognized that in addition to being easier, the root implantation technique more consistently produced a competent autograft valve (Figures 1-5) (3,4).  Many other surgeons worldwide started to perform Ross operations and confirmed good autograft function and early results.  The enthusiasm spread and created a surge in the popularity of the Ross operation.  The concept of the Ross operation providing a “normal” aortic valve, with potential for growth in children and durability for life, was very attractive and easy to adopt and the drawback of right ventricular outflow tract reconstruction with an allograft easy to dismiss.  Oury initiated a Ross registry and regular meetings exclusively devoted to the Ross operation were organized (5).  

   Rumors and reports of operative deaths and a high incidence of progressive autograft dilation and failure as well as stenosis of the allograft in the RVOT created growing concerns about the safety and permanence of the Ross operation.  The number of Ross operations began to decline and has continued to do so over the last 5 years.  The concerns about the safety and longevity of the Ross operation were eventually supported by the data in the Ross registry (5).  

   The focus of the discussion of this review is on the young adult patients for whom performance of the Ross operation is to be compared to that of mechanical or tissue prosthetic valves and allografts. The issues in children are different and the alternatives for aortic valve replacement less attractive than in the young adult.  Autograft growth has been demonstrated and survival and freedom from aortic valve replacement are excellent in children after a Ross operation and the procedure has maintained its standing in this patient population (6-8).  The issues related to the Ross operation in children deserve its own review and will not be addressed here.

Current Aortic Valve Surgery at the Cleveland Clinic

   Although many surgeons strongly promote aortic valve replacement with mechanical valve prosthesis and anticoagulation for the young adult patient with aortic valve disease (9), many patients disapprove of anticoagulation for life and some have other medical conditions contraindicating anticoagulation.  The risk of anticoagulation is patient and medical system related. Anticoagulation requires compliance and discipline.  New regimens for self-testing of INR levels (1-2 times per week) and the possibility of accepting lower INR levels for some mechanical prostheses might reduce but not eliminate the risks (10).

   Surgeons and cardiologists at the Cleveland Clinic have promoted use of repair or tissue valve options during the last decade.  The choice of valve over time for replacement is illustrated in figure 6. In the year 2002 aortic valve operations at the Cleveland Clinic totaled 1071, 1007 replacements and 64 repairs (figures 7).  Sixty-five percent of all isolated aortic valve procedures were performed through a mini-sternotomy.  During the period 1990-2000 the choice of valve in the STS registry for aortic valve patients below the age of 60 years was mechanical valve in 77%, bioprosthesis in 13%, allograft in 5%, and Ross in 5%, indicating a much higher use of mechanical valve prostheses at other U.S. institutions compared to the Cleveland Clinic.

   When advising the patient about choice of valve, we agree on the issues to consider (operative risks and long term survival, risk of thromboembolism, risk of anticoagulation related bleeding complications, risk of endocarditis, other valve related morbidities, valve durability, risk of reoperation(s) and quality of life aspects), but we weigh the arguments differently.  Quality of life aspects are important but more difficult to weigh.  The information is still incomplete to allow direct comparisons of Ross with mechanical or tissue prosthetic valves and allografts on long-term survival and mortality (valve, non-valve related and mortality after reoperations).  

   Operative risks are related to primary procedure and reoperations.  Mortality rate for isolated aortic valve replacement at the Cleveland Clinic in 2002 was 0.7%, for a valve reoperation 2.0% and for combined valve reoperation 3.0%.  Other risks are continuous and cumulative.

   Aortic valve repair is less often possible and technically more difficult than mitral valve repair.   An exception is repair of noncalcified bicuspid valves with pure regurgitation.  The majority of leaking bicuspid valves can be repaired with good intermediate term results (11).  There is less information about the feasibility and durability of repairs of other aortic valve pathologies with pure regurgitation.  An increasing number of surgeons are preserving the aortic valve in cases of aortic dissection or aortic root ectasia or aneurysm. 

   The only certain differences between mechanical and tissue valve protheses or allografts are more anticoagulation related bleeding complications and better durability/freedom from reoperation for mechanical valves. For bioprosthesis and allografts valve durability dependent on patient age is available, being worse in younger patients. Second generation bioprostheses have better durability than first generation. This development has already made a significant difference on valve choice, particularly in the age group between 50-65 years.

Aortic Valve Reoperations

   Use of tissue valves in younger patients means acceptance of future reoperation(s). The 2% risk associated with an aortic valve reoperation compares favorably with the accumulated risk of anticoagulation.  The easiest reoperations are those following previous repair or prosthetic valve replacement.  Yacoub did second time allograft aortic valve and root replacements in 144 patients with an early mortality of 3.4% and long term outcomes comparable to primary allograft aortic valve and root replacement (12). Reoperations after Ross will be addressed below.

The Ross operation, current position, results and issues

   The outcomes in the pioneer series were: 60% survival, 75% freedom from autograft replacement, and 80% freedom from right-sided allograft replacement at 20 years (13). To defend the rationale of putting the allograft in the pulmonary position, Yacoub has randomized patients to Ross or allograft replacement and although follow up is still short, interim results favor the Ross procedure (14). 

