Aortic Xenograft Research Articles

Primary echocardiographic results of the Carpentier-Edwards Perimount Magna.

The aim of this study was to investigate the primary echocardiographic results of aortic valve replacement using 21- and 19-mm Carpentier-Edwards Perimount Magna bioprosthesis aortic xenografts in patients with small aortic annulus. Twenty patients (mean body surface area 1.63±0.16m(2)) underwent aortic valve replacement between June 2008 and December 2009. Eight and 12 patients received 21- and 19-mm Magna bioprostheses, respectively. After 12months, hemodynamic data were obtained by echocardiography to estimate the prosthesis-patient mismatch. At follow-up, significant decreases in peak and mean left ventricular aortic pressure gradients were observed in the 12 patients with aortic stenosis (P<0.05). Regression of the left ventricular mass was observed in all the patients (P<0.05). The mean measured effective orifice area (EOA) and EOA index (EOAI) were 1.61±0.28cm(2) and 0.99±0.16cm(2)/m(2), respectively. Prosthesis-patient mismatch (EOAI ≤0.85) was documented in three patients. The primary echocardiographic findings suggested that the hemodynamic performance of the 19- and 21-mm Carpentier-Edwards Perimount Magna bioprostheses was satisfactory in the patients with a small aortic annulus.

Downregulation of Remodelling Enzymatic Activity Induced by an Angiotensin-converting Enzyme Inhibitor (Perindopril) Reduces the Degeneration of Experimental Abdominal Aortic Aneurysms in a Rat Model

Aims Angiotensin-converting enzyme (ACE) inhibitors have proven their ability to affect vascular wall remodelling, in addition to their anti-hypertensive effects. The aim of this study was to assess the impact of perindopril on the development of abdominal aortic aneurysm (AAA) in a rat model, and its correlation to enzyme activities involved in vascular wall remodelling. Methods The model of the decellularised aortic xenograft in Lewis rat was chosen. Rats were randomised to two groups: group P fed with 3 mg kg −1 of perindopril daily during 30 days, or control group C ( n = 15 per group)). Rats were euthanised at 30 days for analysis. AAA growth and histological changes in the aortic wall were measured by histomorphometry. Proteolytic activities were measured by gelatin zymography of conditioned medium for activematrix metalloproteinase 9/pro-matrix metalloproteinase 9 (MMP9/pro-MMP9) and activeMMP2/pro-MMP2, and by quantitative immunofluorescence tissue for elastase and plasmin. Results The mean maximal diameter of AAAs at 30 days was significantly lower in the treated group P compared with the control group C (2.5 ± 1.0 vs. 4.9 ± 2.1 mm; P < 0.01). The expansion rate of AAAs after 30 days was significantly reduced in group P compared with group C (36 ± 14% vs. 67 ± 23%; P < 0.01). Pro-MMP9 and MMP9 activities were significantly decreased in relative intensity (RI) in group P compared with group C (0.43 ± 0.64 RI vs. 1.02 ± 0.61 RI, P = 0.01; 0.18 ± 0.57 RI vs. 0.66 ± 1.19 RI, P = 0.004). The activation rate of MMP2 was also significantly lower in group P compared with group C (1.27 ± 0.42 vs. 1.67 ± 0.44; P = 0.002). Elastase and plasmin tissue activities were significantly lower in group P compared with group C, respectively (3.9 ± 3.3 vs. 5.8 ± 3.7 IF min −1 g −1,and 25.9 ± 23.9 vs. 49.1 ± 38.7 IF min −1 g −1; P < 0.05). Conclusion After 30 days of treatment by perindopril, a significant decrease in aneurysmal degeneration of the decellularised aortic xenograft AAA model was observed. This phenomenon appears to be induced by a downregulation of enzymes involved in the aortic wall remodelling during aneurysmal degeneration.

