Interventional procedure overview of aortic valve reconstruction using glutaraldehyde-treated autologous pericardium for aortic valve disease
Closed for comments This consultation ended on at Request commenting lead permission
Table 2 Study details
Study no. | First author, date country | Patients (male: female) | Age | Study design | Inclusion criteria | Intervention | Follow up |
|---|---|---|---|---|---|---|---|
1 | Mylonas, 2023 Various | n=1,891 (49.6% male) | 43.2±24.5 years (65±12.3 years for adult patients and 12.3±3.8 years for paediatric patients) | A meta-analysis of reconstructed patient-level data (22 studies) | Eligible literature comprised of original clinical studies which were published in English and reported on demographic, clinical characteristics, and outcomes of paediatric and adult patients undergoing AVNeo using the Ozaki technique. Publication year filters were employed since the original report on the Ozaki procedure was published in March 2011 | Autologous pericardium was used in 90.6% of the included patients. 3.8% had AVNeo with xenologous pericardium. 5.6% used autologous pericardium in certain patients and xenologous products in others without separately reporting their outcomes | Mean follow up of 38.1± 23.8 months (maximum 9.8 years) |
2 | Benedetto, 2021 UK, Various | n=55 (61.8% male) | Mean age 58±15 years | Case series | AVNeo using autologous pericardium in adult patients (>18 years old) was done in University Hospitals Bristol NHS Foundation Trust and University Hospital Coventry & Warwickshire from 2018 to 2020 | AVNeo using autologous pericardium | 12.5±0.9 months |
39 studies. AVNeo: n=1,205 Trifecta: n=8,705 Magna Ease: n=3,137 Freedom Solo: n=1,869 Freestyle: n=4,307 Mitroflow: n=4,760 Autograft aortic valve: n=3,839 | Mean age ranged from 52 to 78 years for AVNeo studies | Meta-analytic comparison (39 studies) | Procedures done with autologous pericardium in adult patients (>18 years) with follow-up data available | AVNeo with autologous pericardium – 7 studies Trifecta – 10 studies Magna Ease – 3 studies Freedom Solo – 4 studies Freestyle – 4 studies Mitroflow – 4 studies Autograft aortic valve – 7 papers Outcomes of interest were the incidence of structural valve degeneration (SVD), endocarditis and reintervention | Not reported | ||
3 | Dilawar, 2022 Various | n=1,427 (52.1% male) | Mean age 64.95 years | A systematic review (12 studies) | Studies investigating the outcome of aortic valve replacement with autologous pericardium | Aortic valve replacement with autologous pericardium | Not reported |
4 | Sá, 2020 Brazil, Russia and Germany | n=106 (35.9% male) | Mean age was 65.4 (range, 38–80 years) | A multicentre study | Patients with small aortic annulus (≤21 mm) and aortic valve diseases from Jan 2017 to Mar 2019 at 3 centres | AVNeo procedure | Not reported |
5 | Boehm, 2022 Germany | n=563 (71.6% male) | Mean age 51.3±15.6 years for AVNeo 67.0±8.8 years for surgical aortic valve replacement (SAVR) | Non-randomised comparative study | Patients who underwent either AVNeo or SAVR between March 2017 and Aprial 2020. AVNeo patients were only included if they had intraoperative measurement of the annulus | AVNeo for trileaflet aortic valve reconstruction using autologous pericardium (Ozaki procedure) | Not reported |
6 | Saudi Arabia | n=92 (65% male) | Mean age 30 years | Case series | Aortic valve reconstruction with pericardium between 1988 and 1995 | Aortic valve reconstruction with bovine pericardium (n=27). Aortic valve reconstruction with glutaraldehyde-treated autologous pericardium (n=65) | 16 years |
Safety studies – the following studies were included to show unique safety events | |||||||
7 | Mikami, 2022 Japan | n=1 (male) | 56 years | Case report | Not reported | AVNeo using autologous pericardium (Ozaki procedure) for aortic stenosis | Not reported |
8 | Bernhardt, 2021 US | n=1 (male) | 56 years | Case report | Not reported | Aortic valve reconstruction using the Ozaki procedure | Not reported |
Procedure technique
Of the 8 studies, 4 detailed the procedure technique of aortic valve reconstruction with glutaraldehyde-treated autologous pericardium. Only 1 study (Halees, 2005) treated autologous pericardium with a 0.5% buffered glutaraldehyde solution for 10 minutes and rinsed it for 10 minutes before use. This was used before Ozaki technique developed. The other 3 studies (Benedetto, 2021; Boehm, 2022; Sá, 2020) treated autologous pericardium with a 0.6% glutaraldehyde solution and rinsed it 3 times for 6 minutes with sterile saline before use. In the meta-analysis (Mylonas, 2023), autologous pericardium was used in 91% of the included patients, while only 4% had AVNeo with xenologous pericardium, and 6% used autologous pericardium in certain patients and xenologous products in others without separately reporting their outcomes. In the meta-analytic comparison (Benedetto, 2021), there were 10 studies that used other biological valve substitutes. All other studies used aortic valve reconstruction with glutaraldehyde-treated autologous pericardium.
