STIMulation Cardiaque et TAVI : évolution Des Troubles Conductifs Atrio-ventriculaires après TAVI
Conditions: Pacemaker Implantation, TAVI
Sponsor: Association de Recherche en Cardiologie des Alpes

 
 
 
 
 
 
 
STIM - TAVI 
STIMulation cardiaque et TAVI : évolution des troubles 
conductifs atrio-ventriculaires après TAVI 
 
 
 
 
 
 
 
 
 
 
 
Date of the protocol : October 15, 2015 
English title : STIMTAVI : Evolution of Atrioventricular Conduction Disorders After TAVI 
 
Main Investigator :  
Dr IRLES Didier  
Cardiology – Annecy Hospital  
FRANCE 
dirles@ch-annecygenevois.fr 
+33 4 50 63 66 03 
 
Scientific Committee :  
French Society of Cardiology  
 
Study Manager : Research department - Annecy Hospital 
 
Statistics Manager :  
Dr JUND Jérôme – Annecy Hospital 
jjund@ch-annecygenevois.fr 
+33 4 50 63 64 48 
 
 

 
 
Summary 
 
 
I. State of the art 
 
II. Study Objectives 
 
III. Criteria for judgments 
 
IV. Population concerned 
 
V. Investigation Method 
 
VI. Regulatory and pharmacovigilance 
 
VII. Collection, processing and data transfer 
 
VIII. Nature of collected data 
 
IX. Data analysis method 
 
X. Research duration and number of patients included 
 
XI. References 
 
 
 
List of Abbreviations 
 
 
ARC: Assistant (e) Clinical Research 
 
AVB: atrioventricular block 
 
TAVI: transcatheter aortic valve implant 
 
A-V: atrioventricular 
 
AAI: Pacing mode with atrial sensing and Pacing 
 
DDD pacing mode with atrial and ventricular sensing/pacing 
 
PM: pacemaker 
 
CI: confidence interval 
 
EGM: endocardial electrogram (leads of the pacemaker) 
 
EKG: electrocardiogram 

 
 
 
I. State of the Art: 
 
Atrioventricular (A-V) conduction disorders are common after Transcatheter Aortic 
Valve Implantation (TAVI) and the average of a pacemaker implantation after TAVI is 
15% to 17% (1) ( 2) (3) (4). 
 
The European Society of Cardiology recommends to implant a permanent 
pacemaker (PM) in case of persistant high-grade A-V block (AVB) within 7 days of a 
TAVI procedure (class I recommendation, level of evidence C) (2). 
 
Some conduction disturbances are transient and might not need a definitive 
indication for pacemaker implantation. A recent study, based on dependency of 
patients to pacing, estimate that in half the patients, conduction disturbances that led 
to the implantation of a pacemaker after TAVI procedure would have disappear 30 
days after the procedure (5). 
 
Many studies tried to better define the indications of these devices. However, their 
evaluation criterias do not allow to prove these pacemakers were useful, because 
these studies are mainly based on the rate of implantation of pacemakers, or on the 
percentage of ventricular pacing. These studies may overestimate the usefulness of 
the pacemaker because of unnecessary ventricular pacing, or underestimate it in 
patients with high grade paroxysmal AVB, that could have been responsible for 
syncope or death (3) (4) (6) (7). 
 
Today some pacemakers allow a better occurrence of spontaneous A-V conduction 
and monitor precisely the atrioventricular conduction. 
The AAI SafeR® mode from Sorin® allows the pacemaker to switch from a single to 
a dual chamber mode in case of AVB; these switches are stored in the memories of 
PM as endocardial electrogram (EGM) which can be validated afterwards. The use of 
this algorithm could allow an accurate assessment of the persistence of high level 
conduction disturbances in patients implanted with a pacemaker after a TAVI 
procedure. A study published in late 2014 using this tool in monitoring post TAVI 
conduction disorders on a small number of patients, other studies used the same tool 
in other cardiac pathologies. 
 
We propose to carry out an observational study of patients implanted with a 
pacemaker using AAI SafeR® mode after a TAVI procedure. This study aims to 
define the persistence or not of high-grade AVB beyond seven days after the 
procedure, based on the analysis of PM memories, and define definitive cardiac 
pacing indications after TAVI procedure. 
 
 
II.OBJECTIFS of the study 
Primary End point : 
Prove persistence or not of high grade conduction disturbances beyond seven days 
after a TAVI procedure in patients in sinus rhythm implanted with a Sorin dual 
chamber Pacemaker programmed in AAI SafeR mode. 
 

 
 
 
Secondary End point: 
Define the factors associated with a higher risk of high level A-V block after a TAVI 
procedure. This analysis will allow us to better define the final pacing indications after 
TAVI. 
 
