Author + information
- Received June 18, 2018
- Revision received July 25, 2018
- Accepted July 31, 2018
- Published online December 17, 2018.
- Mohammad Abdelghani, MDa,b,
- Nader Mankerious, MDa,
- Abdelhakim Allali, MDa,
- Martin Landt, MDa,
- Jatinderjit Kaur, MDa,
- Dmitriy S. Sulimov, MDa,
- Constanze Merten, MDa,
- Susanne Sachse, SCa,
- Julinda Mehilli, MDc,
- Franz-Josef Neumann, MDd,
- Christian Frerker, MDe,
- Thomas Kurz, MDf,
- Mohamed El-Mawardy, MDg,
- Gert Richardt, MDa and
- Mohamed Abdel-Wahab, MDa,h,∗ ()
- aThe Heart Center, Segeberger Kliniken (Academic Teaching Hospital of the Universities of Kiel, Lübeck, and Hamburg), Bad Segeberg, Germany
- bCardiology Department, The Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- cMunich University Center, Ludwig-Maximilians University, and German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
- dHeart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany
- eCardiology Department, Asklepios Clinic St. Georg, Hamburg, Germany
- fCardiology Department, Lübeck University Hospital, Lübeck, Germany
- gCardiology Department, Vivantes Wenckebach Hospital, Berlin, Germany
- hCardiology Department, Heart Center Leipzig – University Hospital, Leipzig, Germany
- ↵∗Address for correspondence:
Dr. Mohamed Abdel-Wahab, Heart Center Leipzig – University Hospital, Strümpellstraße 39, 04289 Leipzig, Germany.
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 = 120; SAPIEN XT [SXT], n = 121) and the nonrandomized CHOICE-Extend registry (Evolut R [ER], n = 100; SAPIEN 3 [S3], n = 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 patients). 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 = 0.002; MRI RF: 10.5 ± 10.2% vs. 4.4 ± 4.5%; p = 0.036) but not in small annuli (0.0% vs. 5.7%; p = 0.50; MRI RF: 4.0 ± 4.1% vs. 4.0 ± 3.4%; p = 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 = 0.24) or small (47.1% vs. 43.8%; p = 0.84) annuli. MRI RF was not different in large annuli (5.0 ± 3.8% vs. 5.0 ± 6.1%; p = 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 = 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.
- aortic stenosis
- hemodynamic performance
- magnetic resonance imaging
- paravalvular leak
- transcatheter aortic valve
With the expansion of the spectrum of patients treated with transcatheter aortic valve replacement (TAVR), individualized selection of the transcatheter heart valve (THV) is becoming a prerequisite to optimize outcomes (1). This implies that the patient’s clinical and anatomic characteristics should dictate the type of THV to be used to minimize risks and maximize benefits. One of the anatomic substrates that could contribute to differential performance of different THV platforms is annular size (2). Annular size is known to influence paravalvular sealing as well as the hemodynamic performance of THVs (3,4).
The CHOICE (Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic CoreValve vs Edwards SAPIEN XT) trial was a randomized comparison of 2 second-generation THV platforms: self-expanding (SE) and balloon-expandable (BE) THVs (5). The CHOICE-Extend registry is a more contemporary cohort involving the next-generation SE and BE THVs, in which “personalized” device selection was left to the discretion of the operator. We sought to explore whether SE and BE THVs would perform differently in larger than in smaller aortic valve annuli. We investigated this concept in data from the randomized CHOICE trial and from the nonrandomized contemporary CHOICE-Extend registry.
The CHOICE trial
The CHOICE trial was an investigator-initiated, open-label, multicenter, randomized trial that enrolled high-risk patients undergoing transfemoral TAVR using a second-generation SE THV (CoreValve, Medtronic, Minneapolis, Minnesota) or BE THV (SAPIEN XT, Edwards Lifesciences, Irvine, California) between March 2012 and December 2013. Patients with pre-existing aortic bioprostheses were excluded. The primary endpoint was device success and was reached in 95.9% of patients in the BE THV group and 77.5% in the SE THV group (p < 0.001) (5). The study was approved by the local ethics committees of all participating centers, and each patient provided written informed consent for inclusion in the trial.
