Commentary: Rainmaking the “next-generation transcatheter aortic valve implantation” by anointing multidisciplinary perceptions (2020)

Central MessageA multidisciplinary approach of decellularization, immunologically modified α-galactosidase, and 3D-printing technology improves the performance of next-gen TAVI.See Article page 14. A multidisciplinary approach of decellularization, immunologically modified α-galactosidase, and 3D-printing technology improves the performance of next-gen TAVI. See Article page 14. Transcatheter aortic valve implantation (TAVI) has been the standard management strategy for aortic stenosis (AS) owing to its durability and fidelity, even in the patients with greater procedural risk.1Cahill T.J. Chen M. Hayashida K. Latib A. Modine T. Piazza N. et al.Transcatheter aortic valve implantation: current status and future perspectives.Eur Heart J. 2018; 39: 2625-2634Crossref PubMed Scopus (107) Google Scholar Introduced in 2002 by Cribier and colleagues,2Cribier A. Eltchaninoff H. Bash A. Borenstein N. Tron C. Bauer F. et al.Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis.Circulation. 2002; 106: 3006-3008Crossref PubMed Scopus (2561) Google Scholar TAVI has revolutionized the care of patients with AS, as evident by drastic increase with success stories of the patients (>300,000 annually) who have undergone TAVI procedure. However, the risk of complications including stroke, concomitant coronary artery diseases, and postoperative lifelong antithrombotic therapeutic regimen offer serious challenges in TAVI-based management strategies.3Ali N. Patel P.A. Lindsay S.J. Recent developments and controversies in transcatheter aortic valve implantation.Eur J Heart Fail. 2018; 20: 642-650Crossref Scopus (8) Google Scholar Even though the outcomes of TAVI are encouraging, the information regarding the fate of TAVI beyond 5 years remains obscure.4Arsalan M. Walther T. Durability of prostheses for transcatheter aortic valve implantation.Nat Rev Cardiol. 2016; 13: 360-367Crossref PubMed Scopus (110) Google Scholar Interestingly, these hurdles are not a limiting factor for TAVI; however, they pave multiple ways for refining the technology to explore alternative modalities for treating the patients with impaired vascular anatomy. In fact, the present-generation TAVI is the fruit of a progressive evolution, especially in the simplification of procedures, sophistication of valve and catheter technologies, incorporation of preprocedural planning using computed tomography imaging, and automation, ensuring the capability to predict the potential complications.1Cahill T.J. Chen M. Hayashida K. Latib A. Modine T. Piazza N. et al.Transcatheter aortic valve implantation: current status and future perspectives.Eur Heart J. 2018; 39: 2625-2634Crossref PubMed Scopus (107) Google Scholar As the TAVI research continues, novel concepts, modifications, and inventions are emerging and proceeding towards perfection. Application of the mechanical valve is limited, owing to the potential risk of bleeding due to the lifelong prophylactic anticoagulant medication administered to minimize thrombus formation. In contrast, the in vivo structural alterations in the biological valve increase the likelihood of reoperation. Interestingly, the advent of xenograft valves from porcine, bovine, and equine origins has significantly improved the hemodynamic profile, durability, and biological performance of TAVI.5Cohen G. Christakis G.T. Joyner C.D. Morgan C.D. Tamariz M. Hanayama N. et al.Are stentless valves hemodynamically superior to stented valves? A prospective randomized trial.Ann Thorac Surg. 2002; 73: 767-778Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar However, the immunogenicity of transplanted xeno-valves and subsequent peril of calcification have been an unaddressed puzzle in clinical cardiology and transplantation medicine. For instance, antigenicity of the carbohydrate moiety, galactose-α1,3-galactose (α-Gal), results in hyperacute immune rejection of the porcine xenograft as well as intensive calcification leading to the graft failure.6Li K.Y.C. Bioprosthetic heart valves: upgrading a 50-year old technology.Front Cardiovasc Med. 2019; 6: 47Crossref Scopus (23) Google Scholar Hence, the field of transplantation cardiology is hankering on next-generation (next-gen) xenografts to overcome such hurdles. In this context, Lim and coinvestigators7Lim H.-G. Jeong S. Kim G.B. Lee W. Son K.H. Kim Y.J. Next-generation transcatheter aortic valve implantation.J Thorac Cardiovasc Surg Open. 2020; 3: 14-24Scopus (1) Google Scholar in the current issue of the Journal demonstrated a promising strategy to address the immunogenicity of α-Gal and subsequent calcification in porcine TAVI using a multidisciplinary approach of decellularization, use of immunologically modified α-galactosidase, and 3-dimensional printing technology in their TAVI-sheep model. This evolving technology is schematically shown in Figure 1. The in vivo performance of the valves following the TAVI was exemplary, with proper stent fitting, outstanding coronary flow, better hemodynamic profile, and improved aortic valve function. Importantly, the study by Lim and colleagues7Lim H.-G. Jeong S. Kim G.B. Lee W. Son K.H. Kim Y.J. Next-generation transcatheter aortic valve implantation.J Thorac Cardiovasc Surg Open. 2020; 3: 14-24Scopus (1) Google Scholar is well appreciated for the minimal α-Gal–triggered immune reaction and calcification over the 8-month period. In addition, the findings in a clinically relevant large animal model could be translated to humans. Certainly, their encouraging findings and multidisciplinary approach inspire the next-gen TAVI and revolutionize the management of AS. However, the study is limited by finite element analysis, insufficient simulation of biomechanics, and lack of mechanistic findings, which warrant further research before clinical trials. Nonetheless, the findings by Lim and colleagues7Lim H.-G. Jeong S. Kim G.B. Lee W. Son K.H. Kim Y.J. Next-generation transcatheter aortic valve implantation.J Thorac Cardiovasc Surg Open. 2020; 3: 14-24Scopus (1) Google Scholar have launched a novel, multidisciplinary technological approach to improve the next-gen xenograft TAVI. In addition, imprinting the antistenotic mediators, prohealing signals, and anticalcification agents using 3-dimensional bioprinting technology would add more savor to the next-gen TAVI. Even though the findings are auspicious, the scrutiny of confounding comorbidities including hypertension and postimplantation complications including vascular injury, bleeding, and stroke warrants further attention before the translation into clinical arena. In conclusion, the multidisciplinary approach of amalgamating the elements/principles of immunology, biomaterials, molecular cardiology, and engineering would bolster next-gen TAVI, soothing the AS sufferers across the planet. Next-generation transcatheter aortic valve implantationJTCVS OpenVol. 3PreviewTranscatheter aortic valve implantation (TAVI) procedures are increasing rapidly, but the durability of tissue valve and periprocedural complications are not satisfactory. Immune reaction to the galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal) and conventional processing protocols of cardiac xenografts lead to calcification. Next-generation TAVI needs to be made with α-Gal–free xenografts by multiple anticalcification therapies to avoid immune rejection and enhance durability, and three-dimensional (3D) printing technology to improve the procedural safety. Full-Text PDF Open Access