European Journal of Cardio-Thoracic Surgery Advance Access published October 31, 2014
Porcine or bovine: does it really matter? Manuel J. Antunes* Centre of Cardiothoracic Surgery, University Hospital and Medical School, Coimbra, Portugal * Corresponding author. Centro de Cirurgia Cardiotorácica, Hospitais da Universidade, 3000-075 Coimbra, Portugal. Tel: +351-239400418; fax: +351-239829674; e-mail: [email protected] (M.J. Antunes).
Keywords: Aortic valve replacement • Porcine • Bovine pericardial • Outcomes
In a paper published in this issue of the European Journal of Cardio-thoracic Surgery, Hickey et al. [1] compare the performance of porcine and bovine pericardial valves implanted in the aortic position with respect to survival and intervention-free survival. This is a retrospective observational study of the National Institute for Cardiovascular Outcomes database on all first-time aortic valve replacements, with or without concomitant coronary artery bypass surgery, performed in England and Wales between April 2003 and March 2013. Approximately two thirds of the 38 040 patients included received a bovine pericardial prosthesis and the remainder had a porcine bioprosthesis implanted. The authors found no difference in survival up to 10 years of followup between the two groups of patients (49.0 and 50.3%, respectively). Similarly, there was no difference in intervention-free survival. Interestingly, however, the authors found ‘some evidence of a protective effect for porcine valves in relatively younger patients’. This work coincides in time with the decision of Edwards Lifesciences, one of the main manufacturers, and pioneer in the field, to discontinue their porcine models, which have been in use since the early 1970s. At that time, the bioprostheses were introduced with the objective of offsetting the thromboembolic complications of the mechanical valves, introduced one decade earlier. But the initial enthusiasm was soon dampened by early reports of biodegradation, especially in younger patients where they were hoped to be a better choice, by avoiding the need for use of anticoagulation [2]. Nonetheless, the bioprostheses remained a good option for older patients and for the last four decades were indicated for patients over 65–70 years of age by the guidelines on both sides of the Atlantic [3, 4]. Thus, the mechanical valves dominated the market and several models were implanted in millions of patients, exceeding 2 million in one model alone, with excellent performance records. But in the last decade, there has been a significant worldwide shift in surgeon’s attitude towards preferring bioprostheses, which are currently used in up to 80% of the patients, also justified by the increasing age of the population. On the other hand, the bovine pericardial valves were pioneered by Marian Ionescu [5] in England in 1976, but their use was only generalized in the 1980s and 1990s. They were initially implanted almost exclusively in the aortic position, and their main objective was the improvement of haemodynamic characteristics of the prosthesis, which were always perceived as less than perfect in the porcine models. In fact, most studies showed a better
haemodynamic performance of the pericardial valves, with greater effective orifice areas and smaller gradients [6]. One issue that deserves special attention is the small aortic root requiring a small prosthesis, thought to be one of the Achilles’ heel of the bioprosthesis. Cases of patient–prosthesis mismatch were more common in the porcine valves. However, a negative impact of the mismatch, at least with respect to survival, has never been completely demonstrated, although faster and better resolution of the myocardial hypertrophy after valve replacement for aortic stenosis was observed in cases with no mismatch [7]. In fact, the series of Hickey et al. [1] showed similar reintervention-free survival in patients with small prostheses (≤21 mm), in whom gradient differences between these two valve types would be most marked. From this point of view, therefore, pericardial valves did not entirely match initial expectations. During their already long history, bioprostheses underwent important evolution and modifications aimed at both prolonging their durability and improving their haemodynamic performance. Several methods of treatment of the biological tissue were introduced, but there is no convincing evidence that any of those had significant impact on durability and freedom from calcification. Valve stents and assembling techniques were also modified and the dynamic properties were effectively ameliorated, thus bringing the porcine closer to the pericardial valves. Finally, there was the introduction of stentless bioprostheses, also with proven better haemodynamic properties, which have had an increasing acceptance, but they do not enter in this discussion. Then, why have the pericardial valves gained advantage over porcine prostheses? Having the above in mind, the decision by many surgeons to prefer pericardial valves was more emotionally based than scientifically proven, as appears to be consubstantiated by the conclusions of the work hereby discussed. It may be argued that there are many more models of bioprostheses than those utilized in this series, hence making generalization difficult, but the number of patients involved should offset these concerns. Interestingly, the two most used models of porcine and pericardial bioprostheses worldwide were also the most commonly used by the British surgeons and low- and moderate-volume surgeons had a greater propensity to use pericardial valves, which could also raise some questions. But there is one important limitation of the study of Hickey et al. [1]: the relatively short follow-up, with a mean of less than 4 years. When analysing the durability of bioprostheses, any follow-up shorter than 10 years must be viewed with some
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ADULT CARDIAC
EDITORIAL COMMENT
European Journal of Cardio-Thoracic Surgery (2014) 1–2 doi:10.1093/ejcts/ezu414
2
M.J. Antunes / European Journal of Cardio-Thoracic Surgery
caution. But their results appear to be confirmed by a meta-analysis recently published in the ICVTS by Yap et al., who found that ‘both bovine and porcine valves have comparable results with regard to the mortality, postoperative functional status and valve durability’ [8]. The market is often driven by factors that may not have a direct relationship with scientific evidence. Although the figures on current utilization of these two types of bioprostheses are not known, it seems obvious that the decision to discontinue porcine valves is market-driven and has little to do with the comparative results of the two valve types. In many places worldwide, the pericardial valve is significantly costlier, which is an important consideration in many cases. So far, other manufacturers have not followed suit, hence porcine valves are likely to stay around for quite some time. Therefore, the paper Hickey et al. [1] published in this issue of the journal should contribute to the peace of mind of those who continue using porcine valves for whatever reason.
