Transcatheter aortic valve implantation is increasingly being used in the treatment of aortic stenosis (Petronio et al. 2011; Spaccarotella et al. 2010), but its place in therapy still needs to be settled. Although the PARTNER trial (Leon et al. 2010) has shown that this less invasive approach can be as effective as open surgery based on traditional valve replacement, the majority of people who are currently subjected to this percutaneous intervention are selected based on the criterion of inoperability (Petronio et al. 2011; Spaccarotella et al. 2010).

Assessing the long-term results in these subjects raises a number of problems because cause-specific mortality cannot be easily separated from all-cause mortality, and all-cause mortality is high due to the age of these subjects. Particular emphasis needs therefore to be placed on the assessment of short term outcomes, among which all-cause 30-day mortality is considered to be the main end-point (Petronio et al. 2011; Spaccarotella et al. 2010).

Spaccarotella et al. (2010) have reviewed the data of this short-term end-point (all-cause 30-day mortality) by examining a series of real-world registries from 7 countries. Table 1 summarises the data on this end-point published by these authors and integrates the information reported in the above-mentioned paper with two additional pieces of information: a) the number of patients enrolled in the various registries (which was not originally reported by Spaccarotella et al.); b) more updated information from the same registries when available.

To better interpret the mortality data reported in Table 1, we carried out a meta-analysis of proportions (Mills et al. 2006; Trinquart and Touze 2009). First, to establish the variance of raw proportions, the transformation of Freeman and Tukey (1950) was applied; second, in order to incorporate heterogeneity (that was anticipated among the included studies), transformed proportions were combined using random effects models (DerSimonian and Laird 1986). Finally, the pooled estimates were back-transformed. Heterogeneity across studies was evaluated using the Cochran`s Q test. Thus, the results were expressed as pooled proportion (%) with 95% confidence interval (95%CI). All these analysis were performed using the freely downloadable software package META for R version 2.13.1 (R Development Core Team 2001).

Figure 1 below illustrates the results of this meta-analysis of proportions. The pooled rate is 8.4% and, more importantly, its 95%CI ranges from 4.8% to 12.9%. Heterogeneity is statistically significant (Cochran`s Q=37.6, df=6, p<0.001; I²=84%). This suggests that the benefits produced by this relatively new intervention can differ substantially between different centres.

Are there any practical implications from these findings? Our view is that governance interventions can be useful for managing this type of innovation and that risk-sharing methods can offer a practical solution in this field. For example, our jurisdiction in the area of Firenze (Toscana, Italy) that includes more than 1,000,000 inhabitants is now considering to introduce a payment-by-results agreement (Garber and McLellan 2007) whereby a full payback of the valve`s acquisition cost (from the manufacturer to our health system) would be requested for all cases that do not survive up to 30 days after the implant.

References

Avanzas P, Munoz-Garcia AJ, Segura J, Pan M, Alonso-Briales JH, Lozano I, Moris C, Suarez de Lezo J, Hernandez-Garcia JM. Percutaneous implantation of the CoreValve self-expanding aortic valve prosthesis in patients with severe aortic stenosis: early experience in Spain. Rev Esp Cardiol. 2010 Feb;63(2):141-8.

Bosmans JM, Belgian Registry TAVI Facts Figures and National Registries. EuroPCR 2010 Paris, Abstract presentation.

Bosmans JM, Kefer J, De Bruyne B, Herijgers P, Dubois C, Legrand V, Verheye S, Rodrigus I; Belgian TAVI Registry Participants. Procedural, 30-day and one year outcome following CoreValve or Edwards transcatheter aortic valve implantation: results of the Belgian national registry. Interact Cardiovasc Thorac Surg. 2011 May;12(5):762-7. Epub 2011 Feb 24.

DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188.

Eltchaninoff H, Prat A, Gilard M, Leguerrier A, Blanchard D, Fournial G, et al, on behalf of the FRANCE Registry Investigators. Transcatheter aortic valve implantation: Early results of the FRANCE (FRench Aortic National CoreValve and Edwards) Registry. Eur Heart J 2011 Jan;32(2):191-7.

