Editor's Note: Commentary based on Sénage T, Le Tourneau T, Foucher Y, et al. Early structural valve deterioration of Mitroflow aortic bioprosthesis: Mode, incidence and impact on outcome in a large cohort of patients. Circulation 2014.

Background

Bioprosthetic heart valves are becoming more commonly used, with bovine pericardial valves playing a prominent role. The most important complication with tissue valves is structural valve deterioration (SVD). The paper by Sénage et al¹ describes the incidence of SVD with the Mitroflow (MF) aortic pericardial valve.

Methods

From 2002 to 2007, 617 patients received MF aortic valves. Follow-up echocardiographic data was obtained from the patients' personal physicians. SVD was defined by a combination of gradient, effective orifice area and regurgitation.

Results

SVD was diagnosed in 39 patients, for a Kaplan-Meier estimate (95% confidence interval) of 8.4% (5.3%, 11.3%) at 5 years. Cox regression showed SVD to have a significant effect on mortality, with a hazard ratio of 7.7 (4.5-13.6).

Conclusions

From the authors' abstract: "In view of the large number of Mitroflow valves implanted worldwide, one can expect an epidemic of SVD and valve-related deaths, which represents a major public health issue, especially in the elderly."

Commentary/Perspective

The authors of this paper base their prediction of "an epidemic of ... valve-related deaths" for the MF aortic valve on their 5-year results using an echocardiographic definition of SVD. But several much longer-term studies, using death and explant as the definition of SVD, have in fact not observed this predicted epidemic. In one of their cited references², a series of 1,516 patients had SVD-free rates at 5, 10, and 15 years of 99%, 83%, and 63%, respectively. And in another of their references³, a series of 1,513 patients had 20-year SVD-free rates of 62%, 72% and 85%, in all patients, those ≥65 years and those ≥70, respectively. Those long-term SVD rates hardly seem like an "epidemic".

The fact that SVD had the alarming hazard ratio of 7.7 for death in this series is because surgery was only offered to 4 (10%) of the 39 SVD cases. And 11 of those who were not re-operated death. This is in contrast to other papers that report both echo-detected SVD and explant for SVD, in which 16/39 (41%)⁴, 16/23 (70%)⁵, 17/19 (89%)⁶, 109/132 (83%)⁷ and 20/27 (74%)⁸ of SVD valves were explanted. It seems that the authors did not take the advice from their own discussion: "... urgent reoperation should be considered once stenosis is severe, even in asymptomatic patients." Thus the real issue with this paper is not that the SVD rate was so high but that the explant rate was so low.

During the time period of this study, the authors also implanted 1,173 Carpentier-Edwards (CE) aortic pericardial valves. Their conclusions would have been more compelling if they had presented the comparative results of a similar SVD incidence/explant analysis for their CE valves.

Finally, there is a technical issue with the method of analysis. Although Figure 3 is labeled "Cumulative Incidence" of SVD, it is in fact the complement of the Kaplan-Meier (KM) estimate. The true Cumulative Incidence function (CIF), which is the appropriate measure of SVD probability^9-10, would be lower than the KM estimate of 8.4% at 5 years. For example, in one of the authors' references where both methods were used³, the KM estimates of SVD were 38%, 28% and 15%, in all patients, those ≥65 years and those ≥70, respectively, whereas the corresponding CIF (true probability) estimates were 11%, 7% and 3%. The value of 8.4% may be lower than the true KM estimate, because some cases of SVD may have been missed due to incompleteness of follow-up. But the (true) CIF estimate will always be less than the KM estimate, simply for technical reasons: they are computed by entirely different formulas.

References

1. Sénage T, Le Tourneau T, Foucher Y, et al. Early Structural Valve Deterioration of Mitroflow Aortic Bioprosthesis: Mode, Incidence and Impact on Outcome in a Large Cohort of Patients. Circulation 2014;130(23):2012-20.
2. Minami K, Zittermann A, Schulte-Eistrup S, et al. Mitroflow synergy prostheses for aortic valve replacement: 19 years experience with 1,516 patients. Ann Thorac Surg 2005;80(5):1699–1705.
3. Yankah CA, Pasic M, Musci M, et al. Aortic valve replacement with the Mitroflow pericardial bioprosthesis: durability results up to 21 years. J Thorac Cardiovasc Surg 2008;136(3):688–96.
4. Kirali K, Guler M, Tuncer A, et al. Fifteen-year clinical experience with the Biocor porcine bioprostheses in the mitral position. Ann Thorac Surg 2001;71(3):811-5.
5. Eichinger WB, Hettich IM, Ruzicka DJ, et al. Twenty-year experience with the St. Jude Medical Biocor bioprosthesis in the aortic position. Ann Thorac Surg 2008;86:1204-10.
6. Aupart MR, Mirza A, Meurisse UA, et al. Perimount pericardial bioprosthesis for aortic calcified stenosis: 18-year experience with 1133 patients. J Heart Valve Dis 2006;15:768-76.
7. Jamieson WR, Burr LH, Miyagishima RT, et al. Carpentier-Edwards supraannular aortic porcine bioprosthe- sis: clinical performance over 20 years. J Thorac Cardiovasc Surg 2005;130:994-1000.
8. Alvarez JR, Sierra J, Vega M, et al. Early calcification of the aortic Mitroflow pericardial bioprosthesis in the elderly. Interactive CardioVascular and Thoracic Surgery 2009;9(5):842–846.
9. Southern DA, Faris PD, Brant R, et al. Kaplan-Meier methods yielded misleading results in competing risk scenarios. J Clin Epidemiol 2006;59:1110-4.
10. Koller MT, Raatz H, Steyerberg EW, Wolbers M. Competing risks and the clinical community: irrelevance or ignorance? Stat Med 2012;31:1089-97.

Keywords: Aortic Valve, Bioprosthesis, Constriction, Pathologic, Kaplan-Meier Estimate, Pericardium, Public Health, Reoperation, Heart Valve Prosthesis

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