Efficacy
Survival
Survival of aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 3 studies and ranged from 88% to 96%. In the meta-analysis of 22 studies (n=1,891), based on the reconstructed individual patient data, the rate of survival at 1-year, 3-year, and 5-year were 93%, 91%, and 88%, respectively (Mylonas 2023).
In a case series of 55 patients, the survival rate was 96% (53/55) at a mean follow up of 12.5±0.9 months (Benedetto 2021).
In a case series of 92 patients treated by aortic valve reconstruction, survival was 89% (24/27) using bovine pericardium at a mean follow up of 12 years, and 91% (59/65) using autologous pericardium at a mean follow up of 10 years (Halees 2005).
Reoperation
Reoperation of aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 6 studies and ranged from 1% to 57%. In the meta-analysis of 22 studies, the rate of reoperation at 1, 3 and 5 years, were 2%, 3% and 4%, respectively. The most common indication for reoperation was infective endocarditis (n=29; 51.5%, 95% CI 18.3 to 84.0), followed by structural valve deterioration (n=10; 34.8%, 95% CI 17.9 to 54.3), while only 2 patients needed redo surgery because of cusp tears (Mylonas 2023).
In a case series of 55 patients, reoperation rate was 2% (1/55). In the meta-analytic comparison of 39 studies, reoperation rate was 1%/patient-year for aortic valve neocuspidisation. When the series by Ozaki was removed, pooled estimates for reoperation were less than 1%/patient-year (Benedetto 2021).
In a systematic review of 12 studies, reoperation rate was 1% (16/1,427) (Dilawar 2022).
In a multicentre study of 106 patients, reoperation rate was less than 4% (4/106). All 4 reoperations were for bleeding: 2 for suture hole bleeding of the aortic wall; 1 for bleeding of the venous cannulation site in the right atrium; 1 for bleeding because of injury to 1 of the internal mammary veins during the placement of sternal wires (Sá 2020).
In a case series of 92 patients, reoperation rate was 57% (37/65) at 16-year follow up. Reasons for reoperation in the autologous pericardium group were endocarditis (11%), mitral/tricuspid valve disease (less than 1%), structural valve degeneration (26%) and aortic valve regurgitation (less than 1%) (Halees 2005).
Technical failure
Technical failure of aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 2 studies and ranged from 1% to 23%. In the meta-analysis of 22 studies, the Ozaki procedure was intraoperatively abandoned in less than 1% (95% CI 0.3 to 1.1) of patients, who subsequently had conventional aortic valve replacement (Mylonas 2023).
In a multicentre study of 106 patients, less than 1% (1/106) of patients needed pacemaker implantation (Sá 2020).
Cardiopulmonary bypass time
Cardiopulmonary bypass time during aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 5 studies and ranged from 74.5 minutes to 170.3 minutes. In the meta-analysis of 22 studies. mean cardiopulmonary bypass time was 135.2 (±35.1) minutes (Mylonas 2023).
In the case series of 55 patients, mean cardiopulmonary bypass time was 136.0 (114.5–166.0) minutes (Benedetto 2021).
In the multicentre study of 106 patients, mean cardiopulmonary bypass time was 109.5±35.0 minutes (Sá 2020).
In the non-randomised comparative study of 563 patients, mean cardiopulmonary bypass time was 163.1 (±33.4) minutes in the AVNeo group and 112.62 (±40.2) minutes in the SAVR group (Boehm 2022).
In the case series of 92 patients, mean cardiopulmonary bypass time was 150 (±33) minutes in the bovine pericardium group and 129 (±25) minutes in the autologous pericardium group (Halees 2005).