   The national Dutch experience with the Ross operation in 343 patients (corresponding to 99% of the Dutch Ross experience) was recently published and should be fairly representative of the performance of the operation with seven centers and many different age groups (mean age 26 years, range 0-55) (15).  Freedom from any valve-related reintervention was 88% at 7 years.  Elkins had an 83% 10 year-actuarial freedom from all valve-related complications (autograft valve degeneration, autograft valve reoperation, homograft valve reoperation or valve-related death) of 83% (16).  Bohm and coworkers report 225 patients with no mortality and excellent short and mid-term result (17).

   The advantages of the Ross operation are low risk of thromboembolic complications and endocarditis and superior hemodynamic performance. Allografts and autografts seem to be better than any prosthetic valves with regard to risk of endocarditis and thromboembolism (18,19).  Using high-intensity Doppler signals, the incidence of microemboli was very low after a Ross operation compared to replacement of the aortic valve with a mechanical prosthesis (20).  The hemodynamic performance of the autograft is better than any other replacement alternative including the allograft.  This is probably important to young and active patients and athletes (21-24).  An increasing number of reports testify to the superiority of allografts in cases of advanced endocarditis and possibly the autograft belong in the same category (25-27).

   The issues with the Ross operation are the operative risk and autograft failure and RVOT allograft degeneration requiring reoperations.  Although the best and larger series show very low mortality with any alternative operation including the Ross operation, the operative risk has to be higher for the more complex operations involving manipulations of the coronary arteries like the allograft Ross or composite graft root replacements.  The operative mortality in larger recent series has been 0-2.6%.  Of particular interest is the reported mortality in the collected series of The Netherlands and Spain, which was 2.6% and 2.4% respectively (15,28).  The slightly higher mortality in these multi-center series including the Ross registry (5) compared to larger single center series confirms the fact that the operative risk of complex operations is surgeon dependent.  Another point is that the mortality is higher for pediatric compared to adult patients.  Harvesting of the autograft means dissection close to the 1st septal branch but injury to this branch has been very infrequent, possibly because of the high level of awareness.  The autograft is a delicate thin walled structure at risk of injury during harvesting and implantation resulting in bleeding. 

   David first recognized and reported progressive autograft dilation as an important cause of autograft failure (29).  The autograft dilation has two phases: immediate as the autograft is exposed to systemic pressure and progressive long-term.  Increased distensibility of the pulmonary root compared to aortic root has been demonstrated (30-32).  Also, in children and growing pigs, the increase in size of the autograft is disproportionate suggesting a combination of dilation and growth (33,34).  When pulmonary allografts were used in the aortic position, they had a very high failure rate (35).  Gerosa and coworker seemed to have somewhat better results when the pulmonary allograft was implanted subcoronary or as an inclusion cylinder (36).  The autograft is living tissue and in most Ross cases, adaptation and remodeling occur preventing progressive dilation and autograft failure (37).  Moderate dilation will not necessarily be associated with autograft failure (38).  Sinus dilation is more innocent than dilation of the sinotubular junction and/or the annulus. Elkins (39) has emphasized the annulus and David the sinotubular junction matching, reduction and support. 

   All Ross surgeons today pay attention to size matching of the annulus and the sinotubular junction although they have different approaches with regard to the support of the autograft.  David had very few failures when root inclusion was used to prevent dilation (40).  Skillington and coworkers consistently use the root inclusion (41).  A few surgeons have gone back to the original subcoronary implantation technique in the few feasible cases with normal roots, however this technique definitely has a learning curve (42).  Schmidtke and coworkers obtained equally good results with all implantation techniques, freestanding root, inclusion, and subcoronary implantation (43).  Today, this group expresses a preference for the subcoronary implantation (44).  Melo and coworkers are also proponents of subcoronary implantation (45).  

   Patients with Marfan’s syndrome or other connective tissue disorders have never been candidates for the Ross operation because of the presumed risk of autograft dilation and failure.  David has raised the question of whether patients with bicuspid aortic valves belong to the same category (46).  In patients with bicuspid valves and associated dilatation of the ascending aorta (figure 8) the pathologic diagnosis on the ascending aorta specimen is almost invariably severe cystic medial degeneration or necrosis.  The same group has suggested matrix remodeling as the underlying mechanism of aortic degeneration and dilatation (47).  Others have, however, presented series of Ross operations on bicuspid valve patients with equally good results (48,49) or did not find any particular pathologic findings in patients with bicuspid aortic valves (50,51).

   Rheumatic valve disease may affect the autograft valve (52).  Young age (<30 years) and associated mitral valve disease were risk factors for autograft failure in patients with rheumatic disease.  The successful use of the Ross operation in patients with aortic valve endocarditis was pioneered by Oswalt and ourselves (53,54).  After removal of the pulmonary artery the Ross operation provides unparalleled exposure facilitating debridement and contributing to a better understanding of the advanced endocarditis pathology of the aortic root (figure 9).

