Valve Hemodynamics Following Transcatheter or Surgical Aortic Valve Replacement in Patients With Small Aortic Annulus

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Valve Hemodynamics Following Transcatheter or Surgical Aortic Valve Replacement in Patients with Small Aortic Annulus ˜ MD , Pierre Voisine MD , Leonardo Guimaraes Siamak Mohammadi MD , Dimitri Kalavrouzioutis MD , Eric Dumont MD , Daniel Doyle MD , Jean-Michel Paradis MD , ` MD , Jerome Wintzer-Wehekind MD , Robert Delarochelliere Lucia Junquera MD , David del Val MD , ´ Guillem Muntane-Carol MD , Afonso B. Freitas-Ferraz MD , Philippe Pibarot PhD , Franc¸ois Dagenais MD , ´ Josep Rodes-Cabau MD PII: DOI: Reference:

S0002-9149(19)31489-4 https://doi.org/10.1016/j.amjcard.2019.12.020 AJC 24348

To appear in:

The American Journal of Cardiology

Received date: Revised date: Accepted date:

4 September 2019 6 December 2019 12 December 2019

˜ MD , Pierre Voisine MD , Siamak Mohammadi MD , Please cite this article as: Leonardo Guimaraes Dimitri Kalavrouzioutis MD , Eric Dumont MD , Daniel Doyle MD , Jean-Michel Paradis MD , ` MD , Robert Delarochelliere Jerome Wintzer-Wehekind MD , Lucia Junquera MD , ´ David del Val MD , Guillem Muntane-Carol MD , Afonso B. Freitas-Ferraz MD , ´ Philippe Pibarot PhD , Franc¸ois Dagenais MD , Josep Rodes-Cabau MD , Valve Hemodynamics Following Transcatheter or Surgical Aortic Valve Replacement in Patients with Small Aortic Annulus, The American Journal of Cardiology (2019), doi: https://doi.org/10.1016/j.amjcard.2019.12.020

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1

Valve Hemodynamics Following Transcatheter or Surgical Aortic Valve Replacement in Patients with Small Aortic Annulus

Leonardo Guimarães, MD, Pierre Voisine, MD, Siamak Mohammadi, MD, Dimitri Kalavrouzioutis, MD, Eric Dumont, MD, Daniel Doyle, MD, Jean-Michel Paradis, MD, Robert Delarochellière, MD, Jerome Wintzer-Wehekind, MD, Lucia Junquera, MD, David del Val, MD, Guillem Muntané-Carol, MD, Afonso B. Freitas-Ferraz, MD, Philippe Pibarot, PhD, François Dagenais, MD, Josep Rodés-Cabau, MD

Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada

Running title: Aortic valve replacement and small aortic annulus Declaration of interest: Dr. Rodés-Cabau has received institutional research grants from Edwards Lifesciences, Medtronic, and Boston Scientific. The other authors have not reported any potential conflict of interest with respect to the content of this paper.

Corresponding author: Josep Rodés-Cabau, MD. Quebec Heart & Lung Institute, Laval University 2725 Chemin Ste-Foy, G1V 4GS Quebec City, Quebec, Canada E-mail: [email protected]

2 ABSTRACT This study aimed to compare the hemodynamic performance of transcatheter and surgical aortic valves in patients with severe symptomatic aortic stenosis and small aortic annulus (SAA) and to determine the valve hemodynamics according to transcatheter valve type. Consecutive SAVR and TAVR patients with SAA were case-matched (1:1) on the basis of sex, body surface area, aortic annulus diameter, and left ventricular ejection fraction. A total of 357 patients in each group constituted the final study population. A second match on the basis of aortic annulus diameter and valve/annulus calcium burden was performed within the TAVR group to compare the valve performance between balloon- (n=52) and self-expanding (n=52) transcatheter valve systems (BEV, SEV). The echocardiograms performed at hospital discharge were used for evaluating valve hemodynamics. The mean annulus diameter of the study population was 19.2±0.3 mm. The TAVR group (vs. SAVR) exhibited lower mean gradient (12±7 mmHg vs. 15±6 mmHg, p<0.001), larger EOA (1.46±0.39 cm2 vs. 1.25±0.37 cm2, p<0.001) and a lower rate of severe PPM (14% vs. 24%, p=0.001). Moderate-severe AR was present in 2.5% of the TAVR recipients vs. none patient in the SAVR group. There were no differences in valve hemodynamics between BEV and SEV, and similar rates of severe PPM were observed in both groups (p=0.488). In conclusion, TAVR presented superior valve hemodynamics and lower incidence of severe PPM compared to SAVR in SAA patients. Similar valve performance results were observed between transcatheter valve types. Key words: Aortic stenosis; small aortic annulus; transcatheter aortic valve replacement; surgical aortic valve replacement

