Life after Trabscatheter Aortic Valve Implantation: a clinical and echocardiographic appraisal

2012 Copyright of the published articles is with the corresponding journal or otherwise with the author. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without the permission of the author or the corresponding journal. Alexandra Maria Gomes da Silva Gonçalves Life after Transcatheter Aortic Valve Implantation: a Clinical and Echocardiographic Appraisal Dissertação de candidatura ao grau de Doutor Europeu apresentada à Faculdade de Medicina da Universidade do Porto Porto 2012 Art.º 48º, § 3º - “A Faculdade não responde pelas doutrinas expendidas na dissertação.” (Regulamento da Faculdade de Medicina da Universidade do Porto – Decreto Lei nº 19337 de 29 de Janeiro de 1931) Corpo Catedrático da Faculdade de Medicina do Porto PROFESSORES CATEDRÁTICOS EFECTIVOS Doutor Manuel Alberto Coimbra Sobrinho Simões Doutor Jorge Manuel Mergulhão Castro Tavares Doutora Maria Amélia Duarte Ferreira Doutor José Agostinho Marques Lopes Doutor Patrício Manuel Vieira Araújo Soares Silva Doutor Daniel Filipe Lima Moura Doutor Alberto Manuel Barros da Silva Doutor José Manuel Lopes Teixeira Amarante Doutor José Henrique Dias Pinto de Barros Doutora Maria Fátima Machado Henriques Carneiro Doutora Isabel Maria Amorim Pereira Ramos Doutora Deolinda Maria Valente Alves Lima Teixeira Doutora Maria Dulce Cordeiro Madeira Doutor Altamiro Manuel Rodrigues Costa Pereira Doutor Rui Manuel Almeida Mota Cardoso Doutor António Carlos Freitas Ribeiro Saraiva Doutor José Carlos Neves da Cunha Areias Doutor Manuel Jesus Falcão Pestana Vasconcelos Doutor João Francisco Montenegro Andrade Lima Bernardes Doutora Maria Leonor Martins Soares David Doutor Rui Manuel Lopes Nunes Doutor José Eduardo Torres Eckenroth Guimarães Doutor Francisco Fernando Rocha Gonçalves Doutor José Manuel Pereira Dias de Castro Lopes Doutor António Albino Coelho Marques Abrantes Teixeira Doutor Joaquim Adelino Correia Ferreira Leite Moreira PROFESSORES JUBILADOS OU APOSENTADOS Doutor Abel Costa Sampaio da Costa Tavares Doutor Abel Vitorino Trigo Cabral Doutor Alexandre Alberto Guerra Sousa Pinto Doutor Amandio Gomes Sampaio Tavares Doutor António Augusto Lopes Vaz Doutor António Carvalho Almeida Coimbra Doutor António Fernandes da Fonseca Doutor António Fernandes Oliveira Barbosa Ribeiro Braga Doutor António Germano Pina Silva Leal Doutor António José Pacheco Palha Doutor António Luis Tomé da Rocha Ribeiro Doutor António Manuel Sampaio de Araujo Teixeira Doutor Belmiro dos Santos Patricio Doutor Candido Alves Hipólito Reis Doutor Carlos Rodrigo Magalhães Ramalhão Doutor Cassiano Pena de Abreu e Lima Doutor Daniel Santos Pinto Serrão Doutor Eduardo Jorge Cunha Rodrigues Pereira Doutor Fernando de Carvalho Cerqueira Magro Ferreira Doutor Fernando Tavarela Veloso Doutor Francisco de Sousa Lé Doutor Henrique José Ferreira Gonçalves Lecour de Menezes Doutor José Augusto Fleming Torrinha Doutor José Carvalho de Oliveira Doutor José Fernando Barros Castro Correia Doutor José Luis Medina Vieira Doutor José Manuel Costa Mesquita Guimarães Doutor Levi Eugenio Ribeiro Guerra Doutor Luis Alberto Martins Gomes de Almeida Doutor Manuel Augusto Cardoso de Oliveira Doutor Manuel Machado Rodrigues Gomes Doutor Manuel Maria Paula Barbosa Doutor Maria da Conceição Fernandes Marques Magalhães Doutor Maria Isabel Amorim de Azevedo Doutor Mário José Cerqueira Gomes Braga Doutor Serafim Correia Pinto Guimarães Doutor Valdemar Miguel Botelho dos Santos Cardoso Doutor Walter Friedrich Alfred Osswald Doutor Alvaro Jerónimo Leal Machado de Aguiar Doutor Manuel António Caldeira Pais Clemente Ao abrigo do Decreto–Lei nº 388/70 fazem parte desta dissertação as seguintes publicações: I. Gonçalves A, Zamorano J. Chapter 10 - Imaging for TAVI. Valvular Medicine Textbook 2011, Springer US; in press II. Goncalves A, Marcos-Alberca P, Zamorano JL. Echocardiography: guidance during valve implantation. EuroIntervention 2010;6 Suppl G:G14-9. III. Goncalves A, Marcos-Alberca P, Almeria C, Feltes G, Rodriguez E, Hernandez-Antolin RA, Garcia E, Maroto L, Fernandez Perez C, Silva Cardoso JC, Macaya C, Zamorano JL. Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation. Eur J Echocardiogr 2011;12:790-7. IV. Goncalves A, Almeria C, Marcos-Alberca P, Feltes G, Hernandez-Antolin R, Rodriguez E, Silva Cardoso JC, Macaya C, Zamorano JL. Three-Dimensional Echocardiography in Paravalvular Aortic Regurgitation Assessment after Transcatheter Aortic Valve Implantation. J Am Soc Echocardiogr 2012;25:47-55. V. Goncalves A, Marcos-Alberca P, Almeria C, Feltes G, Hernandez-Antolin RA, Rodriguez E, Rodrigo JL, Cobiella J, Maroto L, Silva Cardoso JC, Macaya C, Zamorano JL. Quality of life improvement at midterm follow-up after transcatheter aortic valve implantation. Int J Cardiol 2011. [Epub ahead of print] In attachment: Zamorano JL, Badano LP, Bruce C, Chan KL, Goncalves A, Hahn RT, Keane MG, La Canna G, Monaghan MJ, Nihoyannopoulos P, Silvestry FE, Vanoverschelde JL, Gillam LD. EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. Eur Heart J 2011;32:2189-214; J Am Soc Echocardiogr 2011;24:937-65; Eur J Echocardiogr 2011;12:557-84. This research was performed in the Cardiovascular Institute, University Clinic San Carlos, Madrid, under supervision of Professor José Luis Zamorano and co-supervision of Professor José Carlos Silva Cardoso. Funding by the research grant of the European Association of Echocardiography 2010 Part I – Introduction 3 INTRODUCTION Aortic stenosis (AS) is the most frequent native valve disease of the elderly in western industrialized countries.1 Once symptomatic it is responsible for serious disability, restrictions in the normal daily living and reduced life expectancy. 2 Until recently, the only effective treatment was surgical aortic valve replacement.3-4 However, surgery is associated with higher morbidity and mortality rates in the elderly compared with younger patients.5 It is estimated that about 31% of patients with severe AS, older than 75 years are not referred to surgery, or are refused by the cardiac surgeon because of co-morbidities and perceived high surgical risk.6 Transcatheter aortic valve implantation (TAVI) techniques have emerged as an alternative treatment for this group of patients. 7-9 After the first human TAVI procedure, performed by Alain Cribier in April 2002 10 the number of patients has increased exponentially and more than 40 000 patients had undergone TAVI worldwide. 11 Good procedural success and favourable clinical outcomes at short and midterm follow-up have been reported. 12-15 Nevertheless, TAVI is a demanding procedure that requires a multidisciplinary team approach and still faces important safety issues, such as paravalvular leaks, vascular complications, stroke or conduction disorders. An additional challenge is the lack of operator direct visualization. Consequently, this technique greatly depends on imaging, especially on echocardiography, which plays an essential role in identifying patients suitable for the intervention, in providing intra-procedural monitoring and as primary modality for post-procedure follow-up.16 During peri-procedural guidance 2D and 3D transesophageal echocardiography (TEE) can contribute for balloon and prosthesis positioning, to confirm prosthesis normal functioning and to rapidly detect complications.17 Moreover, TEE guidance represents a unique opportunity to firstly assess left ventricle physiology and behavior following afterload release. Most patients referred for TAVI are elderly and present symptomatic AS with heart failure in NYHA class III-IV, in spite of preserved left ventricle (LV) systolic function.18-19 Immediate almost complete afterload normalization and significant clinical improvement at short-term follow-up have been reported.19-21 At medium-term, LV mass reduction and improvement in tissue Doppler velocities have also been described.22 In view of that we performed the first study evaluating the acute hemodynamic effects of TAVI in diastolic performance, immediately after aortic valvuloplasty and prosthesis deployment.23 Aortic regurgitation is the most common complication after TAVI. 14,8 It may occur as a consequence of incomplete expansion, incorrect positioning, restricted cusp motion, or inappropriate prosthetic size.24 As a Life after TAVI: a Clinical and Echocardiographic Appraisal 4 result, in spite of low incidence of prosthesis-patient mismatch, 20 some degree of residual aortic regurgitation (AR) is common, mainly at the paravalvular location. 12, 25 The degree of AR appears to be minor in most patients, however in some it may be responsible for left ventricular remodelling and moderate/severe AR was shown to be a strong predictor of increased mortality and poor treatment response at midterm followup.26-27 Therefore, accurate evaluation and detailed description of AR are essential for proper identification of patients at risk and for appropriate follow-up, but up to now this remained challenging, as no systematic methodology had been proposed. Bearing these concerns in mind, we developed a new method for accurate description of paravalvular AR, based on three-dimensional (3D) transthoracic echocardiography evaluation, suitable for accurate identification of moderate AR and proper 3D echocardiographic follow-up. 28 Patients referred for TAVI are elderly and their expectations for the treatment are beyond procedural success and favourable clinical outcomes. 19, 29 Quality of life improvement is also a major concern for this elderly patient’s profile.7 Clinical benefit and neurohormonal activation reduction has been reported at short term after TAVI, 30 but the midterm results of quality of life were scarce and the reports conflicting.31-32 Further than mortality and hemodynamic valve performance, quality of life assessment is crucial for the evaluation of procedure efficiency and to guide clinical decision-making. Therefore, we looked into changes in the quality of life of patients undergoing TAVI at a midterm follow-up. Finally, considering the new demands placed by TAVI, a partnership between the European Association of Echocardiography and the American Society of Echocardiography, developed the recommendations for the use of echocardiography in new transcatheter interventions, providing an actual reference for echocardiographers participating in new transcatheter treatments for patients with valvular heart disease.16 Setting This study included consecutive patients referred for TAVI at Hospital Clinico San Carlos, Madrid, from April 2009 to April 2010. All patients had severe aortic valve stenosis (aortic valve area ≤1 cm2) and were ineligible for conventional aortic valve replacement, due to an excessive surgical risk, estimated by the logistic EuroSCORE and/or clinical judgment of specific co-morbidities, such as porcelain aorta, severely reduced lung capacity or frailty.7 Part 1 – Introduction 5 References 1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: A population-based study. Lancet. 2006;368:1005-1011 2. Bouma BJ, van Den Brink RB, van Der Meulen JH, Verheul HA, Cheriex EC, Hamer HP, Dekker E, Lie KI, Tijssen JG. To operate or not on elderly patients with aortic stenosis: The decision and its consequences. Heart. 1999;82:143-148 3. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A. Guidelines on the management of valvular heart disease: The task force on the management of valvular heart disease of the european society of cardiology. Eur Heart J. 2007;28:230-268 4. Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Jr., Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC, Jr., Jacobs AK, Adams CD, Anderson JL, Antman EM, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Nishimura R, Page RL, Riegel B. Acc/aha 2006 guidelines 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 (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the society of cardiovascular anesthesiologists endorsed by the society for cardiovascular angiography and interventions and the society of thoracic surgeons. J Am Coll Cardiol. 2006;48:e1-148 5. Alexander KP, Anstrom KJ, Muhlbaier LH, Grosswald RD, Smith PK, Jones RH, Peterson ED. Outcomes of cardiac surgery in patients > or = 80 years: Results from the national cardiovascular network. J Am Coll Cardiol. 2000;35:731-738 6. Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Barwolf C, Levang OW, Tornos P, Vanoverschelde JL, Vermeer F, Boersma E, Ravaud P, Vahanian A. A prospective survey of patients with valvular heart disease in europe: The euro heart survey on valvular heart disease. Eur Heart J. 2003;24:1231-1243 7. Vahanian A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr F, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Von Segesser LK, Walther T. Transcatheter valve implantation for patients with aortic stenosis: A position statement from the european association of cardio-thoracic surgery (eacts) and the european society of cardiology (esc), in collaboration with the european association of percutaneous cardiovascular interventions (eapci). Eur Heart J. 2008;29:1463-1470 8. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187-2198 9. 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. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-1607 10. Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, Leon MB. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: First human case description. Circulation. 2002;106:3006-3008 11. Rodes-Cabau J. Transcatheter aortic valve implantation: Current and future approaches. Nat Rev Cardiol. 2011;9:15-29 12. Grube E, Schuler G, Buellesfeld L, Gerckens U, Linke A, Wenaweser P, Sauren B, Mohr F-W, Walther T, Zickmann B, Iversen S, Felderhoff T, Cartier R, Bonan R. Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the secondand current third-generation self-expanding corevalve prosthesis: Device success and 30-day clinical outcome. Journal of the American College of Cardiology. 2007;50:69-76 Life after TAVI: a Clinical and Echocardiographic Appraisal 6 13. Thomas M, Schymik G, Walther T, Himbert D, Lefevre T, Treede H, Eggebrecht H, Rubino P, Michev I, Lange R, Anderson WN, Wendler O. Thirty-day results of the sapien aortic bioprosthesis european outcome (source) registry: A european registry of transcatheter aortic valve implantation using the edwards sapien valve. Circulation. 2010;122:62-69 14. Rodes-Cabau J, Webb JG, Cheung A, Ye J, Dumont E, Feindel CM, Osten M, Natarajan MK, Velianou JL, Martucci G, DeVarennes B, Chisholm R, Peterson MD, Lichtenstein SV, Nietlispach F, Doyle D, DeLarochelliere R, Teoh K, Chu V, Dancea A, Lachapelle K, Cheema A, Latter D, Horlick E. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: Acute and late outcomes of the multicenter canadian experience. J Am Coll Cardiol. 2010;55:1080-1090 15. Bleiziffer S, Mazzitelli D, Opitz A, Hettich I, Ruge H, Piazza N, Lange R. Beyond the short-term: Clinical outcome and valve performance 2 years after transcatheter aortic valve implantation in 227 patients. J Thorac Cardiovasc Surg. 2011 16. Zamorano JL, Badano LP, Bruce C, Chan KL, Goncalves A, Hahn RT, Keane MG, La Canna G, Monaghan MJ, Nihoyannopoulos P, Silvestry FE, Vanoverschelde JL, Gillam LD. Eae/ase recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. Eur Heart J. 2011;32:2189-2214 17. Goncalves A, Marcos-Alberca P, Zamorano JL. Echocardiography: Guidance during valve implantation. EuroIntervention. 2010;6 Suppl G:G14-19 18. Zajarias A, Cribier AG. Outcomes and safety of percutaneous aortic valve replacement. J Am Coll Cardiol. 2009;53:1829-1836 19. Grube E, Schuler G, Buellesfeld L, Gerckens U, Linke A, Wenaweser P, Sauren B, Mohr FW, Walther T, Zickmann B, Iversen S, Felderhoff T, Cartier R, Bonan R. Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the secondand current third-generation self-expanding corevalve prosthesis: Device success and 30-day clinical outcome. J Am Coll Cardiol. 2007;50:69-76 20. Clavel MA, Webb JG, Pibarot P, Altwegg L, Dumont E, Thompson C, De Larochelliere R, Doyle D, Masson JB, Bergeron S, Bertrand OF, Rodes-Cabau J. Comparison of the hemodynamic performance of percutaneous and surgical bioprostheses for the treatment of severe aortic stenosis. J Am Coll Cardiol. 2009;53:1883-1891 21. Grube E, Buellesfeld L, Mueller R, Sauren B, Zickmann B, Nair D, Beucher H, Felderhoff T, Iversen S, Gerckens U. Progress and current status of percutaneous aortic valve replacement: Results of three device generations of the corevalve revalving system. Circ Cardiovasc Interv. 2008;1:167-175 22. Gotzmann M, Lindstaedt M, Bojara W, Mugge A, Germing A. Hemodynamic results and changes in myocardial function after transcatheter aortic valve implantation. Am Heart J. 2010;159:926-932 23. Goncalves A, Marcos-Alberca P, Almeria C, Feltes G, Rodriguez E, Hernandez-Antolin RA, Garcia E, Maroto L, Fernandez Perez C, Silva Cardoso JC, Macaya C, Zamorano JL. Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation. Eur J Echocardiogr. 2011;12:790-797 24. Détaint D, Lepage L, Himbert D, Brochet E, Messika-Zeitoun D, Iung B, Vahanian A. Determinants of significant paravalvular regurgitation after transcatheter aortic valve implantation: Impact of device and annulus discongruence. JACC: Cardiovascular Interventions. 2009;2:821-827 25. Rodes-Cabau J, Dumont E, De LaRochelliere R, Doyle D, Lemieux J, Bergeron S, Clavel MA, Villeneuve J, Raby K, Bertrand OF, Pibarot P. Feasibility and initial results of percutaneous aortic valve implantation including selection of the transfemoral or transapical approach in patients with severe aortic stenosis. Am J Cardiol. 2008;102:1240-1246 26. Moat NE, Ludman P, de Belder MA, Bridgewater B, Cunningham AD, Young CP, Thomas M, Kovac J, Spyt T, MacCarthy PA, Wendler O, Hildick-Smith D, Davies SW, Trivedi U, Blackman DJ, Levy RD, Brecker SJ, Baumbach A, Daniel T, Gray H, Mullen MJ. Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: The u.K. Tavi (united kingdom transcatheter aortic valve implantation) registry. J Am Coll Cardiol. 2011;58:2130-2138 Part 1 – Introduction 7 27. Gotzmann M, Pljakic A, Bojara W, Lindstaedt M, Ewers A, Germing A, Mugge A. Transcatheter aortic valve implantation in patients with severe symptomatic aortic valve stenosis-predictors of mortality and poor treatment response. Am Heart J. 2011;162:238-245 e231 28. Goncalves A, Almeria C, Marcos-Alberca P, Feltes G, Hernandez-Antolin R, Rodriguez E, Silva Cardoso JC, Macaya C, Zamorano JL. Three-dimensional echocardiography in paravalvular aortic regurgitation assessment after transcatheter aortic valve implantation. J Am Soc Echocardiogr. 2011 29. Piazza N, Grube E, Gerckens U, den Heijer P, Linke A, Luha O, Ramondo A, Ussia G, Wenaweser P, Windecker S, Laborde JC, de Jaegere P, Serruys PW. Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 fr) corevalve revalving system: Results from the multicentre, expanded evaluation registry 1-year following ce mark approval. EuroIntervention. 2008;4:242-249 30. Gotzmann M, Hehen T, Germing A, Lindstaedt M, Yazar A, Laczkovics A, Mumme A, Mugge A, Bojara W. Short-term effects of transcatheter aortic valve implantation on neurohormonal activation, quality of life and 6-minute walk test in severe and symptomatic aortic stenosis. Heart. 2010;96:1102-1106 31. Krane M, Deutsch MA, Bleiziffer S, Schneider L, Ruge H, Mazzitelli D, Schreiber C, Brockmann G, Voss B, Bauernschmitt R, Lange R. Quality of life among patients undergoing transcatheter aortic valve implantation. Am Heart J. 2010;160:451-457 32. Bekeredjian R, Krumsdorf U, Chorianopoulos E, Kallenbach K, Karck M, Katus HA, Rottbauer W. Usefulness of percutaneous aortic valve implantation to improve quality of life in patients >80 years of age. Am J Cardiol. 2010;106:1777-1781 PART II Aims Part II – Aims 11 AIMS This research sought to improve the understanding of transcatheter aortic valve implantation (TAVI), focusing on the importance of the information provided by echocardiography. Additionally the effects of TAVI on quality of life were explored. The aims were: 1. To describe the role of imaging in TAVI, from patient‘s selection to follow-up; 2. To describe the role of echocardiography during TAVI, in terms of procedure guidance and assessment of complications; 3. To determine the acute hemodynamic effects of TAVI in left ventricle diastolic performance, immediately after aortic valvuloplasty and prosthesis deployment; 4. To illustrate an accurate methodology for paravalvular aortic regurgitation evaluation by echocardiography; 5. To evaluate quality of life results at midterm follow-up after TAVI; 6. To contribute for the elaboration of the recommendations for echocardiographers participating in any or all stages of TAVI. Chapter 1 – Imaging for TAVI 19 valves should be evaluated and described. TTE is the first assessment of the aortic annular dimension and anatomic characteristics of the aortic valve. It can be used to describe the number of cusps, mobility, thickness and calcification. The presence of a bicuspid aortic valve is still a contra-indication for TAVI because of the risk of spontaneous aortic dissection or incorrect deployment of the aortic prosthesis due to the elliptical valvular orifice. However, successful TAVI in bicuspid AS has already been reported. 9 As presented in Table 1 the aortic annulus dimension dictates the eligibility for TAVI and prosthesis size, which is determinant to the procedural success. Using TTE the aortic annular dimension is measured in systole, in a parasternal long-axis view, zoomed on the LVOT, at the point of insertion of the aortic valve cusps, from tissue–blood interface to blood–tissue interface—trailing edge to leading edge (Figure 10.2).10 2D Transesophageal echocardiography (TEE) and even 3D TEE evaluation may be necessary when TTE measurements of the annulus are doubtful, particularly if they are near critical cut-offs for valve selection, or if the calcification extends from the aortic valve onto the anterior mitral leaflet or the septum. Figure 10.2 Transthoracic echocardiography parasternal long-axis view for measurement of aortic annular dimension. TRANSESOPHAGEAL ECHOCARDIOGRAPHY TEE is recommended prior to TAVI to a better evaluation of the aortic root anatomy, particularly if there are any concerns about the assessment of the aortic annular size and the number of cusps. The annular diameter at the level of the basal attachment of the aortic valve cusps, measured in systole determines the size of the prosthesis, irrespective of the type of the valve inserted (Table 1). There is a good correlation between TEE aortic annular measurements and TTE results; however TTE to some extent underestimates aortic annular size.11 20 Life after TAVI: a Clinical and Echocardiographic Appraisal When measuring the annular diameter with 2D TEE, there is an assumption of annular circularity, which may result in erroneous measurements in patients whose annuli are more oval shaped. This limitation can be overcome using multiplanar tools of 3D TEE (Figure 10.3)10 or multidetector computed tomography (MDCT). The later will be described in detail underneath in MDCT proper section. The final decision for the appropriate valve size mainly considers the annulus diameter, but in cases of borderline size decisions, the existence of large calcification in the native valve, may require a smaller prosthesis than the annular dimension alone would advise. Up to now there is no gold standard imaging technique for annular sizing for TAVI, but from the practical point of view, TTE complemented with TEE accomplishes good results in most patients. Using short-axis views of the aortic valve the number of cusps can be precisely illustrated and its opening classified as central or eccentric. It is relevant to describe the severity and eventual asymmetry of calcification, as the differences in the tension–force across the valve may cause asymmetric deployment of the prosthesis and increase the risk of compression of the coronary arteries. However TEE presents constrains at the time of calcification evaluation, being MDCT the best method available. 