Comparison of the Acurate Neo Vs Neo2 Transcatheter Heart Valves

Abstract

Background. Few data exist on immediate outcomes of the next-generation Acurate neo2 prosthesis (Boston Scientific), which is distinguished by an active sealing mechanism. We sought to determine procedural outcomes of transfemoral transcatheter aortic valve replacement using the neo2 in comparison with its predecessor, the Acurate neo. Methods. In this retrospective analysis, consecutive neo2 and neo cases were compared from 2 high-volume centers. The primary outcome of interest was the rate of relevant paravalvular regurgitation (PVR), defined as PVR ≥ moderate, or valve-in-valve and/or surgical aortic valve replacement for PVR ≥ moderate. Secondary outcomes of interest were assessed according to Valve Academic Research Consortium (VARC)-3 criteria. Logistic regression analysis was used to identify predictors of relevant PVR. Results. A total of 810 neo2 and 2055 neo cases comprised the study cohort. The rate of relevant PVR was significantly lower in the neo2 group (2.7% vs 4.5%; P=.04). The technical success rate was numerically higher in the neo2 group (91.5% vs 89.3%; P=.10) and the rate of device success at 30 days was significantly higher (86.5% vs 82.9%; P=.02). In the neo group, a greater amount of aortic valve calcification (AVC), the presence of eccentric AVC, less oversizing, and a higher sinotubular junction annulus index were predictors of relevant PVR, whereas in the neo2 population only the presence of eccentric AVC, less oversizing, and a higher sinotubular junction annulus index was predictive. Conclusion. The neo2 valve shows superior outcomes over the neo valve, with a lower burden of PVR and a higher device success rate at 30 days.

J INVASIVE CARDIOL 2022;34(11):E804-E810. Epub 2022 October 21.

Key words:  Acurate, TAVR, paravalvular leak, self-expanding, transcatheter heart valve

The field of transcatheter aortic valve replacement (TAVR) is continuously evolving in terms of knowledge, experience, and technology, all of which have contributed to improved outcomes.^1,2 In particular, iterations of transcatheter heart valve (THV) systems were designed to address open issues, including lower insertion profiles of the delivery catheters, resheathability and retrievability for more precise positioning, and the addition of sealing skirts to decrease paravalvular regurgitation (PVR).³ The Acurate neo (Boston Scientific) is a self-expanding THV that received the CE mark in 2014 and was used in Europe, Canada, South America, and Australia.⁴ Despite its numerous favorable attributes, the main limitation has been the high incidence of PVR ≥ moderate due to its relatively low radial force and the absence of a sealing skirt.⁵ In autumn 2020, the next-generation device, the Acurate neo2, became commercially available.⁶ Even though most of the favorable characteristics were preserved, important modifications were the addition of a radiopaque positioning marker and an active sealing skirt to enhance paravalvular sealing. Currently, the neo2 is under investigation in the United States investigational device exemption trial (NCT03735667), and another postmarket registry (NCT04655248) has completed recruitment, but real-world data are lacking.

The aim of the present study was to analyze the outcomes of transfemoral TAVR using the neo2 system in comparison with the first-generation neo THV, with an emphasis on PVR and its predictors.

Methods

Study cohort and procedure. Consecutive patients with severe native aortic stenosis who underwent transfemoral TAVR using the neo (n = 2055) or neo2 (n = 810) prosthesis between May 2012 and December 2021 at 2 German high-volume centers (Kerckhoff Heart Center, Bad Nauheim; St Josef Hospital, Dortmund) were included in this retrospective analysis. Baseline characteristics, including demographics, comorbidities, risk scores, and echocardiography data as well as procedural data and complications, were collected prospectively in a dedicated database by each participating center. Aggregation and review of all data were managed by a single investigator, and inconsistencies were resolved by direct communication between the centers. Follow-up data were obtained during outpatient visits, from the most recent medical reports, or via telephone interview.

