OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients.METHODS: A prospective, EU-funded, single-arm, multicentre study... Show moreOBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients.METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement.RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9–55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6mm (standard deviation 2.4). The median operation duration was 312min (IQR 234–417), the median cardiopulmonary bypass time was 154min (IQR 118–212) and the median cross-clamp time 121min (IQR 93–150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5h postoperation. There were 3 late deaths, 1 death due to endocarditis 4months postoperatively and 2 unrelated deaths after 5 and 7years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9years [IQR 5.1–6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0mmHg (IQR 7.8–17.6) and regurgitation of median 0.5 (IQR 0–0.5) of grade 0–3 were excellent. At 5years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively.CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics. Show less
Bobylev, D.; Horke, A.; Avsar, M.; Cvitkovic, T.; Boethig, D.; Hazekamp, M.; ... ; Sarikouch, S. 2023
For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease.... Show moreFor decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (+/- 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR. Show less
Chronic kidney disease has restricted treatment options and leads to a lower quality of life, even before the end stage of renal disease is reached. The ability to generate new transplantable... Show moreChronic kidney disease has restricted treatment options and leads to a lower quality of life, even before the end stage of renal disease is reached. The ability to generate new transplantable kidney tissue could help millions of people worldwide and is therefore of great interest. This thesis explores options within regenerative medicine to develop new transplantable kidney tissue from a bio-engineering point of view. Show less
Bobylev, D.; Horke, A.; Boethig, D.; Hazekamp, M.; Meyns, B.; Rega, F.; ... ; Sarikouch, S. 2022
OBJECTIVES: Early results from the prospective ESPOIR Trial have indicated excellent results for pulmonary valve replacement using decellularized pulmonary homografts (DPH).METHODS: A 5-year... Show moreOBJECTIVES: Early results from the prospective ESPOIR Trial have indicated excellent results for pulmonary valve replacement using decellularized pulmonary homografts (DPH).METHODS: A 5-year analysis of ESPOIR Trial patients was performed to provide an insight into the midterm DPH performance. ESPOIR Trial and Registry patients were matched with cryopreserved homografts (CH) patients considering patient age, type of heart defect and previous procedures to present the overall experience with DPH.RESULTS: A total of 121 patients (59 female) were prospectively enrolled (8/2014-12/2016), median age 16.5 years (interquartile range 11.2-29.8), and median DPH diameter 24 mm. One death (73 year-old) occurred during a median follow-up of 5.9 years (5.4-6.4), in addition to 2 perioperative deaths resulting in an overall mortality rate of 2.5%. One case of endocarditis in 637 patient-years was noticed, resulting in an incidence of 0.15% per patient-year. At 5 years, the mean peak gradient was 19.9 mmHg (9.9), mean regurgitation 0.9 (0.6, grade 0-3) and freedom from explantation/any reintervention 97.5% (1.5). The combined DPH cohort, n = 319, comprising both Trial and Registry data, showed significantly better freedom from explantation for DPH 95.5% (standard deviation 1.7) than CH 83.0% (2.8) (P < 0.001) and less structural valve degeneration at 10 years when matched to 319 CH patients [DPH 65.5% (standard deviation 4.4) and CH 47.3% (3.7), P = 0.11].CONCLUSIONS: The 5-year data of the prospective ESPOIR Trial show excellent performance for DPH and low rates of adverse events. ESPOIR Registry data up to 15 years, including a matched comparison with CH, demonstrated statistically significant better freedom from explantation. Show less
Haan, M.J.A. de; Witjas, F.M.R.; Engelse, M.A.; Rabelink, T.J. 2021
The purpose of organ decellularization is to remove all cellular components whilst preserving the extracellular matrix (ECM). It has been hypothesized that this decellularized ECM can be used as a... Show moreThe purpose of organ decellularization is to remove all cellular components whilst preserving the extracellular matrix (ECM). It has been hypothesized that this decellularized ECM can be used as a scaffold for the development of personalized bioengineered kidneys by repopulating it with patient-derived cells. The renal artery, vein, and ureter are most frequently used for whole kidney repopulation. Cell perfusion through the artery and vein enables revascularization of decellularized kidneys. However, adequate repopulation of the epithelial compartment remains unattainable. Although it has become unlikely that recellularized whole kidneys will be the solution to reduce donor organ shortages within the foreseeable future, advances made within the field of whole organ decellularization and recellularization have paved the way for alternatives that actually may help to solve these shortages. This includes ex vivo refurbishment and personalization of discarded donor organs during machine perfusion. Show less
Horke, A.; Tudorache, I.; Laufer, G.; Andreas, M.; Pomar, J.L.; Pereda, D.; ... ; Sarikouch, S. 2020
