Precise reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in new formula: a case report.

BACKGROUND: The current study presents a novel and precise surgical technique for complete reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in a patient with aortic valve disease and endocarditis. The technique aims to provide a more effective and reproducible method for aortic valve repair, with the goal of improving outcomes and quality of life for patients with aortic valve disease. CASE PRESENTATION: A 35-year-old Iranian male with aortic valve disease and endocarditis underwent aortic valve reconstruction surgery. Preoperative echocardiography showed a degenerative aortic valve with severe regurgitation, reduced left ventricular ejection fraction, and specific aortic root dimensions. The surgical technique involved precise measurements and calculations to design the size and shape of the new aortic valve cusps using autologous pericardium, with the goal of optimizing coaptation and function. The surgeon calculated the intercommissural distance based on the aortic annulus diameter to determine cusp size and shape. He tailored the pericardial cusps to have a height equal to 80% of the coaptation margin length. Detailed suturing techniques were used to ensure proper alignment and coaptation of the new cusps. Intraoperative evaluation of the valve function using suction and transesophageal echocardiography showed good coaptation and minimal residual regurgitation. At the 3-year follow-up, the patient had a well-functioning aortic valve with only trivial leak and was in satisfactory clinical condition. CONCLUSIONS: Glutaraldehyde-treated autologous pericardium is a validated leaflet alternative, and the causes of its failure are late annular dilatation and other technique breakdowns. Current evidence reveals that aortic valve reconstruction with glutaraldehyde-treated autologous pericardium is associated with many advantages with the potential to improve patient outcomes and quality of life. Further clinical studies are warranted to evaluate the long-term durability and efficacy of this approach.

Clinical outcomes of aortic root repair using pericardial autograft for acute type a aortic dissection.

BACKGROUND: For acute type A aortic dissection involving the aortic root with root diameter no more than 45 mm, there are various aortic root repair techniques. In this study, a novel surgical technique using a pericardial autograft for aortic root repair was introduced. We described its surgical steps in detail and compare its clinical outcomes with direct suture technique. METHODS: Between July 2017 and August 2022, 95 patients with acute type A aortic dissection who underwent aortic root repair were enrolled, including aortic root repair using pericardial autograft (group A, n = 49) or direct suture (group B, n = 46). The patient's clinical data were retrospectively analyzed, and a 5-year follow-up was conducted. RESULTS: The 30-day mortality, re-exploration for bleeding, postoperative new-onset renal failure requiring continuous renal replacement therapy, stroke, and paraplegia occurred in 3%, 4%, 11%, 5%, and 2% of the overall patients, respectively. There was no significant difference in the 30-day mortality and complication rate between the two groups. The 30-day mortality and re-exploration for bleeding marked the primary endpoint events. Logistic regression analysis indicated that there was a significant correlation between the primary endpoint events and surgical technique (odds ratio, 0.002; 95% confidence interval, 0-0.159; P = 0.026). The aortic valve insufficiency of the two groups were significantly improved after operation (group A, P < 0.001; group B, P < 0.001). During follow-up, there was no significant difference in short-term survival between the two groups after surgery (log-rank P = 0.75), and all patients were free from reoperation for aortic disease. CONCLUSIONS: Patients who underwent aortic root repair using pericardial autograft tended to have reduced 30-day mortality and a lower risk of re-exploration for bleeding. Using pericardial autograft for aortic root repair is a safe and useful approach for patients with acute type A aortic dissection involving the aortic root.

Single patch technique for aortic annulus reconstruction in prosthetic valve endocarditis.

Aortic root reconstruction during aortic root replacement for a patient with prosthetic valve endocarditis and aortic root abscess can be a difficult procedure with many possible complications. In this video case report, we describe our novel technique using a single bovine pericardial patch that avoids deep stitches or external sutures to support the friable annulus. Compared with more standard methods, this approach has shorter cross-clamp and cardiopulmonary bypass times and is less demanding technically.

Blending three repair techniques in a case of complex mitral valve endocarditis.

