Autologous tissue in complex aortic valve disease.

Young patients with complex aortic valve disease involving the aortic root or ascending aorta are a challenge to manage. To use the Ross operation and realize its benefits, the operative technique must include aortic annulus reduction and fixation and replacement of ascending aortic pathology. Special techniques must be used when the cause of the complex disease is active endocarditis of the valve and aortic root. Surgical techniques that allow the use of the Ross operation in these settings and the midterm results in 84 patients are reviewed.

Decellularized human valve allografts.

BACKGROUND: Variable performance of allograft tissues in children and some adults may be linked to an immune response and could be mitigated by reducing implant antigenicity. METHODS: As endothelial and fibroblast cells are the likely source of valve antigenicity, human (CryoValve SG) and sheep pulmonary valves were decellularized using the SynerGraft treatment process. Treated valves were evaluated in vitro using histochemical, biomechanical, and hydrodynamic methods, and compared with standard cryopreserved valves. Four SynerGraft-treated and two cryopreserved sheep pulmonary valves were implanted as root replacements in the right ventricular outflow tract of growing sheep and monitored echocardiographically and histologically at 3 and 6 months. CryoValve SG human pulmonary valves were implanted in 36 patients. RESULTS: SynerGraft treatment reduced tissue antigen expression but did not alter human valve biomechanics or strength. Decellularized sheep allograft valves were functional during the implantation period, and, they became progressively recellularized with recipient cells. In humans, CryoValve SG pulmonary valves did not provoke a panel reactive antibody response. CONCLUSIONS: SynerGraft decellularization leaves the physical properties of valves unaltered and substantially diminishes antigen content. Reduction in implant cellularity enables host recellularization of the matrix, which should favorably impact long-term graft durability.

Humoral immune response to allograft valve tissue pretreated with an antigen reduction process.

The humoral immune response to allograft heart valves as measured by PRA was absent in 52 of 57 (91%) patients at 1 month and was absent in 43 of 49 (88%) at 3 months in allograft valves treated with the SynerGraft process for antigen reduction. Short-term valve function is satisfactory. This may be associated with improved durability and long-term function.

Recellularization of heart valve grafts by a process of adaptive remodeling.

The objective of this study was to investigate if function and durability of connective tissue grafts stems from in vivo revascularization and recellularization. Viability is important for durable valve performance, demonstrated by pulmonary autografts. A pattern of in vivo recellularization occurs in xenogeneic or allogeneic heart valves decellularized prior to implantation, dictated by the tissue matrix and functional biomechanics. Porcine or sheep heart valves were decellularized with the SynerGraft antigen reduction process (a common treatment process to remove all histologically demonstrable leaflet cells), and implanted as pulmonary (n = 11) or aortic valve (n = 9) replacements in sheep. Sheep allograft pulmonary valves (n = 4) were implanted as pulmonary valve replacements. Recellularization was evaluated histologically after 3, 4, 5, 6, and 11 months, with cell phenotypes identified using specific antibodies. SynerGraft heart valves were progressively recellularized beginning with an initial cellular infiltrate, and subsequent repopulation with mature interstitial cells. This process occurs in the conduit and then in the leaflet, and is associated with revascularization of the graft. Functional, fully developed fibrocytes, actively synthesizing type I procollagen (antibody probe) were present within 3 months. As the process matured cell density and distribution became similar to native valve leaflets with localization of smooth muscle actin positive cells at the ventricularis/spongiosa interface. After 11 months, leaflet explants had no detectable inflammatory cells, were as much as 80% repopulated, and had a distribution of smooth muscle actin positive cells similar to that of the natural leaflet. SynerGraft- treated heart valve implants are repopulated by a process typical of adaptive remodeling following implantation. This antigen reduction treatment is the first successful tissue engineering effort obtaining an implant with mature recipient cells capable of matrix protein synthesis. Normal early valve function and durability is maintained.

Ross operation in children: late results.

