The Effect of Subclinical Leaflet Thrombosis and Prosthesis Type on Transcatheter Aortic Valve Degeneration (POPular PET TAVI) (POPularPETTAVI)

The Effect of Subclinical Leaflet Thrombosis and Prosthesis Type on Transcatheter Aortic Valve Degeneration

A multicentre cross-sectional cohort study to assess the difference in bioprosthetic micro-calcification activity, detected with 18F-NaF PET-CT, as early marker of transcatheter valve degeneration, between patients with vs. without subclinical leaflet thrombosis at five years after TAVI; and between patients with intra-annular vs. supra-annular TAVI prostheses.

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Diagnostic test: 18F-sodium fluoride Positron Emission Tomography (18F-NaF PET), Cardiac Computed Tomography (CT), Transthoracic Echocardiography (TTE)

Detailed Description

Subclinical leaflet thrombosis (SCLT) occurs frequently after TAVI and has been associated with an increased risk of valve dysfunction. A persistent form of SCLT may lead to thrombus calcification and valve degeneration and increase the long-term risk of symptomatic bioprosthetic valve deterioration. Intra-annular in comparison to supra-annular TAVI valves have been associated with a higher risk of SCLT and valve thrombosis. Intra-annular valves may create larger neo-sinuses and flow stagnation zones, which favour local thrombogenicity. Whether different prosthesis types lead to a higher degree of transcatheter valve calcification and degeneration is currently unexplored. Recently, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has emerged as a non-invasive modality capable of imaging bioprosthetic micro-calcification activity, which is an early and powerful predictor of valvular dysfunction and eventually valve failure. In the present study, we investigate for the first time, the differences in quantified bioprosthetic micro-calcification activity with 18F-NaF PET as early marker of transcatheter valve degeneration between patients with and without SCLT and between patients with intra-annular vs. supra-annular prostheses at five years after TAVI.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Prof. J.M. ten Berg, MD, PhD, MSc; Email: jurtenberg@gmail.com
• Study Contact Backup: Name: Dirk-Jan van Ginkel, MD; Phone Number: +31 (0)88 320 66 48; Email: d.van.ginkel@antoniusziekenhuis.nl

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
    • Contact: Prof. O. De Backer, MD, PhD
• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Amsterdam UMC
    • Contact: Dr. R. Delewi, MD, PhD
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435 CM
      • Recruiting
      • St. Antonius Hospital
      • Principal Investigator: Prof. J.M. ten Berg, MD, PhD, MSc
      • Contact: Dirk-Jan van Ginkel, MD; Phone Number: +31 (0)88 320 66 48; Email: d.van.ginkel@antoniusziekenhuis.nl
      • Principal Investigator: Dr. M.J. Swaans, MD, PhD
• United Kingdom
  • Edinburgh, United Kingdom
    • Not yet recruiting
    • University of Edinburgh
    • Contact: Prof. M. Dweck, MD, PhD

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

Patients who underwent TAVI about five years ago will be consecutively screened for eligibility from the ongoing, prospective, TAVI registries of the participating study sites and will be asked to undergo hybrid PET-CT imaging and transthoracic echocardiography.

Description

Inclusion Criteria:

• Successful TAVI with Sapien or CoreValve Evolut prosthesis about 5 years ago
• Able to undergo hybrid 18F-NaF PET-CT imaging and transthoracic echocardiography
• Written informed consent

Exclusion Criteria:

• Temporary or chronic oral anticoagulation use after TAVI
• Known severe renal insufficiency
• Known severe paravalvular regurgitation
• History of valve-in-valve procedure
• History of aortic valve re-intervention (including percutaneous paravalvular leak closure)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intra-annular; Patients with an intra-annular Sapien TAVI prosthesis	Diagnostic test: 18F-sodium fluoride Positron Emission Tomography (18F-NaF PET), Cardiac Computed Tomography (CT), Transthoracic Echocardiography (TTE); Patients undergo a hybrid 18F-NaF-PET CT scan and TTE at five years after TAVI
Supra-annular; Patients with a supra-annular CoreValve Evolut TAVI prosthesis	Diagnostic test: 18F-sodium fluoride Positron Emission Tomography (18F-NaF PET), Cardiac Computed Tomography (CT), Transthoracic Echocardiography (TTE); Patients undergo a hybrid 18F-NaF-PET CT scan and TTE at five years after TAVI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantified bioprosthetic micro-calcification activity	18F-NaF uptake originating from any of the bioprosthetic valve leaflets assessed with 18F-NaF Positron Emission Tomography	5 years after TAVI
Subclinical Leaflet Thrombosis	Hypo Attenuated Leaflet Thickening (HALT) assessed with cardiac Computed Tomography	5 years after TAVI
Valve dysfunction	Transvalvular gradients assessed with transthoracic echocardiography	5 years after TAVI

Collaborators and Investigators

• Sponsor: St. Antonius Hospital
• Collaborators: Medtronic; St. Antonius Research Fund

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: TAVI; TAVR; Subclinical Leaflet Thrombosis; Bioprosthetic Valve Deterioration; Intra-annular; Supra-annular
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Thrombosis; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Protective Agents; Cariostatic Agents; Listerine; Fluorides; Sodium Fluoride
• Other Study ID Numbers: NL82791.100.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Decided upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No