Design descriptions of the 2 prostheses and the implantation technique are available in the literature.^4,6 Of note, as of January 2019 the “SLIM” protocol, which involves the use of low amounts of contrast agent and single arterial access, was established at the Kerckhoff Heart Center⁷ and this protocol was used in some of the patients. Patients gave informed consent for the procedure. The study adhered to the Declaration of Helsinki. Due to the retrospective nature of the study, ethical approval was waived by each local ethics committee.

Multidetector computed tomography. Multidetector computed tomography (MDCT) was performed using a 64-slice or 192-slice dual-source scanner (Somatom Definition or Somatom Force; Siemens Healthineers) as previously described.⁸ Dedicated software was used for the analysis of MDCT datasets (3mensio; Pie Medical Imaging).

In addition to standard measurements of aortic root dimensions, the cover index (CI) and sinotubular junction (STJ) annulus index (STJAI) were determined as follows:

CI = [100 × (prosthesis diameter – perimeter derived annulus diameter)]/(prosthesis diameter)

STJAI = (100 × STJ perimeter derived annulus) / STJ

The aortic valve calcium score (AVCS) was measured according to the Agatston method using non-contrast-enhanced MDCT scans.⁹ The calcium density was calculated as AVCS/annular area (AU/cm²).¹⁰ The presence of eccentric aortic valve (AV) calcification and relevant left ventricular outflow tract (LVOT) calcification was determined by visual evaluation of the AV in short-axis views and maximum-intensity projections (Figure 1).¹¹

Assessment of PVR and implantation depth. PVR was assessed at discharge by echocardiography using a 3-class grading scheme (none/trace, mild, moderate, severe) in adherence to existing recommendations.¹² Prosthesis-patient mismatch (PPM) was defined according to Valvular Academic Research Consortium (VARC)-3 criteria.¹² The implantation depth of the prosthesis was determined upon final angiography at the non-coronary cusp (NCC) and the left coronary cusp (LCC), as described previously.¹³

Outcomes of interest. The primary outcome measure was the incidence of relevant PVR,  defined as PVR ≥ moderate on echocardiography at discharge, the implantation of a second valve, or surgical AV replacement for PVR ≥ moderate within 30 days of the index procedure. Secondary outcome measures were 30-day all-cause mortality, technical success, device success at 30 days, and the early safety combined endpoint at 30 days according to the recent VARC-3 document.¹²

Statistical analysis. Continuous data are presented as median and interquartile range (IQR). Group comparisons were performed using the Mann-Whitney U test and the 2-sided Fisher’s exact or the Chi-squared test, as appropriate.

To determine predictors of relevant PVR, univariate logistic regression was performed. The following variables were included: calcium density, presence of eccentric AV calcification, presence of LVOT calcification, presence of a bicuspid valve, CI, STJAI, and valve generation. All variables with P-values <.10 in the univariate analysis were entered into the multivariate analysis with a stepwise, bidirectional, variable elimination process.

For all analyses, a 2-sided P-value <.05 was considered to indicate statistical significance. All analyses were performed with R, version 4.2.1 (R Core Team, 2021).

Results

Baseline data. Baseline characteristics of the study population were similar between neo and neo2 groups (Table 1). Eccentric calcium distribution was more frequent in the neo2 group (14.5% vs 11.5%; P=.032). Both the CI (5.0% [IQR, 3.2-7.1] vs 4.8% [IQR, 2.8-7.0]; P=.05) and the STJAI (14.0% [IQR, 9.7-18.6] vs 13.6% [IQR, 9.1-18.3]; P=.09) were numerically higher in neo2 recipients.