Freeman MF, Tukey JW. Ttrasformations related to the angular and the square root. Ann Math Stat 1950; 21:607-11.

Garber AM, McClellan MB. Satisfaction guaranteed--"payment by results" for biologic agents. N Engl J Med. 2007 Oct 18;357(16):1575-7.

Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607.

Ludman AP, UK Registry TAVI Facts Figures and National Registries. EuroPCR 2010 Paris, Abstract presentation.

Meredith IT. A Snapshot from the Ongoing Australia-New Zealand Medtronic CoreValve Registry. Transcatheter Cardiovascular Therapeutics 2009, September 21-25, 2009. San Francisco, CA, USA.

Mills EJ, Nachega JB, Buchan I, Orbinski J, Attaran A, Singh S, Rachlis B, Wu P, Cooper C, Thabane L, Wilson K, Guyatt GH, Bangsberg DR. Adherence toantiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. JAMA. 2006 Aug 9;296(6):679-90.

Moynagh AM, Scott DJ, Baumbach A, Khavandi A, Brecker SJ, Laborde JC, Brown S, Chowdhary S, Saravanan D, Crean PA, Teehan S, Hildick-Smith D, Trivedi U, Khogali SS, Bhabra MS, Roberts DH, Morgan KP, Blackman DJ; UK CoreValve Collaborative. CoreValve transcatheter aortic valve implantation via the subclavian artery: comparison with the transfemoral approach. J Am Coll Cardiol. 2011 Feb 1;57(5):634-5.

Ormiston J, Meredith I, Walters D, Walton T, Pasupati S, Muller D, Worthlesy S, Yong G, Whitbourn R. TCT-491: Early Effectiveness and Safety Results From the CoreValve Transcatheter Aortic Valve Australia-New Zealand Study. J. Am. Coll. Cardiol. 2010;56;B112-B113 doi:10.1016/j.jacc.2010.08.563 downloaded from content.onlinejacc.org on October 11, 2011.

Petronio AS. Italian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France, Abstract presentation.

Petronio AS, Giannini C, Misuraca L. Current state of symptomatic aortic valve stenosis in the elderly patient. Circ J. 2011 Sep 22;75(10):2324-5.

R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2001. ISBN 3-900051-07-0, URL http://www.R-project.org.

Spaccarotella C, Mongiardo A, Indolfi C. Pathophysiology of aortic stenosis and approach to treatment with percutaneous valve implantation. Circ J. 2010 Dec 24;75(1):11-19.

Tamburino C, Capodanno D, Ramondo A, Petronio AS, Ettori F, Santoro G, Klugmann S, Bedogni F, Maisano F, Marzocchi A, Poli A, Antoniucci D, Napodano M, De Carlo M, Fiorina C, Ussia GP. Incidence and predictors of early and late mortality after transcatheter aortic valve implantation in 663 patients with severe aortic stenosis. Circulation. 2011 Jan 25;123(3):299-308. Epub 2011 Jan 10.

- Trinquart L, Touze E. Pitfalls in meta-analysis of observational studies: lessons from a systematic review of the risks of stenting for intracranial atherosclerosis. Stroke 2009;40:e586-7.

- Zahn R, Gerckens U, Grube E, Linke A, Sievert H, Eggebrecht H, Hambrecht R, Sack S, Hauptmann KE, Richardt G, Figulla HR, Senges J; German Transcatheter Aortic Valve Interventions-Registry Investigators. Transcatheter aortic valve implantation: first results from a multi-centre real-world registry. Eur Heart J. 2011 Jan;32(2):198-204. Epub 2010 Sep 23.

Figure 1.Transcatheter aortic valve implantation: rates of all-cause mortality at
30 days from 7 registries and meta-analysis of proportions based on these rates. Each horizontal line indicates the
95%CI for the event rate.

Competing interests:
None declared

Competing interests: None declared