Pulmonary Valve Conduit Research Articles

Early and late failure of tissue-engineered pulmonary valve conduits used for right ventricular outflow tract reconstruction in patients with congenital heart disease

To identify factors associated with the surgical outcome in patients undergoing right ventricular outflow tract reconstruction (RVOTR) using decellularized tissue-engineered pulmonary valve conduits (TEPVc) and to study their safety and longevity. From April 2006 to April 2010, 93 patients underwent either palliative or corrective RVOTR using Matrix P (37) and Matrix P Plus (56) xenogenic decellularized TEPVc (size range 11-27 mm). Median age and weight at operation were 20 (0.16-290) months and 10.15 (2.65-86) kg respectively. Primary and redo surgery occurred in 40 and 60% of cases, respectively. Eighty-eight patients (94.6%) received conduit implantation in the framework of corrective surgery, whereas in 5 (5.4%) a palliative procedure was undertaken. Follow-up was complete in 91% of patients, with a median duration of 12 months (range: 2 days-51 months). Data analysis included diagnosis, type of surgery (palliative vs. corrective) and age at surgery. Predetermined primary outcomes were represented by conduit failure or dysfunction. Two patients with Matrix P and two with Matrix P Plus died in the early post-operatively phase (4.3%). None of the deaths were conduit-related. One patient died at conduit replacement. Thirty-three patients (35.5%) experienced conduit failure whereas conduit dysfunction occurred in 27 patients (29%). Two-year freedom from conduit failure and dysfunction was 60.2% (95% CI: 50.1-69.6) and 77.4% (95% CI: 67.9-84.7), respectively. Reasons for failure were conduit stenosis in 20 cases (61%), pseudoaneurysm in 3 (9%), conduit dilatation (>50% of original diameter) in 2 (6%), stenosis of distal anastomosis involving pulmonary bifurcation in 6 (18%) and allograft dissection in 2 (6%). Histological examination showed inflammatory giant-type cells in the presence of a poor autologous cell seeding in all explanted specimens. Univariate and multivariate analyses showed an association between age at surgery ≤1 year and conduit dysfunction (adjusted HR: 2.29; 95% CI: 1.01-5.20, P = 0.04). Compared with the other conduit for RVOTR Matrix conduits showed a high incidence of failure. Our results suggest that the use of Matrix conduits for RVOTR should be considered with caution.

Novel Use of Extracellular Matrix Graft for Creation of Pulmonary Valved Conduit

We report the use of a commercially available graft material to create a trileaflet pulmonary valved conduit, which was implanted in a 12-year-old girl with mixed aortic valve disease as part of a Ross procedure. The patient presented with severe aortic insufficiency and left ventricular dilatation following balloon valvuloplasty. The patient lives in Ecuador, where most commonly used replacements for the pulmonary valve are either unavailable or unaffordable. Our technique involves the use of porcine small intestinal submucosal extracellular matrix (SIS-ECM), commercially available as CorMatrix ECM (CorMatrix Cardiovascular, Inc, Tallahassee, Florida) to create a trileaflet-valved conduit.

Imaging for trans-catheter pulmonary stent-valve implantation without angiography: role of intravascular ultrasound

Patients with stenosed biologic pulmonary conduits require redo cardiac surgery to prevent severe right ventricular dysfunction. Following the latest trends, the trans-catheter pulmonary stent-valve implantation represents a new fascinating alternative carrying a lower operative risk, compared with the standard open-heart re-intervention. Traditionally, the pulmonary stent valve is positioned off pump, under fluoroscopic control, and requires angiographies. However, alternative tools not requiring contrast injections for the intra-operative cardiac imaging have to be also considered strongly. The usefulness of intravascular ultrasound for the positioning of aortic endoprosthesis has already been proven in previous reports and, following the same principle, we have started to routinely implant balloon-expandable stent valves (Edwards Sapien™ THV) in stenosed pulmonary valve conduits using intravascular ultrasound for the stent-valve positioning without angiography. We describe the intra-operative intravascular imaging technique with technical details.