Transapical Off-Pump Valve-in-Valve Implantation in Patients With Degenerated Aortic Xenografts

The reoperative risk for degenerated aortic valve xenografts may be increased in elderly patients with comorbidities. We evaluated the off-pump beating heart concept of transapical aortic valve implantation using the valve-in-valve (VinV) concept. Since March 2007, 11 patients with degenerated xenografts received transapical aortic valve implantation using the Edwards Sapien transcatheter heart valve (Edwards Lifesciences, Irvine, CA). After informed consent, all procedures were performed as an off-label use. Mean patient age was 78 +/- 6 years (range, 72 to 89), mean logistic European System for Cardiac Operative Risk Evaluation was 32% +/- 16% (range, 16% to 62%) and mean Society for Thoracic Surgeons score was 7% +/- 3% (range, 3% to 10%). All patients were treated off pump. The transapical aortic valve implantation was successful in all patients, and apical access was uncomplicated in all of them. Total operating room time was 71 +/- 14 minutes. On postoperative echocardiography, there was no paravalvular incompetence in any and mild (first degree) central incompetence in 2 of 11 patients. Sufficient flaring of the inflow and outflow parts of the Sapien prosthesis was observed in all patients, suggesting a stable position and an almost absent risk of late embolization. Maximal transvalvular pressure gradients were 21 +/- 8 mm Hg, and mean echocardiographic pressure gradients were 11 +/- 4 mm Hg. Follow-up extends to 330 +/- 293 days (range, 15 to 1,007), and all patients are well and alive. Valve-in-valve implantation is a truly minimally invasive procedure for redo treatment of failed aortic valve xenografts in high-risk elderly patients. The Edwards Sapien valve is well suited for VinV implantation, and this technique may become a routine procedure to treat degenerated xenografts in the future.

Effect of decellularization protocol on the mechanical behavior of porcine descending aorta.

Enzymatic-detergent decellularization treatments may use a combination of chemical reagents to reduce vascular tissue to sterilized scaffolds, which may be seeded with endothelial cells and implanted with a low risk of rejection. However, these chemicals may alter the mechanical properties of the native tissue and contribute to graft compliance mismatch. Uniaxial tensile data obtained from native and decellularized longitudinal aortic tissue samples was analyzed in terms of engineering stress and fit to a modified form of the Yeoh rubber model. One decellularization protocol used SDS, while the other two used TritonX-100, RNase-A, and DNase-I in combination with EDTA or sodium-deoxycholate. Statistical significance of Yeoh model parameters was determined by paired t-test analysis. The TritonX-100/EDTA and 0.075% SDS treatments resulted in relatively variable mechanical changes and did not effectively lyse VSMCs in aortic tissue. The TritonX-100/sodium-deoxycholate treatment effectively lysed VSMCs and was characterized by less variability in mechanical behavior. The data suggests a TritonX-100/sodium-deoxycholate treatment is a more effective option than TritonX-100/EDTA and SDS treatments for the preparation of aortic xenografts and allografts because it effectively lyses VSMCs and is the least likely treatment, among those considered, to promote a decrease in mechanical compliance.

Transapical off-pump aortic valve-in-a-valve implantation in two elderly patients with a degenerated porcine bioprosthesis

Re-operative heart-valve replacement is a high-risk procedure and even more so in elderly patients. Another option in high-risk patients with a degenerated aortic xenograft is the implant of a second aortic bioprosthesis using a transcatheter approach. We report two cases of patients with a severely degenerated porcine aortic bioprosthesis who were successfully treated by a transapical valve-in-a-valve implantation.

Human Minimally Invasive Off-Pump Valve-in-a-Valve Implantation

Reoperative heart valve replacement for degenerated xenografts is associated with an increased surgical risk. We used our experience with transcatheter transapical aortic valve implantation to perform a transapical off-pump aortic valve-in-a-valve implantation. Hemodynamic function was excellent and the patient had a fast and uneventful recovery.

