J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 2 4 , 2 0 1 8

ª 2 0 1 8 B Y T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y F O UN DA T I O N

P U B L I S H E D B Y E L S E V I E R

Bioprosthetic Valve PerformanceAfter Transcatheter Aortic ValveReplacement With Self-ExpandingVersus Balloon-Expandable Valves inLarge Versus Small Aortic Valve AnnuliInsights From the CHOICE Trial and theCHOICE-Extend Registry

Mohammad Abdelghani, MD,a,b Nader Mankerious, MD,a Abdelhakim Allali, MD,a Martin Landt, MD,a

Jatinderjit Kaur, MD,a Dmitriy S. Sulimov, MD,a Constanze Merten, MD,a Susanne Sachse, SC,a Julinda Mehilli, MD,c

Franz-Josef Neumann, MD,d Christian Frerker, MD,e Thomas Kurz, MD,f Mohamed El-Mawardy, MD,g

Gert Richardt, MD,a Mohamed Abdel-Wahab, MDa,h

ABSTRACT

ISS

OBJECTIVES The aim of this study was to compare self-expanding and balloon-expandable transcatheter heart valves

(THVs) in large versus small aortic valve annuli.

BACKGROUND The degree of THV oversizing varies according to annular size, and this can modify the hemodynamic

performance of self-expanding and balloon-expandable THVs.

METHODS Patients undergoing transcatheter aortic valve replacement in the randomized CHOICE (Comparison of

Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic CoreValve vs Edwards

SAPIEN XT) trial (CoreValve [CV], n ¼ 120; SAPIEN XT [SXT], n ¼ 121) and the nonrandomized CHOICE-Extend

registry (Evolut R [ER], n ¼ 100; SAPIEN 3 [S3], n ¼ 334) were compared for THV performance by echocardiography

(in all patients) and by cardiac magnetic resonance imaging (MRI) regurgitant fraction (RF) (in a subgroup of pa-

tients). Patients were stratified according to aortic valve annular mean diameter into those with large (>23 mm) or

small (#23 mm) annuli.

RESULTS THV percentage oversizing was 19.1 � 6.4% with the CV, 11.4 � 7.0% with the SXT, 18.8 � 4.8% with the ER,

and 3.7 � 5.5% with the S3. Transvalvular mean pressure gradient was lower with the CV and ER than with the SXT and S3

in both the large and small annulus groups. In the randomized CHOICE trial, moderate to severe prosthetic valve

regurgitation (PVR) was more with the CV than the SXT in large annuli (15.1% vs. 0.0%; p ¼ 0.002; MRI RF: 10.5 � 10.2%

vs. 4.4 � 4.5%; p ¼ 0.036) but not in small annuli (0.0% vs. 5.7%; p ¼ 0.50; MRI RF: 4.0 � 4.1% vs. 4.0 � 3.4%;

p ¼ 0.98). In the CHOICE-Extend registry, moderate to severe PVR occurred in 2 patients, and any PVR was not

significantly different between the ER and the S3 in large (41.7% vs. 32.5%; p ¼ 0.24) or small (47.1% vs. 43.8%;

p ¼ 0.84) annuli. MRI RF was not different in large annuli (5.0 � 3.8% vs. 5.0 � 6.1%; p ¼ 0.99) but was significantly

lower with the ER than the S3 in small annuli (2.9 � 2.3% vs. 4.8 � 3.7%; p ¼ 0.023). On multivariate analysis,

transcatheter aortic valve replacement with the ER in small annuli was associated with a lower rate of prosthesis-patient

mismatch than with the S3, with no increased risk for PVR.

CONCLUSIONS Older-generation balloon-expandable THVs were associated with less PVR than self-expanding THVs in

patients with large but not small annuli. The next-generation self-expanding THV has improved sealing in patients with

large annuli and may have potential advantages in patients with small annuli. (J Am Coll Cardiol Intv 2018;11:2507–18)

© 2018 by the American College of Cardiology Foundation.

N 1936-8798/$36.00 https://doi.org/10.1016/j.jcin.2018.07.050

ABBR EV I A T I ON S

AND ACRONYMS

AVAi = indexed aortic valve

area

BE = balloon-expandable

CI = confidence interval

EOA = effective orifice area

MRI = magnetic resonance

imaging

OR = odds ratio

PG = pressure gradient

PPM = prosthesis-patient

mismatch

PVR = prosthetic valve

regurgitation

RF = regurgitant fraction

SE = self-expanding

TAVR = transcatheter aortic

valve replacement

THV = transcatheter heart

valve

From aThe

Bad Segeb

Netherland

(DZHK), p

Germany;

versity HohCardiolog

received in

Boston Sci

received i

research g

they have

Manuscrip

Abdelghani et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 2 4 , 2 0 1 8

Self-Expanding Versus Balloon-Expandable Valves in Small Annuli D E C E M B E R 2 4 , 2 0 1 8 : 2 5 0 7 – 1 8

2508

W ith the expansion of the spec-trum of patients treated withtranscatheter aortic valve

replacement (TAVR), individualized selec-tion of the transcatheter heart valve (THV)is becoming a prerequisite to optimize out-comes (1). This implies that the patient’s clin-ical and anatomic characteristics shoulddictate the type of THV to be used to mini-mize risks and maximize benefits. One ofthe anatomic substrates that couldcontribute to differential performance ofdifferent THV platforms is annular size (2).Annular size is known to influence paravalv-ular sealing as well as the hemodynamic per-formance of THVs (3,4).

The CHOICE (Comparison of TranscatheterHeart Valves in High Risk PatientsWith SevereAortic Stenosis: Medtronic CoreValve vsEdwards SAPIEN XT) trial was a randomizedcomparison of 2 second-generation THVplatforms: self-expanding (SE) and balloon-

expandable (BE) THVs (5). The CHOICE-Extend regis-try is a more contemporary cohort involving the next-generation SE and BE THVs, in which “personalized”device selection was left to the discretion of theoperator. We sought to explore whether SE and BETHVs would perform differently in larger than insmaller aortic valve annuli. We investigated thisconcept in data from the randomized CHOICE trial andfrom the nonrandomized contemporary CHOICE-Extend registry.