During the study period, 4 sizes were available for the SE THV (23, 26, 29, and 31 mm) and 3 sizes for the BE THV (23, 26, and 29 mm). Device size selection was based on sizing charts provided by the manufacturer and the majority of procedures were performed under sedative anesthesia using fluoroscopic guidance.
The CHOICE-Extend registry
The CHOICE-Extend registry is an ongoing nonrandomized, prospective registry, enrolling patients undergoing transfemoral TAVR using a third-generation SE THV (Evolut R, Medtronic) or BE THV (SAPIEN 3, Edwards Lifesciences) in the Heart Center, Segeberger Kliniken (Bad Segeberg, Germany), as of March 2014. The choice of THV type was left to the discretion of the operator and was basically determined by: 1) aortic valve annular measurements (targeting an optimal extent of oversizing that could be sometimes achievable by 1 of the 2 THV platforms but not the other); 2) the extent and distribution of aortic valve and left ventricular outflow tract calcification (targeting minimization of the risk for prosthetic valve regurgitation (PVR) and of annular injury); and 3) the likelihood of coronary obstruction and future percutaneous coronary interventions (favoring the shorter stent height of the SAPIEN 3 in patients with shallow coronary sinuses or a high risk for coronary obstruction or reintervention). During the study period, 4 sizes were available for the SE THV (23, 26, 29, and 34 mm) and 3 sizes for the BE THV (23, 26, and 29 mm). Device size selection was based on sizing charts provided by the manufacturers.
Study design and definitions
In the present analysis, valve-in-valve procedures were excluded, and native aortic valve annuli was classified as large (mean diameter >23 mm) or small (≤23 mm). In the CHOICE trial, computed tomographic annular measurements were available in 191 patients (79.3%), and transesophageal echocardiographic annular measurements were used in the remaining patients. In the CHOICE-Extend registry, computed tomography was routinely used for annular assessment and THV sizing. THV percentage oversizing was calculated as: 100 × (prosthesis nominal diameter − mean annulus diameter)/prosthesis nominal diameter. Aortic valve annular eccentricity index was calculated as: (1 − [minimum diameter/maximum diameter]), and aortic cusp calcification was graded semiquantitatively as follows: no calcification, mild calcification (small isolated spots), moderate calcification (multiple larger spots), or severe calcification (extensive calcifications of all cusps) (5).
Bioprosthetic valve performance was judged on the basis of 30-day echocardiographic and 7- to 14-day cardiac magnetic resonance imaging (MRI) assessments. Echocardiographic valve performance indexes were defined according to the Valve Academic Research Consortium definitions (6,7). The effective orifice area (EOA) of the THV was calculated according to the continuity equation using the left ventricular outflow tract diameter and the velocity measured just proximal to the inflow margin of the THV stent (8). On the basis of EOA indexed to body surface area (7,9), prosthesis-patient mismatch (PPM) was defined as an indexed EOA ≤0.85 cm2/m2 (10). Cardiac MRI was performed in a pre-specified subgroup of patients (intending the inclusion of all patients except for those with MRI-incompatible implanted medical devices, those with claustrophobia, and those who declined participation in the study). Flow measurements were obtained as previously described (11): the forward and reverse volumes within the aortic root were measured, and the regurgitant fraction (RF) was calculated as ([forward flow volume − reverse flow volume]/forward flow volume) × 100. MRI data were analyzed by 2 independent and experienced observers.
