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

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

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

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis

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 Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Yousif Ahmad, MD; Phone Number: 2037857990; Email: yousif.ahmad@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale New Haven Hospital
      • Contact: Yousif Ahmad, MD; Phone Number: 203-785-7990; Email: yousif.ahmad@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

A minimum of 50 and up to 100 adults presenting with symptomatic severe aortic stenosis referred for clinically indicated TAVR at Yale New Haven Hospital who meet all eligibility criteria.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TransAortic Valve Gradient during exercise at 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.	30 days post-TAVR

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in valve cusp thickness at rest	Change in valve cusp thickness (mm) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in valve mobility at rest	Change in valve mobility at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in paravalvular leak at rest	Change in paravalvular leak at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in coefficient of contraction Effective Orifice Area (EOA)/Geometric Orifice Area (GOA) at rest	Change in coefficient of contraction EOA/GOA at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in Dimensionless Velocity Index (DVI) at rest	Change in DVI at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in energy loss coefficient at rest	Change in energy loss coefficient at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in EOA at rest	Change in EOA (cm2) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in aortic valve gradient (peak and mean) at rest	Change in aortic valve gradient (mmHg) (peak and mean) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in aortic valve velocity (peak and mean) at rest	Change in aortic valve velocity (m/s) (peak and mean) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in Left Ventricle (LV) remodeling at rest	Change in LV remodeling at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in leaflet thickening at rest	Change in leaflet thickening at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in coaptation length at rest	Change in coaptation length (mm) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in LV thickness at rest	Change in LV thickness (cm) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in LV Global Longitudinal Strain at rest	Change in LV Global Longitudinal Strain (%) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in Right Ventricular (RV) systolic velocity at rest	Change in RV systolic velocity (cm/s) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in RV systolic pressure (RVSP) at rest	Change in RVSP (mmHg) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) at rest	Change in TAPSE (mm) at rest assessed using echocardiogram reported as absolute values and as changes.	baseline, during hospitalization approximatively 3 days, 30 days, and 12 months post-TAVR
Change in aortic valve gradient (peak and mean) with exercise	Change in gradient (mmHg) (peak and mean) with exercise assessed using echocardiogram reported as absolute values and as changes.	30 days, and 12 months post-TAVR
Change in aortic valve velocity (peak and mean) with exercise	Change in aortic valve velocity (m/s) (peak and mean) with exercise assessed using echocardiogram reported as absolute values and as changes.	30 days and 12 months post-TAVR
Change in DVI with exercise	Change in DVI with exercise assessed using echocardiogram reported as absolute values and as changes.	30 days and 12 months post-TAVR
Change in EOA with exercise	Change in EOA (cm2) with exercise assessed using echocardiogram reported as absolute values and as changes.	30 days and 12 months post-TAVR
Change in RVSP with exercise	Change in RVSP (mmHg) with exercise assessed using echocardiogram reported as absolute values and as changes.	30 days and 12 months post-TAVR
Change in exercise duration	Change in exercise duration (min) reported as absolute values and as changes.	30 days and 12 months post-TAVR
Change in LV Global Longitudinal Strain with exercise	Change in LV Global Longitudinal Strain (%) with exercise assessed using echocardiogram reported as absolute values and as changes.	30 days and 12 months post-TAVR
TAVR Device Success (Valve Academic Research Consortium [VARC]-defined)	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].	during hospitalization approximatively 3 days
Composite Safety Endpoints (VARC-3 defined)	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.	30 days and 12 months post-TAVR

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Anteris Technologies Corporation
• Investigators: Principal Investigator: Yousif Ahmad, MD, Yale University; Study Chair: Alexandra J Lansky, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: 2000033211; YSI-002 (Other Identifier: Yale)

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