In a 39-year-old male with mitral valve endocarditis, after 6 weeks of intravenous antibiotics, echocardiography confirmed multiple vegetations on both leaflets, a flail posterior leaflet flail and contained perforation of the anterior leaflet in a windsock-like morphology. All vegetations, diseased and ruptured chords and the windsock-like contained rupture of the anterior leaflet were carefully resected via a right minithoracotomy and with femoral cannulation. Three repair techniques were blended to reconstruct the valve: (1) A large, infected portion of the prolapsing posterior leaflet was resected in a triangular fashion, and the edges were re-approximated using continuous 5-0 polypropylene sutures. (2) The anterior leaflet defect was repaired with a circular autologous pericardial patch that had been soaked in glutaraldehyde. (3) A set of artificial chords for P2 was created using CV-4 polytetrafluoroethylene sutures and adjusted under repeated saline inflation. A 38-mm Edwards Physio-I annuloplasty ring was implanted. The artificial chords were adjusted again after annuloplasty and then tied. Transoesophageal echocardiography (TEE) confirmed the absence of residual mitral regurgitation and systolic anterior motion and a mean pressure gradient of 3 mmHg. The patient was discharged after 5 days with a peripherally inserted central catheter to complete an additional 4 weeks of intravenous antibiotics and had an uneventful recovery.

A Case of Incidentally Discovered Congenital Complete Pericardial Defect during Lobectomy for Lung Cancer: A Case Report and Literature Review.

An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.

Decellularization and characterization of camel pericardium as a new scaffold for tissue engineering and regenerative medicine.

BACKGROUND: Valvular heart diseases (VHDs) have become prevalent in populations due to aging. Application of different biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of VHD. Aortic valve replacement using tissue-engineered xenografts is a considered approach, and the pericardium of different species such as porcine and bovine has been studied over the last few years. It has been suggested that the animal origin can affect the outcomes of replacement. METHODS: So, herein, we at first decellularized and characterized the camel pericardium (dCP), then characterized dCP with H&E staining, in vitro and in vivo biocompatibility and mechanical tests and compared it with decellularized bovine pericardium (dBP), to describe the potency of dCP as a new xenograft and bio scaffold. RESULTS: The histological assays indicated less decluttering and extracellular matrix damage in dCP after decellularization compared to the dBP also dCP had higher Young Modulus (105.11), and yield stress (1.57 ± 0.45). We observed more blood vessels and also less inflammatory cells in the dCP sections after implantation. CONCLUSIONS: In conclusion, the results of this study showed that the dCP has good capabilities not only for use in VHD treatment but also for other applications in tissue engineering and regenerative medicine.

Heart Transplantation in a Patient With Rheumatic Heart Disease and Severe Left Atrial Calcification.

A 62-year-old woman who had undergone mitral valve replacement 24 years ago was admitted to the hospital with congestive heart failure. She needed heart transplantation for stage D heart failure. Preoperative cardiac computed tomographic scans showed a severely calcified left atrium and a large right atrium. Given that the left atrium's calcification was too severe to suture, the calcified left atrial wall was broadly resected, and the resected left atrial wall was reconstructed with a bovine pericardial patch for anastomosis with the donor's left atrial wall. The operation was completed without heavy bleeding, and the patient was discharged from the hospital with no complications.

Treatment of Aorto-iliac and Infrainguinal Vascular Infections with a Prefabricated Bovine Pericardial Graft.

