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J Thorac Cardiovasc Surg 1999;118:483-490
© 1999 Mosby, Inc.


SURGERY FOR ACQUIRED CARDIOVASCULAR DISEASE

PULMONARY AUTOGRAFT: SHOULD IT BE USED IN YOUNG PATIENTS WITH RHEUMATIC DISEASE?

Shiv Kumar Choudhary, MCha, Alok Mathur, MSa, Rajesh Sharma, MCha, Anita Saxena, DMb, Prem Chopra, MDc, Ruma Roy, MDc, A. Sampath Kumar, MCha

From the Department of Cardiothoracic and Vascular Surgery,a Department of Cardiology,b and the Department of Pathology,c All India Institute of Medical Sciences, New Delhi, India.

Address for reprints: A. Sampath Kumar, Professor, Department of Cardiothoracic and Vascular Surgery, All India Insitute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 
Background: Although pulmonary autograft is being increasingly used to replace the diseased aortic valve with excellent long-term results, its use in the population with rheumatiic disease still needs careful evaluation.
Patients and methods: From October 1993 through March 1998, 102 patients underwent aortic valve replacement with a pulmonary autograft (Ross procedure). The mean age was 27.9 ± 4.2 years (range, 0.8-56 years). The cause was rheumatic disease in 75 patients (73%), bicuspid aortic valve in 26 patients (26%), and myxomatous aortoarteritis in 1 patient (1%). The root replacement technique was used in all. In addition, 31 patients had 33 associated procedures: mitral valve repair (n = 15 patients), open mitral commissurotomy (n = 15 patients), tricuspid repair (n = 2 patients), and homograft mitral valve replacement (n = 1 patient).
Results: Operative mortality was 6.9% (7 patients). Late mortality was 7.8% (8 patients). Follow-up ranged from 1 to 60 months (mean, 25.3 ± 15.4 months) and was 98% complete. Two patients required reoperation for failed mitral valve repair, and 2 other patients underwent reoperation for failure of both the autograft and mitral valve repair. Echocardiographic assessment showed moderate to severe aortic regurgitation in 13 patients, along with thickening of the autograft. All of these patients had rheumatic disease and were young (<30 years). Ten of these patients had undergone associated mitral valve procedure. Morphologic and histopathologic examination of explanted autografts showed features compatible with rheumatic valvulitis.
Conclusion: Pulmonary autograft is susceptible to rheumatic involvement. Young age (<30 years) and associated mitral valve disease are significant risk factors for autograft failure in patients with rheumatic disease. Use of pulmonary autograft in this subgroup of patients requires a cautious approach.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 
Since its first use by RossGo 1 in 1967, the pulmonary autograft has been considered a well-accepted option for aortic valve replacement. It offers the advantages of central laminar flow and freedom from prosthetic valve complications and side effects of anticoagulation.Go Go 2,3 Being a viable autologous transplant, the pulmonary autograft is characterized by absence of primary tissue failure and has potential for growth.Go Go 2-5 The use of a pulmonary autograft in young patients with rheumatic disease is, however, still debatable.Go Go 5-10 Though anecdotal cases of involvement of pulmonary autograft in the rheumatic process have been mentioned,Go Go 6-9 this issue remains undiscussed at large. The present study makes an effort to analyze the suitability of the pulmonary autograft as a substitute for the diseased aortic valve in patients with rheumatic disease.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 
From October 1993 through March 1998, 102 patients underwent aortic valve replacement with a pulmonary autograft (Ross procedure). The cause of the aortic valve lesion was rheumatic in 75 patients (73%) and nonrheumatic in 27 patients (27%; bicuspid aortic valve in 26 patients and myxomatous aortoarteritis in 1 patient). The demographic profile of patients is shown inTable I. Symptoms were dyspnea (93%), palpitation (39%), chest pain (37%), and congestive heart failure (69%). Most of the patients (82%) were in New York Heart Association class III or IV. The clinical diagnosis was severe aortic stenosis in 24 patients (24%), severe aortic regurgitation (AR) in 53 patients (52%), and combined aortic stenosis and AR in 25 patients (25%). In addition, patients with rheumatic disease had associated significant mitral stenosis (n = 16 patients), moderate to severe mitral regurgitation (n = 15 patients), and severe tricuspid regurgitation with stenosis (n = 2 patients).


