Valve Hemodynamic Optimization Based on Doppler-Echocardiography vs Catheterization Measurements Following ViV TAVR

Study Overview
=================
Brief Summary
-----------------
Data on valve performance following ViV-TAVR has usually been obtained with the use of Doppler-echocardiography. However, some reports have shown significant discordances in the evaluation of mean transvalvular gradient between echocardiography and catheterization, with an overestimation of the real gradient with echo (vs. cath) in most cases. Thus, the incidence of procedural-device failure may be lower than that reported in the ViV-TAVR literature,

Detailed Description
-----------------
This is a prospective, multicenter, randomized, single-blinded design trial including patients with surgical aortic bioprosthetic dysfunction in the presence of a stented surgical bioprosthesis with a labeled size ≤25 mm. Following the Heart Team's decision to proceed with a ViV-TAVR procedure with the SAPIEN 3 ULTRA valve (or its subsequent iterations), patients will be randomized to valve hemodynamic optimization according to Doppler-echocardiography versus cardiac catheterization parameters.

Official Title
-----------------
Valve Hemodynamic Optimization Based on Doppler-Echocardiography Versus Catheterization Measurements Following Valve-in-Valve TAVR: A Prospective Randomized Trial

Conditions
-----------------
Aortic Valve Stenosis, Aortic Valve Regurgitation, Prosthesis Failure

Intervention / Treatment
-----------------
* Procedure: Doppler-echocardiography
* Procedure: Invasive hemodynamic measurements


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with surgical aortic bioprosthetic valve failure defined as severe aortic stenosis and/or regurgitation approved for a valve-in-valve procedure by the Heart Team Surgical stented bioprosthetic valve (label size ≤25 mm) TAVR with the SAPIEN 3 Ultra valve Exclusion Criteria: Stentless or sutureless surgical valves Trifecta bioprosthesis Hancock II bioprosthesis High-risk of coronary obstruction (defined either as a virtual transcatheter valve - coronary distance as evaluated by CT <4 mm or based on the criterion of the heart team responsible for the procedure). Impossibility to obtain written informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized in a 1:1 fashion to valve hemodynamic optimization according to Doppler-echocardiography versus cardiac catheterization parameters.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Doppler-echocardiography<br>Following valve implantation, further intervention will be based on Doppler-echocardiographic measurements. | Procedure: Doppler-echocardiography<br>* The TAVR (valve-in-valve) procedure will be performed with the SAPIEN 3 Ultra valve, with valve sizing according to current manufacturer recommendations. Following valve implantation, further intervention will be based on Doppler-echocardiographic measurements. Balloon post-dilation with a non-compliant balloon will be performed in the presence of a residual mean gradient ≥20 mmHg as assessed by Doppler-echocardiography.<br>|
| Other: Invasive hemodynamic measurements<br>Following valve implantation, further interventions will be based on invasive hemodynamic measurements (with simultaneous aortic and ventricular pressure recording). | Procedure: Invasive hemodynamic measurements<br>* The TAVR (valve-in-valve) procedure will be performed with the SAPIEN 3 Ultra valve, with valve sizing according to current manufacturer recommendations. Following valve implantation, further interventions will be based on invasive hemodynamic measurements (with simultaneous aortic and ventricular pressure recording). Balloon post-dilation will be performed with a non-compliant balloon in the presence of a mean residual gradient ≥20 mmHg as assessed by hemodynamic measurements.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Quality of life (Efficacy) | Change in quality of life as evaluated by the Kansas City Cardiomyopathy Questionnaire (KCCQ). All score are represented on a 0-to-100-point scale (lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life).The KCCQ is a 7 domains questionnaire; symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. | 12 months follow-up | 
| Periprocedural complications (Safety) | Periprocedural complications including in-hospital mortality, stroke, annular rupture, coronary obstruction, new-onset left bundle branch block, need for permanent pacemaker implantation and conversion to open heart surgery. | Periprocedural | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual transvalvular gradient | Residual (maximal and mean) transvalvular gradient | 1 month and 12 months follow-up | 
| Combined enpoint: Moderate or severe prothesis-patient mismatch and/or moderate or severe aortic regurgitation (valve performance) | Moderate or severe prothesis-patient mismatch (defines as an index aortic valve area 0.85-0.66 cm2/m2 (moderate), ≤0.65 cm2/m2 (severe) for patient with BMI ˂30km/m2 and 0.70-0.56 cm2/m2 (moderate), ≤0.55 cm2/m2 (severe) for patient with BMI ≥30km/m2 and/or moderate-severe aortic regurgitation (AR) (VARC-3 definition). | 1 month and 12 months follow-up | 
| Heart failure | Evaluated by the New York Heart Association (NYHA) Functional Classification | 1 and 12 months follow-up and yearly up to 5 years | 
| Exercise capacity | Exercise capacity as evaluated by the six-minute wlak test. | 1 month and 12 months follow-up | 
| Changes in Quality of life | severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life).The KCCQ is a 7 domains questionnaire; symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life and self-efficacy. | after 1-year follow-up (yearly up to 5 years) | 
| Clinical safety endpoints | Individually and combined: death, stroke, major of lifethreatening bleeding, pacemaker implantation, myocardial infarction | 1 and 12 months follow-up and yearly up to 5 years | 
| re-hospitalization | Need for re-hospitalization | 1 and 12 months follow-up and yearly up to 5 years | 
| wear and tear deterioration (Structural valve degeneration) | wear and tear evaluated by echocardiography imaging | 1 and 12 months follow-up and yearly up to 5 years | 
| Leaflet disruption (Structural valve degeneration) | leaflet disruption evaluated by echocardiography imaging | 1 and 12 months follow-up and yearly up to 5 years | 
| flail leaflet (Structural valve degeneration) | flail leaflet evaluated by echocardiography imaging | 1 and 12 months follow-up and yearly up to 5 years | 
| leaflet fibrosis and/or calcification (Structural valve degeneration) | leaflet fibrosis and/or calcification evaluated by echocardiography imaging | 1 and 12 months follow-up and yearly up to 5 years | 
| strut fracture or deformation (Structural valve degeneration) | strut fracture or deformation evaluated by echocardiography imaging | 1 and 12 months follow-up and yearly up to 5 years | 
| Valve re-intervention | Need for valve re-intervention | 1 and 12 months follow-up and yearly up to 5 years | 
| Changes in Left ventricle mass | Changes in LV mass | 1-month and 1-year follow-up |