12 The distance from the aortic annulus to the ostia of the coronary arteries should be measured, because patients with cusps length larger than annular-ostial distances are at risk of ostial coronary occlusion at time of valve deployment, as the native cusps will be crushed to the side. Only the right coronary annular-ostial distance Figure 10.3 3D Transesophageal echocardiography assessing shape and measurements of the aortic annulus. Chapter 1 – Imaging for TAVI 21 is possible to measure with 2D TEE, as the left coronary annular-ostial distance requires 3D TEE or MDCT. Using TEE the characteristics of the ascending aorta, the aortic arch, and the descending thoracic aorta should be considered as the presence of large atheromas may increase the risk of peri-procedural embolization at the time of transfemoral approach. MULTIDETECTOR COMPUTED TOMOGRAPHY (MDCT) MDCT has a complementary role to echocardiography and angiography at the time of evaluation of patients before TAVI.13 It provides detailed anatomic visualization of the aortic root, thoraco-abdominal aorta and the iliofemoral access. Nevertheless, MDCT imaging is associated with the administration of iodinated contrast and exposure to ionizing radiation exposure, thus its use should be considered for individual patients based on risk and benefit. Three-dimensional (3D) derived MDCT measurements provide precise dimensions for best prosthesis selection and sizing. Anatomically, the annulus is a crown-shaped 3-dimensional structure rather than a circular plane. However, 2D echocardiography and aortic angiography give the extent of a single diameter, making the assumption of annular orifice circularity. In contrast, 3D MDCT reconstruction of the annulus, orthogonal Figure 10.4 Multidetector computed tomography assessing aortic valve calcification (B) and reconstruction of the aortic root (A, C and D) measuring minimal and maximal diameters, circumference and area at the level of aortic annulus (A). AoAorta. Courtesy of Dr. Pedro Marcos-Alberca 22 Life after TAVI: a Clinical and Echocardiographic Appraisal to the center-axis of the LVOT, allows the assessment of minimal and maximal diameters, circumference and area measurements (Figure 10.4). Although the use of 3D MDCT measurements for best prosthesis sizing may reduce the probability of error and present a more comprehensive definition of the annular size and shape, the mean of the maximum and minimum diameter measurements is comparable to 2D TEE measurement, remaining 2D TEE the most used technique. 11 Moreover, the aortic valve can be assessed in detail, and its morphology precisely described, regarding the number of cusps and the aortic valve area, measured by planimetry. Moreover, in comparison with echocardiography, MDCT has the ability to provide precise description of localization and extent of aortic cusps calcification. Relationships between aortic valve calcification and pos TAVI paravalvular aortic regurgitation have been described, being paravalvular aortic regurgitation associated with a larger aortic annulus and with more severe aortic root calcification.12 Furthermore, dense aortic leaflet calcification measured on contrast MDCT discerned the need for an additional balloon post-dilatation, when using CoreValve TM, for significant paravalvular regurgitation reduction.14 Figure 10.5 Multidetector computed tomography measuring the distance between annulus and coronary ostia. Courtesy of Dr. Pedro Marcos-Alberca At the time of pre-procedural evaluation, MDCT includes a complete assessment of coronary anatomy with conventional coronary angiography, which generally is limited by the advanced calcified disease. However, the relationship between leaflet height and distance between annulus and coronary ostia, can be accurately measured, identifying patients at higher risk for coronary occlusion during the procedure, when the annuluscoronary ostia distance is <11 mm (Figure 10.5). The thoracic aorta evaluation is completed by the measurement of the aortic sinus diameter, sinotubular Chapter 1 – Imaging for TAVI 23 junction and ascending and descending aorta, using centerline reconstructions. The occurrence of significant aneurismal dilatation is considered a contraindication for the use of CoreValve (Table 1). Precise coaxial alignment of the prosthesis along the centerline of the aortic valve and aortic root is important during positioning to decrease the likelihood of complications as prosthesis embolization. MDCT offers the assessment of the aortic root in relation to the body axis and its pre-procedural angle prediction may decrease the number of aortograms required during the procedure, therefore shortening procedure time and contrast usage.15 Finally, MDCT allows the assessment of peripheral vasculature, considering caliber, tortuosity and calcification, being the minimum caliber of the common femoral artery dependent on the size of the prosthesis valve chosen. Using the previous Edward Sapien TM valve it was necessary a common femoral artery with a minimum of 8 mm of diameter, currently a minimum of 6 mm is required for both Edwards-XT TM and CoreValve TM. Tortuosity and calcification are not prohibitive factors, but its combination is an adverse feature for site complications and central embolization. In addition the location of the bifurcation of the femoral artery and the degree of calcification have to be considered the time of deciding the feasibility of the transfemoral access or for choosing the alternative of subclavian or transapical approach. ANGIOGRAPHY Previously to the procedure, aortography produces images of the coronary arteries, thoracic and abdominal aorta. It allows the measurement of vessel diameters, tortuosity and excludes the presence of aorta aneurism. Nevertheless, at time of measuring vessels calcification, angiography presents limitations, being MDCT the best method. Fluoroscopy is used for measurement of aortic annulus, at the time of definitive prosthesis sizing decision and to guide the procedure. The alignment of the three aortic sinuses in the same plane defines the optimal plane and angiography projection for TAVI. Peri-procedural echocardiography during transcatheter aortic valve implantation Peri-procedural 2D and 3D TEE can contribute for balloon and prosthesis positioning, to confirm prosthesis function immediately after implantation and to rapidly detect complications. As in other intervention TEE guided procedures, the use of 3D, by its larger spacial resolution, presents advantages over 2D. It allows a better visualization of the guide wire path through the LV and around the mitral valve and subvalvular apparatus and permits a better evaluation of the prosthesis position on the balloon, relative to the native valve annulus and surrounding structures (Figure 10.6). At the time of valvuloplasty, TEE guidance is especially useful when the valve is not very calcified, as those valves are difficult to image on fluoroscopy and easy observed by TEE. The balloon inflation is performed during rapid right ventricular pacing, though the balloon may accidentally migrate during inflation. TEE can be used to confirm a secure position during inflation and to monitor the behavior of the balloon and its effect on the calcified aortic cusps during inflation. During deployment of the prosthesis, 2D and 3D TEE confirm 24 Life after TAVI: a Clinical and Echocardiographic Appraisal the correct position of the valve and it is usually used in conjunction with fluoroscopy. The optimal position for the Edwards SAPIEN TM valve is with the ventricular side of the prosthesis positioned 2–4 mm below the annulus and for the CoreValve TM, the ventricular edge of the prosthesis should be placed 5–10 mm below the aortic valve annular plane. After the deployment it is important to confirm that all the prosthetic cusps are moving well, that the valve stent has a circular configuration and to exclude significant valvular or paravalvular aortic regurgitation. Mild aortic regurgitation through the prosthesis, until the guidewire is removed and at the next few minutes after deployment is common. Small jets of paravalvular aortic regurgitation are frequent and it may occur even in a successful procedure, however severe aortic regurgitation is a serious complication and additional balloon inflation may be required. Figure 10.6 3D Transesophageal echocardiography showing the catheter and the balloon through the native aortic valve. AoAorta; LVleft ventricle. ASSESSMENT OF COMPLICATIONS Among the various complications assessable by TEE, aortic regurgitation is the most common (Figure 10.7).2,4 It may occur as a consequence of incomplete expansion, incorrect positioning, restricted cusp motion, or inappropriate prosthetic size.16 An undersized prosthesis may result in paravalvular aortic regurgitation. On the opposite, an oversized prosthesis has the risk of suboptimal stent expansion and central aortic regurgitation. Other mechanisms eventually responsible for aortic regurgitation are the presence of severe asymmetric calcification, causing paravalvular aortic leaks, or it may happen as a consequence of residual native aortic valve leaflet tissue prolapsing into the prosthesis, interfering with cusp motion and coaptation. The aortic regurgitation severity should be evaluated by the International recommended criteria.10 Furthermore, in result of prosthesis mismatch, or failed pacing capture, prosthetic embolism may occur. If the embolization happens towards the aorta, it might be resolved through successful transcatheter repositioning, but if it happens towards the LV, surgical removal is usually the only option.17 Chapter 1 – Imaging for TAVI 25 Figure 10.7 2D transesophageal echocardiography showing aortic prosthesis central regurgitation. Other possible complications detectable by TEE are cardiac tamponade, secondary to wire perforation of the left or right ventricle and anew LV dysfunction, which may be secondary to ostial occlusion by fragment embolization or by an obstructive portion of the valve frame, sealing cuff or by native cusp.18 Moreover, sudden worsening of MR may occur due to right ventricular pacing, causing LV asynchrony, or as a consequence of prosthetic misplacement, towards the left ventricle outflow tract, with pressure exerted on the anterior mitral leaflet or by direct damage or distortion of the subvalvular apparatus. 19 A tear or ruptures of the aortic root have been also observed during the procedure after balloon valvuloplasty or prosthesis deployment, especially in the presence of extensive annular calcification or prosthesis oversizing.20 TEE is not mandatory during TAVI, as it usually requires general anesthesia and the probe may also partially obstruct the optimal fluoroscopic view, however it may be the main technique used for procedure guidance, particularly in patients with limited native valve calcification,10 providing the best guidance and rapid assessment of complications. Post-implantation follow-up The imaging follow-up evaluation of patients with transcatheter aortic valves is mainly based on TTE. It is usually performed at the time of hospital discharge, at one month follow-up and at 6 or 12 months, depending on each institution protocol. The echocardiographic evaluation is mostly similar to surgically implanted prostheses, as guided by previously published guidelines for prosthetic valves.21 Nevertheless, the accurate evaluation of aortic regurgitation severity is a main issue, as it may consist of central and paravalvular aortic regurgitation and the latter frequently includes multiple small jets. Colour flow qualitative evaluation is the method most commonly used for the assessment of the regurgitant jet size. The guidelines recommend using the following criteria for jet width based on the %LVOT diameter occupied: 26 Life after TAVI: a Clinical and Echocardiographic Appraisal ≤25% suggests mild, 26–64% suggests moderate, and >65% suggests severe. These methods are limited in the setting of paravalvular jets which are frequently eccentric and irregular in shape. The ASE/EAE guidelines advise that for paravalvular jets, the proportion of the circumference of the sewing ring occupied by the jet gives a semi-quantitative guide to severity: <10% of the sewing ring suggests mild, 10–20% suggests moderate, and >20% suggests severe 21. However, this concept assumes jet continuity, which may not be the case for transcatheter valves and therefore may overestimate the severity in presence of multiple small jets. For the quantitative approach the width of the vena contracta is a robust estimate of regurgitant severity, but in the setting of prostheses, portions of the sewing ring may not be imaged due to acoustic shadowing. In addition, there has been no validation for adding the vena contracta widths of multiple jets as it may be encountered post-TAVI. A new method using 3D TTE vena contracta planimetry has been recently described, showing an accurate alternative for quantitative evaluation and moderate AR recognition of paravalvular aortic regurgitation after TAVI.22 The quantitative methods for calculating regurgitant volume and effective regurgitant orifice area that rely on the comparison of stroke volumes across the aortic valve and a nonregurgitant valve may be also used for prosthetic valves evaluation.21 However, the final interpretation should follow the principle of comprehensive evaluation and integrated approach. At the time of effective orifice area calculation, it is essential that the pre-valvular velocity is recorded proximal to the stent and the post-valvular velocity (typically recorded with continuous-wave Doppler) distal to the stented valve. If the LVOT velocity used in calculations is erroneously recorded within the stent but proximal to the cusps, the result will be an overestimation of valve area.10 Similarly the LVOT diameter should be measured immediately proximal to the stent.23 In selected cases with suspicion of complications such as prosthesis malposition, MDCT by its higher spatial resolution is an appropriate technique, providing accurate information on the position and deployment of prosthesis. Conclusion Patient’s evaluation for TAVI might require the use of multi-imaging modalities. Using echocardiography, MDCT and angiography, an accurate evaluation of aortic stenosis severity, annulus sizing, aortic morphology and peripheral vascular anatomy can be performed. These steps are decisive for appropriate patient selection. During TAVI, TEE along with fluoroscopy may be used for guidance, to evaluate possible complications and the final result. At time of patients’ short and long-term follow-up, echocardiography represents the ideal technique for prosthesis hemodynamic characterization, being MDCT reserved for particularly complex conditions. Chapter 1 – Imaging for TAVI 27 References 1. Vahanian A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr F, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Von Segesser LK, Walther T. Transcatheter valve implantation for patients with aortic stenosis: A position statement from the european association of cardio-thoracic surgery (eacts) and the european society of cardiology (esc), in collaboration with the european association of percutaneous cardiovascular interventions (eapci). Eur Heart J. 2008;29:1463-1470 2. Rodes-Cabau J, Webb JG, Cheung A, Ye J, Dumont E, Feindel CM, Osten M, Natarajan MK, Velianou JL, Martucci G, DeVarennes B, Chisholm R, Peterson MD, Lichtenstein SV, Nietlispach F, Doyle D, DeLarochelliere R, Teoh K, Chu V, Dancea A, Lachapelle K, Cheema A, Latter D, Horlick E. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: Acute and late outcomes of the multicenter canadian experience. J Am Coll Cardiol. 2010;55:1080-1090 3. 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. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-1607 4. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187-2198 5. Lange R, Schreiber C, Gotz W, Hettich I, Will A, Libera P, Laborde JC, Bauernschmitt R. First successful transapical aortic valve implantation with the corevalve revalving system: A case report. Heart Surg Forum. 2007;10:E478-479 6. Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Jr., Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. 2008 focused update incorporated into the acc/aha 2006 guidelines 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 (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, and society of thoracic surgeons. J Am Coll Cardiol. 2008;52:e1-142 7. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A. Guidelines on the management of valvular heart disease: The task force on the management of valvular heart disease of the european society of cardiology. Eur Heart J. 2007;28:230-268 8. Piazza N, de Jaegere P, Schultz C, Becker AE, Serruys PW, Anderson RH. Anatomy of the aortic valvar complex and its implications for transcatheter implantation of the aortic valve. Circ Cardiovasc Interv. 2008;1:74-81 9. Delgado V, Tops LF, Schuijf JD, van der Kley F, van de Veire NR, Schalij MJ, Bax JJ. Successful deployment of a transcatheter aortic valve in bicuspid aortic stenosis: Role of imaging with multislice computed tomography. Circ Cardiovasc Imaging. 2009;2:e12-13 10. Zamorano JL, Badano LP, Bruce C, Chan KL, Goncalves A, Hahn RT, Keane MG, La Canna G, Monaghan MJ, Nihoyannopoulos P, Silvestry FE, Vanoverschelde JL, Gillam LD. Eae/ase recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. Eur Heart J. 2011;32:2189-2214 11. Messika-Zeitoun D, Serfaty JM, Brochet E, Ducrocq G, Lepage L, Detaint D, Hyafil F, Himbert D, Pasi N, Laissy JP, Iung B, Vahanian A. Multimodal assessment of the aortic annulus diameter: Implications for transcatheter aortic valve implantation. J Am Coll Cardiol. 2010;55:186-194 28 Life after TAVI: a Clinical and Echocardiographic Appraisal 12. Schultz CJ, Tzikas A, Moelker A, Rossi A, Nuis RJ, Geleijnse MM, van Mieghem N, Krestin GP, de Feyter P, Serruys PW, de Jaegere PP. Correlates on msct of paravalvular aortic regurgitation after transcatheter aortic valve implantation using the medtronic corevalve prosthesis. Catheter Cardiovasc Interv. 2011;78:446-455 13. Schwartz JG, Neubauer AM, Fagan TE, Noordhoek NJ, Grass M, Carroll JD. Potential role of three-dimensional rotational angiography and c-arm ct for valvular repair and implantation. Int J Cardiovasc Imaging. 2011 14. Schultz C, Rossi A, van Mieghem N, van der Boon R, Papadopoulou SL, van Domburg R, Moelker A, Mollet N, Krestin G, van Geuns RJ, Nieman K, de Feyter P, Serruys PW, de Jaegere P. Aortic annulus dimensions and leaflet calcification from contrast msct predict the need for balloon post-dilatation after tavi with the medtronic corevalve prosthesis. EuroIntervention. 2011;7:564572 15. Gurvitch R, Wood DA, Leipsic J, Tay E, Johnson M, Ye J, Nietlispach F, Wijesinghe N, Cheung A, Webb JG. Multislice computed tomography for prediction of optimal angiographic deployment projections during transcatheter aortic valve implantation. JACC Cardiovasc Interv. 2010;3:1157-1165 16. Détaint D, Lepage L, Himbert D, Brochet E, Messika-Zeitoun D, Iung B, Vahanian A. Determinants of significant paravalvular regurgitation after transcatheter aortic valve implantation: Impact of device and annulus discongruence. JACC: Cardiovascular Interventions. 2009;2:821-827 17. Tuzcu EM. Transcatheter aortic valve replacement malposition and embolization: Innovation brings solutions also new challenges. Catheter Cardiovasc Interv. 2008;72:579-580 18. Webb JG, Chandavimol M, Thompson CR, Ricci DR, Carere RG, Munt BI, Buller CE, Pasupati S, Lichtenstein S. Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation. 2006;113:842-850 19. Goncalves A, Marcos-Alberca P, Zamorano JL. Echocardiography: Guidance during valve implantation. EuroIntervention. 2010;6 Suppl G:G14-19 20. Masson JB, Kovac J, Schuler G, Ye J, Cheung A, Kapadia S, Tuzcu ME, Kodali S, Leon MB, Webb JG. Transcatheter aortic valve implantation: Review of the nature, management, and avoidance of procedural complications. JACC Cardiovasc Interv. 2009;2:811820 21. Zoghbi WA, Chambers JB, Dumesnil JG, Foster E, Gottdiener JS, Grayburn PA, Khandheria BK, Levine RA, Marx GR, Miller FA, Jr., Nakatani S, Quinones MA, Rakowski H, Rodriguez LL, Swaminathan M, Waggoner AD, Weissman NJ, Zabalgoitia M. Recommendations for evaluation of prosthetic valves with echocardiography and doppler ultrasound: A report from the american society of echocardiography’s guidelines and standards committee and the task force on prosthetic valves, developed in conjunction with the american college of cardiology cardiovascular imaging committee, cardiac imaging committee of the american heart association, the european association of echocardiography, a registered branch of the european society of cardiology, the japanese society of echocardiography and the canadian society of echocardiography, endorsed by the american college of cardiology foundation, american heart association, european association of echocardiography, a registered branch of the european society of cardiology, the japanese society of echocardiography, and canadian society of echocardiography. J Am Soc Echocardiogr. 2009;22:975-1014; quiz 1082-1014 22. Goncalves A, Almeria C, Marcos-Alberca P, Feltes G, Hernandez-Antolin R, Rodriguez E, Silva Cardoso JC, Macaya C, Zamorano JL. Three-dimensional echocardiography in paravalvular aortic regurgitation assessment after transcatheter aortic valve implantation. J Am Soc Echocardiogr. 2011 23. Clavel MA, Rodes-Cabau J, Dumont E, Bagur R, Bergeron S, De Larochelliere R, Doyle D, Larose E, Dumesnil JG, Pibarot P. Validation and characterization of transcatheter aortic valve effective orifice area measured by doppler echocardiography. JACC Cardiovasc Imaging. 2011;4:1053-1062 Chapter 2 – Echocardiography: guidance during valve implantation 35 - G5 - Conventional criteria should be used to assess severity using colour Doppler to view the height and width of the regurgitant jet, but 3D TEE is also useful to evaluate the early functioning of the bioprosthesis, and classify the severity of perivalvular or central regurgitation (Video 7). In case of moderate severity, repeat dilation can be performed. However, primary valve dilatation and risk factors such as the amount of calcification, as a surrogate of risk of aortic rupture, have to be considered before proceeding to repeat dilatation. Furthermore, over dilatation of the stent is not recommended since, it might worsen central aortic insufficiency and potential leakage of the aortic wall. Concerning small paravalvular aortic regurgitation jets, their clinical significance is probably benign and not progressive in the majority of patients. 