Differential distribution of structural components and hydration in aortic and pulmonary heart valve conduits: Impact of detergent-based cell removal

Evaluation of the physiological performance of biological scaffolds for tissue engineering applications has been mostly based on biophysical and morphological methods, with limited attention paid to the quantitative contribution of the main structural components to native and/or treated valve assemblies. In the present study quantitation addressed the porcine leaflet, sinus and adjacent wall of aortic and pulmonary valved conduits before and after detergent-based cell removal. Collagen, elastin, glycosaminoglycan, lipid and water contents were expressed in terms of relative concentration and volume fraction in order to assess their effective contribution to the native tissue and to changes following decellularization procedures. The main findings were recognition of unexpectedly large water and underestimated collagen contents, differential distribution of elastin between the sectors and of glycosaminoglycan along the conduits and pulmonary scaffold destabilization upon cell removal, not found in the aortic case. Simultaneous investigations allowed consistent comparisons between native and decellularized tissues and added analytical knowledge crucial for designing realistic constitutive models. We have provided a quantitative structural foundation for earlier biomechanical findings in pulmonary leaflets and the basis for validation of theoretical assumptions still lacking the support of experimental evidence in both conduits. Future insights into the distribution of load-bearing components in human conduits are likely to provide indications important to optimize the surgical positioning of valvular grafts.

Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age☆

The optimal pulmonary valved conduit for infants and small children remains controversial. This report compares the initial insertion outcome of small caliber bovine jugular vein (BJV) (12-14 mm) with pulmonary homografts (PHs) (10-15 mm) in patients under age 2. From December 1998 to August 2009, 84 children (mean age 8.4 + or - 8.5 months) received BJV (n=51) or PH (n=32) conduits. Mean Z score for BJV was 2.2 (range: -0.8 to 3.3) and for PH 2.1 (range: 0.8-4.2; P=0.2). The two cohorts were similar with respect to age, BSA, conduit indication, bypass and cross-clamp time. Graft dysfunction is defined as right ventricular outflow tract obstruction with peak echo-Doppler gradient >40 mmHg and/or grade III/IV conduit valve regurgitation. Graft failure is defined as need for conduit replacement or need for catheter or surgical re-intervention. Follow-up was greater in number in homografts (BJV, 4.4 + or - 3.0 years vs PH, 5.9+/-3.6 years; P=0.05). Early and late mortality were similar (BJV, 80%; PH 88%; P=0.55). No death was graft related. Freedom from dysfunction was improved at 5 and 10 years with BJV (BJV, 90% at 85% vs PH, 71% and 24% P<0.05). Conduit failure trended higher in the PH cohort at 5 and 10 years (BJV, 85% and 67% vs PH, 75% and 45%; P=0.06). Freedom from explantation was significantly better for BJV patients (BJV, 85% vs PH, 47% P<0.001. Freedom from distal conduit stenosis was similar (BJV, 52% vs PH, 44% P=0.36). This study suggests that the early performance of small BJV may be more advantageous than homografts. A BJV conduit is an appropriate first choice for conduit replacement in patients less than 2 years of age.

Morbidity and Mortality Risk Factors in Adults With Congenital Heart Disease Undergoing Cardiac Reoperations

Reoperations represent relatively frequent events in adults with congenital heart disease (ACHD). Cardiac operations in these patients present major difficulties in management and technique. Although reoperations in ACHD are becoming increasingly frequent, limited knowledge exists regarding perioperative risk factors. The study included 164 ACHD patients who underwent cardiac reoperations between January 2002 and December 2007 at our institution. Preoperative and intraoperative data were analyzed to identify morbidity and mortality risk factors. Reoperations included pulmonary valve implantation or conduit replacement in 60, aortic valve/root procedures in 36, residual atrial or ventricular septal defect closure in 19, and Fontan operation/conversion in 19. Hospital mortality was 3.6%. The mean mechanical ventilation time was 26 hours. Mean intensive care unit stay was 3.1 days. Severe postoperative complications occurred in 24 (15.1%). Cardiopulmonary bypass time (p = 0.001), Fontan operation/conversion (p = 0.001), preoperative hematocrit (p = 0.004), previous number of operations (p = 0.001), and preoperative congestive heart failure (p = 0.021) were associated with severe morbidity. No factor was associated with death. Reoperations in ACHD are mostly due to right ventricular outflow tract lesions and were associated with a low mortality rate if performed in a center with a considerable activity and a dedicated program. Severe morbidity is relatively frequent and is generally associated with the preoperative (high hematocrit due to cyanosis, congestive heart failure, and the number of previous operations) and operative (Fontan operation/conversion and cardiopulmonary bypass duration) conditions of the patient.

