Invited Commentary

Abstract

Dr Roselli discloses a financial relationship with Edwards Lifesciences, Metronic, St. Jude, and LivaNova.Advances in technology to treat the aortic valve have not only improved outcomes for our patients but are driving us to improve our understanding of the diseases that affect it. Replacing severely stenotic aortic valves has clearly been shown to prolong survival in comparison with medical therapy alone. Isolated aortic valve replacement can consistently be performed with a mortality rate of less than 1% in some centers. With the improvement of less invasive approaches and the development of transcatheter techniques, more patients are amenable to treatment, with easier recovery after replacement. Long-term survival, however, is most closely correlated with the extent of myocardial remodeling that has occurred up to the point of intervention [1Beach J.M. Mihaljevic T. Rajeswaran J. et al.Ventricular hypertrophy and left atrial dilatation persist and are associated with reduced survival after valve replacement for aortic stenosis.J Thorac Cardiovasc Surg. 2014; 147: 362-369Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar]. For this reason, we don’t typically see aortic valve replacement patients achieving survival equal to that in age-matched and gender-matched control individuals [2van Geldorp M.W. Eric Jamieson W.R. Kappetein A.P. et al.Patient outcome after aortic valve replacement with a mechanical or biological prosthesis: weighing lifetime anticoagulant-related event risk against reoperation risk.J Thorac Cardiovasc Surg. 2009; 137 (886e1–5): 881-886Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar]. If we are to achieve the ideal goal of reversing the natural history of aortic valve disease, we need treatment options that we will be comfortable applying to patients before they become symptomatic in the latest stage of disease. This means not only that we need ultrasafe therapies that do not require long-term anticoagulant therapy with outstanding hydrodynamic performance but that they must be reliably durable for several decades.Bioprosthetic heart valves have undergone several iterative improvements in the past 30 years, and they are now the valve of choice for most patients with aortic valve disease. Even patients under the age of 60 will commonly prefer a bioprosthesis to a mechanical valve. Designs have improved to the point at which nonstructural valve dysfunction is rare. The dominant mode of failure is related to tissue degeneration with or without calcification [3Roselli E.E. Smedira N.G. Blackstone E.H. Failure modes of the Carpentier-Edwards pericardial bioprosthesis in the aortic position.J Heart Valve Dis. 2006; 15 (discussion 427–8): 421-427PubMed Google Scholar].In a very elegant in vitro study of six bovine pericardial valves, Raghav and colleagues [4Raghav V. Okafor I. Quach M. Dang L. Marquez S. Yoganathan A.P. Long-term durability of Carpentier-Edwards Magna Ease valve: a one billion cycle invitro study.Ann Thorac Surg. 2016; 101: 1759-1767Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] demonstrated that mechanical durability and hydrodynamic performance was maintained through more than 1 billion cycles of simulated wear testing (equivalent to 25 years of the cardiac cycle). This study confirms that a superior design has been created for these valves when they are placed into an ideal environment. This is not surprising, given that the basic macrodesign of these valves mimics what is found in nature: three cusps are suspended equidistantly, with significant coaptation to distribute force. Furthermore, the current versions of bioprosthetic valves represent decades of research and development.Certainly, in vitro testing is critical to device development and patient safety. Previous studies have correlated in vitro testing with clinical outcomes, and excellent outcomes have been demonstrated with similar valves in clinical practice. In a series of more than 12,000 patients receiving stented bovine pericardial aortic bioprostheses at the Cleveland Clinic, we demonstrated that the actuarial explant for structural valve deterioration (SVD) at 20 years was only 15% [5Johnston D.R. Soltesz E.G. Vakil N. et al.Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants.Ann Thorac Surg. 2015; 99: 1239-1247Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar]. Part of this may result from the competing risks between death and SVD events, but even in younger patients, reoperation for SVD was uncommon.Despite the promising outcomes demonstrated in this and similar in vitro studies, we don’t fully understand how to eliminate SVD in the biologic environment. What we don't learn from an in vitro study is how the valve interacts with the patient. It is exactly at this patient–prosthesis interface where we need to improve our knowledge.It has long been acknowledged that age is inversely related to bioprosthetic valve durability. With its large numbers, this study by Johnston and colleagues [5Johnston D.R. Soltesz E.G. Vakil N. et al.Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants.Ann Thorac Surg. 2015; 99: 1239-1247Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar] revealed the important role of hydrodynamics in predicting durability. Higher early transvalvular gradients and patient–prosthesis mismatch were among the strongest predictors of SVD, but valve size was not. For the in vitro study by Raghav and colleagues [4Raghav V. Okafor I. Quach M. Dang L. Marquez S. Yoganathan A.P. Long-term durability of Carpentier-Edwards Magna Ease valve: a one billion cycle invitro study.Ann Thorac Surg. 2016; 101: 1759-1767Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], 21-mm and 23-mm bioprostheses were tested because these are the most commonly used sizes. In clinical practice, it is critical that the operator choose the best valve for each individual patient. As we more commonly choose bioprosthetic valves for younger and lower-risk patients, we must better understand how to make that choice. The left ventricular outflow tract and aortic root are irregular and vary between patients. There are rough areas under the valve where chunks of calcium were debrided. The shape of the valve stent may be distorted. Subannular pledgets are commonly used and may affect flow through the prosthesis. These subtle irregularities may play a role in hydrodynamics in the long term, and it would be interesting to see an in vitro model that accounts for these subtle differences. With the increased access to three-dimensional printing based on high-resolution imaging, it may be possible to study this patient– prosthesis interface with better in vitro testing models created from actual patient data.In the meantime, we need to work harder at making the environment where we put the bioprosthetic valve look more like the ideal valve tester and optimize hydrodynamics. It is important to debride the annulus thoroughly and avoid stent distortion. Optimizing the hydrodynamic fit between patient and prosthesis may require root enlargement or more frequent use of stentless bioprostheses. Although data are currently lacking, avoiding pledgets in the outflow tract or the use of sutureless valves may also improve hydrodynamics.The model used in the current study was devoid of calcium. A great deal of attention has been directed at improving tissue processing to limit calcification. Calcium may accumulate as a result of microinjury from stress and exposure of chemoattractants on the surface of the tissue cusps. Histologic assessment of the valve cusps after prolonged exposure to wear testing may provide further knowledge of this mechanism. Surgical aortic valve replacement is more likely to be the treatment option for younger patients now that more elderly patients are treated with transcatheter aortic valve replacement. I look forward to additional analyses from this team to improve the options for treating aortic valve disease. Dr Roselli discloses a financial relationship with Edwards Lifesciences, Metronic, St. Jude, and LivaNova.Advances in technology to treat the aortic valve have not only improved outcomes for our patients but are driving us to improve our understanding of the diseases that affect it. Replacing severely stenotic aortic valves has clearly been shown to prolong survival in comparison with medical therapy alone. Isolated aortic valve replacement can consistently be performed with a mortality rate of less than 1% in some centers. With the improvement of less invasive approaches and the development of transcatheter techniques, more patients are amenable to treatment, with easier recovery after replacement. Long-term survival, however, is most closely correlated with the extent of myocardial remodeling that has occurred up to the point of intervention [1Beach J.M. Mihaljevic T. Rajeswaran J. et al.Ventricular hypertrophy and left atrial dilatation persist and are associated with reduced survival after valve replacement for aortic stenosis.J Thorac Cardiovasc Surg. 2014; 147: 362-369Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar]. For this reason, we don’t typically see aortic valve replacement patients achieving survival equal to that in age-matched and gender-matched control individuals [2van Geldorp M.W. Eric Jamieson W.R. Kappetein A.P. et al.Patient outcome after aortic valve replacement with a mechanical or biological prosthesis: weighing lifetime anticoagulant-related event risk against reoperation risk.J Thorac Cardiovasc Surg. 2009; 137 (886e1–5): 881-886Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar]. If we are to achieve the ideal goal of reversing the natural history of aortic valve disease, we need treatment options that we will be comfortable applying to patients before they become symptomatic in the latest stage of disease. This means not only that we need ultrasafe therapies that do not require long-term anticoagulant therapy with outstanding hydrodynamic performance but that they must be reliably durable for several decades. Dr Roselli discloses a financial relationship with Edwards Lifesciences, Metronic, St. Jude, and LivaNova. Dr Roselli discloses a financial relationship with Edwards Lifesciences, Metronic, St. Jude, and LivaNova. Bioprosthetic heart valves have undergone several iterative improvements in the past 30 years, and they are now the valve of choice for most patients with aortic valve disease. Even patients under the age of 60 will commonly prefer a bioprosthesis to a mechanical valve. Designs have improved to the point at which nonstructural valve dysfunction is rare. The dominant mode of failure is related to tissue degeneration with or without calcification [3Roselli E.E. Smedira N.G. Blackstone E.H. Failure modes of the Carpentier-Edwards pericardial bioprosthesis in the aortic position.J Heart Valve Dis. 2006; 15 (discussion 427–8): 421-427PubMed Google Scholar]. In a very elegant in vitro study of six bovine pericardial valves, Raghav and colleagues [4Raghav V. Okafor I. Quach M. Dang L. Marquez S. Yoganathan A.P. Long-term