Procedural data and outcomes. The distribution of valve sizes was similar between neo2 and neo patients (Table 2). Procedural duration was shorter (45.0 min [IQR, 36.0-55.0] vs 47.0 min [37.0-62.0]; P<.001) in the neo2 group, and the amount of contrast agent utilized was lower (67 mL [IQR, 28-109] vs 90 mL [IQR, 70-120]; P<.001). The latter finding was owing to a more frequent application of a low contrast agent protocol (SLIM) in the neo2 group (48.5% vs 7.6%; P<.001). Predilation was more common in the neo2 group (90.9% vs 73.2%; P<.001), but rates of postdilation did not differ. Implantation depths at the NCC (6.0 mm [IQR, 4.0-6.5] vs 6.0 mm [IQR, 4.0-7.0]; P=.01) and the LCC (5.0 mm [IQR, 3.0-6.5] vs 6.0 mm [IQR, 4.0-6.5]; P<.001) were smaller in the neo2 group.

Technical success was numerically higher in the neo2 group (91.5% vs 89.3%; P=.10) and device success at 30 days was significantly higher (86.5% vs 82.9%; P=.02) (Table 2). Transprosthetic mean gradients were higher among neo2 recipients (8.5 mm Hg [IQR, 6.0-11.0] vs 8.0 mm Hg [IQR, 6.0-11.0]; P=.02). The rate of relevant PVR was significantly lower in the neo2 group (2.7% vs 4.5%; P=.03). Figure 2 depicts the comparative distribution of PVR grades, showing a lower overall burden of PVR across all grades in the neo2 group.

Severe bleeding, defined as Blood Academic Research Consortium (BARC) type 2-4 (14.8% vs 19.8%; P<.01), and major cardiac structural complications according to VARC-3 criteria (0.9% vs 1.9%; P=.048) were less frequent in the neo2 group. All other outcomes were similar, including 30-day all-cause mortality and rates of permanent pacemaker implantation (Table 2).

Predictors of relevant PVR. Univariate and multivariate logistic regression analyses for the total population and for the 2 neo generations separately are shown in Table 3. In the total cohort, higher calcium density, presence of eccentric AV calcification, lower CI, higher STJAI, and the use of first-generation neo devices were independent predictors of relevant PVR.

In the neo group, higher calcium density, presence of eccentric AV calcification, lower CI, and higher STJAI were independent predictors of relevant PVR, whereas among neo2 recipients, only the presence of eccentric AV calcification and a lower CI independently predicted relevant PVR.

Figure 3 illustrates the marked effect of the valve generation in the multivariable regression model, showing that the use of neo2 prostheses was associated with a significantly reduced probability of PVR for the same calcium density. Similarly, for the same probability of PVR, the neo2 prosthesis required a much higher calcium density.

Discussion

Main findings. In patients implanted with the neo2 device, there was a lower overall burden of postprocedural PVR in comparison with those receiving its predecessor, the neo THV. For the neo valve, predictors of relevant PVR included the total AV calcification (calcium density), the presence of eccentric AV calcification, a lower CI, and a higher STJAI, whereas in the neo2 population only the presence of eccentric AV calcification and a lower CI were predictive. Notably, this improvement did not compromise hemodynamic valve performance and pacemaker rates, which were similarly favorable in the 2 groups.

Paravalvular regurgitation. Notwithstanding its balanced profile, the Achilles’ heel of the first-generation neo system has been the relatively high incidence of PVR ≥ moderate owing to the moderate radial force and lack of a sealing skirt. While in most prospective and retrospective observational studies, the rates of PVR ≥ moderate were in an acceptable range (between 4.1% and 7.3%),^4,14,15 2 recent randomized trials (SCOPE I and II) showed relatively high rates of PVR ≥ moderate (approximately 10%).^5,16 This discrepancy may be due to several reasons, including selection bias and the absence of core laboratory echocardiography assessment in observational analyses; in addition, varying center experience, the lack of core laboratory for MDCT measurements, and the absence of screening committees to ensure uniform sizing approaches may have played a role in the SCOPE trials.