BACKGROUND AND AIM OF THE STUDY: Although the Ross operation has become the accepted aortic valve replacement in children, the long-term fate of the pulmonary autograft valve remains unknown. To assess mid-term and late results of autograft valve durability, patient survival and valve-related morbidity, a retrospective review of patients (age range: 3 days to 17 years) having a Ross operation between November 1986 and May 2001 were reviewed. METHODS: Medical records and patient contacts with all but two of 167 current survivors of 178 consecutive patients having an aortic valve replacement as a Ross operation have been completed during the past two years. The most recent echocardiographic evaluation was reviewed for autograft valve and homograft valve function. RESULTS: Operative mortality was 4.5% (8/178), with three late deaths (two were non-valve-related) for an actuarial survival of 92+/-3% at 12 years. Actuarial freedom from autograft valve degeneration (reoperation or severe insufficiency of autograft valve or valve-related death) was 90+/-4% at 12 years. Autograft valve degeneration was not affected by technique of insertion (141 root replacement, 37 intra-aortic), aortic valve morphology (157 bicuspid or unicuspid, 26 tricuspid), or age at operation. Autograft valve degeneration was worse in patients with a primary lesion of aortic insufficiency than in those with aortic stenosis (p = 0.03). Autograft valve reoperation was required in 12 patients, with autograft valve replacement in seven. Actuarial freedom from autograft replacement was 93+/-3% at 12 years. Homograft valve replacement was required in seven patients, with actuarial freedom from replacement of 90+/-4% at 12 years. Eight additional patients have homograft valve obstruction (gradient > or =50 mmHg), and seven have severe pulmonary insufficiency. CONCLUSION: Survival and freedom from aortic valve replacement are excellent in children. Homograft valve late function remains a concern, and efforts to improve homograft durability should be encouraged.

Aortic valve replacement: comparison of late survival between autografts and homografts.

BACKGROUND: Autografts (AG) and homografts (HG) are currently considered the best choices for replacement of the diseased aortic valve in young adults, although few data exist comparing their late outcome. Nonhomogeneous populations and evolving operative techniques confound existing comparisons. METHODS: To help clarify these issues, we reviewed our results with 238 hospital survivors (aged 17 to 82 years) undergoing operation between 1986 and 1999. All operations were done as root replacements, and patients needing concomitant valve replacement were excluded. RESULTS: Mean age of the 145 AGs and 93 HGs was 35 +/- 13 years and 49 +/- 17 years, respectively (p < 0.001). Previous aortic valve replacement was done in 12 (8%) AG and 32 (34%) HG patients (p = 0.001), and active endocarditis was present at time of current operation in 10 (7%) AG and 25 (27%) HG patients (p = 0.001). Maximum follow-up was 12.2 years for AGs and 12.8 years for HGs. Late survival at 10 years was 77% +/- 11% for AGs and 67% +/- 9% for HGs (p = 0.13). Freedom from AG or HG degeneration at 10 years was 97% +/- 2% and 79% +/- 10% (p = 0.63). Freedom from valve-related complications at 10 years was 73% +/- 10% and 64% +/- 10% (p = 0.93), respectively. Freedom from all reoperations at 10 years was 88% +/- 5% for AG and 72% +/- 11% for HG (p = 0.67). CONCLUSIONS: Autografts and HGs have comparable late survival. The incidence of valve degeneration is low for both AG and HG up to about 8 years at which point there may be a trend toward an advantage for AG over the HG, suggesting benefit for the younger patient.

Body surface area as a predictor of aortic and pulmonary valve diameter.

