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J Thorac Cardiovasc Surg 2000;120:148-155
© 2000 The American Association for Thoracic Surgery

SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE

Pulmonary homograftShould it be used in the aortic position?

From Cardiothoracic Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Address for reprints: A. Sampath Kumar, MCh, Professor, Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India (E-mail: askumar{at}medinst.ernet.in ).

	Abstract

Top Abstract Introduction Patients and methods Results Discussion References

 
Objective: Retrospective analysis was performed to determine the suitability of pulmonary homograft as an aortic valve substitute.
Methods: From January 1994 through June 1999, 147 patients (mean age, 32.2 ± 17.3 years) underwent aortic valve replacement with either an aortic homograft (group 1: n = 103, 25 fresh antibiotic preserved and 78 cryopreserved) or a pulmonary homograft (group 2: n = 44, 11 antibiotic preserved and 33 cryopreserved). In group 1 a scalloped subcoronary technique was used in 64 patients, and a root replacement technique was used in 39 patients. In group 2 the scalloped subcoronary technique was used in 34 patients, and the root replacement technique was used in 10 patients.
Results: There were 131 operative survivors (group 1 = 91; group 2 = 40). Follow-up ranged from 2 to 62 months. In group 1 none of the patients had significant aortic regurgitation during the hospital stay. Three patients (all having undergone the scalloped subcoronary technique) had moderate aortic regurgitation after 6 to 32 months. In group 2, 10 patients (9 having undergone the scalloped subcoronary technique and 1 having undergone the root replacement technique) developed significant regurgitation: 2 intraoperatively, 5 in the early postoperative period before discharge from the hospital, and 3 during late follow-up 6 to 12 months postoperatively. Among the various risk factors analyzed for overall homograft failure, use of a pulmonary homograft was the single independent predictor of valve failure (odds ratio, 8.6; 95% confidence interval, 1.9-39; P = .006).
Conclusion: Pulmonary homograft, when inserted by means of a scalloped subcoronary technique, is not a suitable aortic valve substitute.

	Introduction

Top Abstract Introduction Patients and methods Results Discussion References

 
With reports of excellent results, the suitability of aortic valve replacement with an aortic valve homograft is well established. ^1-3 However, limited availability of the aortic homografts is an important factor for their restricted use. Pulmonary homograft was considered an alternative substitute to the diseased aortic valve, ⁴ but its use was abandoned after initial trials. ^5,6 Considering the excellent long-term results of pulmonary autografts in the aortic position, ^7,8 which are further supported by the experienced work showing minimal differences between pulmonary and aortic homografts, ⁹ and considering that the pulmonary valve can withstand the higher mechanical stress in systemic circulation, ¹⁰ investigators had a renewed interest in pulmonary homografts. ^11-20 However, the use of pulmonary homografts remained in dispute because various investigators reported contrasting results. We started using pulmonary homografts for aortic valve replacement in 1994, and in the present retrospective study we analyze our results to ascertain their suitability.

	Patients and methods

Top Abstract Introduction Patients and methods Results Discussion References

 
Patients
A total of 147 patients (101 male subjects) with an age range from 5 to 68 years (mean, 32.2 ± 17.3 years) underwent aortic valve replacement with either an aortic (group 1, n = 103) or pulmonary homograft (group 2, n = 44). The causes of aortic valve disease and associated lesions are shown in Tables I and II. All the patients were assigned to New York Heart Association (NYHA) class III or IV, and 26 patients had frank congestive heart failure.

Homograft preparation and preservation
The majority of the homografts (n = 141) were obtained from cadaveric donors. Six homografts were procured either from cardiac transplant recipients or from multiorgan donors not suitable for cardiac transplantation. The donor age ranged from 15 to 48 years. From cadaveric donors, hearts were procured within 24 hours of death, and valves were dissected under sterile conditions. Homografts were treated with antibiotic solution ²¹ for 48 hours at 4°C. In initial experience, antibiotic-preserved homografts were used directly within 40 days. In the latter part of our experience, the homografts were cryopreserved in a preservative solution consisting of RPMI-1640 tissue culture medium (Roswell Park Memorial Institute tissue culture medium 1640) with 10% fetal calf serum and 10% dimethylsulfoxide. After sterile packaging, the homografts were frozen gradually (–1°C/min) up to –80°C and then were stored in the vapor phase of liquid nitrogen at a temperature between –150°C and –190°C.