   For the patients requiring reoperation for autograft failure, all feasible options and have been used, including valve repair remodeling according to David (55,56) In our practice, most valves were replaced (see below) while Elkins reported repair of six out eleven (57). 

   The problem of failure of the pulmonary allograft used to replace the pulmonary valve and artery is equally troublesome.  The early failures were thought to be due to an immune reaction. RVOT allograft degeneration has been associated previously with Ross operation as a reoperation, younger age, younger donors, and shorter duration of cryopreservation (58-60).  In most instances, the RVOT obstruction has been supravalvular rather than valvular.  Early findings have demonstrated a severe inflammatory reaction around the allograft and formation of thick scar tissue (61). Allograft replacement of the failed allograft seems to be the most frequent solution but others and we have also used RVOT patch enlargement.

   There are no published long-term follow up of patients reoperated for autograft or allograft failures.

Cleveland Clinic and Copenhagen experience with the Ross operation

   The first patient who underwent a Ross operation in Copenhagen was a 14 year-old boy from Greenland with aortic valve endocarditis, root abscess, and VSD with multi-organ failure.  The second patient was 18 years old with an infected composite graft with an abscess and pseudoaneurysm around the graft and he had undergone 4 previous heart operations.  The successful execution and excellent outcome of these first two Ross operations initiated an aggressive application and use of the Ross operation for different aortic valve and root pathologies in adults and children.

   During the time period 1992 through 1997, 120 Ross operations were performed in Copenhagen with a very standardized root replacement technique (62) for a variety of pathologies (63).  A third of the patients had active or remote endocarditis (64).  No complete follow up has been performed since I left Copenhagen.  However, echocardiography follow up of 68 Copenhagen patients was performed during 2001 and 2002 with the following results: Aortic regurgitation (AR) was 0 or trace in thirty patients, 1+ in thirty patients, 2+ in five patients, 3+ in one patient, and 4+ in two patients. RVOT gradients were >20mmHg in 14 patients but >40mmHg in only 3 patients.  Three patients had 3+ to 4+ pulmonic regurgitation.

   The Cleveland Clinic has two Ross series: one early from 1993-96, which comprised 68 patients and a recent series, which started in 2000, and consisting of 16 patients to date.  The follow up echocardiography studies of the first series were reviewed in 2001 at 5 years.  There was no AR in 40% of the 68 patients, 1+ AR was present in 20%, 2+ in 7%, and 3+ in 33%.  There was significant but unimpressive dilatation of the annulus as well as of the sinotubular junction over time.  24% had an RVOT gradient of >20mmHg, none had a gradient >40mmHg but 5 underwent RVOT reoperation.  Eleven of the 68 patients have been reoperated, 6 for AR, 3 for AR and RVOT-PS and 2 for RVOT-PS. 

   Recently we made a comparison of freedom from reoperation for structural valve degeneration after valve repair, Ross procedure, allograft root replacement and pericardial prosthetic valve replacement at different ages.  This comparison suggested a long-term advantage of repairs and Ross procedures in the younger patients while pericardial valves and allograft performed equally well or better in patients who were 50 years or older (Figures 10,11).

Cleveland Clinic and Copenhagen experience of reoperations after previous Ross

   Our combined total experience with reoperations after a previous Ross operation includes 28 reoperations in 26 patients, 16 for autograft failure, 5 for pulmonary allograft stenosis and 6 for both autograft failure and allograft stenosis.  One patient was reoperated due to left coronary artery ostial stenosis.

   Identified causes of autograft failure in the 21 cases were: intraoperative autograft tear, one; autograft dilation, nine (with cusp prolapse in 3; with cusp perforation in 1); cusp prolapse five (figure 12); cusp perforation three, endocarditis in three, and quadricuspid autograft valve in one; information was lacking in 2 patients.  Preoperative potential risk factors for autograft failure were: bicuspid aortic valve (11 patients), endocarditis (1 patient), rheumatic valve disease (1 patient), dilated ascending aorta (6/13), and hypertension (2 patients).  All the Ross operations had been performed as root replacement with one root inclusion.  Only 1 had more than 1+ AR out of the OR. At reoperation 5 autografts were repaired (Figure 13); the other 16 were replaced with allograft or a prosthetic valve.

   RVOT stenosis with gradients higher than 60mmHg was an indication for reoperation in 5, all within the first year.  One patient had RV failure.  The stenosis was supravalvular in 2/3 and valvular in 1/3.  One had pulmonary allograft valve endocardits with large vegetations but the autograft was well functioning and not affected.  Most pulmonary allografts were replaced but an RVOT outflow patch was placed in 2 cases.  In reality, the RVOT reoperations I have performed have not been that easy due to severe inflammatory reaction around the allograft (figure 14).  I have seen recurrent stenosis in two cases, one after replacement and one after outflow patch.

Present approach to the Ross operation

Patient selection

   Contraindications include Marfan’s syndrome and other connective tissue disorders. Patients with bicuspid aortic valves might belong in the same category and are candidates only if they have no or mild aortic dilation.  Rheumatic valve disease, poor left ventricular function, need for replacement of another valve, a bleeding disorder and concomitant medical issues and comorbidities are relative contraindications.