FK778 in Experimental Xenotransplantation: A Detailed Analysis of Drug Efficacy

This study examines the efficacy of FK778 regimens for prevention of different phases of xenograft rejection. Antibody and complement tissue depositions were measured by immunofluorescence in a discordant ex vivo rat-to-human heart perfusion model of hyperacute rejection with immunosuppressant-enriched human blood. The concordant hamster-to-rat aortic xenotransplantation model was used to assess host cellular (lymphocyte activation, mixed lymphocyte reaction [MLR]) and humoral responsiveness (xenoantibody production) as well as histologic xenograft rejection. Recipients were treated for 14 days with FK778, tacrolimus, sirolimus or combination regimens at varying doses. Antibody binding during hyperacute rejection was unaffected by the immunosuppressive treatment, but complement deposition was reduced in the following order: tacrolimus > FK778 approximately sirolimus. FK778 most effectively reduced complement factor 5 in vitro. In untreated rats with hamster aortic xenografts, a large infiltrative response was observed within the grafts with extensive myocyte necrosis. Tacrolimus > FK778 approximately sirolimus dose-dependently diminished xenograft infiltration and in the same order reduced vessel-wall myocyte necrosis. Tacrolimus approximately FK778 > sirolimus reduced in vivo lymphocyte CD25 expression and tacrolimus > FK778 approximately sirolimus diminished MLR. Xenoreactive IgM and IgG antibody production levels were vigorously upregulated a few days after transplantation, but were significantly reduced by tacrolimus > FK778 approximately sirolimus. Combination regimens revealed no significant benefit when compared with the corresponding monotherapy groups. FK778 mildly interfered with hyperacute rejection and markedly suppressed acute humoral and cellular aortic xenograft rejection. However, T-cell-dependent host responses were most potently suppressed by tacrolimus, and the overall efficacy of FK778 was similar to that of sirolimus.

Stentless full root aortic valve replacement is as safe as stented xenograft implantation

The technically demanding full root aortic valve replacement necessitating coronary ostia reimplantation leads to controversial hesitation by some surgeons despite superior haemodynamics and excellent long term clinical performances of the stentless xenografts. To determine the justification we compared our clinical data of stentless full root replacements with stented aortic xenograft implantations.

Randomized stentless versus conventional aortic xenograft implantation: Eight year follow-up

Objectives: Aim of this study was to evaluate the eight year results after randomized stentless versus conventional xenograft aortic valve replacement (AVR).

The Carpentier-Edwards Perimount Magna aortic xenograft: a new design with an improved hemodynamic performance

This study compares the implantation characteristics and the hemodynamic performance of the new Carpentier-Edwards Perimount Magna (CEPM) xenograft with those of the standard Perimount (CEPS) valve in the aortic position. Eighty consecutive patients surviving an aortic valve replacement with either the CEPS valve (n=40) or the CEPM prosthesis (n=40) in the supra-annular position were retrospectively reviewed. One year follow-up was complete and hemodynamic performance assessed by Doppler echocardiography. The mean valve size implanted was 21.3+/-1.7 mm (CEPS) vs. 22.2+/-1.8 mm (CEPM). The average mean pressure gradient was 13.6+/-5.1 mmHg in the CEPS group and 9.6+/-3.3 mmHg in the CEPM group (P<0.0001). Mean and peak gradients were slightly lower and the effective orifice areas (EOA) were larger for the Magna prosthesis than for the comparable standard valves: 19 mm (1.58+/-0.2 vs. 1.28+/-0.1 cm(2)), 21 mm (1.90+/-0.4 vs. 1.69+/-0.4 cm(2)), 23 mm (2.07+/-0.3 vs. 1.86+/-0.3 cm(2)), 25 mm (2.30+/-0.1 vs. 1.89+/-0.5 cm(2)). The average indexed EOA was statistically different between groups (CEPS 0.98+/-0.21 cm(2)/m(2) vs. CEPM 1.20+/-0.25 cm(2)/m(2)). Patient-prosthesis mismatch (indexed EOA<or=0.85 cm(2)/m(2)) was present in 40.7% (CEPS) vs. 16.6% (CEPM) of the patients with valve sizes <or=21 mm. Our study demonstrates that the Magna prosthesis significantly reduces the incidence of patient-prosthesis mismatch when compared to the standard Perimount valve in the aortic position.