18 In the context of acute and severe hypotension, cardiac effusion or cardiac tamponade secondary to wire perforations might be found, as well as left ventricular dysfunction and wall motion abnormalities secondary to an obstructive portion of the valve frame or the sealing cuff being placed directly over a coronary ostium. Conduction abnormalities might also be detected by the echocardiographer, more commonly in prostheses extending farther into the ventricle. Worsening of mitral regurgitation can occur, due to right ventricular pacing or due to the direct mechanical effect of the ventricular edge of the prosthesis on the anterior leaflet of the valve. Using the antegrade apical approach, direct damage or distortion in subvalvular apparatus might occur, leading to acute mitral regurgitation. Therefore, a careful monitoring of the mitral valve during and after implantation is needed. Stroke is also a potential complication of this procedure, with rates ranging from 0% to 10%. 14 Even if potential causes of stroke, such as prolonged hypotension or air embolism from left ventricle apical cannulation cannot be assessed by echocardiography, other causes such as atheroembolism from the ascending aorta and aortic arch or aortic leaflet fragmented material embolisation, should be searched for and highlighted, in order to avoid this potentially lethal complication. 19 Tear or rupture of the aortic root has been reported, with a risk of 0.5%, secondary to excessive balloon dilation or prosthesis oversizing in context of extensive annular calcification (Figure 9). 20 If this complication occurs, the procedure has to be converted to a conventional surgical technique. Prosthetic embolism is the extreme complication that might occur in consequence of prosthesis mismatch. In case of valve embolisation towards the aorta, it might be resolved through successful transcatheter repositioning. However, if embolisation to the left ventricle occurs, surgical removal is usually the only option. 21,22 Finally, procedural failure can take place. It may be caused by inability to cross the native aortic valve with the guidewire or with the device after valvuloplasty by the inability to pass the device through the aortic arch, upstream migration of the device or extreme malpositioning. 10 Conclusion/future directions The number of patients referred to TAVI is rapidly increasing and innovative advances, such as subclavian access or transapical approach, are being presented today for those with no conventional transfemoral access. 23 Good communications between the operating team and precise guidance are crucial to procedure success and early detection of potential complications. In conclusion, 3D TEE monitoring should be used as a standard procedure during TAVI, in combination with 2D TEE. 3D TEE provides more accurate information to the interventional cardiologist during positioning, deployment as well as early functional evaluation of the prosthesis, and consequently makes the procedure safer. References 1. Vahanian A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr F, Nataf P, Piérard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Von Segesser LK, Walther T; European Association of Cardio-Thoracic Surgery; European Society of Cardiology; European Association of Percutaneous Cardiovascular Interventions.Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2008;29:1463-70. 2. Grube E, Buellesfeld L, Mueller R, Sauren B, Zickmann B, Nair D, Beucher H, Felderhoff T, Iversen S, Gerckens U. Progress and current status of percutaneous aortic valve replacement: results of three device generations of the CoreValve Revalving system. Circ Cardiovasc Interv. 2008;1:167-75. 3. Himbert D, Descoutures F, Al-Attar N, Iung B, Ducrocq G, Détaint D, Brochet E, Messika-Zeitoun D, Francis F, Ibrahim H, Nataf P, Vahanian A. Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis. J Am Coll Cardiol. 2009;54:303-11. 4. Rodés-Cabau J, Dumont E, De LaRochellière R, Doyle D, Lemieux J, Bergeron S, Clavel MA, Villeneuve J, Raby K, Bertrand OF, Pibarot P. Feasibility and initial results of percutaneous aortic valve implantation including selection of the transfemoral or transapical approach in patients with severe aortic stenosis. Am J Cardiol. 2008;102:1240-6. 5. Webb JG, Chandavimol M, Thompson CR, Ricci DR, Carere RG, Munt BI, Buller CE, Pasupati S, Lichtenstein S. Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation. 2006;113:842-850. 6. Grube E, Laborde JC, Gerckens U, Felderhoff T, Sauren B, Buellesfeld L, Mueller R, Menichelli M, Schmidt T, Zickmann B, Iversen S, Stone GW. Percutaneous implantation of the CoreValve self-expanding Part I – Guidance for transcatheter aortic and mitral valve implantation 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273. 274. 275. Figure 9. Two-dimensional transesophageal echocardiography long axis view showing aortic root rupture during TAVI. LV, left ventricle; AA, ascending aorta; LVOT, left ventricle outflow tract. Life after TAVI: a Clinical and Echocardiographic Appraisal 36 - G6 - Echocardiography: guidance during valve implantation valve prosthesis in highrisk patients with aortic valve disease: The Siegburg first-inman study. Circulation. 2006;114:1616-1624. 7. Ferrari E, Sulzer C, Rizzo E, von Segesser LK. A fully echo-guided trans-apical aortic valve implantation. Eur J Cardiothorac Surg. 2009;36:938-40. 8. Marcos-Alberca P, Zamorano JL, Sánchez T, Maroto L, Pérez de Isla L, Almería C, Macaya C, Rodríguez E. Intraoperative monitoring with transesophageal real-time three-dimensional echocardiography during transapical prosthetic aortic valve implantation. Rev Esp Cardiol. 2010;63:352-6. 9. Aregger F, Wenaweser P, Hellige GJ, Kadner A, Carrel T, Windecker S, Frey FJ. Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement. Nephrol Dial Transplant. 2009;24:2175-9. 10. Moss RR, Ivens E, Pasupati S, Humphries K, Thompson CR, Munt B, Sinhal A, Webb JG. Role of echocardiography in percutaneous aortic valve implantation. JACC Cardiovasc Imaging. 2008;1:15-24. 11. Rodríguez E, Maroto L, Cobiella J, Silva J, Bañuelos C, HernándezAntolín R, Zamorano JL, Ginestal F. Transapical aortic valve implantation. Initial experience. Rev Esp Cardiol. 2009;62:933-6. 12. Doddamani S, Bello R, Friedman MA, Banerjee A, Bowers JH, Jr, Kim B, Vennalaganti PR, Ostfeld RJ, Gordon GM, Malhotra D, Spevack DM. Demonstration of left ventricular outflow tract eccentricity by real time 3D echocardiography: implications for the determination of aortic valve area. Echocardiography. 2007;24:860-866. 13. Pérez de Isla L, Zamorano J, Pérez de la Yglesia R, Cioccarelli S, Almería C, Rodrigo JL, Aubele AL, Herrera D, Mataix L, Serra V, Macaya C. Quantification of aortic valve area using three-dimensional echocardiography. Rev Esp Cardiol. 2008;61:494-500. 14. Masson JB, Kovac J, Schuler G, Ye J, Cheung A, Kapadia S, Tuzcu ME, Kodali S, Leon MB, Webb JG. Transcatheter aortic valve implantation: review of the nature, management, and avoidance of procedural complications. JACC Cardiovasc Interv. 2009;2:811-20. 15. Détaint D, Lepage L, Himbert D, Brochet E, Messika-Zeitoun D, Iung B, Vahanian A. Determinants of significant paravalvular regurgitation after transcatheter aortic valve: implantation impact of device and annulus discongruence. JACC Cardiovasc Interv. 2009;2:821-7. 16. Tops LF, Wood DA, Delgado V, Schuijf JD, Mayo JR, Pasupati S, Lamers FP, van der Wall EE, Schalij MJ, Webb JG, Bax JJ. Noninvasive evaluation of the aortic root with multislice computed tomography implications for transcatheter aortic valve replacement. JACC Cardiovasc Imaging. 2008;1:321–30. 17. Walther T, Dewey T, Borger MA, Kempfert J, Linke A, Becht R, Falk V, Schuler G, Mohr FW, Mack M. Transapical aortic valve implantation: step by step. Ann Thorac Surg. 2009;87:276-83. 18. Rallidis LS, Moyssakis IE, Ikonomidis I, Nihoyannopoulos P. Natural history of early aortic paraprosthetic regurgitation: a five-year followup. Am Heart J. 1999;138:351-7. 19. Berry C, Cartier R, Bonan R. Fatal ischemic stroke related to non permissive peripheral artery access for percutaneous aortic valve replacement. Catheter Cardiovasc Interv. 2007;69:56–63. 20. Buchbinder M. CoreValve 18 French ReValving experience. International safety/efficacy studies and post CE mark registry. Preliminary results of percutaneous aortic valve replacement (PAVR). Data collected through March 15, 2008. Presented at the 57 th Annual Scientific Session of the American College of Cardiology, 2008. 21. Tuzcu ME. Transcatheter aortic valve replacement malposition and embolization: innovation brings solutions also new challenges. Catheter Cardiovasc Interv. 2008;72:579-80. 22. Perez de Isla L, Rodriguez E, Zamorano J. Transapical aortic prosthesis misplacement. J Am Coll Cardiol. 2008;9;52:2043. 23. Latsios G, Gerckens U, Grube E. Transaortic transcatheter aortic valve implantation: A novel approach for the truly “no-access option” patients. Catheter Cardiovasc Interv. 2009 [Epub ahead of print]. Online data supplement Video 1. Real-time 3D transesophageal echocardiography showing aortic balloon valvuloplasty. Video 2. Real-time 3D transesophageal echocardiography showing aortic prosthesis deployment. Video 3. Full volume zoom 3D transesophageal echocardiography, showing restricted movement of the anterior leaflet of the mitral valve caused by the ventricular edge of aortic prosthesis. Videos 4 and 5. Real-time 3D transesophageal echocardiography showing regular aortic prosthesis implantation. Video 6. Two-dimensional transesophageal echocardiography long axis view showing moderate perivalvular regurgitation caused by asymmetric calcification. Videos 7 and 8. Full volume 3D transesophageal echocardiography showing central aortic regurgitation jet caused by incomplete expansion of the device, which was too large for the aortic root. 276. 277. 278. 279. 280. 281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291. 292. 293. 294. 295. 296. 297. 298. 299. 300. 301. 302. 303. 304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. CHAPTER 3 Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation Chapter 3 – Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation 39 ..................................................................................................................................................................................... ..................................................................................................................................................................................... Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation Alexandra Gonc¸alves1,2, Pedro Marcos-Alberca1, Carlos Almeria1, Gisela Feltes1, Enrique Rodrı ´guez1, Rosa Ana Herna ´ndez-Antolı ´n1, Eulogio Garcia1, Luis Maroto1, Cristina Fernandez Perez3, Jose ´C. Silva Cardoso2, Carlos Macaya1, and Jose ´Luis Zamorano1* 1 Cardiovascular Institute, Hospital Clı ´nico San Carlos, Plaza de Cristo Rey, Madrid 28040, Spain; 2 University of Porto Medical School, Porto, Portugal; and 3 Unit of Methodology of the Investigation and Clinical Epidemiology, Preventive Medicine Department, Hospital Clı ´nico San Carlos, Madrid, Spain Received 2 May 2011; accepted after revision 1 August 2011 Aims Data regarding the effects of TAVI on LV after are scarce and conflicting results have been reported immediately after aortic valvuloplasty. This study aimed to determine the acute haemodynamic effects of transcatheter aortic valve implantation (TAVI) in left ventricle (LV) diastolic performance, immediately after aortic valvuloplasty and prosthesis deployment. Methods and results Sixty-one patients with severe aortic valve stenosis, and preserved LV systolic function submitted to successful TAVI, were included. All procedures were guided through transoesophageal echocardiography, and parameters of diastolic function were evaluated before and minutes after TAVI. The mean age was 83.5+6 years and mean log EuroSCORE was 18.2 +9.4. Before the procedure, all patients presented LV diastolic dysfunction. Immediately after TAVI, fewer patients presented a restrictive pattern [27 (44.3%), before the procedure, vs. 20 (34.4%), after TAVI (P¼0.047)], and an increase in E wave deceleration time (211.2+75.5 vs. 252.7 +102.3 cm/s, P¼0.001), in E wave velocity (109.5 +41.2 vs. 120.3 +43.6 cm/s, P¼0.025), and in isovolumetric relaxation time (83 +36.5 vs. 97.1 +36.0 ms, P¼0.013) was observed. On multivariate analysis of covariance (ANCOVA), adjusting to LV systolic function, heart rate, blood pressure, and haematocrit values, the results remained significant. Patients referred to percutaneous approach had invasive haemodynamic data collected, showing a decrease in LV end-diastolic pressure after valve implantation [18.8 +5.7 vs. 14.7 +4.7, mean difference 24.1 (95% CI: 25.9; 22.9)]. Patients with a restrictive pattern immediately after TAVI presented a smaller decrease in LV end diastolic pressure (23.3 +4.7) than those with diastolic dysfunction grade I or II (29.5 +4.7; P¼0.017). Conclusion This is the first study describing LV diastolic performance during TAVI. Our results show improvement in diastolic function parameters in patients with preserved LV systolic function, immediately after successful TAVI. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Aortic valve stenosis †Aortic prosthesis †Diastolic dysfunction †Left ventricle (LV) †Transcatheter aortic valve implantation (TAVI) Introduction Transcatheter aortic valve implantation (TAVI) techniques have emerged as an alternative treatment for patients with severe aortic stenosis and high surgical risk. 1 Since the first-in-man experience in 2002, 2 thousands of patients have been treated with this technique worldwide with procedural success rates of �95%. 1,3,4 Most patients referred for TAVI are elderly and present symptomatic aortic stenosis with heart failure in NYHA classes III and IV, *Corresponding author. Tel/Fax: +34 91 330 32 90, Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. &The Author 2011. For permissions please email: [email protected] European Journal of Echocardiography doi:10.1093/ejechocard/jer147 European Journal of Echocardiography Advance Access published August 23, 2011 at Universidade do Porto on August 24, 2011ejechocard.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 40 in spite of preserved left ventricle (LV) systolic function. 1,5 Myocardial hypertrophy in consequence of cellular hypertrophy and cellular matrix hyperplasia occurs before the development of systolic dysfunction, 6 being diastolic dysfunction the primarily responsible for heart failure symptoms. After aortic valve replacement (AVR), clinical improvement is expected and diastolic stiffness along with relaxation normalization is observed in late follow-up. 7 In patients submitted to TAVI, several studies have already shown immediate almost complete normalization in afterload and a significant decrease in pressure gradient, between the aorta and the LV, as well as clinical improvement at short term. 4,5,8 At medium-term follow-up, LV mass reduction and improvements in tissue Doppler velocities have been reported, 9 and one study has described early regression of septal hypertrophy 1 month after TAVI. 10 However, so far the acute changes in left ventricular diastolic performance after TAVI and its consequences in patients’ clinical outcome are unknown. Conflicting results from invasive haemodynamic measurements after aortic balloon valvuloplasty have been reported and worsening of diastolic indexes was described. 11,12 Nevertheless, the technique applied on TAVI is different, as well as the favourable clinical outcomes, 1 in opposition to the disappointing results after aortic valvuloplasty. 13,14 This study aimed to determine the acute haemodynamic effects of TAVI in LV diastolic performance, immediately after aortic valvuloplasty and prosthesis deployment. Methods Population Sixty-one patients with severe aortic stenosis (aortic valve area ≤1 cm 2 ) and preserved LV systolic function (ejection fraction ≥50%), submitted to successful TAVI in one tertiary centre from April 2009 to April 2010, were included. These patients were obtained from a series of 97 consecutive patients who underwent TAVI, after excluding those with LV systolic dysfunction (9 patients), atrial fibrillation or ventricular pacemaker rhythm (7 patients), concomitant moderate to severe mitral valve disease (6 patients), aortic regurgitation (3 patients), and those whose procedure was not totally guided through transoesophageal echocardiography 15 (11 patients). Indications and contraindications for TAVI have been described previously elsewhere. 1,5,16 Patients were referred for TAVI due to an excessive risk for AVR, which was estimated using the logistic EuroSCORE and/or clinical judgement. 17 Ten (16.4%) elderly patients were considered inoperable on the basis of comorbidities or risk factors such as pulmonary hypertension (defined as a pulmonary systolic pressure .50 mmHg as estimated by Doppler echocardiography or measured by cardiac catheterization) or frailty or porcelain aorta (5, 8.2% patients). No systematic tests were performed for the evaluation of frailty, being its conception based on medical criteria. 18 Porcelain aorta was defined as wide circumferential calcification of the thoracic aorta when assessed by computed tomography and/or fluoroscopy. Transthoracic echocardiography On the previous day of the procedure, all patients performed a conventional transthoracic echocardiogram with bidimensional and Doppler assessment, which was completed with three-dimensional (3D) analysis (X4-1 probe, Philips Medical Systems, Andover, MA, USA). The following measurements were obtained in all patients: LV mass calculated with the American Society of Echocardiography (ASE) recommended formula, mean transvalvular gradient calculated with the Bernoulli formula, aortic valve area measured by the continuity equation and early (E′) and late (A′) diastolic peak velocities from Doppler tissue imaging measured at septal and lateral mitral annulus. Considering the superior accuracy and reproducibility of 3D echocardiography, left atrium (LA) volume, LV systolic and diastolic volumes, and resulting ejection fraction were calculated with direct volumetric analysis. 19 Valvular insufficiencies and diastolic function were graded according to international recommendations. 20,21 Transcatheter aortic valve implantation TAVI was performed with fluoroscopy and TEE guidance, under general anaesthesia using techniques described in detail in previous reports. 22,23 Nineteen patients (31.1%) implanted an Edwards SAPIEN (Edwards Lifesciences, Irvine, CA, USA) aortic valve thought anterograde transapical approach and 42 (68.9%) were submitted to the retrograde transfemoral approach. Among these, a Corevalve (Medtronic CoreValve Percutaneous System, Medtronic CV) was implanted in 23 (54.8%) patients and an Edwards SAPIEN valve in 19 (45.2%). Two valve sizes are available, 23and 26-mm expanded diameters for Edwards SAPIEN valve and 26 and 29 mm for CoreValve. The aortic prosthesis size was decided according to the annulus diameter, measured with transoesophageal echocardiography. Transoesophageal echocardiography protocol During the procedure, data were recorded using TEE with real-time 3D capability (i.e. 33 echocardiography system, X7-2t probe, 7MHz, Philips Medical Systems, Eindhoven, the Netherlands). TEE was performed in the moments previously to intervention and it was repeated few minutes after aortic valve implantation (5.7 +2.4 min), for later comparison between TEE results before and after TAVI. Pulsed wave spectral Doppler was recorded using mid-oesophageal views at four-chamber view, with the sample volume at the leaflet tips for transmitral inflow pattern assessment, and five-chamber view, with the sample volume between leaflet tips and LV outflow tract, for simultaneous imaging of mitral inflow and aortic valve closure clicks. Basal short-axis views were used to assess pulmonary veins flow and at least two pulmonary veins (one left and one right) were recorded. Colour M-mode Doppler in mid-oesophageal four-chamber view was used for recording transmitral flow for later measurement of propagation velocity. Transgastric mid short-axis view of the LV was recorded for LV systolic and diastolic area measurements. Deep transgastric longaxis view was used for continuous Doppler flow assessment through the aortic valve and pulsed Doppler recording at the LV outflow tract in order to calculate the effective aortic valve area before and after TAVI. Off line analysis of the images captured was performed and using the average measurement of at least three consecutive cardiac cycles, the following measurements were obtained: transmitral E wave and A wave peak velocity, E wave deceleration time, isovolumetric relaxation time (IVRT), isovolumetric contraction time, ejection time (ET), pulmonary venous flow peak systolic velocity (S), peak diastolic velocity (D), peak atrial reversal (Ar) velocity and duration (Adur), and colour M-mode flow propagation velocity (Vp). Mean and maximum transvalvular gradients were calculated with the Bernoulli formula and the aortic valve area measured by the continuity equation. Subsequently, the E/Aratio, S/Dratio, and LV fractional area change were calculated. The latter was chosen for LV systolic function A. Gonc¸alves et al.Page 2 of 8 at Universidade do Porto on August 24, 2011ejechocard.oxfordjournals.orgDownloaded from Chapter 3 – Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation 41 estimation because of the best convenience at the acute scenario, using transoesophageal echocardiography. The probe used presents 3D echocardiography capabilities, which were regularly employed for guiding the procedure, but it has no tissue Doppler software included, consequently tissue Doppler measurements were not available during the procedure. After aortic valve deployment, the presence of complications such as aortic regurgitation, cardiac effusion or cardiac tamponade, LV dysfunction or wall motion abnormalities, mitral valve damage or prosthesis misplacement were described. 20 In order to evaluate diastolic function from the beginning to the end of the procedure, modified ASE recommendations with the exclusion of tissue Doppler parameters were used. 21 Mild diastolic dysfunction was defined by mitral E/Aratio ,0.8 and DT .200 ms or E/Aratio ,0.8 and IVRT ≥100 ms, along with predominant systolic flow in pulmonary venous flow (S.D); moderate diastolic dysfunction by mitral E/Aratio from 0.8 to 1.5 along with diastolic predominance in pulmonary venous flow (S,D) with at least one of the following: DT from 160 to 200 ms, IVRT ,90 ms or Ar velocity .35 cm/s. Severe diastolic dysfunction/restrictive pattern was defined by E/Aratio ≥2 with DT ≤160 ms, or with IVRT ≤60 ms, along with diastolic predominance in pulmonary venous flow (S,D). 