Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience.

OBJECTIVES: Decellularized homografts have shown auspicious early results when used for pulmonary valve replacement (PVR) in congenital heart disease. The first clinical application in children was performed in 2002, initially using pre-seeding with endogenous progenitor cells. Since 2005, only non-seeded, fresh decellularized allografts have been implanted after spontaneous recellularization was observed by several groups. METHODS: A matched comparison of decellularized fresh pulmonary homografts (DPHs) implanted for PVR with cryopreserved pulmonary homografts (CHs) and bovine jugular vein conduits (BJVs) was conducted. Patients' age at implantation, the type of congenital malformation, number of previous cardiac operations and number of previous PVRs were considered for matching purposes, using an updated contemporary registry of right ventricular outflow tract conduits (2300 included conduits, >12 000 patient-years). RESULTS: A total of 131 DPHs were implanted for PVR in the period from January 2005 to September 2015. Of the 131, 38 were implanted within prospective trials on DPH from October 2014 onwards and were therefore not analysed within this study. A total of 93 DPH patients (58 males, 35 females) formed the study cohort and were matched to 93 CH and 93 BJV patients. The mean age at DPH implantation was 15.8 ± 10.21 years (CH 15.9 ± 10.4, BJV 15.6 ± 9.9) and the mean DPH diameter was 23.9 mm (CH 23.3 ± 3.6, BJV 19.9 ± 2.9). There was 100% follow-up for DPH, including 905 examinations with a mean follow-up of 4.59 ± 2.76 years (CH 7.4 ± 5.8, BJV 6.4 ± 3.8), amounting to 427.27 patient-years in total (CH 678.3, BJV 553.0). Tetralogy-of-Fallot was the most frequent malformation (DPH 50.5%, CH 54.8%, BJV 68.8%). At 10 years, the rate of freedom of explantation was 100% for DPH, 84.2% for CH (P = 0.01) and 84.3% for BJV (P= 0.01); the rate of freedom from explantation and peak trans-conduit gradient ≥50 mmHg was 86% for DPH, 64% for CH (n.s.) and 49% for BJV (P < 0.001); the rate of freedom from infective endocarditis (IE) was 100% for DPH, 97.3 ± 1.9% within the matched CH patients (P = 0.2) and 94.3 ± 2.8% for BJV patients (P = 0.06). DPH valve annulus diameters converged towards normal Z-values throughout the observation period, in contrast to other valve prostheses (BJV). CONCLUSIONS: Mid-term results of DPH for PVR confirm earlier results of reduced re-operation rates compared with CH and BJV.

Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report.

BACKGROUND: Degeneration of xenografts or homografts is a major cause for reoperation in young patients after pulmonary valve replacement. We present the early results of fresh decellularized pulmonary homografts (DPH) implantation compared with glutaraldehyde-fixed bovine jugular vein (BJV) and cryopreserved homografts (CH). METHODS AND RESULTS: Thirty-eight patients with DPH in pulmonary position were consecutively evaluated during the follow-up (up to 5 years) including medical examination, echocardiography, and MRI. These patients were matched according to age and pathology and compared with BJV (n=38) and CH (n=38) recipients. In contrast to BJV and CH groups, echocardiography revealed no increase of transvalvular gradient, cusp thickening, or aneurysmatic dilatation in DPH patients. Over time, DPH valve annulus diameters converge toward normal z-values. Five-year freedom from explantation was 100% for DPH and 86 ± 8% and 88 ± 7% for BJV and CH conduits, respectively. Additionally, MRI investigations in 17 DPH patients with follow-up time >2 years were compared with MRI data of 20 BJV recipients. Both patient groups (DPH and BJV) were at comparable ages (mean, 12.7 ± 6.1 versus 13.0 ± 3.0 years) and have comparable follow-up time (3.7 ± 1.0 versus 2.7 ± 0.9 years). In DPH patients, the mean transvalvular gradient was significantly (P=0.001) lower (11 mm Hg) compared with the BJV group (23.2 mm Hg). Regurgitation fraction was 14 ± 3% and 4 ± 5% in DPH and BJV groups, respectively. In 3 DPH recipients, moderate regurgitation was documented after surgery and remained unchanged in follow-up. CONCLUSIONS: In contrast to conventional homografts and xenografts, decellularized fresh allograft valves showed improved freedom from explantation, provided low gradients in follow-up, and exhibited adaptive growth.

Clinical application of tissue engineered human heart valves using autologous progenitor cells.

BACKGROUND: Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. METHODS AND RESULTS: Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. CONCLUSIONS: TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.