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Table I. Demographic profile of patients
 
Selection criteria.
All patients less than 60 years of age undergoing aortic valve replacement were offered the option of the Ross procedure. Aortic valve replacement with a mechanical prosthesis was performed when the patient opted for it or when aortic root diameter was 30 mm or more. Other exclusion criteria for the Ross procedure included associated mitral valve disease requiring prosthetic valve replacement, emergency operation, left ventricular dysfunction, aortopulmonary mismatch, and bicuspid/regurgitant pulmonary valve. The use of the pulmonary autograft in young patients with rheumatic disease was abandoned recently as a result of our observations.

Operative technique.
Intraoperative transesophageal echocardiography was performed for all patients. Surgical procedures were performed under moderately hypothermic (28°C) cardiopulmonary bypass. Antegrade cold blood cardioplegia (4°C) and topical cooling with ice slush was used for myocardial protection. If required, the mitral valve procedure was done first before the Ross procedure was begun.

The technique of autograft harvesting and insertion was essentially the same as mentioned by Oury and associatesGo 11 and as described previously by us.Go 12 After the pulmonary artery was separated from the aorta, the pulmonary artery was opened transversely and the pulmonary valve was inspected. If found suitable, it was harvested and kept in the right ventricular cavity for further use. The diseased aortic valve was excised, and the right coronary ostium was separated as a button. The aortotomy incision was extended posteriorly on both sides to meet below the left coronary ostium. Thus the aorta was divided completely, leaving the left coronary ostium attached to a tongue of distal aortic wall. The autograft was inserted as in a root replacement. Proximally, the autograft was sutured to the aortic anulus with a triangulated running polypropylene suture. The left coronary sinus of the autograft was slit open to within 3 to 4 mm of the cusp to receive the tongue of the distal aorta containing the left coronary ostium. Distal aortic anastomosis was performed with running polypropylene suture. The right coronary button was implanted in the autograft. The right ventricle–pulmonary artery continuity was re-established with either an antibiotic preserved (n = 47 patients) or cryopreserved pulmonary/aortic homograft (n = 55 patients).

In addition, 31 patients had 33 associated procedures: open mitral commissurotomy (n = 15 patients), mitral valve repair (n = 15 patients), tricuspid valve repair (n = 2 patients), and homograft mitral valve replacement (n = 1 patient). The technique of mitral valve repair has been described earlier.Go Go 13,14

The mean aortic crossclamp and cardiopulmonary bypass times for the isolated Ross procedure were 119.3 ± 24.6 minutes (range, 84-190 minutes) and 145.8 ± 26.3 minutes (range, 123-220 minutes), respectively. The mean ischemic and bypass times for the Ross procedure combined with mitral procedure were 134.3 ± 28.5 minutes (range, 110-228) minutes) and 167.3 ± 31.4 minutes (range, 141-276 minutes), respectively.

The autograft function was assessed intraoperatively by transesophageal echocardiography and subsequently by transthoracic/transesophageal echocardiography before discharge from the hospital. Echocardiographic assessment was performed subsequently at intervals of 6 months.

None of the patients with the isolated Ross procedure received anticoagulants or antiplatelet agents. Patients who had undergone mitral valve annuloplasty with a Teflon collar received antiplatelet therapy for 6 months.

All patients under 45 years of age and with rheumatic involvement were treated with antibiotic prophylaxis to prevent recurrence of rheumatic fever, using long-acting benzathine penicillin delivered intramuscularly every 3 weeks.

Statistical analysis.
For the purpose of analysis, patients have been divided into rheumatic and nonrheumatic groups, based on the cause of the aortic lesion. All the interval/ratio parameters are expressed as mean ± standard deviation, and the categoric variables are expressed as percentages. Acturial estimates have been calculated with the Kaplan-Meier techniqueGo 15 and are reported with standard error of the estimate. Comparison of these estimates among subgroups has been performed with the Mantel-Cox (log-rank) test.Go 16 Prognostic factors for late failure have been identified by Cox’s proportional hazard model. All statistical analysis has been performed with the SPSS for Windows 6.0 software package (SPSS Inc, Chicago, Ill).