Bovine jugular veins as pulmonary valved conduits in adults – experience at 5 years with 64 implantations

Objective: Adults needing pulmonary valved conduits usually receive homografts. Mid-term durability of bovine jugular veins in children was comparable to homografts; calcification remained absent. We present results of 64 bovine jugular vein implantations in adults in pulmonary position.

Immunologically Untreated Fresh Xenograft Implantation in a Pig-to-Goat Model

Immunologically untreated frozen-stored xenografts show controlled rejection and repair due to reduced cellularity in our previous study. To clarify the issue, we compared results obtained using fresh and frozen-stored xenografts. Porcine pulmonary valved conduits were prepared without immunologic treatment and implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass immediately after harvest without frozen storage (the fresh group) or after frozen storage (-70 degrees C for 3 - 7 days) (the frozen group). Four goats were assigned to be raised for 3 (N = 1) or 6 (N = 3) months postoperatively in each group. One goat in the frozen group assigned for the 6-month observation expired at 2 months postoperatively because of thrombotic occlusion of the pulmonary valve. The other goats survived until the scheduled sacrifice. According to echocardiographic findings, one animal sacrificed at 3 months in the frozen group showed more than a moderate degree of pulmonary regurgitation, but all animals in the fresh group showed less than a mild degree. On gross examination, leaflets were slightly better preserved in the fresh group and aneurysmal dilatation of the pulmonary artery was observed at 3 months only in the frozen group. Microscopically, pulmonary arteries showed less severe degenerative changes in the fresh group. Moreover, in the fresh group, viable donor valve cells were still present until 3 months postoperatively (though it disappeared at 6 months postoperatively) and a linear endothelial lining of viable host cells was prominent on all leaflets, whereas this was not the case in the frozen group. In conclusion, fresh xenografts preserved cellular viability and showed fewer degenerative changes than frozen-stored xenografts. Thus, immunologically untreated fresh xenografts could provide a potential valve substitute with distinctive advantages in terms of self-healing potential as compared with frozen-stored xenografts.

Biomechanical Properties of Decellularized Porcine Pulmonary Valve Conduits

Tissue-engineered heart valves constructed from a xenogeneic or allogeneic decellularized matrix might overcome the disadvantages of current heart valve substitutes. One major necessity besides effective decellularization is to preserve the biomechanical properties of the valve. Native and decellularized porcine pulmonary heart valve conduits (PPVCs) (with [n = 10] or without [n = 10] cryopreservation) were compared to cryopreserved human pulmonary valve conduits (n = 7). Samples of the conduit were measured for wall thickness and underwent tensile tests. Elongation measurement was performed with a video extensometer. Decellularized PPVC showed a higher failure force both in longitudinal (+73%; P < 0.01) and transverse (+66%; P < 0.001) direction compared to human homografts. Failure force of the tissue after cryopreservation was still higher in the porcine group (longitudinal: +106%, P < 0.01; transverse: +58%, P < 0.001). In comparison to human homografts, both decellularized and decellularized cryopreserved porcine conduits showed a higher extensibility in longitudinal (decellularized: +61%, P < 0.001; decellularized + cryopreserved: +51%, P < 0.01) and transverse (decellularized: +126%, P < 0.001; decellularized + cryopreserved: +118%, P < 0.001) direction. Again, cryopreservation did not influence the biomechanical properties of the decellularized porcine matrix.

Time‐related Histopathologic Analyses of Immunologically Untreated Porcine Valved Conduits Implanted in a Porcine‐to‐Goat Model

This study was performed to evaluate the clinical feasibility of use of immunologically nontreated xenogenic valves, using a porcine-to-goat pulmonary valved conduit implantation model. Porcine pulmonary valve conduits were prepared with no specific immunological treatment and implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were assigned at predetermined intervals (1 day, 1 week, and 3, 6, and 12 months) as two animals for each interval. Echocardiographic examinations of the valves were performed before sacrifice. Upon retrieving the xenograft specimens, they were inspected visually and microscopically. Ten of the 12 animals survived the predetermined observation periods. Variable degrees of pulmonary regurgitation were the main findings on echocardiographic evaluations. On gross examination of the explanted specimens, all leaflets, except in one animal that prematurely died, were fairly well preserved. They were slightly shortened but free of thrombosis or vegetation. Aneurysmal dilatations of the anterior wall of the implanted pulmonary artery were observed in one of 12-month-survival animals and in another one of 3-month-survival animals. Microscopically, the three components of implanted xenografts (the pulmonary artery, valve, and infundibulum) were shown to be gradually replaced with host cells in time, while maintaining structural integrity. The nuclei of the donor tissue disappeared through pyknosis and karyolysis. In conclusion, immnunologically untreated xenogenic pulmonary valved conduits can be an alternative potential as valve substitutes with distinctive advantages of providing self-healing potential, despite a few problems observed in the current study such as occurrences of pulmonary regurgitation and sporadic cases of aortic aneurysm.

