TAVI with the Evolut platform for bicuspid aortic valve stenosis: the international, multicentre, prospective BIVOLUTX registry

Selected in EuroIntervention Journal by A. Beneduce , A. N. Calik

The single-arm BIVOLUTX registry provides an accurate picture of contemporary practice and clinical outcomes of TAVI in BAV patients with AS, adding valuable prospective evidence to the field.

Reviewers

Alessandro Beneduce

@ABeneduceMD

Interventional cardiologist / Cardiologist

IRCCS Ospedale San Raffaele - Milan, Italy

Ali Nazmi Calik

@ANazmiCalik

Interventional cardiologist / Cardiologist

Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Center - Istanbul, Türkiye

Our Comment

Central illustration: Clinical outcomes after TAVI with Evolut Pro/R34 in bicuspid patients. AR: aortic regurgitation; IQR: interquartile range; PPM: patient-prosthesis mismatch
Source: EuroIntervention Journal

Central illustration: Clinical outcomes after TAVI with Evolut Pro/R34 in bicuspid patients. AR: aortic regurgitation; IQR: interquartile range; PPM: patient-prosthesis mismatch
Source: EuroIntervention Journal

Why this study – the rationale/objective?

Transcatheter aortic valve implantation (TAVI) has progressively expanded towards younger and low-risk patients suffering from symptomatic aortic stenosis (AS).[1] However, bicuspid aortic valve (BAV) patients have been excluded from major randomized clinical trials that validated TAVI across the spectrum of surgical risk, and evidence supporting TAVI in this setting is limited to observational studies, generally including highly selected patients.[2,3] BAV anatomy poses several anatomical and technical challenges for TAVI. Indeed, despite encouraging results obtained using new-generation devices, clinical outcomes are still affected by a relevant incidence of significant paravalvular leak (PVL), permanent pacemaker implantation (PPM), and periprocedural stroke.[4]

Recent studies highlighted that highly calcified BAV anatomical phenotypes are associated with increased risk of procedural complications and midterm mortality and that self-expanding and balloon-expandable devices might perform differently in this setting.[5,6] Furthermore, optimal prosthesis sizing method in BAV anatomy is controversial.[7] The present study by Tchétché et al. aimed to evaluate valve performance and clinical outcomes of TAVI with the self-expanding, supra-annular Evolut PRO device (Medtronic) in contemporary BAV patients and explore the impact of different multislice computed tomography (MSCT) sizing algorithms.

How was it executed - the methodology?

BIVOLUTX was an investigator-initiated, international, multicenter, prospective registry of consecutive BAV patients scheduled for TAVI using the Evolut PRO (23, 26, 29 mm) and Evolut R (34 mm) THVs (Medtronic) in 14 countries. The Sievers classification was used to define the BAV anatomy. [8] The trial comprised symptomatic BAV AS patients over the age of 18, with anatomical suitability for the Evolut platform and a life expectancy of more than a year.

The primary outcome was valve performance, defined as a mean aortic valve gradient <20 mmHg or peak velocity <3 m/s and no moderate or severe prosthetic valve regurgitation at 30 days. Secondary outcomes were 30-day and 1-year all-cause and cardiovascular mortality, significant patient-prosthesis mismatch (PPM), defined as an aortic valve area (AVA) < 0.6 cm2/m2, and the ellipticity index at 30 days. An independent clinical event committee analyzed all study endpoints following the updated Valve Academic Research Consortium 3 (VARC-3) criteria. [9]

What is the main result?

Baseline Clinical Characteristics, Sizing and Procedural Details

Of 3,777 TAVI patients, 206 (5.4%) had BAV, 152 were deemed eligible for the BIVOLUTX study, and 149 underwent TAVI procedure with Evolut PRO and R 34 platforms. The patients were mostly male (63.1%), with an average age of 78. The mean Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE) II score was 2.6% and 2.8%, respectively. The mean aortic valve area (AVA) was 0.7 (0.6-0.9) cm2, the mean peak velocity was 4.2 (3.9-4.5) m/s, and the mean aortic valve gradient was 45.5 (38.3-52.8) mmHg.

Overall, two different sizing methodology was used. The sizing was according to the annulus size in 77 patients (51.7%), whereas THV size was determined by the combination of annular and supra-annular dimensions (ICD: inter-commissural distance 4 cm above the annulus) for 72 patients (48.3%). Type 1 L-R was the most common BAV phenotype (72.5%), with type 0 and type 2 phenotypes present in 10.1% and 3.3% of patients, respectively. In 52 patients (34.9%), a calcified raphe was detected.