OBJECTIVES: Decellularized aortic homografts (DAH) may provide an additional aortic valve replacement option for young patients due to their potential to overcome the high early failure rate of... Show moreOBJECTIVES: Decellularized aortic homografts (DAH) may provide an additional aortic valve replacement option for young patients due to their potential to overcome the high early failure rate of conventional allogenic and xenogenic aortic valve prostheses.METHODS: A prospective, European Union-funded, single-arm, multicentre, safety study was conducted in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement.RESULTS: One hundred and forty-four patients (99 male) were prospectively enrolled between October 2015 and October 2018, mean age 33.6 +/- 20.8 years; 45% had undergone previous cardiac operations. Mean implanted DAH diameter 22.6 +/- 2.4 mm and mean durations for the operation, cardiopulmonary bypass and cross-clamp were 341 +/- 140, 174 +/- 80 and 126 +/- 43 min, respectively. There were 2 early deaths (1 LCA thrombus on day 3 and 1 ventricular arrhythmia 5 h postop) and 1 late death due to endocarditis 4 months postoperatively, resulting in a total mortality of 2.08%. One pacemaker implantation was necessary and 1 DAH was successfully repaired after 6 weeks for early regurgitation following subcoronary implantation. All other DAH were implanted as a free-standing root. After a mean follow-up of 1.54 +/- 0.81 years, the primary efficacy end points peak gradient (mean 11.8 +/- 7.5 mmHg) and regurgitation (mean 0.42 +/- 0.49, grade 0-3) were excellent. At 2.5 years, freedom from explantation/endocarditis/bleeding/stroke was 98.4 +/- 1.1%/99.4 +/- 0.6%/99.1 +/- 0.9%/99.2 +/- 0.8%, respectively, with results almost identical to those in an age-matched Ross operation cohort of 212 patients (mean age 34 years) despite DAH patients having undergone >2x more previous procedures.CONCLUSIONS: The initial results of the prospective multicentre ARISE trial show DAH to be safe for aortic valve replacement with excellent haemodynamics in the short follow-up period. Show less
Horke, A.; Bobylev, D.; Avsar, M.; Meyns, B.; Rega, F.; Hazekamp, M.; ... ; Sarikouch, S. 2020
OBJECTIVES: Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and... Show moreOBJECTIVES: Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and mechanical AVR imposes constant anticoagulation with the inherent risks.METHODS: The study design was a prospective, multicentre follow-up of all paediatric patients receiving decellularized aortic homografts (DAHs) for AVR in 8 European centres.RESULTS: A total of 106 children (77 boys) were operated (mean age 10.1 +/- 4.8 years, DAH diameter 20.5 +/- 3.8 mm). A total of 60 (57%) had undergone previous surgical interventions: 34 with 1, 15 with 2 and 11 with >3. There was one early death in a 12-year-old girl, who underwent her fourth aortic valve operation, due to intracerebral haemorrhage on extracorporeal membrane oxygenation after coronary reimplantation problems following 3-sinus reconstruction 1 year earlier. One 2-year-old patient died due to sepsis 2 months postoperatively with no evidence for endocarditis. In addition, a single pacemaker implantation was necessary and a 2.5-year-old girl underwent successful HTx due to chronic myocardial failure despite an intact DAH. After a mean follow-up of 3.30 +/- 2.45 years, primary efficacy end points mean peak gradient (18.1 +/- 20.9 mmHg) and regurgitation (mean 0.61 +/- 0.63, grade 0-3) were very good. Freedom from death/explantation/endocarditis/bleeding/stroke at 5 years was 97.8 +/- 1.6/85.0 +/- 7.4/100/100/100% respectively. Calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.9 years), lower than in Ross patients (9.4 years) and in the same range as mechanical AVR (12.8 years).CONCLUSIONS: Even though the overall number of paediatric DAH patients and the follow-up time span are still limited, our data suggest that DAHs may present a promising additional option for paediatric AVR. Show less
Boethig, D.; Horke, A.; Hazekamp, M.; Meyns, B.; Rega, F.; Puyvelde, J. van; ... ; Sarikouch, S. 2019
OBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date.METHODS: Prospective... Show moreOBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date.METHODS: Prospective European multicentre trial evaluating DPH for pulmonary valve replacement. Matched comparison of DPH to bovine jugular vein (BJV) conduits and cryopreserved homografts (CH) considering patient age, type of heart defect and previous procedures.RESULTS: In total, 121 patients (59 female) were prospectively enrolled (August 2014-December 2016), age 21.3 +/- 14.4 years, DPH diameter 24.4 +/- 2.8 mm. No adverse events occurred with respect to surgical handling; there were 2 early deaths (30 + 59 years) due to myocardial failure after multi-valve procedures and no late mortality (1.7% mortality). After a mean follow-up of 2.2 +/- 0.6 years, the primary efficacy end points mean peak gradient (16.1 +/- 12.1 mmHg) and regurgitation (mean 0.25 +/- 0.48, grade 0-3) were excellent. One reoperation was required for recurrent subvalvular stenosis caused by a pericardial patch and 1 balloon dilatation was performed on a previously stented LPA. 100% follow-up for DPH patients operated before or outside the trial (n = 114) included in the ESPOIR Registry, age 16.6 +/- 10.4 years, diameter 24.1 +/- 4.2 mm, follow-up 5.1 +/- 3.0 years. The combined DPH cohort, n = 235, comprising both Trial and Registry data showed significantly better freedom from explantation (DPH 96.7 +/- 2.1%, CH 84.4 +/- 3.2%, P = 0.029 and BJV 82.7 +/- 3.2%, P = 0.012) and less structural valve degeneration at 10 years when matched to CH, n = 235 and BJV, n = 235 (DPH 61.4 +/- 6.6%, CH 39.9 +/- 4.4%, n.s., BJV 47.5 +/- 4.5%, P = 0.029).CONCLUSIONS: Initial results of the prospective multicentre ESPOIR Trial showed DPH to be safe and efficient. Current DPH results including Registry data were superior to BJV and CH. Show less
