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Optimal Oversizing in Transcatheter Aortic Valve Replacement with the Self-Expanding Evolut Valve System
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Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of the Journal of Invasive Cardiology or HMP Global, their employees, and affiliates.
J INVASIVE CARDIOL 2024. doi:10.25270/jic/24.00011. Epub March 4, 2024.
Abstract
Objectives. Transcatheter valve oversizing has been associated with reduced paravalvular leaks (PVL) and valve migration risk. However, no optimal cut-off oversizing value has been defined for the Evolut system (Medtronic). The aim of this study was to assess the relationship between the degree of oversizing and moderate-to-severe PVL and determine the optimal oversizing cut-off value.
Methods. We conducted a multicenter study that included 740 consecutive patients with multidetector computed tomography (CT) data. Valve size was selected according to manufacturer recommendations, with oversizing ranging from 10% to 30%. The primary endpoint was moderate-to-severe PVL.
Results. The median age was 84 years (79-87 years), with 58.4% women, and a median EuroSCORE II of 4.1% (2.4-7.3%). Moderate-to-severe PVL was observed in 7.0% of the patients. An inverse relationship was found between oversizing and both PVL (11.4%, 8.6%, 5.4%, and 2.7% for quartiles Q1 to Q4; P = .007) and the need for post-dilation (P = .016). The multivariable analysis showed an association between oversizing and PVL (OR: 0.915 for each 1% increase [95% CI, 0.864-0.969; P = .002]). The optimal oversizing cut-off value to predict PVL was 20%, and PVL was significantly higher in patients with oversizing less than 20% (10.5% vs.4.2%, P < .001). There were no differences in major clinical events according to the degree of oversizing, and a higher oversizing did not translate into an increased risk of permanent pacemaker (18.4% vs.18.3%, P = .976).
Conclusions. In TAVR with the Evolut valve, a higher oversizing was associated with lower rates of moderate-to-severe PVL and a lower need for post-dilation, with no negative impact on procedural and early clinical outcomes. A 20% oversizing threshold could be suggested to reduce PVLs. Further prospective studies are warranted to validate optimal oversizing for this valve system.
Introduction
Moderate-to-severe paravalvular leaks (PVLs) have been associated with an unfavorable prognosis in patients undergoing transcatheter aortic valve replacement (TAVR).1 Thus, reducing the occurrence of PVL to a minimal degree is a crucial aim in current TAVR procedures. Optimal aortic annulus sizing based on multidetector computed tomography (MDCT) measurements has become an essential part of TAVR planning, as device oversizing has been associated with lower rates of moderate-to-severe PVL in several types of transcatheter bioprostheses.2,3 In particular, for the self-expandable supra-annular prostheses, an inverse correlation between oversizing and PVL has been shown with the first-generation Corevalve prosthesis (Medtronic),4 and more recently for patients with unusually large annuli with new generation devices.5 However, no optimal cut-off oversizing value has been defined for new generation supra-annular valves.
To date, only a limited number of prosthesis sizes are available for the second- and third-generation supra-annular Evolut valve systems (23 mm, 26 mm, 29 mm, and 34 mm; Medtronic) for annuli with a perimeter ranging from 56.5 to 94.2 mm. Although a chart has been proposed by the manufacturer as a guide for valve size selection according to MDCT measurements, appropriate device choice remains a challenge in the planning of many TAVR procedures, since the degree of oversizing may largely vary depending on the valve sizes available for a specific annulus.
The purpose of this multicenter study was to evaluate the relationship between the degree of oversizing and moderate-to-severe PVL in patients undergoing TAVR with the new generation supra-annular valves Evolut R/PRO/PRO+, and to explore optimal oversizing cut-off values for such devices.
Methods
Patient population and procedures. Our study was based on prospectively collected data from 4 high-volume TAVR centers in Canada and Europe. A consistent database design was used for data collection, including baseline and procedural variables and outcomes, in all participating centers. This was a retrospective, non-prespecified analysis that was performed to shed some light on a clinically significant research question. All consecutive patients with severe aortic valve stenosis and available MDCT data having undergone TAVR with an Evolut R/Evolut PRO/Evolut PRO+ device between February 2015 and April 2023 in the participating centers were included in the analysis. Patients undergoing a valve-in-valve procedure, those with no available data regarding PVL measured by echocardiography at discharge, as well as patients with an annular size outside the manufacturer’s recommended range for sizing chart or a non-recommended extreme oversizing percentage value (< 10% or > 30%) were excluded.