Aortic cross-clamp time
Aortic cross-clamp time during aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 5 studies and ranged from 64.7 minutes to 158.1 minutes. In the meta-analysis of 22 studies, mean aortic cross-clamp time was 106.8 (±24.8) minutes (Mylonas 2023).
In the case series of 55 patients, mean aortic cross-clamp time was 108.0 (95.0–131.5) minutes (Benedetto 2021).
In the multicentre study of 106 patients, mean aortic cross-clamp time was 84.4±19.7 minutes (Sá 2020).
In the non-randomised comparative study of 563 patients, mean aortic cross-clamp time was 136.1 (±22) minutes in the AVNeo group and 85.4 (±31.5) minutes in the SAVR group (Boehm 2022).
In the case series of 92 patients, mean aortic cross-clamp time was 100 (±20) minutes in the bovine pericardium group and 95 (±20) minutes in the autologous pericardium group (Halees 2005).
Aortic valve pressure gradient
Aortic valve pressure gradient was reported in 5 studies. In the meta-analysis of 22 studies, preoperative peak and MPG were estimated at 74.5±21.6 mmHg and 58.7±29.5 mm Hg, respectively. Mean postoperative peak and MPG were 17.4±9.2 mmHg and 7.7±3.7 mmHg respectively. Late peak and MPG were 15.7±7.4 mmHg and 11.4±6.4 mmHg, respectively (Mylonas 2023).
In the case series of 55 patients, peak and mean transvalvular gradients were 16±3.7 and 9±2.2 mmHg, respectively (Benedetto 2021).
In a systematic review of 12 studies, improvement of haemodynamic performance 1 week after surgery or at discharge was reported. The average preoperative peak pressure gradient ranged from 66.0±28.2 to 92.0±31.2 mmHg, while the postoperative peak pressure gradient ranged from 10.6±3.3 to 23.4±10.7 mmHg (Dilawa, 2022).
In the multicentre study of 106 patients, average postoperative peak and MPG were 11.8±5.9 mmHg and 7.3±3.5 mmHg (mean±SD), respectively (Sá 2020).
In the non-randomised comparative study of 563 patients, MPG in the AVNeo group were 8.0 mmHg±3.6, while MPG in the SAVR group were 8.3 mmHg±3.6 (Boehm 2022).
Aortic valve function
Aortic valve function after aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 5 studies. In the meta-analysis of 22 studies, 37% (95% CI 15.4 to 61.2) of the patients had trace AR, 5% (95% CI 1.1–10.1) had minor AI, and less than 1% (95% CI 0 to 2.3) had moderate AI at latest follow up. No cases of severe AI have been reported following Ozaki procedures (Mylonas 2023).
In the case series of 55 patients, there was a significant improvement in NYHA class compared to baseline with all but 2 patients in class NYHA I–II (p<0.001) (Benedetto 2021).
In the multicentre study of 106 patients, effective orifice area (EOA) and indexed EOA (iEOA) averaged 2.5±0.4 cm2 and 1.3±0.3 cm2/m2 after surgery, respectively. EOA and iEOA significantly increased by 1.8±0.1 cm2 (p<0.001) and 0.9±0.1 cm2/m2 (p<0.001), respectively, in comparison to preoperative measures (Sá 2020).
In the non-randomised comparative study of 563 patients, the AVNeo group revealed significantly larger EOAs (AVNeo group: EOA=2.4 cm2±0.8 versus SAVR group: EOA=2.1 cm2±0.5, respectively; p<0.001) at discharge. EOAI was greater in the AVNeo group, with an average EOAI =1.23 cm2/m2±0.4 in the AVNeo cohort versus 1.02 cm2/ m2±0.3 in the SAVR group (p<0.001)(Boehm 2022).
In the case series of 92 patients, aortic valve function was reported as good (5/7) and mildly impaired (2/7) in the patients in the bovine pericardium group, and as good (46% [13/28]), mildly impaired (29% [8/28]), moderately impaired (21% [6/28] and severely impaired [1/28]) in the autologous pericardium group, at 16-years follow up (Halees 2005).
Length of intensive care unit stay
Length of intensive care unit stay after aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 3 studies. In the meta-analysis of 22 studies, mean length of intensive care unit stay was 3.3±5.1 days (Mylonas 2023).
In the case series of 55 patients, mean length of intensive care unit stay was 5 (SD=5.03) days (Benedetto 2021).