The Preferable Use of Port Access Surgical Technique for Right and Left Atrial Procedures

We analyzed the results of mitral valve operations, either alone or in any combination with the tricuspid valve surgeries in the period from January 2001 till June 2004. The period was divided into two parts, classical sternotomy part (C) (110 patients) and minimally invasive port access part (PA) (105 patients), later being used from December 2002 till now. Also, what we were interested in was the total hospital cost of both types of the procedures and if there are any advantages of port access over the classical sternotomy. The mean age was 61.2 +/- 10.2 and 60.3 +/- 12.4 (C versus PA) and mean additive Euroscore was 6.5 versus 4.8 (C versus PA). There were statistically significant differences (P < .0001) in cardiopulmonary bypass time (CPB) and aortic cross-clamp time (AXT) between both groups: CPB C versus PA: 98.3 +/- 33.5 minutes versus 149.2 +/- 44.2 minutes (mean +/- sd), AXT C versus PA: 62.9 +/- 20.6 minutes versus 88.3 +/- 26.8 minutes (mean +/- sd). There were no statistically significant differences in mortality and stroke for both the groups (mortality P = 1, stroke P = .53). There were statistically significant differences in favor of the port access over the classical one for: intensive unit stay (P = .004), postoperative stay in days (P < .0001), blood transfusion (P < .0001), postoperative thoracic bleeding (P < .0001), and extubation time in hours (P < .0001). Furthermore, costs analyses showed that the average total patient cost was less for port access (P < .0005). The differences between endo and classical type suggested that the port access type of surgery is 20% cheaper than the classical one. We may conclude that port access surgery is an acceptable alternative to classical type of surgery, also in complex pathology of the mitral and tricuspid valve.

Surgical Treatment in a Patient with Multiple Systemic Complications of Prosthetic Aortic Valve Endocarditis: Case Report

A 31-year-old woman who had undergone aortic and mitral valve replacement 1 year previously was hospitalized with suspected prosthetic valve endocarditis. Freestyle stentless aortic xenograft was successfully replaced using freestanding total aortic root replacement techniques at the left ventricular outflow tract position, and aorta-to-right coronary artery bypass was also applied with a saphenous vein graft. The patient developed multiple systemic problems during the preoperative and postoperative periods and was successfully treated with intensive interventions. She was discharged at the postoperative fourth month, and the following 28 months were uneventful.

Replacement of the Aortic Valve and Ascending Aorta With an Extended Root Stentless Xenograft

Purpose We present an early series to determine the technical feasibility of simultaneous aortic valve and complete ascending aortic replacement using a longer stentless aortic xenograft, harvested with an extended root. Description The stentless xenograft valved conduits commercially available are too short for complete ascending aorta replacement, and usually a prosthetic tube graft is required distally. Evaluation To avoid this extra prosthetic conduit distally a number of stentless aortic xenografts with extended conduit were obtained from a supplier (Medtronic Inc). They were inserted in 6 elderly patients (67.8 ± 7.1 years) who all required aortic valve and ascending aorta replacements owing to pathologic dilation. Conclusions In all cases an extra prosthetic conduit was avoided, and the length of the available biological conduit comfortably allowed total ascending aortic replacement without tension. The advantages therefore were one less suture line, cost saving regarding the prosthetic conduit, shorter cross-clamping time, and possibly shorter time spent on hemostasis.

Giant anastomotic pseudoaneurysm complicating aortic xenograft replacement

A 74-year-old woman was referred for investigation of a 2-week history of progressive dyspnea. Her medical history included an aortic valve replacement with a stentless bioprosthesis followed 13 months later by the replacement of the aortic root with a porcine xenograft. Transesophageal echocardiography revealed a giant circular pseudoaneurysm of the aortic xenograft with compression of the prosthetic aortic valve and concomitant severe aortic regurgitation. Dehiscence of the proximal graft anastomosis was also diagnosed, and a possible distal anastomotic dehiscence was suspected. The latter turned out intraoperatively to be an almost complete dehiscence of the right coronary artery. The patient died intraoperatively.

Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis.

To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury. VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms. Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed. Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls. VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.

Freestyle xenograft implantation technique for reducing aortic insufficiency.

The Freestyle aortic xenograft has been shown to be safe and effective for aortic valve replacement. However,implantation is often complicated by aortic valve insufficiency, which could lead to premature valve failure. We describe an implantation technique that can potentially prevent aortic insufficiency.