Procedures were performed according to each hospital protocol. Repositioning was performed when needed and post-dilation was considered in cases of intraprocedural moderate-to-severe PVL at the operator’s discretion. Bioprothesis size was determined by local heart teams, and manufacturer recommendations were taken into account. Access was transfemoral by default, though alternative access — mainly transarterial (transcarotid, transaxillary) — was used in cases with suboptimal iliofemoral anatomy. Baseline demographic, clinical, and echocardiographic parameters were collected upon admission. Informed consent was obtained from all patients prior to the intervention. Anonymized data were used for analyses, in accordance with the ethics committees of each participating center.
Baseline MDCT data and oversizing calculation. MDCT was performed in all patients prior to TAVR to obtain valve measurements and evaluate the most appropriate access route. 3Mensio software (Pie Medical) was used for the analysis in most cases. Using a manually traced virtual ring as previously described,6 the perimeter of the annulus was measured for all patients, since this has been shown to be better than the area at taking annulus eccentricity into account, which is an essential factor when implanting self-expandable valves.
The oversizing degree was calculated as a percentage, as previously described,4 using the following formula: [(valve perimeter - annulus perimeter) / annular perimeter] x 100. The degree was used as the main variable in the analyses.
Study endpoints. The primary endpoint of the study was moderate-to-severe PVL at discharge as evaluated by echocardiography.7 Secondary endpoints included post-dilation, need for permanent pacemaker, and other clinical events according to Valve Academic Research Consortium-3 (VARC-3) criteria.8
Statistical analysis. Patients were distributed in quartiles of oversizing used in TAVR procedures. Bar chart graphs were shown for moderate-to-severe PVL and for post-dilation according to oversizing quartiles. Frequencies were used for categorical variables. Continuous variables were presented as mean ± standard deviation when normally distributed and as median (interquartile range [IQR]) if non-normally distributed. A receiver-operating characteristics (ROC) curve and the Youden index were used to find the optimal cut-off value of oversizing. According to this cut-off, comparisons of baseline and procedural parameters as well as clinical outcomes were performed between patients above and below such threshold. The Student's t-test was used for parametric variables, Mann-Whitney tests for non-parametric variables, and chi-squared tests (or Fisher’s tests when appropriate) for categorical variables. A multivariable logistic regression analysis to evaluate potential predictors of moderate-to-severe PVL was performed based on all variables achieving statistical significance (P < .05) in univariable analyses. The results were reported as odds ratios and 95% CIs. Statistical significance was set at P < .05. All analyses were performed with the SPSS statistical software package version 29.0 (IBM).
Results
Study population. A total of 740 patients receiving a new generation supra-annular self-expandable valve (Evolut R, Evolut PRO, Evolut PRO+) with available MDCT-derived annulus measurements prior to the procedure were included in the analysis. All excluded patients (and the reasons) are reported in Figure 1.
The main baseline characteristics of the study population are shown in Table 1. The median (IQR) age of the population was 84 years (79-87 years), 58.4% were women, and the median EuroSCORE II was 4.1% (2.4%-7.3%). A transfemoral approach was used in most patients (89.1%), and an Evolut PRO/Evolut PRO+ device was implanted in 63% of the patients. The median aortic annulus perimeter was 74.0 mm (69.5-80.0 mm), and the most commonly used valve size was 29 mm, with a median oversizing degree in the overall population of 20.8% (16.7%-25.2%).
Clinical outcomes. Details on periprocedural and in-hospital outcomes are summarized in Table 2. The valve prosthesis was successfully implanted in 92.4% of the cases. There were no cases of annulus rupture, and a second prosthesis was required in 2.8% of the patients. The most common in-hospital complication was permanent pacemaker implantation (18.4%), followed by major vascular complications (5.3%). Moderate-to-severe PVL at discharge was present in 7.0% of the cases. More specifically, moderate-to-severe PVL was 8.0% with the Evolut R valve, and this was slightly lower with the new generation Evolut PRO/PRO+ valve (6.4%). However, this difference did not reach significance (P = 0.41).
Impact of oversizing. An inverse relationship was found between quartiles of oversizing and moderate-to-severe PVL at discharge: 11.4% of PVL for Q1 (10%-17%) of oversizing, 8.6% for Q2 (17%-21%), 5.4% for Q3 (21%-25%), and 2.7% for Q4 (25%-30%) (P = .007) (Figure 2).