24 Data expected to interfere in diastolic function parameters namely heart rate, systolic and diastolic blood pressure, and haematocrit value were evaluated when starting the procedure and few minutes after valve implantation. Invasive haemodynamic data Patients referred for the percutaneous approach (n¼42) had invasive haemodynamic measurements performed. For the purpose of this study, LV end diastolic pressure measured immediately before and after implantation was considered. This protocol was approved by the local ethics committee and all patients gave written informed consent for participation. The authors are solely responsible for the design and conduct of this study, analyses, and its final contents. Statistical analysis Categorical variables were expressed as percentages and continuous variables as mean (SD) unless otherwise specified. Continuous variables were compared between groups using an unpaired t-test (for normally distributed variables) or the Mann–Whitney U-test (for nonnormally distributed variables). Multivariate regression analysis of covariance (ANCOVA) was used to compare continuous variables and categorical variables relation with major outcomes. The confounders shown to present significant variation in univariate analysis (systolic and diastolic blood pressure, heart rate, haematocrit, and fractional area change of LV) were sequentially included in the model executed for each outcome variable. For assessing the level of agreement, Cohen’s kappa was used for categorical variables. All reported probability values are two-tailed, and P,0.05 was considered statistically significant. Analyses were performed with the SPSS statistical software package (version 16.0) (SPSS Inc, Chicago, IL, USA). Results Patient characteristics Among the 61 patients included in this prospective study, the mean age was 83.5 +6 years and mean log EuroSCORE was 18.2 +9.4. LV concentric hypertrophy was present in 44 (72%) patients, 45 (73.8%) had LA volume ≥34 mL/m 2 and 29 (47.5%) had E/E′ ratio .15. Only patients with preserved LV systolic function were included, but all patients presented LV diastolic dysfunction. Thirty-one (50.8%) showed a restrictive pattern when using the ASE recommendations 20 and 27 (44.3%), when the classification is modified, excluding tissue Doppler parameters (Cohen’s kappa level of agreement ¼0.679). Overall, and according to intervention, baseline patients’ characteristics and echocardiography data are presented in Table 1. Most characteristics were similar in both groups, but patients referred to transapical approach were younger (78 +8 vs. 85 +4, P¼0.001), presented more commonly dyslipidemia (89.5 vs. 50%, P¼0.004), peripheral vascular disease (63.2 vs. 14.3%, P,0.001), and renal impairment (47.4 vs. 21.4% P¼0.041). Echocardiographic haemodynamic parameters immediately after transcatheter aortic valve implantation In the few minutes immediately after prosthesis deployment, mean aortic pressure gradient decreased to normal parameters (8+ 3 mmHg). Mild aortic regurgitation, central or perivalvular was present in 30 (49.2%) patients after the procedure, but none ended with moderate or severe aortic regurgitation. There was a decrease in ET and an increase in E wave maximum velocity, E wave deceleration time, E/Aratio and IVRT. In spite of all patients having preserved LV systolic function, LV fraction area change significantly increased [difference of means 8.1 (95% CI: 4.4–11.8)] after the procedure. No significant variation was found in the comparative analysis of grade I or II of LV diastolic function (Figure 1); nevertheless, there was a significant reduction in a restrictive pattern after TAVI, as 27 (44.3%) patients presented a restrictive pattern before the procedure vs. 20 (34.4%) after TAVI (P¼ 0.047). Comparative results from univariate analysis of TEE and clinical parameters during TAVI are presented in Table 2. A significant decrease in blood pressure, heart rate, and haematocrit, as well as an increase in LV fractional area change, was observed after aortic valve implantation (Table 2). Using the ANCOVA, we assessed the modification of the intervention effect on primary outcome variables and confounders during TAVI in the overall population. The results presented in Table 3showed the absence of significant differences according to the type of procedure. However, a tendency for a smaller decrease in ET [percutaneous: 228.8 (95% CI: 246.5; 211.1) vs. transapical: 26.3 (95% CI: 227.5; 214.9)] and for a larger reduction in Vp slope [percutaneous: 20.095 (95% CI: 216.9; 216.8) vs. transapical: 210.8 (95% CI: 220.7; 20.97)] after prosthesis deployment could be observed in the transapical subgroup. Subsequently, a multivariate ANCOVA was performed in order to assess the effect of potential confounders in main outcome variables variation. The modifications in the diastolic function parameters observed remained significant when adjusted in the multivariate models performed (Table 4). We found a significant increase in the E wave deceleration time [41.5 (95% CI: 18.0– 65.1)] in the global population; however, the multivariate analysis with the ANCOVA model showed that it occurred mainly in Acute LV diastolic function improvement after TAVI Page 3 of 8 at Universidade do Porto on August 24, 2011ejechocard.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 42 patients in whom the haematocrit value remained stable. In those with an important decrease in the haematocrit minutes after TAVI, the E wave deceleration time remained constant. The baseline demographic and clinical characteristics presented in Table 1, as well as the type or size of prosthesis were individually tested for each diastolic parameter and confounders, but none had significant effect on the results obtained after the intervention. Invasive haemodynamic parameters immediately after transcatheter aortic valve implantation In the group of patients submitted to the percutaneous approach (n¼42), invasive haemodynamic measurements were performed and significant decrease in LV end-diastolic pressure, after valve implantation was found [18.8 +5.7 vs. 14.7 +4.7, mean difference 24.1 (95% CI: 25.9; 22.9)]. Patients with a restrictive pattern immediately after TAVI had a smaller decrease in LV end diastolic pressure (23.3 +4.7) than those presenting diastolic dysfunction grade I or II after the procedure (29.5 +4.7; P¼0.017). Discussion This is the first study describing acute haemodynamic changes regarding diastolic function parameters during TAVI. We present a representative group of patients among those being currently submitted to TAVI. 25 These elderly patients with degenerative aortic stenosis have severe heart failure symptoms, several comorbidities, high EuroSCORE, and multiple cardiovascular risk factors. The ones submitted to transapical approach have been considered by others as a particular group with more comorbidities and higher Logistic EuroScore. 25 Our patients referred to transapical approach had more frequently renal impairment and peripheral ............................................................................................................................................................................... Table 1 Baseline characteristics of the study population Variables Overall (n561) Percutaneous (n542) Transapical (n519) P-value Age (years) 83 (6) 85 (4) 78 (8) 0.001 Female [n(%)] 38 (62.3) 29 (69.0) 9 (47.4) 0.154 Log EuroSCORE (%) 18.2 (9.4) 18.1 (7.8) 18.4 (12.4) 0.930 Body surface area (m 2 ) 1.6 (0.2) 1.7 (0.19) 1.9 (0.15) 0.680 Hypertension [n(%)] 52 (85.2) 36 (85.7) 16 (84.2) 1.0 Diabetes [n(%)] 15 (24.6) 8 (19.9) 7 (36.8) 0.199 Dyslipidemia [n(%)] 38 (62.3) 21 (50.0) 17 (89.5) 0.004 Coronary artery disease [n(%)] 22 (36.1) 15 (37.5) 7 (36.8) 1.0 Previous PCI or prior CABG [n(%)] 16 (26.2) 9 (21.4) 7 (36.8) 0.224 NYHA functional class 0.853 II 5 (8.2) 4 (9.5) 1 (5.3) III 53 (86.9) 36 (85.7) 17 (89.5) IV 3 (4.9) 2 (4.8) 1 (5.3) COPD [n(%)] 24 (39.3) 16 (38.1) 8 (42.1) 0.784 Renal impairment 18 (29.5) 9 (21.4) 9 (47.4) 0.041 Creatinine (mg/dL) 1.3 (0.7) 1.2 (0.7) 1.5 (0.7) 0.199 Peripheral vascular disease 18 (29.5) 6 (14.3) 12 (63.2) ,0.001 Nt-ProBNP (pg/mL) a 3208 (1794–6318) 3721 (2034–6529) 3200 (1319–8692) 0.739 Pulmonary hypertension 9 (14.8) 8 (25.0) 1 (14.3) 1.0 Mean aortic pressure gradient (mmHg) 54 (14) 56 (16) 51 (10) 0.221 Aortic peak pressure gradient (mmHg) 90 (22) 91 (24) 87 (20) 0.610 Aortic valve area (cm 2 ) 0.6 (0.1) 0.6 (0.1) 0.6 (0.1) 0.167 LV EF (%) 63 (9) 62 (10) 63 (9) 0.621 LA index volume (mL/m 2 ) 47 (24) 49 (28) 43 (12) 0.322 LV mass index (g/m 2 ) 132 (42) 137 (44) 121 (35) 0.197 E/E′ratio 21 (13) 23 (13) 17 (10) 0.210 Diastolic dysfunction Grade I 22 (36.1) 15 (35.7) 7 (36.8) 0.452 Grade II 8 (13.1) 3 (7.1) 5 (26.3) 0.212 Grade III 31 (50.8) 24 (57.1) 7 (36.8) 0.321 CABG, coronary artery bypass grafting; COPD, chronic obstructive pulmonary disease; EF, ejection fraction; LA, left atrium; LV, left ventricle; log EuroSCORE, logistic European System for Cardiac Operative Risk Evaluation; Nt-ProBNP, NT portion B-type natriuretic peptide; PCI, percutaneous coronary intervention. a Presented as median and interquartile range. A. Gonc¸alves et al.Page 4 of 8 at Universidade do Porto on August 24, 2011ejechocard.oxfordjournals.orgDownloaded from Chapter 3 – Acute left ventricle diastolic function improvement after transcatheter aortic valve implantation 43 vascular disease; however, they were younger and the mean Logistic EuroSCORE was similar to those referred to TAVI through percutaneous approach. This might be explained by the number of patients referred to transapical approach for porcelain aorta (5; 26.3%), which were younger and with fewer comorbidities, but still being refused for AVR. Left ventricle remodelling in severe aortic stenosis In this study, the population was restricted to patients with preserved LV systolic function, which in fact represents most of the patients treated with TAVI. 1,5 These patients, in addition to the age-related changes in diastolic function parameters, with increased passive stiffness and abnormal relaxation, also present LV hypertrophy, LA dilatation, and myocardium fibrosis in result of the chronic pressure overload. 26,27 During the LV remodelling process, the myocytes and fibroblasts proliferation initially result in asymptomatic abnormal tissue Doppler velocities and diastolic dysfunction, in spite of normal ejection fraction. However, in the absence of treatment, global systolic dysfunction and/or symptoms eventually develop, leading to death unless the valve is replaced. 28 Immediate left ventricle diastolic response after transcatheter aortic valve implantation Severe LV diastolic dysfunction prevailed at baseline, but it significantly improved after the procedure (Figure 1). This result was supported by the invasive measurement of LV end diastolic pressure. Analysing echocardiographic parameters, fewer patients presented severe LV diastolic dysfunction after the procedure, mostly because of the E wave deceleration time increase, which may be the result of increased relaxation and compliance and Figure 1 Patients’ diastolic dysfunction classification at baseline and after transcatheter aortic valve implantation. Diastolic dysfunction 21 definition according ASE recommendations modified by the exclusion of tissue Doppler parameters. ............................................................................................................................................................................... Table 2 Overall univariate analysis of transoesophageal echocardiography and clinical parameters during transcatheter aortic valve implantation (n561) Variables Data at baseline Data minutes after TAVI Difference of means (95% CI) P-value Mean aortic pressure gradient (mmHg) 54 (14) 8 (3) 246.4 (250.3; 242.6) ,0.001 Aortic peak pressure gradient (mmHg) 90 (22) 16 (6) 273.9 (279.9; 268.1) ,0.001 E wave (cm/s) 109.5 (41.2) 120.3 (43.6) 10.5 (1.4; 20.2) 0.025 A wave (cm/s) 100.6 (40.7) 96.1 (38.9) 23.7 (214.3; 26.8) 0.482 E wave/A wave 1.2 (0.8) 1.5 (1.1) 0.29 (0.01; 0.57) 0.040 E wave deceleration time (ms) 211.2 (75.5) 252.7 (102.3) 41.6 (17.2; 65.9) 0.001 IVRT (ms) 83 (36.5) 97.1 (36.0) 14.1 (3.2; 25.1) 0.013 ET (ms) 314.9 (32.2) 293.1 (46.5) 221.8 (235.6; 28.0) 0.002 S/D1.1 (0.8) 1.2 (0.5) 0.36 (20.29; 0.37) 0.817 Ar (cm/s) 25.1 (11.1) 22.9 (10.5) 3.1 (1.2; 5.4) 0.092 Adur (ms) 124.3 (29.9) 121.8 (51.1) 2.9 (0.9; 6.8) 0.438 Vp (cm/s) 62.1 (20.0) 57.4 (28.9) 24.6 (214.9; 25.6) 0.366 LV diastolic area (cm 2 ) 17.9 (3.9) 17.8 (4.1) 20.07 (21.1; 20.9) 0.880 LV systolic area (cm 2 ) 8.4 (3.5) 7.0 (3.4) 21.4 (22.3; 20.5) 0.002 LV fractional area change (%) 54 (14) 62 (14) 8.1 (4.4; 11.8) ,0.001 Clinical parameters HR (b.p.m.) 79 (16) 75 (14) 24.0 (27.9; 20.07) 0.046 BP systolic (mmHg) 130 (19) 122 (17) 27.9 (213.2; 22.6) 0.004 BP diastolic (mmHg) 67 (11) 59 (11) 28.5 (211.1; 25.8) ,0.001 Haematocrit (%) 35.4 (4.7) 33.1 (3.8) 22.5 (23.8; 21.3) ,0.001 BP, blood pressure; D, pulmonary venous flow peak diastolic velocity; ET, ejection time; HR, heart rate; IVRT, isovolumetric relaxation time; LV, left ventricle; S, pulmonary venous flow peak systolic velocity; Vp, colour M-mode flow propagation velocity. Acute LV diastolic function improvement after TAVI Page 5 of 8 at Universidade do Porto on August 24, 2011ejechocard.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 44 LV end diastolic pressure reduction. Accordingly, the IVRT increase after TAVI suggests a significant reduction in LA pressure. In patients with major decline in the haematocrit during the procedure, the haemodynamic response with transient tachycardia in consequence of acute preload reduction may have constrained the deceleration time increase. The increase in E wave maximum velocity may be explained by alterations in preload or in LV relaxation. During the intervention, the indirect parameters of preload evaluation were LV diastolic area, which remained constant, and haematocrit value, which did not significantly affect E wave velocity increase. Thus, we consider that the augmented LA LV pressure gradient during early diastole is consequence of an ameliorated LV relaxation, in response of immediate, complete, and sustained afterload release. The diastolic function parameters presented similar results whether the procedure was performed by transapical or percutaneous approach. However, in patients submitted to TAVI through transapical approach, the Vp slope decline was evident (Table 3). This parameter has limitations in patients with preserved LV systolic function, but it represents LV suction force and its slowing is consistent with an apical suction reduction. 21 This is in accordance with the technical procedure, where the LV apex puncture is performed. Possibly, the reduced sample size of patients submitted to transapical approach may explain the absence of statistic difference in Vp slope between both groups. Therefore, this result should be expected in those patients and it should not be interpreted as lone criteria of abnormal LV filling pressures. The acute improvement in diastolic function parameters found in our study is in agreement with the results obtained in patients with hypertrophic obstructive cardiomyopathy after septal ablation. In those patients, it was described an immediate improvement of diastolic function along with LV outflow tract pressure gradient reduction. However, after septal ablation, there is a reduction in systolic function, in opposition to LV ejection fraction improvement usually observed after TAVI. 15 After aortic valvuloplasty, the immediate load-dependent responses reported have been inconsistent, 11,12 which is not surprising given the limited and ................................................................................. ............................................................................................................................................................................... Table 3 Analysis of the intervention effect on primary outcome variables and confounders during transcatheter aortic valve implantation in the overall population (n561) Variables Difference of means (95% CI) P-value Percutaneous (n542) Transapical (n519) E wave (cm/s) 12.4 (0.6; 24.2) 7.3 (29.4; 24.1) 0.624 E wave/A wave 0.3 ( 20.05; 0.7) 0.3 (20.21; 0.78) 0.954 E wave deceleration time (ms) 44.0 (15.6; 72.4) 36.2 (214.9; 87.3) 0.770 IVRT (ms) 13.1 (21.7; 28.0) 16.4 (1.5; 31.2) 0.788 ET (ms) 228.8 ( 246.5; 211.1) 26.3 (227.5; 214.9) 0.132 Vp slope (cm/s) 20.095 ( 216.9–16.8) 210.8 (220.7; 20.97) 0.303 LV fractional area change (%) 9.6 (4.9; 14.2) 4.8 (21.4; 11.1) 0.232 HR (bpm) 23.4 ( 28.5; 21.7) 25.4 (211.7; 20.87) 0.630 BP systolic (mmHg) 25.0 (210.8; 20.79) 214.2 (225.5; 22.8) 0.108 BP diastolic (mmHg) 27.8 ( 211.0; 24.6) 29.8 (214.9; 24.7) 0.486 Haematocrit (%) 22.2 ( 23.7; 20.7) 23.3 (25.6; 21.0) 0.414 BP, blood pressure; ET, ejection time; HR, heart rate; IVRT, isovolumetric relaxation time; LV, left ventricle; Vp, colour M-mode flow propagation velocity. ............................................................................................................................................................................... Table 4 Analysis of covariance multivariate analysis of transoesophageal echocardiography and clinical parameters during transcatheter aortic valve implantation in the overall population (n561) Variables Baseline a Minutes after TAVI a Difference of means (95% CI) P-value E wave (cm/s) 109.5 (98.9; 120.1) 120.3 (109.2; 131.5) 10.8 (1.4; 20.2) 0.025 b E wave/A wave 1.2 (0.9; 1.4) 1.5 (1.2; 1.8) 0.30 (0.03; 0.56) 0.002 E wave deceleration time (ms) 211.2 (191.7; 230.6) 252.7 (226.8; 278.7) 41.5 (18.0; 65.1) ,0.001 IVRT (ms) 83.0 (73.8; 92.8) 97.1 (87.9; 106.4) 14.2 (3.3; 25.0) 0.003 ET (ms) 314.9 (306.6; 323.2) 294.8 (284.2; 305.3) 220.2 (232.8; 27.5) 0.026 ET, ejection time; LV, left ventricle; IVRT, isovolumetric relaxation time; Vp, colour M-mode flow propagation velocity. a Data presented as adjusted mean (95% CI). b Univariate—none of the confounders had a significant effect on the mean E wave variation during the procedure. A. Gonc¸alves et al.Page 6 of 8 at Universidade do Porto on August 24, 2011ejechocard.oxfordjournals.orgDownloaded from Chapter 4 – Three-Dimensional Echocardiography in Paravalvular Aortic Regurgitation Assessment after Transcatheter Aortic Valve Implantation 51 best frame for AR jet visualization in two orthogonal long-axis views was selected. Then we cropped the data set along the axis of the AR jet, from the aortic side to the level of the vena contracta, in a plane that was exactly perpendicular to the long axis of the AR jet. Subsequently, we performed planimetry (Figure 6) using the methodology previously validated by Fang et al. 12 In patients with more than one independent leak, the vena contracta was taken as the sum of all individual vena contracta areas. This protocol was approved by the local ethics committee, and all patients gave written informed consent for participation. Reproducibility Two experienced operators blinded to 2D echocardiographic results analyzed separately 3D color data sets, worked through the multiplanar reconstruction tools, and performed the vena contracta planimetry in patients with AR. Statistical Analysis Categorical variables are expressed as percentages and continuous variables as mean 6SD unless otherwise specified. Continuous variables were compared between groups using unpaired ttests (for normally distributed variables) or the Mann-Whitney Utest (for variables not normally distributed). Kendall’s t(nonparametric test) was calculated for the assessment of correlations between vena contracta measurements by 3D TTE and 2D TTE and AR volume. The diagnostic efficiency of vena contracta width and planimetry was assessed using receiver operating characteristic curve analysis. All reported Pvalues are two tailed, and Pvalues < .05 were considered to indicate statistical significance. Analyses were performed using SPSS version 16.0 (SPSS, Inc., Chicago, IL). RESULTS Among the 72 patients included, 39 (54.2%) were women, the mean age was 82 68 years, and the mean log European System for Cardiac Operative Risk Evaluation score was 19.2 69.9. Overall, and according to intervention, baseline patients’ characteristics and echocardiographic data are presented in Table 1. Most characteristics were similar in both groups, but patients who underwent a transapical approach were younger (77 69 vs 84 65 years, P= .003) and presented more commonly with peripheral vascular disease (65.2% vs 14.3%, P< .001). A retrograde transfemoral approach was performed in 49 patients (68.1%). Among these, Edwards Sapien aortic valves were implanted in 28 (57.1%) and CoreValve devices in 21 (42.9%). All patients (n= 23) referred for TAVI using the transapical approach underwent implantation of Edwards Sapien valves. TTE Using AR volume for the accurate classification of AR severity, 43 patients (57.4%) demonstrated AR; 10 (13.3%) had central AR, and 33 (44.0%) had paravalvular AR jets. Moderate AR was present in eight patients (11.3%) and was restricted to patients with paravalvular AR. Thirty-six paravalvular jets were identified, as three patients had two independent leaks from different positions. The paravalvular region from 12 to 3 o’clock was the most common location for mild as well as for moderate paravalvular AR jets, but no correlation with aortic valve calcification severity or asymmetry was found. Figure 1 Paravalvular AR assessed by 2D echocardiography in the parasternal long-axis view. This image illustrates a vena contracta width of 2 mm. It was acquired from the same patient shown in Figure 6.Ao, Aorta; LA, left atrium; LV, left ventricle. Figure 2 (A) Three-dimensional transthoracic echocardiographic four-heartbeat full-volume acquisition. (B) Left ventricular ejection fraction and stroke volume determination by direct volumetric analysis. Journal of the American Society of Echocardiography Volume 25 Number 1 Gonc ¸alves et al 49 Life after TAVI: a Clinical and Echocardiographic Appraisal 52 Transthoracic echocardiographic data at follow-up are presented in Table 2. Left ventricular ejection fraction, left ventricular mass, and aortic valve area were similar between all groups of patients, regardless of AR presence or severity, but patients with moderate AR had larger end-diastolic volumes than those with mild AR (66.1 618.6 vs 48.4 621.9 mL/m 2 ,P= .044). Vena contracta widths were similar between patients with moderate and mild AR (2.1 60.53 vs 1.9 6 0.16 mm, P= .16), but vena contracta planimetry by 3D TTE was larger in patients with moderate AR than in those with mild AR (0.30 60.12 vs 0.09 60.07 cm 2 ,P= .001). Vena contracta planimetry on 3D TTE was better correlated with AR volume than vena contracta width on 2D TTE (Kendall’s t= 0.82 [P< .001] vs 0.66 [P< .001]). The area under the receiver operating characteristic curve for moderate AR assessment also showed better accuracy of vena contracta planimetry (area under the curve, 0.96; 95% confidence interval, 0.91–1.0) than vena contracta width (area under the curve, 0.35; 95% confidence interval, 0.15–0.55) (Figure 7). Reproducibility Vena contracta planimetry was traced by two blinded independent operators, and a low absolute difference of 0.005 60.075 between the two measurements was observed. Absolute interobserver variability was 12.4 611.5%, and Pearson’s correlation was significant between observers (r= 0.86, P< .001). Figure 3 Paravalvular AR assessed with Live 3D color, using the iCrop tool. Two orthogonal 2D views and the 3D reconstruction are obtained simultaneously. (A) Paravalvular AR view from the left ventricle (LV) (arrows). (B) Paravalvular AR view from the aortic root (arrows). Depending on the location of the cut plane in relation to the aortic prosthesis, the area of the paravalvular AR jet varies as viewed in the short-axis orientation. Figure 4 Live 3D transthoracic echocardiographic multiplanar reconstruction for aortic prosthesis (AP) ring assessment. LA, Left atrium; LV, left ventricle. 