Quantitative variables are summarized as mean ± SD or as median (interquartile range or range) and were compared using 2-sided unpaired Student’s t-tests or Mann-Whitney U tests as appropriate. Categorical variables are summarized as frequencies and proportions and were compared using the chi-square test. Binary logistic regression analysis was performed to identify factors associated with the risk for PVR and PPM after TAVR, and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and p values are presented. All analyses were performed using SPSS version 24 (IBM, Armonk, New York). All probability values were 2 tailed, and p values <0.05 were considered to indicate statistical significance.
The CHOICE trial and the CHOICE-Extend registry
In the CHOICE trial, the second-generation SE THV (CoreValve) was implanted in 120 patients, while the second-generation BE THV (SAPIEN XT) was implanted in 121. In the CHOICE-Extend registry, the third-generation SE THV (Evolut R) was implanted in 135 patients (100 with native aortic stenosis and available multislice computed tomographic data) and the third-generation BE THV (SAPIEN 3) in 354 (334 with native aortic stenosis and available multislice computed tomographic data), within the period from March 2014 to November 2017.
As shown in Figure 1, the overall population’s aortic valve annular diameter was 23.8 ± 2.0 mm (range 19.3 to 29.0 mm) in the CHOICE trial (CoreValve vs. SAPIEN XT: 23.7 ± 1.9 mm vs. 24.0 ± 2.0 mm; p = 0.171) 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 mm vs. 25.2 ± 2.5 mm; p < 0.001). The THV nominal diameter was 27.4 ± 1.9 mm in the CHOICE trial (CoreValve 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-Extend registry (Evolut R vs. SAPIEN 3: 29.5 ± 3.0 mm vs. 26.2 ± 2.3 mm; p < 0.001). The percentage THV diameter 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 registry (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 was 52.5% in the CHOICE trial (CoreValve vs. SAPIEN XT: 59.0% vs. 46.9%; p = 0.133) and of moderate to severe PVR was 5.6% (9.6% vs. 2.1%; p = 0.046), while in the CHOICE-Extend registry, the incidence of any PVR was 37.8% (Evolut R vs. SAPIEN 3: 45.2% vs. 35.9%; p = 0.129), and moderate to severe PVR occurred in only 2 patients (0.5%). Transvalvular mean pressure gradient (PG) was 7.9 ± 3.5 mm Hg in the CHOICE trial (CoreValve vs. SAPIEN XT: 6.6 ± 3.1 mm Hg vs. 9.0 ± 3.4 mm Hg; p < 0.001) and 10.5 ± 4.4 mm Hg in the CHOICE-Extend registry (Evolut R vs. SAPIEN 3: 6.8 ± 2.9 mm Hg vs. 11.5 ± 4.2 mm Hg; p <0.001).
Comparison of sizing and performance of SE versus BE THVs in patients with large versus small aortic valve annuli
Aortic valve annular diameter was >23 mm (large annulus) in 147 patients in the CHOICE trial and in 312 patients in the CHOICE-Extend registry. Annular diameter was ≤23 mm (small annulus) in 94 patients in the CHOICE trial and in 122 patients in the CHOICE-Extend registry.
Tables 1 and 2 compare the baseline and procedural characteristics 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 chosen with the CoreValve than with the SAPIEN XT in both groups (29 ± 1 mm vs. 27 ± 2 mm; p = 0.113, in the large annulus group; 27 ± 2 mm vs. 25 ± 1 mm; p < 0.001, in the small annulus group), resulting in significantly higher percentage THV oversizing in relation to native annular diameter with the CoreValve than with the 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 CoreValve devices were oversized (i.e., THV nominal diameter greater than native annular diameter), and all but 5 patients in the SAPIEN XT arm were oversized.
In the CHOICE-Extend registry, a larger THV diameter was chosen with the Evolut R than with the SAPIEN 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 THV oversizing in relation to native annular diameter with the 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 annulus group). In the large annulus group, 100% of Evolut R THVs were oversized, while 69.9% of SAPIEN 3 THVs were oversized (p < 0.001). In the small annulus group, 97.7% of Evolut R THVs were oversized versus 79.5% of SAPIEN 3 THVs (p = 0.005).