SEE PAGE 2519

METHODS

THE CHOICE TRIAL. The CHOICE trial was aninvestigator-initiated, open-label, multicenter, ran-domized trial that enrolled high-risk patients under-going transfemoral TAVR using a second-generation

Heart Center, Segeberger Kliniken (Academic Teaching Hospital

erg, Germany; bCardiology Department, The Academic Medical

s; cMunich University Center, Ludwig-Maximilians University,

artner site Munich Heart Alliance, Munich, Germany; dHearteCardiology Department, Asklepios Clinic St. Georg, Hamburg

spital, Lübeck, Germany; gCardiology Department, Vivantes

y Department, Heart Center Leipzig – University Hospital, Leipz

stitutional research grants from St. Jude Medical, Biotronik,

entific. Dr. Mehilli has received lecture fees from Abbott Vascu

nstitutional grants from Abbott Vascular and Edwards Lifes

rants from Edwards Lifesciences, Biotronik, Medtronic, and Bos

no relationships relevant to the contents of this paper to disc

t received June 18, 2018; revised manuscript received July 25, 201

SE THV (CoreValve, Medtronic, Minneapolis, Minne-sota) or BE THV (SAPIEN XT, Edwards Lifesciences,Irvine, California) between March 2012 and December2013. Patients with pre-existing aortic bioprostheseswere excluded. The primary endpoint was devicesuccess and was reached in 95.9% of patients inthe BE THV group and 77.5% in the SE THV group(p < 0.001) (5). The study was approved by the localethics committees of all participating centers, andeach patient provided written informed consent forinclusion in the trial.

During the study period, 4 sizes were available forthe SE THV (23, 26, 29, and 31 mm) and 3 sizes forthe BE THV (23, 26, and 29 mm). Device size selec-tion was based on sizing charts provided by themanufacturer and the majority of procedures wereperformed under sedative anesthesia using fluoro-scopic guidance.

THE CHOICE-EXTEND REGISTRY. The CHOICE-Extendregistry is an ongoing nonrandomized, prospectiveregistry, enrolling patients undergoing transfemoralTAVR using a third-generation SE THV (Evolut R,Medtronic) or BE THV (SAPIEN 3, Edwards Life-sciences) in the Heart Center, Segeberger Kliniken(Bad Segeberg, Germany), as of March 2014. The choiceof THV type was left to the discretion of the operatorand was basically determined by: 1) aortic valveannular measurements (targeting an optimal extent ofoversizing that could be sometimes achievable by 1 ofthe 2 THV platforms but not the other); 2) the extentand distribution of aortic valve and left ventricularoutflow tract calcification (targeting minimization ofthe risk for prosthetic valve regurgitation (PVR) and ofannular injury); and 3) the likelihood of coronaryobstruction and future percutaneous coronary in-terventions (favoring the shorter stent height of theSAPIEN 3 in patients with shallow coronary sinuses ora high risk for coronary obstruction or reintervention).During the study period, 4 sizes were available for theSE THV (23, 26, 29, and 34 mm) and 3 sizes for the BE

of the Universities of Kiel, Lübeck, and Hamburg),

Center, University of Amsterdam, Amsterdam, the

and German Centre for Cardiovascular Research

Center Freiburg-Bad Krozingen, Bad Krozingen,

, Germany; fCardiology Department, Lübeck Uni-

Wenckebach Hospital, Berlin, Germany; and the

ig, Germany. Drs. Richardt and Abdel-Wahab have

and Medtronic. Dr. Abdel-Wahab is a proctor for

lar, Biotronik, and Edwards Lifesciences; and has

ciences. Dr. Neumann has received institutional

ton Scientific. All other authors have reported that

lose.

8, accepted July 31, 2018.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 2 4 , 2 0 1 8 Abdelghani et al.D E C E M B E R 2 4 , 2 0 1 8 : 2 5 0 7 – 1 8 Self-Expanding Versus Balloon-Expandable Valves in Small Annuli

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THV (23, 26, and 29 mm). Device size selection wasbased on sizing charts provided by the manufacturers.

STUDY DESIGN AND DEFINITIONS. In the presentanalysis, valve-in-valve procedures were excluded,and native aortic valve annuli was classified as large(mean diameter >23 mm) or small (#23 mm). In theCHOICE trial, computed tomographic annular mea-surements were available in 191 patients (79.3%), andtransesophageal echocardiographic annular mea-surements were used in the remaining patients. In theCHOICE-Extend registry, computed tomography wasroutinely used for annular assessment and THVsizing. THV percentage oversizing was calculated as:100 � (prosthesis nominal diameter � mean annulusdiameter)/prosthesis nominal diameter. Aortic valveannular eccentricity index was calculated as: (1 �[minimum diameter/maximum diameter]), and aorticcusp calcification was graded semiquantitatively asfollows: no calcification, mild calcification (smallisolated spots), moderate calcification (multiplelarger spots), or severe calcification (extensive calci-fications of all cusps) (5).

Bioprosthetic valve performance was judged on thebasis of 30-day echocardiographic and 7- to 14-daycardiac magnetic resonance imaging (MRI) assess-ments. Echocardiographic valve performance indexeswere defined according to the Valve AcademicResearch Consortium definitions (6,7). The effectiveorifice area (EOA) of the THV was calculated accordingto the continuity equation using the left ventricularoutflow tract diameter and the velocity measured justproximal to the inflow margin of the THV stent (8). Onthe basis of EOA indexed to body surface area (7,9),prosthesis-patient mismatch (PPM) was defined as anindexed EOA #0.85 cm2/m2 (10). Cardiac MRI wasperformed in a pre-specified subgroup of patients(intending the inclusion of all patients except for thosewith MRI-incompatible implanted medical devices,those with claustrophobia, and those who declinedparticipation in the study). Flow measurements wereobtained as previously described (11): the forwardand reverse volumes within the aortic root weremeasured, and the regurgitant fraction (RF) wascalculated as ([forward flow volume � reverse flowvolume]/forward flow volume) � 100. MRI data wereanalyzed by 2 independent and experiencedobservers.

STATISTICAL METHODS. Quantitative variables aresummarized as mean � SD or as median (interquartilerange or range) and were compared using 2-sidedunpaired Student’s t-tests or Mann-Whitney U testsas appropriate. Categorical variables are summarizedas frequencies and proportions and were compared

using the chi-square test. Binary logistic regressionanalysis was performed to identify factors associatedwith the risk for PVR and PPM after TAVR, and oddsratios (ORs) with corresponding 95% confidence in-tervals (CIs) and p values are presented. All analyseswere performed using SPSS version 24 (IBM, Armonk,New York). All probability values were 2 tailed, and pvalues <0.05 were considered to indicate statisticalsignificance.

RESULTS

THE CHOICE TRIAL AND THE CHOICE-EXTEND REG-

ISTRY. In the CHOICE trial, the second-generation SETHV (CoreValve) was implanted in 120 patients, whilethe second-generation BE THV (SAPIEN XT) wasimplanted in 121. In the CHOICE-Extend registry, thethird-generation SE THV (Evolut R) was implanted in135 patients (100 with native aortic stenosis andavailable multislice computed tomographic data) andthe third-generation BE THV (SAPIEN 3) in 354 (334with native aortic stenosis and available multislicecomputed tomographic data), within the period fromMarch 2014 to November 2017.