50 Gonc ¸alves et al Journal of the American Society of Echocardiography January 2012 Chapter 4 – Three-Dimensional Echocardiography in Paravalvular Aortic Regurgitation Assessment after Transcatheter Aortic Valve Implantation 53 Figure 5 Representation of paravalvular AR jets location according to the face of a clock. Conventional 2D transthoracic echocardiographic views are represented. (A) Parasternal short-axis view. (B) Parasternal long-axis view. (C) Apical five-chamber view. (D) Apical three-chamber view. Figure 6 AR Live 3D color analysis using multiplanar reconstruction tools. After selecting the best frame for AR jet visualization in two orthogonal long axis views (A,B), the data set was cropped through the perpendicular plane of the AR jet long axis, from the aortic side to the level of the vena contracta (C).(A) Coronal axis view. (B) Sagittal axis view. (C) Axial axis view, with planimetry of the vena contracta. (D) Multiplanar simultaneous axis view. Ao, Aorta; LV, left ventricle. Journal of the American Society of Echocardiography Volume 25 Number 1 Gonc ¸alves et al 51 Life after TAVI: a Clinical and Echocardiographic Appraisal 54 DISCUSSION AR After TAVI This study shows an additional contribution of 3D TTE to 2D TTE for the accurate evaluation of AR after TAVI, using AR volume as a reference standard. We found an AR prevalence of 57.4% at midterm follow-up, which was mainly caused by paravalvular AR. Among all, most patients presented with mild AR (48.6%), and moderate AR was restricted to patients with paravalvular AR. This result is consistent with data reported from studies assessing AR immediately after TAVI 3 or at midterm follow-up. 17,18 Favorable outcomes are expected in patients with mild AR, 5,19 but paravalvular AR severity can change over time, as observed in patients with AR after aortic valve replacement. 6 Significant AR may cause hemodynamic deterioration, and it was shown that mild paravalvular leaks after TAVI cause Table 1 Baseline characteristics of the study population Variable Overall (n= 72) Percutaneous (n= 49) Transapical (n= 23) P Clinical characteristics Age (y) 82 68 84 65 77 610 .003 Women 39 (54.2%) 30 (61.2%) 9 (39.1%) .133 Log EuroSCORE (%) 19.1 69.9 19.2 68.2 18.8 613.0 .544 Hypertension 59 (81.9%) 41 (83.7%) 18 (78.3%) .820 Diabetes 20 (27.8%) 11 (22.4%) 9 (39.1%) .234 Dyslipidemia 44 (61.1%) 25 (51.0%) 19 (82.6%) .021 Coronary artery disease 30 (41.7%) 19 (38.8%) 11 (47.8%) .638 Previous PCI or prior CABG 24 (33.3%) 13 (26.5%) 11 (47.8%) .129 COPD 29 (40.3%) 19 (38.8%) 10 (43.5%) .903 Renal impairment 20 (27.8%) 11 (22.4%) 9 (39.1%) .234 Peripheral vascular disease 22 (30.6%) 7 (14.3%) 15 (65.2%) <.001 Echocardiographic characteristics Mean aortic pressure gradient (mm Hg) 52 616 54 616 47 613 .073 Aortic peak pressure gradient (mm Hg) 86 624 88 624 81 624 .198 Aortic valve area (cm 2 ) 0.6 60.1 0.6 60.1 0.6 60.1 .465 LVEF (%) 59 613 58 614 59 613 .865 Systolic aortic annular diameter (mm) 21.2 62.4 21.2 62.5 21.2 62.3 .972 Device Edwards Sapien valve 23 mm 24 (47.1%) 16 (57.1%) 8 (34.8%) .105 26 mm 27 (52.9%) 12 (42.9%) 15 (65.2%) CoreValve 26 mm 19 (90.5%) 19 (90.5%) 0 — 29 mm 2 (9.5%) 2 (9.5%) 0 CABG, Coronary artery bypass grafting; COPD, chronic obstructive pulmonary disease; EuroSCORE, European System for Cardiac Operative Risk Evaluation; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention. Data are expressed as mean 6SD or as number (percentage). Table 2 Transthoracic echocardiographic results at follow-up (n= 72) Variable AR None (n= 29) Mild (n= 35) P*Moderate (n= 8) P † Left ventricular ejection fraction (%) 63.9 611.4 60.4 610.6 .227 58.6 613.2 .696 Left ventricular mass (g/m 2 ) 121.9 639.1 125.4 642.6 .769 130.0 627.7 .784 Aortic peak pressure gradient (mm Hg) 17.6 610.0 14.9 67.4 .245 17.4 67.8 .437 Mean aortic pressure gradient (mm Hg) 8.4 64.5 7.5 63.4 .418 9.0 65.1 .395 Left ventricle end-diastolic volume (mL/m 2 ) 44.0 616.3 48.4 621.9 .477 66.1 618.6 .044 Aortic valvular area (cm 2 ) 1.9 60.6 2.0 60.6 .605 1.9 60.6 .680 AR volume (mL) — 22.2 65.5 — 41.3 66.4 <.001 Vena contracta width (mm) — 2.3 60.6 — 2.0 60.5 .139 Vena contracta planimetry (cm 2 ) — 0.09 60.06 — 0.29 60.1 .001 Data are expressed as mean 6SD. *No versus mild AR. †Mild versus moderate AR. 52 Gonc ¸alves et al Journal of the American Society of Echocardiography January 2012 Chapter 4 – Three-Dimensional Echocardiography in Paravalvular Aortic Regurgitation Assessment after Transcatheter Aortic Valve Implantation 55 a significantly higher workload on the left ventricle than in an equivalently sized surgically implanted bioprosthesis. 20 The presence of postprocedural significant AR (defined as $2/4) was described as strong independent predictor of in-hospital death after TAVI, 21 and long-term follow-up is essential to further define the impact of AR on clinical outcomes. Accordingly, at 5-month followup, our study showed larger end-diastolic volumes in patients with moderate AR than in those with mild AR, which can be interpreted as the direct consequence of left ventricular remodeling caused by the chronic volume overload. Three-Dimensional Echocardiography The feasibility of visualizing valvular regurgitant jets with 3D color flow imaging has been previously demonstrated, and a better correlation between 3D transthoracic echocardiographic AR vena contracta planimetry and aortography, compared with conventional 2D transthoracic echocardiographic AR width, was shown. 12 Moreover, 3D TEE 13 is superior to 2D TEE in the evaluation of paravalvular prosthetic regurgitation. It provides more information regarding the location and a more accurate estimate of aortic and mitral valve prosthetic paravalvular defect size compared with 2D TEE. 22,23 Nevertheless, until now, no data regarding the evaluation of aortic paravalvular leaks with 3D TTE have been presented. The methodology proposed in this study allowed the precise localization of AR jets. By acquiring 3D color volumes from apical windows and analyzing views cropped in short-axis orientation, we found that the paravalvular region from 12 to 3 o’clock (corresponding to the usual location of the commissural junction between the left and right aortic cusps) was the most common location for paravalvular AR. This systematized description is fundamental once the prosthesis is implanted, as the native aortic cusps are smashed into the paravalvular region and the native references are partially lost. However, in this study, we did not find a correlation between the aortic valve calcification severity or leaflet asymmetry and the presence of paravalvular AR, which is consistent with previous results using computed tomography. 24 Using one 3D image acquisition, instead of the views in single 2D cut planes, it is possible to analyze the complete morphology of the AR color flow stream in the region of its origin. Consequently, the view from any level can be obtained, and the direction and extension of paravalvular AR jets can be assessed objectively, overcoming the assumptions needed to analyze AR jet extension, direction, and vena contracta shape using 2D imaging. 8 Figure 3 shows an example of paravalvular AR viewed simultaneously from the aortic root and from the left ventricular outflow tract; this figure demonstrates that depending on the location of the cut plane in relation to the aortic prosthesis, the area of the paravalvular AR jet varies as viewed in the short-axis orientation. This highlights the potential errors inherent to the analyses in single short-axis views from 2D imaging, in which the image orientation relative to the axis of the jet is unknown. Simultaneously, Figure 3A depicts a short-axis view of the color jet cross-sectional area and left ventricular outflow tract cross-sectional area, which is also a semiquantitative measure of AR severity. At the same time, from the aortic root (Figure 3B), we can visualize the proximal isovelocity surface. AR volume was used for quantitative AR severity classification by the difference between 3D TTE–derived left ventricular stroke volume and the right ventricular stroke volume. Left ventricular volumes assessed by 3D TTE have higher accuracy and better concordance with cardiac magnetic resonance compared with 2D TTE 25 ; consequently, we used 3D volumetric calculation of left ventricular stroke volume. This method overcame the risk for AR volume overestimation, when measuring the flow integral in the left ventricular outflow tract, because when the sample volume is placed too close to the prosthetic valve, proximal acceleration may lead to overestimation of velocity and consequently an overestimation of AR volume. Considering vena contracta measurements, our results showed a better correlation of 3D transthoracic echocardiographic vena contracta planimetry with AR volume than vena contracta width assessed by 2D TTE (Kendall’s t= 0.82 [P< .001] vs 0.66 [P< .001]). Consistently, a better accuracy for moderate AR diagnosis by vena contracta planimetry was shown by the area under the receiver operating characteristic (Figure 7). In fact, vena contracta width by 2D TTE provides a robust estimation of the size of the effective regurgitant orifice area in native valves, but once the jet presents an irregular shape, as frequently found in paravalvular leaks, its value is restricted and may not reflect AR severity. 7,12 Moreover, the vena contracta width was similar between patients with moderate and mild AR, while vena contracta planimetry was larger in patients with moderate AR than in those with mild AR. These results support the use of vena contracta planimetry as an additional tool for quantitative measurement of paravalvular AR. Indeed, vena contracta area by 3D transthoracic echocardiographic sequential cropping has been previously validated in patients with AR in native aortic valves. 12 However, until now, widespread 3D color echocardiography has been limited by restricted temporal resolution and a narrow color sector. Besides, the 3D color image could only be reconstructed from several heartbeats, which often causes stitching artifacts. 26 In this study, we used Live 3D color from the X5-1 PureWave microbeamforming xMATRIX probe. Even if 3D color frame rates are still lower than 2D rates, a considerable improvement from the previous X4 transthoracic echocardiographic probe could be observed. We were able to acquire the 3D color image with four heartbeats, minimizing stitching artifacts, and with all paravalvular area inside of the same volume acquisition. Consequently, the assessment of the real shape of the vena contracta and its planimetry was confidently performed. Nevertheless, despite the improvement in 3D images, a satisfactory acoustic window is still a fundamental requirement for proper visualization and interpretation. In this study, we had four patients with Figure 7 Receiver operating characteristic (ROC) curves for vena contracta width by 2D TTE (area under the curve, 0.35; 95% confidence interval, 0.15–0.55) and vena contracta planimetry by 3D TTE (area under the curve, 0.96; 95% confidence interval, 0.91–1.0) for the diagnosis of moderate AR. Journal of the American Society of Echocardiography Volume 25 Number 1 Gonc ¸alves et al 53 Life after TAVI: a Clinical and Echocardiographic Appraisal 56 unacceptable apical windows. These patients were part of the group without AR, and consequently there was no interference with AR results obtained, but limitations may occur when trying to apply 3D transthoracic echocardiographic analysis in patients with inadequate acoustic windows. Once a patient presents a poor window on 2D TTE, there is no expectation of improvement using 3D TTE. In those cases, TEE is the technique that can provide secure information. Because this study was performed 5 months after TAVI, we were able to include patients in whom TAVI was performed through a transapical route. It would have been impossible to study these patients immediately after the TAVI procedure, because image quality would have been reduced by the subcutaneous hematomas that result from left anterolateral minithoracotomy. Moreover, we must consider that a certain level of expertise is necessary for proper image acquisition, interpretation, and reproducibility of results. When using this methodology for paravalvular AR analysis in clinical practice, it may increase the time devoted to the transthoracic echocardiographic study, specially until achieving confidence with the method, but if we consider that we are adding significant information for appropriate quantification of paravalvular AR, we will be dedicating time to a higher standard in the performance of echocardiography. Further studies will certainly assess its clinical impact. Limitations In this study, moderate AR was restricted to patients with paravalvular AR, so the interpretation of vena contracta planimetry results can be applied only to patients with paravalvular AR. Our results are based on the latest 3D transthoracic echocardiographic technology available for clinical practice, but 3D echocardiography still has lower frame rates than 2D echocardiography, which may present restrictions on flow data interpretation and require a higher level of expertise at the time of data acquisition and image interpretation. We are presenting a single–time frame evaluation of patients with paravalvular AR. Additional studies are required for the assessment of the clinical benefit of this methodology at long-term follow-up. CONCLUSIONS In this study, we have proposed an alternative methodology for paravalvular AR assessment after TAVI. Using vena contracta planimetry by 3D TTE, we have described an accurate methodology for paravalvular AR jet evaluation and moderate AR classification. REFERENCES 1. Vahanian A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, et al. 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Journal of the American Society of Echocardiography Volume 25 Number 1 Gonc ¸alves et al 55 CHAPTER 5 Quality of life improvement at midterm follow-up after transcatheter aortic valve implantation ATTACHMENT EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 69 RECOMMENDATIONS EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease Jose L. Zamorano1*†, Luigi P. Badano2, Charles Bruce3, Kwan-Leung Chan4, Alexandra Gonc¸alves5, Rebecca T. Hahn6, Martin G. Keane7, Giovanni La Canna8, Mark J. Monaghan9, Petros Nihoyannopoulos10, Frank E. Silvestry7, Jean-Louis Vanoverschelde11, and Linda D. Gillam12‡ Document Reviewers: European Association of Echocardiography (EAE): Alec Vahanian, Vito Di Bello, Thomas Buck; American Society of Echocardiography (ASE): The ASE Guidelines and Standards Committee and the ASE Board of Directors 1 University Clinic San Carlos, Madrid, Spain; 2 University of Padua, Padua, Italy; 3 Mayo Clinic, Rochester, MN, USA; 4 University of Ottawa Heart Institute, Ottawa, Ontario, Canada; 5 University of Porto, Porto, Portugal; 6 Columbia University Medical Center, New York, NY, USA; 7 University of Pennsylvania School of Medicine, Philadelphia, PA, USA; 8 San Raffaele Scientific Institute, Milan, Italy; 9 King’s College Hospital, London, UK; 10 Imperial College London, Hammersmith Hospital, NHLI, London, UK; 11 Cliniques Universitaires Saint-Luc, Brussels, Belgium; and 12 Gagnon Cardiovascular Institute, Morristown, NJ, USA Received 17 May 2011; accepted after revision 19 May 2011 The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Transcatheter aortic valve implantation †Transcatheter mitral repair †Transcatheter paravalvular leak closure †Echocardiography Introduction Until recently, transcatheter therapy for valvular heart disease was limited to balloon valvuloplasty. However, the introduction of devices for transcatheter aortic valve implantation (TAVI), mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, anticipating growing use of transcatheter valve therapies and, along with it, an expanding need for informed echocardiographic evaluation, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed these recommendations. It is intended that this document *Corresponding author. Tel/fax: +34 91 544 8940, Email: [email protected] † Writing Group chair (EAE). ‡ Writing Group co-chair (ASE); writing group members are listed in alphabetical order. Published on behalf of the European Society of Cardiology. All rights reserved. &The Author 2011. For permissions please email: [email protected] European Heart Journal (2011) 32, 2189–2214 doi:10.1093/eurheartj/ehr259 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 70 will complement the earlier ASE guideline for Echocardiographyguided interventions 1 and will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease. Transcatheter aortic valve implantation TAVI is a new technique with the potential for transforming the treatment of patients with aortic stenosis (AS). The technology is currently being evaluated in patients with severe symptomatic AS who are at high risk for conventional open heart surgery or considered inoperable. In the future, however, there may be expanded indications for TAVI. At this stage of development, TAVI remains a challenging technology that requires a multidisciplinary team approach involving interventional cardiologists, surgeons, anaesthesiologists, and imaging specialists. Imaging indeed plays a central role in successfully implementing TAVI as it is needed at each step of the procedure including patient selection, choice of procedural access, prosthetic choice and sizing, procedural guidance, and detection of early and late complications. Introduction In April 2002, Cribier et al. 2 reported the first successful implantation of a bovine pericardial bioprosthesis mounted within a stainless steel balloon-expandable stent in a patient with severe AS who presented in cardiogenic shock. After this first-in-man implantation, the procedure was attempted on a compassionate basis in several other patients with an equine pericardial modification of the original valve design. Valve placement was initially done via an antegrade transseptal approach. This was a challenging procedure, owing to the need for transseptal puncture, the tortuous navigation of the valve assembly across the mitral and aortic valves, and the guide wire interaction with the mitral valve apparatus, which often caused severe mitral regurgitation (MR). These limitations prompted technical improvements in the size and steerability of the delivery system which allowed for the development of the more practical retrograde transfemoral approach. Additional changes in the structure of the valve (processed bovine pericardium and extended skirt height) resulted in the Edwards SAPIENTM valve. For patients with poor peripheral vascular access, a transapical approach was subsequently developed. 3 The SAPIENTM valve received European approval (CE Mark) for both transfemoral and transapical approaches in 2007. In 2005, Grube et al. 4 first reported the use of a different type of percutaneous valve system designed for the aortic position, the CoreValveTM system. This received CE mark in 2007. The CoreValveTM valve is self-expandable and offers the advantage of being self-centring and partially repositionable. Expansion and refinement of transcatheter approaches for aortic valve implantation is an area of active research and development with a variety of devices in the pipeline, but only the SAPIENTM and CoreValveTM valves have been approved. Both have been reported to have excellent flow characteristics with core-lab-adjudicated mean aortic valve area (AVA) and mean gradient at 1 year of 1.5 cm 2 and 11 mmHg, respectively, for the SAPIENTM valve, 5 and site-reported mean gradients of 8 mmHg at 1 year for the CoreValveTM. 6 Current status of Edwards SAPIENTM and CoreValveTM systems in Europe and North America European approval of both the Edwards SAPIENTM and CoreValveTM valves was granted in 2007, in the absence of a randomized trial and depending on data from a series of relatively small studies and registry reports. A newer generation modification of the Edwards valve, the Edwards SAPIENTM XT, received CE mark in 2010. Both the SAPIENTM and CoreValveTM valves are available in Canada for compassionate use for the treatment of patients with severe AS who are considered inoperable or at very high surgical risk. Although neither of these valves has been approved for commercial or compassionate use in the USA, the Edwards SAPIENTM valve was approved for use as an investigational device in a pivotal trial (PARTNER US; Placement of AoRTic traNscatheterER valves) and results were recently published. 5,7 A US randomized multicentre trial evaluating the CoreValveTM valve is underway, and a US randomized multicentre trial evaluating the SAPIENTM XT valve has been approved. Transcatheter aortic valve prostheses Echocardiographers need to be familiar with the design of the two available prostheses, the Edwards SAPIENTM valve and the Medtronic CoreValveTM valve. Each valve has specific characteristics and different aortic anatomic requirements. Thus, a precise echocardiographic evaluation is essential for appropriate patient selection ‘The Edwards SAPIENTM valve’ is a balloon-expandable valve based on Cribier’s original design. 