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

Abstract

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.

Keywords: Congenital heart disease; Decellularization; Homograft; Pulmonary valve replacement; Tissue engineering.