As shown in Figure 1, the overall population’s aorticvalve annular diameter was 23.8 � 2.0 mm (range 19.3to 29.0 mm) in the CHOICE trial (CoreValve vs. SAPIENXT: 23.7� 1.9mmvs. 24.0� 2.0mm; p¼0.171) and 24.9� 2.5 mm (range 18.0 to 31.0 mm) in the CHOICE-Extend registry (Evolut R vs. SAPIEN 3: 23.6 � 2.1 mmvs. 25.2 � 2.5 mm; p < 0.001). The THV nominaldiameter was 27.4 � 1.9 mm in the CHOICE trial (Cor-eValve vs. SAPIEN XT: 28.1� 1.7 mm vs. 26.6 � 1.8 mm;p < 0.001) and 26.9 � 2.8 mm in the CHOICE-Extendregistry (Evolut R vs. SAPIEN 3: 29.5 � 3.0 mm vs.26.2 � 2.3 mm; p < 0.001). The percentage THV diam-eter oversizing was 15.2 � 7.7% in the CHOICE trial(CoreValve vs. SAPIEN XT: 19.1 � 6.4% vs. 11.4 � 7.0%;p < 0.001) and 7.2 � 8.3% in the CHOICE-Extend reg-istry (Evolut R vs. SAPIEN 3: 18.8� 4.8% vs. 3.7� 5.5%;p < 0.001).

The 30-day incidence of any (mild or more) PVR was52.5% in the CHOICE trial (CoreValve vs. SAPIEN XT:59.0% vs. 46.9%; p ¼ 0.133) and of moderate to severePVR was 5.6% (9.6% vs. 2.1%; p ¼ 0.046), while in theCHOICE-Extend registry, the incidence of any PVRwas37.8% (Evolut R vs. SAPIEN 3: 45.2% vs. 35.9%;p ¼ 0.129), and moderate to severe PVR occurred inonly 2 patients (0.5%). Transvalvular mean pressuregradient (PG) was 7.9 � 3.5 mm Hg in the CHOICE trial(CoreValve vs. SAPIENXT: 6.6� 3.1mmHg vs. 9.0� 3.4mm Hg; p < 0.001) and 10.5 � 4.4 mm Hg in theCHOICE-Extend registry (Evolut R vs. SAPIEN 3: 6.8 �2.9 mm Hg vs. 11.5 � 4.2 mm Hg; p <0.001).

FIGURE 1 Overview of the CHOICE Trial and CHOICE-Extend Registry

Summary of native aortic valve annular size, transcatheter heart valve (THV) sizing, and bioprosthetic valve performance indexes of the self-

expanding (SE) (top) and balloon-expandable (BE) THVs (bottom) in the CHOICE (Comparison of Transcatheter Heart Valves in High Risk

Patients With Severe Aortic Stenosis: Medtronic CoreValve vs Edwards SAPIEN XT) trial and the CHOICE-Extend registry. PG ¼ pressure

gradient; PVR ¼ prosthetic valve regurgitation.

Abdelghani et al. J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 2 4 , 2 0 1 8

Self-Expanding Versus Balloon-Expandable Valves in Small Annuli D E C E M B E R 2 4 , 2 0 1 8 : 2 5 0 7 – 1 8

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COMPARISON OF SIZING AND PERFORMANCE OF SE

VERSUS BE THVs IN PATIENTS WITH LARGE VERSUS

SMALL AORTIC VALVE ANNULI. Aortic valve annulardiameter was >23 mm (large annulus) in 147 patientsin the CHOICE trial and in 312 patients in theCHOICE-Extend registry. Annular diameter was#23 mm (small annulus) in 94 patients in theCHOICE trial and in 122 patients in the CHOICE-Extend registry.

Tables 1 and 2 compare the baseline and proceduralcharacteristics of SE versus BE THVs in the 2 groups(large and small aortic valve annuli) in both cohorts.In the CHOICE trial, a larger THV diameter was chosenwith the CoreValve than with the SAPIEN XT in bothgroups (29 � 1 mm vs. 27 � 2 mm; p ¼ 0.113, in the largeannulus group; 27 � 2 mm vs. 25 � 1 mm; p < 0.001,in the small annulus group), resulting in significantlyhigher percentage THV oversizing in relation to nativeannular diameter with the CoreValve than withthe SAPIEN XT (14 � 4% vs. 9 � 6%; p < 0.001, in

the large annulus group; 18�4% vs. 12� 5%; p<0.001,in the small annulus group). Eventually, all CoreValvedevices were oversized (i.e., THV nominal diametergreater than native annular diameter), and all but 5patients in the SAPIEN XT arm were oversized.

In the CHOICE-Extend registry, a larger THVdiameter was chosen with the Evolut R than with theSAPIEN 3 (31.0 � 2.5 mm vs. 27.0 � 1.9 mm; p < 0.001,in the large annulus group; 26.9 � 1.9 mm vs. 23.5 �1.1 mm; p < 0.001, in the small annulus group),resulting in significantly higher percentage THVoversizing in relation to native annular diameter withthe Evolut R than with the SAPIEN 3 (18.6 � 4.4% vs.2.9 � 5.4%; p < 0.001, in the large annulus group; 19.1� 5.2% vs. 6.2 � 5.3%; p < 0.001, in the small annulusgroup). In the large annulus group, 100% of Evolut RTHVs were oversized, while 69.9% of SAPIEN 3 THVswere oversized (p < 0.001). In the small annulusgroup, 97.7% of Evolut R THVs were oversized versus79.5% of SAPIEN 3 THVs (p ¼ 0.005).

TABLE 1 Baseline and Procedural Characteristics of Patients With Large or Small Aortic Valve Annuli Stratified According to

Transcatheter Heart Valve Implanted (Results From the Randomized CHOICE Trial)

Large Annulus (n ¼ 147) Small Annulus (n ¼ 94)

CoreValve(n ¼ 69)

SAPIEN XT(n ¼ 78) p Value

CoreValve(n ¼ 51)

SAPIEN XT(n ¼ 43) p Value

Baseline clinical characteristicsAge, yrs 81.2 � 5.3 81.1 � 7.1 0.892 82.3 � 6.1 82.0 � 6.1 0.764Female 39 (56.5) 32 (41.0) 0.070 47 (92.2) 37 (86.0) 0.504BSA, m2 1.84 � 0.19 1.87 � 0.17 0.224 1.73 � 0.19 1.72 � 0.15 0.905Body mass index, kg/m2 26.8 � 5.0 26.7 � 3.9 0.972 26.3 � 5.6 25.7 � 4.8 0.612STS-PROM score 5.66 � 3.26 5.53 � 2.77 0.792 6.93 � 4.75 5.64 � 3.37 0.141NYHA functional class 0.98 0.675

II 10 (14.5) 10 (12.8) 8 (15.7) 7 (16.3)III 40 (58.0) 47 (60.3) 34 (66.7) 26 (60.5)IV 16 (23.2) 17 (21.8) 8 (15.7) 7 (16.3)