BACKGROUND: The use of biological grafts provides acceptable mid- and long-term results in native or prosthetic vascular infections. Several reports describe the successful use of bovine pericardium in case of vascular infections, mainly as a large patch to be sutured as a tubular graft. Recently, a novel prefabricated bovine pericardium graft (Biointegral Surgical No-React® Inc, Mississauga, ON, Canada) has been introduced in clinical practice with promising results. In this study, we report our preliminary experience utilizing Biointegral Surgical graft in case of native and or prosthetic aorto-iliac and infrainguinal infection. METHODS: We retrospectively analyzed data from 20 patients with native or prosthetic aorto-iliac and infrainguinal infection who underwent in situ reconstruction (ISR) with a Biointegral Surgical No-React bovine pericardium prosthesis between October 2020 and February 2023 at the Vascular Surgery Unit of the Fondazione Policlinico Universitario Gemelli - IRCCS in Rome, Italy. All patients followed a standardized protocol including postoperative anticoagulation and long-term intravenous antibiotics. RESULTS: The indication for surgery was: mycotic aortic aneurysm in 4 patients (20%), graft infection after abdominal aortic repair in 11 patients (55%), peripheral graft infection in 5 patients (25%). Complete excision of the infected aorta or prosthetic graft, surgical debridement and ISR were performed in all patients. Hospital mortality rate was 5% (n = 1) and graft-related mortality of 0%. During follow-up (median 13 months, range 6-34 months), reinfection was 5.2% and primary graft patency 94.7%. CONCLUSIONS: The use of prefabricated bovine pericardial grafts represents a promising option for the treatment of native and prosthetic aorto-iliac and infrainguinal infections. The application of this biological graft with a standardized postoperative protocol has been associated with a satisfactory patency and reinfection rate without increased bleeding complications.

Outcomes post Ozaki procedure among children with aortic valve disease at Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania: a retrospective descriptive study.

BACKGROUND: Aortic valve reconstruction using glutaraldehyde-treated autologous pericardium, also called Ozaki procedure, is a surgical procedure for patients with aortic valve disease. Gratifying results have been reported in adult patients, however, limited published data is available in paediatric population. This study looked at clinical characteristics and early outcomes of children who underwent Ozaki procedure at our Institute. METHODS: This was a retrospective descriptive study conducted on children who underwent aortic valve reconstruction at Jakaya Kikwete Cardiac Institute (JKCI) from January 2019 through December 2022. Medical records of these children were reviewed to extract data on demographics, clinical characteristics, redo surgical interventions and survival. RESULTS: A total of 10 children underwent Ozaki procedure during the study period. Eight children had severe aortic regurgitation while 2 had severe aortic stenosis preoperatively. All children had either none or trivial aortic regurgitation immediately after surgery. None of them had redone operations throughout the follow-up period. There was no in-hospital mortality, however, one child died one-year after surgery. The mean follow-up period was 1.6 years with the longest follow-up time of 4 years. CONCLUSION: Ozaki procedure showed encouraging early results among children with aortic valve disease who underwent surgical repair by this technique. Future studies with larger sample sizes and longer follow up periods to evaluate long-term results in this population are recommended.

Evaluation of pericardium patch graft thickness in patients with Ahmed glaucoma valve implantation: an anterior segment OCT study.

PURPOSE: To evaluate the changes in thickness of tissues, specifically the pericardium patch graft (PPG) covering the silicone tube in Ahmed Glaucoma Valve (AGV) surgery. STUDY DESIGN: Prospective observational study. METHODS: This study included cases with refractory glaucoma that underwent AGV implantation with PPG coverage. Conjunctival epithelium, stroma and PPG thickness covering the tube were measured using anterior segment optical coherence tomography (AS-OCT) at 1, 6 and 12 months. Additionally, the same measurements were taken 1500 µm away from the tube as a control for the central measurements. RESULTS: Twenty-seven eyes of 27 patients were evaluated in the study. Although PPG thickness decreased significantly in both regions, the amount of reduction was more pronounced centrally. Centrally, the reduction rate was 21.2% and 34.8% during the 1-6 months period and 6-12 months period, while peripherally it was 3.5% and 5.1%, respectively. No change was observed in the thickness of the epithelium during the follow-up period. There was a significant thinning of the stroma in the central and peripheral regions during the 1-6 months period (30.5% and 17%, respectively). No cases of exposure were observed during the follow-up period. CONCLUSION: Although the most evident thinning of the layers covering the tube was observed in the early postoperative period, PPG showed a stable decrease even in the late period. The progressive reduction in the PPG thickness observed also in the peripheral region indicates that factors beyond mechanical forces contribute to this degenerative process. AS-OCT could be a valuable non-invasive tool in clarifying this process.

Physician Made Bovine Pericardial Tube Grafts in Aortic Infection: A European Multicentre Study.

