Structural integrity of collagen and elastin in SynerGraft® decellularized-cryopreserved human heart valves.

SynerGraft® (SG) decellularized-cryopreserved cardiac valve allografts have been developed to provide a valve replacement option that has reduced antigenicity, retained structural integrity, and the ability to be stored long-term until needed for implantation. However, it is critical to ensure that both the SG processing and cryopreservation of these allografts do not detrimentally affect the extracellular matrix architecture within the tissue. This study evaluates the effects of SG decellularization and subsequent cryopreservation on the extracellular matrix integrity of allograft heart valves. Human aortic and pulmonary valves were trisected, with one-third of each either left fresh (no further processing after dissection), decellularized, or decellularized and cryopreserved. Two-photon laser scanning confocal microscopy was used to visualize collagen and elastin in leaflets and conduits. The optimized percent laser transmission (OPLT) required for full dynamic range imaging of each site was determined, and changes in OPLT were used to infer changes in collagen and elastin signal intensity. Collagen fiber crimp period and collagen and elastin fiber diameter were measured in leaflet tissue. Statistically significant differences in OPLT and the dimensional characteristics of collagen and elastin in study groups were determined through single factor ANOVA. The majority of donor-aggregated average OPLT observations showed no statistically significant differences among all groups, indicating no difference in collagen or elastin signal strength. Morphometric analysis of collagen and elastin fibers revealed no significant alterations in treated leaflet tissues relative to fresh tissues. Collagen and elastin structural integrity within allograft heart valves are maintained through SynerGraft® decellularization and subsequent cryopreservation.

Performance of the CryoValve SG human decellularized pulmonary valve in 342 patients relative to the conventional CryoValve at a mean follow-up of four years.

OBJECTIVE: This study compared clinical outcomes of patients receiving CryoValve SG decellularized pulmonary valves with those of patients receiving conventionally processed CryoValve pulmonary valves. METHODS: All consecutive patients undergoing Ross procedures and right ventricular outflow tract reconstructions with SG valves at 7 institutions (February 2000-November 2005) were assessed retrospectively (193 Ross procedures, 149 right ventricular outflow tract reconstructions). Patient, procedural, and outcome data were compared with those from 1246 conventional implants (665 Ross procedures, 581 right ventricular outflow tract reconstructions). Hemodynamic function was assessed at latest follow-up. RESULTS: Follow-up was complete for 99% in SG group and 94% in conventional group, with mean follow-ups of 4.0 years (range, 0-6.7 years) for SG and 3.7 years (range, 0-6.7 years) for conventional. Five-year cumulative survivals and freedoms from adverse events were comparable between SG and conventional valves. Among patients undergoing Ross procedures, peak gradient at last follow-up was lower with SG valves (P < .01); no difference was observed in the right ventricular outflow tract reconstruction population. Pulmonary insufficiency was significantly reduced with SG valves in patients undergoing both Ross procedures (P < .01) and right ventricular outflow tract reconstructions (P < .01). Valve type was not a significant predictor of valve-related failure in propensity-adjusted analysis of either procedure. CONCLUSIONS: CryoValve SG decellularized pulmonary valves have acceptable clinical outcomes and favorably compare with conventionally processed valves. Improved hemodynamic function observed with SG valves could signify improved long-term outcomes and may be due to the decreased antigenicity of these valves.

Ross operation: 16-year experience.

OBJECTIVE: We performed a review of a consecutive series of 487 patients undergoing the Ross operation to identify surgical techniques and clinical parameters that affect outcome. METHODS: We performed a prospective review of consecutive patients from August 1986 through June 2002 and follow-up through August 2004. Patient age was 2 days to 62 years (median, 24 years), and 197 patients were less than 18 years of age. The Ross operation was performed as a scalloped subcoronary implant in 26 patients, an inclusion cylinder in 54 patients, root replacement in 392 patients, and root-Konno procedure in 15 patients. Clinical follow-up in 96% and echocardiographic evaluation in 77% were performed within 2 years of closure. RESULTS: Actuarial survival was 82% +/- 6% at 16 years, and hospital mortality was 3.9%. Freedom from autograft failure (autograft reoperation and valve-related death) was 74% +/- 5%. Male sex and primary diagnosis of aortic insufficiency (no prior aortic stenosis) were significantly associated with autograft failure by means of multivariate analysis. Freedom from autograft valve replacement was 80% +/- 5%. Freedom from endocarditis was 95% +/- 2%. One late thromboembolic episode occurred. Freedom from allograft reoperation or reintervention was 82% +/- 4%. Freedom from all valve-related events was 63% +/- 6%. In children survival was 84% +/- 8%, and freedom from autograft valve failure was 83% +/- 6%. CONCLUSIONS: The Ross operation provides excellent survival in adults and children willing to accept a risk of reoperation. Male sex and a primary diagnosis of aortic insufficiency had a negative effect on late results.

Pulmonary autografts in patients with severe left ventricular dysfunction.