[2]
[3]
[4]
[5]
[6]
[7]
REFERENCES [8] [1] Hickey GL, Grant SW, Bridgewater B, Kendall S, Bryan AJ, Kuo J et al. A comparison of outcomes between bovine pericardial and porcine valves
in 38040 patients in England and Wales over 10 years. Eur J Cardiothorac Surg 2014, doi:10.1093/ejcts/ezu307. Antunes MJ, Santos LP. Performance of glutaraldehyde-preserved porcine bioprosthesis as a mitral valve substitute in a young population group. Ann Thorac Surg 1984;37:387–92. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H et al. Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1–44. Nishimura RA, Otto CM, Bonow RO, Ruiz CE, Carabello BA, Skubas NJ et al. 2014 AHA/ACC Guideline for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57–e185. Tandon AP, Smith DR, Whitaker WL, Ionescu MI. Long-term haemodynamic evaluation of aortic pericardial xenograft. Br Heart J 1978;40: 602–7. Cosgrove DM, Lytle BW, Gill CC, Golding LA, Stewart RW, Loop FD et al. In vivo hemodynamic comparison of porcine and pericardial valves. J Thorac Cardiovasc Surg 1985;89:358–68. Tasca G, Brunelli F, Cirillo M, Amaducci A, Mhagna Z, Troise G et al. Mass regression in aortic stenosis after valve replacement with small size pericardial bioprosthesis. Ann Thorac Surg 2003;76: 1107–13. Yap KH, Murphy R, Devbhandari M, Venkateswaran R. Aortic valve replacement: is porcine or bovine valve better? Interact CardioVasc Thorac Surg 2013;16:361–73.
Porcine or bovine: does it really matter? Manuel J. Antunes* Centre of Cardiothoracic Surgery, University Hospital and Medical School, Coimbra, Portugal * Corresponding author. Centro de Cirurgia Cardiotorácica, Hospitais da Universidade, 3000-075 Coimbra, Portugal. Tel: +351-239400418; fax: +351-239829674; e-mail: [email protected] (M.J. Antunes).
Keywords: Aortic valve replacement • Porcine • Bovine pericardial • Outcomes
In a paper published in this issue of the European Journal of Cardio-thoracic Surgery, Hickey et al. [1] compare the performance of porcine and bovine pericardial valves implanted in the aortic position with respect to survival and intervention-free survival. This is a retrospective observational study of the National Institute for Cardiovascular Outcomes database on all first-time aortic valve replacements, with or without concomitant coronary artery bypass surgery, performed in England and Wales between April 2003 and March 2013. Approximately two thirds of the 38 040 patients included received a bovine pericardial prosthesis and the remainder had a porcine bioprosthesis implanted. The authors found no difference in survival up to 10 years of followup between the two groups of patients (49.0 and 50.3%, respectively). Similarly, there was no difference in intervention-free survival. Interestingly, however, the authors found ‘some evidence of a protective effect for porcine valves in relatively younger patients’. This work coincides in time with the decision of Edwards Lifesciences, one of the main manufacturers, and pioneer in the field, to discontinue their porcine models, which have been in use since the early 1970s. At that time, the bioprostheses were introduced with the objective of offsetting the thromboembolic complications of the mechanical valves, introduced one decade earlier. But the initial enthusiasm was soon dampened by early reports of biodegradation, especially in younger patients where they were hoped to be a better choice, by avoiding the need for use of anticoagulation [2]. Nonetheless, the bioprostheses remained a good option for older patients and for the last four decades were indicated for patients over 65–70 years of age by the guidelines on both sides of the Atlantic [3, 4]. Thus, the mechanical valves dominated the market and several models were implanted in millions of patients, exceeding 2 million in one model alone, with excellent performance records. But in the last decade, there has been a significant worldwide shift in surgeon’s attitude towards preferring bioprostheses, which are currently used in up to 80% of the patients, also justified by the increasing age of the population. On the other hand, the bovine pericardial valves were pioneered by Marian Ionescu [5] in England in 1976, but their use was only generalized in the 1980s and 1990s. They were initially implanted almost exclusively in the aortic position, and their main objective was the improvement of haemodynamic characteristics of the prosthesis, which were always perceived as less than perfect in the porcine models. In fact, most studies showed a better