In the multicentre study of 106 patients, median intensive care unit was 1.5±1.2 days (Sá 2020).
Safety
Mortality
Mortality was reported in 5 studies. In the meta-analysis of 22 studies, in-hospital mortality was less than 1% (95% CI 0.1 to 1.7, I2=20%, p=0.21). There were no in-hospital paediatric deaths, while the rate of in-hospital deaths for adults was 1% (95% CI 0.3 to 2.6, I2=31%, p=0.11). In the autologous pericardium group, in-hospital mortality was 1% (95% CI 0.2 to 2.4, I2=32%, p=0.13) while there were no in-hospital deaths in the xenologous pericardium cohort. Late mortality was 2% (95% CI 0.2 to 4.7, I2=78%, p< 0.001) during a mean follow up of 38.1±23.8 months (maximum 9.8 years). In the adult cohort, late mortality rates were 3% (95% CI 0.4 to 6.3, I2=84%, p<0.001), while in the paediatric group late mortality was 0.6% (95% CI 0.0 to 3.9, I2 =0%, p=0.98). Patients that had Ozaki reconstruction using autologous pericardium had a 2% (95% CI 0.1 to 5.5, I2=82%, p<0.001) late mortality rate, while no fatality was noted in the xenologous pericardium group (Mylonas 2023).
In the case series of 55 patients, there was 1 in-hospital death and 1 late death (Benedetto 2021).
In a systematic review of 12 studies, 2% (25/1427) of patients died.16% of all mortality had a cardiac cause, including leaflet dehiscence which eventually led to multiorgan dysfunction syndrome, endocarditis/paravalvular abscess, cardiac tamponade, and fatal thoracic haemorrhage. Most occurred immediately after surgery or within 1 year after discharge. Non-cardiac causes of mortality including pneumonia, cancer, etc. mostly occurred later, years after patients had been discharged (Dilawar 2022).
In the multicentre study of 106 patients, less than 2% (2/106) of patients had in-hospital deaths, which was both because of non-cardiac causes (Sá 2020).
In the case series of 92 patients, in-hospital deaths from cardiac causes were reported in 3% (2/65) of patients treated by aortic valve reconstruction using autologous pericardium. Late deaths from cardiac causes were reported in 3% (2/65) of patients in the autologous pericardium group. Death at reoperation was reported in 2% (1/65) of patients in the autologous pericardium group (Halees 2005).
In-hospital events
In-hospital events after aortic valve reconstruction with glutaraldehyde-treated autologous pericardium was reported in 5 studies. In the meta-analysis of 22 studies, 2 patients had reoperation because of cusp tears (Mylonas 2023).
In the case series of 55 patients, the postoperative course was uneventful for all but 1 patient (80-year-old) who developed pneumonia, respiratory failure and later died of sepsis. In the meta-analytic comparison of 39 studies, AVNeo showed a similar incidence of valve-related events compared to other valve substitutes included in the analysis and autograft AV (Benedetto 2021).
In a systematic review of 12 studies, there were 3 (less than 1%) and 13 (less than 1%) thromboembolic and endocarditis events that occurred respectively (Dilawar 2022).
In the multicentre study of 106 patients, no thromboembolic events were recorded (Sá 2020).
In the non-randomised comparative study of 563 patients, 4% (4/105) of patients of the AVNeo group and 4% (14/458) of patients in the SAVR cohort had a severe mismatch with an EOAI<0.65 cm2/m2 (p=0.557) (Boehm 2022).
Cusp calcification
Cusp calcification was reported in 3 studies. In the meta-analysis of 22 studies, premature calcification of the neo-leaflets was identified in most patients(Mylonas 2023).
In a systematic review of 12 studies, 1 study reported valve extension with glutaraldehyde-preserved autologous pericardium in mitral valve repair. In their series, they found no calcification of autologous pericardium in 64 cases with 6 months to 9 years of follow up (Dilawar 2022).
In the case series of 92 patients, cusp calcification was reported in less than 4% (1/28) patients in the autologous pericardium group (Halees 2005).
Endocarditis
Cusp calcification was reported in 3 studies. In the meta-analysis of 22 studies, 52% of patients who needed reoperation had infective endocarditis (95% CI 18.3 to 84.0). The risk of endocarditis per patient per year was less than 1% (Mylonas 2023).