3 INTRODUCTION TAVR has been associated with superior hemodynamic performance (lower residual transvalvular gradient, lower rate of severe PPM) compared with SAVR.1 Moreover, it has been suggested that TAVR may be preferable to SAVR in patients with SAA in order to avoid the adverse impact on suboptimal valve hemodynamics on left ventricular mass regression and survival.2 However, no studies to date have focused exclusively on patients with SAA undergoing SAVR or TAVR. Also, scarce data exist on valve hemodynamics according to different transcatheter valve types in patients with SAA.3,4 Thus, the objectives of our study were, in patients with severe symptomatic aortic stenosis and SAA, (i) to compare the hemodynamic performance of transcatheter and surgical aortic valves, and (ii) to determine the valve hemodynamics according to transcatheter valve type (balloon- vs. self-expanding transcatheter valve systems). METHODS A total of 7,864 consecutive patients underwent AVR (SAVR: 6,634, isolated SAVR: 1875, TAVR: 1,230) at our institution between 2007 and 2018. Of these, 944 patients with severe symptomatic aortic stenosis had a small aortic annulus (SAVR: 565, TAVR: 377) defined as an annulus diameter ≤ 21 mm as measured by transthoracic echocardiography. All patients were included in a prospective registry database. Patients were evaluated by the heart team and then selected for SAVR or TAVR according to the evidence available at different times during the study period. SAVR and TAVR patients were case-matched (1:1) on the basis of sex, body surface area, aortic annulus diameter, and left ventricular ejection fraction (LVEF) as determined by echocardiography.1 A total of 714 patients constituted the case-matched and final study population for the comparison between SAVR (n=357) and TAVR (n=357) recipients. The study flowchart

4 is presented in Figure 1. SAVR interventions were performed through standard midline sternotomy with cardiopulmonary bypass. The size of stented, stentless and sutureless valves was determined by the diameter of the aortic annulus as measured by precalibrated cylindrical sizers and proprietary valve sizers. The types of surgical bioprostheses used in this study were divided in 3 types: 1) stented valves: Mitroflow (Sorin), Mosaic (Medtronic), Epic (St Jude Medical), Perimount Magna Ease Pericardial (Carpentier-Edwards) and Trifecta (St Jude Medical), 2) stentless valves: SoloFreedom (Sorin), and 3) sutureless valves: Perceval (Sorin) and Enable 3f (Medtronic). The type of surgical bioprosthesis was determined by the cardiac surgeon responsible for the case. TAVR procedures were performed by a heart team using standard techniques, under general

anesthesia

or

sedation

with

fluoroscopy/angiography

and

transesophageal/transthoracic echocardiography guidance. The types of transcatheter aortic valves used were: 1) balloon-expandable valves: Cribier-Edwards, Edwards SAPIEN, SAPIEN XT and SAPIEN 3 (Edwards Lifesciences), and 2) self-expandable valves: Corevalve (Medtronic), EVOLUT R (Medtronic), Engager (Medtronic), Portico (St. Jude Medical), Acurate (Boston Scientific) and HLT Meridian (HLT). In a comparative analysis of the valve performance between balloon- and selfexpanding transcatheter valve systems, patients who received a SAPIEN XT/3 valve (n= 170) were matched (1:1) with those who received a CoreValve/Evolut R valve (n= 67) on the basis of aortic annulus diameter as evaluated by echocardiography and calcium burden of the aortic valve/annulus as determined by non-contrast computed tomography. A total of 104 patients were matched and constituted the final study population for the