Right ventricular outflow tract reconstruction for pulmonary regurgitation after repair of tetralogy of Fallot. Preliminary results

Pulmonary regurgitation after tetralogy of Fallot (ToF) repair is associated with right ventricular dilatation, failure and arrhythmia. Timing and technique for re-intervention remain controversial. Our recent approach is to reconstruct the dilated right ventricle outflow tract (RVOT) as a fibro-muscular sleeve to support a pulmonary homograft valve conduit in orthotopic position. Indication is based on clinical and magnetic resonance (MR) criteria. We reviewed all patients who underwent RVOT reconstruction between January 2004 and February 2005. There were seven children (mean age 14+/-2 years) operated 13+/-2 years after ToF repair, and 12 adults (mean age 30+/-15 years) operated 23+/-10 years after ToF repair. Exercise testing and MR evaluation prior to surgery and at 1 year postoperative follow-up were compared. There was no operative mortality. At 1 year, pulmonary regurgitation was mild or less in 16/19 patients. Right ventricular (RV) end-diastolic (158+/-51 to 103+/-36ml/m(2), p<0.001) and end-systolic volumes (85+/-42 to 49+/-24ml/m(2), p=0.001) fell significantly. Importantly, effective RV stroke volume (43+/-10 to 48+/-7ml/m(2), p=0.019) and left ventricular (LV) stroke volume (43+/-7 to 47+/-7ml/m(2), p=0.009) increased significantly. The mean RV/LV end-diastolic volume ratio fell markedly in both children and adults (2.22+/-0.62 to 1.38+/-0.52). However, no improvement in maximal VO(2) on exercise was noted in either group. RVOT reconstruction restored valve function, improved RV dimensions and left and right stroke volumes. Maximal exercise capacity did not improve in either children or adults.

Invited commentary

Although enhanced knowledge and technological advances are making the total correction for the majority of congenital heart defects routine and safe, either the initial implantation of a biological valved conduit or conduit replacement inevitably lead to repeat surgery and represent one of the more frustrating issues of our field in need of a long-term solution. For reconstruction of the right ventricular outflow tract, valved homograft conduits have the best track record and are considered the gold standard. However, for small patients, small sized homografts are scarce and even when larger ones can be downsized (ie, bicuspidized), they present limitations with regards to patient-conduit size mismatch and resistance to degeneration, and they fare as poorly as other known xenograft valves. The current article [1Schreiber C. Sassen S. Kostolny M. et al.Early graft failure of small-sized porcine-valved conduits in reconstruction of the right ventricular outflow tract.Ann Thorac Surg. 2006; 82: 179-186Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar] is the third clinical report on the Shelhigh No-React porcine-valved conduit, confirming the poor results already observed by others [2Ishizaka T. Ohye R.G. Goldberg C.S. et al.Premature failure of small-sized Shelhigh No-React porcine pulmonic valve conduit model NR-4000.Eur J Cardiothoracic Surg. 2003; 23: 715-718Crossref PubMed Scopus (34) Google Scholar, 3Pearl J.M. Cooper D.S. Bove K.E. Manning P.B. Early failure of the Shelhigh pulmonary valve conduit in infants.Ann Thorac Surg. 2002; 74: 542-548Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar], which lead the authors to abandon implantation in their own practice, and to discourage the use of this conduit by others. The fact that 62% of their patients were under 1 year of age illustrates the problem known to us all in finding appropriately sized small homografts, and this justifies their trial to find a better and more practical “off the shelf” alternative. However, just as with other xenografts, the authors found that the Shelhigh No-React formed an extensive neointimal peel leading to early conduit stenosis and failure, although gross calcification was not noted. Despite efforts by the manufacturers to produce a nonimmunogenic product, the presence of a nonspecific macrophage and granulocyte-mediated inflammatory response still pointed to a foreign-body reaction. Therefore, the concerns and condemnation of this conduit by the authors are validly argued and well illustrate the ongoing search for an ideal alternative to reconstruct the right ventricular outflow tract. Accordingly the inevitable life-long threat of multiple reoperations for any given patient and the associated risks continue to motivate many research groups to focus their efforts on the quest for the tissue-engineered grail (ie, the “perfect biological valve”). Curiously the authors gave no justification for full heparinization followed by oral anticoagulation to an international normalized ratio of 2 to 3 for at least 3 months, and they did not state if some patients eventually required longer anticoagulation and for which reasons. Most centers would agree that unless a proven advantage in terms of patient benefit or conduit longevity or both can be demonstrated with this practice, anticoagulation could and should be avoided for biological implants.

