Porcine Bioprosthetic Valves Research Articles

Redo isolated tricuspid valve replacement in a patient with isolated persistent left superior vena cava: a case report

BackgroundRedo isolated tricuspid valve surgery has high in-hospital mortality and morbidity and is a challenging procedure. We report a successful case of redo isolated tricuspid valve replacement for structural valve deterioration of a bioprosthesis in a patient with isolated persistent left superior vena cava (PLSVC).Case presentationAn 81-year-old man with a history of tricuspid valve replacement using a porcine bioprosthetic valve 9 years previously presented with dyspnea on exertion. Right heart failure due to worsening transvalvular leakage in the bioprosthetic tricuspid valve was considered to be the cause of his symptoms, and the decision was made to replace the tricuspid valve. An isolated PLSVC is considered to be an obstacle in right-sided heart valve surgery. The PLSVC was located deep to the left of the pulmonary artery and, after some effort, was cannulated by obtaining an excellent surgical view using retraction sutures on the left side of the pericardium. Cardiopulmonary bypass was initiated after cannulation of the ascending aorta, PLSVC, and femoral vein. After cross-clamping of the ascending aorta, cold blood cardioplegic arrest was induced under moderate hypothermia, and the PLSVC and inferior vena cava were snared. The right atrium was opened and the prosthetic tricuspid valve was examined. One of the leaflets was shortened, which appeared to cause the transvalvular leak. The prosthetic valve was explanted, the annulus was trimmed, and a new bioprosthetic valve was implanted. The postoperative course was uneventful.ConclusionsIt is important to treat structural valve deterioration of a prosthetic tricuspid valve in a timely manner. We hope that our intervention timing and surgical strategy can help surgeons to consider early intervention in similar cases, even if there are surgical obstacles such as isolated PLSVC.

Transcatheter Arterial Embolization for Atraumatic Splenic Rupture in TEE-negative Endocarditis: A Case Report.

Spontaneous splenic rupture is an extremely rare complication of infective endocarditis. We present a case of a 56-year-old immunocompetent female with porcine bioprosthetic mitral valve replacement, automated implanted cardioverter-defibrillator, and atrial fibrillation on apixaban who was found to have in-hospital atraumatic splenic rupture complicating infective endocarditis with Haemophilus parainfluenza. The rupture was treated successfully by endovascular embolization. Usual treatment with six weeks of antibiotics provided durable cure without further complication, and no surgical intervention was needed for either the valve or spleen. Transcatheter arterial embolization should be considered early in atraumatic splenic rupture. Relevant abdominal and cerebral imaging should be considered in all cases of suspected or confirmed infective endocarditis where unexplained symptoms are present.

Bovine pericardial versus porcine bioprosthetic aortic valves: A nationwide population-based cohort study in Korea

ObjectiveTo compare the clinical outcomes of aortic valve replacement (AVR) using bovine pericardial and porcine bioprostheses, utilizing a nationwide administrative claims database. MethodsAdult patients (age ≥40 years) who underwent bioprosthetic AVR, without other valve replacements, between 2003 and 2018 were identified from the Korean National Health Insurance Service database. The outcomes of interest were all-cause mortality, cardiac mortality, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. Baseline adjustment was performed using propensity score matching. Time-related outcomes were evaluated using a competing risk analysis, with death as a competing risk. ResultsAmong the 7714 patients who underwent bioprosthetic AVR, 5621 (72.9%) received bovine pericardial prostheses and 2093 (27.1%) received porcine bioprostheses. After matching, 1937 pairs were included in the final analysis. During follow-up (median, 4.49 years; interquartile range, 2.83-8.20 years), the use of porcine bioprostheses was associated with a higher risk of aortic valve reoperation (adjusted hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.16 to 3.01); however, no significant differences were observed in cumulative incidences of all-cause mortality, cardiac mortality, thromboembolism, or major bleeding. Subgroup analyses revealed that the use of bovine valves was associated with improved survival in patients with diabetes mellitus, whereas in patients undergoing dialysis, porcine valves exhibited better survival than bovine valves. ConclusionsIn this large nationwide cohort study of patients undergoing bioprosthetic aortic valve replacement, the use of porcine prostheses was significantly associated with an increased risk of reoperation compared with the use of bovine prostheses, supporting previous findings.

