REVIVE-FR Registry

Bioprosthetic valve failure (BVF) is an increasingly relevant clinical problem as younger patients with severe aortic stenosis undergo surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and may outlive the expected durability of their implanted valve. BVF can result from structural valve deterioration, non-structural valve dysfunction, valve thrombosis, or endocarditis. Depending on the underlying mechanism, anatomical characteristics, surgical risk, and clinical circumstances, treatment options include transcatheter valve-in-valve implantation into a failed surgical bioprosthesis (TAVI-in-SAVR), repeat transcatheter aortic valve implantation within a failed transcatheter heart valve (THV-in-THV or redo-TAVI), surgical explantation of the failed transcatheter heart valve, or medical management without reintervention.

Evidence regarding the comparative outcomes of these management strategies remains limited, particularly for patients undergoing surgical explantation and those managed conservatively. Repeat transcatheter procedures may be associated with complications such as coronary obstruction, impaired coronary access, and elevated residual transvalvular gradients. Preprocedural computed tomography (CT) may help identify anatomical characteristics associated with these risks, including the virtual transcatheter heart valve-to-coronary distance (VTC), the virtual transcatheter heart valve-to-sinotubular junction distance (VTSTJ), and the height of the neoskirt formed by the displaced leaflets of the failed prosthesis.

REVIVE-FR is a multicenter French registry designed to collect real-world clinical data on patients with bioprosthetic valve failure managed using different treatment strategies. The registry will include patients undergoing TAVI-in-SAVR, redo-TAVI (THV-in-THV), surgical explantation of a failed transcatheter heart valve, or medical management without reintervention.

Baseline characteristics, procedural data where applicable, and follow-up information will be collected. Assessments will include clinical outcomes, echocardiographic findings, and CT-based anatomical measurements. The registry will evaluate procedural success using a VARC-3-adapted composite endpoint and safety outcomes according to VARC-3 definitions at 30 days. Clinical, echocardiographic, and CT-based outcomes will also be assessed at 1 year and, where data are available, at 2 years.

The registry aims to characterize outcomes across the different management strategies and identify patient-related, anatomical, and valve-related factors associated with complications and clinical benefit. Particular attention will be given to the mechanisms of bioprosthetic valve failure and CT-derived predictors of coronary obstruction and other complications associated with repeat transcatheter valve implantation. Patients receiving medical management without reintervention will provide a real-world reference cohort to improve understanding of the clinical course of BVF in the absence of further valve intervention.

In addition, data from the redo-TAVI cohort are intended to be combined with data from another registry to support a larger, adequately powered analysis of outcomes following THV-in-THV procedures. Overall, REVIVE-FR is intended to expand the available evidence on the management of bioprosthetic valve failure and support a better understanding of the benefits, risks, and clinical outcomes associated with the available treatment strategies. The study combines prospective enrollment with a partial, exceptional retrospective identification of eligible cases from January 2025 onward.

• TAVI-in-SAVR (Valve-in-Valve) (Procedure): Transcatheter aortic valve implantation within a failed surgical aortic bioprosthetic valve in patients with bioprosthetic valve dysfunction, using a SAPIEN 3 Ultra or SAPIEN 3 Ultra RESILIA valve via anatomically suitable transfemoral access.
• THV-in-THV (Redo-TAVI) (Procedure): Repeat transcatheter aortic valve implantation within a previously implanted transcatheter heart valve with Stage II or III structural valve deterioration according to VARC-3, using a SAPIEN 3 Ultra or SAPIEN 3 Ultra RESILIA valve via anatomically suitable transfemoral access.
• Surgical Explantation of a Failed Transcatheter Heart Valve (Procedure), also known as THV Explantation, TAVR Explant: Surgical explantation of a previously implanted transcatheter heart valve with valve dysfunction of any mechanism, as determined by the Heart Team. Subsequent surgical aortic valve replacement may be performed according to the clinical treatment strategy
• Medical management (Other), also known as Conservative Management,: Guideline-directed medical therapy and clinical surveillance for patients with a failing transcatheter heart valve due to Stage II or III structural valve deterioration according to VARC-3 or infective endocarditis, without transcatheter valve reintervention or surgical explantation

Primary outcomes

• REVIVE-FR Success at 30 Days [30 days after procedure]: Proportion of patients in the TAVI-in-SAVR, THV-in-THV, and Explant-TAVR cohorts achieving REVIVE-FR success, a VARC-3-adapted composite endpoint. Success requires correct positioning of a single prosthetic heart valve in the proper anatomic location; intended valve performance (mean gradient <20 mmHg, peak velocity <3.0 m/s, Doppler velocity index ≥0.25, and less than moderate aortic regurgitation); and freedom from mortality, coronary obstruction, unplanned coronary revascularization, and surgery or intervention related to the device. The endpoint is assessed separately for each of the three interventional cohorts and does not apply to the Medical-Management cohort.
• Early Safety at 30 Days [30 days after procedure]: Determine VARC-3 defined early safety at 30 days: * Freedom from all-cause mortality * Freedom from all Stroke * Freedom from all VARC type 2-4 bleeding * Freedom from all major vascular, access-related, or cardiac structural complication * Freedom from all acute kidney injury stage III/IV * Freedom from all moderate/severe aortic regurgitation * Freedom from all new permanent pacemaker implantations due to procedure-related conduction abnormalities * Freedom from all surgery/intervention related to the device These events will be adjudicated. Number and percentage of subjects with early safety at 30 days as per VARC-3 definition, along with individual component of the success, will be presented.