BACKGROUND: Predicting cardiac valve size from noncardiac anatomic measurements would benefit pediatric cardiologists, adult cardiologists, and cardiac surgeons in a number of decision-making situations. Previous studies correlating valve size with body size have been generated with the use of fixed autopsy specimens, angiography, and echocardiography, but primarily in the young. This study examines the relation of body surface area to measurements of the left ventricular-aortic junction (aortic valve anulus diameter) and the right ventricular-pulmonary trunk junction (pulmonary valve anulus diameter) in 6801 hearts across a wide spectrum of ages. METHODS: From June 1985 to October 1998, cardiac valves from 6801 donated hearts were analyzed morphologically. Donor age was newborn to 59 years (mean 31 +/- 17 years; median 32 years). Calculated body surface areas ranged from 0.18 to 3.55 m(2). Aortic (n = 4636) and pulmonary valve diameters (n = 5480) were measured from enucleated valves suitable for allograft transplantation. Mean valve sizes were computed for ranges in body surface area in 0.1-m(2) increments. RESULTS: For adult men (age >/= 17 years), the mean aortic valve diameter was 23.1 +/- 2.0 mm (n = 2214) and the mean pulmonary valve diameter was 26.2 +/- 2.3 mm (n = 2589). For adult women, the mean aortic valve diameter was 21.0 +/- 1.8 mm (n = 1156) and the mean pulmonary valve diameter was 23.9 +/- 2.2 mm (n = 1408). The mean indexed aortic valve area was 2.02 +/- 0.52 cm(2)/m(2) and the pulmonary valve area 2.65 +/- 0.52 cm(2)/m(2). Between 82% and 85% of the variability was explained by the size of the patient. Regression equations were developed both overall and separately for men and women, although the additional contribution of sex above that of body size was less than 1%. CONCLUSIONS: Aortic and pulmonary valve diameters are closely related to body size. Thus, body surface area, when used in conjunction with other clinically accepted evaluations, is a useful tool for estimating normal aortic and pulmonary valve size.

The Ross operation: a 12-year experience.

BACKGROUND: The Ross operation, originally introduced as a scalloped subcoronary implant with an 80% survival and 85% freedom from reoperation, has recently been modified to a root replacement which is now the most utilized implant technique. The mid and late results of this operative technique and comparison of intra-aortic implants and root replacement in a single institution are reported. METHODS: The records of 328 patients who had a Ross operation at the University of Oklahoma (August 1986 to July 1998) were reviewed to assess operative technique and patient-related factors on survival, autograft valve function, homograft valve function, valve-related complications, and need for reoperation. RESULTS: Operative survival was 95.4% with an actuarial survival of 89% +/- 5% at 8 years. Freedom from replacement of the pulmonary autograft was 94% +/- 3% at 8 years, freedom from reoperation on the pulmonary homograft was 90% +/- 4% at 8 years, and freedom from autograft valve reoperation or dysfunction (3+ autograft valve insufficiency) was 83% +/- 6% at 9 years. The incidence of autograft valve reoperation and late autograft valve dysfunction was decreased by root replacement. Annulus reduction and fixation improved early results in patients with aortic insufficiency and annulus dilatation. CONCLUSIONS: Early results have been excellent, as the development of late autograft valve dysfunction or dilatation has been rare. The excellent hemodynamic results with a limited incidence of reoperation and replacement of the autograft valve justify its continued use.

Normalization of left ventricular dimensions after Ross operation with aortic annular reduction.

BACKGROUND: Fifty-seven patients (August 1995 to November 1998) with a dysplastic dilated aortic root, a relative contraindication to the Ross operation, received an extended Ross operation with aortic annulus reduction and external cuff fixation (age 14-54 years). To assess the efficacy of these operations, echocardiographic assessment of autograft valve function and left ventricular function and dimensions were reviewed. METHODS: Preoperative and postoperative assessment of 27 patients with aortic insufficiency (AI group) and 30 patients with aortic stenosis (>20 mm Hg peak gradient) and aortic insufficiency (AS group) were compared. Aortic annulus size, valvular gradient, valve insufficiency, left ventricular dimensions at end-systole and end-diastole, left ventricular fractional shortening, and left ventricular mass were assessed. RESULTS: There was one late death. Aortic annulus size, degree of AI, left ventricular internal dimensions, and left ventricular mass were all significantly reduced (p<0.05) postoperatively in the AI group. Mean peak pressure gradients for this group were 6.8+/-6.7 mm Hg before operation and 8.7+/-6.4 mm Hg at 1 year after operation. Peak pressure gradient, aortic annulus size, degree of AI, left ventricular internal dimensions, and left ventricular mass were significantly reduced (p<0.05) in the AS group. Mean fractional shortening was within normal limits pre- and postoperatively for both groups. CONCLUSIONS: Regression of left ventricular dilatation and hypertrophy, excellent autograft valve function, and survival suggest that this modification of the Ross operation may be offered to patients with a dysplastic aortic root requiring aortic valve replacement.