In vitro re-endothelialization of detergent decellularized heart valves under simulated physiological dynamic conditions

The production of viable biological heart valves is of central interest in tissue engineering (TE). The aim of this study was to generate decellularized heart valves with an intact ultra-structure and to repopulate these with endothelial cells (EC) under simulated physiological conditions. Decellularization of ovine pulmonary valve conduits was performed under agitation in detergents followed by six wash cycles. Viability of EC cultures exposed to washing solution served to prove efficiency of washing. Resulting scaffolds were free of cells with preserved extracellular matrix. Biomechanical standard tension tests demonstrated comparable parameters to native tissue. Luminal surfaces of decellularized valvular grafts were seeded with ovine jugular vein EC in dynamic bioreactors. After rolling culture for 48 h, pulsatile medium circulation with a flow of 0.1 L/min was started. The flow was incremented 0.3 L/min/day up to 2.0 L/min (cycle rate: 60 beats/min), while pH, pO2, pCO2, lactate and glucose were maintained at constant physiological levels. After 7 days, a monolayer of cells covered the inner valve surface, which expressed vWF, indicating an endothelial origin. A complete endothelialization of detergent decellularized scaffold can be achieved under simulated physiological circulation conditions using a dynamic bioreactor system, which allows continuous control of the culture environment.

Tissue Engineering of Heart Valves

Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction. Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88+/-0.19% versus 30.20+/-3.93% migrated cells [mean+/-SEM]; cusps, 0.10+/-0.06% versus 10.24+/-1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (wall, 5.03+/-0.14% versus 24.31+/-2.38%; cusps, 3.18+/-0.38% versus 10.24+/-1.83%). SDS-PAGE of the pulmonary heart valve tissue revealed that considerable amounts of proteins with different molecular weights that were not detected in the human equivalent remain in the decellularized porcine heart valve. We describe for the first time that the remaining potential of decellularized pulmonary heart valves to attract monocytic cells depends strongly on whether porcine or human scaffolds were used. These findings will have an important impact on further investigations in the field of heart valve tissue engineering.

Time Related Histopathologic Changes of Acellularized Xenogenic Pulmonary Valved Conduits

A biologically engineered xenogenic heart valve based on the concept of acellularization offers promise as a means of overcoming the limitations of current prosthetic valves. We evaluated the process of repopulation by recipient cells on an acellularized xenograft treated with a saline (NaCl)-sodium dodecyl sulfate (SDS) solution. Porcine pulmonary valved conduits acellularized with NaCl-SDS solution were implanted in the right ventricular outflow tract of goats under cardiopulmonary bypass. The goats were sacrificed at 1 week and at 1, 3, 6, and 12 months after implantation. Echocardiographic evaluations of the valves were performed before sacrifice. Visual inspections and histopathologic examinations of the explanted xenogenic valved conduits were performed. Immunohistochemical staining was used to identify the composition of the recellularized cells. Fibroblasts and myofibroblasts were stained by vimentin and smooth muscle actin, and endothelial cells were stained by factor VII related antigen and CD31. Echocardiographic examinations of implanted acellularized xenogenic pulmonary valves revealed satisfactory function except for mild regurgitation and stenosis. On gross examination, all leaflets were well preserved, and no calcification was observed. Microscopic analysis of the acellularized leaflets showed progressive cellular ingrowth over time. The recellularization started from the leaflet base and progressed toward the free margin. Microthrombi were detected on unrecellularized portions. Inflammatory response was detected in the early phase, although it gradually subsided. At 6 months after implantation, cellular ingrowth by fibroblasts, myofibroblasts, and endothelial cells progressed up to 50% of the leaflet's height and progressively increased to 70% after 12 months. Extracellular matrices were regenerated by repopulating cells on the recellularized portion. This study suggests that acellularized xenogenic porcine valved conduits are biocompatible heart valve prostheses that are repopulated with autologous cells and extracellular matrices over a reasonable span of time and preserve the functional integrity without degeneration or calcification of leaflets.

