Five-year 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) 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 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (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 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [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 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, 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.

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

Figure 1:

This figure shows freedom from homograft explantation, endocarditis and valve degeneration for the ARISE cohort as Kaplan–Meier curves.

Figure 2:

Details on freedom from explantation according to Kaplan–Meier and the functional status in the 144 ARISE patients and in all 358 implanted DAH to date with up to 15 years of follow-up. The dashed boxes in the ARISE patients indicate patients with missing echo data for 2023. The dashed boxes for the whole DAH group indicate the years in which follow-ups in Moldovia could only be performed via telephone due to the COVID19 pandemic and the war in the Ukraine. DAH: decellularized aortic homografts.

Figure 3:

ARISE Registry Data of all 215 DAH implanted in young adults compared with recently published meta-analysis data from several AVR options in young adult patients. Perioperative and linearized annual adverse events such as death, reoperation or reintervention, valve degeneration, thrombotic and bleeding events, and endocarditis are summarized to provide an estimate of adverse events in the long-term. In order to estimate the statistical significance of these performance comparisons, we assumed a decrease in the numbers of patients at risk proportional to the decrease in our DAH population. Multiplying expected adverse event rates and estimated patient numbers resulted in event incidence rates. Poisson distribution based 95% confidence intervals were calculated for each year and valve group. Ross results include right ventricular procedures. Other data were taken from recent large-scale meta-analyses from Takkenberg et al. [5, 16, 2].