The Allegra Transcatheter Heart Valve: Long-term Clinical and Echocardiographic Outcomes

Objectives. The Allegra-THV is a novel, self-expanding THV with supra-annular bovine leaflets. The valve is available in 3 different sizes and is delivered through an 18 French sheath. To determine the safety and efficacy of the Allegra transcatheter heart valve (THV; Biosensors) for the treatment of severe aortic valve stenosis under real-world conditions.

Methods. Consecutive patients undergoing transcatheter aortic valve replacement  (TAVR) at the Heart-Centre Lucerne with the Allegra-THV were included. Echocardiographic data were collected at baseline, before discharge, and at 1-year follow-up; clinical outcomes were recorded for up to 3 years. Clinical endpoints were defined according to the definitions of the Valve-Academic-Research-Consortium.

Results. One hundred-three patients (age 81 ± 7 years, 63% women) were enrolled. Median European System for Cardiac Operative Risk Evaluation II score was 4.1% (IQR 1.8%-4.2%). Mean aortic valve gradient was 6.9 ± 3.3 mm Hg and 7.7 ± 3.3 mm Hg, and an effective orifice area was 2.1 ± 0.5 cm² and 2.0 ± 0.5 cm² at 30 days and 1-year follow-up, respectively. More than mild paravalvular leak was observed in 2.0% of patients at 30 days and 3.3% at 1 year. At 1-year follow-up, 14.7% of patients required implantation of a new permanent pacemaker, 1 patient had endocarditis with an uneventful clinical course and good THV-function after antibiotic therapy, and no thrombosis, structural-valve-detoriation (SVD), or non-SVD had occurred. At 3-year follow-up, rates of all-cause and cardiovascular mortality were 31.4% and 18.8%, respectively.

Conclusions. Transfemoral implantation of the Allegra-THV resulted in favorable clinical and echocardiographic outcomes at up to 3-year follow-up. Head-to-head randomized clinical trials are necessary to determine if the Allegra-THV valve performs as well as current generation valves.

The Allegra-THV (New Valve Technology/Biosensors GmbH) is a self-expanding THV designed to be implanted in a 3-step deployment process that facilitates a stable position during implantation. The Allegra-THV received Conformité Européene mark approval in 2017. Favorable short-term results were reported from a single center experience^1,2 and a larger multicenter registry.³ However, data regarding safety and efficacy beyond 30 days is missing. Herein, we report procedural data and mid-term echocardiographic and clinical data from a prospective single center registry.

Patients and study design. This prospective study was investigator-initiated and based on data from the Heart Center Lucerne in Lucerne, Switzlerand. The study was approved by the Swiss Ethics Committee (SwissTAVI Registry. ClinicalTrials.gov Identifier: NCT01368250). All patients provided written informed consent for data acquisition and prospective follow-up. Consecutive patients with severe symptomatic aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) with the Allegra-THV between April 2015 and March 2022 were included. Treatment was conducted according to the institution’s standard of care. The NVT Allegra bioprosthesis and the Allegra TF transfemoral delivery systems (New Valve Technology/Biosensors GmbH) have been previously described.^3-5 The supra-annular prosthesis consists of a self-expanding nitinol frame with bovine pericardial leaflets and anticalcification treatment.

Clinical, echocardiographic, procedural, and clinical outcome data were prospectively collected. One-year follow-up included echocardiography data as well as clinical endpoints, which were defined according to the updated definitions of the Valve Academic Research Consortium (VARC-3) and included mortality, stroke (disabling and nondisabling), myocardial infarction, bleeding, vascular complications, acute kidney injury, and other complications related to transcatheter aortic valve replacement.⁶

Statistics. Data are presented as mean ± SD for continuous variables, and as numbers and frequencies for categorical variables. Unpaired and paired continuous variables were compared using unpaired and paired Student’s t-tests or the Wilcoxon rank sum test, as appropriate. Comparison of categorical variables was performed using chi-square or Fisher’s exact tests. Clinical events were calculated using Kaplan-Meier estimates. Statistical analyses were conducted with STATA´s statistical software package (Version 16.1; StataCorp). A P-value of less than .05 was considered as statistically significant.