Acellularized porcine heart valve scaffolds for heart valve tissue engineering and the risk of cross-species transmission of porcine endogenous retrovirus

Objective Acellularized porcine heart valve scaffolds have been successfully used for heart valve tissue engineering, creating living functioning heart valve tissue. However, there is concern about the possibility of porcine endogenous retrovirus transmission. In this study we investigated whether acellularized porcine heart valve scaffold causes cross-species transmission of porcine endogenous retrovirus in a sheep model. Methods Acellularized porcine pulmonary valve conduits (n = 3) and in vitro autologous repopulated porcine pulmonary valve conduits (n = 5) were implanted into sheep in the pulmonary valve position. Surgery was carried out with cardiopulmonary bypass support. The animals were killed 6 months after the operation. Blood samples were collected regularly up to 6 months after the operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, explanted tissue-engineered heart valves were tested for porcine endogenous retrovirus after 6 month in vivo. Results Porcine endogenous retrovirus DNA was detectable in acellularized porcine heart valve tissue. However, 6 months after implantation of in vitro and in vivo repopulated acellularized porcine heart valve scaffolds, no porcine endogenous retrovirus sequences were detectable in heart valve tissue and peripheral blood. Conclusion Acellularized porcine matrix scaffolds used for creation of tissue-engineered heart valves do not transmit porcine endogenous retrovirus.

Role of inflammation and ischemia after implantation of xenogeneic pulmonary valve conduits: histological evaluation after 6 to 12 months in sheep.

Commercially available biological heart valve prostheses undergo degenerative changes, which finally lead to complete destruction. Here we evaluate the role of inflammation and ischemia after implantation of xenogeneic heart valve conduits (XPC) generated by novel concepts of tissue engineering. Acellularized (a-)XPC and autologus re-seeded (s-)XPC were implanted into sheep. Samples were taken as follows: after acellularization (n = 2), after re-seeding (n = 2), 6 months (seeded/non-seeded: n = 3/5), 9 months (n = 2/5), and 12 months (n = 3/2) post implantation. Five native porcine conduits served as control. Using histological methods, samples were evaluated for pathological changes and existence/density of microvessels. Prior to implantation a-XPC were completely free of cells. Six months after implantation, leaflets and pulmonary arteries of s-XPC and a-XPC showed good endothelial surface coverage. Microvessel density within the myocardial cuffs and pulmonary vessel walls were comparable to control in all grafts. However, 6, 9 and 12 months after implantation pathological severe microvessel ingrowth, calcification and cellular infiltrations were observed on a-XPC and s-XPC valves, whereas myocardial cuffs and XPC-artery walls showed only mild degenerative alterations. Inflammatory reactions play a pivotal role in the degeneration of a-XPC and s-XPC. Thus, since ischemia seems to have little or no influence on this process, inflammation inductive factors should be the center of interest.

In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation

Background Approaches to in vivo repopulation of acellularized valve matrix constructs have been described recently. However, early calcification of acellularized matrices repopulated in vivo remains a major obstacle. We hypothesised that the matrix composition has a significant influence on the onset of early calcification. Therefore, we evaluated the calcification of acellularized allogenic ovine (AVMC) and xenogenic porcine (XVMC) valve matrix conduits in the pulmonary circulation in a sheep model. Methods Porcine (n = 3) and sheep (n = 3) pulmonary valve conduits were acellularized by trypsin/EDTA digestion and then implanted into healthy sheep in pulmonary valve position using extracorporeal bypass support. Transthoracic echocardiography (TTE) was performed at 12 and 24 weeks after the implantation. The animals were sacrificed at week 24 or earlier when severe calcification of the valve conduit became evident by TTE. The valves were examined histologically and biochemically. Results All AVMC revealed severe calcification after 12 weeks with focal endothelial cell clustering and no interstitial valve tissue reconstitution. In contrast, after 24 weeks XVMC indicated mild calcification on histologic examination (von Kossa staining) with histologic reconstitution of valve tissue and confluent endothelial surface coverage. Furthermore, immunohistologic analysis revealed reconstitution of surface endothelial cell monolayer (von Willebrand factor), and interstitial myofibroblasts (Vimentin/Desmin). Conclusions Porcine acellularized XVMC are resistant to early calcification during in vivo reseeding. Furthermore, XVMC are repopulated in vivo with valve-specific cell types within 24 weeks resembling native valve tissue.