2 The current-generation valve is composed of a cylindrical stainless steel balloon-expandable stent into which three symmetric leaflets made of bovine pericardium are mounted (Figure 1A). The stent also has a polyethylene terephthalate fabric skirt that decreases paravalvular leaks. The valve is available in two sizes, oversized in relation to the aortic annulus to reduce the degree of paravalvular regurgitation (PVR); a 23 mm prosthesis for transverse aortic annular diameters of 18–21 mm (measured at the level of aortic cusp insertion) and a 26 mm prosthesis for aortic annular diameters of 22–25 mm. The valve may be deployed via a transfemoral or transapical route. Because of the large valve size, sheath size is a significant factor with respect to procedural complications. A newer generation valve, the Edwards SAPIENTM XT as well as NovaFlexTM transfemoral and AscendraTM transapical delivery systems, has recently received CE mark in Europe. The delivery system has a smaller calibre (18 F) and the valve stent is thinner and comprised a cobalt-chromium frame (Figure 1B), providing improved radial strength and enhanced circularity. Transfemoral ‘retrograde’ delivery technique Transfemoral placement is undertaken using an introducer sheath with an internal calibre of 22 or 24 F depending on the valve size. 8,9 After femoral artery vascular access is achieved, a balloon aortic valvuloplasty is performed during rapid right ventricular pacing. Subsequently, the stented valve, crimped onto the delivery J.L. Zamorano et al.2190 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 71 balloon, is advanced under fluoroscopic guidance, using a manually deflectable-guiding catheter that facilitates atraumatic navigation of the valve around the aortic arch and centring the guide wire through the native valve commissures. The valve is then positioned in a subcoronary position using fluoroscopic and/or transoesophageal echocardiography (TEE) guidance. Once the proper position has been achieved, the valve is deployed under rapid right ventricular pacing. Transapical delivery technique This more invasive approach requires an anterolateral minithoracotomy, ideally performed in a hybrid operative suite. Prior to the creation of a sterile field, the location of the apex is identified by palpation and confirmed by transthoracic echocardiography (TTE). Subsequently, the pericardium is opened near the left ventricular (LV) apex, a sheath is inserted directly into the LV cavity, and a guide wire is used to cross the aortic valve under fluoroscopic and TEE guidance. Aortic balloon valvuloplasty is then performed during rapid pacing after which the 26 F sheath is inserted permitting deployment of the prosthetic valve. Procedural success and early clinical outcomes Recent preliminary data reported from the SAPIENTM Aortic Bioprosthesis European Outcome SOURCE Registry, 10 a clinical post-commercialization ‘real-world’ registry of patients undergoing TAVI with the Edwards SAPIENTM valve, included 1038 consecutive patients (575 apical and 463 transfemoral) from 32 sites. Overall short-term procedural success was 93.8%. The incidence of valve embolization and coronary obstruction was 0.6 and 0.3%, respectively. Thirty-day mortality was 6.3% in transfemoral patients and 10.3% in transapical patients. Illustrating the steep learning curve with the procedure, Webb et al., 11 reporting a single institution’s experience of 113 patients noted that mortality fell from 12.3% in the initial half to 3.6% in the second half of the experience. In the report of 1-year results for Cohort B of the PARTNER trial (inoperable patients randomized to either TAVI or medical therapy including valvuloplasty), 1-year survival was 50.7% in the TAVI arm vs. 30.7% in the medical arm. 5 This is the only randomized trial to date comparing TAVI with surgery or medical therapy. The results of Cohort A [699 high-risk surgical patients, Society of Thoracic Surgeons (STS) score ≥10 or a predicted operative mortality ≥15%, randomized to either surgery or transfemoral/transapical valve implantation, depending on vascular access] were recently presented, 7 showing non-inferiority with regard to mortality at 1 year. In both PARTNER and the 1-year SOURCE reports, vascular complications at the time of intervention were associated with reduced survival. ‘The CoreValveTM ReValving system’ prosthesis consists of porcine pericardial tissue sewn to form a trileaflet valve mounted within an asymmetrical self-expanding nitinol frame (Figure 2). Once deployed, the point of coaptation of the leaflets is supra-annular. The current-generation nitinol frame is .50 mm in length and is hourglass-shaped. The lower portion of the frame affixes the valve to the LV outflow tract (LVOT) and Figure 2 The CoreValveTM ReValving system. Figure 1 (A) The Edwards SAPIENTM valve and (B) the Edwards SAPIEN-XTTM valve. Use of echocardiography in new transcatheter valvular interventions 2191 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 72 has the greatest radial strength, but care must be taken not to impinge on the anterior mitral leaflet. The mid-portion of the prosthesis has a constrained waist that must be deployed at the level of the sinuses of Valsalva and the coronary ostia, so as not to jeopardize coronary flow. It has a high radial force to firmly anchor the prosthesis and prevent migration or paravalvular leakage. Finally, the upper section (outflow) has the lowest radial force and is designed to fix and stabilize the prosthesis in the ascending aorta. The prosthetic size is determined by the external diameter of the ventricular end; the 26 and 29 mm prostheses have midportion diameters of 22 and 24 mm, aortic end-diameters of 40 and 43 mm, and prosthetic lengths of 55 and 53 mm, respectively. The 26 mm prosthesis is designed for patients with aortic annular diameters of 20–23 mm, whereas the 29 mm prosthesis is suitable for patients with 24–27 mm aortic annuli. However, the design of this prosthesis, with a broader upper segment to secure it to the ascending aortic wall, mandates that the height and width of the aortic sinuses and the ascending aortic diameter be carefully measured. In the presence of ascending aortic diameters .45 mm and/or aortic annular diameters ,20 or .27 mm, this device should not be implanted. The delivery system of the CoreValveTM has evolved from an initial 25 F to the current 18 F device, which allows completely percutaneous arterial access and the possibility of avoiding general anaesthesia. CoreValveTM delivery technique The CoreValveTM is designed for retrograde delivery through arterial access, although there are case reports of deployment using a transapical route. 12 Vascular access can be obtained with or without standard surgical cut down of the common iliac, common femoral, or subclavian arteries. The procedure can be performed under general anaesthesia or with local anaesthesia in combination with mild systemic sedation/analgesia. After femoral artery access has been secured, a balloon aortic valvuloplasty of the calcified stenotic aortic valve is performed during rapid right ventricular pacing. After this valvular dilation, the prosthesis is deployed and implanted retrogradely over a stiff guide wire. Postdilation of the CoreValveTM prosthesis can be performed at the discretion of the operator depending on the perceived proper placement of the device angiographically and the degree of aortic regurgitation. Procedural success and early clinical outcomes Recently, Piazza et al. 13 reported procedural success and outcomes at 30 days in 636 patients with symptomatic AS, who underwent implantation with the third-generation CoreValveTM during the first year of the multicentre expanded CoreValveTM evaluation registry. Procedural success was achieved in 97.2% patients. Procedural death occurred in 1.5% of the patients. The combined incidence of procedural death, myocardial infarction, and stroke was 2.5%. At 30 days, all-cause mortality was 8%, one half of these deaths being judged to be procedure-related. Permanent pacemaker implantation was needed in 9.3% of the patients. TTE performed prior to discharge demonstrated a significant reduction in mean transaortic pressure gradients (from 49 +14 to 3 + 2 mmHg). Patient selection for transcatheter aortic valve implantation Appropriate screening and patient selection, based on clinical criteria and careful analysis of cardiovascular anatomy, is crucial for the success of TAVI. Selection of candidates is complex and involves a multidisciplinary team evaluation and the use of multiple imaging modalities in order to fully delineate the anatomy of the aortic valve, aorta, and peripheral vasculature. Although not the focus or scope of these recommendations, the clinical criteria for patient selection are briefly described below. Clinical criteria The consensus statement on TAVI from 2008 recommends the use of this procedure in high-risk patients or those with contraindications for surgery. 14 Risk evaluation is usually performed using the Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) and/or the STS Predicted Risk of Mortality Score. High surgical risk is defined by a logistic EuroSCORE of ≥15–20% or an STS mortality risk score of ≥10%. However, these scores have clear limitations and their predictive capacity may be reduced in high-risk patients who represent a small proportion of the population from which the scores were constructed. Moreover, the suitability of these scores for assessing risk during TAVI has been questioned 15 since co-morbidities that are less significant for TAVI considerably increase the risk of surgical aortic valve replacement (AVR), especially in elderly patients. Patient characteristics that might favour TAVI over AVR include prior cardiac surgery with grafts and/or adhesions, previous chest radiation therapy, porcelain aorta, liver cirrhosis, pulmonary hypertension, right ventricular failure, or marked patient frailty. 16,17 Nevertheless, TAVI is not recommended for patients whose life expectancy is less than 1 year or who cannot expect significant improvement in quality of life. 14 In clinically suitable patients for TAVI, the evaluation of the size, tortuosity, and calcification of peripheral arteries by angiography, multislice computed tomography (MSCT), or magnetic resonance imaging assists in choosing between transfemoral and transapical approaches. 18 Echocardiographic evaluation Echocardiography is critical in the assessment of candidates for TAVI, providing both anatomic and haemodynamic information. Transthoracic echo Transthoracic echo plays a key role in establishing the presence of severe AS with Doppler assessment of peak and mean transaortic gradients as well as AVA calculation by the continuity equation. 19 According to the current guidelines, severe AS is defined by an AVA of ≤1 cm 2 (,0.6 cm 2 /m 2 ) or a mean aortic valve gradient of ≥40 mmHg. 20,21 However, the requirements for SAPIENTM implantation as defined in the PARTNER trial are a valve area of ,0.8 cm 2 , a peak transvalvular velocity of ≥4 m/s and/or a mean gradient of ≥40 mmHg, targeting patients with particularly severe (critical) stenosis. Although a full discussion of the pitfalls in diagnosing severe AS is beyond the scope of this document, two groups where the diagnosis of severe AS may be challenging should be noted. Patients J.L. Zamorano et al.2192 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 73 may present with low gradients, despite valve areas within the severe range in the presence of severe LV systolic dysfunction. This may pose the dilemma of distinguishing between true severe AS and pseudo-severe AS in which reduced LV systolic function contributes to the reduction in calculated valve area. Dobutamine stress echocardiography has been shown to distinguish between the two and provide useful information concerning contractile reserve. 22 Additionally, attention has recently been focused on patients with low gradients and normal LV ejection fraction but low flow AS 23 for whom calculation of projected valve area under normal flow states may be useful. Cardiac catheterization is no longer recommended for determining the severity of AS, except in exceptional cases with conflicting data on echocardiography. 20,21 Once the diagnosis of severe valvular AS is clear, echocardiography must determine whether the patient’s anatomy is suitable for TAVI. Using TTE, assessing the annular dimension and detailed anatomic characteristics of the aortic valve, including the number, mobility, and thickness of cusps, as well as the extent and distribution of calcification should be described. Currently, bicuspid aortic valve is an exclusion criterion for TAVI because an elliptical valvular orifice may predispose to an increased risk of incomplete and incorrect deployment of the aortic prosthesis. Moreover, the risk of aortic complications, such as spontaneous aortic dissection, may be increased, due to abnormal arterial wall structure. 17 That said, cases of successful TAVI in bicuspid AS have been reported. 18 Accurate sizing is critical to TAVI procedural success. Annular dimension is a key measurement as this determines eligibility for TAVI and guides the selection of valve type and size. Prior sections have described criteria for selecting valve size based on aortic annular, sinus of Valsalva, and ascending aortic dimensions. Undersizing the prosthesis can result in device migration or significant paravalvular aortic regurgitation. Moreover, even if severe procedural complications do not occur, prosthesis mismatch may result. Oversizing predisposes to complications related to vascular access or to difficulties when crossing the native aortic valve with the delivery system. There is also the risk of under-expansion with consequent redundancy of leaflet tissue, creating folds that will generate regions of compressive and tensile stress that may cause central aortic regurgitation or reduction in valve durability. 24 Annular diameter is typically measured in systole, in a parasternal long-axis view, zoomed on the LVOT. The measurement is taken at the point of insertion of the aortic valve cusps, from tissue–blood interface to blood–tissue interface—trailing edge to leading edge (Figure 3A), regardless of the degree of calcification of the aortic cusps. When transthoracic two-dimensional (2D) echocardiographic measurements of the annulus are uncertain, particularly if measurements are near critical cut-offs for valve selection or if calcification extends from the aortic valve onto either the anterior mitral leaflet or the septum, TEE +3D evaluation may be necessary. The resolution of 3D TTE is currently inadequate for assistance in annular measurements in most subjects. LV and right ventricular dimensions and function, aortic regurgitation, and the structure and function of the other valves should be evaluated. 25 The presence of haemodynamically significant LVOT obstruction due to basal septal hypertrophy represents a contraindication as septal hypertrophy is a potential cause of prosthesis displacement during or after implantation. These patients are potential candidates for myomectomy. The presence of an LV thrombus must be excluded, as it represents a contraindication to the procedure. The presence of a patch in the LV as well as significant pericardial calcification is a contraindication for TAVI using the transapical approach. 14 Transoesophageal echo TEE is recommended prior to TAVI if there are any concerns about the assessment of the aortic root anatomy, aortic annular size, or number of cusps. Since patients with symptomatic AS tolerate hypotension poorly, sedation should be performed carefully with an emphasis on effective topical anaesthesia. The aortic root is a direct continuation of the LVOT and extends from the basal attachment of the aortic valvular cusps to the level of the sinotubular junction. 24 The diameter of the root varies considerably along its length, but it is the annular diameter at the level of the basal attachment of the aortic valve cusps, measured in systole, that dictates the size of the prosthesis, irrespective of the type of the valve inserted (Figure 3B). TEE aortic annular measurements correlate well with TTE, although the latter underestimates TEE-measured aortic annular size with a mean difference of 1.36 mm (95% confidence interval, 1.75–4.48 mm). 26 There is concern that the assumption of annular circularity made by 2D echo may result in erroneous annular measurements in patients whose annuli are more ovalshaped. However, a strategy based on 2D TEE measurements has been shown to provide good clinical results when compared with MSCT. 27 Currently, there is no consensus regarding the gold standard imaging technique for annular sizing, although, from a practical perspective, TTE performs this task adequately in most patients. Transoesophageal echocardiography protocol The pre-procedure TEE evaluation may be performed as part of screening or as the initial step of intra-procedural monitoring. Using the long-axis view (usually around 110–1308), the LVOT and upper septum should be assessed since the presence of a subaortic septal bulge may create an obstacle to proper seating of the aortic prosthesis. 24 Using short-axis views, the opening of the aortic valve should be classified as central or eccentric and the severity, location, and symmetry of aortic valve calcification accurately described. During TAVI, the prosthesis anchors according to the resistance of the subleaflet tissue. During implantation, the native cusps are crushed against the aortic wall and the differences in the tension–force across the valve may cause asymmetric deployment of the prosthesis and contribute to the risk of compression of the coronary arteries during TAVI. 8 In order to minimize the risk of coronary occlusion, it is essential to know the distance from the aortic annulus to the ostia of the coronary arteries and to compare this with the length of the cusps measured in a long-axis view. Although the cusps are typically shorter than the annular-ostial distances, patients in whom the cusp length exceeds the annular-ostial distances are at risk of ostial coronary occlusion when the valve is deployed and the Use of echocardiography in new transcatheter valvular interventions 2193 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 74 native cusps crushed to the side. Although the determination of the right coronary annular-ostial distance should be possible with 2D TEE (Figure 4), measurement of the left coronary annular-ostial distance requires 3D TEE (see below) or MSCT. It is also important to assess the characteristics of the ascending aorta, the aortic arch, and the descending thoracic aorta since the presence of aortic arch atheromas may increase the risk of peri-procedural embolization and therefore favour a transapical approach. Peri-procedural echocardiography during transcatheter aortic valve implantation Two-dimensional echocardiography Although TTE clearly plays an important role in patient selection for TAVI, its role during the actual procedure is limited. In patients undergoing TAVI via a transapical approach, TTE can be helpful in locating and marking the position of the LV apex in order to guide the thoracotomy. However, there are a number of points to remember when doing this: (i) it is important to use two orthogonal TTE apical views; (ii) the apex should be located with the surgeon and echocardiographer on the same side of the patient so that both can agree on the optimum intercostal space; and (iii) once the skin is marked with the optimal position, it is essential that the patient and/or the skin not be moved. Such movement may occur as surgical drapes are being applied and may change the position of the skin mark relative to the ribs. The use of peri-procedural TEE is variable. The technique can aid balloon positioning during valvuloplasty, detect postvalvuloplasty aortic regurgitation, aid prosthesis positioning during implantation, confirm prosthesis function immediately postimplantation, and rapidly detect complications. However, the use of peri-procedural TEE usually requires general anaesthesia and the probe may also partially obstruct the optimal fluoroscopic view. Therefore, some operators feel that these disadvantages outweigh the many advantages of peri-procedural TEE. However, it should be noted that the transapical approach will always require general anaesthesia anyway and some centres have reported transfemoral implantation with TEE guidance using only moderate sedation. Moreover, to avoid obstructing the fluoroscopic view, the TEE probe may be retracted during the actual valve implantation and be rapidly repositioned following deployment. Transnasal TEE is a relatively new technique 28,29 that can be used to monitor TAVI. Although its image quality is not quite as good as conventional TEE and transnasal TEE does not currently have 3D capability, this approach could be considered in patients where general anaesthesia is not deemed appropriate. Some sites have also adapted intracardiac echo (ICE) for TAVI, although ICE poses additional challenges in securing adequate windows. As described more fully in a subsequent section, 3D TEE conveys certain advantages over 2D TEE during TAVI. For example, the 3D depth perspective makes it easier to visualize the position of the prosthesis on the balloon relative to the native valve annulus and surrounding structures. It also facilitates appreciation of the guide wire path through the LV and around the mitral valve subvalvular apparatus. Both transapical and transfemoral TAVI procedures commence with balloon valvuloplasty. This is designed to split the valve commissures and make subsequent valve implantation easier. TEE can be used to guide positioning of the balloon relative to Figure 4 The ostium of the right coronary artery can be identified using a long-axis view of the left ventricular outflow tract permitting the measurement of the annular-ostial distance and the length of the right coronary cusp. Figure 3 Annular sizing with two-dimensional transthoracic echocardiography (A) and transoesophageal echocardiography (B). The image should be aligned to avoid oblique measurements. J.L. Zamorano et al.2194 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 75 the aortic valve and is especially useful when the valve is not very calcified and, consequently, difficult to image on fluoroscopy. It may also help in the final decision-making concerning the appropriate valve size, because a valve with bulky calcification and small sinuses may require a smaller prosthesis than the annular dimension alone would suggest. Although balloon inflation is normally performed during rapid right ventricular pacing to reduce cardiac output, the balloon may still migrate during inflation, particularly in patients with extensive subaortic septal hypertrophy or a small sinotubular junction. Loss of right ventricular capture and premature restoration of the native rhythm may also result in balloon migration. TEE may be used to confirm a stable position during inflation and to monitor the behaviour of the calcified aortic cusps during inflation as they are pushed back into the sinuses and towards the coronary ostia (Figure 5A) During deployment of the prosthesis, TEE is very helpful in confirming the correct position of the valve and is usually used in conjunction with fluoroscopy for this purpose. In patients with limited native valve calcification or for valve-in-valve procedures where TAVI is used in the setting of another bioprosthesis, TEE may be the main technique used for guidance. The optimal position for the Edwards SAPIENTM valve is with the ventricular side of the prosthesis positioned 2–4 mm below the annulus in the LVOT. Examples of 2D TEE imaging during prosthesis positioning and deployment are shown in Figure 5Band C. Since the CoreValveTM has a different structure, the ventricular edge of the prosthesis should be placed 5–10 mm below the aortic valve annular plane. A normally positioned CoreValveTM is shown in Figure 6. Immediately following deployment, TEE is used to confirm satisfactory positioning and function of the prosthesis (Figure 7Aand B). This requires a combination of 2D imaging and Doppler evaluation with 3D also used if available. When the prosthesis is positioned too low, it may impinge on the mitral valve apparatus (Figure 8) or it may be difficult to stabilize in patients with marked subaortic septal hypertrophy. The native valve cusps may also fold over the top of the prosthesis and impede its function. If the prosthesis is implanted too high, it may migrate up the aorta, obstruct the coronary ostia, or be associated with significant PVR. It is important to confirm that all the prosthetic cusps are moving well, that the valve stent has assumed a circular configuration (using 2D or 3D views), and that there is no significant valvular or PVR. Some regurgitation through the prosthesis will be common, whereas the delivery apparatus and/or guide wire remain across the valve and may persist, to a lesser degree, after their removal as it may take a few minutes post-implant for the leaflets to completely recover from being crimped for deployment. Until this occurs, the cusps may not coapt completely and mild valvular regurgitation may be transiently observed. Transgastric TEE views with continuous-wave, pulsed-wave, and colour Doppler should be used to confirm satisfactory prosthetic Figure 5 (A) Two-dimensional transoesophageal echocardiography image of balloon inflation during valvuloplasty (arrow). Note electrocardiogram showing rapid right ventricular pacing. Image is aligned to show left ventricular outflow tract (LVOT), at 1208.(B) Two-dimensional transoesophageal echocardiography image showing lower edge of the valve crimped onto the balloon prior to deployment. Differentiating the valve from the balloon may be difficult and is facilitated with three-dimensional imaging. (C) Two-dimensional transoesophageal echocardiography image during valve deployment. Red arrows identify the ends of the stent while the yellow arrow identifies the balloon margin. Electrocardiogram displays rapid right ventricular paced rhythm. Figure 6 Shortand long-axis views (derived using a threedimensional transoesophageal echocardiography probe) of a normally deployed CoreValveTM. LVOT, left ventricular outflow tract. Use of echocardiography in new transcatheter valvular interventions 2195 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 76 functioning before the probe is finally removed. This window is essential to ensure that all regurgitant jets are detected (Figure 9). PVR, not infrequently with multiple jets, is common following TAVI, though trace to mild and with a benign stable course in the majority of patients. 