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 
Early deaths.
There were 7 early deaths (6.9%). Four of the initial 12 patients died; 3 deaths were attributed to excessive bleeding and its sequelae. After a modificationGo 17 in the operative technique in the next 90 patients, there were 3 operative deaths (3.3%), caused by myocardial dysfunction (n = 2 patients) and ventricular arrhythmias (n = 1 patient).

Early echocardiographic results.
In all patients, intraoperative transesophageal echocardiography revealed no or trivial AR. Two patients had mild (2/4+) mitral regurgitation. Transthoracic echocardiography performed before discharge from the hospital showed mild (2/4+) AR in 1 patient.

Late deaths.
There were 8 late deaths (7.8%). Infective endocarditis was the cause of death in 4 patients (2 patients underwent reoperation). One patient, who had undergone associated homograft mitral valve replacement, died after 6 months of mitral homograft failure. In another patient, the initial mitral valve repair failed; at reoperation, a partial mitral homograft replacement was performed. However, the mitral homograft failed and the patient died after 2 months. In an additional 2 patients (patients 1 and 13, Table II), the autograft failed and the patients died of congestive heart failure 24 and 5 months after the operation, respectively.


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Table II. Demographic and clinical profile of patients with significant AR
 
Reoperation.
Five patients required exploration for excessive hemorrhage in the immediate postoperative period. Two patients required an operation for fungal endocarditis. Both patients died. In 2 patients, mitral valve repair failed after 26 months and 31 months, respectively. In the first patient, a partial mitral valve replacement with cryopreserved homograft was performed, but the patient died after 3 months. In the other patient, the mitral valve was replaced with a prosthetic valve. In addition, in 2 other patients (patients 2 and 4,Table IIGo), autograft and associated mitral valve repair failed after 12 months and 24 months. In both the patients, aortic and mitral valves were replaced with prosthetic valves. Both the patients survived and are doing well after 30 months and 12 months, respectively.

Recurrent rheumatic fever.
Two boys (patients 1 and 4,Table IIGo), 11 and 13 years old, who had initially undergone the Ross procedure associated with mitral valve repair were admitted 8 and 12 months, respectively, after the operation with acute rheumatic activity and congestive heart failure. There was no history of joint pains in either of the patients. Erythrocyte sedimentation rate and antistreptolysin titers were raised significantly in both the cases. Both patients had experienced the development of severe AR and moderate-to-severe mitral regurgitation. The first patient had not complied with penicillin prophylaxis after the operation. The second patient was receiving regular penicillin prophylaxis. Both patients underwent decongestion and were discharged with advice for reoperation. Patient 1 died after 6 months; patient 4 underwent reoperation, and both the aortic and mitral valves were replaced with prosthetic valves.

In addition, 2 other patients (14 and 17 year olds, male) also had a history of joint pains and fever during their follow-up but did not have laboratory or clinical evidence of recurrent rheumatic activity at the time of examination.

Late echocardiographic follow-up.
Follow-up was 98% complete. Two patients in the rheumatic group were lost to follow-up. The remaining 93 patients (68 in the rheumatic group; 25 in the nonrheumatic group) underwent regular echocardiographic assessment. Follow-up ranged from 1 to 60 months (mean, 25.3-15.4 months).

Autograft function.
In the rheumatic group, 13 patients experienced the development of moderate (3/4+) or severe (4/4+) AR 8 to 48 months after the operation(Fig 1). This included the 2 patients who had recurrent rheumatic fever. In most, the significant (3-4/4+) AR developed 12 to 24 months after the operation. Two of these patients died, and 2 of the patients underwent reoperation. In addition, 7 other patients in the rheumatic group experienced the development of mild (2/4+) AR. Characteristically, all these patients were young (<30 years of age), and 10 of them also had multivalvular lesions at the time of the initial operation. Demographic and clinical profiles of patients with significant AR after operation and their echocardiographic findings are shown inTable IIGo.



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Fig. 1. Temporal occurrence of significant AR after the Ross procedure in the rheumatic group.