Invasive, echocardiographic, and magnetic resonance indexes of bioprosthetic valve performance
Tables 3 and 4 summarize procedural, in-hospital, and 30-day parameters of the hemodynamic performance of SE versus BE THVs in the 2 groups (large and small aortic valve annuli) in both cohorts (the CHOICE trial and CHOICE-Extend registry). In the CHOICE trial, 30-day indexed EOA (on Doppler echocardiography) was not significantly different between the CoreValve and the SAPIEN XT in either group of annular size. In contrast, transvalvular mean PG was lower after CoreValve than after SAPIEN XT implantation, in both the large annulus group (7 ± 3 mm Hg vs. 8 ± 3 mm Hg; p = 0.006) and the small annulus group (7 ± 3 mm Hg vs. 10 ± 4 mm Hg; p < 0.001). Moderate to severe PVR was significantly more frequent after CoreValve than after SAPIEN XT implantation in large annuli (15.1% vs. 0.0%; p = 0.002) but not in small annuli (0.0% vs. 5.7%; p = 0.495). Cardiac MRI data were available in a subgroup of patients (n = 90): 47 in the large annulus group (CoreValve, n = 16; SAPIEN XT, n = 31) and 43 in the small annulus group (CoreValve, n = 18; SAPIEN XT, n = 25). Online Table 1 compares patients who underwent MRI early after TAVR and those who did not undergo MRI. MRI RF was higher after CoreValve than after SAPIEN XT implantation in large annuli (10.5 ± 10.2% vs. 4.4 ± 4.5%; p = 0.036) but not in small annuli (4.0 ± 4.1% vs. 4.0 ± 3.4%; p = 0.975).
In the CHOICE-Extend registry, 30-day indexed EOA was significantly larger after Evolut R than after SAPIEN 3 implantation in both groups (1.08 ± 0.33 cm2/m2 vs. 0.86 ± 0.22 cm2/m2, p < 0.001, in large annuli; 1.04 ± 0.28 cm2/m2 vs. 0.80 ± 0.19 cm2/m2, p < 0.001, in small annuli). Moderate to severe PVR occurred in only 2 patients (both had SAPIEN 3 implantation), and any (mild or more) PVR was not significantly different between Evolut R and SAPIEN 3 in large annuli (41.7% vs. 32.5%; p = 0.243) and in small annuli (47.1% vs. 43.8%; p = 0.836). To account for imbalances in the baseline and procedural characteristics of patients who received Evolut R and those who received SAPIEN 3 THVs, multivariate regression analysis was conducted (Tables 5 and 6). On multivariate regression analysis, TAVR with the Evolut R (vs. the SAPIEN 3) was associated with a trend toward a higher incidence of mild or greater PVR in large annuli (OR: 1.92; 95% CI: 0.97 to 3.81; p = 0.063) but not in small annuli (OR: 1.22; 95% CI: 0.51 to 2.90; p = 0.652), after accounting for aortic valve calcification severity and aortic annular diameter and eccentricity. After accounting for aortic valve area index and left ventricular ejection fraction at baseline, aortic valve annular diameter indexed to body surface area, and balloon post-dilatation, TAVR with the Evolut R (vs. the SAPIEN 3) was associated with a trend toward a lower rate of PPM in large annuli (OR: 0.475; 95% CI: 0.220 to 1.024; p = 0.057) and was significantly associated with less PPM in the small annulus group (OR: 0.163; 95% CI: 0.052 to 0.504; p = 0.002).