A total of 103 patients undergoing TAVR with the Allegra THV were enrolled (Table 1). Mean age was 81.1 ± 6.6 years, and 63% were women. Mean aortic valve area was 0.77 ± 0.16 cm², and mean transvalvular gradient was 44.9 ± 12.8 mm Hg. Median European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was 4.1% (interquartile range [IQR] 1.8-4). Conscious sedation or no sedation was used in all patients. Pre-dilatation was performed in 96 patients (93%), implantation with rapid pacing in 100 patients (97%), and post-dilatation was required in 28 patients (28%) (Table 2). Acute device success was 94% (97 patients). Device success was not achieved in the remaining 6 patients due to moderate paravalvular regurgitation immediately after the procedure (2 patients) or incorrect positioning of the THV, requiring implantation of a different self-expandable THV (2 patients) or vascular complications (2 patients).

Echocardiographic outcomes. Echocardiographic follow-up was performed in 100% of the patients at 30 days and in 98% at 1 year. Aortic valve area (effective orifice area) increased from 0.77 ± 0.16 cm² at baseline to 2.1 ± 0.5 cm² at 30 days and 2.0 ± 0.5 cm² at 1 year (Table 3, Figure 1A). Mean aortic valve gradient decreased from 44.9 ± 12.8 mm Hg at baseline to 6.9 ± 3.3 mm Hg at 30 days and 7.7 ± 3.3 mm Hg at 1 year. Greater than mild paravalvular leaks (PVLs) were observed in 2.0% of the patients at 30 days and 3.3% at 1 year.

Clinical outcomes. The rates of all-cause mortality and cardiovascular mortality at 3-year follow-up were 31.4% and 18.8%, respectively (Figure 2). Stroke or transient ischemic attack (TIA) during the first year after transcatheter aortic valve implantation occurred in 5 patients (4.9%) (Table 3, Figure 3). One TIA and 1 fatal stroke occurred on the day of the procedure. Another disabling stroke was noted 1 day after valve implantation. The remaining 2 minor, non-disabling strokes occurred between the first month after the procedure and 1-year follow-up.

Major vascular complications or major/life-threatening bleeding, each occurred in 8 patients (7.8%). A new permanent pacemaker was implanted in 14 patients (14.7%) at 1-year follow-up (Figure 3). At baseline, 50 patients (49%) were classified as New York Heart Association (NYHA) functional class III or IV, which improved to 8% (8 patients) and 7% (6 patients) at 30-day and 1-year follow-up, respectively.

Prosthetic valve durability. Bioprosthetic valve dysfunction was documented in 1 patient at 1-year follow-up (stage 1). Five months after THV implant, endocarditis of the THV with Enteroccus faecalis was suspected in this patient, and intravenous antibiotic therapy was initiated. The patient recovered without any further sequelae and had excellent function of the THV during echocardiocraphic follow-up. No thrombosis, structural valve detoriation (SVD), or non-SVD was recorded at 1-year follow-up.

Results of this study confirm the high rate of procedural success and low 1-month mortality rate that were previously reported for the Allegra THV,^4,5 and extends those results to 3-year follow-up. Favorable valve hemodynamics with a very low mean gradient persisted after 1 year. Acceptable rates of new pacemaker and more-than-mild PVL suggest that the stent has a well-balanced radial force.

Short-term outcomes. The data presented herein show procedural success rates with the Allegra THV comparable to rates previously reported from single^1,2 and multicenter³ studies. All-cause mortality at 1-month follow-up was 2.9% in our study, which corresponds closely to the 1.2% to 5% previously reported  for the Allegra THV,^3,5,7 and 1.4% to 2.2% for other THVs^8-10 in populations with low-to-intermediate surgical risk.

Rates of procedural complication for the Allegra THV (major vascular complication in 7.8% and major/life-threatening bleeding in 7.8% of patients) were slightly higher than those for other self-expandable THVs; Evolut R valve (Medtronic) had rates of 6.9% and 3.7%,⁸ Acurate neo valve (Boston) had rates of 3.2% and 1.3%,⁹ a balloon-expandable Sapien 3 THV (Edwards) valve had rates of 4.3% and 5.0%,¹⁰ and a mechanically-expandable THV (Lotus valve; Boston Scientific had rates of 3.4% and 3.6%,¹¹ respectively.