Reconstruction of right ventricular outflow tract with stentless xenografts in Ross procedure.

To investigate whether the use of a stentless porcine aortic xenograft can be an alternative for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure, 9 patients underwent the Ross procedure and RVOT reconstruction with a stentless xenograft since January 2000. After the aortic valve was replaced with a pulmonary autograft, a stentless xenograft with a xeno- pericardial roll was implanted in the RVOT. One patient required subsequent aortic valve replacement because of severe regurgitation of the pulmonary autograft. All patients recovered well from the operation. The right ventricle-pulmonary arterial pressure gradient was 18 +/- 7 mm Hg at discharge and was not significantly increased during the 2-year follow-up period. Although 1 patient died of ventricular arrhythmia 5 months after, his cardiac function was normal, and transpulmonary valve pressure was 19 mm Hg in the follow-up. The other 7 patients are currently in New York Heart Association functional Class I. Although long-term follow-up is required to explain the durability, the stentless xenograft with a pericardial roll is considered to be an alternative for reconstruction of the RVOT within 2 years after the Ross procedure.

The effects of cryopreserved aortic xenografts on secondary cardiac xenografts

The effects of cryopreserved aortic xenografts on secondary cardiac xenografts

Intraoperative Transesophageal Echo-Doppler Evaluation of Stentless Aortic Xenografts. Incidence and Significance of Moderate Gradients

Background: The aim of this study was to assess the utility of intraoperative transesophageal echocardiography (TEE) in the evaluation of patients undergoing aortic valve replacement with the CryoLife-O'Brien® (CLOB) Stentless Porcine Aortic Bioprosthesis. Methods: Between May 1994 and March 1995, 26 patients (15 men, mean age 68.4±10.78 years) had a CLOB valve in the aortic position. Transprosthetic gradients and valve regurgitation were detected by intraoperative TEE. Prosthetic regurgitation and transvalvular gradients were evaluated at six-month intervals using transthoracic echo-Doppler (TTE). Results: The majority of implants resulted in low gradients (83.7%), with only four patients exhibiting a moderate gradient (15.3%). Color flow Doppler imaging showed central aortic regurgitation in only four of 25 patients (trivial, n = 4; mild, n = 1). There was one paravalvular leak (trivial. n= 1). At follow-up examination (mean 37±12 months), 24 of 25 patients exhibited low mean gradients (7.25±2.81 mmHg). At follow-up one patient who had low velocities in the LVOT at perioperative evaluation exibited a moderate gradient (45 mmHg) with an effective orifice area of 0.8–0.9 cm2. Conclusions: Intraoperative TEE was effective in assessing prosthetic stentless valve function.

Intraoperative transesophageal echo-Doppler evaluation of stentless aortic xenografts. Incidence and significance of moderate gradients

Background: The aim of this study was to assess the utility of intraoperative transesophageal echocardiography (TEE) in the evaluation of patients undergoing aortic valve replacement with the CryoLife–O’Brien® (CLOB) Stentless Porcine Aortic Bioprosthesis. Methods: Between May 1994 and March 1995, 26 patients (15 men, mean age 68.4±10.78 years) had a CLOB valve in the aortic position. Transprosthetic gradients and valve regurgitation were detected by intraoperative TEE. Prosthetic regurgitation and transvalvular gradients were evaluated at six-month intervals using transthoracic echo-Doppler (TTE). Results: The majority of implants resulted in low gradients (83.7%), with only four patients exhibiting a moderate gradient (15.3%). Color flow Doppler imaging showed central aortic regurgitation in only four of 25 patients (trivial, n=4; mild, n=1). There was one paravalvular leak (trivial, n=1). At follow-up examination (mean 37±12 months), 24 of 25 patients exhibited low mean gradients (7.25±2.81 mmHg). At follow-up one patient who had low velocities in the LVOT at perioperative evaluation exibited a moderate gradient (45 mmHg) with an effective orifice area of 0.8–0.9 cm 2. Conclusions: Intraoperative TEE was effective in assessing prosthetic stentless valve function.