Biomimetic proteoglycans as a tool to engineer the structure and mechanics of porcine bioprosthetic heart valves.

The utility of bioprosthetic heart valves (BHVs) is limited to certain patient populations because of their poor durability compared to mechanical prosthetic valves. Histological analysis of failed porcine BHVs suggests that degeneration of the tissue extracellular matrix (ECM), specifically the loss of proteoglycans and their glycosaminoglycans (GAGs), may lead to impaired mechanical performance, resulting in nucleation and propagation of tears and ultimately failure of the prosthetic. Several strategies have been proposed to address this deterioration, including novel chemical fixatives to stabilize ECM constituents and incorporation of small molecule inhibitors of catabolic enzymes implicated in the degeneration of the BHV ECM. Here, biomimetic proteoglycans (BPGs) were introduced into porcine aortic valves ex vivo and were shown to distribute throughout the valve leaflets. Incorporation of BPGs into the heart valve leaflet increased tissue overall GAG content. The presence of BPGs also significantly increased the micromodulus of the spongiosa layer within the BHV without compromising the chemical fixation process used to sterilize and strengthen the tissue prior to implantation. These findings suggest that a targeted approach for molecularly engineering valve leaflet ECM through the use of BPGs may be a viable way to improve the mechanical behavior and potential durability of BHVs.

Commentary on bovine pericardial versus porcine bioprosthetic mitral valves: results from a Korean Nationwide Cohort Study.

Commentary on bovine pericardial versus porcine bioprosthetic mitral valves: results from a Korean Nationwide Cohort Study.

Bovine pericardial versus porcine bioprosthetic mitral valves: results from a Korean Nationwide Cohort Study.

Comparisons of long-term clinical outcomes of mitral valve replacement (MVR) between bovine pericardial and porcine bioprostheses are conflicting, with limited research in large-scale real-world clinical settings. This study examined clinical outcomes in MVR according to bioprosthesis type using a national administrative claims database. This study included adult patients undergoing bioprosthetic MVR between 2003 and 2018 using administrative health care data from the Korean National Health Insurance Service database. Propensity score matching with competing risk analysis was used to compare the clinical outcomes according to the type of bioprosthesis. The end points were death, cardiac death, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. A total of 3151 patients underwent bioprosthetic MVR with bovine pericardial (n = 1628, 51.7%) or porcine (n = 1523, 48.3%) bioprostheses. After matching, 1170 pairs were included in the final analysis. During follow-up (median 4.49 years, interquartile range 1.87 -8.75 years), death occurred in 1178 patients (6.8%/patient-year), comprising 730 (4.3%/patient-year) cardiac death. No significant differences were noted between the bovine and porcine groups in the cumulative incidences of death from any cause [adjusted hazard ratio (aHR), 1.00; 95% confidence interval (CI), 0.87-1.14], cardiac mortality (aHR, 0.96; 95% CI, 0.81-1.14), or reoperation (aHR, 1.01; 95% CI, 0.72-1.41). This study on a nationwide comparison between bovine and porcine bioprostheses in MVR found no significant differences in clinical outcomes including mortality, and valve-related reoperation.

Outcomes of bovine versus porcine surgical aortic valve replacement.

There are no guidelines regarding the use of bovine pericardial or porcine valves for aortic valve replacement, and prior studies have yielded conflicting results. The current study sought to compare short- and long-term outcomes in propensity-matched cohorts of patients undergoing isolated aortic valve replacement(AVR) with bovine versus porcine valves. This was a retrospective study utilizing an institutional database of all isolated bioprosthetic surgical aortic valve replacements performed at our center from 2010 to 2020. Patients were stratified according to type of bioprosthetic valve (bovine pericardial or porcine), and 1:1 propensity-score matching was applied. Kaplan-Meier survival estimation and multivariable Cox regression for mortality were performed. Cumulative incidence functions were generated for all-cause readmissions and aortic valve reinterventions. A total of 1502 patients were identified, 1090 (72.6%) of whom received a bovine prosthesis and 412 (27.4%) of whom received a porcine prosthesis. Propensity-score matching resulted in 412 risk-adjusted pairs. There were no significant differences in clinical or echocardiographic postoperative outcomes in the matched cohorts. Kaplan-Meier survival estimates were comparable, and, on multivariable Cox regression, valve type was not significantly associated with long-term mortality (hazard ratio: 1.02, 95% confidence interval: 0.74, 1.40, p = .924). Additionally, there were no significant differences in competing-risk cumulative incidence estimates for all-cause readmissions (p = .68) or aortic valve reinterventions (p = .25) in the matched cohorts. The use of either bovine or porcine bioprosthetic aortic valves yields comparable postoperative outcomes, long-term survival, freedom from reintervention, and freedom from readmission.