Early failure of the shelhigh pulmonary valve conduit in infants

Background. The ideal valved conduit for right-sided (pulmonary) reconstruction in infants and children remains elusive. Desired characteristics include availability, ease of implantation, and longevity. Cryopreserved homografts are most commonly used, but availability of small sizes and limited durability remain problematic. The Shelhigh porcine-valved conduit (SPVC) with its No-React anticalcification properties was developed as a potential alternative to homografts. Methods. During a 10-month period, 8 patients underwent seven successful SPVC implantations. Median age was 9.5 days. Six conduits were less than 12 mm in diameter (range, 9 to 19 mm). Results. The early and late survival rates were 100%. During a mean follow-up of 18 months, five conduits were replaced at 6, 10, 12, 12, and 13 months for severe obstruction. Actuarial conduit failure at 12 months was 72%. Explanted SPVCs demonstrated marked pseudointimal peel formation along the original intima with an intense granulomatous inflammatory reaction. The intimal reaction was severely fibrogenic, but calcification was not present. For comparison, we retrospectively reviewed the cases of 23 infants receiving cryopreserved homografts during an overlapping period. Twelve patients, 6 of them neonates, were less than 90 days old. Mean homograft size was 13 mm (range, 8 to 15 mm), with nine less than 13 mm. During a mean follow-up of 26 months, six conduits were replaced at 7, 12, 12, 16, 20, and 35 months (sizes 13, 17, 14, 12, 10, and 12 mm, respectively). Only three of nine homografts less than 13 mm in size were replaced during a mean follow-up of 12 months. The overall homograft replacement rate was 17% at 22 months ( p = 0.005) compared with the SPVC). Conclusions. Although the SPVC appears to resist calcification, a marked foreign-body type of reaction results in pseudointimal peel formation and early conduit stenosis. In its present configuration, the SPVC in not a suitable valved conduit for use in infants. Although not ideal, the cryopreserved homograft has superior longevity to the SPVC.

De Vega tricuspid annuloplasty for tricuspid regurgitation in children

Background. Significant tricuspid valve regurgitation (TR) occurs with other congenital heart defects, typically after repair of right-sided obstructive lesions. Since 1991, we applied the De Vega tricuspid annuloplasty technique for TR in children. Methods. Forty-one children, aged 5 months to 22.7 years (mean, 9.9 years) underwent 42 De Vega tricuspid annuloplasties for moderate or severe TR during correction of other heart defects. One child had a De Vega during primary ventricular septal defect repair. The remaining patients had prior repair of tetralogy of Fallot or pulmonary atresia, or both (19 patients), double-outlet right ventricle (6 patients), pulmonary stenosis (4 patients), pulmonary atresia and intact ventricular septum (3 patients), complete atrioventricular septal defect (3 patients), and other diagnoses (6 patients). At the time of the De Vega, 37 patients (88%) had pulmonary valve replacement or right ventricular to pulmonary artery conduit replacement. Other procedures included aortic or mitral repair or replacement (6 patients), atrial septal defect and ventricular septal defect closure (5 patients), pulmonary arterioplasty (6 patients), and tracheoplasty (1 patient). Results. There were no deaths at follow-up of 3.4 ± 2.1 years; 1 child required cardiac transplantation 17 months postoperatively. Early postrepair echocardiography quantified TR as absent or mild (34 patients; 81%), mild-to-moderate (4 patients), moderate (3 patients), and severe (1 patient). The most recent echocardiogram showed moderate TR in 11 patients and severe TR in 2 patients (both with recurrent right ventricular hypertension). One child required tricuspid valve replacement 3 years later and 1 child had redo De Vega at the time of conduit re-replacement. No other child has symptomatic TR, significant tricuspid stenosis, or De Vega-related pacemaker implantation. Conclusions. The De Vega tricuspid annuloplasty safely provides excellent relief of TR, usually in children undergoing pulmonary valve replacement or conduit replacement. Although echocardiographic TR tends to increase with time (especially with right ventricular hypertension), it rarely requires reintervention or causes symptoms.