Diabetes mellitus 21 (30.4) 25 (32.1) 0.86 11 (21.6) 13 (30.2) 0.354Hypertension 62 (89.9) 70 (89.7) 1.00 48 (94.1) 41 (95.3) 1Coronary artery disease 50 (72.5) 53 (67.9) 0.592 29 (56.9) 20 (46.5) 0.408Previous MI 11 (15.9) 13 (16.7) 1.00 5 (9.8) 1 (2.3) 0.214Peripheral arterial disease 15 (21.7) 12 (15.4) 0.395 7 (13.7) 8 (18.6) 0.58Previous stroke 10 (14.5) 17 (21.8) 0.291 4 (7.8) 9 (20.9) 0.079Chronic pulmonary disease 17 (24.6) 23 (29.5) 0.579 7 (13.7) 4 (9.3) 0.541Serum creatinine, mg 1.22 � 0.58 1.14 � 0.46 0.318 1.10 � 0.42 1.00 � 0.41 0.230Atrial fibrillation 19 (28.4) 29 (38.7) 0.343 10 (20.0) 10 (23.8) 0.858

Baseline echocardiographic and MSCT characteristicsAVA index, cm2/m2 0.43 � 0.11 0.40 � 0.11 0.198 0.40 � 0.12 0.40 � 0.13 0.961Transvalvular peak PG, mm Hg 70.3 � 20.8 66.7 � 20.8 0.292 71.9 � 23.1 72.4 � 25.1 0.910Transvalvular mean PG, mm Hg 43.2 � 14.4 42.4 � 15.1 0.756 42.8 � 13.6 44.9 � 16.2 0.512Aortic regurgitation (>mild) 8 (12.3) 10 (13.3) 1.00 16 (32.0) 7 (16.3) 0.095Mitral regurgitation (>mild) 15 (22.7) 24 (31.6) 0.263 23 (46.0) 20 (46.5) 1.00Tricuspid regurgitation (>mild) 19 (29.2) 28 (36.8) 0.374 16 (32.0) 7 (16.7) 0.146LV ejection fraction, % 54.6 � 11.1 51.5 � 13.8 0.140 55.4 � 12.9 54.4 � 14.0 0.712Systolic PAP, mm Hg 38.6 � 14.8 37.7 � 12.4 0.719 40.1 � 11.9 36.8 � 14.3 0.283Septal wall thickness, mm 14.7 � 3.5 14.7 � 3.2 0.972 14.2 � 2.5 14.7 � 2.7 0.453Posterior wall thickness, mm 12.3 � 2.9 12.3 � 3.2 0.979 13.5 � 3.1 13.4 � 3.0 0.857LV end-systolic diameter, mm 32.5 � 10.9 36.5 � 9.5 0.100 32.0 � 8.6 31.5 � 6.7 0.813LV end-diastolic diameter, mm 46.1 � 9.3 48.5 � 8.8 0.196 46.5 � 7.2 46.3 � 7.8 0.956Annular diameter, mm 25.0 � 1.3 25.2 � 1.4 0.346 21.9 � 1.0 21.9 � 1.0 0.995Annular diameter/BSA, mm/m2 13.7 � 1.3 13.5 � 1.3 0.399 12.8 � 1.3 12.8 � 1.3 0.989Annular eccentricity index* 0.19 � 0.08 0.18 � 0.06 0.440 0.18 � 0.07 0.19 � 0.07 0.606

Procedural characteristicsPre-dilatation 60 (87.0) 78 (100.0) 0.001 46 (90.2) 43 (100.0) 0.060THV diameter 29.0 � 0.9 27.4 � 1.6 0.113 26.9 � 1.6 25.2 � 1.3 <0.001% THV oversizing 13.9 � 3.7 8.5 � 5.5 <0.001 18.4 � 4.3 12.2 � 5.3 <0.001Post-dilatation 35 (50.7) 18 (23.1) 0.001 24 (47.1) 6 (14.0) 0.001

Values are mean � SD or n (%). *Annular eccentricity index was calculated as: 1 � (minimum diameter/maximum diameter).

AVA ¼ aortic valve area; BSA ¼ body surface area; CHOICE ¼ Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: MedtronicCoreValve vs Edwards SAPIEN XT; LV ¼ left ventricular; MI ¼ myocardial infarction; MSCT ¼ multislice computed tomography; NYHA ¼ New York Heart Association; PAP ¼pulmonary artery pressure; PG ¼ pressure gradient; STS-PROM ¼ Society of Thoracic Surgeons Predicted Risk of Mortality; THV ¼ transcatheter heart valve.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 1 1 , N O . 2 4 , 2 0 1 8 Abdelghani et al.D E C E M B E R 2 4 , 2 0 1 8 : 2 5 0 7 – 1 8 Self-Expanding Versus Balloon-Expandable Valves in Small Annuli

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INVASIVE, ECHOCARDIOGRAPHIC, AND MAGNETIC

RESONANCE INDEXES OF BIOPROSTHETIC VALVE

PERFORMANCE. Tables 3 and 4 summarize proce-dural, in-hospital, and 30-day parameters of the he-modynamic performance of SE versus BE THVs in the2 groups (large and small aortic valve annuli) in bothcohorts (the CHOICE trial and CHOICE-Extend regis-try). In the CHOICE trial, 30-day indexed EOA (onDoppler echocardiography) was not significantlydifferent between the CoreValve and the SAPIEN XTin either group of annular size. In contrast,

transvalvular mean PG was lower after CoreValve thanafter SAPIEN XT implantation, in both the largeannulus group (7 � 3 mm Hg vs. 8 � 3 mm Hg;p ¼ 0.006) and the small annulus group (7 � 3 mm Hgvs. 10 � 4 mm Hg; p < 0.001). Moderate to severe PVRwas significantly more frequent after CoreValve thanafter SAPIEN XT implantation in large annuli (15.1%vs. 0.0%; p ¼ 0.002) but not in small annuli (0.0% vs.5.7%; p ¼ 0.495). Cardiac MRI data were available in asubgroup of patients (n ¼ 90): 47 in the large annulusgroup (CoreValve, n ¼ 16; SAPIEN XT, n ¼ 31) and 43 in

TABLE 2 Baseline and Procedural Characteristics of Patients With Large or Small Aortic Valve Annuli Stratified According to

Transcatheter Heart Valve Implanted (Results From the CHOICE-Extend Registry)

Large Annulus (n ¼ 312) Small Annulus (n ¼ 122)

Evolut R(n ¼ 56)

SAPIEN 3(n ¼ 256) p Value

Evolut R(n ¼ 44)

