Size Up Bicuspid with the LIra MEthod: the SUBLIME Study (SUBLIME)

SUBLIME: Size Up Bicuspid with the LIra MEthod: the SUBLIME Study

Transcatheter aortic valve replacement (TAVR) outcomes in patients with raphe-type bicuspid aortic valve (BAV) are still suboptimal for the non negligible rate of stroke and permanent pacemaker implantation. There is still lack of consensus on the optimal sizing method for prosthesis selection in BAV patients.

The objective of the present study is to evaluate the efficacy and safety of the LIRA sizing method in raphe-type BAV patients undergoing TAVR.

Study Overview

• Status: Recruiting
• Conditions: Bicuspid Aortic Valve (BAV)

Detailed Description

Bicuspid aortic valve (BAV) still represents a challenge for percutaneous treatment due to the peculiar anatomy.

BAV patients have been historically excluded from major randomized controlled trials.

Observational data have showed a high rate of paravalvular leak (PVL) with the use of self-expanding prostheses and a non-negligible rate of annular rupture with the use of balloon expandable valves.

More recent data have shown better outcomes with current generation prostheses although the rate of stroke and permanent pacemaker implantation remains high.

These suboptimal results, possibly related to BAV different anatomy, have advocated the use of different sizing method for prosthesis selection in this setting.

Recent evidence has shown that transcatheter heart valve (THV) anchoring in BAV patients might occur at the raphe-level, defined as the LIRA (Level of Implantation at the RAphe) plane. Thus, a novel supra-annular sizing method based on the measurement of the perimeter at the raphe-level, the LIRA-method, has been developed in our center and validated in small cohorts of patients.

The aim of our study is to evaluate the efficacy and safety of the LIRA method in raphe-type bicuspid patients undergoing TAVR.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Prof. Matteo Montorfano, MD; Phone Number: 0039/02/26437331; Email: montorfano.matteo@hsr.it
• Study Contact Backup: Name: Barbara Bellini, MD; Phone Number: 0039/02/26437331; Email: bellini.barbara@hsr.it

Study Locations

• Italy
  • Brescia, Italy, 25100
    • Recruiting
    • Fondazione Poliambulanza
    • Contact: Andrea Buono, MD
  • Brescia, Italy, 25100
    • Recruiting
    • Spedali Civili
    • Contact: Mauro Massussi, MD
  • Milan, Italy, 20100
    • Recruiting
    • Ospedale San Donato
    • Contact: Riccardo Gorla, MD
  • Roma, Italy, 00100
    • Recruiting
    • San Camillo Hospital
    • Contact: Francesco DE Felice MD
• Switzerland
  • Luzern, Switzerland, 6009
    • Recruiting
    • Luzerner Kantonsspital
    • Contact: Stefan Toggweiler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients over 18 years old with severe aortic stenosis and type 1 or 2 BAV undergone TAVR with self-expanding supra-annular prostheses sized according to the LIRA method

Description

Inclusion Criteria:

• All patients over 18 years old with severe aortic stenosis and type 1 or 2 BAV according to Sievers classification) undergone TAVR with self-expanding supra-annular prostheses sized according to the LIRA method between September 2018 and June 2024

Exclusion Criteria:

• Redo-TAVR
• TAVR performed in emergency setting
• TAVR performed for severe aortic regurgitation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
BAV patients underoging TAVR; Patients with bicuspid aortic valve undergoing TAVI for severe aortic stenosis with sizing performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device success	Device success as defined by VARC 3 criteria : presence of technical success, freedom from mortality, freedom from surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complications, intended performance of the valve (less than moderate aortic regurgitation, mean gradient < 20 mmHg, peak velocity <3 m/s, doppler velocity index >0.25).	Up to 30 days after TAVI procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of partecipants with TAVI-related Adverse Events as assessed by VARC 3 criteria.	All-cause mortality; All stroke; VARC type 2-4 bleeding; Major vascular, access-related, or cardiac structural complication; Acute kidney injury stage 3 or 4; New permanent pacemaker due to procedure- related conduction abnormalities; Surgery or intervention related to the device	Up to 30 days after TAVI procedure
Clinical efficacy	Freedom from all-cause mortality, freedom from all stroke, freedom from hospitalization for procedure -or-valve-related causes, freedom from KCCQ Overall Summary score <45 or decline from baseline >10 point	Up to 1 year after TAVI procedure
Technical success	Freedom from mortality; successful access, delivery and retrieval of the delivery system; correct positioning of a single prosthetic heart valve into the proper anatomical location; freedom from surgey or intervention related to the device or to a major vascular or access-related, or cardiac structural.	At exit from procedure room
Intended performance of the valve	Less than moderate aortic regurgitation, mean gradient < 20 mmHg, peak velocity <3 m/s, doppler velocity index >0.25	Up to 30 days after TAVI procedure