BACKGROUND: Performing a Ross operation in patients with severe left ventricular dysfunction is controversial. The objective in this retrospective study was to determine the outcome of 15 patients with aortic valve disease (11 had aortic insufficiency and 4 had aortic insufficiency and aortic stenosis) associated with reduced left ventricular function (ejection fraction < 40%) treated with a pulmonary autograft. METHODS: We identified 15 patients with severe left ventricular dysfunction from 226 consecutive pulmonary autograft procedures done between age 18 and 50 years from 1986 to 2001. Patients had documented preoperative ejection fraction less than 40% and were in New York Heart Association class III or IV. Preoperative ejection fraction ranged from 18% to 37% (mean, 31% +/- 6.5%). Transthoracic echocardiograms obtained preoperatively and at 1-week, 6-month, and 1- and 2-year intervals were reviewed. Records were evaluated for survival, clinical status, left ventricular function, and valve function. RESULTS: There were no operative deaths, late deaths, or reoperations. All patients had follow-up examinations within the past year and are clinically well (67% > 2 years follow-up). Ten of 15 patients (67%) had substantially improved ventricular function (> 20% increase). The average ejection fraction increased from 31% +/- 7% preoperatively to 51% +/- 11% at 2 years, and the increase is significant from 1 week on (p < 0.02). Average left ventricular mass index decreased by 41% at 6 months (n = 10; p = 0.009) and by 44% at 2 years (n = 9; p = 0.02). Mean Z values for left ventricular mass decreased from 7.6 to 3.6 after more than 2 years (p = 0.007). CONCLUSIONS: The Ross operation is an appropriate option in adults age 50 or younger in the presence of decreased left ventricular ejection fraction. Neither operative mortality nor postoperative sequelae were identified in our subset of patients. Excellent survival and ventricular recovery are predicted.

Effect of prior aortic valve intervention on results of the Ross operation.

BACKGROUND AND AIM OF THE STUDY: Patient-related factors, aortic insufficiency, bicuspid aortic valve, aortic annulus dilatation, ascending aortic dilatation or aneurysm, and aortic valve endocarditis have been suggested as affecting the results of the Ross operation. The study aim was to assess the impact of prior aortic valve intervention on early and late results of a Ross operation. METHODS: A total of 399 patients who underwent surgery between August 1986 and September 2000 were reviewed retrospectively. The patients were grouped as: no prior aortic valve intervention (NOAVI, n = 219); prior aortic valvuloplasty (AVP, n = 106); prior balloon aortic valvuloplasty (AVB, n = 40); and prior aortic valve replacement (AVR, n = 34). Details of operative and late mortality, autograft valve function, and homograft valve function were analyzed. RESULTS: Operative mortality was higher for AVB (10%; three deaths in neonates) than the other groups (from 2.3% to 5.9%) (p = 0.084). Freedom from autograft valve degeneration, defined as severe autograft valve insufficiency, non-endocarditis autograft valve reoperation or valve-related death, ranged from 93 +/- 3% for AVP to 76 +/- 8% for NOAVI at 10 years (p = 0.43). Freedom from homograft reoperation in the pulmonary position was 100% for AVB at six years, and 99 +/- 1% for AVP, 82 +/- 8% for NOAVI, and 70 +/- 13% for AVR at 10 years (p = 0.0026). CONCLUSION: There appears to be no significant difference between patients with and without prior aortic valve surgery, with respect to operative mortality or late autograft function. However, patients with prior AVR appear to have a significantly higher homograft reoperation rate after a Ross operation, the reasons for which are uncertain.

Prognosis after aortic root replacement with cryopreserved allografts in adults.

BACKGROUND: Aortic root replacement with cryopreserved allografts is associated with excellent hemodynamics, little endocarditis, low thromboembolic event rates, and no need for anticoagulation. There is, however, concern regarding the long-term durability of this valve substitute, especially in younger patients. Meta-analysis and microsimulation were used to calculate age-specific long-term prognosis after allograft aortic root replacement based on current evidence. METHODS: Our center's experience with cryopreserved allograft aortic root replacement in 165 adult patients was combined in a meta-analysis with reported and individual results from four other hospitals. Using this information, the microsimulation model predicted age- and gender-specific total and reoperation-free and event-free life expectancy. RESULTS: The pooled results comprised 629 patients with a total follow-up of 1860 patient-years (range 0 to 12.8 years). Annual risks were 0.6% for thromboembolism, 0.05% for bleeding, 0.5% for endocarditis, and 0.5% for nonstructural valve failure. Structural allograft failure requiring reoperation occurred in 15 patients, and a patient age-specific Weibull function was constructed accordingly. Calculated total life expectancy varied from 27 years in a 25-year-old to 12 years in a 65-year-old male; corresponding actual lifetime risk of reoperation was 89% and 35%, respectively. CONCLUSIONS: Cryopreserved aortic allografts have an age-related limited durability. This results in a considerable lifetime risk of reoperation, especially in young patients. The combination of meta-analysis and microsimulation provides an appropriate tool for estimating individualized long-term outcome after aortic valve replacement and can be useful both for patient counseling and prognostic research purposes.

Is tissue-engineered heart valve replacement clinically applicable?

Tissue engineering of a heart valve has progressed dramatically in three different arenas: a biodegradable stented valve seeded with autogenous cells, decellularized allograft and xenograft valves that are seeded with autogenous cells, and decellularized allograft and xenograft valves that repopulate by adaptive remodeling in vivo. Preclinical evaluation and implants in sheep have been accomplished in each of these arenas, and clinical use of this emerging technology is occurring in the latter two. The clinical use of decellularized allografts that repopulate in vivo is expanding; however, its impact on allograft durability remains unknown.