Pulmonary autograft root replacement: mid-term results.

BACKGROUND AND AIMS OF THE STUDY: The Ross operation was first performed as a root replacement in 1974, and only limited mid- and long-term results assessing durability and adaptation of the pulmonary root to systemic pressures are available. We reviewed our experience to assess function of the autograft valve and the autograft pulmonary root, and its adaptation to systemic pressures. METHODS: A total of 244 operative survivors (median age 22 years; range: 1 week to 62 years) were reviewed. Clinical follow up (within one year) was available on 98% of cases, and echocardiographic assessment within one year on 93%. Autograft and homograft valve function, aortic annulus diameter, autograft root sinus diameter and ascending aortic diameter were determined on the most recent echocardiogram. RESULTS: Actuarial freedom from autograft valve degeneration (non-endocarditis autograft valve reoperation or severe autograft valve insufficiency or valve-related death) was 95 +/- 3% at 5 years and 93 +/-4% at 10 years. Actuarial freedom from all valve-related complications (autograft valve degeneration, autograft valve reoperation, homograft valve reoperation or valve-related death) was 90 +/- 4% at 5 years and 83 +/-6% at 10 years. Actuarial freedom from autograft valve replacement was 98 +/- 2% at 5 years and 96 +/- 4% at 10 years. Actuarial survival rate was 98 +/- 2% at 5 years and 86 +/- 9% at 10 years. Aneurysmal dilation of the autograft root occurred in two patients; this was not associated with autograft valve degeneration, and these patients were followed closely. CONCLUSIONS: At 10 years, the Ross root replacement has a low risk of valve degeneration, valve-related complications and autograft valve replacement, and patient survival is excellent. Autograft valve reoperation and homograft valve reoperation have been the only significant late valve-related complications. Techniques to reduce autograft reoperation have been introduced, and hopefully methods to mediate the immunological response to the homograft valve will reduce the incidence of failure. Significant aneurysmal dilation of the pulmonary autograft root is rare.

Advantage of autograft and homograft valve replacement for complex aortic valve endocarditis.

BACKGROUND: There are advantages to using homografts and autografts as aortic valve replacements, particularly in patients with infective endocarditis. To better define these advantages, we reviewed our 13-year experience with the surgical management of infective endocarditis involving the aortic valve and root. METHODS: From 1986 through 1998, 81 adults with aortic valve endocarditis underwent valve replacement (AVR). The mean age of the 65 men and 16 women was 44 +/- 14 years. Sixty-three (78%) patients had active endocarditis at the time of operation. Non-native valve endocarditis was present in 29 (36%) patients, in 9 of whom the infection was a recurrence. Aortic valve replacements were performed with 46 homografts (homo-AVR), 25 autografts (Ross-AVR), and 10 prosthetic valves (prosth-AVR). Among Ross-AVR and homo-AVR patients, 11 required mitral valve replacement or repair (homo-Ross DVR). Follow-up was 90% complete within 2 years of the end of the study with a mean of 3.7 +/- 3.4 years. RESULTS: Early mortality was 16% (13 of 81 patients). This was 12% (3 of 25 patients) for Ross-AVR, 17% (8 of 46 patients) for homo-AVR, and 20% (2 of 10 patients) for prosth-AVR. Overall late mortality was 10% (7 of 68 patients) with a valve-related late mortality of 7% (5 of 68 patients). Actuarial survival at 5 years was 88% +/- 9% in Ross-AVR, 69% +/- 11% in homo-AVR, and 29% +/- 22% in prosth-AVR (p = 0.03). Endocarditis recurred in 12.5% (1 of 8 patients) with prosth-AVR and 3% (2 of 60 patients) in homo-Ross AVR. CONCLUSIONS: Valve replacement in the presence of native and prosthetic endocarditis remains a formidable challenge. Autografts and homografts are the preferred replacement aortic valves for these patients even if concomitant mitral valve replacement is required, and risk of valve-related death or recurrent endocarditis is low at medium-term follow-up.