Surgical technique
Intraoperative transesophageal echocardiography was performed in all the patients and, depending on aortic root diameter, an appropriately sized homograft was selected. Patients with an aortic root diameter greater than 30 mm received a prosthetic valve. A standard moderately hypothermic or normothermic cardiopulmonary bypass with antegrade, cold, hyperkalemic blood cardioplegia was used in all the cases.

Among patients in group 1, in 64 patients a scalloped subcoronary implantation technique, as described by Ross, ²² was used. In 35 patients the root replacement technique of Elkins ²³ was used. In 4 patients both the diseased aortic valve and the ascending aorta were replaced by a valved homograft conduit. Among patients in group 2, the scalloped subcoronary technique was used in 34 patients, the root replacement technique was used in 9 patients, and a valved homograft conduit was used in 1 patient. For the purpose of analysis, patients in whom a valved homograft conduit was used were included in the root replacement group. In group 1, 25 patients received an antibiotic-preserved valve, and 78 patients received a cryopreserved valve. In group 2, 11 patients received an antibiotic-preserved homograft, and 33 patients received a cryopreserved homograft. In 73 patients 81 additional procedures were performed (Table III).

Follow-up and assessment of valve function
A transthoracic echocardiographic evaluation was carried out 5 to 7 days postoperatively before discharge from the hospital. Subsequently, patients were followed up in the outpatient department, and transthoracic-transesophageal echocardiography was performed 1, 3, and 6 months postoperatively and then at every 6 months. On echocardiography, aortic regurgitation was graded according to published criteria. ²⁴ Significant aortic regurgitation was considered with aortic regurgitation of grade III or IV severity. Valve-related events were reported as per prescribed guidelines. ²⁵

Statistical analysis
Continuous or interval-related variables were expressed as mean values ± SD. Categoric variables were expressed as percentages. Groups were compared by the ² and Student t tests. Actuarial estimates have been calculated by using the Kaplan-Meier technique. ²⁶

The incidence of homograft failure was examined in relation to a variety of variables (Appendix I). The native anulus sizes and homograft sizes were also categorized (ie, <25 mm and 25 mm). Crude relative risks (RRs) with 95% confidence intervals (CIs) were computed. Logistic regression models based on the generalized estimating equations described by Liang and Zeger ²⁷ were used to generate adjusted odds ratios as estimates of adjusted RRs with appropriate 95% CIs. Variables were included in the final model for adjustment if their presence in the logistic models altered the crude RR by at least 10%, except for age, year of surgery, cardiopulmonary bypass time, and aortic crossclamp times, which were included in all models. Statistical analysis was performed with the use of the SAS system (SAS, Inc, Cary, NC).

	Results

Top Abstract Introduction Patients and methods Results Discussion References

 
Early results
Early mortality
In group 1, there were 12 early deaths (12%). Cause of death included low-output syndrome (n = 4), intractable ventricular arrhythmia (n = 2), progressive left ventricular dysfunction (n = 3), infective endocarditis (n = 2), and catastrophic hemorrhage (n = 1). In group 2, 4 (9%) patients died during the hospital stay, and the causes included low-output syndrome (n = 1), ventricular arrhythmia (n = 1), infective endocarditis (n = 1), and progressive left ventricular dysfunction (n = 1).

Survivors
Among survivors, 91 (69%) patients received an aortic homograft (23 antibiotic-preserved and 68 cryopreserved homografts), and 40 (31%) patients received a pulmonary homograft (10 antibiotic-preserved and 30 cryopreserved homografts). Profiles of these patients are shown in Table IV.

Two patients who underwent aortic valve replacement with a cryopreserved pulmonary homograft placed by means of a scalloped subcoronary technique had significant aortic regurgitation intraoperatively, as detected by transesophageal echocardiography. In both patients the homograft was replaced with a mechanical prosthesis. In addition, 2 more patients (patient 5 and 7, Table V) showed signs of mild aortic regurgitation on intraoperative transesophageal echocardiography. In the remaining patients there was no aortic regurgitation.

Late results
Follow-up ranged from 2 to 62 months (mean follow-up: group 1, 24.5 ± 13.2 months; group 2, 23.4 ± 12.9 months) and was 97% complete.

Late mortality
In group 1 there were 3 (3%) late deaths. Two patients died 3 and 5 months postoperatively as a result of Aspergillus -induced endocarditis. Another patient died as a result of progressive left ventricular dysfunction after 24 months.