Preoperative evaluation

   The pulmonary valve should be normal by echocardiographic examination for the patient to be considered a candidate.  Patients with bicuspid aortic valves or pulmonary artery to aorta size mismatch should undergo aortic scanning by CT or MRI.  Coronary catheterization is not performed routinely.

Operative technique

   Intraoperative transesophageal echocardiography is mandatory.  Bicaval cannulation and vacuum assisted venous drainage secures good drainage and prevents airlocks. When retrograde cardioplegia is used, good protection of the right ventricle by additional antegrade cardioplegia to the right coronary artery is important.

   A high transverse aortotomy is performed, high to provide aortic wall for support.  The aortic valve pathology is evaluated and the aortic valve removed.

   The main pulmonary artery is incised beyond the commissures and the valve carefully inspected, the cusps are counted and caredfully inspected for quality, integrity and shape.  The cusps should be normal and only minimal fenestrations are accepted.  A perfect bicuspid valve could be acceptable.  The pulmonary artery is separated from the aorta, staying close to the aorta, and entering the right, natural plane separating right and left ventricular muscle.  The right ventricle is incised 5mm proximal to the mid-cusp level. The first septal branch is often exposed laterally in the natural septal plane (figures 15,16,17).  The autograft is carefully inspected and trimmed for implantation.  Hemostasis in the dissection bed is attended to at this stage.  Infusion of retrograde cardioplegia reveals the venous bleeder, which are the most important.  Arterial bleeders are attended to immediately after removal of the aortic cross clamp.

   Implantation technique is decided and the aortic root is prepared appropriately.  In the most recent cases a semi-inclusion technique has been used, preparing coronary buttons for reimplantation while preserving the rest of the root including a ring of aortic wall at the sinotubular junction for autograft support. The aortic anulus is measured and if needed, downsized and supported with two annular purse string sutures tied over a Hegar dilator the size of the predicted normal annulus diameter according to BSA as introduced by Elkins.

   The proximal suture line is horizontal at midcusp level including the previously placed purse string sutures and performed with a running 3-0 monofilament sutures.  The autograft is oriented to place the anterior pulmonary valve commissure corresponding to the membraneous septum.  Great attention is paid to perfect spacing of the sutures. Implantation is deep within the annulus.  The coronary arteries are reimplanted in anatomical positions with running 5-0.  The distal autograft to aorta anastomosis includes the native aortic wall ring for support and is performed with running 4-0.  The autograft valve is higher and it is important that the aortic incision is high enough to allow the autograft commissures to stretch. In case of mild dilation and size discrepancy the aorta is reduced with a longitudinal wedge resection (aortoplasty) or replaced.

   RVOT reconstruction is performed using a pulmonary allograft, selected to be generous in size both in diameter and length and sewn in place in anatomical orientation with running 4-0.

   Immediately after declamping the autograft harvest site is checked once again for bleeders.  Additional sutures in the autograft are placed with care recognizing its delicate structure and risk of tear and distortion.  Transmural suturing in the autograft when pressurized should be avoided.

Specific intraoperative considerations and comments on technique

   Candidates for aortic valve repair are carefully selected and a limited amount of time, <30 minutes is spent on the repair attempt before deciding on a Ross procedure. Abandoning the Ross operation is considered in the following situations: (a) significant size mismatch, (b) suspicion of connective tissue disorder (aortic annulus and aortic root dilated to 150% of predicted diameter), (c) the pulmonary autograft appears exceptionally thin, (d) the autograft valve is damaged during harvest.

   Compared to the technique we originally described (62) there are few modifications, and are related mainly to more emphasis on annulus reduction and support of the annulus, the autograft and the sinotubular junction.  Reduction aortoplasty with a mildly dilated aorta is acceptable and is supported in a recent paper by Kamada and associates (65).  We remain faithful to the concept of minimal use of foreign material.  We have not performed subcoronary implantation.

   The final issue is the intraoperative post pump echocardiography and how to deal with autograft valve regurgitation (Figure 18).  I would be concerned if there is >1+ regurgitation.  The management approach must be individualized and adjusted to the actual situation, the mechanism of the regurgitation, probability of success and safety of going back to manipulate the autograft.

The Top Hat or Ross II procedure

   In spite of limited success with mitral valve replacement with stored inverted pulmonary allograft valve, Kabbani and Ross worked out the “Top Hat” procedure for use of pulmonary autografts for replacement of the mitral valve (66).  The name of the procedure “The Top Hat” describes the main principles of the implantation technique, the autograft being implanted supra-annular inside a vascular prosthesis.  Kabbani has reported excellent autograft function in 36 out 43 patients up to 36 months (67).  Kumar reported good immediate outcome in 8 out of 10 patients (68) and Pomar has also tried the procedure (69).  It is too early to have a firm idea about the feasibility and potential role for this technically demanding procedure.  At present, “Top Hat” is too complex to become widely accepted but might have a future in the hands of a few master surgeons working under difficult conditions in developing countries where prosthetic valves and anticoagulation monitoring are not readily available.