30 On the other hand, severe aortic regurgitation may occur as a consequence of incomplete expansion or incorrect positioning of the device, restricted cusp motion, or inappropriate prosthetic size. 31 An undersized prosthesis is expected to be associated with paravalvular aortic regurgitation. In contrast, an oversized prosthesis may result in suboptimal stent expansion, impaired cusp mobility, and central aortic regurgitation. Moreover, in the presence of severe asymmetric calcification of the native aortic valve, deficient (asymmetric) accommodation of the stent may occur, causing PVR of varying severity. The approach to assessing post-TAVI aortic regurgitation is discussed in detail in a later section. However, in the context of the immediate postimplantation assessment, conventional criteria including using colour jet dimensions, vena contracta, pressure half-time, and quantitative Doppler may all be helpful. 32,33 Three-dimensional TEE is an additional tool to evaluate the early function of the bioprosthesis and define the severity and precise location of paravalvular and/or central regurgitation. 34 Additionally, the patient’s haemodynamic status and aortography may all help identify the patient with excessive regurgitation. In the case of moderate paravalvular aortic regurgitation, supplementary balloon dilation can be performed. However, the risk of aortic rupture, cusp trauma, and over dilatation of the stent, all of which might worsen central aortic insufficiency, must be considered. Aortic regurgitation has also been reported as a consequence of residual native aortic valve leaflet tissue prolapsing into the prosthesis, interfering with cusp motion and coaptation. This may result from deficient containment of residual native aortic tissue by the prosthesis 35 and/or positioning the valve too low. The extreme consequence of prosthesis mismatch (or failed pacing capture) is prosthetic embolism. If the embolization occurs towards the aorta, it might be resolved through successful transcatheter repositioning, but if it happens towards the LV, surgical removal is usually the only option. 36,37 During the procedure, the echocardiographer may be alerted to acute, severe hypotension. Possible explanations identifiable by TEE are cardiac tamponade secondary to wire perforation of the left or right ventricle, LV dysfunction, or severe aortic regurgitation. Left ventricular dysfunction with acute wall motion abnormalities may be secondary to ostial occlusion by fragment embolization or by an obstructive portion of the valve frame, sealing cuff, or native cusp. 8 Although this complication may be fatal, successful management of ostial occlusions with percutaneous angioplasty or bypass surgery has been reported. 38 Another possible complication of TAVI is sudden worsening of MR. This may occur due to right ventricular pacing (LV asynchrony) or as a consequence of prosthetic misplacement with Figure 7 Two-dimensional transoesophageal echocardiography images showing an optimally implanted SAPIENTM valve in (A) a diastolic long-axis view and (B) a systolic short-axis view, LVOT, left ventricular outflow tract. Figure 8 Two-dimensional transoesophageal echocardiography long-axis view of a SAPIENTM valve that has been implanted too low. Note the position of the strut adjacent to the anterior mitral leaflet. LVOT, left ventricular outflow tract; MV, mitral valve. J.L. Zamorano et al.2196 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 83 reverberation artefact/acoustic shadowing from the posterior valve ring, such that anteriorly located PVR may be difficult to identify. These technical difficulties also limit 3D TEE imaging, which is not as helpful as in the setting of mitral prostheses. In addition to mid-oesophageal longand short-axis views (Figure 24Aand B), the transgastric view should be routinely attempted and a good display of the LVOT can be obtained by using a longitudinal imaging plane at about 100–1208with leftward flexion of the transducer (Figure 24C). A zero-degree deep transgastric view with anteflexion and leftward angulation may also be helpful (Figure 24D). Paravalvular aortic regurgitation can usually be appreciated using these views, although the spatial resolution of images from this window may be inadequate to provide accurate localization of the paravalvular jet(s). In assessing aortic prosthetic valves, the location of the coronary arteries should be routinely assessed. A coronary ostium low in Figure 21 Schematic diagram for use in describing the location and extent of sites of paravalvular regurgitation using as main references the aorta (Ao) and the left atrial appendage (LAA). On the left is the echocardiographic view and on the right the anatomic view. Reprinted with permission from Luigi M. 80 Figure 20 Two-dimensional transoesophageal views in a patient with a mechanical mitral bileaflet prosthetic valve and paravalvular regurgitation. (A) The area of dehiscence is visualized as a defect (arrow) at the posterior aspect of the valve ring with demonstration of paravalvular regurgitation by colour-flow imaging. (B) The guide wire (arrows) has been passed through the defect. (C) The closure device (arrow) is open. (D) The closure device is positioned securely in the defect and colour-flow imaging shows only mild residual paravalvular regurgitation. LA, left atrium; LV, left ventricle. Use of echocardiography in new transcatheter valvular interventions 2203 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 84 the aortic sinus close to the valve ring may pose a significant technical problem in transcatheter paravalvular leak closure and affect the choice of closure device. 59,60 The left main ostium can usually be imaged with the transverse plane at the aortic sinus level with the aortic root in the short axis, although, as previously noted, measuring the annular-ostial distance requires 3D imaging. The proximal 1–2 cm of the right coronary artery can usually be visualized by slowly sweeping the aortic sinus from the annulus to the sinotubular junction using the transverse plane at 0–458 or in the long-axis view of the aortic root (1208) where it is seen to leave the aorta at 6 o’clock. The locations of the coronary ostia and orientation of the aortic sinuses (right coronary, left coronary, and non-coronary) serve as useful internal landmarks when communicating the location of the paravalvular jet(s) to the interventionalist. In addition to the jet width and jet area, a flow convergence area in the aortic root should be carefully sought. The presence of a clearly defined flow convergence not only pinpoints the location of dehiscence but also indicates that the regurgitation is significant. 33 Peri-procedural echocardiography during transcatheter repair of paravalvular regurgitation Although there is some experience is performing aortic paravalvular leak closure with ICE, TEE is considered to be an integral part of transcatheter closure of PVR 57,58,61 –63 and has a role in the selection of appropriate patients, facilitation of the procedure, and assessment of the results (Table 2). Since most patients should already have had a comprehensive TEE before being accepted for the procedure, usually only a brief goal-oriented preprocedure TEE is performed to confirm the location(s) and severity of PVR. A real-time 3D image using the zoom option can be acquired to provide the interventionalist with a display of the paravalvular defect, particularly in the mitral position. 57,59 However, care must be taken to avoid misdiagnosing areas of echo Figure 22 Transoesophageal three-dimensional view of a mechanical mitral bileaflet prosthetic valve from the atrial perspective. (A) The dehiscence (arrow) at the posterior aspect of the valve ring is seen. (B) The guide wire (arrows) has been passed through the dehiscence. (C) Following placement of the first occluder (arrow), a guide wire has been positioned to permit placement of a second occlude for residual regurgitation (not shown). (D) At the conclusion of the procedure, two adjacent occluders are present (double arrows). AV, aortic valve. Figure 23 Transoesophageal three-dimensional colour-flow imaging shows the origin of the paravalvular mitral regurgitant jet (arrow) at end systole. J.L. Zamorano et al.2204 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 85 drop-out as paravalvular defects and confirmation with colour mapping should be performed. In addition, volume sets are needed to measure the areas of dehiscence for device sizing and to display the associated regurgitant jet(s). If the dehiscence is large (exceeding 25% of the circumference), a single device is unlikely to be sufficient. Additionally, when the defect is larger than 25% of the circumference, the prosthesis may rock and it may be inadvisable to proceed with device closure because of the high risk of device embolization. 58,60 With small defects where closure may be contemplated to correct haemolysis, smaller and less bulky devices such as coils can be used for closure. 57,58 Since anticoagulation may have been withheld in these patients, thrombus formation on the prosthetic valve or within the cardiac chambers should be excluded. The presence of intracardiac thrombus increases the risk of thrombo-embolic events during the procedure and mandates that the procedure be postponed. When the antegrade approach is used, TEE may be used to guide the transseptal puncture and help minimize the risk of inadvertent puncture of the aorta or atrial wall. TEE also can help guide the passage of the guide wire and catheter through the defect (Figure 20B). Real-time 3D TEE has been shown to be particularly helpful in this regard (Figure 22Band Figure 25). Injection of contrast has also been used to identify the position of the tip of the catheter in relation to the defect. 58 During deployment of the Figure 24 Transoesophageal mid-oesophageal long- (A) and short-axis (B) views of an aortic mechanical bileaflet valve show two paravalvular aortic regurgitant jets (arrows), best seen in the short-axis view. The transgastric view with leftward flexion confirms the presence of the two jets (arrows) (C), but the deep transgastric view shows only one jet (D). LA, left atrium; LV, left ventricle. Table 2 Role of peri-procedural transoesophageal echocardiography in device closure for paravalvular regurgitation Confirm location(s) and severity of paravalvular regurgitation Exclude prosthetic and intracardiac thrombi or vegetations Facilitate guide wire and catheter placement Assess seating of the closure device Ensure proper functioning of the prosthetic valve Assess residual paravalvular regurgitation Detect complications such as air embolism or tamponade Figure 25 Real-time three-dimensional image from a left atrial perspective showing the path of the guide wire (arrow) as it passes through the interatrial septum (left), across the left atrium and through the paravalvular defect. Use of echocardiography in new transcatheter valvular interventions 2205 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 86 closure device, TEE helps to ensure proper positioning of the opened occluder over the paravalvular defect and proper seating of the device (Figure 20Cand D). Simultaneously, function of the prosthetic valve, particularly if this is a mechanical prosthesis, should be assessed to ensure that the occluder does not impede proper opening and closing of the prosthetic leaflets/discs (Figure 26). With mechanical prosthetic valves, fluoroscopy should also be used to assess the motion of the leaflet(s). 58,62 The occluder device is not released until proper device seating and prosthetic valve function are assured. After release of the device, TEE is performed to assess residual PVR, which is not uncommon after the procedure (Figure 27D). If the residual regurgitation is severe, placement of additional devices can be considered (Figure 28). Other complications such as air embolism and haemopericardium can also be readily detected by TEE. 57,58 Percutaneous mitral valve intervention Introduction MR is an important cause of morbidity and mortality in developed countries. 64,65 The most common causes of MR are degenerative and functional (ischaemic and non-ischaemic), with an age-related epidemiological burden consisting of a peak incidence in patients over 70 years of age. 64 Open surgical correction, using mitral valve repair or replacement, is currently accepted as the best available treatment of MR. 21 However, there is a need for alternative treatment options. For example, a significant number of patients with severe MR are denied surgery on the basis of age, LV dysfunction, and/or co-morbidities. 66 The survival rate of these nonoperated patients is lower than that of those who undergo surgery. In addition, patients with less-than-severe MR that is uncorrected at the time of first cardiac surgery may develop significant MR over time and be denied reoperation on the basis of increased risk. In clinical practice, the presence of severe MR has favoured surgical over percutaneous revascularization in those with coronary artery disease, because of the need to perform concomitant mitral repair/replacement but access to transcatheter treatment of MR might permit simultaneous transcatheter revascularization and mitral repair as an alternative to surgery. Finally, some patients might need prophylactic MR correction in order to tolerate potentially high-risk therapies for non-cardiac disease. Thus, substantial efforts have been made to carry out less invasive mitral valve repair using various percutaneous strategies with the goals of decreasing morbidity and mortality and offering repair to patients at high risk for surgery. 67 As with surgical mitral repair, the echocardiographic assessment of mitral functional anatomy and the determination of the mechanism of MR are mandatory to select patients who can benefit from percutaneous intervention and to tailor the repair strategy. Both degenerative and functional/ischaemic MR can be suitable for percutaneous valve repair through a variety of approaches including those that offer direct leaflet repair, direct or indirect annular remodelling, and ventricular remodelling. Two-dimensional echocardiography supplemented by a real-time 3D imaging is also essential to guide and evaluate the effectiveness of the chosen percutaneous repair technique. Figure 26 Transoesophageal view in diastole before the procedure shows full opening of the disc of a mitral single leaflet mechanical valve (A), with no limitation to flow on colour-flow imaging (B). Following the implantation of an occluder device (arrow), the disc motion is restricted (C), and colour-flow imaging shows turbulent transvalvular flow (D). LA, left atrium. J.L. Zamorano et al.2206 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 87 Percutaneous therapies and current experience Percutaneous repair techniques can be categorized into four general approaches, the majority patterned on surgical interventions: (i) Indirect annuloplasty-coronary sinus techniques (ii) Direct annuloplasty (iii) Leaflet repair (iv) Ventricular remodelling Table 3summarizes the clinical experience with available devices for percutaneous mitral valve repair. However, it should be noted that this is a rapidly changing field with the frequent introduction of new devices and withdrawal/redesign of existing devices. Thus, subsequent paragraphs will focus on general principles of echocardiographic evaluation of the mitral valve that are applicable to all devices with a detailed discussion of procedural echocardiography limited to the MitraClipTM. This device has been most extensively evaluated and is, consequently, the only device with CE mark and the only device (while still investigational) that has completed pivotal trial evaluation and is available for compassionate use in the USA. Percutaneous annuloplasty techniques Percutaneous annuloplasty techniques mimic surgical annular remodelling in order to reverse mitral leaflet coaptation abnormalities and related MR. This approach is targeted to selected patients with functional/ischaemic MR and may be more effective when annular dilation/deformation is predominant. Based on surgical annuloplasty experience, common MR mechanisms that might be corrected by percutaneous annuloplasty include symmetrical leaflet tethering due to LV remodelling or leaflet coaptation loss arising from annular dilation. Hypothetically, patients with extreme asymmetrical tethering (especially when the posterior leaflet shows a tethering angle ≥458) might not be suitable for percutaneous annuloplasty. 68 However, an analysis of treatment failures with individual devices using detailed 3D echocardiographic imaging will be essential to identify better the subset of patients for whom device therapy might be most suitable. MR arising from structural mitral valve abnormalities, including prolapse/flail Figure 27 (A) Transoesophageal colour-flow imaging of an aortic mechanical bileaflet valve in short-axis shows two paravalvular regurgitant jets (arrows). (B) The guide wire (arrows) has been passed through the posterior dehiscence. (C) The occluder device (arrow) is deployed. (D) The posterior paravalvular regurgitant is no longer present, but the anterior regurgitant jet is again detected. LA, left atrium. Figure 28 Three-dimensional transoesophageal echocardiography image from a left atrial perspective demonstrating three closure devices (arrows) surrounding a bileaflet mitral prosthesis. Use of echocardiography in new transcatheter valvular interventions 2207 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 88 for ruptured chordae tendinae, fibrotic or calcified leaflet restriction, or annular calcification, should not be considered for this procedure. Indirect annuloplasty-coronary sinus techniques Coronary sinus annuloplasty attempts to re-shape the anteroposterior annular dimension to correct the mitral leaflet apposition– coaptation abnormality underlying the MR. The rationale of this approach is based on the anatomical relationship between the coronary sinus/great cardiac vein and the posterior annulus. Several techniques (Table 3) have been proposed that involve placing a device within the coronary sinus/great cardiac vein to attempt septal–lateral diameter reduction and/or mitral annulus ‘cinching’. To achieve therapeutic goals, transcoronary sinus approaches should provide an appropriate degree of tension to reduce MR without slipping and fracturing. The variable distance between the coronary sinus and the mitral annulus, as demonstrated by CT studies, may affect procedural success. In some patients, the coronary sinus is located above the annular level in contact with the left atrial wall. Annular devices in these patients theoretically would cinch the left atrial wall without annular re-shaping and therefore might not reduce MR. An additional concern of indirect annuloplasty is the risk of coronary ischaemic events due to the close but variable relationship between the coronary sinus and the left circumflex artery. 69 Finally, these devices pose at least a theoretical risk of coronary sinus thrombosis or rupture. Direct annuloplasty Some devices have proposed to remodel the annulus using a direct ventricular approach. Approaches used, to date, have included collagen shrinkage through the application of radiofrequency, 70 and transventricular suture annuloplasty. Mitral leaflet repair Percutaneous mitral leaflet repair aims to reproduce surgical techniques of improving leaflet coaptation and reducing/eliminating MR. The tested edge-to-edge Alfieri surgical technique 71,72 is mimicked by the percutaneous MitraClipTM system. Other experimental approaches, including chordal replacement or cutting, are currently under development. The MitraClipTM system is a polyester fabric-covered cobalt– chromium implant with two arms which can be opened and closed with a steerable-guiding mechanism (Figure 29). The MitraClipTM is easily imaged with TEE permitting reliable step-by-step procedural guidance as detailed below. Under general anaesthesia, an antegrade (transseptal) approach is used with the device aligned at the A2–P2 interface perpendicular to the commissure using a sophisticated guiding/positioning system and echocardiographic/fluoroscopic guidance. The device is deployed after successfully grasping the regurgitant target zone of the mitral leaflet. If needed, an additional clip may be placed to achieve satisfactory reduction in MR. The MitraClipTM system ............................................................................................................................................................................... Table 3 Approaches to percutaneous mitral repair Approach Device Manufacturer Clinical experience Coronary sinus annuloplasty 69 MONARC Edward Lifesciences EVOLUTION I and II trials with core-lab evaluation a CARILLON Cardiac Dimension AMADEUS trial PTMA Viacor PTOLEMY trial Direct annuloplasty 70 QuantumCor QuantumCor Pre-clinical testing Accucinch Guided Delivery Pre-clinical testing Percutaneous Annuloplasty System Mitralign First-in-man cases performed Ventricular remodelling 71,72,75 iCoapsys Myocor First-in-man cases performed Leaflet repair 77 MitraClip Evalve EVEREST I–II trial with core-lab evaluation Mobius Edwards Lifesciences Clinical studies without core-lab evaluation a EVOLUTION II trial suspended. Figure 29 MitraClipTM device for mitral repair. Arms of the device are in the open position. J.L. Zamorano et al.2208 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 89 is effective in selected patients with either degenerative or functional MR. In degenerative MR, the percutaneous clip anchors the flail and/ or prolapsed leaflet, whereas, in patients with functional MR, it improves coaptation of the tethered leaflet(s) to reduce the time and force required to close the valve. Additionally, the clip creates a tissue bridge between the two mitral leaflets. As a result, it limits annular dilatation and supports the durability of the repair. Finally, the clip restrains the LV wall by restricting LV dilatation and induces reverse LV remodelling, which, in patients with functional/ischaemic MR, may further reduce tethering and resultant regurgitation. The procedure has been tested in the safety–feasibility EVEREST I trial that reported procedural success, defined as successful implant with reduced MR ≤2+, in 79 of 107 (74%) patients. 73 All results were core-lab-adjudicated. The core-labadjudicated randomized controlled EVEREST II trial, comparing percutaneous vs. surgical repair, has recently been reported. 