Cardiac MRI data were available in a subgroup of patients (n = 150): 96 in the large annulus group (Evolut R, n = 30; SAPIEN 3, n = 66) and 55 in the small annulus group (Evolut R, n = 19; SAPIEN 3, n = 36). Online Table 2 summarizes the differences between patients who underwent MRI early after TAVR and those who did not undergo MRI. MRI RF was not different between the Evolut R and the SAPIEN 3 in large annuli (5.0 ± 3.8% vs. 5.0 ± 6.1%; p = 0.996) but was significantly lower after Evolut R than after SAPIEN 3 implantation in small annuli (2.9 ± 2.3% vs. 4.8 ± 3.7%; p = 0.023) (Figure 2).
Online Table 3 summarizes baseline and procedural characteristics and early outcomes of patients in the CHOICE-Extend registry stratified according to the implanted THV (Evolut R vs. SAPIEN 3). Online Table 4 summarizes some relevant baseline, procedural, and valve performance characteristics of the Evolut R versus the SAPIEN 3 stratified into small valves (26-mm Evolut R vs. 23-mm SAPIEN 3), medium-sized valves (29-mm Evolut R vs. 26-mm SAPIEN 3), and large valves (34-mm Evolut R vs. 29-mm SAPIEN 3). The incidence of severe PPM was significantly less (0% vs. 27%; p = 0.011) with the small Evolut R (26 mm) than with the small SAPIEN 3 (23 mm), while it was not different with medium and large valve sizes. The need for balloon post-dilatation was significantly higher with the Evolut R than with the SAPIEN 3 with medium and large but not small valve sizes (26-mm Evolut R vs. 23-mm SAPIEN 3: 25% vs. 22%; p = 0.784). MRI RF was not different between the Evolut R and the SAPIEN 3 in medium and large valve sizes but tended to be lower with the small Evolut R than with the small SAPIEN 3 (3.0 ± 2.6% vs. 5.3 ± 3.8%; p = 0.059).
The main finding of the present study is that SE THVs seem to be superior to BE THVs in patients with small aortic valve annuli, resulting in low rates of PPM and at least comparable rates of PVR.
The CHOICE trial was the first randomized multicenter trial comparing 2 THV platforms (SE vs. BE THVs). The CHOICE-Extend registry is, in contrast, a single-center, nonrandomized, all-comers registry. The differences between the 2 datasets are not confined to their designs but rather involve further key distinctions. First, whereas the CHOICE trial was run at a relatively early stage of the wide adoption of TAVR (2012 to 2013), the CHOICE-Extend registry involves a more contemporary TAVR experience, which is in part enlightened by the lessons learned from the CHOICE trial. For instance, the difference in device success rate between SE and BE THVs in the CHOICE trial was evident in large annuli but trivial in small annuli (5). Therefore, the SE Evolut R was 2-fold more frequently used in patients with small annuli than in those with large annuli in contemporary practice (the CHOICE-Extend registry). Second, in addition to the matured experience and the improved techniques practiced in the CHOICE-Extend registry, the introduction of improved THV technologies (e.g., SAPIEN 3 with a sealing skirt, Evolut R with 1 extra size [34 mm] and with repositionability potential) likely has contributed to improving the results. Finally, the “personalized” selection of the device in the registry (Online Table 3) compared with the randomization in the trial might have contributed to the improved outcomes in some of the THV performance indexes.
With these differences in mind, the changes between the results of the second- and third-generation SE and BE THVs (Figure 1) can be more reasonably interpreted. The overall incidence of any as well as moderate to severe PVR was less with the third- than with the second-generation THVs. The most remarkable change was that of the incidence of moderate to severe PVR with SE THVs (CoreValve vs. Evolut R: 9.6% vs. 0.0%).
SE THVs had better paravalvular sealing in smaller than in larger annuli in both cohorts. In the CHOICE trial, moderate to severe PVR on echocardiography was higher after CoreValve than after SAPIEN XT implantation in large (15% vs. 0%) but not in small annuli (0% vs. 6%). On MRI, the RF was higher after CoreValve 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 to severe PVR was rare (0.5%). On quantitative assessment of PVR severity by cardiac MRI, the RF was higher after SAPIEN 3 than after Evolut R implantation in small annuli (average 3% vs. 5%), with no difference noted in large annuli (5% vs. 5%). The latter assessment, by MRI, although limited by being available in only a subgroup of patients, exhibits 2 important strengths: 1) it is a quantitative assessment that is more precise and accurate than echocardiography, especially with small regurgitations (with third-generation THVs) (12); and 2) it was performed by MRI specialists blinded to clinical and echocardiographic data.