Conclusion

  Although the Ross operation may not have lived up to our highest expectations, it is still a competitive alternative (19), meeting objective performance criteria established for new prosthetic heart valves.  The operation is still evolving and results are improving.  Its greatest advantages are growth potential, normal hemodynamic performance, lowest risk of thromboembolic complications, and potential for life durability.  The safety of the Ross operation requires a large allograft experience and regular performance of Ross procedures.  Ideally, the surgeon should master the whole spectrum of aortic valve operation alternatives, including aortic valve repair or preservation and Ross procedure. The congenital heart surgeons are in a better position to learn to master all the options. Ross operations have also been successfully used in more complex cases and patients with severe left ventricular dysfunction (63,70,71).  

   The young adult patient chooses a  Ross operation because he believes in a good chance of getting a normal aortic valve for life.  According to the results of the published large series, that could still be true.  From our experience, with reoperations after previous Ross it seems quite possible to lower the failure rate by a more cautious patient selection and technical perfection of the operation.  Technically there is no cut-off age for the Ross operation but the older the patient, the less convincing the benefits of Ross when compared to the alternatives.  Currently, a life expectancy of more than 20 years is the rule of thumb in our practice.

   Right-sided reoperations, although equally disturbing to the patient, were expected to be easier and to have low risk.  Many patients have a benign mode of failure not necessitating replacement as illustrated by Ross’ own series.  Neither prevention nor treatment of RVOT allograft stenosis have found final satisfactory solutions as yet.  We are still looking for a better alternative to pulmonary allograft RVOT reconstruction. Different autologous tissue conduits have been tried and used but their wider feasibility and durability are yet to be proven.  Re-using the bad aortic valve in the pulmonary position has been successfully tried (72,73).  

   Non-immunogenic allo- or xenografts is another route under exploration but not ready for wider application (74).  

   The arguments against anticoagulation include lifestyle/socioeconomic, medical, and in young women, the desire to become pregnant. A study by Notzold and coworkers provided evidence that patients having pulmonary autografts have greater benefit in terms of quality of life, as compared with recipients of mechanical valve substitutes (75).  

  The patient must be given information in such a way as to allow her/him to understand the issues and the options.  Conceptually, valve repair remains the most attractive alternative and is always favored by the patient and his cardiologist.  The Ross operation has contributed to our improved understanding of the aortic valve and to expanding the group of patients, in whom repair is possible.  

   Future generation bioprosthetic valves may well make allografts and Ross operations obsolete.  However, limitations of present day bioprosthetic valves have kept allografts and pulmonary autografts in contention as an alternative.¨

References

1.  Ross DN. Replacement of aortic and mitral valves with a pulmonary autograft.Lancet.      1967;2:956-8. 

2.  Robles A, Vaughan M, Lau JK, Bodnar E, Ross DN. Long-term assessment of aortic valve      replacement with autologous pulmonary valve. Ann Thorac Surg. 1985;39:238-42. 

3.  Stelzer P, Elkins RC. Pulmonary autograft: an American experience. J Card Surg.      1987;2:429-33. 

4.  Stelzer P, Jones DJ, Elkins RC. Aortic root replacement with pulmonary autograft. Circulation.      1989;80:III209-13. 

5.  Oury JH, Hiro SP, Maxwell JM, Lamberti JJ, Duran CM. The Ross procedure: Current registry      results. Ann Thorac Surg 1998;66(6 suppl):S162-S165 

6.  Elkins RC, Knott-Craig CJ, Ward KE, McCue C, Lane MM. Pulmonary autograft in children:      realized growth potential. Ann Thorac Surg. 1994;57:1387-93; discussion 1393-4. 

7.  Al-Halees Z, Pieters F, Qadoura F, Shahid M, Al-Amri M, Al-Fadley F. The Ross procedure is      the procedure of choice for congenital aortic valve disease. J Thorac Cardiovasc Surg.      2002;123:437-41. 

8.  Elkins RC, Lane MM, McCue C. Ross operation in children: late results. J Heart Valve Dis.      2001;10:736-41. 

9.  Stahle E. Ross procedure in adults – a valid option for whom? Scand Cardiovasc J 2002;36:2-5

10. Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral      anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis 1998;5:19-24. 

11. Casselman FP, Gillinov AM, Akhrass R, Kasirajan V, Blackstone EH, Cosgrove DM.      Intermediate-term durability of bicuspid aortic valve repair for prolapsing leaflet. Eur J      Cardiothorac Surg 1999;15:302-8. 

12. Hasnat K, Birks EJ, Liddicoat J, Hon JK, Edwards S, Glennon S, Yacoub MH. Patient       outcome and valve performance following a second aortic valve homograft replacement.      Circulation 1999;100(19 Suppl):II42-7 

13. Matsuki O, Okita Y, Almeida RS, McGoldrick JP, Hooper TL, Robles A, Ross DN. Two      decades’ experience with aortic valve replacement with pulmonary autograft. J Thorac      Cardiovasc Surg. 1988;95:705-11. 