A first step to address this shortcoming of the neo prosthesis was a minimal iteration with an active sealing mechanism of the neo2 valve, which is based on the same stent frame and hence has the same radial force as the neo device.⁶ The substantial decrease in PVR across all grades shown in the present study confirms for the first time the clinical efficacy of this sealing skirt. In particular, the reduction of mild or mild-to-moderate PVR may be of prognostic relevance.¹⁷ Accordingly, the calcium density as an indicator of the overall calcium burden of the device landing zone only was an independent predictor of relevant PVR in the neo group, but not in the neo2 group.

Nonetheless, the presence of eccentric AV calcification independently predicted relevant PVR in both neo and neo2 cases, which suggests that the sealing skirt may not suffice to compensate for the low radial force of the neo platform in this specific anatomic subset. It is likely that eccentric calcium hinders full and symmetric expansion of the stent frame, and, in particular, proper apposition, which is required for optimal paravalvular sealing.

A notable finding is that the presence of LVOT calcification was not an independent predictor of relevant PVR for either the neo or the neo2 valve. This is in contrast to most other THV types, where LVOT calcification has adverse effects on outcomes.¹⁸ A possible explanation for this observation may be that the implanted neo or neo2 platform exhibits less interaction with the LVOT.

Procedural aspects. There are several procedural aspects that need further explanation. The higher rate of predilation in the neo2 group may be ascribed to a change in procedural strategy over time. On the other hand, the similar rate of postdilation may be surprising but could be attributed to the higher proportion of eccentric AV calcification in the neo2 group. The lower amount of contrast agent in the neo2 group is due to the larger proportion of cases that were performed using a low contrast agent protocol, as previously described.⁷ The higher incidence of severe bleeding and major cardiac structural complications in the neo group most likely is the result of a learning curve over time.

Study limitations. The present analysis is constrained by its retrospective, non-randomized character. The relatively long time period of study inclusion introduces bias due to learning curve effects, different procedural approaches (eg, the SLIM low contrast agent protocol), and various sizing and pre-/postdilation strategies. There was no monitoring of adverse events and imaging data were not adjudicated by a core laboratory. LVOT calcification and eccentric AV calcification were assessed visually without any further quantification. These limitations notwithstanding, these results are from the largest database thus far originating from 2 high-volume centers employing the neo platform.

Conclusion

The neo2 valve provides superior outcomes over the neo valve, resulting in a lower burden of PVR and a higher device success rate at 30 days without compromising hemodynamic valve performance and pacemaker rates, which were similarly favorable in both groups. The active sealing mechanism of the neo2 valve seems to be efficient and to a certain degree offsets severe, but non-eccentric, AV calcification.

Acknowledgments. We thank Elizabeth Martinson, PhD, of the KHFI Editorial Office for her editorial assistance.

Affiliations and Disclosures

*Joint first authors.

From ¹Kerckhoff Heart Center, Bad Nauheim, Germany; ²Kerckhoff Heart Center, Department of Cardiology, Bad Nauheim, Germany; ³Justus-Liebig University of Giessen, Department of Cardiology, Giessen, Germany; ⁴German Center for Cardiovascular Research (DZHK), Rhein-Main Partner Site, Bad Nauheim, Germany; ⁵St Johannes Hospital, Department of Cardiology, Dortmund, Germany; and ⁶the Department of Internal Medicine, Carl von Ossietzky University, Oldenburg, Germany.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kim reports personal fees from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, Meril Life Sciences, and Shockwave Medical. Dr Blumenstein reports proctor fees from Boston Scientific. Dr Choi reports speaker/proctor fees from Edwards Lifesciences, Cytosorbents, and Getinge. Dr Hamm is on the advisory board for Medtronic. Dr Charitos reports proctor fees from Boston Scientific. Dr Möllmann reports proctor fees and/or speaker honoraria from Abbott, Biotronic, Edwards Lifesciences, and Boston Scientific. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript accepted May 25, 2022.

Address for correspondence:  Won-Keun Kim, MD, PhD, Kerckhoff Heart Center, Department of Cardiology, Benekestrasse 2-8, 61231 Bad Nauheim. Email: w.kim@kerckhoff-klinik.de

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