Ross procedure for ascending aortic replacement.

BACKGROUND: Patients with aortic valve disease and aneurysm or dilatation of the ascending aorta require both aortic valve replacement and treatment of their ascending aortic disease. In children and young adults, the Ross operation is preferred when the aortic valve requires replacement, but the efficacy of extending this operation to include replacement of the ascending aorta or reduction of the dilated aorta has not been tested. METHODS: We reviewed the medical records of 18 (5.9%) patients with aortic valve disease and an ascending aortic aneurysm and 26 (8.5%) patients with dilation of the ascending aorta, subgroups of 307 patients who had a Ross operation between August 1986 and February 1998. We examined operative and midterm results, including recent echocardiographic assessment of autograft valve function and ability of the autograft root and ascending aortic repair or replacement to maintain normal structural integrity. RESULTS: There was one operative death (2%) related to a perioperative stroke. Forty-two of 43 survivors have normal autograft valve function, with trace to mild autograft valve insufficiency, and one patient has moderate insufficiency at the most recent echocardiographic evaluation. None of the patients has dilatation of the autograft root or of the replaced or reduced ascending aorta. CONCLUSIONS: Early results with extension of the Ross operation to include replacement of an ascending aortic aneurysm or vertical aortoplasty for reduction of a dilated ascending aorta are excellent, with autograft valve function equal to that seen in similar patients without ascending aortic disease.

Cryopreserved homograft valves in the pulmonary position: risk analysis for intermediate-term failure.

OBJECTIVE: The purpose of this study was to examine the durability of cryopreserved homografts used to replace the "pulmonary" valve and to identify factors associated with their late deterioration. METHODS: We reviewed our entire experience (1985-1997) with 331 survivors in whom cryopreserved homograft valves (pulmonary, n = 304; aortic, n = 27) were used to reconstruct the pulmonary outflow tract. Median age was 14 years (range, 2 days-62 years). Operations included Ross operation (n = 259), tetralogy of Fallot (n = 41), truncus arteriosus (n = 14), Rastelli operation (n = 11), and others (n = 6). Median follow-up was 3.8 years (range, 0.2-11.2 years); late echographic follow-up was complete for 97% of patients. Homograft failure was defined as the need for explantation and valve-related death; homograft dysfunction was defined as a pulmonary insufficiency grade 3/4 or greater and a transvalvular gradient of 40 mm Hg or greater. RESULTS: Homograft failure occurred in 9% (30 of 331 patients; Kaplan-Meier); freedom from failure was 82% +/- 4% at 8 years. Homograft dysfunction occurred in 12% (39 of 331 patients), although freedom from dysfunction was 76% +/- 4% at 8 years. For aortic homografts, this was 56% +/- 11%, compared to 80% +/- 4% for pulmonary homografts (P =.003). For patients aged less than 3 years (n = 38), this was 51% +/- 12%, compared with 87% +/- 4% for older patients (P =.0001). By multivariable analysis, younger age of homograft donors, non-Ross operation, and later year of operation were associated with homograft failure; younger age of homograft donors, later year of operation, and use of an aortic homograft were associated with homograft dysfunction. CONCLUSIONS: Homograft valves function satisfactorily in the pulmonary position at mid-term follow-up. The pulmonary homograft valve appears to be more durable than the aortic homograft valve in the pulmonary position.

Ross operation and aneurysm or dilation of the ascending aorta.

