The Edwards Inspiris® bioprosthesis includes treated bovine pericardium leaflets that make up RESILIA® tissue. This tissue treatment involves stable coverage of free aldehydes that prevents calcium adherence and includes glycerolization for dry storage. Standardized animal testing has shown that this process significantly reduces leaflet calcification and pannus formation. The initial 5-year results from the first COMMENCE, which enrolled 689 patients, as well as follow-up from another prospective Polish study with 133 patients, have been reported. In both studies, no structural valve deterioration (SVD) was observed according to the joint criteria of the Society of Thoracic Surgeons (STS)/American Association for Thoracic Surgery (AATS)/European Association for Cardio-Thoracic Surgery (EACTS). However, since structural valve deterioration (SVD) in patients with aortic bioprostheses begins to accelerate after 5-7 years of follow-up, this follow-up was extended to 10 years in a cohort of patients who consented to this extended follow-up (n=225), and was carried out at 10 of the participating centers.
The mean age of the patients was 67 ± 12 years. No patient was lost to the extended follow-up, although 7 died between the 5th and 7th year and 2 underwent valve explantation. The cumulative follow-up in the cohort that reconsented to the follow-up was 1736.9 patient-years, with an average follow-up time of 7.7 ± 0.7 years. The reconsenting group included fewer women, had fewer patients in NYHA functional class III or IV, predominantly underwent more median sternotomies, and received larger prosthesis sizes (85.4% with implants > 21mm) compared to the non-reconsenting cohort (77.8%).
Seven-year freedom from overall death and overall reintervention was 85.4% and 97.2% respectively; while freedom from structural failure was 99.3%. Meanwhile, freedom from stroke, major bleeding, paravalvular insufficiency, and non-structural prosthetic failure was 94%, 90.9%, 99.5%, and 99.5%, respectively. Of the 12 reinterventions observed, only 2 cases were due to SVD on days 1848 and 2190. Neither of the patients belonged to the under-65 age group. The second patient had stage 3 chronic kidney disease, which could contribute to the structural degeneration. The rest of the reinterventions were due to endocarditis (n = 7), non-structural failure (n = 2), and aortic dilation (n = 1). No patient presented more than mild intraprosthetic or paravalvular insufficiency (only 2.5% exhibited trivial paravalvular insufficiency). Over the 7 years, the transvalvular gradients and effective valvular area remained stable.
The authors concluded that this is the study with the longest follow-up of the Edwards Inspiris RESILIA® prosthesis and that it presents both a very low rate of reintervention due to structural deterioration and a high safety profile, although longer follow-up is required.
COMMENTARY:
The present extended follow-up study of 7 years for the Edwards Inspiris RESILIA® prosthesis represents an improvement in structural deterioration rates compared to the previous model of the same prosthesis (Edwards Magna Ease®), which showed in an 8-year follow-up in patients with a similar average age of 68 years, a 93.6% (95% CI = 89.3% – 97.8%) reintervention rate for SVD in the study by Tsui et al.
Interestingly, the two observed structural degenerations occurred, as previously mentioned, in patients older than 65 years, while none under that age (n = 92) exhibited such complications. In a Swedish registry with nearly 17,000 patients with a significantly older average age than that of the present study (72.6 ± 8.5 years), the rate of reintervention for SVD varied from 3.0% (95% CI = 2.6% – 3.5%) for the Edwards Perimount® prosthesis to 9.3% (95% CI = 7.3% – 11.3%) for the Sorin Soprano® with an average follow-up of 7.1 years.
The limitations of the work include the absence of a control group for comparison and the possibility of selection bias at the time of reconsenting for the extended follow-up study. Apart from this subgroup being numerically smaller and thus offering less statistical power, the patients who reconsented were, as mentioned regarding the total cohort, significantly more often male, with a lower NYHA class and, more importantly for the progression of structural deterioration, were implanted with larger prostheses with lower mean gradients. The number of patients between 50 and 65 years was small (n = 71), making it difficult to draw definitive conclusions in this regard.
The disclosed results of the Edwards Inspiris RESILIA® prosthesis are excellent, with very low rates of structural deterioration after an average follow-up of nearly 8 years. Although it is true that the structural deterioration of bioprostheses shows a progressive increase from those 5-7 years across all prosthesis models, the significantly younger average age of the patients, compared to other preceding series, suggests that the durability of the prosthesis could indeed be significantly better than previous models and other marketed bioprostheses, especially in younger ages. In the large Swedish study mentioned previously, the 7-year reintervention rates for SVD were higher for all prostheses in absolute terms with significantly older average ages. In the case of the Edwards Perimount® prosthesis, the absolute difference was more than 6 years (from 65.1 to 71.4 years), and for the other two prostheses, it was more than 10 years (with average ages of 75 and 76.1 years, respectively). These age differences suggest that durability is likely to be superior with this prosthesis.