Long-term results of a stented bioprosthetic valve in the aortic position: structural valve deterioration and valve haemodynamic deterioration of bovine pericardial and porcine valves.

This study compared the clinical outcomes of bovine and porcine bioprosthetic valves based on structural valve deterioration (SVD) and valve haemodynamic deterioration (VHD) in the aortic position. From January 1995 to December 2014, patients who underwent aortic valve replacement (AVR) using a bovine pericardial valve or porcine valve were enrolled. SVD and VHD were defined according to the mean transprosthetic gradient and the grade of aortic regurgitation on transthoracic echocardiography. The propensity score matching was used to adjust for differences in preoperative and operative characteristics. A total of 520 patients were enrolled. Of these, 372 patients underwent AVR using a bovine pericardial valve and 148 patients underwent AVR using a porcine valve. Then, 135 pairs of patients were extracted after propensity score matching. The median follow-up duration was 8.2 years (interquartile range, 5.4-11.3). Among the matched patients, no significant differences occurred in overall survival (survival at 10 years: 64.7% vs 70.9%) or cardiac death (cumulative incidence at 10 years: 14.2% vs 13.1%) between the 2 groups. The cumulative incidence of moderate or greater SVD and VHD was significantly higher in the porcine valve group than in the bovine valve group (SVD at 10 years-porcine: 29.8% vs bovine: 13%; VHD at 10 years-porcine: 19.8% vs bovine: 3.8%, respectively). However, no significant differences were noted in the cumulative incidence of severe SVD and severe VHD between the 2 groups. The bovine pericardial valve should be considered in AVR because the cumulative incidences of moderate or greater SVD and VHD were significantly lower than those of the porcine valve.

Bidirectional Glenn shunt with tricuspid valve resection in patients with infective endocarditis.

Bidirectional Glenn shunt with tricuspid valve resection in patients with infective endocarditis.

Comparative analysis of structural valve deterioration and long-term clinical outcomes after bovine pericardial versus porcine bioprosthetic mitral valve replacement

BackgroundThis study aimed to compare long-term outcomes, including durability, after bovine pericardial valve replacement with those after porcine mitral valve replacement (MVR).MethodsWe enrolled 309 patients who underwent MV replacement (mean age: 65.8±11.5 years; 68.9% females) with Carpentier-Edwards PERIMOUNT bovine pericardial valves (bovine MVR group, n=241) or Hancock II porcine bioprosthesis (porcine MVR group, n=68). The mean clinical and echocardiographic follow-up durations were 81.4±60.0 and 57.8±53.3 months, respectively. Structural valve deterioration (SVD) was defined as prosthetic mitral valve (MV) regurgitation or stenosis of greater than moderate degree combined with a motion limitation, tear, or perforation of prosthetic valve leaflet on follow-up echocardiography. Propensity score (PS)-adjusted multivariable analyses were performed.ResultsThirty-day mortality rate was 6.4% (20/309 patients). SVD occurred in 50 patients (33 and 17 patients in the bovine and porcine MV replacement groups, respectively). Cumulative incidences of SVD at 5, 10, and 15 years were 3.2%, 15.9%, and 32.4%, respectively, in the bovine MVR group and 1.9%, 15.3%, and 41.7%, respectively, in the porcine MVR group. Cumulative incidences of SVD in the two groups were not different in competing risk analysis (P=0.23). Other clinical outcomes including overall survival and cumulative incidences of cardiac death and MV-related events were not statistically significantly different between the groups in PS-adjusted multivariable analyses.ConclusionsLong-term clinical outcomes including SVD were not different between the bovine and porcine bioprosthesis MVR groups during average 7 years of clinical follow-up after MVR.

