Prospective Arm of Conduct - Edwards SAPIEN3 PPI Registry

Study Overview
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Brief Summary
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There are procedure related risk factors for permanent pacemaker implantation (PPI) that can be identified and assessed in a prospective cohort of 300 patients at high risk for PPI Prospective, multicenter, European registry in patients at high risk for PPI undergoing TAVI with the Edwards SAPIEN 3 valve. Additional assessment of calcification using a CT data core lab. Statistical analysis of the dataset obtained with respect to the objectives of the registry.

Detailed Description
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Permanent pacemaker implantation is a widely recognized clinical event associated with TAVI becoming evident within a few days after the procedure. While a number of registries have documented the rates of PPI with different valves, much less evidence has been provided for patient based characteristics (e.g. RBBB etc.) affecting the likelihood of PPI and for procedural variables (e.g. implantation hieght, valve size etc.) that should be considered to perform as safe and minimal invasive procedure as possible. Prior Research To date there are 8 published reports on pacemaker rates and predictors associated with the use of the Edwards SAPIEN 3 THV. These studies suggest that the need for pacemaker implantation in single centers ranges between 14.4 and 20.4% based on patient numbers between 131 and 335 patients. These analyses resulted in the identification of pre-existing conduction disturbance, aortic valve calcification, heavily calcified LVOT, RBBB, persistent complete heart blocks, prolonged QRS duration or short membranous septum as patient related factors associated with PPI during Edwards SAPIEN 3 THV TAVI. Similarly, procedural variables such as implantation height /oversizing as procedure related variables are associated with PPI after TAVI. The literature regarding procedure related variables associated with permanent pacemaker implantation in patients receiving an Edwards SAPIEN 3 valve shows multivariable analyses with slightly different views to the requested procedural variables. Tarantini et al. suggest a higher valve implantation (ventricular ratio >60/40 at qualitative assessment or depth <8mm at qualitative assessment). A similar outcome was reported by De Torres-Alba et al.. Due to the longer stent of the SAPIEN 3 they suggest an even higher implantation, intending a shorter extension of the stent into the LVOT by increasing the percentage of the stent in the aorta to >70%. Schwerg et al. compare the PPI rate in low implantation with high implantation independently from the patients pre-existing conduction disturbances, and suggest to minimize the risk of PPI by choosing a higher implantation technique with the central marker 2 mm or more over the annular plane. Furthermore Mauri et al. encourage to choose a implantation height of <25.5% (Implantation height was expressed as the percentage of the ventricular part of the stent frame in relation to the overall stent frame length). Another procedural factor is found to be aortic annulus oversizing ratios which are known to prevent paravalvular leakage. Leber et al. show the rate of post-procedural permanent pacemakers tended to be lower in patients with <15% oversizing compared to those with >25% oversizing for Edwards Sapien XT. Using SAPIEN 3 valves Husser et al. show a higher PPI rate in patients with out of range oversizing. Gonska et al. conclude that neither implantation height nor oversizing has an effect on PPI rate. On the other hand the need for pre-dilatation by balloon valvuloplasty and post-implant dilatation have not been identified as potential contributing factors for PPI as it is believed the impact of the dilatation on the conduction tissue is transient and short lived. Nevertheless, pre- and post-dilatation should be further considered and analysed. Hypothetically, also the following procedural parameters, which have not been investigated in detail so far, could be risks for PPIs: Stiff guidewire use or a no touch policy and should be considered in this research. Limitations of prior research Current evidence though is limited by patient numbers versus event rates (with a max. of 62 PPI considered in any of the available datasets) resulting in a limited power in multivariable analyses, the single center design of these ventures, the lack of a consistent definition of variables potentially associated with PPI and the unexplained differences in the number and type of variables identified. Aims This registry aims to assess procedural variables and to verify risk factors in a prospective multicenter registry. To identify predictors of PPI patients with a high risk for PPI will be preferably included to increase the power compared to pre-existing database analyses from single centres. The target is to identify general procedural predictors and to verify risk factors of PPI post TAVI with the Edwards SAPIEN 3 valve which when identified and avoided will reduce the need of PPI in the future.

Official Title
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Edwards SAPIEN 3 PPI Registry - A Retrospective Survey and Prospective Identification of Procedure Related Variables Associated With Permanent Pacemaker Implantation in Patients Receiving an Edwards SAPIEN 3 Valve

Conditions
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Aortic Valve Stenosis, AV Block, Bundle-Branch Block

Intervention / Treatment
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* Procedure: transcatheter valve implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing transfemoral SAPIEN 3 implantation because of aortic stenosis, at least 1 of the identified risk factors from the retrospective part to ensure a minimum risk of 33% for PPI (presumed: pre-existing conduction disturbance, aortic valve calcification, heavily calcified LVOT, RBBB, persistent complete heart blocks, QRS duration or short membranous septum,to be confirmed); Exclusion Criteria: exclusion of patients with prior pacemaker, with indications for pacemaker implantation prior to TAVI valve in valve implantation or without informed consent
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with aortic stenosis<br>Patients receiving Edwards SAPIEN 3 aortic transcatheter valve Implantation, who are with a high risk for PPI | Procedure: transcatheter valve implantation<br>* aortic transcatheter valve implantation using Edwards SAPIEN 3 valve<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of permanent pacemaker implantation after TAVI in high risk patients | Need for permanent pacemaker implantation after TAVI in high risk patients. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation depth | Measurement in peri-interventional aortic angiograms. Mean implantation depth (% ventricular part of the stent frame) | up to 30 days after intervention | 
| Valve sizing | Measurement of aorta in pre-operative contrast multislice computed tomographic Images, compared to the implanted valve sizing. Percentage of oversizing will be calculated using the formula (nominal prosthesis area/multislice computed tomographic area - 1) x 100 | up to 30 days after intervention | 
| Dilatation | Ratio in patients, who get a dilatation before or at intervention as well as thereafter (discharge, FU) | 1 year | 
| Expiration data | cause of death | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter aortic valve implantation, Pacemaker, Aortic valve calcification, PPI