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Investigators: Principal Investigator: Prof. Matteo Montorfano, MD, IRCCS San Raffaele Scientific Institute

Publications and helpful links

General Publications

• Hayashida K, Bouvier E, Lefevre T, Chevalier B, Hovasse T, Romano M, Garot P, Watanabe Y, Farge A, Donzeau-Gouge P, Cormier B, Morice MC. Transcatheter aortic valve implantation for patients with severe bicuspid aortic valve stenosis. Circ Cardiovasc Interv. 2013 Jun;6(3):284-91. doi: 10.1161/CIRCINTERVENTIONS.112.000084. Epub 2013 Jun 11.
• Bauer T, Linke A, Sievert H, Kahlert P, Hambrecht R, Nickenig G, Hauptmann KE, Sack S, Gerckens U, Schneider S, Zeymer U, Zahn R. Comparison of the effectiveness of transcatheter aortic valve implantation in patients with stenotic bicuspid versus tricuspid aortic valves (from the German TAVI Registry). Am J Cardiol. 2014 Feb 1;113(3):518-21. doi: 10.1016/j.amjcard.2013.10.023. Epub 2013 Nov 9.
• Perlman GY, Blanke P, Dvir D, Pache G, Modine T, Barbanti M, Holy EW, Treede H, Ruile P, Neumann FJ, Gandolfo C, Saia F, Tamburino C, Mak G, Thompson C, Wood D, Leipsic J, Webb JG. Bicuspid Aortic Valve Stenosis: Favorable Early Outcomes With a Next-Generation Transcatheter Heart Valve in a Multicenter Study. JACC Cardiovasc Interv. 2016 Apr 25;9(8):817-824. doi: 10.1016/j.jcin.2016.01.002.
• Yoon SH, Lefevre T, Ahn JM, Perlman GY, Dvir D, Latib A, Barbanti M, Deuschl F, De Backer O, Blanke P, Modine T, Pache G, Neumann FJ, Ruile P, Arai T, Ohno Y, Kaneko H, Tay E, Schofer N, Holy EW, Luk NHV, Yong G, Lu Q, Kong WKF, Hon J, Kao HL, Lee M, Yin WH, Park DW, Kang SJ, Lee SW, Kim YH, Lee CW, Park SW, Kim HS, Butter C, Khalique OK, Schaefer U, Nietlispach F, Kodali SK, Leon MB, Ye J, Chevalier B, Leipsic J, Delgado V, Bax JJ, Tamburino C, Colombo A, Sondergaard L, Webb JG, Park SJ. Transcatheter Aortic Valve Replacement With Early- and New-Generation Devices in Bicuspid Aortic Valve Stenosis. J Am Coll Cardiol. 2016 Sep 13;68(11):1195-1205. doi: 10.1016/j.jacc.2016.06.041.
• Iannopollo G, Romano V, Buzzatti N, De Backer O, Sondergaard L, Merkely B, Prendergast BD, Giannini F, Colombo A, Latib A, Granada JF, Chieffo A, Montorfano M. A novel supra-annular plane to predict TAVI prosthesis anchoring in raphe-type bicuspid aortic valve disease: the LIRA plane. EuroIntervention. 2020 Jun 25;16(3):259-261. doi: 10.4244/EIJ-D-19-00951. No abstract available.
• Iannopollo G, Romano V, Buzzatti N, Ancona M, Ferri L, Russo F, Bellini B, Granada JF, Chieffo A, Montorfano M. Supra-annular sizing of transcatheter aortic valve prostheses in raphe-type bicuspid aortic valve disease: the LIRA method. Int J Cardiol. 2020 Oct 15;317:144-151. doi: 10.1016/j.ijcard.2020.05.076. Epub 2020 May 28.
• Iannopollo G, Romano V, Esposito A, Guazzoni G, Ancona M, Ferri L, Russo F, Bellini B, Buzzatti N, Curio J, Prendergast B, Montorfano M. Update on supra-annular sizing of transcatheter aortic valve prostheses in raphe-type bicuspid aortic valve disease according to the LIRA method. Eur Heart J Suppl. 2022 May 18;24(Suppl C):C233-C242. doi: 10.1093/eurheartj/suac014. eCollection 2022 May.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: TAVR; LIRA method; Bicuspid aortic Valve
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Bicuspid Aortic Valve Disease
• Other Study ID Numbers: SUBLIME

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No