Secondary outcomes

• Clinical Outcomes at 1 Year [1 year after procedure]: Composite of freedom from all-cause mortality, stroke, and valve- or procedure-related rehospitalization in the TAVI-in-SAVR, THV-in-THV, and Explant-TAVR cohorts.
• Valve Durability at 1 Year [1 year after procedure]: Incidence of subclinical and clinical transcatheter heart valve thrombosis and Stage II/III structural valve degeneration according to VARC-3, assessed by echocardiography and 1-year CT where available.
• All-Cause and Cardiovascular Mortality in the Medical-Management Cohort [1 year, and optional 2 years after procedure]: All-cause and cardiovascular mortality will be assessed descriptively in patients managed medically for a failing transcatheter heart valve. Results will be reported as the number and percentage of patients, where appropriate. This outcome is intended for descriptive characterization and is not powered for direct comparison with the interventional cohorts.
• Heart Failure Hospitalization in the Medical-Management Cohort [1 year; and optional 2-year after procedure]: Occurrence of hospitalization for heart failure during follow-up will be assessed descriptively in the Medical-Management cohort. Results will be reported descriptively and are not intended for direct statistical comparison with the interventional cohorts
• Unplanned Aortic Valve Reintervention in the Medical-Management Cohort [1 year; and optional 2-year after procedure]: Occurrence of unplanned aortic valve reintervention, including crossover to TAVI-in-SAVR, THV-in-THV, or surgical explantation, will be assessed descriptively in patients initially managed medically.
• Echocardiographic Progression of Transcatheter Heart Valve Failure [1 year; and optional 2-year after procedure]: Progression of transcatheter heart valve failure will be assessed descriptively using echocardiographic findings, including changes in VARC-3 structural valve degeneration stage and, in patients with endocarditis, resolution or persistence of endocarditis.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Men and women, ≥ 18 years, with a documented indication for transcatheter or surgical reintervention\] on a failed aortic bioprosthesis, or a documented diagnosis of failing THV managed medically, in one of the following four categories:

* Failed surgical bioprosthetic valve (any brand/model), with SVD or other bioprosthetic valve dysfunction, indicated for TAVI-in-SAVR; planned new valve SAPIEN 3 Ultra or SAPIEN 3 Ultra RESILIA; planned and anatomically suitable transfemoral access.
* Failed THV (any brand), with Stage II or III SVD according to VARC-3, indicated for THV-in-THV; planned new valve SAPIEN 3 Ultra or SAPIEN 3 Ultra RESILIA; planned and anatomically suitable transfemoral access.
* Failed THV (any brand), any VARC-3 failure mechanism, indicated for surgical explantation (Explant-TAVR cohort) per Heart Team decision.
* Failing THV (any brand), due to Stage II or III SVD per VARC-3 or due to infective endocarditis, managed medically - i.e., without TAVI-in-SAVR, THV-in-THV, or surgical explantation - for the Medical-Management comparator cohort.

For all cohorts, the local Heart Team must consider the patient suitable and indicated for the planned management strategy. For retrospectively identified cases (any cohort): the index procedure was performed, or THV failure was diagnosed, on or after 1 January 2025, with data retrievable from source records, and no opposition to retrospective data use expressed by the patient or next of kin, in line with applicable French provisions. Retrospective THV-in-THV cases from REVALVE-participating centers are eligible only per the restriction described in Section 3.3. Signed informed consent is required for prospective cases; non\[MZ22.1\]-opposition applies to retrospective cases

Exclusion Criteria - TAVI-in-SAVR and THV-in-THV Cohorts:

* Planned non-transfemoral access (e.g., transapical, transaortic, transcaval, subclavian/axillary).
* Prior mechanical aortic valve prosthesis.
* Anticipated need for a concomitant cardiac surgical procedure favoring surgical explantation over a transcatheter approach.
* Emergency/salvage (non-elective) procedure.
* Presence of LV thrombus.
* Active malignancy or ongoing chemotherapy; life expectancy below 12 months
* Lack of informed consent.

Exclusion Criteria - Medical-Management Cohort:

* Concurrent or planned TAVI-in-SAVR, THV-in-THV, or surgical explantation for the same THV failure episode.
* Malignancy or ongoing chemotherapy; life expectancy below 12 months.
* Lack of informed consent or non-opposition.