5 comparison between balloon-expandable (n=52) and self-expandable (n=52) transcatheter valves. All echocardiographic data were collected prospectively at baseline and at hospital discharge (mean of 9±7 days and 5±3 days for SAVR and TAVR groups, respectively). PPM was considered moderate or severe when the indexed EOA was ≦ 2

2

2

2

0.85 cm /m and ≦0.65 cm /m , respectively. The indexed EOA may overestimate the severity of PPM in obese patients (body mass index ≧30 kg/m2), and lower cut-offs of 2

2

indexed EOA were used in such cases (i.e., ≦0.70 cm /m for moderate PPM and ≦0.55 cm2/m2 for severe PPM).5 The presence, degree, and type of aortic regurgitation (AR) was recorded in all patients. The degree of AR was classified as follows: none/trivial, mild, moderate, and severe.6 Categorical variables were reported as number (percent) and continuous variables as mean ± SD or median (IQR). Group comparisons were analyzed with the Student t test or Mann-Whitney U depending of variable distribution for continuous variables and the chi-square test of Fisher exact test for categorical variables. Propensity score matching analyses, using a one-to-one matching process, were performed to adjust intergroup (TAVR group vs. SAVR group) and balloon-expanding (SAPIEN XT/3) group vs. selfexpanding (CoreValve/Evolut R) group differences in selected baseline characteristics. A continuous propensity score analysis was performed to adjust for the intergroup clinical differences. Continuous variables were checked for the assumption of linearity in the logit and the graphical representations suggested linear relationships. Interactions between variables were allowed only if it was supported clinically and statistically (P<0.20). The goodness-of-fit of the model using the Hosmer-Lemeshow test indicated

6 that the final model had a good fit (χ2=3.64 with df=8; P=0.89). Matching was then performed on the propensity score without replacement of case and control subjects (1:1 matching) using the greedy algorithm. Differences were considered statistically significant when p < 0.05. The data were analyzed using SAS statistical software, version 9.4 (SAS Institute Inc., Cary, North Carolina). RESULTS Table 1 summarizes clinical, tomographic and echocardiographic baseline characteristics. TAVR patients were older and exhibited a higher risk profile. The majority of patients were women and had a small body surface area. The mean annulus dimeter of the study population was 19.2 ± 0.3 mm, with no differences between TAVR and SAVR groups in baseline echocardiographic characteristics (Table 1 and Figure 2). Valve sizes grouped according to aortic bioprosthesis type are shown in Table 2. In the TAVR group, 261 patients (73%) were treated with balloon-expanding valves and 234 patients (66%) received a ≤ 23 mm valve. Bigger valves (26 mm) were more frequent when using self-expanding transcatheter valve systems. The second most implanted transcatheter valve size was 26-mm (24%). Stented valves were used in 85% of all surgical procedures and the 21-mm valve size was the most commonly implanted in the SAVR group (46%). Aortic root enlargement and Bentall procedures were not used in SAVR patients. Doppler echocardiography data at hospital discharge in TAVR and SAVR groups are shown in Table 3. The TAVR group exhibited a lower mean transprosthetic gradient larger EOA and a lower rate of severe PPM (p≤0.001 for all). Moderate-severe AR was present in 2.5% of the TAVR recipients versus none patient in the SAVR group. The

7 results of a more contemporary subanalysis comparing the newer generation transcatheter valves (SAPIEN 3, EVOLUT R) and sutureless surgical valves are summarized in Table 4 and Figure 3. The newer generation transcatheter valves were associated with a lower mean gradient, larger EOA, and a tendency to lower incidence of severe PPM. There was only one patient (0.9%) in the TAVR group with residual moderate-severe AR. A total of 104 TAVR patients (52 balloon-expanding [SAPIEN XT/3], 52 selfexpanding [CoreValve/Evolut R]) were case-matched on the basis of aortic annulus diameter and valve/annulus calcium burden. The mean aortic annulus diameter was 19.2 ± 0.9 mm, and the median (IQR) valve/annulus calcium burden was 1104 (847-2253) Agatston units, with no differences between groups (annulus diameter: 19.1 ± 0.9 and 19.2 ± 0.9 mm in balloon- and self-expanding groups, respectively, p=0.379; calcium burden: 1324 (882-2336) and 1372 (811-2128) Agaston units in balloon- and selfexpanding groups, respectively, p=0.966). In the balloon-expanding group, 31 and 21 patients received SAPIEN XT and SAPIEN 3 valves, respectively, and in the selfexpanding group, 3 and 49 patients received CoreValve and EVOLUT R valves, respectively. Valve hemodynamic results according to transcatheter valve type as determined by echocardiography at hospital discharge are shown in Table 5. The mean transvalvular gradient and EOA were similar in both groups. The incidence of severe PPM was also similar between groups. There was one patient in balloon-expanding group (1.9%) and two patients in the self-expanding group (3.8%) with moderate-severe aortic regurgitation (p=0.558). DISCUSSION