SAPIEN 3(n ¼ 78) p Value

Baseline clinical characteristicsAge, yrs 81.4 � 5.1 80.9 � 6.3 0.549 81.6 � 4.6 80.3 � 6.1 0.251Female 22 (39.3) 81 (31.6) 0.276 41 (93.2) 69 (88.5) 0.534BSA, m2 1.92 � 0.16 1.97 � 0.22 0.068 1.74 � 0.18 1.77 � 0.18 0.435Body mass index, kg/m2 27.6 � 4.1 28.2 � 5.5 0.358 26.0 � 5.4 26.8 � 4.0 0.393STS-PROM score 3.7 � 2.5 5.0 � 3.9 0.017 5.2 � 5.8 5.0 � 3.4 0.830NYHA functional class 0.481 0.502II 26 (46.4) 106 (41.4) 25 (56.8) 42 (53.8)III 22 (39.3) 117 (45.7) 10 (22.7) 25 (32.1)IV 2 (3.6) 17 (6.6) 4 (9.1) 4 (5.1)

Diabetes mellitus 14 (25.0) 80 (31.5) 0.422 11 (25.0) 17 (21.8) 0.823Hypertension 52 (92.9) 224 (87.8) 0.356 39 (88.6) 69 (88.5) 1.00Coronary artery disease 37 (66.1) 177 (69.1) 0.638 19 (43.2) 48 (61.5) 0.060Previous MI 8 (14.3) 29 (11.3) 0.501 4 (9.1) 6 (7.7) 0.746Peripheral arterial disease 14 (25.0) 44 (17.2) 0.186 10 (22.7) 12 (15.4) 0.334Previous stroke 7 (12.5) 31 (12.1) 1.00 3 (6.8) 7 (9.0) 1.00Serum creatinine 1.07 � 0.37 1.24 � 0.80 0.019 1.02 � 0.60 0.99 � 0.30 0.709Atrial fibrillation 27 (48.2) 110 (43.3) 0.598 18 (40.9) 21 (26.9) 0.10

Baseline echocardiographic and MSCT characteristicsAVA index, cm2/m2 0.53 � 0.16 0.45 � 0.16 <0.001 0.56 � 0.19 0.50 � 0.17 0.069Transvalvular peak PG, mm Hg 63.1 � 20.1 67.6 � 25.1 0.149 60.3 � 18.5 69.0 � 24.7 0.048Transvalvular mean PG, mm Hg 40.4 � 13.9 43.7 � 17.1 0.182 39.1 � 13.9 44.4 � 15.9 0.065Aortic regurgitation (>mild) 7 (12.5) 35 (13.9) 1.00 7 (15.9) 16 (21.1) 0.632Mitral regurgitation (>mild) 15 (26.8) 56 (22.1) 0.484 16 (6.4) 18 (23.1) 0.142Tricuspid regurgitation (>mild) 7 (12.5) 38 (15.2) 0.682 12 (27.3) 12 (15.4) 0.154LV ejection fraction 57.2 � 10.3 54.0 � 12.9 0.047 60.9 � 8.3 59.4 � 10.7 0.422Systolic pulmonary artery pressure, mm Hg 35.8 � 11.6 37.9 � 15.4 0.283 34.1 � 12.4 36.1 � 14.1 0.494Ventricular septal thickness, mm 13.4 � 2.8 14.5 � 2.8 0.015 12.8 � 2.9 13.6 � 3.0 0.158Posterior wall thickness, mm 11.1 � 3.6 11.8 � 2.7 0.192 10.8 � 3.0 11.0 � 3.0 0.806LV end-systolic diameter, mm 31.1 � 8.8 36.0 � 9.5 0.002 26.8 � 8.6 31.0 � 9.8 0.040LV end-diastolic diameter, mm 44.0 � 8.2 47.9 � 8.9 0.007 37.9 � 8.0 43.9 � 6.6 <0.001Annulus diameter, MSCT, mm 25.1 � 1.3 26.2 � 2.0 <0.001 21.7 � 1.0 22.0 � 1.0 0.072Annular diameter/BSA, mm/m2 16.8 � 1.9 15.8 � 2.9 0.001 16.5 � 2.6 15.0 � 2.6 0.002Annular eccentricity index, MSCT 0.22 � 0.06 0.19 � 0.08 0.002 0.232 � 0.059 0.209 � 0.079 0.096Aortic valve calcification 0.117 0.206Mild 18 (32.1) 51 (20.1) 17 (38.6) 21 (27.6)Moderate 28 (50.0) 138 (54.3) 25 (56.8) 45 (59.2)Severe 10 (17.9) 65 (25.9) 2 (4.5) 10 (13.2)

Procedural characteristicsPre-dilatation 19 (33.9) 73 (28.5) 0.423 6 (13.6) 13 (16.7) 0.797THV diameter 31.0 � 2.5 27.0 � 1.9 <0.001 26.9 � 1.9 23.5 � 1.1 <0.001% THV oversizing 18.6 � 4.4 2.9 � 5.4 <0.001 19.1 � 5.2 6.2 � 5.3 <0.001Post-dilatation 25 (44.6) 24 (9.4) <0.001 14 (31.8) 14 (17.9) 0.116

Values are mean � SD or n (%).

Abbreviations as in Table 1.

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the small annulus group (CoreValve, n ¼ 18; SAPIENXT, n ¼ 25). Online Table 1 compares patients whounderwent MRI early after TAVR and those who didnot undergo MRI. MRI RF was higher after CoreValvethan after SAPIEN XT implantation in large annuli(10.5 � 10.2% vs. 4.4 � 4.5%; p ¼ 0.036) but not insmall annuli (4.0 � 4.1% vs. 4.0 � 3.4%; p ¼ 0.975).

In the CHOICE-Extend registry, 30-day indexedEOA was significantly larger after Evolut R than

after SAPIEN 3 implantation in both groups (1.08�0.33cm2/m2 vs. 0.86 � 0.22 cm2/m2, p < 0.001, in largeannuli; 1.04 � 0.28 cm2/m2 vs. 0.80 � 0.19 cm2/m2,p < 0.001, in small annuli). Moderate to severe PVRoccurred in only 2 patients (both had SAPIEN 3implantation), and any (mild or more) PVR was notsignificantly different between Evolut R and SAPIEN 3in large annuli (41.7% vs. 32.5%; p¼0.243) and in smallannuli (47.1% vs. 43.8%; p ¼ 0.836). To account for

TABLE 3 Thirty-Day Hemodynamic Outcomes of Patients With Large or Small Aortic Valve Annuli Stratified According to Transcatheter

Heart Valve Implanted (Results From the Randomized CHOICE Trial)

Large Annulus (n ¼ 147) Small Annulus (n ¼ 94)

CoreValve(n ¼ 69)

SAPIEN XT(n ¼ 78) p Value

CoreValve(n ¼ 51)

SAPIEN XT(n ¼ 43) p Value

Echocardiographic parameters*

Effective orifice area index, cm2/m2 1.21 � 0.37 1.08 � 0.33 0.101 1.16 � 0.32 1.06 � 0.26 0.224

Prosthesis-patient mismatch† 6 (16.2) 12 (26.1) 0.300 4 (15.4) 7 (23.3) 0.517

Transvalvular peak PG, mm Hg 12.5 � 5.7 14.9 � 4.8 0.019 12.6 � 5.7 18.8 � 8.0 0.001