Aortic valve disease and aneurysmal dilation of the ascending aorta are managed by prosthetic valve conduit replacement or homograft replacement. Requirement of anticoagulation, risk of thromboembolism or bleeding, and increased risk for homograft degeneration in young patients suggest that a Ross root replacement with replacement or reduction of the ascending aorta could be a preferred alternative. To assess efficacy, the present review was undertaken. Between April 19, 1995, and February 1999, 64 patients (age, 8 months to 59 years; median age, 37 years) had a Ross operation, with resection of the ascending aorta in 30 and reduction aortoplasty in 34. Annular fixation was performed in 57 patients, with aortic annulus reduction in 39. Clinical evaluation with echocardiogram was completed within 1 year of closure in 62 patients. There was one operative death and one non-valve-related late death. Autograft valve insufficiency (AI) was 0 to trace in the perioperative period in all patients. One patient developed progressive annular dilation with moderate AI at 2 months. Reoperation with annular reduction and fixation restored autograft valve function. Postoperative mean aortic annulus diameter was 22.5+/-0.4 mm (Z-value, -0.2+/-0.2) and 23.2+/-0.8 mm (Z-value, -0.02+/-0.5) at 1 year. Aortic sinus diameter was 33+/-6 postoperative and 36+/-5 at 1 year. The autograft root sinus diameter was greater than 39 mm in 11 patients at the most recent echocardiogram. Mean echocardiography measurements of the aortic root have been constant during the postoperative follow-up period. Two patients have required reoperation for homograft obstruction 1.3 and 2.1 years after operation. Ross root replacement of the aortic valve with resection or reduction aortoplasty can be performed with a low operative risk and limited morbidity. Its early durability appears to be similar to other Ross operations.

A 26-year experience with surgical management of tetralogy of Fallot: risk analysis for mortality or late reintervention.

BACKGROUND: Over the past decade repair of tetralogy of Fallot (TOF) in infancy has gained favor. It is still uncertain what effect early complete repair will have on survival or late reoperation on the right ventricular outflow tract. METHODS: To assess these outcomes, we reviewed our experience (1971-1997) with 294 patients undergoing operation at one institution. Median follow-up was 10.6 years (range, 0.1 to 26 years), and was complete for 90.2% patients. RESULTS: Primary complete repair was done in 199 patients (68%), and a staged repair in 62 patients (21%). Thirty-three patients had only a palliative procedure. Sixty-eight patients (23.1%) had complex pathologic processes, including pulmonary atresia in 53. Hospital mortality for primary repair was 11.1% (22/199), for staged repair was 17.7% (11/62), and for palliative procedures was 15.5% (16/103 procedures). Since 1990 mortality has been 2.1%, 11.8%, and 0% respectively (p < 0.001), despite younger age at repair (0.6+/-0.1 versus 2.1+/-0.2 years; p < 0.001). Multivariate analysis identified longer period of hypothermic circulatory arrest, pulmonary artery patch angioplasty, earlier year of operation, and closure of the foramen ovale as risk factors for hospital death. For hospital survivors 20-year survival was 98%+/-3% for TOF with pulmonary stenosis and 88%+/-9% for TOF with pulmonary atresia (p=0.09). Reintervention on the right ventricular outflow tract was needed in 14.1% (37/261) patients. Freedom from reintervention on the right ventricular outflow tract at 20 years was 86%+/-4% for TOF with pulmonary stenosis and 43%+/-16% for TOF with pulmonary atresia (p=0.001). For the subgroup TOF with pulmonary stenosis, this was 85%+/-5% after primary repair and 91%+/-8% after staged repair (not significant). At 15-year follow-up, this was 78%+/-10% for patients not older than 1 year at operation compared with 88%+/-4% for older patients (not significant). CONCLUSIONS: Early mortality after primary repair of TOF has significantly improved and late survival is excellent. Primary repair in infancy does not increase risk for reintervention on the right ventricular outflow tract.

The Ross operation in children: 10-year experience.