Likewise, an inverse association was shown between quartiles of oversizing and the need for balloon post-dilation (P = .016) (Figure 3). According to the Youden index based on a ROC-curve, the optimal cut-off value of oversizing to predict moderate-to-severe PVL was 20%, with an area under the curve of 0.650 (95% CI, 0.580-0.720) (Figure 4). Baseline, procedural, and in-hospital parameters are reported in Tables 1 and 2 for patients below or above this oversizing threshold (n = 333 and n = 407 patients with oversizing < 20% or ≥ 20%, respectively). Baseline characteristics were comparable between groups, except for a slightly higher EuroSCORE II value in the higher oversizing group. Procedural results were similar in both groups, except for a significantly higher rate of pre-dilation (27.6% vs 19.9%, P = .013) and post-dilation (26.4% vs 19.4%, P = .023) in the lower oversizing group. As for clinical outcomes, moderate-to-severe PVL was shown to be significantly higher in the group with a lower oversizing (10.5% vs 4.2%, P < .001). There were no differences in major clinical events based on the degree of oversizing; specifically, no increased need for permanent pacemaker was found in the higher oversizing group (18.4% vs 18.3%, P = .976).
Predictors of PVL. The multivariable logistic regression analysis showed a significant association between the degree of oversizing and moderate-to-severe PVL at discharge (OR 0.915 for each increase in 1%; 95% CI, 0.864-0.969; P = .002) (Table 3).
Discussion
The main findings of this study can be summarized as follows: (1) a higher degree of valve oversizing was associated with a significant reduction in PVL in patients undergoing TAVR with the Evolut valve system, and a lower valve oversizing was identified as independent predictor of PVL; (2) oversizing was inversely related to the need for balloon post-dilation; (3) a higher degree of valve oversizing was not associated with an increased risk of conduction disturbances leading to permanent pacemaker implantation; (4) current recommendations of the manufacturer on oversizing are in line with the findings in our study; and (5) an optimal oversizing cut-off value of 20% was identified in our population for the Evolut valve system with the sizes available at the time of the study.
With a limited number of different prosthesis sizes being available in the market, both valve choice and degree of oversizing are crucial decisions for the heart team when preparing for TAVR procedures. Inappropriate valve oversizing can trigger potential adverse clinical outcomes, such as significant PVL, with major prognostic consequences. This becomes even more important when deciding the valve size in borderline cases. A higher degree of oversizing not only results in lower rates of moderate-to-severe PVL, but also in a reduced need for post-dilation,4 which implies a lower risk for severe complications associated with post-dilation, such as stroke9,10 or annulus rupture.11,12 This should be particularly considered in cases with a high degree of calcification at the annulus level when establishing the trade-off between the risk resulting from excessive oversizing and the expected unfavorable consequences of post-dilation after valve deployment.
A certain degree of oversizing has been shown to reduce PVL.3 However, how much oversizing would be optimal? To the best of our knowledge, no optimal cut-off value based on a large multicenter experience has been proposed for the Evolut valve system to date. The oversizing cut-off value to predict moderate-to-severe PVL in our population was at least 20%. A small series in a single-center study, in which several valve models were analyzed, found a similar value (17.6%) to predict the absence of PVL in 75 patients undergoing TAVR with new-generation supra-annular Evolut bioprostheses.13 Drakopoulou et al found a slightly lower oversizing threshold value of 14% in a single center study of 152 patients with the Corevalve and Evolut R prosthesis.14 Further prospective studies are warranted to confirm our findings on optimal oversizing threshold. On the other hand, patients undergoing TAVR with balloon-expandable valves usually require less oversizing than self-expandable valves. This is likely due to the higher radial force required in self-expandable devices to stabilize the prosthesis within the aortic annulus. Ki et al proposed a cut-off value of at least 10.2% for the balloon-expandable Sapien system (Edwards Lifesciences).13
In balloon-expandable valves, Yang et al showed the need for a higher degree of oversizing in the old-generation Sapien XT compared with the newer generation Sapien 3.15 The latter includes a sealing skirt,15 which probably translates into the need for a lower oversizing degree in newer generation devices. The new generation Evolut PRO and PRO+ also incorporate an external wrap that increases sealing of the annulus, aiming at potentially reducing PVL.16 This feature could eventually require less degree of oversizing. However, when adding the type of valve (Evolut R vs PRO/PRO+) in our multivariable analysis, the new generation device did not seem to be associated with a lower rate of moderate-to-severe PVL, and the degree of valve oversizing remained an independent predictor of PVL after adjusting for valve type. Although these results did not reach statistical significance in our study — probably due to the limited number of patients —it would be interesting to investigate this in a larger population. Of note, manufacturer recommendations regarding valve sizing have remained similar for all generations of Evolut valve systems.