Transvalvular mean PG, mm Hg 6.6 � 3.1 8.2 � 2.62 0.006 6.7 � 3.2 10.2 � 4.2 <0.001

Aortic regurgitation (echocardiography) 0.006 0.218

None 21 (39.6) 32 (52.5) 13 (43.3) 19 (54.3)

Mild 24 (45.3) 29 (47.5) 17 (56.7) 14 (40.0)

Moderate 8 (15.1) 0 0 2 (5.7)

MRI assessment‡

MRI regurgitation fraction, % 10.5 � 10.2 4.4 � 4.5 0.036 4.00 � 4.12 3.97 � 3.37 0.975

Values are mean � SD or n (%). *Performed at 30 days post-TAVR. †Defined as an effective orifice area index (at 30 days post-TAVR) #0.85 cm2/m2. ‡Cardiac MRI wasperformed 7 to 14 days after the procedure in 90 patients: 47 in the large annulus group (23% [n ¼ 16] with CoreValve vs. 40% [n ¼ 31] with SAPIEN XT, p ¼ 0.035) and 43 inthe small annulus group (35% [n ¼ 18] with CoreValve vs. 58% [n ¼ 25] with SAPIEN XT, p ¼ 0.038).

MRI ¼ magnetic resonance imaging; TAVR ¼ transcatheter aortic valve replacement; other abbreviations as in Table 1.

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imbalances in the baseline and procedural character-istics of patients who received Evolut R and thosewho received SAPIEN 3 THVs, multivariate regressionanalysis was conducted (Tables 5 and 6). On multi-variate regression analysis, TAVR with the Evolut R(vs. the SAPIEN 3) was associated with a trend towarda higher incidence of mild or greater PVR in largeannuli (OR: 1.92; 95% CI: 0.97 to 3.81; p ¼ 0.063)but not in small annuli (OR: 1.22; 95% CI: 0.51 to2.90; p ¼ 0.652), after accounting for aortic valvecalcification severity and aortic annular diameterand eccentricity. After accounting for aortic valve area

TABLE 4 Thirty-Day Hemodynamic Outcomes of Patients With Large

Transcatheter Heart Valve Implanted (Results From the CHOICE-Exten

Large Annulus (

Evolut R(n ¼ 56)

SAPIE(n ¼ 2

Echocardiographic parameters*

Effective orifice area index, cm2/m2 1.08 � 0.33 0.86 �Prosthesis-patient mismatch 10 (21.7) 98 (43

Transvalvular peak PG, mm Hg 12.7 � 5.1 19.8 �Transvalvular mean PG, mm Hg 6.8 � 2.8 10.9 �Aortic regurgitation (echocardiography)

None 28 (58.3) 158 (6

Mild 20 (41.7) 74 (31

Moderate 0 2 (0.

MRI assessment†

MRI regurgitation fraction, % 5.0 � 3.8 5.0 �

Values are mean � SD or n (%). *Performed at 30 days post-TAVR. †Cardiac MRI was perBE THVs in the large annulus groups and in 19 with SE THVs and 36 with BE THVs in th

BE ¼ balloon-expandable; SE ¼ self-expanding; other abbreviations as in Tables 1 an

index and left ventricular ejection fraction atbaseline, aortic valve annular diameter indexed tobody surface area, and balloon post-dilatation, TAVRwith the Evolut R (vs. the SAPIEN 3) was associatedwith a trend toward a lower rate of PPM in large annuli(OR: 0.475; 95% CI: 0.220 to 1.024; p ¼ 0.057) andwas significantly associated with less PPM in thesmall annulus group (OR: 0.163; 95% CI: 0.052 to0.504; p ¼ 0.002).

Cardiac MRI data were available in a subgroup ofpatients (n ¼ 150): 96 in the large annulus group(Evolut R, n ¼ 30; SAPIEN 3, n ¼ 66) and 55 in the

or Small Aortic Valve Annuli Stratified According to

d Registry)

n ¼ 312) Small Annulus (n ¼ 122)

N 356) p Value

Evolut R(n ¼ 44)

SAPIEN 3(n ¼ 78) p Value

0.22 <0.001 1.04 � 0.28 0.80 � 0.19 <0.001

.2) 0.008 10 (33.3) 42 (59.2) 0.029

8.0 <0.001 11.6 � 4.8 23.5 � 7.2 <0.001

3.9 <0.001 6.6 � 3.1 13.3 � 4.3 <0.001

0.346 0.836

7.5) 18 (52.9) 41 (56.2)

.6) 16 (47.1) 32 (43.8)

9) 0 0

6.1 0.996 2.9 � 2.3 4.8 � 3.7 0.023

formed 7 to 14 days after the procedure in 151 patients: 30 with SE THVs and 66 withe small annulus groups.

d 3.

TABLE 5 Multivariate Logistic Regression Analysis of the Predictors of Mild or Greater

Prosthetic Valve Regurgitation After Transcatheter Aortic Valve Replacement With the

Next-Generation Transcatheter Heart Valves (Results From the CHOICE-Extend Registry)

Large Annulus Small Annulus

OR (95% CI) p Value OR (95% CI) p Value

Evolut R (vs. SAPIEN 3) 1.92 (0.97–3.81) 0.063 1.22 (0.51–2.90) 0.652

Aortic valve calcification* 1.70 (1.16–2.49) 0.006 1.22 (0.63–2.37) 0.563

Aortic valve annular eccentricity index 1.12 (0.03–37.97) 0.949 0.03 (0.00–13.93) 0.256

Aortic valve annular mean diameter 1.10 (0.96–1.25) 0.169 0.88 (0.57–1.34) 0.538

*OR per class increment (mild, moderate, and severe).

CHOICE ¼ Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis:Medtronic CoreValve vs Edwards SAPIEN XT; CI ¼ confidence interval; OR ¼ odds ratio.

TABLE 6 Multivariat

Prosthesis-Patient Mi

Next-Generation Tran

Evolut R (vs. SAPIEN 3

Aortic valve area index

LV ejection fraction

Annular mean diamete

Balloon post-dilatation

Abbreviations as in Tables

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small annulus group (Evolut R, n ¼ 19; SAPIEN 3,n ¼ 36). Online Table 2 summarizes the differencesbetween patients who underwent MRI early afterTAVR and those who did not undergo MRI. MRI RFwas not different between the Evolut R and theSAPIEN 3 in large annuli (5.0 � 3.8% vs. 5.0 � 6.1%;p ¼ 0.996) but was significantly lower after Evolut Rthan after SAPIEN 3 implantation in small annuli(2.9 � 2.3% vs. 4.8 � 3.7%; p ¼ 0.023) (Figure 2).