74 In the per-protocol analysis, MitraClipTM therapy was able to reduce MR in 72.4% of patients vs. 87.8% of patients treated surgically. The overall 30-day major adverse event rate (designed to show superiority) in the MitraClipTM arm was similar for both functional and degenerative MR patient subgroups, and both lower than the surgical control group. In addition, the MitraClipTM system demonstrated consistent results in both functional and degenerative MR patients with significant improvement at 1 year from baseline measures of heart function, symptoms, and quality of life, thus meeting the goal of the study to show non-inferiority to surgery. Other recent clinical experiences have been published, providing additional support to the EVEREST data. In a two-centre study, Tamburino et al. 75 reported 97% successful implantations in 31 high-risk patients with ischaemic or degenerative MR as defined by the EVEREST criteria. In a single-centre study of 51 subjects at high surgical risk, Franzen et al. 76 reported clinical improvement in 49 successfully implanted patients. However, unlike the EVEREST trials, neither of these studies had core-lab evaluation of MR. Long-term observational studies are needed to confirm the stability of MitraClipTM implantation, sustained MR reduction, and clinical improvement. Ventricular remodelling Devices based on the concept of ventricular remodelling have been designed in recognition of the fact that abnormal ventricular geometry with displacement of the papillary muscles is an important element in the pathogenesis of functional MR. Although a surgical approach to ventricular remodelling as a treatment for functional MR (CoapsysTM) has been evaluated in a core-lab-adjudicated trial and shown to have improved survival and fewer adverse events (although more MR) than the control surgical approach, 77 this and other ventricular remodelling devices remain experimental with meaningful extrapolation to transcatheter approaches yet to come. Assessment of the functional anatomy of mitral valve for percutaneous repair The mitral valve apparatus is a complex anatomic structure composed of the mitral annulus, two discrete leaflets (anterior and posterior), and chordae which attach both leaflets to anterolateral and posteromedial LV papillary muscles. Importantly, mitral geometry and function are also influenced by the geometry and function of the left atrium and LV. The posterior leaflet is further separated into three discrete, named scallops P1, P2, and P3 (from lateral to medial). Although the anterior mitral leaflet is typically not anatomically divided, its segments are named A1–A3 to mirror the segmentation of the opposing posterior leaflet scallops. The mitral annulus is a complex saddle-shaped structure with peaks anteriorly and posteriorly, and nadirs medially and laterally. The anterior aspect of the mitral annulus is a rigid fibrous band that is shared with the aorta (aorto-mitral fibrosa or curtain), whereas the remaining medial, lateral, and posterior aspects are more vulnerable to remodelling and distortion of shape. MR may occur due to diverse clinical and anatomic processes. The pathophysiological triad, a concept first described by Carpentier, separates the ‘disease’ that produces a mitral valve lesion, from the resulting ‘anatomic lesion’ that ensues from that disease, and the subsequent ‘type of valve dysfunction’ that results. Furthermore, Carpentier classified MR into three basic but distinct types of valve dysfunction. Type I dysfunction is characterized by normal mitral leaflet motion and is typically seen in atrial fibrillation with atrial and mitral annular dilation, as well as in endocarditis with valve perforation. Type II dysfunction is characterized by excessive systolic leaflet motion and is seen in degenerative mitral valve disease with prolapse and/or flail of the mitral leaflets. Type IIIa dysfunction is characterized by reduced leaflet motion in both systole and diastole as is seen in rheumatic mitral disease and Type IIIb dysfunction is characterized by reduced systolic leaflet motion, as is typically seen in patients with dilated cardiomyopathy or MR due to ischaemic LV remodelling. Considerations for edge-to-edge repair Percutaneous edge-to-edge repair may be accomplished with an implantable clip MitraClipTM that approximates the middle scallops of the mitral valve, creating a double orifice mitral valve. As such, the predominant mechanism of MR must originate from the central mitral scallops, A2 and P2. The guidelines for selection of patients for MitraClipTM mirror the selection criteria used in the two EVEREST trials. Patients with degenerative MR (Carpentier Type II dysfunction) with either prolapse or flail of the A2 and/or P2 scallops are candidates for the MitraClipTM, and in EVEREST II, represented approximately two-thirds of those evaluated. Similarly, patients with functional MR, either due to dilated cardiomyopathy or ischaemic LV remodelling, are also candidates provided the dominant MR jet arises from A2 to P2. In EVEREST II, these patients accounted for one-third of those enrolled. In EVEREST II, patients with significant MR originating from the medial or lateral aspects of the valve were excluded, as were those with rheumatic disease, endocarditis, and a mitral valve area of ,4 cm 2 . Relative contraindications also include abnormal thickness of the leaflets or calcification that would impede grasping by the device arms. Additional functional anatomic exclusions for percutaneous MitraClipTM repair exist. In patients with functional MR, those with a coapting surface length ,2 mm and/or a coaptation depth of .11 mm are excluded. In patients with degenerative Use of echocardiography in new transcatheter valvular interventions 2209 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 90 MR, those with a flail height of .10 mm and a flail width of .15 mm are excluded (Figures 30–33). Echocardiography for edge-to-edge clip repair Patient selection At present, patient selection involves a consensus between the patients and treating physicians as well as agreement that the patient is anatomically eligible based on TTE and TEE findings. Clinical indications include: (i) Patients who are at high risk for surgery (excessive comorbidity). This may include patients with advanced chronic obstructive airway disease, renal failure, diabetes mellitus, etc. (ii) Patients with previous cardiac surgery for whom any re-do operation increases the peri-operative risk. This includes patients with functional MR after CABG surgery. (iii) Patients who decline surgery. In addition to confirming the presence of 3–4+MR using the combined approach recommended by ASE/EAE guidelines, 45 echocardiography is used to determine anatomic suitability for the device. TTE is typically used as an initial screen but TEE, ideally with 3D, is necessary to confirm eligibility. For patients with functional MR, there needs to be sufficient leaflet tissue for mechanical coaptation. This is evaluated by TEE from the four-chamber view by measuring the coaptation length and depth. As previously noted, for optimal results, coaptation length must be ≥2 mm and coaptation depth ≤11 mm (Figure 30). Although an initial assessment may be performed with TTE, these parameters, particularly coaptation length, typically require TEE for precise measurement (Figure 31). For patients with flail mitral valves, the TEE view should be aligned to demonstrate the maximal excursion of the flail segment [typically mid-oesophageal zero degree angulated to show the A2–P2 scallops and/or the long-axis view of the LVOT Figure 30 Schematic representation of the requirements for MitraClipTM in patients with functional mitral regurgitation. Reprinted with permission from Feldman et al. 73 Figure 31 Transoesophageal echocardiography images depicting measurement of coaptation length (A) and coaptation depth (B). LA, left atrium; LV, left ventricle. J.L. Zamorano et al.2210 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Chapter 6 – EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease 91 (100–1608) that also shows these scallops]. The inter-commissural view (55–758) may also be helpful. The distance separating the tip of the flail segment from its opposing normally coapting leaflet is termed as the flail gap. Leaflet grasping is facilitated when this distance is ,10 mm (Figures 32 and 33). This measurement is readily accomplished with 2D TEE. Although 3D TEE provides the clearest delineation of the involved segment with en face views from the left atrial perspective, 3D quantitation is limited since there is no calibration of these views. However, adequate sizing can be achieved using the intercommissural 2D view with complementary information available in some patients using the transgastric short-axis view of the valve. The flail/prolapse width should be ,15 mm. TTE +TEE will also identify patients whose regurgitation is on the basis of rheumatic disease or endocarditis or who have other anatomic exclusions as described previously. Peri-procedural echocardiography Echocardiography is the primary imaging modality used at all stages of the percutaneous mitral clip procedure, complementing fluoroscopy. 78 Transseptal catheterization During the transseptal puncture, TEE is helpful in guiding precise positioning of the transseptal catheter, first in puncturing the atrial septum and second in positioning the MitraClipTM guiding catheter. The primary views are the mid-oesophageal short-axis view (30–608) and bicaval 908view at the level of the aortic valve. These can be simultaneously displayed with biplane imaging using 3D probes. The transseptal puncture should be performed through the posterior-mid aspect of the fossa in a posterior and superior direction. This is to facilitate the ultimate positioning of the clip delivery system. During transseptal puncture, TEE identifies the position of the needle tip by detecting the tenting it creates on the adjacent septum rather than on the basis of directly imaging the needle tip. The puncture site should sit 3.5–4.0 cm above the leaflets. If the position of the catheter is suboptimal, the needle may be repositioned prior to puncturing the septum. Advancing the clip delivery system towards the mitral leaflets Once the correct transseptal puncture has been made, the mitral clip delivery system is angled down towards the mitral leaflets, aiming for A2–P2. Correct positioning can be ascertained from the inter-commissural (55–758) projection demonstrating medial–lateral alignment and the LV outflow (100– 1608) projection demonstrating posterior–anterior alignment. Three-dimensional TEE (3D zoom with a large field of view) greatly facilitates this part of the procedure as it provides an en face view of the mitral leaflets and approaching clip (Figure 34). Figure 32 Schematic showing key measurements in selecting patients with mitral flail for MitraClipTM. Reprinted with permission from Feldman et al. 73 Figure 33 Two-dimensional transoesophageal image of a flail P2 scallop showing the measurement of the flail gap. Use of echocardiography in new transcatheter valvular interventions 2211 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Life after TAVI: a Clinical and Echocardiographic Appraisal 92 Positioning the clip above the regurgitant orifice and orientation of the clip arms The optimal position of the clip delivery system is immediately above the regurgitant orifice, which will be the target of the clip. The target orifice is chosen using the maximal PISA effect. The clip should be oriented perpendicular to the commissure, something easily assessed with 3D zoom imaging. However, if 3D is not available, the transgastric short-axis view may be used for this purpose. Entry into the left ventricle and pull-back to grasp the leaflets As viewed from the LVOT position (100–1608), the clip with the arms closed will cross the mitral leaflets and enter the LV. Here, 3D echo (or alternatively the transgastric short-axis view) permits a rapid check that the arms of the mitral clip device are still perpendicular to the line of coaptation as the delivery system may rotate as it is advanced. Once the delivery system is in the LV, the clip arms open and the device is pulled back towards the left atrium, simultaneously grasping both leaflets with the device grippers (Figure 35). Using the LV outflow and inter-commissural views (60–708), capture of both leaflets must be verified and the clip closed. If either leaflet is inadequately captured, the clip is reopened and re-advanced into the LV and the process is repeated. Once both leaflets have been satisfactorily clipped, a quick assessment of residual MR with colour Doppler is performed. Additionally, it is essential to exclude mitral stenosis, particularly if two clips have been deployed. This is accomplished by measuring the transvalvular gradient with continuous-wave Doppler and planimetering the two orifices using ideally 3D or alternatively transgastric short-axis views. If MR reduction is satisfactory and the degree of stenosis is acceptable (mean gradient ≤5 mmHg), the clip is fully deployed by detaching it from the delivery system. At this point, a final assessment of MR is performed. 79 If there is significant residual regurgitation and the source of the residual regurgitation is amenable to correction with a second clip, a second clip may be placed using a similar overall approach but using the first clip as a reference point. In assessing the degree of residual MR, it is important that the systolic blood pressure approximate normal values for the patient as functional MR, in particular, is afterload-dependent. Using 3D echocardiography, it is possible to observe the repaired valve en face from both atrial (Figure 36) and ventricular perspectives, documenting the eccentricity, if any, of the dual orifices created by the device. Moreover, 3D colour displays also provide good definition of the site(s) of any residual regurgitation (Figure 37). Detection of complications TEE provides a method for early detection of many of the potential complications of clip placement including perforation of the atrial wall, resulting in pericardial effusion, partial dehiscence of the Figure 34 Three-dimensional transoesophageal echocardiography image from the left atrial perspective showing the MitraClipTM delivery system directed towards the mitral orifice. Real-time three-dimensional imaging greatly facilitates the process of ensuring that the clip is appropriately directed/ aligned. MV, mitral valve. Figure 35 Two-dimensional transoesophageal echocardiography images showing the left ventricular outflow tract view used to monitor advancement of the MitraClipTM delivery system across the mitral valve (A), opening of the clip arms (B), and pull back across the valve with closure of the device arms to grasp the free edges of A2 and P2 (C). LA, left atrium; LV, left ventricle. J.L. Zamorano et al.2212 at Universidade do Porto on September 9, 2011eurheartj.oxfordjournals.orgDownloaded from Part IV – Conclusions 99 CONCLUSIONS • Patient’s evaluation before TAVI may require the use of multi-imaging modalities, namely echocardiography, multidetector computed tomography and angiography. • During TAVI, 2D and 3D transesophageal echocardiography, along with fluoroscopy can be used for procedure guidance, to identify possible complications and the final result. • Patients referred for TAVI commonly present severe left ventricular diastolic dysfunction, but it significantly improves immediately after the procedure. • Paravalvular aortic regurgitation is common at midterm follow-up after TAVI. • We proposed an alternative new methodology for paravalvular aortic regurgitation assessment after TAVI. Using vena contracta planimetry by 3D transthoracic echocardiography, we described an accurate methodology for paravalvular aortic regurgitation jet evaluation and severity classification. • TAVI significantly improves symptoms and quality of life in patients with severe aortic stenosis ineligible for conventional aortic valve replacement. Using the Minnesota Living with Heart Failure Questionnaire, we found an impressive improvement in physical and psychological dimensions at 6.5 months follow-up. • Patients with peripheral vascular disease had a less impressive improvement in quality of life after TAVI. • The echocardiographic assessment of patients undergoing TAVI places demands on echocardiographers that differ from those of the routine evaluation. In a partnership from the European Association of Echocardiography with the American Society of Echocardiography we presented the recommendations for the use of echocardiography in new transcatheter interventions, from patient’s selection to procedure guidance and follow-up. PART V Abstract Part V – Abstract 103 ABSTRACT Transcatheter aortic valve implantation (TAVI) has been recently recognized as an alternative treatment for patients with severe aortic stenosis ineligible for conventional aortic valve replacement. However, it is a demanding procedure that requires a multidisciplinary team approach, in which proper clinical evaluation and imaging play an essential part. This research was intended to improve the knowledge on transcatheter aortic valve implantation (TAVI), with a particular focus on the importance of the information provided by echocardiography. We aimed to describe the role of echocardiography on this procedure, to determine the acute hemodynamic effects of TAVI in left ventricular diastolic performance and to describe a new accurate methodology for paravalvular aortic regurgitation evaluation. Additionally we evaluated the results on quality of life at midterm follow-up after the procedure. We followed a cohort of patients referred for TAVI at Hospital Clínico San Carlos, Madrid, included from April 2009 to April 2010. Pre-procedure assessment included medical history, physical examination, transthoracic and transesophageal echocardiography, coronary angiography, aortography, iliac-femoral arteriography and when necessary, computed tomography angiography. 2D and 3D Transesophageal echocardiography was performed during the procedure. Quality of life assessment was performed before the procedure and at midterm follow-up, in conjunction with 2D and 3D transthoracic echocardiography. We described that 2D and 3D transesophageal echocardiography is useful for patients’ selection, procedure guidance and to evaluate possible TAVI complications. We found that patients referred for TAVI commonly present severe left ventricle diastolic dysfunction and it significantly improves immediately after the procedure. We created a new alternative methodology for paravalvular aortic regurgitation assessment. Using 3D transthoracic echocardiography, the vena contracta planimetry accurately recognizes moderate paravalvular aortic regurgitation. We found that TAVI, either transfemoral or transapical, significantly improves quality of life at midterm follow-up and that patients with peripheral vascular disease have a less impressive improvement in quality of life after TAVI. Part V – Abstract 105 RESUMO A implantação de válvula aórtica transcateter (TAVI) foi recentemente reconhecida como tratamento alternativo para doentes com estenose aórtica severa não elegíveis para substituição valvular aórtica convencional. Porém, a TAVI é um procedimento complexo que requer uma abordagem multidisciplinar e em que a avaliação clínica e imagiológica apropriada é fundamental. Esta tese teve como objectivo ampliar o conhecimento médico sobre TAVI, com enfoque particular na importância da ecocardiografia. Pretendemos descrever o papel da ecocardiografia, determinar os efeitos hemodinâmicos agudos da TAVI na função diastólica do ventrículo esquerdo, descrever uma nova metodologia para avaliação de insuficiência paravalvular aórtica e avaliar os resultados sobre a qualidade de vida a médio prazo após o procedimento. Efectuamos o seguimento de uma coorte de doentes referenciados para TAVI no Hospital Clínico San Carlos, Madrid, incluídos desde Abril 2009 a Abril 2010. A avaliação pré-procedimento incluiu história clínica completa, ecocardiograma transtorácico e transesofágico, angiografia coronária, aortografia, angiografia ilíaco-femoral e quando necessário angiotomografia cardíaca. Durante o procedimento efectuamos monitorização ecocardiográfica 2D e 3D. O questionário de qualidade de vida foi aplicado antes do procedimento e na avaliação aos 6 meses, data que o ecocardiograma transtorácico 2D e 3D foi repetido. Neste trabalho descrevemos a relevância da ecocardiografia transesofagica 2D e 3D na selecção dos doentes para TAVI, na monitorização durante o procedimento e na avaliação de possíveis complicações. Verificamos que os doentes propostos para TAVI apresentam frequentemente disfunção diastólica severa, mas que esta melhora significativamente imediatamente após o procedimento. Sugerimos uma metodologia alternativa para avaliação precisa da insuficiência paravalvular aórtica, utilizando a planimetria da vena contracta, adquirida por ecocardiografia transtorácica 3D. Finalmente, verificamos que a TAVI, por abordagem transfemoral ou transapical melhora significativamente a qualidade de vida a médio prazo e que os doentes com insuficiência vascular periférica apresentam uma melhoria de qualidade de vida menos marcada. ACKNOWLEDGMENTS In January 2009, I started what was meant to be a 3 months fellowship echocardiography training programme at Hospital Clínico San Carlos, Madrid. Immediately after my arrival, Professor José Zamorano realized my interest in advanced imaging modalities and especially on the imaging role in intervention. Our first conversations radically changed the course of my career. The excitement and the motivation for research made me apply to the European Association of Echocardiography research grant, which allowed me to pursuit the investigation we had begun and accomplish the publication of results. I am most grateful to Professor José Zamorano, for always ensuring that all the conditions for a proper investigation were provided, for a direct supervision of my work, and also for his generous friendship, for being always available and willing to move forward and for his endless enthusiasm and motivation to proceed. This was definitive for the success of this work. I would like to thank the exceptional colleagues from the Cardiovascular Institute that cheerfully received me and shared their knowledge in an environment of effective team work, enthusiasm and friendship. I would particularly thank to Dr. Carlos Almeria, Dr. Pedro Marcos-Alberca and Dra. Gisela Feltes, who actively participated in this investigation. Thank you to the staff from Hemodynamic Laboratory, Cardiac Surgery and personal from the Imaging Laboratory that always happily collaborated with the sole interest of contributing for the progress of our research. I would like to thank to Professor José Carlos Silva-Cardoso, my Co-Mentor, for supporting my projects, for being available for an active discussion of ideas and for transmitting the motivation to proceed. I am most grateful to Professor Mª Júlia Maciel, with whom I had the honour to learn Clinical Cardiology and who always gives me her confidence, plus the tools and the encouragement to go forward. I would like to thank Professor Ana Azevedo for her precious lesions on statistics and for her example of integrity and respect for science. My gratefulness to Dr. Ricardo Lopes, my dear friend and colleague, who supported me at all times in Porto and in our common stay in Madrid. Finally, I would like to thank to my family. My parents, Agostinho e Fátima, my grandmother Melinha and my brother Augusto. Thank you for being always there for me and for giving me the basis and the solid structure of home. Thank you to my cousin Fernanda, who is always nearby ready to help. At last my recognition goes to my other half, Bruno, who takes my projects seriously and always gives his bright understanding and contribution to make them better.