There were 4 (9%) late deaths in group 2. One patient (patient 1, Table V) died after 2 months as a result of congestive heart failure. Mediastinitis with secondary hemorrhage was the cause of death in 1 patient. Endocarditis (Aspergillus -induced endocarditis in 1, and Staphylococcus aureus –induced endocarditis in the other) was the cause of late mortality in 2 patients.

Valve-related events and clinical status
There were 3 reoperations. Two patients (1 in group 1 and 1 in group 2) were reoperated on for fungal endocarditis (Aspergillus) 6 and 5 months postoperatively, respectively. Both the patients died as a result of overwhelming fungal infection.

One patient (patient 5, Table V) developed severe aortic regurgitation after 6 months and was reoperated on after 18 months. The pulmonary homograft was replaced with a mechanical prosthesis. At reoperation, valve cusps were found to be thin and transparent. There was no coaptation with each other. All the cusps were intact. Microscopically, the endothelial and mesenchymal cells were characteristically absent, and only the fibrous skeleton of the valve was left in situ.

Clinically, 102 patients are currently in NYHA class I, and 12 are in class II (left ventricular dysfunction in 8, significant mitral regurgitation in 2, and significant aortic regurgitation in 2). Six patients are in NYHA class III (left ventricular dysfunction in 5 and severe mitral regurgitation in 1).

Valve function
In patients with moderate aortic regurgitation at discharge, the severity increased, and 4 of them had severe aortic regurgitation over a period of 2 to 6 months (1 underwent a second operation and 1 died). In 1 patient (patient 6, Table V) the degree of aortic regurgitation remained the same after a follow-up of 18 months.

An additional 6 patients (3 in group 1 and 3 in group 2) had significant aortic regurgitation over a follow-up of 6 to 36 months. Profiles of these patients are shown in Table VI. Two of these patients (patients 3 and 5, Table VI) had mild aortic regurgitation at the time of discharge.

View larger version (32K): [in this window] [in a new window]   Fig. 1. Probability of freedom from significant aortic regurgitation (Kaplan-Meier) in operative survivors who either received an aortic or a pulmonary homograft.

	Discussion

Top Abstract Introduction Patients and methods Results Discussion References

Investigators have found that the ultrastructure of the pulmonary homograft cusps and that of the aortic homograft cusps is the same, with no substantial ultrastructural difference. ^9,15 Although the pulmonary leaflets are thinner than the aortic leaflets, with a lesser content of elastic tissue in the ventricular layer, the ultimate tensile strength was similar for both the aortic and pulmonary valves. ¹⁵ Gorczynski and colleagues ¹⁰ have also demonstrated that breaking strain for the aortic and pulmonary valve leaflets is similar because even though the pulmonary leaflets are thinner, they do have greater tensile strength than the aortic leaflets. Pragliola and colleagues ¹⁷ have further demonstrated a larger coapting surface with a pulmonary valve than with an aortic valve. Despite these favorable morphologic and mechanical characteristics, investigators ^18,28 were reluctant to use pulmonary valves in the systemic circulation because of concern about the durability of the pulmonary structures subjected to systemic pressure. Although both clinical and experimental studies ^7,8,10 have shown the suitability of the pulmonary autografts in systemic circulation, the results could not be reproduced with the pulmonary homografts. Lack of antigenicity and absolute vitality of the autograft may be the chief contributors to the excellent results obtained by use of an autograft. However, another significant difference appears to be the use of different techniques for insertion of a pulmonary autograft and a pulmonary homograft. In recent decades, the root replacement technique is the preferred technique for autograft insertion, whereas most of the investigators have used either a scalloped subcoronary technique or intra-aortic cylinder technique for pulmonary homograft insertion.

Similar to the experience of others, ^14,15,17,20 we also had a high failure rate with pulmonary homografts inserted by means of a scalloped subcoronary technique. There were fewer failures when a root replacement technique was used, which was also evidenced by others. ¹⁷ We believe that because of the delicate and frail structure of the pulmonary homograft, it is very difficult to maintain the normal geometry of the pulmonary homograft during intra-aortic implantation, by using either the scalloped subcoronary or cylinder technique. The same belief is shared by others. ^17,20 This is evident from early failures of implanted pulmonary homografts in our experience and the experience of other investigators. ^4,15-20 In most of these reports ^4,15-20,29 either prolapse of one of the cusps or central regurgitation as a result of altered geometry was responsible for the failure of the pulmonary homograft.