14. Aklog L, Carr-White GS, Birks EJ, Yacoub MH. Pulmonary autograft versus aortic homograft      for aortic valve replacement: interim results from a prospective randomized trial. J Heart Valve      Dis. 2000 Mar;9(2):176-88; discussion 188-9. 

15. Takkenberg JJ, Dossche KM, Hazekamp MG, Nijveld A, Jansen EW, Waterbolk TW, Bogers      AJ; Dutch Ross Study Group. Report of the Dutch experience with the Ross procedure in 343      patients. Eur J Cardiothorac Surg. 2002;22:70-7. 

16. Elkins RC, Lane MM, McCue C, Ward KE. Pulmonary autograft root replacement: mid-term      results. J Heart Valve Dis. 1999;8:499-503; discussion 503-6. 

17. Bohm JO, Botha CA, Hemmer W, Roser D, Starck CT, Blumenstock G, Rein JG. The Ross      operation in 225 patients: a five-year experience in aortic root replacement. J Heart Valve Dis      2001;10:742-9 

18. O’Brien MF, Harrocks S, Stafford EG, Gardner MA, Pohlner PG, Tesar PJ, Stephens F. The      homograft aortic valve: a 29-year, 99.3% follow up of 1,022 valve replacements. J Heart Valve      Dis 2001;10:334-44.

19. Moidl R, Simon P, Aschauer C, Chevtchik O, Kupilik N, Rodler S, Wolner E, Laufer G. Does      the Ross operation fulfill the objective performance criteria established for new prosthetic heart      valves? J Heart Valve Dis 2000;9:190-4. 

20. Notzold A, Droste DW, Hagedorn G, Berndt S, Kaps M, Graf B, Sievers HH. Circulating      microemboli in patients after aortic valve replacement with pulmonary autografts and       mechanical valve prostheses. Circulation. 1997;96:1843-6. 

21. Oury JH, Doty DB, Oswalt JD, Knapp JF, Mackey SK, Duran CM. Cardiopulmonary response to      maximal exercise in young athletes following the Ross procedure. Ann Thorac Surg 1998;66(6      Suppl):S153-4. 

22. Pibarot P, Dumesnil JG, Briand M, Laforest I, Cartier P. Hemodynamic performance during      maximum exercise in adult patients with the ross operation and comparison with normal controls      and patients with aortic bioprostheses. Am J Cardiol. 2000;86:982-8. 

23. Sievers HH, Schmidtke C, Graf B. Hemodynamics of semilunar valves at rest and exercise at      an average of more than two years after the Ross procedure. J Heart Valve Dis.      2001;10:166-169;discussion 169-70. 

24. Laforest I, Dumesnil JG, Briand M, Cartier PC, Pibarot P. Hemodynamic performance at rest      and during exercise after aortic valve replacement: comparison of pulmonary autografts versus      aortic homografts. Circulation. 2002;106(12 Suppl 1):I57-I62. 

25. Niwaya K, Knott-Craig CJ, Santangelo K, Lane MM, Chandrasekaran K, Elkins RC. Advantage      of autograft and homograft valve replacement for complex aortic valve endocarditis. Ann Thorac      Surg. 1999;67:1603-8. 

26. Sabik JF, Lytle BW, Blackstone EH, Marullo AG, Pettersson GB, Cosgrove DM. Aortic root      replacement with cryopreserved allograft for prosthetic valve endocarditis. Ann Thorac Surg.      2002;74:650-9; discussion 659. 

27. Prat A, Saez de Ibarra JI, Vincentelli A, Decoene C, Fabre OH, Jegou B, Savoye C. Ross      operation for active culture-positive aortic valve endocarditis with extensive paravalvular      involvement. Ann Thorac Surg. 2001;72:1492-5; discussion 1495-6. 

28. Concha M, Pradas G, Juffe A, Caffarena JM, Montero A, Aranda PJ. Comprehensive      experience with the Ross operation in Spain. Eur J Cardiothorac Surg. 2003;24:521-526. 

29. David TE, Omran A, Webb G, Rakowski H, Armstrong S, Sun Z. Geometric mismatch of the      aortic and pulmonary roots causes aortic insufficiency after the Ross procedure. J Thorac      Cardiovasc Surg. 1996;112:1231-7; discussion 1237-9. 

30. Vesely I, Casarotto DC, Gerosa G. Mechanics of cryopreserved aortic and pulmonary      homografts. J Heart Valve Dis. 2000;9:27-37. 

31. Okazaki Y, Takarabe K, Furukawa K, Higuchi S, Rikitake K, Ohtsubo S, Natsuaki M, Itoh T.      Distensibility of the pulmonary autograft under systemic pressure. J Heart Valve Dis.      2002;11:231-5. 

32. Nagy ZL, Fisher J, Walker PG, Watterson KG. The in vitro hydrodynamic characteristics of the      porcine pulmonary valve and root with regard to the ross procedure. J Thorac Cardiovasc Surg.      2000;120:284-9. 

33. Schoof PH, Hazekamp MG, van Wermeskerken GK, de Heer E, Bruijn JA, Gittenberger-de      Groot AC, Huysmans HA. Disproportionate enlargement of the pulmonary autograft in the aortic      position in the growing pig. J Thorac Cardiovasc Surg. 1998;115:1264-72. 