 
In patients with rheumatic pathogenesis, probability of normal autograft function without significant regurgitation at 60 months was 60% ± 13%(Fig 2). This was significantly less than the expected value in patients with nonrheumatic pathogenesis (60% vs 100%) (P = .04). The probability of normal autograft function was 41% ± 14% in the patients with rheumatic involvement who were less than 30 years of age. This was significantly less than that in the patients with rheumatic involvement who were over 30 years of age (41% vs 100%; P = .001).



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Fig. 2. The probability of freedom from significant AR after the Ross procedure (Kaplan-Meier).

 
Among patients who had undergone additional mitral valve procedures at the time of initial operation, 10 patients experienced autograft failure. The probability of normal autograft function in patients who had undergone an associated mitral valve procedure was 39% ± 18%, whereas it was 93% ± 4% in those who patients who had undergone an isolated Ross procedure (P = .002).

In the rheumatic group, various risk factors for late failure were analyzed separately and included age (<30 years vs >30 years), sex, chronologic order of surgery, associated mitral disease, associated tricuspid disease, previous cardiac procedure, and presence of congestive heart failure. Age less than 30 years (P = .001) and associated mitral valve disease (P = .04) were independent predictors of autograft failure. The Cox proportional hazard analysis was also used to predict the risk with age as continuous variable. The hazard function equation
h (t,xt) = ho(t) e–0.114 x age
yielded a hazard risk of 0.89 (95% confidence limit, 0.81-0.98), suggesting a progressive decrease in the risk of autograft failure with advancement of age.

Mitral valve function.
In the rheumatic group, 29 survivors who had undergone an associated mitral valve procedure, 11 patients experienced significant mitral regurgitation; 3 patients underwent mitral valve replacement with a prosthetic valve, and 1 patient underwent a partial homograft mitral valve replacement. In 1 patient, the mitral homograft was inserted initially and failed after an interval of 6 months, leading to death.

Homograft function.
Significant right-sided homograft valve dysfunction (gradient, >40 mm Hg) was present in 3 patients. In 2 patients, gradients were located at the distal pulmonary anastomosis; in 1 patient it was located at the level of valve. One additional patient experienced moderate pulmonary regurgitation. In all 4 patients, a pulmonary homograft was used. All these patients are free of symptoms.


    Morphologic features of failed autografts
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 
Echocardiographic appearance.
All the cusps of failed autografts were thickened, and the echocardiographic picture was indistinguishable from that of aortic valve with chronic rheumatic regurgitation(Fig 3). Five more patients had thickened autograft cusps although Doppler examination showed either trivial or mild (1-2/4+) AR. Besides cuspal thickening, in 2 patients with significant AR, the aortic root was dilated.



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Fig. 3. Transesophageal echocardiograms show thickening of the cusps of the autograft (arrow). A, Long axis. B, Short axis. LV, Left ventricle; AO, aorta.

 
Operative findings.
In both the patients who underwent reoperation for failed autograft, all 3 cusps of the autograft were thickened and retracted and failed to coapt. However, there was no commissural fusion or prolapse of any of the cusps. The geometry of all the aortic sinuses was maintained in both of the patients, and there was no dilatation of the aortic root.

Microscopic examination.
Microscopic examination of explanted autograft cusps revealed valvular thickening, fibrosis, and an active chronic inflammation with remarkable small vessel and intimal proliferation(Fig 4). The neovascularization was most marked near the base of the cusps. The picture was compatible with valvulitis of rheumatic involvement.



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Fig. 4. A, Photomicrograph of pulmonary autograft shows vascularization of the leaflet. There are thick- and thin-walled blood vessels. (Hematoxylin-eosin stain; original magnification x400.) B, Photomicrograph of pulmonary autograft shows thick-walled blood vessels and focal lymphomononuclear infiltrate within the valve leaflet. (Hematoxylin-eosin stain; original magnification x400.)