Besides early failure, 3 of our patients who had received a pulmonary homograft had late valve failure. Two of these (patients 3 and 5, Table VI) had mild aortic regurgitation at the time of discharge. Thus these failures may also be considered results of the altered geometry of the homograft, leading to progressive aortic regurgitation. Other investigators have found intrinsic valve failure in the form of cusp rupture or cusp perforation as a cause of late homograft failure. ^5,20,30 Although pulmonary valves are identical to aortic valves in respect to ultrastructural and mechanical qualities, intrinsic structural failure is reported more commonly and after a shorter interval with a pulmonary homograft. Mair and colleagues ²⁰ postulate that because of the delicate nature of the pulmonary homograft, minor alterations in the geometry of the valve do occur at the time of intra-aortic implantation. These changes are so subtle that they are overlooked easily and may not necessarily produce graft incompetence in the early phase but lead to minimal unphysiologic stress to the cusps. This minimal unphysiologic stress, in a subsequent time course, can cause material fatigue and, consequently, structural failure of the valve.

The size of the used homograft is another important consideration. Because the pulmonary homografts are inherently larger than the aortic homografts, they might be selected for implantation in the large, often dilated anulus, the pathology of which would favor continued dilatation and early homograft failure. Two of our patients (patients 5 and 7, Table V) had a large anulus (28 and 30 mm, respectively), and homografts with one size smaller than the aortic root were inserted, as is our practice during insertion of an aortic homograft. Both these homografts failed as a result of central incompetence. Others ^11,15 have suggested a pulmonary homograft slightly larger than the aortic root to counteract this. They believe that minor changes in homograft geometry at the time of insertion are neutralized by the choice of a large homograft due to availability of a larger coaptation surface. Another option is reducing and remodeling the aortic anulus ^31-33 at the time of implantation of the homograft. However, we believe that in patients with a large aortic anulus, pulmonary homograft valve should not be used, and if required, a root replacement technique with a homograft slightly larger than the native root is a better option in such conditions.

To conclude, we believe that a pulmonary homograft, when inserted by means of a scalloped subcoronary technique, is not a suitable aortic valve substitute. Although the root replacement technique appears safe, a larger and longer study is required to judge its suitability.

	Acknowledgments

	References

Top Abstract Introduction Patients and methods Results Discussion References

 

1. O’Brein MF, Stafford EG, Gardner MAH, et al. A comparison of aortic valve replacement with viable cryopreserved and fresh allograft valves, with a note on chromosomal studies. J Thorac Cardiovasc Surg 1987;94:812-23. [Abstract]
   
2. Barratt-Boyes BG, Roche AHG, Subramanyan R, Premberton JR, Whitlock RML. Long term follow-up of patients with antibiotic sterilized aortic homograft valve inserted freehand in the aortic position. Circulation 1987;75:768-75. [Abstract/Free Full Text]
   
3. Kirklin JK, Smith D, Novick W, et al. Long-term function of cryoperserved aortic homografts: a ten-year study. J Thorac Cardiovasc Surg 1993;106:154-66. [Abstract]
   
4. Manhas DR, Rittenhouse EA, Mohri H, Marendino KA. Aortic valve replacement with a pulmonic valve homograft: a report of 9 cases. J Thorac Cardiovasc Surg 1970;59:432-7. [Medline]
   
5. O’Brien MF. In discussion of Mair et al.²⁰
   
6. Yacoub MH. In discussion of Mair et al.¹⁴
   
7. Ross D, Jackson M, Davies J. Pulmonary antograft-aortic valve replacement: long term results. J Card Surg 1991;6(Suppl 4):529-33. [Medline]
   
8. Ross DN, Jackson M, Davis J. The pulmonary autograft: a permanent aortic valve. Eur J Cardiothorac Surg 1992;6:113-7. [Abstract]
   
9. Livi U, Abdulla AK, Parker R, Olsen EJ, Ross DN. Viability and morphology of aortic and pulmonary homografts. J Thorac Cardiovasc Surg 1987;93:755-60. [Abstract]
   
10. Gorczynski A, Trenker M, Anisimowicz L, et al. Biomechanics of the pulmonary autograft valve in the aortic position. Thorax 1982;37:535-9. [Abstract]
    
11. Lupinetti FM, Lemmer JH, Ferguson DW, Stanford W, Behrendt DM. Aortic valve replacement with pulmonary or aortic valve allografts. Circulation 1991;84(Suppl):III-89-93.
    