In the case series of 55 patients, 3 patients presented with endocarditis at follow up (2 new occurrences of endocarditis after 5 and 12 months from index operation with 1 patient needing aortic reintervention and 1 recurrence of endocarditis after 2 months from index operation). In the meta-analytic comparison of 39 studies, AVNeo was associated with an incidence rate of less than 1%/patient-year for endocarditis. When the series by Ozaki was removed, pooled estimates were less than 1%/patient-year for endocarditis (Benedetto 2021).
In a systematic review of 12 studies, endocarditis was the reason for 69% of reoperations (Dilawar 2022).
In the multicentre study of 106 patients, no patient needed reoperation because of early infective endocarditis (Sá 2020).
In the case series of 92 patients, endocarditis leading to reoperation was reported in 11% (7/65) of patients who had aortic valve reconstruction using autologous pericardium (Halees 2005).
Other
In a case report, a 56-year-old man on chronic haemodialysis with a history of left nephrectomy for Wilms' tumour had AVNeo using autologous pericardium (Ozaki procedure) for aortic stenosis because of a bicuspid aortic valve 6 years ago. The aortic stenosis gradually progressed and a decrease in the left ventricular ejection fraction was observed. He had a reoperative aortic valve replacement using a mechanical valve. Intraoperative findings showed severe calcification at the site where the autologous pericardium was sutured to the annulus. However, the degeneration of the valve leaflets themselves was mild (Mikami 2022).
A 56-year-old male presented with aortic valve endocarditis and severe AI. He underwent successful aortic valve reconstruction by the Ozaki procedure. It was complicated by post-pericardiotomy syndrome and cardiac tamponade after the procedure (Bernhardt 2021).
Anecdotal and theoretical adverse events
Expert advice was sought from consultants who have been nominated or ratified by their professional society or royal college. They were asked if they knew of any other adverse events for this procedure that they had heard about (anecdotal), which were not reported in the literature. They were also asked if they thought there were other adverse events that might possibly occur, even if they had never happened (theoretical).
They listed the following anecdotal adverse events:
Early fibrosis of the leaflets (1 patient developed a thrombus on 1 of the leaflets within a year of the procedure), early failure and regurgitation of the newly constructed aortic valve.
They listed the following theoretical adverse events:
Increased risk of postoperative aortic regurgitation.
Clot formation and embolisation.
The valve reconstruction is not successful, and patient might need a prosthetic valve (this is normally done at the same operation so does prolong the operation slightly but with minimal risk).
Infective endocarditis (this is a potential complication for any cardiac procedure and in fact using prosthetic valves increases the risk of endocarditis while having autologous pericardium in the aortic position would decrease it).
Failure of the valve at follow up (this has been noted in the very young population 5–10-years-old as in same cases the leaflets have calcified).
Four professional expert questionnaires for this procedure were submitted. Find full details of what the professional experts said about the procedure in the specialist advice questionnaires for this procedure.
Validity and generalisability
No randomised controlled trials on aortic valve reconstruction with glutaraldehyde-treated autologous pericardium were identified. Eight studies were included in the key evidence summary, including 1 meta-analysis, 1 case series and meta-analytic comparison study, 1 systematic review, 2 case series, 1 non-randomised comparative study and 2 case reports. Most of the evidence in the meta-analysis and systematic review is from case series or retrospective cohort studies.
Research was done in various countries worldwide, including the UK.
The procedures were done by specialists with training in tertiary referral centres.
There is a lack of long-term outcomes of AVNeo. The longest mean or median follow up was 16 years, but this was a case series published in 2005 (Halees 2005).
In the meta-analysis, paediatric series were included and there was a direct comparison between autologous to xenologous pericardium for AVNeo. There was limited evidence to compare Ozaki technique to aortic valve reconstruction or to the Ross procedure. The choice of pericardium does not seem to influence patient outcomes (Mylonas 2023).
AVNeo's midterm risk of valve-related events is comparable to most biological valve substitutes (Benedetto 2021).
In 1 non-randomised study comparing AVNeo with SAVR, AVNeo showed superior results for EOA and EOAI at discharge compared to replacement with a surgical aortic valve bioprosthesis. Long-term follow up is needed (Boehm 2022).
None of the papers included in tables 2 and 3 reported that the study was funded by a company.
How are you taking part in this consultation?
You will not be able to change how you comment later.
You must be signed in to answer questions