Early results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement: the ARISE study and ARISE Registry data

Abstract

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 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 >2× 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.

Keywords: Allografts; Aortic valve disease; Decellularization; Tissue engineering.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

Figures

Figure 1:

Patient inclusion within the prospective multicentre ARISE trial by centre.

Figure 2:

Twenty four-year-old male patient, 1/2009 aortic valve replacement with 25 mm Carpentier Edwards Perimount valve (will of patient) and supracommissural replacement of the ascending aorta using a 24-mm Hemashield vascular prosthesis. (A, B) Severe calcified aortic stenosis and impaired left ventricular function with pleural effusion. (C, D) Extended aortic valve replacement including the Hemashield prosthesis using a long decellularized homograft provided by the European Homograft Bank and explanted bioprosthesis. (E, F) CMR at discharge. (G, H) Postoperatively LV function recovery due to a large effective orifice area and normal valve function in the 36 months follow-up so far. No signs of ascending aorta dilatation. EF: ejection fraction; EOA: effective orifice area.

Figure 3:

Freedom from death and freedom from allograft explantation for the ARISE study patients.

Figure 4:

Freedom from aortic valve stenosis and regurgitation for the ARISE study patients.

Figure 5:

Freedom from any reintervention and endocarditis for the ARISE study patients.

Figure 6:

ARISE Registry data of all 223 decellularized aortic homograft (DAH) implanted to date compared with recently published meta-analysis data from several AVR options in young adult patients. Perioperative and annual adverse events such as death, reoperation or reintervention, valve degeneration, thrombotic and bleeding events and endocarditis were summarized to provide an estimate of adverse events in the long term. Additionally, actually observed adverse DAH events are shown in Kaplan–Meier function equivalent ±95% CI. Data taken from Refs [4, 15, 16]. AVR: aortic valve replacement; CI: confidence interval.