8 The results of this study, which represents the largest series to date comparing the hemodynamic results of TAVR versus SAVR in patients with SAA, can be summarized as follows: 1) TAVR was associated with better valve hemodynamics (lower transvalvular gradient, larger EOA) compared to SAVR, with a much lower incidence (close to 2 times) of severe PPM, but a slightly higher rate of moderate-severe AR, 2) the improved valve hemodynamics associated with TAVR was maintained in the subgroup of patients receiving a newer generation transcatheter and surgical (sutureless) valves, 3) there were no significant differences in valve hemodynamics or residual moderate-severe AR between balloon- and self-expanding transcatheter valves. Multiple randomized trials have shown the overall superior hemodynamic results of TAVR vs. SAVR regarding post-operative transvalvular gradient and valve area.7–11 The present analysis, including a large cohort of contemporary real-world SAVR and TAVR patients, and using a strict methodology including the most relevant criteria impacting valve hemodynamics for the case-matching, confirmed the superior hemodynamic results of TAVR in patients with SAA, with a lower transvalvular gradient, larger EOA and a much lower rate (14% vs. 24%) of severe PPM. The ongoing VIVA trial (NCT03383445), a randomized study comparing valve hemodynamics following TAVR vs. SAVR in SAA patients, will provide definitive data about the optimal treatment of these patients. Few studies have compared the hemodynamic performance between TAVR and sutureless bioprostheses, with contradictory results.12–14 Our study, including a limited cohort of sutureless valve recipients, also showed the superior hemodynamics of the newer generation transcatheter valves vs. sutureless valves, with a rate of severe PPM

9 half as much in the TAVR group. Despite native calcified leaflet removal prior to valve implantation, the correct sizing process in sutureless valves can be difficult and excessive oversizing may be associated with increased gradients15, which may partially explain the observed differences between transcatheter and sutureless valves. However, these results need to be confirmed in future studies including a much larger cohort of patients. It is well known that TAVR is associated with a higher incidence of residual paravalvular leaks compared to SAVR.1,16,17 However, in the SAA population, the incidence of residual AR seems to be lower likely due to a better sealing of the aortic annulus (as compared to larger annulus dimensions) by the transcatheter valve.18 Additionally, the improved transcatheter valve sizing based on 3D computed tomography measurements of the aortic annulus along with the arrival of newer generation transcatheter valves with antiparavalvular leak properties have translated into dramatic reductions in residual leaks post-TAVR.19,20 In the present study, the rate of moderatesevere AR was as low as 2.5% (0.9% in those patients who received the newer generation Sapien 3 and Evolut R valves), suggesting that the good results of TAVR vs. SAVR regarding valve hemodynamics are only partially counterbalanced by slightly higher rates of residual AR. The supra-annular position of the valve leaflets in some transcatheter selfexpanding valves (e.g. CoreValve/Evolut valve system) has been suggested to result in better hemodynamics and lower PPM rates, but scarce and controversial data exist in patients with SAA.3,4,21–24 In our study including a combination of older and newer generation transcatheter valves systems, we failed to find any significant differences in valve hemodynamics between valve types. Although no reliable comparisons between