As baseline and procedural differences existed between patients who received Evolut R and SAPIEN 3 valves, multivariate analysis accounting for these differences was conducted and confirmed the improved paravalvular sealing of Evolut R in the small annular group.
On the basis of the manufacturer’s recommendations, the percentage diameter oversizing of the CoreValve ranges from 12% to 30% for the 23-, 26-, and 29-mm sizes but ranges from 7% to 19% for the 31-mm device. In the CHOICE trial, moderate to severe PVR was observed in 33.3% of patients who received the 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 section). This comes in line with a recently published comparison of the 31-mm CoreValve with the smaller sizes, which revealed higher rates of post-dilatation and implantation of a second THV and a lower rate of device success in the 31-mm device group (13). Introduction of the 34-mm Evolut R addressed this problem. Improved performance of the third-generation (vs. second-generation) SE THV in large annuli is largely to be ascribed to the introduction of the 34-mm device. The 34-mm Evolut R addresses almost the same spectrum of annular diameters treated previously with the 31-mm CoreValve (26 to 30 mm), thus allowing “sufficient” oversizing (12% to 31%) even in the upper part of the scale of annular size, a subgroup of patients who had the highest rate of PVR in the CHOICE trial. SE THV percentage 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 effects of the repositionability feature and of a better “personalized” selection of the device type are not to be overlooked. A tendency of the operator to choose the Evolut R (rather than the SAPIEN 3) in patients with less heavily calcified aortic valve complexes (Online Table 3) is a possible contributing factor to the improved rate of PVR with the third-generation SE THV. Accounting for differences in aortic valve calcification unmasked a trend toward a higher incidence of PVR after TAVR with the Evolut R in large annuli. Interestingly, such a trend was not seen in small annuli, even after accounting for relevant confounders.
Data from the pivotal randomized trials and prospective registries of TAVR with the SE THV (14) revealed an unequivocal relationship between THV oversizing and the risk for PVR. In a study that included patients enrolled in the CoreValve US Extreme Risk Pivotal Trial (15) or CoreValve US High Risk Pivotal Trial (16) (n = 1,023), the incidence of moderate to severe PVR increased progressively (from 6.3% to 17.6%) with decreasing degree of THV oversizing (14). THV oversizing was lower in patients treated 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 with the 31-mm CoreValve (31.9%) than other device sizes (7.7% to 16.4%). Adherence to sizing recommendations was achieved in 71.6% (perimeter-based sizing) to 75.8% (diameter-based sizing) of patients, and the rate of 30-day outcomes (including death, stroke, and need for pacemaker) was not influenced by the degree of oversizing (14).
We observed a remarkable decline of percentage oversizing of the BE THVs, from 11.4 ± 7.0% with the SAPIEN XT to 3.7 ± 5.5% with the SAPIEN 3 despite similar manufacturer’s sizing recommendations. This trend toward less oversizing of BE THVs was driven in part by data on the risk for excessive oversizing of these valves. Safety of “excessive” oversizing of SE THVs compared with BE THVs was shown in a study that compared SE THVs and BE THVs sized with moderate (5% to 20%) versus excessive (>20%) oversizing (17). In the moderate oversizing group, SE THVs more often required post-dilatation, while in the excessive oversizing group, annular rupture occurred only with BE THVs. This latter risk for annulus injury, in addition to the better sealing properties of the SAPIEN 3, explains why operators tend to systematically less oversize the SAPIEN 3 compared with the SAPIEN XT. In the PARTNER (Placement of Transcatheter Aortic Valve) II SAPIEN 3 intermediate-risk trial, any degree of oversizing was achieved in 63.2% to 76.9% (according to the method of sizing) (18). The incidence of moderate to severe PVR was highest in patients with no oversizing (7.8% to 13.2%), less so in patients with modest oversizing of <10% (2.8% to 4.2%), and lowest in patients with oversizing of ≥10% (0.3%). In line with our findings, the extent of oversizing was lower with the 23-mm SAPIEN 3 (average 6.5%), more so with the 26-mm device (7.5%), and highest with the 29-mm size (12.9%) (18). Inversely proportionate to the extent of oversizing, any PVR occurred in 57.1% of patients who received 23-mm devices, in 45.2% of patients who received 26-mm devices, and in 39.0% of patients who received 29-mm devices (18).