OBJECTIVE: This study examines outcome and durability of physician made bovine pericardial tube grafts in aortic infections in all anatomical locations. METHODS: This was a retrospective and prospective international multicentre study. Peri-operative and long term outcomes of patients undergoing in situ aortic reconstruction for native or graft infections with physician made bovine pericardial tube grafts between January 2008 and December 2020 in four European tertiary referral centres were analysed. The primary endpoint was recurrent aortic infection. Secondary endpoints were persistent infection, aortic re-operation for infection, graft related complications, and death. RESULTS: One hundred and sixty eight patients (77% male, mean age 67 ± 11 years) were identified: 38 (23%) with native and 130 (77%) with aortic graft infection. The thirty day mortality rate was 15% (n = 26) overall, 11% (n = 4), and 17% (n = 22) for native and aortic graft infections, respectively (p = .45). Median follow up was 26 months (interquartile range [IQR] 10, 51). Estimated survival at one, two, three, and five years was 64%, 60%, 57%, and 50%, and significantly better for native (81%, 77%, 77%, and 69%) than for graft infections (58%, 55%, 51%, and 44%; p = .011). Nine patients (5.3%) had persistent infection and 10 patients (6%) had aortic re-infection after a median of 10 months (IQR 5, 22), resulting in an estimated freedom from re-infection at one, two, three, and five years of 94%, 92%, 90%, and 86%. Estimated freedom from graft complications at one, two, three, and five years was 91%, 89%, 87%, and 87%. CONCLUSION: This multicentre study demonstrates low re-infection rates when using physician made bovine pericardial tube grafts, comparable to those of other biological grafts. The rate of graft complications, mainly anastomotic aneurysms and stenoses, was low, while graft degeneration was absent. Physician made bovine pericardial tube grafts are an excellent tool for in situ reconstruction in the setting of native aortic infection or aortic graft infection.

Outcomes Following Use of Bovine Pericardium (Xenoprosthetic) Grafts for Reconstruction of Mycotic Aortic Aneurysms and Infected Aortic Grafts: A Systematic Review and Meta-Analysis.

BACKGROUND: Infected aortic grafts and mycotic aneurysms represent one of the most complex challenges faced by vascular surgeons. Treatment has progressed from extra-anatomical bypass to in situ reconstruction. Additionally, bovine pericardium reconstruction (BPR) has increased, due to accessibility and reduced lower limb morbidity. There remains, however, limited evidence for its use. The aim is to pool all known data to understand outcomes following BPR of mycotic aneurysms or infected vascular grafts. METHODS: A systematic review was conducted in November 2021 with subsequent computerized meta-analysis of the pooled results and a final search in March 2022. Three databases, Excerpta Medica dataBASE (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), and National Institutes of Health PubMed (PubMed), were searched for the search term "(bovine OR xenoprosthetic) AND (aneurysm)", according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: From 9 studies, there were 133 patients: 67% graft infections and 33% mycotic aneurysms. Fifty-seven percent of reconstructions were in the abdominal aorta and 33% were in the thoracic aorta. One hundred fifty-eight pathogens were identified, including Staphylococcus aureus (23%), Candida albicans (13%), and Escherichia coli (13%). In 12%, no microorganisms were identified. Thirty-day mortality was 19.14% (CI 10.83-28.71), late mortality was 19.08% (confidence interval [CI] 7.76-32.83), and overall mortality was 40.20% (CI 29.82-50.97). One patient died intraoperatively. There were a total of 151 in-hospital complications after 30 days postoperation. Common complications were acute renal failure (17%), pneumonia (14%), delirium (12%), respiratory insufficiency (11%) and renal insufficiency (7%). Lower limb ischemia was low, occurring in 5.66% (CI 0.54-13.82) of patients. Loss of graft patency leading to reintervention occurred in 1.20% (CI 0.00-7.71) of the grafts. Reinfection rate was 0.00% (CI 0.00-1.21). CONCLUSIONS: This meta-analysis highlights low reinfection and high graft patency using BPR with medium-length follow-up; however, there remain limited long-term and comparative data regarding options for aortic reconstruction. As expected in this complex cohort, the complication rate and 30-day mortality remain high.