10 studies are possible due to the different methods used for annulus measurements (CT vs. echocardiography), the very small annulus diameter of our population (mean of 19 mm), the more extensive matching criteria (not limited to annulus diameter) used, and the combination of older and newer generation transcatheter valves, may explain some of the differences between studies. Study limitations. Although data was prospectively entered in a dedicated database, this analysis was of retrospective nature. Also, annulus diameter was assessed using echocardiographic measures since the vast majority of patients undergoing SAVR did not have a CT-angiography scan available. Valve performance was evaluated only at hospital discharge (and not at 30 days) and data was interpreted by experienced echocardiographers, but no central echocardiographic core lab was available. Moreover, detailed medical treatment and pressure status at echocardiographic assessment were not available. No aortic annular enlargement techniques were used in this study and most patients received stented surgical bioprostheses, which may have contributed to the inferior results of SAVR in this population. However, this series represents the real-world practice in a high surgical volume center, and probably reflects the usual treatment of SAA patients in many centers worldwide. Finally, no data was available in the SAVR group regarding symptoms and functional status at follow-up, and future studies are needed to evaluate the clinical impact of valve hemodynamic differences between groups. In conclusion, patients with severe aortic stenosis and SAA, TAVR was associated with superior valve hemodynamics and a much lower incidence of PPM compared to SAVR. These differences seemed to persist with the use of last generation transcatheter and surgical (sutureless) valves.

11

ACKNOWLEGMENTS Drs. Junquera, del Val and Muntané-Carol are supported by a grant of the Fundacion Alfonso Martin Escudero (Madrid, Spain). Dr. Rodés-Cabau holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions.

12 REFERENCES 1. 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. 2. Pibarot P, Weissman NJ, Stewart WJ, Hahn RT, Lindman BR, McAndrew T, Kodali SK, Mack MJ, Thourani VH, Miller DC, Svensson LG, Herrmann HC, Smith CR, RodesCabau J, Webb J, Lim S, Xu K, Hueter I, Douglas PS, Leon MB. Incidence and sequelae of prosthesis-patient mismatch in transcatheter versus surgical valve replacement in highrisk patients with severe aortic stenosis: a PARTNER trial cohort--a analysis. J Am Coll Cardiol 2014;64:1323–1334. 3. Rogers T, Steinvil A, Gai J, Torguson R, Koifman E, Kiramijyan S, Negi S, Lee SY, Okubagzi P, Satler LF, Ben-Dor I, Pichard AD, Waksman R. Choice of BalloonExpandable Versus Self-Expanding Transcatheter Aortic Valve Impacts Hemodynamics Differently According to Aortic Annular Size. Am J Cardiol 2017;119:900–904. 4. Abdelghani M, Mankerious N, Allali A, Landt M, Kaur J, Sulimov DS, Merten C, Sachse S, Mehilli J, Neumann FJ, Frerker C, Kurz T, El-Mawardy M, Richardt G, AbdelWahab M. Bioprosthetic Valve Performance After Transcatheter Aortic Valve Replacement With Self-Expanding Versus Balloon-Expandable Valves in Large Versus Small Aortic Valve Annuli: Insights From the CHOICE Trial and the CHOICE-Extend Registry. JACC Cardiovasc Interv 2018;11:2507–2518.

13 5. Lancellotti P, Pibarot P, Chambers J, Edvardsen T, Delgado V, Dulgheru R, Pepi M, Cosyns B, Dweck MR, Garbi M, Magne J, Nieman K, Rosenhek R, Bernard A, Lowenstein J, Vieira MLC, Rabischoffsky A, Vyhmeister RH, Zhou X, Zhang Y, Zamorano J-L, Habib G. Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2016;17:589–590. 6. Kappetein AP, Head SJ, Généreux P, Piazza N, Mieghem NM van, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, Es G-A van, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodés-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Am Coll Cardiol 2012;60:1438–1454. 7. 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, PARTNER Trial Investigators. Transcatheter versus surgical aorticvalve replacement in high-risk patients. N Engl J Med 2011;364:2187–2198. 8. Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, Doshi D, Cohen DJ, Pichard AD, Kapadia S, Dewey T, Babaliaros V, Szeto WY, Williams MR, Kereiakes D, Zajarias A, Greason KL, Whisenant BK, Hodson RW, Moses JW, Trento A, Brown DL, Fearon WF, Pibarot P,