Prior studies have shown the use of a higher degree of oversizing in women with small aortic annuli.13 Although our study showed a similar trend (60.9% and 55.3% of women in the higher and lower oversizing groups, respectively), this difference did not achieve statistical significance.
Unlike some studies with balloon-expandable valves,17-19 but in line with prior publications on self-expandable valve systems,4,5 our findings did not show a higher rate of permanent pacemaker implantation with higher degrees of oversizing. These contrasting results may be explained by differences in the design of such devices. However, larger studies are required before drawing any solid conclusions.
Several factors have been shown to predict PVL; potential patient factors include the degree of aortic valve leaflet calcification, annulus eccentricity, and discordant sizing.1 Since patient characteristics such as anatomic features of the valve or degree of calcification cannot be modified, acting on procedural factors such as oversizing is key. In fact, in cases of significant valvular calcification, small sinus of Valsalva diameters, or bicuspid valves, the operator could decide to intentionally undersize in order to avoid possible critical complications.4
The results of this study highlight the importance of 3-dimensional imaging (ie, MDCT) of the aortic annulus in order to choose appropriate sizing due to the eccentric morphology of the native annulus.20 For self-expandable valves in particular, using annular perimeter is of utmost importance, since such prostheses tend to adapt to native anatomies.21The use of 2-dimensional imaging (ie, transesophageal echocardiography) may result in an unwanted undersizing.22 MDCT is therefore now considered the gold-standard for valve sizing.6 Recommended valve size charts for the Evolut valve system are currently based on such measures, and our findings confirm their usefulness.
Limitations. Even though this study was based on prospectively collected data, our analysis is retrospective and non-prespecified, and has the limitations generally associated with such a design. Nonetheless, using prospective, real-world, multicenter data from a period of self-expandable TAVR use provides a unique opportunity to shed some light on a relevant clinical question that may guide implantation decisions in current clinical practice. Our study focuses solely on supra-annular self-expandable new-generation Evolut valves; thus, these results cannot be extrapolated to other types of bioprostheses. Selection bias cannot be excluded, as choice of the valve was at the operator’s discretion, and the number of patients that were excluded from TAVR due to challenging anatomy in the planning MDCT is unknown. Additionally, some variability regarding annulus sizing measurements may be present among the participating centers. There was no echo core lab in this study, and echo measurements were performed by the echocardiographists in each participating center. However, the echocardiographists involved in this study were highly experienced, blinded to the degree of valve oversizing, and followed the recommendations of the American Society of Echocardiography.7 Also, some studies have suggested a progressive reduction in PVL over time after the implantation of CoreValve/Evolut valve systems, and further studies should assess the impact of oversizing in long-term PVL.2,23 Finally, data regarding depth of implantation, which could have had an impact on degree of oversizing, were not available.
Conclusions
In patients undergoing TAVR with Evolut R/PRO/PRO+ bioprostheses, a higher degree of oversizing was associated with lower rates of moderate-to-severe PVL and a lower need for post-dilation, with no negative impact on procedural and early clinical outcomes, including permanent pacemaker. An appropriate oversizing should be considered when using the new generation self-expandable supra-annular Evolut valve, and a 20% threshold could be a guide to reduce the likelihood of PVLs. Further prospective studies are warranted to validate these findings.
Affiliations and Disclosures
From the 1Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada; 2Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; 3Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy; 4Cardiology Department, Instituto Clínic Cardiovascular, Hospital Clínic, Barcelona, Spain and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Acknowledgments: Silvia Mas-Peiro has received a research grant from the “Fundación Alfonso Martín Escudero” (Madrid, Spain). Dr. Rodés-Cabau holds the Research Chair “Fondation Famille Jaques Larivière” for the Development of Structural Heart Interventions.
Disclosures: Dr. Morís is a proctor for Medtronic. Dr. Rodés-Cabau has received institutional research grants and consultant/speaker fees from Medtronic and Edwards Lifesciences. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.
Address for correspondence: Josep Rodés-Cabau, MD, PhD, Quebec Heart & Lung Institute, Laval University, 2725 chemin Ste Foy, Quebec City, QC, Canada. E-mail: josep.rodes@criucpq.ulaval.ca
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