Prospective Validation of a Pre-Specified Algorithm for the Management of Conduction Disturbances Following Transcatheter Aortic Valve Replacement. (PROMOTE)

Prospective Validation of a Pre-Specified Algorithm for the Management of Conduction Disturbances Following Transcatheter Aortic Valve Replacement. The PROMOTE Study

The high incidence and variety of conduction disturbances post-TAVR represents a major challenge in the periprocedural management of TAVR recipients. Despite the growing body of knowledge on this topic, the large variability in the management of these complications has translated into a high degree of uncertainty regarding the most appropriate treatment of a large proportion of such patients. The implementation of a pre-specified treatment strategy translating into a more uniform practice regarding the management of conduction disturbances post-TAVR applied to a large cohort of patients would permit to identify the benefits and drawbacks of each specific aspect of the treatment algorithm proposal. This may also help to improve both the management and clinical outcomes of the complex group of patients with conduction disturbances associated with TAVR. In the end, the final objective of a pre-specified strategy for managing conduction disturbances post-TAVR should be to obtain a low rate of PPM without increasing the risk of sudden death or life threatening arrhythmic events following hospital discharge, and all this while avoiding an excessive prolongation of the hospitalization period following the TAVR procedure.

Study Overview

• Status: Recruiting
• Conditions: Transcatheter Aortic Valve Replacement; Permanent Pacemaker Implantation; Conduction Disturbances

Detailed Description

The objectives of the study are:

• Feasibility: to validate and determine the applicability of a pre-specified algorithm for managing conduction disturbances in consecutive patients undergoing TAVR, also evaluating the percentage of patients included in each group of the algorithm strategy.
• Efficacy: (i) to evaluate the rate of permanent pacemaker implantation in-hospital and at 30 days compared to that of the year prior to the implementation of the protocol, (ii) to determine the incidence of sudden death at 30 days and at 1-year follow-up.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Melanie Côté, MSc; Phone Number: 2646 418-656-8711; Email: melanie.cote@criucpq.ulaval.ca
• Study Contact Backup: Name: Josep Rodés-Cabau, MD; Phone Number: 418-656-8711; Email: josep.rodes@criucpq.ulaval.ca

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Recruiting
    • IUCPQ
    • Principal Investigator: Josep Rodes-Cabau
    • Contact: Melanie Cote, MSc; Phone Number: Rodes-Cabau 4186568711; Email: melanie.cote@criucpq.ulaval.ca
    • Contact: Josep Rodes-Cabau, MD; Phone Number: 4186568711; Email: josep.rodes@criucpq.ulaval.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients with aortic valve disease undergoing transcatheter aortic valve replacement without prior permanent pacemaker

Description

Inclusion Criteria:

-Patients with aortic valve disease undergoing transcatheter aortic valve replacement

Exclusion Criteria:

• Prior permanent pacemaker
• Failure to provide signed informed consent for data collection
• Impossibility for a follow-up
• Unwillingness to follow the pre-specified strategy for the management of conduction disturbances