 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 
The pulmonary autograft is considered the most suitable alternative for the diseased aortic valve.Go Go 2-5 With the recent reports of involvement of autograft in rheumatic process, there is serious concern about its use in the rheumatic population.Go Go 8,9 Although in only a few casesGo Go 5-9 could rheumatic involvement of the autograft be demonstrated histopathologically at reoperation, progressive AR in the absence of aortic root dilatation in a patient with rheumatic heart disease strongly favors rheumatic involvement. In both of our patients who underwent reoperation, rheumatic valvulitis could be demonstrated. In addition, echocardiography of regurgitant autografts was indistinguishable from that of native regurgitant aortic valve involved in the rheumatic process. Besides the morphologic and histopathologic appearance of regurgitant autografts, the exclusive existence of failed autografts in the rheumatic group in our study also suggests the rheumatic cause as a significant risk factor for autograft failure.

What could have led to autograft failure in patients with rheumatic conditions? Obviously, in patients where rheumatic valvulitis was demonstrated at reoperation, recurrence of the rheumatic activity was the cause of autograft failure. In some of the reported cases,Go Go Go Go 5,6,8,9 there was history and laboratory evidence suggesting recurrence of rheumatic fever. Two of our patients in whom the autograft failed also had recurrent rheumatic fever. One of these patients showed evidence of rheumatic valvulitis at reoperation. In underdeveloped countries, a typical history suggestive of rheumatic fever may not always be present, and the patient may directly have features of carditis.Go 18 This was also observed in patient 2. The patient had demonstrable rheumatic valvulitis at reoperation but never gave a history suggestive of rheumatic fever after the initial Ross procedure. The involvement of the pulmonary valve in the chronic rheumatic process is rare.Go Go 19-21 Involvement in the chronic rheumatic process appears to be related to the mechanical force the valve faces during its closed state. This is the highest in the mitral valve and the lowest in the pulmonary valve. Somehow, when the pulmonary autograft is transplanted to the aortic position, it becomes susceptible to chronic rheumatic involvement. However, when there is severe pulmonary hypertension, the pulmonary valve is still free from rheumatic involvement in its native position.

In 1 of the reported cases,Go Go 5,6 recurrence of rheumatic activity was attributed to the cessation of penicillin prophylaxis. This was the case with 1 of our patients also. But another 3 of our patients who received regular prophylaxis also experienced recurrent rheumatic activity. Halees and colleaguesGo 8 have also questioned the compliance to and efficacy of penicillin prophylaxis. This may be partly due to the failure of penicillin prophylaxis as a result of higher infection rates in a malnourished population who live in very over-crowded conditions.Go Go Go 18,22,23

Characteristically, among the rheumatic group, all the patients with a failed autograft were young (<30 years of age). Because rheumatic fever is more prevalent in a younger population,Go Go Go 18,22-24 this further supports the possibility of recurrent rheumatic activity in this subgroup of patients. However, if all the failures are related to recurrent rheumatic activity, the incidence of relapse becomes unacceptably high. There may be some other mechanism by which autografts fail in patients with rheumatic etiology. It is possible that pulmonary valves that appear grossly normal at operation and echocardiographically may have been affected microscopically during recent rheumatic activity; and when subjected to higher stress in the aortic position, these valves develop pathologic changes and fail.

Most of the investigators have attributed the autograft failure mainly to technical errors during the learning curve.Go Go 25,26 This does not appear to be the case in our series. In all the patients except 1, who experienced the development of significant AR, there was no or trivial regurgitation at the time of discharge from the hospital. Only 1 patient had mild AR. It was only in the subsequent time course that these patients experienced the development of progressively significant AR. In our series, autograft failure is exclusively limited to the rheumatic population and is evenly distributed chronologically. These facts suggest that technical errors during the learning curve were not responsible for autograft failure in our patients.

We have used a root replacement technique for pulmonary autograft insertion in which a tongue of the posterior wall of the aorta with the left main coronary artery was left behind while the aorta was divided posteriorly. This tongue of aortic wall was sutured to the left pulmonary sinus. This technique carries a potential risk of altering the geometry of the sinotubular junction of the pulmonary root and may predispose to subsequent AR. In our experience, patients with both rheumatic and nonrheumatic etiology had identical technique, and thus the use of this technique could not explain the occurrence of significant AR in the patients with rheumatic etiology alone.