BACKGROUND: The Ross operation, first performed in children in 1968, may be the ideal aortic valve replacement. Technical demands of the operation and two valves at risk have delayed acceptance. A review of our experience to assess midterm and long-term results with the Ross operation is presented. METHODS: The records of 150 consecutive patients, aged 7 days to 21 years (median age, 12 years, 75% less than 15 years) were reviewed. Follow-up was complete within the last 12 months (median, 2.8 years; range, 1 month to 10 years). Echocardiographic assessment was available on 116 (71%) within 1 year of closure and in 136 (91%) within 2 years. RESULTS: Survival was 97.3% at 8 years. Late autograft valve dysfunction required replacement in 2 and reoperation with restitution of autograft function in 6. Freedom from reoperation for autograft dysfunction is 90% +/- 4% at 8 years. Freedom from reoperation for homograft obstruction is 94% +/- 3% at 8 years. Pulmonary homograft dysfunction (gradient > 40 mm Hg) was present in 4 additional patients. Freedom from reoperation on the homograft or a gradient of 40 mm Hg is 89% +/- 4% at 8 years. All patients have a normal, active lifestyle, without anticoagulants for their aortic valve replacement. CONCLUSIONS: The Ross operation is the preferred operative replacement in children requiring aortic valve replacement.

Congenital aortic valve disease. Improved survival and quality of life.

OBJECTIVE: The purpose of the study was to assess the effect of recent trends in surgical management, including use of the Ross Operation, on improved survival and quality of life in patients treated surgically for aortic valve (AV) disease at Oklahoma Children's Hospital. BACKGROUND: Surgical treatment of congenital AV disease has proved to be palliative, but newer procedures may be improving outcomes. METHODS: A retrospective review of 301 patients, age 1 day to 26 years (median, 5 years), having a surgical AV procedure or aortic balloon valvuloplasty at Children's Hospital of Oklahoma between 1960 and February 1996, was conducted. Information was collected on all prior and subsequent operations, and follow-up within 1 year was 96% complete. RESULTS: Survival for all patients was 90% +/- 2% at age 10 years and 73% +/- 8% at age 25. By age 5, 52% +/- 4% had required an AV procedure, 89% +/- 3% by age 15. Patient survival was affected adversely by the diagnosis of valvar aortic stenosis, 79% +/- 6% at age 25 compared to 95% +/- 4% for subvalvar aortic stenosis or aortic insufficiency (p = 0.01). The AV morphology did not affect survival, but patients with a bicuspid or unicuspid valve required operative intervention at an earlier age. Survival after autograft replacement of the AV (Ross Operation) was significantly better than for other types of valve replacement (p = 0.0043). Quality of life as assessed by need for reoperation favors the use of the Ross Operation, with freedom from reoperation at 9 years of 87% +/- 7% compared to 55% +/- 5% in all patients after first AV surgery (p = 0.003). CONCLUSIONS: The Ross Operation appears to have a significant advantage in survival and quality of life in children requiring a valve replacement as a first operation or after a prior AV procedure.

Improved results in the management of surgical candidates with lung cancer.

BACKGROUND: Perioperative mortality and morbidity after lung resection for carcinoma are generally reported to be 3% to 6% and 15% to 30%, respectively, and higher in the elderly and those with limited cardiopulmonary reserve. METHODS: To minimize this risk and extend the surgical option to more high-risk patients, we adopted a protocol in 1991 that included preoperative digitalis, subcutaneous heparin and venoocclusive stockings, aggressive perioperative pulmonary toilet, and video-directed limited resections for many patients with limited pulmonary reserve. In October 1996, we reviewed our results with 173 consecutive patients (median age, 60 years; range, 17 to 89 years) undergoing operation for suspected lung carcinoma. Forty-one patients were 70 years old or older, and 70 patients were considered high risk on the basis of advanced age (> or = 70 years), poor cardiac or pulmonary reserve, or serious medical comorbidity. Procedures included pneumonectomy (n = 31), lobectomy (n = 83), bilobectomy (n = 12), and limited resection (n = 45). Two patients had unresectable disease. RESULTS: Hospital mortality was 1.6% (3/173) and morbidity was experienced by 15% (26/173). Among the high-risk subgroup mortality was 4.2% (3/70) and morbidity was 20% (14/70; p < 0.03). For the older patients these values were 4.8% (2/41) and 17.9% (7/41), respectively. CONCLUSIONS: Morbidity and mortality from lung resections may be minimized with the perioperative management strategy outlined above. This would allow more high-risk patients to benefit from surgical resection, and do so with an acceptably low risk.

Chromosomal localization of a human mucin gene (MUC8) and cloning of the cDNA corresponding to the carboxy terminus.