Mechanical failure analysis of patch materials used in aortic arch reconstruction: implications for clinical practice.

OBJECTIVES: Thick-patch pulmonary homograft, autologous pericardium and CardioCel Neo are common patch materials for aortic arch reconstruction. Insufficient data exist on sutured patch strength and limits of use. We evaluated failure strength of these materials to develop a failure prediction model for clinical guidance. METHODS: Patch failure strength was evaluated via sutured uniaxial and burst pressure testing. In sutured uniaxial testing, patches were sutured to aortic or Dacron tabs and pulled to failure. In burst pressure testing, patches were sewn into porcine aortas or Dacron grafts and pressurized to failure. Failure membrane tension was calculated. A prediction model of membrane tension versus vessel diameter was generated to guide clinical patch selection. RESULTS: Combining sutured uniaxial and burst pressure test data, pulmonary homograft failure strength {0.61 [interquartile range (IQR): 0.44, 0.78] N/mm, n = 21} was less than half that of autologous pericardium [2.22 (IQR: 1.65, 2.78) N/mm, n = 15] and CardioCel Neo [1.31 (IQR: 1.20, 1.42) N/mm, n = 20]. Pulmonary homograft burst pressure [245 (IQR: 202, 343) mmHg, n = 7] was significantly lower than autologous pericardium [863 (IQR: 802, 919) mmHg, n = 6] and CardioCel Neo [766 (IQR: 721, 833) mmHg, n = 6]. Our model predicts failure limits for each patch material and outlines safety margins for combinations of aortic diameter and pressure. CONCLUSIONS: Sutured failure strength of thick-patch pulmonary homograft was significantly lower than autologous pericardium and CardioCel Neo. Patient selection (predicted postoperative arch diameter and haemodynamics) and blood pressure management must be considered when choosing patch material for arch reconstruction. In older children and adolescents, autologous or bovine pericardium may be more suitable materials for aortic patch augmentation to minimize the risk of postoperative patch failure.

Predictors of Mid-Term AVNeo Insufficiency.

INTRODUCTION: Aortic stenosis (AS) is the most common valvular heart disease and the most common indication for aortic valve replacement in adults. Aortic valve neocuspidization (AVNeo) with fixed autologous pericardium, also known as the Ozaki procedure, is a possible alternative treatment of AS. Autopericardial valves save the dynamics and physiological anatomy of the aortic root, however, the service life of autopericardial leaflets is limited. There is no data about factors that may influence the development of AVNeo insufficiency. Here, we assessed the effect of autopericardial leaflet symmetry on the development of aortic insufficiency after Ozaki procedure. METHODS: This study included 381 patients with AS who underwent Ozaki procedure. Patients were divided into group 1 (171 patients with symmetric aortic root) and group 2 (210 patients with asymmetric aortic root). RESULTS: The maximum observation period was up to 65 months. Sixteen cases of aortic insufficiency were detected in group 1, and 33 cases were detected in group 2. Based on the results of Cox regression, the predictors of aortic insufficiency in the late postoperative period are age and asymmetry of neocusps. According to results of Kaplan-Meier analysis, insufficiency of AVNeo in the maximum follow-up period after surgical correction of AS for group 1 patients was significantly lower than for group 2 patients (P=0.006). CONCLUSION: Asymmetric neocusps increase the risk of aortic insufficiency in the mid-term period after Ozaki procedure. And the older the patients at the time of surgery, the less likely they develop AVNeo insufficiency.

Safety, Effectiveness, and Hemodynamic Performance of the Bovine Pericardium Organic Valvular Bioprosthesis.