InvestigatorsGo Go 8,9 have found that preoperative AR is a common accompaniment to subsequent autograft failure. Although, in all our patients with a failed autograft, AR was the predominant physiologic lesion, we failed to attach any significance to it. This may be because of the fact that in our experience all young patients with rheumatic pathogenesis had predominant AR.

Coexisting mitral valve pathologic feature is a serious concern in the rheumatic population. Associated mitral valve disease that requires a surgical procedure at the time of the initial procedure was a strong predictor of autograft failure. Among 29 survivors who underwent an associated mitral valve procedure, 10 patients (35%) experienced autograft failure. Similarly, of 13 patients with a failed autograft, 10 patients (76%) had undergone a concomitant mitral valve procedure. The high incidence of failed mitral valve procedure in these patients, in itself, is an important cause of morbidity and reoperation and thus limits the usefulness of the Ross procedure in this subgroup.

Considering the poor results in young patients with rheumatic etiology (<30 years of age), we have abandoned the use of the Ross procedure in this subgroup of patients. Similarly, coexisting mitral disease, usually present in the younger subgroup, also disfavors the Ross procedure.


    Acknowledgments
 
We thank Mr Rajvir Singh, MSc (Stat), for statistical analysis of the work.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Morphologic features of failed...
 Discussion
 References
 

  1. Ross DN. Replacement of the aortic and mitral valve with pulmonary autograft. Lancet 1967;2:956-8.[Medline]
  2. Gerosa G, Mckay R, Ross DN. Replacement of the aortic valve or root with a pulmonary autograft in children. Ann Thorac Surg 1991;51:424-9.[Abstract]
  3. Ross DN, Jackson M, Davies J. The pulmonary autograft: a permanent aortic valve. Eur J Cardiothorac Surg 1992;6:113-7.[Abstract]
  4. Elkins RC, Santangelo K, Randolph JD, et al. Pulmonary autograft replacement in children: The ideal solution? Ann Surg 1992;216:363-71.[Medline]
  5. Schoof PH, Cromme-Dijkhus AH, Bogers AJJC, et al. Aortic root replacement with pulmonary autograft in children. J Thorac Cardiovasc Surg 1994;107:367-73.[Abstract/Free Full Text]
  6. DeVries H, Bogers AJJC, Schoof PH, et al. Pulmonary autograft failure caused by a relapse of rheumatic fever. Ann Thorac Surg 1994;57:750-1.[Medline]
  7. Kumar N, Prabhakar G, Gometza B, et al. The Ross procedure in young rheumatic population: early clinical and echocardiographic profile. J Heart Valve Dis 1993;2:376-9.[Medline]
  8. Halees ZA, Kumar N, Gallo R, Gometza B, Duran CMG. Pulmonary autograft for aortic valve replacement in rheumatic disease: a caveat. Ann Thorac Surg 1995;60:S172-6.
  9. Pieters FA, al-Halees Z, Zwaan FE, Hatle L. Autograft failure after the Ross operation in a rheumatic population: pre- and post-operative echocardiographic observations. J Heart Valve Dis 1996;5:404-9.[Medline]
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  13. Kumar AS, Kumar RV, Shrivastva S, Venugopal P, Sood AK, Gopinath N. Mitral valve reconstruction: early results of a modified Cooley technique. Tex Heart Inst J 1992;19:107-11.[Medline]
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  16. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Resp 1966;50:163-70.
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  21. Kumar AS, Iyer KS, Chopra P. Quadrivalvular heart disease. Int J Cardiol 1985;7:66-9.[Medline]
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  25. Gerosa G, McKay R, Davies J, Ross DN. Comparison of the aortic homograft and the pulmonary autograft for aortic valve in root replacement in children. J Thorac Cardiovasc Surg 1991;102:51-61.[Abstract]
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Received for publication Jan 29, 1999. Revisions requested March 23, 1999; revisions received April 20, 1999. Accepted for publication May 7, 1999.


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Journal Watch CardiologyHome page
Ross Procedure Inappropriate for Younger Patients with Rheumatic Heart Disease
Journal Watch Cardiology, October 14, 1999; 1999(1014): 1 - 1.
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