haemodynamic performance of the pericardial valves, with greater effective orifice areas and smaller gradients [6]. One issue that deserves special attention is the small aortic root requiring a small prosthesis, thought to be one of the Achilles’ heel of the bioprosthesis. Cases of patient–prosthesis mismatch were more common in the porcine valves. However, a negative impact of the mismatch, at least with respect to survival, has never been completely demonstrated, although faster and better resolution of the myocardial hypertrophy after valve replacement for aortic stenosis was observed in cases with no mismatch [7]. In fact, the series of Hickey et al. [1] showed similar reintervention-free survival in patients with small prostheses (≤21 mm), in whom gradient differences between these two valve types would be most marked. From this point of view, therefore, pericardial valves did not entirely match initial expectations. During their already long history, bioprostheses underwent important evolution and modifications aimed at both prolonging their durability and improving their haemodynamic performance. Several methods of treatment of the biological tissue were introduced, but there is no convincing evidence that any of those had significant impact on durability and freedom from calcification. Valve stents and assembling techniques were also modified and the dynamic properties were effectively ameliorated, thus bringing the porcine closer to the pericardial valves. Finally, there was the introduction of stentless bioprostheses, also with proven better haemodynamic properties, which have had an increasing acceptance, but they do not enter in this discussion. Then, why have the pericardial valves gained advantage over porcine prostheses? Having the above in mind, the decision by many surgeons to prefer pericardial valves was more emotionally based than scientifically proven, as appears to be consubstantiated by the conclusions of the work hereby discussed. It may be argued that there are many more models of bioprostheses than those utilized in this series, hence making generalization difficult, but the number of patients involved should offset these concerns. Interestingly, the two most used models of porcine and pericardial bioprostheses worldwide were also the most commonly used by the British surgeons and low- and moderate-volume surgeons had a greater propensity to use pericardial valves, which could also raise some questions. But there is one important limitation of the study of Hickey et al. [1]: the relatively short follow-up, with a mean of less than 4 years. When analysing the durability of bioprostheses, any follow-up shorter than 10 years must be viewed with some
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ADULT CARDIAC
EDITORIAL COMMENT
European Journal of Cardio-Thoracic Surgery (2014) 1–2 doi:10.1093/ejcts/ezu414
2
M.J. Antunes / European Journal of Cardio-Thoracic Surgery
caution. But their results appear to be confirmed by a meta-analysis recently published in the ICVTS by Yap et al., who found that ‘both bovine and porcine valves have comparable results with regard to the mortality, postoperative functional status and valve durability’ [8]. The market is often driven by factors that may not have a direct relationship with scientific evidence. Although the figures on current utilization of these two types of bioprostheses are not known, it seems obvious that the decision to discontinue porcine valves is market-driven and has little to do with the comparative results of the two valve types. In many places worldwide, the pericardial valve is significantly costlier, which is an important consideration in many cases. So far, other manufacturers have not followed suit, hence porcine valves are likely to stay around for quite some time. Therefore, the paper Hickey et al. [1] published in this issue of the journal should contribute to the peace of mind of those who continue using porcine valves for whatever reason.
[2]
[3]
[4]
[5]
[6]
[7]
REFERENCES [8] [1] Hickey GL, Grant SW, Bridgewater B, Kendall S, Bryan AJ, Kuo J et al. A comparison of outcomes between bovine pericardial and porcine valves
in 38040 patients in England and Wales over 10 years. Eur J Cardiothorac Surg 2014, doi:10.1093/ejcts/ezu307. Antunes MJ, Santos LP. Performance of glutaraldehyde-preserved porcine bioprosthesis as a mitral valve substitute in a young population group. Ann Thorac Surg 1984;37:387–92. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H et al. Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg 2012;42:S1–44. Nishimura RA, Otto CM, Bonow RO, Ruiz CE, Carabello BA, Skubas NJ et al. 2014 AHA/ACC Guideline for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57–e185. Tandon AP, Smith DR, Whitaker WL, Ionescu MI. Long-term haemodynamic evaluation of aortic pericardial xenograft. Br Heart J 1978;40: 602–7. Cosgrove DM, Lytle BW, Gill CC, Golding LA, Stewart RW, Loop FD et al. In vivo hemodynamic comparison of porcine and pericardial valves. J Thorac Cardiovasc Surg 1985;89:358–68. Tasca G, Brunelli F, Cirillo M, Amaducci A, Mhagna Z, Troise G et al. Mass regression in aortic stenosis after valve replacement with small size pericardial bioprosthesis. Ann Thorac Surg 2003;76: 1107–13. Yap KH, Murphy R, Devbhandari M, Venkateswaran R. Aortic valve replacement: is porcine or bovine valve better? Interact CardioVasc Thorac Surg 2013;16:361–73.