Online Table 3 summarizes baseline and proce-dural characteristics and early outcomes of patientsin the CHOICE-Extend registry stratified accordingto the implanted THV (Evolut R vs. SAPIEN 3). OnlineTable 4 summarizes some relevant baseline, proce-dural, and valve performance characteristics of theEvolut R versus the SAPIEN 3 stratified into smallvalves (26-mm Evolut R vs. 23-mm SAPIEN 3),medium-sized valves (29-mm Evolut R vs. 26-mmSAPIEN 3), and large valves (34-mm Evolut R vs. 29-mm SAPIEN 3). The incidence of severe PPM wassignificantly less (0% vs. 27%; p ¼ 0.011) with thesmall Evolut R (26 mm) than with the small SAPIEN 3(23 mm), while it was not different with medium andlarge valve sizes. The need for balloon post-dilatationwas significantly higher with the Evolut R than with

e Logistic Regression Analysis of the Predictors of

smatch After Transcatheter Aortic Valve Replacement With the

scatheter Heart Valve (Results From the CHOICE-Extend Registry)

Large Annulus Small Annulus

OR (95% CI) p Value OR (95% CI) p Value

) 0.475 (0.220–1.024) 0.057 0.163 (0.052–0.504) 0.002

0.125 (0.020–0.765) 0.025 0.358 (0.027–4.666) 0.433

0.963 (0.942–0.985) 0.001 0.968 (0.926–1.012) 0.152

r/BSA 0.738 (0.608–0.896) 0.002 0.798 (0.571–1.117) 0.189

0.830 (0.377–1.826) 0.643 7.650 (2.023–28.930) 0.003

1, 3, and 5.

the SAPIEN 3 with medium and large but not smallvalve sizes (26-mm Evolut R vs. 23-mm SAPIEN 3:25% vs. 22%; p ¼ 0.784). MRI RF was not differentbetween the Evolut R and the SAPIEN 3 in mediumand large valve sizes but tended to be lower withthe small Evolut R than with the small SAPIEN 3(3.0 � 2.6% vs. 5.3 � 3.8%; p ¼ 0.059).

DISCUSSION

The main finding of the present study is that SE THVsseem to be superior to BE THVs in patients with smallaortic valve annuli, resulting in low rates of PPM andat least comparable rates of PVR.

The CHOICE trial was the first randomized multi-center trial comparing 2 THV platforms (SE vs. BETHVs). The CHOICE-Extend registry is, in contrast, asingle-center, nonrandomized, all-comers registry.The differences between the 2 datasets are notconfined to their designs but rather involve furtherkey distinctions. First, whereas the CHOICE trial wasrun at a relatively early stage of the wide adoption ofTAVR (2012 to 2013), the CHOICE-Extend registry in-volves a more contemporary TAVR experience, whichis in part enlightened by the lessons learned from theCHOICE trial. For instance, the difference in devicesuccess rate between SE and BE THVs in the CHOICEtrial was evident in large annuli but trivial in smallannuli (5). Therefore, the SE Evolut R was 2-fold morefrequently used in patients with small annuli thanin those with large annuli in contemporary practice(the CHOICE-Extend registry). Second, in additionto the matured experience and the improved tech-niques practiced in the CHOICE-Extend registry,the introduction of improved THV technologies(e.g., SAPIEN 3 with a sealing skirt, Evolut R with1 extra size [34 mm] and with repositionabilitypotential) likely has contributed to improving theresults. Finally, the “personalized” selection ofthe device in the registry (Online Table 3) comparedwith the randomization in the trial might havecontributed to the improved outcomes in some ofthe THV performance indexes.

With these differences in mind, the changesbetween the results of the second- and third-generation SE and BE THVs (Figure 1) can be morereasonably interpreted. The overall incidence of anyas well as moderate to severe PVR was less withthe third- than with the second-generation THVs.The most remarkable change was that of the inci-dence of moderate to severe PVR with SE THVs(CoreValve vs. Evolut R: 9.6% vs. 0.0%).

SE THVs had better paravalvular sealing in smallerthan in larger annuli in both cohorts. In the CHOICE

FIGURE 2 Assessment of Prosthetic Valve Regurgitation by Magnetic Resonance Imaging After Transcatheter Aortic Valve Replacement

in Large and Small Annuli

Mean regurgitant fraction (RF) measured by cardiac magnetic resonance imaging (MRI) in patients treated with self-expanding transcatheter

heart valves (THVs) (CoreValve or Evolut R) versus balloon-expandable THVs (SAPIEN XT or SAPIEN 3) in large and small aortic valve annuli.

Data are derived from the CHOICE (Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic

CoreValve vs Edwards SAPIEN XT) trial (top) and the CHOICE-Extend registry (bottom).

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trial, moderate to severe PVR on echocardiographywas higher after CoreValve than after SAPIEN XTimplantation in large (15% vs. 0%) but not in smallannuli (0% vs. 6%). On MRI, the RF was higher afterCoreValve than after SAPIEN XT implantation in large(average 11% vs. 4%) but not in small (4% vs. 4%)annuli. In the CHOICE-Extend registry, moderate tosevere PVR was rare (0.5%). On quantitative assess-ment of PVR severity by cardiac MRI, the RF washigher after SAPIEN 3 than after Evolut R implanta-tion in small annuli (average 3% vs. 5%), with nodifference noted in large annuli (5% vs. 5%). Thelatter assessment, by MRI, although limited by beingavailable in only a subgroup of patients, exhibits 2important strengths: 1) it is a quantitative assessmentthat is more precise and accurate than echocardiog-raphy, especially with small regurgitations (withthird-generation THVs) (12); and 2) it was performed

by MRI specialists blinded to clinical and echocar-diographic data.

As baseline and procedural differences existedbetween patients who received Evolut R and SAPIEN3 valves, multivariate analysis accounting for thesedifferences was conducted and confirmed theimproved paravalvular sealing of Evolut R in thesmall annular group.

On the basis of the manufacturer’s recommenda-tions, the percentage diameter oversizing of the Cor-eValve ranges from 12% to 30% for the 23-, 26-, and29-mm sizes but ranges from 7% to 19% for the31-mm device. In the CHOICE trial, moderate to severePVR was observed in 33.3% of patients who receivedthe 31-mm CoreValve compared with 21.0% and 8.3%of patients who received the 29-mm and 26-mm sizes,respectively (data not mentioned in the results sec-tion). This comes in line with a recently published

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comparison of the 31-mm CoreValve with thesmaller sizes, which revealed higher rates of post-dilatation and implantation of a second THV and alower rate of device success in the 31-mm devicegroup (13). Introduction of the 34-mm Evolut Raddressed this problem. Improved performance ofthe third-generation (vs. second-generation) SE THVin large annuli is largely to be ascribed to theintroduction of the 34-mm device. The 34-mm Evo-lut R addresses almost the same spectrum of annulardiameters treated previously with the 31-mm Cor-eValve (26 to 30 mm), thus allowing “sufficient”oversizing (12% to 31%) even in the upper part of thescale of annular size, a subgroup of patients who hadthe highest rate of PVR in the CHOICE trial. SE THVpercentage oversizing in large annuli was 13.9 � 3.7%in the CHOICE trial and 18.6 � 4.4% in the CHOICE-Extend registry. Regardless, the contributing effectsof the repositionability feature and of a better“personalized” selection of the device type are not tobe overlooked. A tendency of the operator to choosethe Evolut R (rather than the SAPIEN 3) in patientswith less heavily calcified aortic valve complexes(Online Table 3) is a possible contributing factor tothe improved rate of PVR with the third-generationSE THV. Accounting for differences in aortic valvecalcification unmasked a trend toward a higher inci-dence of PVR after TAVR with the Evolut R in largeannuli. Interestingly, such a trend was not seen insmall annuli, even after accounting for relevantconfounders.