Durability of Pulmonary Valve Replacement with Large Diameter Stented Porcine Bioprostheses

There is limited information about durability of large diameter porcine bioprostheses implanted for pulmonary valve replacement (PVR). We studied patients who underwent surgical PVR from 2002-2019 with a stented porcine bioprosthetic valve (BPV) with a labeled size ≥27 mm. The primary outcome was freedom from reintervention. During the study period, 203 patients underwent PVR using a porcine BPV ≥27 mm, 94% of whom received a Mosaic valve (Medtronic Inc., Minneapolis, MN). Twenty patients underwent reintervention from 3.4-12.0 years after PVR: 5 surgical and 15 transcatheter PVR procedures. The indication for reintervention was regurgitation in 13 patients, stenosis in 2, mixed disease in 4, and endocarditis in 1. Estimated freedom from reintervention was 97±1% at 5 years and 82±4% at 10 years, and freedom from prosthesis dysfunction (moderate or severe regurgitation and/or a maximum Doppler gradient ≥50 mm Hg) over time was 91±2% at 5 years and 74±4% at 10 years. Younger age and smaller true valve diameter were associated with shorter freedom from reintervention, but valve oversizing was not. The durability of large stented porcine bioprostheses in the pulmonary position is generally excellent, particularly in adolescents and adults, similar to various other types of BPV. In the current study, relative valve size was not associated with valve longevity, although the low event-rate in this population was a limiting factor.

ABO blood type and risk of porcine bioprosthetic aortic valve degeneration: SWEDEHEART observational cohort study

ObjectiveBlood type A antigen on porcine aortic bioprostheses might initiate an immune reaction leading to an increased frequency of structural valve deterioration in patients with blood type B or O....

The Stented Porcine Bioprosthesis: A 50-Year Journey Through Hopes and Realities

The year 2018 marked the 50th anniversary of the first implant of a commercially manufactured stented porcine bioprosthesis. During the subsequent years considerable clinical and pathologic research was done to evaluate the overall performance of such devices and to identify the leading causes of failure. This brief review covers 5 decades, summarizing the initial hopes and the realities faced by surgeons who have believed from the start in these cardiac valve substitutes. From reported failures and long-term results a new generation of durable and reliable stented porcine bioprosthetic valves is currently available.

Survival after Aortic Valve Replacement with Bovine or Porcine Valve Prostheses: A Systematic Review and Meta-Analysis.

Bovine and porcine bioprostheses are commonly used for surgical aortic valve replacement. It is unknown if the long-term survival differs between the two valve types.We performed a systematic review and meta-analysis to compare survival in patients who underwent aortic valve replacement and received a bovine or a porcine prosthesis. We performed a systematic search of Medline, Embase, Web of Science, and the Cochrane Library. Cohort studies that compared survival between patients who underwent aortic valve replacement and received either a bovine or a porcine bioprosthesis and that reported overall long-term survival with hazard ratio (HR) and 95% confidence interval (CI) were included. Two authors independently reviewed articles considered for inclusion, extracted the information from each study, and performed the quality assessment. We performed a meta-analysis using a random effects model to calculate the pooled HR (95% CI) for all-cause mortality. We did sensitivity analyses to assess the robustness of our findings. Seven studies published between 2010 and 2015 were included, and the combined study population was 49,190 patients. Of these, 32,235 (66%) received a bovine, and 16,955 (34%) received a porcine bioprosthesis. There was no significant difference in all-cause mortality between patients who received a bovine compared with a porcine bioprosthesis (pooled HR 1.00, 95% CI: 0.92-1.09). Heterogeneity between studies was moderate (55.8%, p = 0.04). This systematic review and meta-analysis suggest no difference in survival between patients who received a bovine versus a porcine bioprosthesis after aortic valve replacement. Our study provides valuable evidence for the continuing use of both bovine and porcine bioprosthetic valves for surgical aortic valve replacement.

“The smiling valve”: Incidental fluoroscopic finding of a stented Hancock porcine bioprosthetic valve during coronary angiogram

A 60-year-old male patient with type 2 diabetes mellitus (DM)and hypertension presented to cardiology department (January2018) with exertional dyspnea [New York Heart Association(NYHA) class II] since last two months. General examinationrevealed pulsus parvus et tardus along with systolic blood pressure(SBP) of 90 mmHg in right hand supine position. Cardiovascu-lar examination revealed heaving apex, grade IV/VI late peakingsystolic murmur at aortic area with decreased intensity of aor-tic closure sound. Previously, in 2010 also he had presented withNYHA class II dyspnea and exertional giddiness.