14 Hahn RT, Jaber WA, Anderson WN, Alu MC, Webb JG. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med 2016;374:1609– 1620. 9. Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S, Oh JK, U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med 2014;370:1790–1798. 10. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, Mumtaz M, Adams DH, Deeb GM, Maini B, Gada H, Chetcuti S, Gleason T, Heiser J, Lange R, Merhi W, Oh JK, Olsen PS, Piazza N, Williams M, Windecker S, Yakubov SJ, Grube E, Makkar R, Lee JS, Conte J, Vang E, Nguyen H, Chang Y, Mugglin AS, Serruys PWJC, Kappetein AP, SURTAVI Investigators. Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med 2017;376:1321–1331. 11. Rodés-Cabau J, Pibarot P, Suri RM, Kodali S, Thourani VH, Szeto WY, Svensson LG, Dumont E, Xu K, Hahn RT, Leon MB. Impact of aortic annulus size on valve hemodynamics and clinical outcomes after transcatheter and surgical aortic valve replacement: insights from the PARTNER Trial. Circ Cardiovasc Interv 2014;7:701– 711. 12. Santarpino G, Pfeiffer S, Jessl J, Dell’Aquila AM, Pollari F, Pauschinger M, Fischlein T. Sutureless replacement versus transcatheter valve implantation in aortic valve stenosis: a propensity-matched analysis of 2 strategies in high-risk patients. J Thorac Cardiovasc Surg 2014;147:561–567.

15 13. Dionne PO, Poulin F, Bouchard D, Généreux P, Ibrahim R, Cartier R, Lamarche Y, Demers P. Early Hemodynamic Results in Patients With Small Aortic Annulus After Aortic Valve Replacement. Innovations (Phila) 2017;12:254–258. 14. Kamperidis V, Rosendael PJ van, Weger A de, Katsanos S, Regeer M, Kley F van der, Mertens B, Sianos G, Ajmone Marsan N, Bax JJ, Delgado V. Surgical sutureless and transcatheter aortic valves: hemodynamic performance and clinical outcomes in propensity score-matched high-risk populations with severe aortic stenosis. JACC Cardiovasc Interv 2015;8:670–677. 15. Cerillo AG, Amoretti F, Mariani M, Cigala E, Murzi M, Gasbarri T, Solinas M, Chiappino D. Increased Gradients After Aortic Valve Replacement With the Perceval Valve: The Role of Oversizing. Ann Thorac Surg 2018;106:121–128. 16. 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, PARTNER Trial Investigators. Transcatheter versus surgical aorticvalve replacement in high-risk patients. N Engl J Med 2011;364:2187–2198. 17. Hahn RT, Pibarot P, Stewart WJ, Weissman NJ, Gopalakrishnan D, Keane MG, Anwaruddin S, Wang Z, Bilsker M, Lindman BR, Herrmann HC, Kodali SK, Makkar R, Thourani VH, Svensson LG, Akin JJ, Anderson WN, Leon MB, Douglas PS. Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: a longitudinal study of echocardiography parameters in cohort A of the PARTNER trial (placement of aortic transcatheter valves). J Am Coll Cardiol 2013;61:2514–2521.

16 18. 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;2:821–827. 19. Binder RK, Webb JG, Willson AB, Urena M, Hansson NC, Norgaard BL, Pibarot P, Barbanti M, Larose E, Freeman M, Dumont E, Thompson C, Wheeler M, Moss RR, Yang T, Pasian S, Hague CJ, Nguyen G, Raju R, Toggweiler S, Min JK, Wood DA, Rodés-Cabau J, Leipsic J. The impact of integration of a multidetector computed tomography annulus area sizing algorithm on outcomes of transcatheter aortic valve replacement: a prospective, multicenter, controlled trial. J Am Coll Cardiol 2013;62:431– 438. 20. Puri R, Chamandi C, Rodriguez-Gabella T, Rodés-Cabau J. Future of transcatheter aortic valve implantation - evolving clinical indications. Nat Rev Cardiol 2018;15:57–65. 21. Nombela-Franco L, Ruel M, Radhakrishnan S, Webb JG, Hansen M, Labinaz M, Thompson C, Fremes S, Dumont E, DeLarochellière R, Doyle D, Urena M, Mok M, Ribeiro HB, Roifman I, Watkins S, Dumesnil JG, Pibarot P, Rodés-Cabau J. Comparison of hemodynamic performance of self-expandable CoreValve versus balloon-expandable Edwards SAPIEN aortic valves inserted by catheter for aortic stenosis. Am J Cardiol 2013;111:1026–1033. 22. Kaya D, Tanriverdi Z, Dursun H, Colluoglu T. Echocardiographic outcomes of selfexpandable CoreValve versus balloon-expandable Edwards SAPIEN XT valves: the comparison of two bioprosthesis implanted in a single centre. Int J Cardiovasc Imaging 2016;32:1371–1378.