Although the remarkable reduction of oversizing with BE THVs in recent practice should theoretically be associated with a proportional increase in the overall incidence of PVR, this is apparently compensated for by a very effective paravalvular sealing skirt, but probably at the expense of a higher residual transvalvular PG and a higher incidence of PPM. In the present analysis, BE THVs tended to yield smaller EOA and a higher residual PG than SE THVs in the CHOICE trial, and the differences were significant in the CHOICE-Extend registry. Multivariate regression analysis (Table 6) revealed that the use of the Evolut R was significantly associated with a lower risk for PPM, especially in patients with small annuli. The supra-annular leaflet function in SE THVs (as opposed to an intra-annular level in BE THVs) could lead to a larger effective orifice and lower residual gradients, regardless of annular size. However, the systematic “generous” oversizing of SE THVs could also be an explanation for the favorable systolic performance.
Unlike the CHOICE trial, the CHOICE-Extend registry is a nonrandomized study, and baseline differences existed between patients treated with SE versus BE THVs. Improved performance of SE THVs can partially be ascribed to the use of this device in patients with, for example, less landing zone calcification. Although we accounted for these differences in multivariate analysis, our findings need to be further confirmed, ideally in a randomized setting. Although sought for in most of the CHOICE trial patients and all CHOICE-Extend registry patients, MRI data were available in a relatively small subgroup of patients. The high rate of pacemaker implantations in TAVR patients, in addition to other contraindications of MRI, accounts for the majority of the cases without MRI data. Although these limitations are unavoidable (being inherent to the MRI technology), interpretation of the MRI data should be cautious, taking into account the differences between patients with versus without MRI (summarized in Online Tables 1 and 2). Finally, the CHOICE trial involved outmoded valve iteration. However, the larger part of the body of evidence on TAVR is derived from experience with this iteration, and extrapolation to newer iterations is a common practice, although not supported by adequate evidence. It was therefore intended to combine the contemporary data with the older data to emphasize the similarities and differences between both iterations.
Bioprosthetic valve performance in patients with small aortic valve annuli seems to be better with SE THVs than with BE THVs. The improved performance includes comparable PVR and less PPM.
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.
Drs. Richardt and Abdel-Wahab have received institutional research grants from St. Jude Medical, Biotronik, and Medtronic. Dr. Abdel-Wahab is a proctor for Boston Scientific. Dr. Mehilli has received lecture fees from Abbott Vascular, Biotronik, and Edwards Lifesciences; and has received institutional grants from Abbott Vascular and Edwards Lifesciences. Dr. Neumann has received institutional research grants from Edwards Lifesciences, Biotronik, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- indexed aortic valve area
- confidence interval
- effective orifice area
- magnetic resonance imaging
- odds ratio
- pressure gradient
- prosthesis-patient mismatch
- prosthetic valve regurgitation
- regurgitant fraction
- transcatheter aortic valve replacement
- transcatheter heart valve
- Received June 18, 2018.
- Revision received July 25, 2018.
- Accepted July 31, 2018.
- 2018 American College of Cardiology Foundation
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