Reducing immunoreactivity of porcine bioprosthetic heart valves by genetically-deleting three major glycan antigens, GGTA1/β4GalNT2/CMAH

Bioprosthetic heart valves (BHVs) originating from pigs are extensively used for heart valve replacement in clinics. However, recipient immune responses associated with chronic calcification lead to structural valve deterioration (SVD) of BHVs. Two well-characterized epitopes on porcine BHVs have been implicated in SVD, including galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) whose synthesis are catalyzed by α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Ac hydroxylase (encoded by the CMAH gene), respectively. It has been reported that BHV from αGal-knockout pigs are associated with a significantly reduced immune response by human serum. Moreover, valves from αGal/Neu5Gc-deficient pigs could further reduce human IgM/IgG binding when compared to BHV from αGal-knockout pigs. Recently, another swine xenoantigen, Sd(a), produced by β-1,4-N-acetyl-galactosaminyl transferase 2 (β4GalNT2), has been identified. To explore whether tissue from GGTA1, CMAH, and β4GalNT2 triple gene-knockout (TKO) pigs would further minimize human antibody binding to porcine pericardium, TKO pigs were successfully produced by CRISPR/Cas9 mediated gene targeting. Our results showed that the expression of αGal, Neu5G and Sd(a) on TKO pigs was negative, and that human IgG/IgM binding to pericardium was minimal. Moreover, the analysis of collagen composition and physical characteristics of porcine pericardium from the TKO pigs indicated that elimination of the three xenoantigens had no significant impact on the physical proprieties of porcine pericardium. Our results demonstrated that TKO pigs would be an ideal source of BHVs. Statement of significanceSurgical heart valve replacement is an established lifesaving treatment for diseased heart valve. Bioprosthetic heart valves (BHVs) made from glutaraldehyde-fixed porcine or bovine tissues are widely used in clinics but exhibit age-dependent structural valve degeneration (SVD) which is associated with the immune response against BHVs. Three major xenoantigens present on commercial BHVs, Galactosea α1,3 galactose (αGal), N-glycolylneuraminic acid (Neu5Gc) and glycan products of β-1,4-N-acetyl-galactosaminyl transferase 2 (β4GalNT2) are eliminated through CRISPR/Cas9 mediated gene targeting in the present study. The genetically modified porcine pericardium showed reduced immunogenicity but comparable collagen composition and physical characteristics of the pericardium from wild-type pigs. Our data suggested that BHVs from TKO pigs is a promising alternative for currently available BHVs from wild-type pigs.

Surgical Management of Ebstein’s Anomaly with Atrial Septal Defect in a Young Lady: A Case Report

Ebstein’s anomaly is a rare congenital heart defect accounting for <1% of all cases. It is commonly associated with other cardiac malformations particularly, 50% of the patients are associated with atrial septal defect. We report a 22-year-old lady diagnosed to have Ebstein’s anomaly with small atrial septal defect. She was surgically managed in Bangabandhu Sheikh Mujib Medical University by replacing the defective tricuspid valve withSt Jude Medical Epic porcine bio-prosthetic heart valve along with plication of atrialized portion of right ventricle and direct closure of the atrial septal defect.This resulted in excellent symptomatic improvement.University Heart Journal Vol. 12, No. 1, January 2016; 37-39