However, the two reinterventions for SVD discussed at 5 and 6 years post-surgery in patients over 65 years old make us think that the new tissue is not infallible. In the previously mentioned Swedish study, the 15-year reintervention rate was excellent for the Edwards Perimount®, Medtronic Mosaic®/Hancock®, and St. Jude (Abbott) Biocor®/Epic® prostheses, being around 5% in all cases; although it is true that in relation to what was discussed about older average ages, the overall survival at those 15 years was only 28%, 18%, and 20%, respectively. This implies that the impact of structural deterioration is minimized since the patients die before requiring a reintervention for SVD, as has occurred in multiple moderate and high-risk TAVI studies, or low-risk ones with older ages.
Similar to this study, the PERIGON study is evaluating the long-term results of the Medtronic Avalus® prosthesis, which is also a bioprosthesis made from bovine pericardium fixed with 0.5% glutaraldehyde and treated with anti-calcification AOA (alpha-amino oleic acid). After an average follow-up of 5 years, no patient showed structural deterioration (according to the criteria of Akins et al.) neither in the group over 65 years old (n = 442 at risk at 5 years) nor in the group of 149 patients under 65 years also at risk at 5 years (average age of 58 years).
Apart from the limitations mentioned in the study itself, it is noteworthy that the criteria for structural degeneration are based on the criteria of Akins et al. (essentially the need for valve reoperation), similar to what occurs in the PERIGON study, which makes the comparability of these results with those reported according to VARC-2 criteria limited.
In conclusion, I believe that the results of the Edwards Inspiris RESILIA® prosthesis are excellent and promising regarding a future extension of the indications for biological prostheses in subgroups of young and low-risk patients. However, as is the case with all biological prostheses, it is imperative to wait for a longer follow-up of a considerably larger number of real-life patients to assume that the durability of this type of tissue preservation provides less structural deterioration than other current or previous models and to make the decision to extend its indication indiscriminately to patients under 65 years of age.
Finally, I cannot fail to comment that the philosophy of this reflection should be extrapolated to all the studies that are evaluating the TAVI strategy (for example, with the Edwards Sapien 3 Ultra RESILIA® prosthesis) in young, low-risk patients with a significantly longer survival than that of older patients or those with a higher surgical risk. The decision to drastically change indications in such influential documents in daily clinical decisions as clinical practice guidelines should be cautious and await longer follow-ups, necessarily longer as the surgical risk is lower and the life expectancy of the candidates is higher.
REFERENCES:
Bavaria JE, Griffith B, Heimansohn DA, Rozanski J, Johnston DR, Bartus K, et al. Five-year outcomes of the COMMENCE trial investigating aortic valve replacement with RESILIA tissue. Ann Thorac Surg. 2023;115:1429-36. doi: 10.1016/j.athoracsur.2021.12.058.
Bartus K, Litwinowicz R, Bilewska A, Stapor M, Bochenek M, Rozanski J, et al. Final 5-year outcomes following aortic valve replacement with a RESILIA_tissue bioprosthesis. Eur J Cardio Thorac Surg. 2021;59:434-41. doi: 10.1093/ejcts/ezaa311.
Tsui S, Rosenbloom M, Abel J, Swanson J, Haverich A, Zacharias J, et al. Eightyear outcomes of aortic valve replacement with the Carpentier-Edwards PERIMOUNT Magna Ease valve. J Card Surg. 2022;37:4999-5010. doi: 10.1111/jocs.17140.
Akins CW, Miller DC, Turina MI, Kouchoukos NT, Blackstone EH, Grunkemeier GL, et al. Guidelines for reporting mortality and morbidity after cardiac valve interventions. J Thorac Cardiovasc Surg. 2008;135:732-8. doi: 10.1016/j.athoracsur.2007.12.082.
Kiaii BB, Moront MG, Patel HJ, Ruel M, Bensari FN, Kress DC, Liu F, Klautz RJM, Sabik JF 3rd. Outcomes of Surgical Bioprosthetic Aortic Valve Replacement in Patients Aged ≤65 and >65 Years. Ann Thorac Surg. 2023 Sep;116(3):483-490. doi: 10.1016/j.athoracsur.2021.12.057.
