Clinical trial NCT03715894: Prospective Arm of Conduct - Edwards SAPIEN3 PPI Registry
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aortic Valve Stenosis
AV Block
Bundle-Branch Block
Keywords: Transcatheter aortic valve implantation
Pacemaker
Aortic valve calcification
PPI
Lead sponsor: Institut für Pharmakologie und Präventive Medizin
Sponsor class: NETWORK
Collaborators: name: Edwards Lifesciences
First posted: 2018-10-23
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing transfemoral transcatheter valve implantation with the SAPIEN 3 valve with at least one identified risk factor for PPI

Brief summary: 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: 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

1. patient based characteristics (e.g. RBBB etc.) affecting the likelihood of PPI and for
2. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurence of permanent pacemaker implantation after TAVI in high risk patients
timeFrame: 1 year
Secondary outcomes:
measure: Implantation depth
timeFrame: up to 30 days after intervention
measure: Valve sizing
timeFrame: up to 30 days after intervention
measure: Dilatation
timeFrame: 1 year
measure: Expiration data
timeFrame: 2 years
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: University Clinic Tübingen, Department of Internal Medicine III
state: Baden-Württemberg
city: Ulm
country: Germany
facility: University Clinic Ulm, Department of Internal Medicine II
state: Baden-Württemberg
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum
state: Nordrhein-Westfalen
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Linköping,
country: Sweden
facility: Dept of Cardiology, Linköping University Hospital,
Study officials:
affiliation: University Clinic Tübingen, Tübingen, Germany - Department of Internal Medicine III
name: Tobias Geisler, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bob-Manuel T, Nanda A, Latham S, Pour-Ghaz I, Skelton WP 4th, Khouzam RN. Permanent pacemaker insertion in patients with conduction abnormalities post transcatheter aortic valve replacement: a review and proposed guidelines. Ann Transl Med. 2018 Jan;6(1):11. doi: 10.21037/atm.2017.10.21.
citation: De Torres-Alba F, Kaleschke G, Diller GP, Vormbrock J, Orwat S, Radke R, Reinke F, Fischer D, Reinecke H, Baumgartner H. Changes in the Pacemaker Rate After Transition From Edwards SAPIEN XT to SAPIEN 3 Transcatheter Aortic Valve Implantation: The Critical Role of Valve Implantation Height. JACC Cardiovasc Interv. 2016 Apr 25;9(8):805-813. doi: 10.1016/j.jcin.2015.12.023. Epub 2016 Mar 23.
citation: Maeno Y, Abramowitz Y, Kawamori H, Kazuno Y, Kubo S, Takahashi N, Mangat G, Okuyama K, Kashif M, Chakravarty T, Nakamura M, Cheng W, Friedman J, Berman D, Makkar RR, Jilaihawi H. A Highly Predictive Risk Model for Pacemaker Implantation After TAVR. JACC Cardiovasc Imaging. 2017 Oct;10(10 Pt A):1139-1147. doi: 10.1016/j.jcmg.2016.11.020. Epub 2017 Apr 12.
citation: Tarantini G, Mojoli M, Purita P, Napodano M, D'Onofrio A, Frigo A, Covolo E, Facchin M, Isabella G, Gerosa G, Iliceto S. Unravelling the (arte)fact of increased pacemaker rate with the Edwards SAPIEN 3 valve. EuroIntervention. 2015 Jul;11(3):343-50. doi: 10.4244/EIJY14M11_06.
citation: Mauri V, Reimann A, Stern D, Scherner M, Kuhn E, Rudolph V, Rosenkranz S, Eghbalzadeh K, Friedrichs K, Wahlers T, Baldus S, Madershahian N, Rudolph TK. Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement With the SAPIEN 3. JACC Cardiovasc Interv. 2016 Nov 14;9(21):2200-2209. doi: 10.1016/j.jcin.2016.08.034.
citation: Gonska B, Seeger J, Kessler M, von Keil A, Rottbauer W, Wohrle J. Predictors for permanent pacemaker implantation in patients undergoing transfemoral aortic valve implantation with the Edwards Sapien 3 valve. Clin Res Cardiol. 2017 Aug;106(8):590-597. doi: 10.1007/s00392-017-1093-2. Epub 2017 Mar 10.
citation: Husser O, Pellegrini C, Kessler T, Burgdorf C, Thaller H, Mayr NP, Kasel AM, Kastrati A, Schunkert H, Hengstenberg C. Predictors of Permanent Pacemaker Implantations and New-Onset Conduction Abnormalities With the SAPIEN 3 Balloon-Expandable Transcatheter Heart Valve. JACC Cardiovasc Interv. 2016 Feb 8;9(3):244-254. doi: 10.1016/j.jcin.2015.09.036.
citation: Schwerg M, Fulde F, Dreger H, Poller WC, Stangl K, Laule M. Optimized Implantation Height of the Edwards SAPIEN 3 Valve to Minimize Pacemaker Implantation After TAVI. J Interv Cardiol. 2016 Aug;29(4):370-4. doi: 10.1111/joic.12302. Epub 2016 May 31.
citation: Fujita B, Kutting M, Seiffert M, Scholtz S, Egron S, Prashovikj E, Borgermann J, Schafer T, Scholtz W, Preuss R, Gummert J, Steinseifer U, Ensminger SM. Calcium distribution patterns of the aortic valve as a risk factor for the need of permanent pacemaker implantation after transcatheter aortic valve implantation. Eur Heart J Cardiovasc Imaging. 2016 Dec;17(12):1385-1393. doi: 10.1093/ehjci/jev343. Epub 2016 Jan 12.