Update in Bioprosthetic Valve Tissue Technology

Quick Takes

  • RESILIA (Model 11000A [Edwards Lifesciences; Irvine, CA]) is a novel tissue preservation technology used in a bioprosthetic valve designed to reduce calcification and structural valve deterioration (SVD).
  • COMMENCE (Prospective, Non-Randomized, Multicenter Clinical Evaluation of Edwards Pericardial Bioprostheses With a New Tissue Treatment Platform) demonstrated low rates of SVD when bioprosthetic valves with RESILIA tissue were used in low-risk aortic stenosis patients, albeit with a limited definition of SVD.
  • If RESILIA tissue proves superior to other technologies, it merits study in transcatheter heart valves.

Despite the widespread adoption of transcatheter aortic valve replacement (TAVR), surgical aortic valve replacement (SAVR) remains common.1 In patients with aortic stenosis undergoing aortic valve replacement, guidelines recommend SAVR if the patient is younger than 65 years of age regardless of surgical risk and give a Class I recommendation for SAVR and TAVR in patients 65-80 years old.2 Bioprosthetic valves are recommended over mechanical valves in SAVR patients over 65 years old because valve durability often exceeds life expectancy, and they avoid the need for lifelong anticoagulation with a vitamin K antagonist.2 Still, bioprosthetic valves degrade overtime, and valve failure is associated with mortality and need for reintervention. Better valve durability could alleviate the need for reintervention, improve outcomes, and make bioprosthetic valves a treatment option for younger patients.

The terminology of prosthesis deterioration and failure has changed over time. Clear definitions are necessary in order to appropriately compare treatments. Bioprosthetic valve dysfunction comprises four elements: SVD, non-SVD, valve thrombosis, and endocarditis. SVD, defined as permanent intrinsic changes to the valve that result in irreversible degeneration or dysfunction, often results in stenosis or regurgitation and is the major cause of bioprosthetic valve failure (BVF) in SAVR.3 BVF is the clinical manifestation of valve dysfunction, manifesting as either severe hemodynamic SVD, valve dysfunction requiring reintervention, or valve-related death. Variations in prior definitions of SVD and BVF have produced a wide range of findings regarding SAVR valve durability. Updated consensus definitions are more sensitive and focus on echocardiographic evidence of valve compromise to define and quantify SVD and BVF.3

COMMENCE is a prospective, non-randomized, multicenter trial that evaluated the safety and efficacy of the Carpentier-Edwards PERIMOUNT Magna Ease (Edwards Lifesciences; Irvine, CA) aortic valve implanted with RESILIA tissue in low-risk SAVR patients.4 RESILIA is a novel bovine pericardial tissue designed to reduce leaflet calcification via a proprietary tissue-preservation method that blocks free aldehyde groups and inhibits their binding to calcium. RESILIA is preserved with glycerol, which allows for dry storage and does not require rinsing prior to implantation, reducing exposure to additional calcium-binding molecules. In preclinical studies, RESILIA significantly reduced leaflet calcification and had superior hemodynamic performance compared to commercially available pericardial tissue valves.5 COMMENCE enrolled 689 patients with a mean age of 67 years and Society of Thoracic Surgeons score of 2%.4 The primary safety endpoint was the rate of SVD, defined as valve dysfunction determined by autopsy, reoperation, or clinical investigation.4,6 The primary efficacy endpoints were valve hemodynamic performance and improvement in New York Heart Association functional class. After 4 years of follow-up, no patients experienced SVD by their definition.4 The average peak and mean transvalvular gradients at 4 years were 21 mmHg and 11 mmHg, respectively, which were similar to values obtained at discharge from the index hospitalization. New York Heart Association functional class was improved in 66.7% of patients at 1 year and 63% of patients at 4 years.4

The COMMENCE results are encouraging but difficult to interpret considering the components of the primary endpoint. Although the reported incidence of SVD in this study is low, modern definitions incorporating hemodynamic indicators of valve failure would likely increase the number of patients meeting the primary endpoint. The lack of common endpoints hinders comparisons with other surgical bioprostheses. Bourguignon et al. evaluated a cohort of 2,659 patients who underwent SAVR with the Carpentier-Edwards PERIMOUNT bioprosthesis. Operative mortality was 2.8%, and the incidence of severe SVD (mean gradient >40 mmHg or severe aortic regurgitation) was 5.9% after mean follow-up of 6.7 years.7 Another study of 672 consecutive patients at low surgical risk undergoing bioprosthetic SAVR used modern definitions of SVD and reported subclinical and clinically relevant SVD in 30.1% and 6.6% of patients, respectively, at 10 years.8 Although the RESILIA tissue appears to perform well, longer follow-up and analyses using updated definitions of SVD are necessary to fully understand the potential benefits of the novel tissue preparation.