Data from the pivotal randomized trials and pro-spective registries of TAVR with the SE THV (14)revealed an unequivocal relationship between THVoversizing and the risk for PVR. In a study thatincluded patients enrolled in the CoreValve USExtreme Risk Pivotal Trial (15) or CoreValve US HighRisk Pivotal Trial (16) (n ¼ 1,023), the incidence ofmoderate to severe PVR increased progressively(from 6.3% to 17.6%) with decreasing degree of THVoversizing (14). THV oversizing was lower in patientstreated with the 31-mm CoreValve (average 12.8%)than other CoreValve sizes (average 15.7% to 17.8%),and THV oversizing of #10% was more frequent withthe 31-mm CoreValve (31.9%) than other device sizes(7.7% to 16.4%). Adherence to sizing recommenda-tions was achieved in 71.6% (perimeter-based sizing)to 75.8% (diameter-based sizing) of patients, and therate of 30-day outcomes (including death, stroke, andneed for pacemaker) was not influenced by the degreeof oversizing (14).

We observed a remarkable decline of percentageoversizing of the BE THVs, from 11.4 � 7.0% with the

SAPIEN XT to 3.7 � 5.5% with the SAPIEN 3 despitesimilar manufacturer’s sizing recommendations.This trend toward less oversizing of BE THVs wasdriven in part by data on the risk for excessiveoversizing of these valves. Safety of “excessive”oversizing of SE THVs compared with BE THVs wasshown in a study that compared SE THVs and BETHVs sized with moderate (5% to 20%) versusexcessive (>20%) oversizing (17). In the moderateoversizing group, SE THVs more often required post-dilatation, while in the excessive oversizing group,annular rupture occurred only with BE THVs. Thislatter risk for annulus injury, in addition to thebetter sealing properties of the SAPIEN 3, explainswhy operators tend to systematically less oversizethe SAPIEN 3 compared with the SAPIEN XT. In thePARTNER (Placement of Transcatheter Aortic Valve)II SAPIEN 3 intermediate-risk trial, any degree ofoversizing was achieved in 63.2% to 76.9% (accord-ing to the method of sizing) (18). The incidence ofmoderate to severe PVR was highest in patients withno oversizing (7.8% to 13.2%), less so in patientswith modest oversizing of <10% (2.8% to 4.2%), andlowest in patients with oversizing of $10% (0.3%). Inline with our findings, the extent of oversizing waslower with the 23-mm SAPIEN 3 (average 6.5%), moreso with the 26-mm device (7.5%), and highest withthe 29-mm size (12.9%) (18). Inversely proportionateto the extent of oversizing, any PVR occurred in 57.1%of patients who received 23-mm devices, in 45.2% ofpatients who received 26-mm devices, and in 39.0%of patients who received 29-mm devices (18).

Although the remarkable reduction of oversizingwith BE THVs in recent practice should theoreticallybe associated with a proportional increase in theoverall incidence of PVR, this is apparently compen-sated for by a very effective paravalvular sealingskirt, but probably at the expense of a higher residualtransvalvular PG and a higher incidence of PPM. Inthe present analysis, BE THVs tended to yield smallerEOA and a higher residual PG than SE THVs in theCHOICE trial, and the differences were significant inthe CHOICE-Extend registry. Multivariate regressionanalysis (Table 6) revealed that the use of theEvolut R was significantly associated with a lower riskfor PPM, especially in patients with small annuli.The supra-annular leaflet function in SE THVs (asopposed to an intra-annular level in BE THVs) couldlead to a larger effective orifice and lower residualgradients, regardless of annular size. However, thesystematic “generous” oversizing of SE THVs couldalso be an explanation for the favorable systolicperformance.

PERSPECTIVES

WHAT IS KNOWN? TAVR with the first- and second-

generation SE THVs is associated with a higher rate of PVR than

with BE THVs.

WHAT IS NEW? SE THVs have a low rate of PVR and

PPM in patients with small aortic valve annuli. The

next-generation SE THV tends to outperform BE THVs in

this patient subset.

WHAT IS NEXT? A randomized comparison of the next-

generation SE and BE THVs will provide more robust insights into

the differential performance of both platforms in different

clinical and anatomic subgroups.

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STUDY LIMITATIONS. Unlike the CHOICE trial, theCHOICE-Extend registry is a nonrandomized study,and baseline differences existed between patientstreated with SE versus BE THVs. Improved perfor-mance of SE THVs can partially be ascribed to the useof this device in patients with, for example, lesslanding zone calcification. Although we accounted forthese differences in multivariate analysis, our find-ings need to be further confirmed, ideally in a ran-domized setting. Although sought for in most of theCHOICE trial patients and all CHOICE-Extend registrypatients, MRI data were available in a relatively smallsubgroup of patients. The high rate of pacemakerimplantations in TAVR patients, in addition to othercontraindications of MRI, accounts for the majority ofthe cases without MRI data. Although these limita-tions are unavoidable (being inherent to the MRItechnology), interpretation of the MRI data should becautious, taking into account the differences betweenpatients with versus without MRI (summarized inOnline Tables 1 and 2). Finally, the CHOICE trialinvolved outmoded valve iteration. However, thelarger part of the body of evidence on TAVR is derivedfrom experience with this iteration, and extrapolationto newer iterations is a common practice, althoughnot supported by adequate evidence. It was thereforeintended to combine the contemporary data with theolder data to emphasize the similarities and differ-ences between both iterations.

CONCLUSIONS

Bioprosthetic valve performance in patients withsmall aortic valve annuli seems to be better with SETHVs than with BE THVs. The improved performanceincludes comparable PVR and less PPM.

ADDRESS FOR CORRESPONDENCE: Dr. MohamedAbdel-Wahab, Heart Center Leipzig – UniversityHospital, Strümpellstraße 39, 04289 Leipzig, Germany.E-mail: mohamed.abdel-wahab@medizin.uni-leipzig.de.

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KEY WORDS annulus, aortic stenosis,echocardiography, hemodynamicperformance, magnetic resonance imaging,paravalvular leak, regurgitation,transcatheter aortic valve

APPENDIX For supplemental tables, pleasesee the online version of this paper.