34. Solymar L, Sudow G, Holmgren D. Increase in size of the pulmonary autograft after the Ross      operation in children: growth or dilation? J Thorac Cardiovasc Surg. 2000;119:4-9. 

35. Mair R, Peschl F, Gross C, Klima U, Hinterreiter H, Bruecke P. The pulmonary homograft as      aortic valve substitute: 7 years’ follow up. Eur J Cardiothorac Surg. 1997;11:910-6. 

36. Gerosa G, Ross DN, Brucke PE, Dziatkowiak A, Mohammad S, Norman D, Davies J, Sbarbati      A, Casarotto D. Aortic valve replacement with pulmonary homografts. Early experience. J       Thorac Cardiovasc Surg. 1994;107:424-36; discussion 436-7. 

37. Carr-White GS, Afoke A, Birks EJ, Hughes S, O’Halloran A, Glennen S, Edwards S, Eastwood      M, Yacoub MH. Aortic root characteristics of human pulmonary autografts. Circulation.      2000;102(19 Suppl 3):III15-21. 

38. Simon-Kupilik N, Bialy J, Moidl R, Kasimir MT, Mittlbock M, Seebacher G, Wolner E, Simon P.      Dilatation of the autograft root after the Ross operation. Eur J Cardiothorac Surg 2002;21:470-3

39. Niwaya K, Elkins RC, Knott-Craig CJ, Santangelo KL, Cannon MB, Lane MM. Normalization of      left ventricular dimensions after Ross operation with aortic annular reduction. Ann Thorac Surg.      1999;68:812-8; discussion 818-9. 

40. David TE, Omran A, Ivanov J, Armstrong S, de Sa MP, Sonnenberg B, Webb G. Dilation of the      pulmonary autograft after the Ross procedure. J Thorac Cardiovasc Surg. 2000;119:210-20. 

41. Skillington PD, Fuller JA, Grigg LE, Yapanis AG, Porter GF. Ross procedure. Inserting the      autograft using a fully supported root replacement method; techniques and results. J Heart      Valve Dis. 1999 Nov;8(6):593-600. 

42. Willems TP, Takkenberg JJ, Steyerberg EW, Kleyburg-Linkers VE, Roelandt JR, Bos E, van      Herwerden LA. Human tissue valves in aortic position: determinants of reoperation and valve      regurgitation. Circulation. 2001;103:1515-21. 

43. Schmidtke C, Bechtel J, Hueppe M, Noetzold A, Sievers HH. Size and distensibility of the      aortic root and aortic valve function after different techniques of the Ross procedure. J Thorac      Cardiovasc Surg 2000;119:990-7. 

44. Sievers H, Dahmen G, Graf B, Stierle U, Ziegler A, Schmidtke C. Midterm results of the Ross      procedure preserving the patient’s aortic root. Circulation. 2003;108(10 Suppl 1):II55-60. 

45. Melo JQ, Abecasis M, Neves JP, Canada M, Ribeiras R, Parreira L, Andrade N, Calquinha J,      Ferreira JM, Rebocho MJ, Seabra-Gomes R. What are the limits for the Ross operation?      Cardiovasc Surg. 1996;4:526-9. 

46. de Sa M, Moshkovitz Y, Butany J, David TE. Histologic abnormalities of the ascending aorta      and pulmonary trunk in patients with bicuspid aortic valve disease: clinical relevance to the      Ross procedure. J Thorac Cardiovasc Surg 1999;118:588-94. 

47. Fedak PW, De Sa MP, Verma S, Nili N, Kazemian P, Butany J, Strauss BH, Weisel RD, David      TE. Vascular matrix remodeling in patients with bicuspid aortic valve malformations:      Implications for aortic dilatation. J Thorac Cardiovasc Surg. 2003 Sep;126(3):797-805. 

48. Koul B, Lindholm CJ, Koul M, Roijer A. Ross operation for bicuspid aortic valve disease in      adults: is it a valid surgical option? Scand Cardiovasc J. 2002;36:48-52. 

49. Favaloro R, Stutzbach P, Gomez C, Machain A, Casabe H. Feasibility of the Ross procedure:      its relationship with the bicuspid aortic valve. J Heart Valve Dis. 2002;11:375-82. 

50. Parai JL, Masters RG, Walley VM, Stinson WA, Veinot JP. Aortic medial changes associated      with bicuspid aortic valve: myth or reality? Can J Cardiol. 1999;15:1233-8. 

51. Luciani GB, Barozzi L, Tomezzoli A, Casali G, Mazzucco A. Bicuspid aortic valve disease and      pulmonary autograft root dilatation after the Ross procedure: a clinicopathologic study. J Thorac      Cardiovasc Surg. 2001 Jul;122(1):74-9. 

52. Pieters FA, al-Halees Z, Zwaan FE, Hatle L. Autograft failure after the Ross operation in a      rheumatic population: pre- and postoperative echocardiographic observations. J Heart Valve       Dis. 1996;5:404-8; discussion 408-9. 