With implants of transcatheter aortic valves now outpacing surgical ones,1 the durability of transcatheter heart valves is of widespread interest. The NOTION (Nordic Aortic Valve Intervention) trial compared the durability of a self-expanding TAVR valve with SAVR bioprostheses in primarily low-risk patients. After 6 years, the rate of SVD was significantly higher for SAVR than TAVR (24% vs. 4.8%), driven by higher transvalvular gradients in the surgical group; rates of BVF and death were similar between groups.9 Analyses from the PARTNER 2 (Placement of Aortic Transcatheter Valves 2) trial cohort of intermediate-risk patients showed higher rates of SVD and BVF using the second-generation SAPIEN XT (Edwards Lifesciences; Irvine, CA) transcatheter valve compared to surgical valves, but it showed similar rates in patients receiving the third-generation SAPIEN 3 (Edwards Lifesciences; Irvine, CA) valve.10 Comparisons between TAVR and SAVR in low-risk patients, using the newest generations of transcatheter prostheses, have only limited duration of follow-up at this time.11,12

If RESILIA tissue proves superior to what has been used previously, its success may merit implementation in TAVR valves as well. Notably, RESILIA tissue would have to sustain the mechanical stress and microtrauma imparted on TAVR valve leaflets from mounting the valve on a catheter and crimping the leaflets, as well as balloon inflation in balloon-expandable valves.13 Such advances in tissue technology like RESILIA will need to be evaluated in rigorous trials, preferably randomized, with TAVR and SAVR cohorts.

References

  1. Carroll JD, Mack MJ, Vemulapalli S, et al. STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement. J Am Coll Cardiol 2020;76:2492-516.
  2. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;77:450-500.
  3. Capodanno D, Petronio AS, Prendergast B, et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2017;38:3382-90.
  4. Johnston DR, Griffith BP, Puskas JD, Bavaria JE, Svensson LG, COMMENCE Trial Investigators. Intermediate-term outcomes of aortic valve replacement using a bioprosthesis with a novel tissue. J Thorac Cardiovasc Surg 2020;S0022-5223(20)30474-8.
  5. Flameng W, Hermans H, Verbeken E, Meuris B. A randomized assessment of an advanced tissue preservation technology in the juvenile sheep model. J Thorac Cardiovasc Surg 2015;149:340-5.
  6. Akins CW, Miller DC, Turina MI, et al. Guidelines for reporting mortality and morbidity after cardiac valve interventions. Ann Thorac Surg 2008;85:1490-5.
  7. Bourguignon T, Bouquiaux-Stablo AL, Candolfi P, et al. Very long-term outcomes of the Carpentier-Edwards Perimount valve in aortic position. Ann Thorac Surg 2015;99:831-7.
  8. Rodriguez-Gabella T, Voisine P, Dagenais F, et al. Long-Term Outcomes Following Surgical Aortic Bioprosthesis Implantation. J Am Coll Cardiol 2018;71:1401-12.
  9. S√łndergaard L, Ihlemann N, Capodanno D, et al. Durability of Transcatheter and Surgical Bioprosthetic Aortic Valves in Patients at Lower Surgical Risk. J Am Coll Cardiol 2019;73:546-53.
  10. Pibarot P, Ternacle J, Jaber WA, et al. Structural Deterioration of Transcatheter Versus Surgical Aortic Valve Bioprostheses in the PARTNER-2 Trial. J Am Coll Cardiol 2020;76:1830-43.
  11. Leon MB, Mack MJ, Hahn RT, et al. Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk. J Am Coll Cardiol 2021;77:1149-61.
  12. Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med 2019;380:1706-15.
  13. Dvir D, Bourguignon T, Otto CM, et al. Standardized Definition of Structural Valve Degeneration for Surgical and Transcatheter Bioprosthetic Aortic Valves. Circulation 2018;137:388-99.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Imaging, Interventions and Structural Heart Disease, Angiography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Coronary Angiography, Transcatheter Aortic Valve Replacement, Aortic Valve, Bioprosthesis, Calcium, Glycerol, Heart Valve Prosthesis, Aortic Valve Insufficiency, Reoperation, Constriction, Pathologic, Life Expectancy, Patient Discharge, Follow-Up Studies, Stress, Mechanical, Vitamin K 2, Consensus, Prospective Studies, Aldehydes, Aortic Valve Stenosis, Echocardiography, Hemodynamics, Thrombosis, Endocarditis, Catheters, Surgical Instruments, Tissue Preservation, Technology, Anticoagulants, Family Characteristics


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