A partial cDNA (pAM1) encoding a major airway mucin glycoprotein with novel tandem repetitive sequence has recently been cloned (Shankar, V., M. S. Gilmore, R. C. Elkins, and G. P. Sachdev. 1994. Biochem. J. 300:295-298). In this article, we report additional new sequence derived by 3'-rapid amplification of cDNA ends technique. The sequence corresponds to a stop codon, 3'-untranslated region of 458 bp, a polyadenylation signal, and poly A+ tail, and represents the extreme carboxy terminus of MUC8. A plasmid construct (pAM3) in pBluescript was generated by in-frame ligation of pAM1 to the 479-bp 3'UTR of MUC8. A 5'-end 325-bp fragment of this cDNA subcloned into the protein fusion and expression vector pET28b(+) was used to generate fusion protein under the control of T7 promoter. The purified fusion protein as well as synthetic peptide corresponding to the MUC8 repeat sequence (TSCPRPLQEGTPGS) were used to raise polyclonal antibodies in rabbits. The antiserum to the fusion protein and to the synthetic peptide reacted with the deglycosylated major tracheobronchial mucin. Immunohistochemical studies using the above antibodies localized the MUC8 protein product to submucosal glands in human tracheal epithelium. Furthermore, the gene from which this cDNA is derived, was mapped to chromosome 12 using DNA from a panel of human-mouse somatic cell hybrids. Fluorescence in situ hybridization was used to assign the regional localization to 12q24.3. Since the eight known human mucin genes map to other chromosomes, we have named this gene MUC8, in accordance with mucin gene nomenclature.

Evaluation of cryopreserved homografts in the right ventricular outflow tract after the Ross procedure: intermediate-term follow up.

BACKGROUND AND AIMS OF THE STUDY: The Ross procedure involves replacing a transplanted pulmonary valve with a cryopreserved homograft in order to re-establish right ventricle-pulmonary artery continuity. This study reviews mid-term results of such surgery in children and young adults. METHODS: Since November 1986, 114 patients have undergone the Ross procedure at the Children's Hospital of Oklahoma using cryopreserved pulmonary homografts (n = 113) and aortic homograft (n = 1) to reconstruct the right ventricular outflow tract. Graft size ranged from 16 to 32 mm. Ninety-three patients (mean age at implant 10.4 years (range: 0.8-22 years) have had complete mean follow up of 3.2 years (range: 5 months to 8.4 years) after surgery. Homograft evaluation included clinical reports and comparison of early post-implant and latest echocardiography. Measurements of homograft valve annulus and peak instantaneous Doppler gradient were compared; quality of valve leaflets, location of obstruction, and the degree of pulmonary regurgitation were assessed. RESULTS: Compared with early postoperative data, mean homograft annulus size decreased by 15% (p < 0.0001); in 88% of patients, the decrease ranged from one to nine millimeter. Peak Doppler gradient increased significantly (from 10 to 17 mmHg, p < 0.0001); 25% of patients developed gradients > 25 mmHg, and four had gradients > 50 mmHg. Significant obstruction developed most often at the supravalvular level or in the homograft conduit itself. This usually occurred within one year of implant, and was associated with calcification and contracture of the homograft wall. Significant pulmonary regurgitation developed in 19 cases (20%), but was more than mild in only three. Leaflet integrity was maintained except in those who developed severe stenosis or regurgitation. Two patients have undergone re-operation for homograft stenosis 2.8 and 5.4 years respectively after the Ross procedure; one has developed recurrent severe stenosis in the homograft four months later. CONCLUSIONS: After the Ross procedure: (i) Pulmonary homografts undergo significant annular reduction in most patients, though this is usually not associated with the development of significant obstruction. (ii) Peak Doppler gradients across the homograft increase in most patients, though only 4% develop more than mild obstruction. (iii) Mild pulmonary regurgitation is common (20%); moderate or severe regurgitation is rare and usually develops in concert with severe stenosis. (iv) Severe homograft valve degeneration usually occurs within one year of implant, and may reflect an immune-mediated response.