durability of Carpentier-Edwards Magna Ease valve: a one billion cycle invitro study.Ann Thorac Surg. 2016; 101: 1759-1767Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] demonstrated that mechanical durability and hydrodynamic performance was maintained through more than 1 billion cycles of simulated wear testing (equivalent to 25 years of the cardiac cycle). This study confirms that a superior design has been created for these valves when they are placed into an ideal environment. This is not surprising, given that the basic macrodesign of these valves mimics what is found in nature: three cusps are suspended equidistantly, with significant coaptation to distribute force. Furthermore, the current versions of bioprosthetic valves represent decades of research and development. Certainly, in vitro testing is critical to device development and patient safety. Previous studies have correlated in vitro testing with clinical outcomes, and excellent outcomes have been demonstrated with similar valves in clinical practice. In a series of more than 12,000 patients receiving stented bovine pericardial aortic bioprostheses at the Cleveland Clinic, we demonstrated that the actuarial explant for structural valve deterioration (SVD) at 20 years was only 15% [5Johnston D.R. Soltesz E.G. Vakil N. et al.Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants.Ann Thorac Surg. 2015; 99: 1239-1247Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar]. Part of this may result from the competing risks between death and SVD events, but even in younger patients, reoperation for SVD was uncommon. Despite the promising outcomes demonstrated in this and similar in vitro studies, we don’t fully understand how to eliminate SVD in the biologic environment. What we don't learn from an in vitro study is how the valve interacts with the patient. It is exactly at this patient–prosthesis interface where we need to improve our knowledge. It has long been acknowledged that age is inversely related to bioprosthetic valve durability. With its large numbers, this study by Johnston and colleagues [5Johnston D.R. Soltesz E.G. Vakil N. et al.Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants.Ann Thorac Surg. 2015; 99: 1239-1247Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar] revealed the important role of hydrodynamics in predicting durability. Higher early transvalvular gradients and patient–prosthesis mismatch were among the strongest predictors of SVD, but valve size was not. For the in vitro study by Raghav and colleagues [4Raghav V. Okafor I. Quach M. Dang L. Marquez S. Yoganathan A.P. Long-term durability of Carpentier-Edwards Magna Ease valve: a one billion cycle invitro study.Ann Thorac Surg. 2016; 101: 1759-1767Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], 21-mm and 23-mm bioprostheses were tested because these are the most commonly used sizes. In clinical practice, it is critical that the operator choose the best valve for each individual patient. As we more commonly choose bioprosthetic valves for younger and lower-risk patients, we must better understand how to make that choice. The left ventricular outflow tract and aortic root are irregular and vary between patients. There are rough areas under the valve where chunks of calcium were debrided. The shape of the valve stent may be distorted. Subannular pledgets are commonly used and may affect flow through the prosthesis. These subtle irregularities may play a role in hydrodynamics in the long term, and it would be interesting to see an in vitro model that accounts for these subtle differences. With the increased access to three-dimensional printing based on high-resolution imaging, it may be possible to study this patient– prosthesis interface with better in vitro testing models created from actual patient data. In the meantime, we need to work harder at making the environment where we put the bioprosthetic valve look more like the ideal valve tester and optimize hydrodynamics. It is important to debride the annulus thoroughly and avoid stent distortion. Optimizing the hydrodynamic fit between patient and prosthesis may require root enlargement or more frequent use of stentless bioprostheses. Although data are currently lacking, avoiding pledgets in the outflow tract or the use of sutureless valves may also improve hydrodynamics. The model used in the current study was devoid of calcium. A great deal of attention has been directed at improving tissue processing to limit calcification. Calcium may accumulate as a result of microinjury from stress and exposure of chemoattractants on the surface of the tissue cusps. Histologic assessment of the valve cusps after prolonged exposure to wear testing may provide further knowledge of this mechanism. Surgical aortic valve replacement is more likely to be the treatment option for younger patients now that more elderly patients are treated with transcatheter aortic valve replacement. I look forward to additional analyses from this team to improve the options for treating aortic valve disease. Long-Term Durability of Carpentier-Edwards Magna Ease Valve: A One Billion Cycle In Vitro StudyThe Annals of Thoracic SurgeryVol. 101Issue 5PreviewDurability and hemodynamic performance are top considerations in selecting a valve for valve replacement surgery. This study was conducted in order to evaluate the long-term mechanical durability and hydrodynamic performance of the Carpentier-Edwards PERIMOUNT Magna Ease Bioprostheses, through 1 billion cycles (equivalent to 25 years). Full-Text PDF