Defining Exercise Hemodynamics and Function After Transcatheter Aortic Valve Replacement (DEFINE-TAVR) Study.

Completed

• Conditions: Aortic Valve Stenosis

• Registration Number: NCT05567809
• Lead Sponsor: Yale University

Brief Summary

The purpose of this study is to help understand how the replacement valve functions over time, both at rest and during exercise.

Detailed Description

The objective of this single-center registry is to evaluate prosthetic valve hemodynamics and function over time in patients undergoing clinically indicated transcatheter aortic valve replacement (TAVR) for symptomatic severe aortic stenosis. Specific goals include:

* Describe valve hemodynamics at rest (baseline, post-procedure, 30 days, 1 year) and with exercise (at 30 days and 1 year) after TAVR implantation to define valve function and hemodynamics over time.

* Compare valve hemodynamics and function at rest and exercise between self-expanding and balloon expandable valves.

Study Timeline

• Study First Submitted: 2022-09-28
• Study First Submitted QC: 2022-09-30
• Study First Posted: 2022-10-05
• Study Start: 2022-10-25
• Primary Completion: 2025-01-21
• Study Completion: 2025-01-21
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-18
• Last Update Posted: 2025-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Male or non-pregnant female ≥18 years of age
• Clinically indicated for TAVR
• Aortic annular size measures 21-25 mm diameter based on pre-procedure Computed Tomography Angiography (CTA)
• Able to exercise and, in the judgment of the investigator, is likely to be physically able to comply with the protocol requirements regarding exercise echocardiography
• Willing to comply with protocol-specified follow-up evaluations
• The participant or legally authorized representative, has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

Exclusion Criteria

• Previously implanted prosthetic aortic valve (i.e., planned valve-in-valve TAVR)
• Known mental or physical illness or known history of substance abuse that may cause non-compliance with the protocol, confound the data interpretation, or is associated with a life expectancy of less than one year
• Left ventricular ejection fraction (LVEF) <35%
• Presenting with cardiogenic shock at the time of the index procedure
• Planned to undergo any cardiac surgical procedure in the following 12 months
• The index procedure results in an unsuccessful TAVR, defined as procedural major adverse events (death, disabling stroke, or life-threatening or disabling bleeding), need for a second prosthesis implant, or conversion to emergent surgery

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
TransAortic Valve Gradient during exercise at 30 days post-TAVR	30 days post-TAVR	TransAortic Valve Gradient (mmHg) during exercise at 30 days post procedure, as assessed by the Echocardiographic Core Laboratory and summarized as peak and mean.

Secondary Outcome Measures

Name	Time	Method
Change in valve cusp thickness at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in valve cusp thickness (mm) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in EOA at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in EOA (cm2) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in valve mobility at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in valve mobility at rest assessed using echocardiogram reported as absolute values and as changes.
Change in paravalvular leak at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in paravalvular leak at rest assessed using echocardiogram reported as absolute values and as changes.
Change in energy loss coefficient at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in energy loss coefficient at rest assessed using echocardiogram reported as absolute values and as changes.
Change in aortic valve gradient (peak and mean) at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in aortic valve gradient (mmHg) (peak and mean) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in LV thickness at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in LV thickness (cm) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in LV Global Longitudinal Strain at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in LV Global Longitudinal Strain (%) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in Right Ventricular (RV) systolic velocity at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in RV systolic velocity (cm/s) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in aortic valve velocity (peak and mean) with exercise	30 days and 12 months post-TAVR	Change in aortic valve velocity (m/s) (peak and mean) with exercise assessed using echocardiogram reported as absolute values and as changes.
Change in exercise duration	30 days and 12 months post-TAVR	Change in exercise duration (min) reported as absolute values and as changes.
Change in Left Ventricle (LV) remodeling at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in LV remodeling at rest assessed using echocardiogram reported as absolute values and as changes.
Change in leaflet thickening at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in leaflet thickening at rest assessed using echocardiogram reported as absolute values and as changes.
Change in LV Global Longitudinal Strain with exercise	30 days and 12 months post-TAVR	Change in LV Global Longitudinal Strain (%) with exercise assessed using echocardiogram reported as absolute values and as changes.
Composite Safety Endpoints (VARC-3 defined)	30 days and 12 months post-TAVR	Composite safety endpoint reported as a proportion of participants who died or experienced neurological events or life-threatening bleeding or acute kidney injury or coronary artery obstruction requiring intervention or major vascular complications or valve-related dysfunction requiring repeat procedure evaluated at 30 days and 12 months.
TAVR Device Success (Valve Academic Research Consortium [VARC]-defined)	during hospitalization approximatively 3 days	TAVR Device Success evaluated post-procedure/pre-discharge during hospitalization approximatively 3 days, defined as: absence of procedural mortality AND correct positioning of a single prosthetic heart valve into the proper anatomical location AND intended performance of the prosthetic heart valve (defined as no prosthesis-patient mismatch \[VARC-defined\] and mean aortic valve gradient \<20 mm Hg or peak velocity \<3 m/s, AND no moderate or severe prosthetic valve regurgitation \[VARC-defined\] \[site and Core Laboratory-reported\].
Change in coefficient of contraction Effective Orifice Area (EOA)/Geometric Orifice Area (GOA) at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in coefficient of contraction EOA/GOA at rest assessed using echocardiogram reported as absolute values and as changes.
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in TAPSE (mm) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in EOA with exercise	30 days and 12 months post-TAVR	Change in EOA (cm2) with exercise assessed using echocardiogram reported as absolute values and as changes.
Change in Dimensionless Velocity Index (DVI) at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in DVI at rest assessed using echocardiogram reported as absolute values and as changes.
Change in aortic valve velocity (peak and mean) at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in aortic valve velocity (m/s) (peak and mean) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in coaptation length at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in coaptation length (mm) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in RV systolic pressure (RVSP) at rest	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR	Change in RVSP (mmHg) at rest assessed using echocardiogram reported as absolute values and as changes.
Change in aortic valve gradient (peak and mean) with exercise	30 days, and 12 months post-TAVR	Change in gradient (mmHg) (peak and mean) with exercise assessed using echocardiogram reported as absolute values and as changes.
Change in DVI with exercise	30 days and 12 months post-TAVR	Change in DVI with exercise assessed using echocardiogram reported as absolute values and as changes.
Change in RVSP with exercise	30 days and 12 months post-TAVR	Change in RVSP (mmHg) with exercise assessed using echocardiogram reported as absolute values and as changes.

Trial Locations

Locations (1)

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States