The overall stroke rate at 30 days was 1.9%, comparable to rates previously reported for the Allegra THV^1-3 and other THVs (1.4%-4.9%).^11-14 The rate of new permanent pacemaker implantation at 30 days (9.9%) was slightly lower than previously reported for the Allegra THV³ and other THVs (balloon,¹⁴ mechanical,¹¹ or other self-expanding¹³), but similar to the 9.9% rate for the Acurate neo device cited in the SAVI-TF registry.¹²

Echocardiographic outcomes at 1-month follow-up demonstrated excellent hemodynamic performance of the Allegra THV, similar to short-term results of previous studies with this THV.^3-5,7 By systematic use of the cusp-overlap technique, we implanted the THV as high as possible, resulting in a very low rate (2%) of greater-than-mild PVL at 30-day follow-up. This finding compares favorably with previous reports on the Allegra THV,³ and is similar to¹² or better than¹³ 30-day follow-up rates for other self-expandable devices. 

Long-term outcomes. Our results provide the first long-term data on mortality for the Allegra THV. At 3-year follow-up, all-cause mortality and cardiovascular mortality were 31.4% and 18.8%, respectively. These rates compare well to mortality rates for other THVs in real-world registries. In the SOURCE 3 registry (Observational Study to Evaluate Safety and Performance of SAPIEN 3 THV System in Real Life Practice), the overall mortality at 3 years was 32% for men and 26% for women, while cardiovascular mortality was 19% for men and 17% for women.¹⁵ Three-year all-cause and cardiovascular mortality for the CoreValve prosthesis (Medtronic) in the ADVANCE (CoreValve Advance International Post Market Study) registry were 34% and 22%, respectively.¹⁶ In the Neo AS CE-mark study for the Accurate neo2 (Boston Scientific), the respective rates were 26% and 18%.¹⁷

The low mean gradients and large effective orifice areas observed in the present study at 1-year follow-up confirm previous observations at 30-day follow-up. These results probably reflect the supra-annular design of the device, which seems to provide similar or even more favorable results than other self-expandable THVs.^12,13 Greater-than-mild PVL was found in 2.0% of patients at 30 days and in 3.3% at 1-year follow-up. These rates are similar to¹² or better than¹³ 1-year follow-up rates for other self-expandable devices. 

Limitations. The current study had some limitations. This was an observational, retrospective single-arm study, making it difficult to compare endpoints with results of other studies using different THVs. Echocardiography and other assessments were performed according to the standard clinical practice of our center. Echocardiographic outcomes and adverse events were based on site-reported data, and were not independently adjudicated. Nevertheless, the present study provides the largest clinical experience with the Allegra THV to a 3-year follow-up, and provides useful information on safety and efficacy for clinicians.

The present real-world study confirms the efficacy and safety of the Allegra THV observed in previous short-term studies. Favorable echocardiographic outcomes observed at 30 days have been extended to 1 year, and long-term clinical outcomes are comparable to those for other THVs. Head-to-head randomized clinical trials are necessary to determine if the Allegra-THV valve performs as well as current generation valves.

From the Heart Center Lucerne, Luzerner Kantonsspital, Lucerne, Switzerland.

Disclosures: Dr Wolfrum serves as a proctor for Biosensors. Dr Toggweiler serves as a consultant and proctor for Medtronic, Boston Scientific, Edwards Lifesciences and Biosensors; a proctor for Edwards Lifesciences and Abbott Vascular; and as a consultant for Medira, Shockwave, Teleflex, AtHeart Medical, Veosource, and Polares Medical; has received institutional research grants from Boston Scientific, Fumedica and Novartis; and holds equity in Hi-D Imaging. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Stefan Toggweiler, MD, Cardiology Division, Heart Center Lucerne, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Luzern, Switzerland. Email: stefan.toggweiler@luks.ch