NCT04281771: APPOSE

Assessment of Paravalvular Leak After TAVI by Hemodynamic Measurements and Cardiac MRI

Active, enrolled NA Last updated 19 January 2024

What this trial tests

NA trial testing cardiac MRI in Transcatheter Aortic Valve Replacement in 92 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

17 September 2019

Primary endpoint
27 November 2021

28 October 2026

Quick facts

Lead sponsor	Radboud University Medical Center
Phase	NA
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	92
Start date	17 September 2019
Primary completion	27 November 2021
Estimated completion	28 October 2026
Sites	1 location across Netherlands

Drugs / interventions tested

• cardiac MRI

Conditions studied

• Transcatheter Aortic Valve Replacement — all drugs for Transcatheter Aortic Valve Replacement →
• Hemodynamic Monitoring — all drugs for Hemodynamic Monitoring →
• Aortic Valve Insufficiency — all drugs for Aortic Valve Insufficiency →
• Aortic Valve Stenosis — all drugs for Aortic Valve Stenosis →

Sponsor

Radboud University Medical Center

Who can join

18 and older, any sex, with Transcatheter Aortic Valve Replacement or Hemodynamic Monitoring. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Rationale: Transcatheter aortic valve implantation (TAVI) has become the standard therapy for elderly patients with high surgical risks. Paravalvular leakage after TAVI is relatively common and there is conflicting evidence regarding the clinical impact of mild paravalvular leakage in self-expanding devices. Prospective data for self-expanding devices are required to compare the extent of paravalvular leakage as a result of device design. Grading paravalvular leakage after TAVI is difficult. Echocardiography and angiography systematically underestimate paravalvular leakage (PVL) as compared to cardiac MRI. Hemodynamic measurements are used to aid decision making directly after TAVI implantation. Prospective data comparing hemodynamic measurements with cardiac MRI are needed to design an optimal strategy to grade paravalvular leakage peri-operatively in order to optimize TAVI outcomes. The combination of aortic valve stenosis, angiodysplasia and von Willebrand Disease type 2A (vWD-2A) is known as Heyde syndrome. Previous studies have shown a decrease in angiodysplastic lesions after TAVI. However, since PVL after TAVI is relatively common, angiodysplastic lesions tend to reoccur. Prospective data comparing the severity of PVL to the severity of both vWD-2A and angiodysplasia are lacking.

Objective: To assess procedural hemodynamic measurements in patients with paravalvular regurgitation quantified by means of cardiac MRI (CMR) and to analyse its association with impaired clinical outcome during 5-year follow-up. Secondary objectives are to assess whether the severity of vWD-2A correlates with the severity of PVL measured by cardiac MRI, and to prospectively assess the success percentage of TAVI in the treatment of angiodysplasia.

Study design: This is a prospective, single-center clinical trial. Patients will receive a TAVI. After implantation different hemodynamic indices of PVL will be assessed. Within 4-8 weeks after TAVI a cardiac MRI will be performed to quantify the amount of PVL. Standardized clinical follow-up will take place at discharge, 30 days, 3 months, 6 months and 1 year. Telephone follow-up will take place at 2, 3, 4 and 5 years after TAVI. In patients with known angiodysplasia or iron deficiency anemia e.c.i., a videocapsule endoscopy (VCE) will take place before TAVI and 6 months after TAVI. Of note, for the substudy on Heyde syndrome, patients with a different type of TAVI valve (i.e. no Abbott Portico valve) are also allowed to participate.

Study population: Approximately 80 patients with severe symptomatic aortic valve stenosis with an indication for TAVI will be included. At least 76 patients with a cardiac MRI that is of sufficient quality to quantify the amount of PVL will be included.

Intervention: Patients will undergo cardiac MRI on top of standard clinical care within 4-8 weeks after TAVI. A subgroup of patients will also undergo a VCE.

Main study parameters/endpoints: The primary endpoint is defined as PVL regurgitation fraction as measured by cardiac MRI. One secondary endpoint will comprise a composite of device success, early safety and clinical efficacy as defined by the Valve Academic Research Consortium-2 (VARC-2) (1) and will comprise death, vascular complications, stroke/TIA, life-threatening bleeding requiring transfusion, and acute kidney injury requiring dialysis. Another secondary endpoint will be the reduction of angiodysplastic lesions after TAVI as determined by VCE.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The hemodynamic indices can be assessed in a standard fashion using a fluid filled pigtail catheter that is placed in the left ventricle as part of the routine protocol. Following TAVI, enrolled patients will undergo cardiac MRI to assess PVL. The risk of cardiac MRI after TAVI implantation is negligible. Extra blood samples will be taken. After one year, patients will be followed by telephonic follow-up. Risk/benefit: the expected benefit is a structured clinical follow-up at 1, 2, 3, 4 and 5 years, at the cost of an extra visit to undergo cardiac MRI.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Assessment of paravalvular regurgitation after transcatheter aortic valve replacement using 2D multi-velocity encoding and 4D flow cardiac magnetic resonance.
   Rooijakkers MJP, El Messaoudi S, Stens NA, van Wely MH, et al · · 2024 · cited 9× · PMID 38306632 · DOI 10.1093/ehjci/jeae035
2. Gastrointestinal Angiodysplasia Resolution After Transcatheter Aortic Valve Implantation.
   Goltstein LCMJ, Rooijakkers MJP, Thierens NDE, Schoormans SCM, et al · · 2024 · cited 2× · PMID 39476231 · DOI 10.1001/jamanetworkopen.2024.42324
3. Periprocedural Assessment of Paravalvular Regurgitation After Transcatheter Aortic Valve Replacement Using Diastolic Delta and Videodensitometry.
   Rooijakkers MJP, Elkoumy A, Stens NA, van Wely MH, et al · · 2024 · cited 2× · PMID 39268670 · DOI 10.1161/jaha.124.035587
4. Construct validity of automated assessment of invasively measured hemodynamics during transcatheter aortic valve replacement.
   Stens NA, Versteeg GAA, Rooijakkers MJP, de Lange R, et al · · 2025 · PMID 40984991 · DOI 10.1093/ehjdh/ztaf069
5. Paravalvular Leak After Transcatheter Aortic Valve Implantation: Importance of Preprocedural Variables and Intraprocedural Assessment.
   Sá MP, Bloom JP, Osho AA. · · 2024 · PMID 39268674 · DOI 10.1161/jaha.124.037850