12. Konertz W, Tandler R, Hasfeld M, Fahrenkamp A, Breithardt G, Schled HH. Aortic valve replacement with cryopreserved pulmonary allograft. J Card Surg 1994;9:43-9. [Medline]
    
13. Mair R, Harringer W, Gross C, Hartl P, Wimmer-Greinecker G, Brucke P. Early results of cryopreserved pulmonary allografts as aortic valve substitude. Eur J Cardiothorac Surg 1992;6:485-9. [Abstract]
    
14. Mair R, Harringer W, Wimmer-Greinecker G, et al. Aortic valve replacement with cryopreserved pulmonary allografts: five years’ follow-up. Ann Thorac Surg 1995;60:S185-5.
    
15. Gerosa G, Ross DN, Brucke PE, et al. Aortic valve replacement with pulmonary homografts: early experience. J Thorac Cardiovasc Surg 1994;107:424-37. [Abstract/Free Full Text]
    
16. Konertz W, Tandler R, Hasfeld M, Fahrenkamp A, Breithardt G, Schled HH. Aortic valve replacement with cryopreserved pulmonary allograft. J Card Surg 1994;9:43-9.
    
17. Pragliola C, Pennestri F, Manasse E, Marchetti C, Gaudino M, Possati GF. The use of pulmonary allografts for aortic valve replacement. J Cardiovasc Surg 1996;37:603-7. [Medline]
    
18. McCarthy JF, Subbareddy K, Dervan PA, Wood AE. Is use of the pulmonary valve allograft justified as an aortic valve substitude? Eur J Cardiothorac Surg 1996;10:105-9. [Abstract]
    
19. Gaudino M, Van-Geldorp T, Daenen W, Kalmar P, Goffin Y. Are pulmonary homografts subjected to pulmonary hypertension more appropriate for aortic valve replacement than normal pulmonary homografts? Results of echocardiography in a multicentric study. Eur J Cardiothorac Surg 1997;11:676-81. [Abstract]
    
20. Mair R, Peschl F, Gross C, Klima U, Hinterreiter H, Bruecke P. The pulmonary homografts as aortic valve substitute: 7 years’ follow-up. Eur J Cardiothorac Surg 1997;11:910-6. [Abstract]
    
21. Kirklin JW, Barratt-Boyes BG. Morphology, diagnostic criteria, natural history, techniques, results and indications. In: Kirklin JW, Barratt-Boyes BG, editors. Cardiac surgery. 2nd ed. New York: Churchill Livingstone; 1993. p. 561.
    
22. Ross D. Technique of aortic valve replacement with a homograft: orthotopic replacement. Ann Thorac Surg 1991;52:154-6. [Abstract]
    
23. Oury JH, Angell WW, Eddy AC, et al. Pulmonary autograft: past, present and future. J Heart Valve Dis 1993;3:365-75.
    
24. Perry GJ, Helmeke F, Nanda MC, Byard C, Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol 1987;9:952-9. [Abstract]
    
25. Edmunds LH, Clark RE, Cohn LH, Grunkemeier GL, Miller C, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. Ann Thorac Surg 1996;62:9325.
    
26. Kaplan EL, Meier P. Nonparameteric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
    
27. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13-22. [Abstract/Free Full Text]
    
28. Barratt-Boyes BG. In discussion of Gerosa et al.¹⁵
    
29. Pomar J. In discussion of Mair et al.²⁰
    
30. Von Geldorp T. In discussion of Mair et al.²⁰
    
31. Kirklin JW, Barratt-Boyes BG. Tailoring of the large aortic root. In: Kirklin JW, Barratt-Boyes BG, editors. Cardiac surgery. 2nd ed. New York: Churchill Livingstone; 1993. p. 555.
    
32. David TE, Feindel CM, Bose J. Repair of the aortic valve in patients with aortic insufficiency and aortic root aneurysm. J Thorac Cardiovasc Surg 1995;109:345-52. [Abstract/Free Full Text]
    
33. Duran C, Kumar N, Gometza B, Al Halees Z. Indications and limitations of aortic valve reconstruction. Ann Thorac Surg 1991;52:447-54. [Abstract]
    

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