Xenoantigenicity of porcine decellularized valves

BackgroundThe xenoantigenicity of porcine bioprosthetic valves is implicated as an etiology leading to calcification and subsequent valve failure. Decellularization of porcine valves theoretically could erase the antigenicity of the tissue leading to more durable prosthetic valves, but the effectiveness of decellularization protocols in regard to completely removing antigens has yet to be verified. Our hypothesis was that decellularization would remove the more abundant α-gal antigens but not remove all the non α-gal antigens, which could mount a response.MethodsPorcine aortic valves were decellularized with 1% sodium dodecyl sulfate for 4 days. Decellularized cusps were evaluated for α-gal epitopes by ELISA. To test for non α-gal antigens, valves were implanted into sheep. Serum was obtained from the sheep preoperatively and 1 week, 1 month, and 2 months postoperatively. This serum was utilized for anti-porcine antibody staining and for quantification of anti-pig IgM and IgG antibodies and complement.ResultsDecellularized porcine cusps had 2.8 ± 2.0% relative α-gal epitope as compared to fresh porcine aortic valve cusps and was not statistically significantly different (p = 0.4) from the human aortic valve cusp which had a 2.0 ± 0.4% relative concentration. Anti-pig IgM and IgG increased postoperatively from baseline levels. Preoperatively anti-pig IgM was 27.7 ± 1.7 μg/mL and it increased to 71.9 ± 12.1 μg/mL average of all time points postoperatively (p = 0.04). Preoperatively anti-pig IgG in sheep serum was 44.9 ± 1.5 μg/mL and it increased to 72.6 ± 6.0 μg/mL average of all time points postoperatively (p = 0.01). There was a statistically significant difference (p = 0.00007) in the serum C1q concentration before valve implantation (2.5 ± 0.2 IU/mL) and at averaged time points after valve implantation (5.3 ± 0.3 IU/mL).ConclusionsDecellularization with 1% sodium dodecyl sulfate does not fully eliminate non α-gal antigens; however, significant reduction in α-gal presence on decellularized cusps was observed. Clinical implications of the non α-gal antigenic response are yet to be determined. As such, evaluation of any novel decellularized xenografts must include rigorous antigen testing prior to human trials.

A Review on the Biomechanical Effects of Fatigue on the Porcine Bioprosthetic Heart Valve.

Characterization of the mechanisms of degeneration of porcine bioprosthetic heart valves (BHV) during long-term cyclic loading is required for predicting and ultimately preventing their failure. Isolation of purely mechanical effects from host biological ones is a necessary first step in understanding the fatigue process as a whole. Thus, in this review we focus on mechanical factors alone as a means of isolating their role in altering biomechanical properties and ultimately their contribution to the fatigue damage process. Mechanical evaluations included tension controlled biaxial, 3-point flexural, and uniaxial failure tests performed on cuspal tissue following 0, 50, 100, 200, and 300 × 106 in vitro accelerated test cycles. Overall, biaxial mechanical results indicate a decreasing radial extensibility that can be explained by stiffening of the effective collagen fiber network as well as a small decrease in the splay of the collagen fibers. Moreover, these results suggest that the loss in flexural rigidity with fatigue that we have previously measured (ASAIO 1999; 45:59-63) may not be because of loss of collagen stiffness alone, but also to fiber debonding and degradation of the amorphous extracellular matrix. We discuss the implications of these results that point toward the development of chemical-treatment methods that seek to maintain the integrity of the amorphous extracellular matrix to ultimately extend BHV long-term durability.

Hydrodynamic Assessment of Aortic Valves Prepared from Porcine Small Intestinal Submucosa.

Infants and children born with severe cardiac valve lesions have no effective long term treatment options since currently available tissue or mechanical prosthetic valves have sizing limitations and no avenue to accommodate the growth of the pediatric patient. Tissue engineered heart valves (TEHVs) which could provide for growth, self-repair, infection resistance, and long-term replacement could be an ideal solution. Porcine small intestinal submucosa (PSIS) has recently emerged as a potentially attractive bioscaffold for TEHVs. PSIS may possess the ability to recruit endogenous cardiovascular cells, leading to phenotypically-matched replacement tissue when the scaffold has completely degraded. Our group has successfully implanted custom-made PSIS valves in 4 infants with critical valve defects in whom standard bioprosthetic or mechanical valves were not an option. Short term clinical follow-up has been promising. However, no hydrodynamic data has been reported to date on these valves. The purpose of this study was to assess the functional effectiveness of tri-leaflet PSIS bioscaffolds in the aortic position compared to standard tri-leaflet porcine bioprosthetic valves. Hydrodynamic evaluation of acute PSIS function was conducted using a left heart simulator in our laboratory. Our results demonstrated similar flow and pressure profiles (p>0.05) between the PSIS valves and the control valves. However, forward flow energy losses were found to be significantly greater (p<0.05) in the PSIS valves compared to the controls possibly as a result of stiffer material properties of PSIS relative to glutaraldehyde-fixed porcine valve tissue. Our findings suggest that optimization of valve dimensions and shape may be important in accelerating de novo valve tissue growth and avoidance of long-term complications associated with higher energy losses (e.g. left ventricular hypertrophy). Furthermore, long term animal and clinical studies will be needed in order to conclusively address somatic growth potential of PSIS valves.