53. Oswalt JD, Dewan SJ. Aortic infective endocarditis managed by the Ross procedure. J Heart      Valve Dis. 1993;2:380-4. 

54. Joyce F, Tingleff J, Aagaard J, Pettersson G. The Ross operation in the treatment of native       and prosthetic aortic valve endocarditis. J Heart Valve Dis. 1994;3:371-6. 

55. Schmidtke C, Stierle U, Sievers HH. Valve-sparing aortic root remodeling for pulmonary      autograft aneurysm. J Heart Valve Dis. 2002;11:504-5. 

56. Leyh RG, Kofidis T, Fischer S, Kallenbach K, Harringer W, Haverich A. Aortic root      reimplantation for successful repair of an insufficient pulmonary autograft valve after the Ross      procedure. J Thorac Cardiovasc Surg. 2002;124:1048-9. 

57. Elkins RC, Lane MM, McCue C. Pulmonary autograft reoperation: incidence and management.      Ann Thorac Surg. 1996;62:450-5. 

58. Raanani E, Yau TM, David TE, Dellgren G, Sonnenberg BD, Omran A. Risk factors for late      pulmonary homograft stenosis after the Ross procedure. Ann Thorac Surg. 2000;70:1953-7s 

59. Sakaguchi H, Elkins RC, Lane MM, McCue C. Effect of prior aortic valve intervention on results      of the Ross operation. J Heart Valve Dis. 2003;12:423-9. 

60. Bohm JO, Botha CA, Hemmer W, Starck C, Blumenstock G, Roser D, Rein JG. Older patients      fare better with the Ross operation. Ann Thorac Surg. 2003;75:796-801. 

61. Carr-White GS, Kilner PJ, Hon JK, Rutledge T, Edwards S, Burman ED, Pennell DJ, Yacoub      MH. Incidence, location, pathology, and significance of pulmonary homograft stenosis after the      Ross operation. Circulation. 2001;104(12 Suppl 1):I16-20. 

62. Joyce F, Tingleff J, Pettersson G. A systematic technical approach to the Ross operation. J      Heart Valve Dis. 1996;5:391-401; discussion 401-3. 

63. Joyce F, Tingleff J, Pettersson G. Changing indications for the Ross operation. Semin Thorac      Cardiovasc Surg. 1996;8:336-44. 

64. Pettersson G, Tingleff J, Joyce FS. Treatment of aortic valve endocarditis with the Ross      operation. Eur J Cardiothorac Surg. 1998;13:678-84. 

65. Kamada TT, Imanaka KK, Ohuchi HH, Asano HH, Tanabe HH, Kato MM, Ogiwara MM, Yamabi      HH, Yokote YY, Kyo SS. Mid-term Results of Aortoplasty for Dilated Ascending Aorta      Associated with Aortic Valve Disease. Ann Thorac Cardiovasc Surg. 2003;9:253-6. 

66. Ross DN, Kabbani S. Mitral valve replacement with a pulmonary autograft: the mitral top hat. J      Heart Valve Dis. 1997;6:542-5. 

67. Kabbani SS, Jamil H, Hammoud A, Nabhani F, Hariri R, Sabbagh N, Ross DN. Use of the      pulmonary autograft for mitral replacement: short- and medium-term experience. Eur J      Cardiothorac Surg. 2001;20:257-61. 

68. Roy S, Mohanty A, Kumar AS. Pulmonary autograft mitral valve replacement: initial experience      with the Ross II procedure. Indian Heart J. 2002;54:276-8. 

69. Mestres CA, Pomar JL. Mitral valve replacement with a pulmonary autograft: initial experience.       J Heart Valve Dis. 2000;9:169. 

70. Bohm JO, Botha CA, Hemmer W, Roser D, Starck C,Blumenstock G, Rein JG. The Ross      operation as a combined procedure and in complicated cases—is there an increased risk?      Thorac Cardiovasc Surg. 2001;49:300-5. 

71. Gauthier SC, Barton JG, Lane MM, Elkins RC. Pulmonary autografts in patients with severe left      ventricular dysfunction. Ann Thorac Surg. 2003;76:689-93. 

72. Deleon SY, Quinones JA, Vitullo DA, Hofstra J, Fisher EA, Gamponia R, Torres L, Lopez 
     W, Zamora R. Semilunar valve switch in aortic insufficiency. Eur J Cardiothorac Surg.      1995;9:631-5. 

73. Chang JP, Kao CL, Hsieh MJ. Double-switch Ross procedure. Ann Thorac Surg.      2002;73:1988-9.

74. Simon P, Kasimir MT, Seebacher G, Weigel G, Ullrich R, Salzer-Muhar U, Rieder E, Wolner E.      Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients.      Eur J Cardiothorac Surg. 2003;23:1002-6; discussion 1006. 

75. Notzold A, Huppe M, Schmidtke C, Blomer P, Uhlig T, Sievers HH. Quality of life in aortic valve      replacement: pulmonary autografts versus mechanical prostheses. J Am Coll Cardiol.      2001;37:1963-6.

HUMOR IN EGYPT