17 23. Tarantini G, Purita PAM, D’Onofrio A, Fraccaro C, Frigo AC, D’Amico G, Fovino LN, Martin M, Cardaioli F, Badawy MRA, Napodano M, Gerosa G, Iliceto S. Long-term outcomes and prosthesis performance after transcatheter aortic valve replacement: results of self-expandable and balloon-expandable transcatheter heart valves. Ann Cardiothorac Surg 2017;6:473–483. 24. Enríquez-Rodríguez E, Amat-Santos IJ, Jiménez-Quevedo P, Martín-Morquecho I, Tirado-Conte G, Pérez-Vizcayno MJ, Gómez de Diego JJ, Arnold R, Aldazábal A, Rojas P, Agustín A de, Del Trigo M, Gutiérrez H, San Román JA, Macaya C, Nombela-Franco L. Comparison of the Hemodynamic Performance of the Balloon-expandable SAPIEN 3 Versus Self-expandable Evolut R Transcatheter Valve: A Case-matched Study. Rev Esp Cardiol (Engl Ed) 2018;71:735–742.

18

FIGURE LEGENDS Figure 1. Flowchart of the study population.

19 Figure 2. Hemodynamic comparison between TAVR and SAVR (Central Illustration). A. Effective orifice area and mean aortic gradient at discharge. B. PPM and severe PPM at discharge.

20

Figure 3. Hemodynamic comparison between transcatheter (SAPIEN 3, EVOLUT R) and sutureless surgical valves. A. Effective orifice area and mean aortic gradient at discharge. B. PPM and severe PPM at discharge.

21

Table 1. Baseline demographic, CT scan and echocardiographic characteristics, according to the type of aortic valve replacement (TAVR, SAVR). Variable Demographic characteristics Age (years) Female sex Body mass index (kg/m2) Body surface area (m2) Society of Thoracic Surgery – Predicted risk of mortality (%) Computed tomorgraphy data (n=226) Annulus minimal diameter (mm) Annulus maximal diameter (mm) Annulus mean diameter (mm) Valve/annulus calcium burden (Agatston units) Echocardiographic characteristics Aortic annulus diameter (mm) Indexed annulus diameter (mm/m2) Left ventricular ejection fraction (%) Peak aortic gradient (mmHg) Mean aortic gradient (mmHg) Moderate or severe aortic regurgitation Values are n (%), mean ± SD or median (IQR).

TAVR (n=357)

SAVR (n=357)

p value

80 ± 8 285 (80%) 27 ± 7 1.7 ± 0.2

74 ± 9 285 (80%) 27 ± 5 1.7 ± 0.2

<0.001 1.00 0.834 0.985

7.4 ± 5.1

3.0 ± 2.1

<0.001

19.9 ± 2.3 24.6 ± 3.0 22.3 ± 2.3

-

-

1673 (953-2545)

-

-

19.2 ± 0.9 11.6 ±1.3 57 ± 12 73 ± 27 44 ±18 80 (22%)

19.3 ± 0.9 11.6 ± 1.2 57 ± 10 71 ± 27 42 ± 18 71 (20%)

0.701 0.963 0.617 0.198 0.235 0.464

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Table 2. Distribution of label surgical prosthesis size according to the type of aortic bioprosthesis. Prosthesi s size (mm)

Transcatheter aortic valve replacement Balloonexpandabl e (n=261)

Selfexpanding(n=9 6)

Overal l (n=357 )

202 (77.4%)

25 26 27 29

25 (26.0%) 8 (8.3%)

49 (18.8%)

38 (39.6%) 6 (6.3%)

3 (1.1%)

Small Medium Large Values are n (%).