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
No ECG changes in patients without pre-existing RBBB; Patients with no new conduction disturbances on the ECG performed immediately post-TAVR (and no episodes of HAVB/CHB during the procedure) have a very low risk of developing HAVB/CHB or any conduction disturbance within the hours-days following the procedure. In these cases, temporary pacing will be discontinued at the end of the procedure. However, continuous ECG monitoring until hospital discharge is recommended. A 12-lead ECG is recommended 24 hours after the procedure. If no arrhythmic episodes and no ECG changes occur within the 24 hours post-procedure, the patient can be safely discharged (the day after TAVR) with no other monitoring measures in case of otherwise uneventful clinical course (absence of other TAVR related adverse events). If the patient has to remain hospitalized because of other reasons or TAVR complications, telemetry would be recommended (but no strictly required) for the detection of post-TAVR tachyarrhythmias or late ECG changes.
Patients with pre-existing RBBB; A temporary pacing wire is recommended to be maintained for 24 hours (or at least overnight) in all patients with prior RBBB, along with telemetry and daily ECG during the entire hospitalization period (minimum of 2 days). If any ECG changes occur during the initial 2-3 days, patients can be managed according to the proposed strategy (see management strategies for groups 3 and 5). If no ECG changes or significant bradyarrythmias occur within the 2-3 days following the procedure, the patient can be discharged. Considering that the increased risk of life threatening bradyarrhythmias in these patients may extend beyond the hospitalization period, the use of continuous ECG monitoring systems (minimum of 48 hours, up to 4 weeks) may be considered.
ECG changes in patients with prior conduction disturbances; Any significant increase in PR or QRS interval will indicate to continuing the temporary pacing for 24 hrs, with daily ECG and telemetry for 1-2 days. If the ECG changes regress in <24 hrs, an earlier removal of the temporary pacing may be considered. Also, a strategy of multiple ECGs during the first 24 hrs may be considered. If ECG changes regress or no further changes occur the patient can be discharged with no PPM at 2 days post-TAVR. If 24 hrs post-TAVR, the PR and QRS interval remain stable but >240 or >150 ms, respectively, and ≥20 ms longer than baseline, maintaining the temporary pacing wire for another 24 hrs is recommended. If no decrease in the PR or QRS duration occurs at day 2, the patient can be considered at risk for more advanced conduction disturbances requiring PPM. The use of an EP study may be a reasonable option for deciding PPM in those patients with prior conduction disturbances with worsening of ECG changes post-TAVR
New-onset LBBB; Temporary pacing for 24 hrs is recommended, in all patients with new-onset LBBB post-TAVR. Earlier removal of the temporary pacing and discharged at day 1 can be considered if LBBB resolves in <24 hrs. If LBBB persists but no further progression of the duration of the QRS or PR interval is observed at day 1, temporary pacing can be discontinued. If no further ECG changes are observed up to day 2-3 post-TAVR, the patient can be discharged. These patients are however at increased risk of HAVB/CHB requiring PPM, and continuous ECG monitoring and/or EP studies may be considered. If further prolongation of the QRS or PR interval is observed at day 1, the temporary pacing is recommended for an additional 24 hrs. If the prolongation of the QRS or PR intervals continues at day 2, evaluation with EP studies or PPM implantation may be considered. The occurrence of any episode of HAVB/CHB following TAVR in a patient with new-onset LBBB will be considered an indication for PPM
HAVB/CHB during the periprocedural period; Maintaining temporary pacing in patients with procedural persistent HAVB/CHB, and monitoring in intensive care unit are recommended. If HAVB/CHB persists at 24 hrs, PPM is recommended. If HAVB/CHB recovers the day after TAVR, the temporary pacing can be removed and the patient can remain hospitalized for 1 day. If another episode of HAVB/CHB occurs, PPM is recommended. If no other episode of HAVB/CHB occurs, and no other features potentially justifying PPM exist the patient can be discharged. Temporary pacing is recommended for 24 hrs in patients with transient HAVB during the procedure, with telemetry and daily ECG for 2 days. Discontinuing temporary pacing may be considered in those cases with brief episodes of HAVB/CHB and normal ECG. If no recurrent episodes of HAVB/CHB occur, and the patient has no other potential indications for PPM the patient can be discharged at day 2. PPM would be indicated if any recurrent episode of HAVB/CHB occurs during the hospitalization period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of successful algorithm implementation and percentage of patients in each arm of the pre-specified algorithm	1 year follow-up
Incidence of permanent pacemaker implantation	At 30-day follow-up
Incidence of permanent pacemaker implantation	At 1-year follow-up
Incidence of sudden death	At 30-day follow-up
Incidence of sudden death	At 1-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate, timing of and reasons for permanent pacemaker implantation	Rate, timing of and reasons for permanent pacemaker implantation in each group of the pre-specified algorithm	Before hospital discharge (between 1 to 30 days)
Rate, timing of and reasons for permanent pacemaker implantation	Rate, timing of and reasons for permanent pacemaker implantation in each group of the pre-specified algorithm	At 30-day follow-up
Rate, timing of and reasons for permanent pacemaker implantation	Rate, timing of and reasons for permanent pacemaker implantation in each group of the pre-specified algorithm	At 1 year follow-up
Rate and timing of sudden death	Rate and timing of sudden death in each group of the pre-specified algorithm	At 30-day follow-up
Rate and timing of sudden death	Rate and timing of sudden death in each group of the pre-specified algorithm	At 1-year follow-up
Evaluation of arrhythmic events in patients with continuous ECG monitoring	Evaluation of arrhythmic events in patients with continuous ECG monitoring at hospital discharge	After hospital discharge (up to 1-year)
Evaluation of the rate and timing of permanent pacemaker implantation		After hospital discharge (up to 1-year)
Rate of PPI among valve types	Compare rate of permanent pacemaker implantation among different valve types	At 30-day follow-up
Rate of PPI among valve types	Compare rate of permanent pacemaker implantation among different valve types	At 1-year follow-up
Pace dependency and pacing rate	Determine the pace dependency and pacing rate in patients with periprocedural permanent pacemaker implantation (overall and in each subgroup of the algorithm)	At 30-day follow-up
Pace dependency and pacing rate	Determine the pace dependency and pacing rate in patients with periprocedural permanent pacemaker implantation (overall and in each subgroup of the algorithm)	At 1-year follow-up
Factors associated with sudden death or permanent pacemaker implantation	Determine factors associated with sudden death or permanent pacemaker implantation during the follow-up period overall and in each algorithm group	At 30-day follow-up
Factors associated with sudden death or permanent pacemaker implantation	Determine factors associated with sudden death or permanent pacemaker implantation during the follow-up period overall and in each algorithm group	At 1-year follow-up

Collaborators and Investigators

• Sponsor: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Publications and helpful links

General Publications

• Auffret V, Puri R, Urena M, Chamandi C, Rodriguez-Gabella T, Philippon F, Rodes-Cabau J. Conduction Disturbances After Transcatheter Aortic Valve Replacement: Current Status and Future Perspectives. Circulation. 2017 Sep 12;136(11):1049-1069. doi: 10.1161/CIRCULATIONAHA.117.028352.
• Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodes-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Eur Heart J. 2012 Oct;33(19):2403-18. doi: 10.1093/eurheartj/ehs255.
• Puri R, Chamandi C, Rodriguez-Gabella T, Rodes-Cabau J. Future of transcatheter aortic valve implantation - evolving clinical indications. Nat Rev Cardiol. 2018 Jan;15(1):57-65. doi: 10.1038/nrcardio.2017.116. Epub 2017 Aug 24.
• Kolte D, Vlahakes GJ, