1. Quebec Heart & Lung Institute Laval University, Quebec City, Canada
Conduction Disturbances Post-TAVR: Current Status and Future Perspectives
Josep Rodés-Cabau
Quebec Heart & Lung Institute
Laval University, Quebec City, Canada

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
Edwards Lifesciences, Medtronic
Company Names
All TVT 2016 faculty disclosures are listed online and on the app.

3. TAVR and Conduction Disturbances Incidence of LBBB%

4. TAVR and Conduction Disturbances Incidence of PPM
Pour le pace, même differences sont observés entre le deux valves avec une incidence de 7% et autour 26% après l’implantation de une valve edwards et une corevalve, respectivement.

5. Univariate Predictors of PPI Multivariate Predictors of PPI
Predictors of PPM Post-TAVR
Studies n
Univariate Predictors of PPI
D’Ancona et al. (2011)
n=322
Age
Absence of coronary disease
Erkapic et al. (2010)
n=50
RBBB
Corevalve
Koos et al. (2011)
n=80
Corevalve device
Roten et al. (2010)
n=67
Amiodarone use
Betablocker use
Valvuloplasty balloon size
HTA
Jilahiawi et al. (2009)
n=34
Left-axis deviation
LBBB with left-axis deviation
Interventricular septum >17mm
Noncoronary cusp thickness> 8mm
Heart-rate limiting medication
Baan et al. (2010)
Left ventricular outflow tract diameter
Mitral annular calcification
Postimplantation effective-orifice area
Latsios et al. (2010)
Left ventricular ejection fraction
QRS duration
Agatston score
Studies n
Multivariate Predictors of PPI
Piazza et al. (2010)
n=43
QRS duration
Interventricular septum thickness
Ferreira et al. (2010)
n=27
Depth of implantation
Haworth et al. (2010)
n=29
RBBB
Annulus diameter
Munoz-Garcia et al. (2010)
n=61
HTA
RBB
Dilatation of ascending aorta
Fraccaro et al. (2011)
n=64
Male sex
Guetta et al. (2011)
N=70
Pulmonary hypertension
Khawaja et al. (2011)
n=243
Interventricular septum diameter
Left-axis deviation
Prolonged QRS duration
Peri-implantation AVB
Calcification below the aortic valve
Depth of implantation
Valve type
RBBB
Plus des études sont analysé les prédicteurs de l’implantation d’un pm après tavi, et les plus frequent observés lors que des analyses multivariés son al presence une block de la branch droite, l’utilisation de une corevalve et la profondeur de l’implantation de la valve

6. PPM Post-TAVR According to Valve Type%
28.7 28
16.4
12.6
11.5
11.7
9.7
8.9 6
Edwards SAPIEN/
SAPIEN XT
CoreValve
PorticoTM
ACURATETM
SAPIEN 3
Corevalve Evolut R
JenaValveTM
Direct Flow Medical®
Lotus
Adapted from Urena M, Rodés-Cabau J. Eurointervention 2015; Suppl W:101-5

7. Mean/Median Follow-up, years
Impact of PPM on Late Clinical Outcomes
Study n
Intervention
Mean/Median Follow-up, years
Endpoints
Results
(PPI vs. No PPI)
Bagur et al. (2011)
780
SAVR
3.3
Mortality
4% vs. 26%, p=0.12
Raza et al. (2011)
6,268
Any cardiac surgery
7.2 ± 5.0
Adjusted HR: 1.30, p=0.17
D’Ancona et al. (2011)
322
TAVR
(ES) 1
16 vs.19%, p=0.30
Bullesfeld et al. (2012)
353
(ESV, CV)
Death, stroke and MI
Adjusted HR: 1.06, p=0.90
Adjusted HR: 0.98, p= 0.87
De Carlo et al. (2012)
275
(CV)
1.8
12.5% vs 11.8%, p=0.90
Biner et al. (2014)
230 ES CV
1.6
Death and CV events
HR: 1.02, p=0.94
HR: 0.89, p=0.62
Urena et al. (2014)
1,516
(ES, CV)
1.9±1.4
Death or rehospitalization for HF
Adjusted HR: 0.98, p=0.87
Adjusted HR: 1.0, p=0. 98
Mouillet et al. (2015)
833
Death, stroke and bleeding
Heart Failure
16.9 vs. 16.3, p=0.832
32.4 vs. 31.3, p=0.774
11.0 vs , p=0.893
Nazif et al. (2015)
1,973
Death and any rehospitalization
26 vs. 18%, p= 0.08
42 vs. 33%, p=0.007
Impact of PPM on mortality after surgery

8. Impact of PPM on Late Clinical Outcomes
Impact of PPM on mortality after surgery
Regueiro et al. Circulation Intv 2016

9. Impact of PPM on LVEF No PPI 30-day PPI 54 56 58 60 62 Baseline
Discharge
Follow-up
Left ventricular ejection fraction (%)
P=0.017, between both groups
P=0.003, between discharge and follow-up accross groups
P=0.001, between discharge and follow-up for no PPI groups
P=0.412, between baseline and discharge accross groups
P=0.061, between discharge and follow-up for 30-day PPI group
30-day PPI
No PPI
Urena et al. Circulation 2014;29:

10. Permanent pacemaker implantation is indicated for third- degree and advanced second- degree AV block at any anatomic level associated with postoperative AV block that is not expected to resolve after cardiac surgery. (Level of Evidence: C)
Epstein et al. Circulation 2013

11. Br Current European Guidelines Brignole et al. Europace 2013
Mirar si anado la disfunciòn sinusal
Brignole et al. Europace 2013

12. Timing of PPM Post-TAVR
Nazif et al.
JACC Intv 2015; 2015;8:60–9

13. PPM dependency after TAVR
Study n
Type of valve
Incidence of PPM (%)
Indications for PPM
PPM dependency* at follow-up (%)
Fracaro et al. (2011) 67 CV 39
Current guidelines 24
Goldenberg et al. (2013)
178 EV 18
2nd and 3erd degree AVB
New-onset LBBB
New-onset LBBB± PR>200 29
Van der Boon et al. (2013)
167 22
At the discretion of the physician 44
Kirsten al. (2014)
105 52
Ramazzina et al. (2014) 97
ESV 36
New-onset LBBB± PR>200 at de discretion of the physician
*Differences in the definition of pacemaker dependency, and timings

14. TAVI and Conduction Disturbances Evolution of LBBB Over Time
202 patients without prior conduction disturbances
Urena et al. JACC 2012;60:

15. LBBB Post-TAVR and PPM at Follow-Up
Studies showing association between LBBB and AVB and syncope
Regueiro et al. Circulation Intv 2016

16. LBBB and Mortality at Follow-Up
Studies showing association between LBBB and AVB and syncope
Regueiro et al. Circulation Intv 2016

17. LBBB and Sudden Cardiac Death
Urena et al. JACC 2015;65:437-48

18. Reveal LINQ™ Insertable Cardiac Monitoring System (Medtronic)
59 minutes of ECG storage (30min of patient-activated
episodes, 27min of automatically detected episodes and
2min of longest AF episodes stored since last
interrogation)
Titanium nitride coated subcutaneous electrodes to
improve sensing
Auto-activated triggers
Tachycardia
Bradycardia
Asystole
Atrial fibrillation
Patient-activated trigger
MR conditional at 1.5 and 3.0 Tesla
Wireless Transmission with MyCareLink Patient Monitor
Medtronic CareAlert® notifications
Estimated longevity= 3 years
Size – 1.2 cc

19. SJM Confirm™ Implantable Cardiac Monitor (St Jude Medical)
48 minutes of ECG storage (147 episodes)
Subcutaneous electrodes for simplified procedure
4 Auto-activated triggers
Tachycardia
Bradycardia
Asystole
Atrial fibrillation
Patient-activated trigger
MR conditional at 1.5 Tesla
Clinician-programmable
AF duration
Pre- and Post-triggers
Priority of ECG storage
Streamline Follow-Up with the MerlinTM Patient Care System
Estimated longevity= 3 years
Size – 6.5 cc

20. BioMonitor (Biotronik)
60 minutes of ECG storage (can transmit up to six ECGs daily
via home monitoring
Titanium electrodes coating and silicone device coating
Three-vector signal detection (three ECG channels converting
them to one ECG input signal
Daily remote data transfer without patient interaction
Auto-activated triggers
High ventricular rate
Bradycardia
Asystole
Atrial fibrillation
Sudden rate drop
Patient-activated trigger
MR conditional at 1.5 and 3.0 Tesla
Estimated longevity= 6.4 years
Size – 5 cc
10.1g

21. MARE study (NCT02153307) Study Description
Prospective observational study including patients undergoing TAVI with either self-or balloon-expandable valves who develop new-onset LBBB persistent at day 3 post-TAVR. Included patients will receive an implantable loop recorder Reveal ICM LINQ and be followed in outpatient clinic visits at 1,12,24 and 36 months after TAVI.
Study start date: January 2014
Estimated enrollment: 100 patients
Current enrollment: 94 patients enrolled
Sapien XT=28
Sapien 3=24
Corevalve=16
Evolut R=26
Amendment: increased sample size
Valve type
NCT
Primary Outcomes: - Rate and timing of high degree or complete AVB
- Incidence of arrhythmic events identified by the ICM
leading to a change in treatment or major adverse event

22. Assessment of Arrhythmias in Patients Undergoing TAVI using a Small Insertable Cardiac Monitoring Device (Reveal)
(NCT )
Study Description
Prospective observational study including patients undergoing TAVI to investigate the incidence, nature and prognostic significance of AV-conduction disturbances and arrhythmias before, during and after the procedure using a small implantable cardiac monitoring system (Reveal LINQ)
Study start date: March 2016
Estimated enrollment: 100 patients
Estimated Study Completion Date: December 2018
Study design: - Prior to TAVI the ICM will be inserted. The device will be interrogated just
prior to readmission for TAVI and thereafter at 1,3,6, and 12 months of follow-up. The
incidence of symptomatic as well as silent brady- and tachyarrhythmias will be recorded, and
its impact on medical and device treatment as well as clinical outcomes analyzed.
Primary Outcomes: - Number of patients with incidence of new onset atrial fibrillation and
complete AVB within 12 months after TAVI.

23. Indication of Permanent Cardiac Parcing After TAVI (TAVISTIM)
(NCT )
HV Electrophysiology Study in TAVI Patients (HESITATE)
(NCT )
Study Description
Prospective interventional parallel assignment study including patients under-going TAVI through femoral approach to confirm that standard criterion for pacing are reliable in post-TAVI conduction disorders and to analyze the contribution of a systemic electrophysiological study.
Study Description
Prospective, single center non-randomized pilot study in which patients will undergo an electrophysiology study during TAVI procedure.
Study start date: January 2016
Estimated enrollment: 100 patients
Estimated Study Completion Date: December 2017
Study start date: August 2014
Estimated enrollment: 165 patients
Estimated Study Completion Date: August 2016
Assessment of the Prognosis of Persistent LBBB after TAVI by an Electrophysiological and Remote Monitoring Risk-adapted Algorithm (LBBB-TAVI)
(NCT )
Study Description
Prospective interventional parallel assignment study including patients under-going TAVI with de novo LBBB, persistent 24-hour after the procedure will received a endocavitary electrophysiological exploration.
Study start date: June 2015
Estimated enrollment: 200 patients
Estimated Study Completion Date: December 2017

24. Take-Home Message
The occurrence of conduction disturbances remains the most frequent complication of TAVR
Increasing evidence on the negative clinical impact of conduction disturbances post-TAVR
Prevention: valve type, higher transcatheter valve positioning
Management of high-degree AVB post-TAVR: a period of observation might be reasonable before pacemaker implantation in order to identify transient conduction disorders and avoid unnecessary pacemaker implants
Management of new-onset LBBB post-TAVR: no definite recommendation can be made from available data. Further studies (continuous ECG monitoring devices) are needed to better determine i) the clinical impact of this conduction disturbance, and ii) the factors associated with progression-regression of LBBB over time