OBJECTIVE: To assess actual data on the safety, effectiveness, and hemodynamic performance of Bovine Pericardium Organic Valvular Bioprosthesis (BVP). METHODS: The BIOPRO Trial is an observational, retrospective, non-comparative, non-randomized, and multicenter study. We collected data from 903 patients with symptomatic, moderate, or severe valve disease who underwent BVP implants in the timeframe from 2013 to 2020 at three Brazilian institutions. Death, valve-related adverse events (AEs), functional recovery, and hemodynamic performance were evaluated at the hospital, at discharge, and six months and one year later. Primary analysis compared late (> 30 days after implant) linearized rates of valve-related AEs, such as thromboembolism, valve thrombosis, major hemorrhage, major paravalvular leak, and endocarditis, following objective performance criteria (OPC). Analysis was performed to include at least 400 valve-years for each valve position (aortic and mitral) for complete comparisons to OPC. Kaplan-Meier survival and major adverse cardiovascular and cerebrovascular event analyses were also performed. RESULTS: This retrospective study analyzed follow-up data collected from 903 patients (834.2 late patient-years) who have undergone surgery for 455 isolated aortic valve replacement (50.4%), 382 isolated mitral valve replacement (42.3%), and 66 combined valve replacement or other intervention (7.3%). The linearized rates of valve-related AEs were < 2 × OPC. One-year survival rates were 95.1% and 92.7% for aortic and mitral valve replacement, respectively. This study demonstrated an improvement in the New York Heart Association classification from baseline and hemodynamic performance within an expected range. CONCLUSION: According to this analysis, BVP meets world standards for safety and clinical efficacy.

Ozaki Procedure Plus Aortic Annular Enlargement in an Extremely Narrow Aortic Annulus: A Surgical Challenge.

We report a 19-year-old woman with a history of percutaneous aortic valve (AV) balloon valvuloplasty 3 years ago. She was admitted with severe symptomatic AV stenosis with narrow aortic annulus. We decided to perform AV reconstruction with autologous pericardium. However, surgical findings revealed a very narrow AV annulus with a unicuspid valve; therefore, an AV enlargement was added.

A New Technique for De Novo Tricuspid Valve Construction Using Autologous Pericardium.

Treatment of tricuspid valve endocarditis remains an unsolved problem. When the native valve is unsalvageable, implanting a prosthetic valve becomes a problem of its own. This is a case of de novo tricuspid valve construction using autologous pericardium after prosthetic tricuspid valve reinfection.

Outcomes of vein reconstruction using bovine pericardial patch.

BACKGROUND: The bovine pericardium is a good alternative material to the autogenous vein in vascular reconstruction. This study aimed to evaluate the results of angioplasty in venous reconstruction using bovine pericardium and identify the risk factors for significant complications. MATERIAL AND METHODS: A retrospective review was performed of the demographic data, clinical characteristics, and complications of patients who underwent vessel repair using bovine pericardium between February 2012 and December 2020. Univariate analysis was used to compare complication frequencies within several categories. RESULTS: There were 36 cases of patch angioplasty using bovine pericardium. The median age was 65 years; 61% of them were men. Of the 36 venous repairs, 31 (86.1%) were from cancer surgery and five (13.9%) were from iatrogenic injury. Patch shape was used in 27 cases (75.0%), while tube shape was used in nine cases (25.0%). The incidence of occlusion and partial thrombus was five (13.9%) and three (8.3%) cases, respectively. Of the nine tube-shaped angioplasties, four (44.4%) required reoperation due to early thrombosis (three cases) and hematoma (one case). CONCLUSION: The use of a bovine pericardial patch in the reconstruction of a damaged vein from tumor invasion or iatrogenic injury is feasible. However, the complication rate of vessel patency remains substantial, especially in cases of iatrogenic injury or when a tube-shaped form is used for repair.

Pulmonary Valve Reconstruction Using Autologous Pericardium: A Promising Technique to Consider.

Pulmonary valve (PV) surgical treatment is uncommon in adults; however, when it is indicated, replacement with a prosthesis is suggested. Nevertheless, mechanical prostheses have an inherent risk of complications derived from anticoagulation and thrombosis, and biologic prostheses do not have adequate long-term durability. In this context, PV reconstruction surgery emerges as an alternative, avoiding anticoagulation and promising good durability. We present our experience with this procedure in 3 patients with severe PV insufficiency and 1 patient with severe PV stenosis.