The most frequent Evolut valve sizes were 29 and 34 mm (49.0% and 36.9%, respectively). In 130 cases (87.2%), balloon predilation was performed. Forty-five patients (30.2%) needed THV repositioning for implant depth optimization. Due to initial malpositioning, three patients (2.0%) received more than one THV. In 83 patients (55.7%), post-dilatation was performed. Overall, the procedural details for annular-based sizing and combination sizing were similar.

Outcomes

At 30 days, the primary outcome of valve performance was observed in 142/149 (95.3%) patients: 74/77 (96.1%) versus 68/72 (94.4%); p=0.9, in the annular and combination sizing groups, respectively. The mean aortic gradient was 7.2 (5.4-9.5) mmHg. Paravalvular aortic regurgitation was trivial in 8 patients (7.5%), mild in 86 patients (81.1%), mild to moderate in 9 patients (8.5%), and moderate in 3 patients (2.8%). The 30-day cardiac and non-cardiac mortality rates were 2.6% and 1.3%, respectively. Twenty-nine patients (19.5%) required new pacemaker implantation. PPM was found in 13/143 (9.0%) surviving individuals and was severe in 2 (1.3%).

At one year, 13 patients were lost to follow-up, 15 (11.0%) had died, and 5 (3.3%) were due to cardiovascular causes. The valve function was preserved, as indicated by a mean AVA of 2.1 (1.8-2.5) cm2, an indexed AVA of 1.1 (0.9-1.4), and a mean aortic gradient of 8.1 (6.2-11.1) mmHg. One (1.6%) patient experienced moderate to severe regurgitation. A new pacemaker implantation was necessary for 33 patients (25.6%). Severe PPM was observed in three cases (4.8%).

Overall, 30-day and 1-year clinical and echocardiographic results were comparable among sizing methodologies.

Critical reading and the relevance for clinical practice:

The single-arm BIVOLUTX registry provides an accurate picture of contemporary practice and clinical outcomes of TAVI in BAV patients with AS, adding valuable prospective evidence to the field. The study included an almost all-comers AS population, with the indication for TAVI based on the local Heart Team and operator’s assessment of anatomical suitability for the Evolut platform. This approach yields the first relevant observation: the prevalence of BAV in a contemporary cohort of AS patients undergoing evaluation for TAVI reached 5.4%, and of these patients, 73.4% were considered eligible for TAVI with the Evolut platform. The included population was relatively older and had a slightly higher surgical risk profile than observed in the Evolut Low-Risk Bicuspid Study.[2]

The next relevant observation is related to the type of BAV anatomy that has been treated. Sievers type-1 accounted for 86.6% of cases (with R-L being the most frequently observed subtype), followed by type-0 in 10.1% of cases and type-2 in 3.3%. The overall calcium burden was significant, and a calcified raphe was present in 34.9% of cases. However, the valve anatomical risk profile according to Yoon’s classification and aortic root aortic configuration (tube, flare, taper) was not reported in the manuscript but will likely be the object of a pre-specified MSCT analysis.[5][7]

From a procedural standpoint, predilatation was almost routinely performed, the repositioning feature of the Evolut platform was essential in nearly one-third of cases, and post-dilatation was broadly used mainly to improve the circularity and expansion of the frame. The use of cerebral embolic protection devices was not specified in the study protocol.

The evaluation by an echocardiographic core laboratory and the rigorous assessment of clinical outcomes by an independent clinical event committee according to the contemporary VARC-3 criteria strengthen the study results. Interestingly, optimal hemodynamic valve performance and a device success rate of >90% were observed at 30 days without significant differences according to the sizing method. On the other hand, the rate of disabling stroke (3.2% at 30 days and 4.7% at 1 year) and PPM (19.5% at 30 days and 25.6% at 1 year) is not negligible. This observation might be explained by anatomical features and procedural strategies, raising the question of the need for cerebral embolic protection devices in this special population and stimulating the debate around implementing a dedicated cusp overlap technique to limit implantation depth.

The BIVOLUTX registry adds an essential piece of evidence on the way to a randomized comparison of TAVI and surgery in BAV anatomy. However, although we are clearly making progress, we still have to answer key questions to design a randomized clinical trial: (1) what is the ideal BAV anatomy for TAVI? (2) which device type should be preferred (self-expanding or balloon-expandable)? (3) what should be the sizing method and the implantation technique? (4) do we need a dedicated TAVI device for BAV or a specific leaflet modification technology? Until then, we will continue building evidence one step at a time.

Watch the interview of Didier Tchétché by Waqar Ahmed

References

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