 
 III.CRITERIA of JUDGEMENT 
 
High level persistent A-V Block in patients after TAVI procedure is defined: 
 
- Either by the analysis of the pacemaker memories showing the switches to DDD 
mode after one or more of these three reasons: 
• a succession of at least 2 consecutive  blocked P waves  
• more than 3 blocked P waves among 12 consecutive cycles 
• ventricular pause for over 2 seconds with at least one blocked P wave  
 
- Either by the presence of a high level AVB during the pacemaker interrogation 
 
We classify as transitional AVB (D7 persistent, non-persistent beyond 1 month), and 
permanent AVB (persistent beyond 1 month). 
 
 
IV. POPULATION STUDIED 
 
Inclusion criterias: 
All patients over 18 years who underwent implantation of a TAVI and that were 
implanted during the hospitalization with a dual chamber pacemaker Sorin®, set in 
AAI SafeR ® or AAI SafeR-R® mode. 
 
 
Exclusion criterias: 
- Patients with life expectancy at hospital discharge estimated as less than 1 year 
- TAVI procedure failure 
- Patients refusing to be involved in the study 
- Patients implanted with a PM of a brand different than Sorin® during the hospital 
phase or implanted Sorin® PM but not set in a AAI or AAI SafeR SafeR-R mode 
- Patients with PM implant before TAVI 
- Permanent AF at the implantation time 
- Patients with Single or Triple chamber PM  
 
 
V.INVESTIGATION METHODE 
 
We propose a prospective, observational, multicenter study of patients implanted with 
a Sorin® PM set in a AAI SafeR® or AAI SafeR-R® mode, after a TAVI procedure. 
The follow-up period will be at least 1 year after implantation of the pacemaker. 
Only data related to monitoring of A-V conduction disorders is collected during this 
study. 

 
 
The PM implantation decision and the choice of treatments are up to the local 
investigators. 
 
The scientific committee has to validate the protocol, ensure the scientific and ethical 
oversight of the study, ensure the confidentiality of the study and the compliance the 
investigators with the commitments of this protocol and good clinical practices rules 
and ethics. 
An annual report will be provided to the scientific committee and the participating 
centers. 
Submissions for communications or publications will be sent to the scientific 
committee and sponsors before presentation or publication. 
 
 
VI. REGULATORY AND PHARMACOVIGILANCE 
 
The study will not alter the therapeutic attitude of medical teams. The protocol has no 
influence on medical prescription in the hospital and in the long-term monitoring. No 
visit outside the conventional monitoring visits or special exams are required as part 
of the study. The study will therefore not need the authorization of people protection 
committee (apart from an advisory opinion on the non-interventional nature of the 
study) or AFSSAPS. It was submitted to the CCTIRS (advisory committee on the 
treatment of research information in health matters) and the CNIL (national 
commission on informatics and liberties), and has received the necessary 
authorizations. 
 
The principal investigator agrees to remind health professionals involved in the study 
their legal and regulatory obligations (Articles L. 5121-25 and R. 5121-161 of the 
public health code). The principal investigator is not responsible for the declaration of 
adverse events related to the subject of the study and occurred during it. 
 
 
VII. Collection, processing and data transfer 
 
According to the texts about law and liberties last modified the 6 January 1978, all 
patients before involved in the study will receive an information note on the 
transmission and use of their data (Annex 1). Patients may orally refuse to participate 
to the study. 
Data entry will be undertaken by the clinical research associate and the investigator 
in each participating center, bound by professional secrecy : inclusion data at the first 
postoperative visit, and during monitoring visits at the end of the study. The entry will 
be made on an electronic case report form (e-CRF), protected by passwords. The 
analysis will be performed on a computer database specifically created for this study. 
The access to the database will be secured and customized by a user name and 
password. The PM interrogation files will be sent to the investigating center, for a 
centralized reading of the memorized EGM by an independent adjudication 
committee. 
The electronic case report forms will be stored respecting the anonymity of patients. 
Patients will be identified by an inclusion number, the first three letter of their first 
name, the first two letters of their last name, and their month and year of birth. Each 

 
 
center will have to store the correspondence between the inclusion numbers and 
identity of the patient on a list that must remain confidential under the responsibility of 
the investigator of the center. 
The database of informations collected will not be duplicated and will be stored on a 
single computer, protected by access codes, under the responsibility of the principal 
investigator in the center. 
Patient information notes, protocol, e-mails, trial documents and patient identity 
match list with the inclusion numbers will be stored by the centers for at least 15 
years. The anonymised data will be kept by the principal investigator of the study for 
the same duration after the end of the research, in accordance with good clinical 
practice guide. 
 
