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

Abstract

OBJECTIVESDecellularized 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.METHODSA 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).RESULTSA 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).CONCLUSIONSMid-term results of DPH for PVR confirm earlier results of reduced re-operation rates compared with CH and BJV.

Cardiovascular Applications of Magnesium Alloys

“…It should not, if possible, trigger any thrombogenic effects. The graft must integrate into the host tissue and have the ability to grow, when used in children [69][70][71]. Furthermore, an easy manufacturing process, the shelf life of the vascular prostheses and readily available supply for an acute emergency, all play very important roles.…”

Application of a Fresh Decellularized Pulmonary Allograft for Pulmonary Valve Replacement in Japan

“…Sarikouch et al reported good clinical results for more than 10 years with a fresh decellularized heart valve. 10 According to that report, compared with other valves such as homografts or Contegra ® , which are commonly used in Europe and the USA for patients with CHD accompanied mainly with RVOT dysfunction, the recurrence avoidance rate is significantly lower with fresh decellularized heart valves. Moreover, in Japan, for patients with CHD who have RVOT dysfunction, reconstruction is performed during infancy using artificial materials such as a transannular patch if the annulus cannot be preserved.…”

“…Moreover, they reported no evidence of significant early activation of the cellular immune response 7 with extracellular matrix formation, which provided superior performance and showed growth potential corresponding with the excellent mid-term results of these valves in clinical use. 10 In Japan, re-operations for relatively young CHD patients with valvular dysfunction are increasing yearly, and the medical need for decellularized heart valves is considered very high. Therefore, in 2013 we started a joint clinical study of the safety of decellularized heart valve implantations with the Hannover Medical School.…”

Heart Valve Replacements with Regenerative Capacity

“…In vitro cultured TEHVs based on decellularized human pulmonary valves seeded with endothelial cells have demonstrated excellent hemodynamic performance and good functionality in clinical trials up to 10 years [59]. Thanks to the good functionality and the lack of degeneration, calcification and immunoreactivity, the use of decellularized allografts for both pulmonary and aortic valves is promising, with minimal occurrence of re-operations and possibility for adaptive growth [62,63]. Unfortunately, the availability of allografts is limited by donor shortage, leaving unmet the need for off-the-shelf available regenerative heart valve replacements.…”