Stentl ess Sutureles (n=33 s (n=21) ) 6 (18.2%)

1 (4.8%)

Overall (n=357) 83 (23.2%)

7 (1.9%)

7 (2.7%)

21

23

Stented (n=303) 76 (25.1% )

19 20

Surgical aortic valve replacement

19 (19.8%)

227 (63.6% ) 8 (2.2%) 87 (24.4% ) 6 (1.7%) 22 (6.2%)

151 (49.8% ) 63 (20.8% ) 12 (4.0%)

13 (39.4%)

164(45.9 %)

14 (42.4%)

77 (21.6%) 12 (3.4%)

1 (0.3%)

1 (0.3%) 5 (23.8%) 12 (57.1%) 3 (14.3%)

5 (1.4%) 12 (3.4%) 3 (0.8%)

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Table 3. Valve hemodynamics following aortic valve replacement. Transcatheter Surgical aortic aortic valve valve Variable replacement replacement (n=357) (n=357) Left ventricular ejection 57 ± 10 57 ± 9 fraction (%) Peak transvalvular gradient 23 ± 12 29 ± 12 (mmHg) Mean transvalvular gradient 12 ± 7 15 ± 6 (mmHg) Effective orifice area (cm2) 1.46 ± 0.39 1.25 ± 0.37 Indexed effective orifice area 0.88 ± 0.25 0.75 ± 0.22 (cm2/m2) Moderate or severe aortic 9 (2.5%) 0 (0) regurgitation Moderate prosthesis-patient 142 (40%) 200 (56%) mismatch Severe prosthesis-patient 50 (14%) 84 (24%) mismatch Values are n (%) or mean ± SD.

p value

0.361 <0.001 <0.001 <0.001 <0.001 <0.001 0.001

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Table 4. Hemodynamic comparison between newer generation transcatheter valves (Sapien 3, Evolut R) and sutureless surgical valves. Variable Sapien 3/Evolut R (n=109) Sutureless valves (n=21) p value Left ventricular ejection 56 ± 10 55 ± 13 0.657 fraction (%) Peak aortic gradient (mmHg) 22 ± 11 30 ± 12 0.009 Mean aortic gradient (mmHg) 12 ± 6 16 ± 6 0.016 2 Effective orifice area (cm ) 1.55 ± 0.41 1.23 ± 0.37 0.003 Indexed effective orifice area 0.91 ± 0.25 0.74 ± 0.21 0.010 (cm2/m2) Moderate to severe aortic 1 (0.9%) 0 (0) regurgitation Moderate prosthesis-patient 34 (31%) 12 (57%) 0.023 mismatch Severe prosthesis-patient 11 (10%) 5 (24%) 0.080 mismatch Values are n (%) or mean ± SD.

25

Table 5. Valve hemodynamics following transcatheter aortic valve replacement, according to transcatheter valve type. Balloon-expanding valve Self-expanding valve Variable p value (n=52) (n=52) Left ventricular ejection 55 ± 12 57 ± 10 0.253 fraction (%) Peak transvalvular gradient 20 ± 8 20 ± 13 0.688 (mmHg) Mean transvalvular gradient 11 ± 5 10 ± 7 0.429 (mmHg) Effective orifice area (cm2) 1.59 ± 0.47 1.58 ± 0.35 0.922 Indexed effective orifice area 0.96 ± 0.28 0.95 ± 0.24 0.777 (cm2/m2) Moderate or severe aortic 1 (1.9%) 2 (3.8%) 0.558 regurgitation Moderate prosthesis-patient 18 (35%) 12 (23%) 0.194 mismatch Severe prosthesis-patient 6 (12%) 3 (6%) 0.488 mismatch Values are n (%) or mean ± SD.

26

Authors Contribution Leonardo Guimaraes, Josep Rodés-Cabau: conceptualization ideas, methodology, formal analysis, investigation, writing-original draft preparation, visualization preparation Pierre Voisine, Siamak Mohammadi, Dimitri Kalavrouzioutis, Eric Dumont, Daniel Doyle, Jean-Michel Paradis, Robert Delarochellière, Jerome Wintzer-Wehekind, Lucia Junquera, David del Val, Guillem Muntané-Carol, Afonso B. Freitas-Ferraz, Philippe Pibarot, François Dagenais: investigation, writing-review and editing preparation