 
VIII. NATURE OF COLLECTED DATA 
 
The data collected allow us to characterize our population and to determine the 
variables associated with the primary and secondary endpoints, only as part of the 
objective of our research. 
The collected variables are listed in the report form (Appendix 2) 
 
 
IX. DATA ANALYSIS METHOD 
 
The registry analysis will be conducted by the Statistical Service of the Annecy 
regional public hospital (Centre Hospitalier Annecy Genevois). We will describe the 
characteristics of our population (age, sex, cardiac history, cardiac functional signs, 
EKG, data from the TAVI procedure (type and size of implant, valvular calcification, 
implant height, surgical approach). According to the main goal, we will determine the 
incidence of high level A-V block in patients involved in the study, after reviewing and 
validation of the PM memories by an independent adjudication committee. In 
accordance with the secondary objective, we will study the factors associated with 
the primary outcome: gender, age, preexisting conduction disturbances (complete 
right bundle branch block, left anterior hemiblock, first degree A-V block), high grade 
AVB during the TAVI procedure, worsening of conduction disturbances during the 
procedure or within the next hour (appearance of a left bundle branch block, QRS 
widening beyond 120ms, prolongation of PR beyond 200ms ), worsening of HV 
conduction time immediately after the procedure TAVI or later (if scanning is 
performed), implantation of a Medtronic® CoreValve prosthesis (compared to a 
Edwards® Sapien prosthesis), height of the implantation of the valve, oversizing. 
 
 
X. STUDY DURATION  AND NUMBER OF PATIENTS INCLUDED 
 
With the assumption of a frequency of 50% endpoint and a power of 80%, with 200 
patients included the 95% confidence interval would be 43-57% (Wilson’s method) 
(5). 
Considering that 20% of patients enrolled will be lost we plan to include 250 patients. 
This study will begin in June 2014 for a period of 2 years. 
 

 
 
Suggérer une modification 
XI. REFERENCES 
 
 
 
1. 
Gilard M, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, et 
al. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J 
Med. 2012 May 3;366(18):1705-15. 
2. 
Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, 
Breithardt OA, et al. 2013 ESC Guidelines on cardiac pacing and cardiac 
resynchronization therapy: the Task Force on cardiac pacing and resynchronization 
therapy of the European Society of Cardiology (ESC). Developed in collaboration 
with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013 
Aug;34(29):2281-329. 
3. 
Erkapic D, De Rosa S, Kelava A, Lehmann R, Fichtlscherer S, Hohnloser SH. 
Risk for permanent pacemaker after transcatheter aortic valve implantation: a 
comprehensive analysis of the literature. J Cardiovasc Electrophysiol. 2012 
Apr;23(4):391-7. 
4. 
Siontis GC, Juni P, Pilgrim T, Stortecky S, Bullesfeld L, Meier B, et al. 
Predictors of permanent pacemaker implantation in patients with severe aortic 
stenosis undergoing TAVR: a meta-analysis. J Am Coll Cardiol. 2014 Jul 
15;64(2):129-40. 
5. 
Bjerre Thygesen J, Loh PH, Cholteesupachai J, Franzen O, Sondergaard L. 
Reevaluation of the indications for permanent pacemaker implantation after 
transcatheter aortic valve implantation. J Invasive Cardiol. 2014 Feb;26(2):94-9. 
6. 
Bates MG, Matthews IG, Fazal IA, Turley AJ. Postoperative permanent 
pacemaker implantation in patients undergoing trans-catheter aortic valve 
implantation: what is the incidence and are there any predicting factors? Interact 
Cardiovasc Thorac Surg. 2011 Feb;12(2):243-53. 
7. 
Frohlig G, Gras D, Victor J, Mabo P, Galley D, Savoure A, et al. Use of a new 
cardiac pacing mode designed to eliminate unnecessary ventricular pacing. 
Europace. 2006 Feb;8(2):96-101. 
8. 
Bleiziffer S, Ruge H, Horer J, Hutter A, Geisbusch S, Brockmann G, et al. 
Predictors for new-onset complete heart block after transcatheter aortic valve 
implantation. JACC Cardiovasc Interv. 2010 May;3(5):524-30. 
9. 
Erkapic D, Kim WK, Weber M, Mollmann H, Berkowitsch A, Zaltsberg S, et al. 
Electrocardiographic and further predictors for permanent pacemaker requirement 
after transcatheter aortic valve implantation. Europace. 2010 Aug;12(8):1188-90. 
10. 
Courvoisier DS, Combescure C, Agoritsas T, Gayet-Ageron A, Perneger TV. 
Performance of logistic regression modeling: beyond the number of events per 
variable, the role of data structure. J Clin Epidemiol. 2011 Sep;64(9):993-1000.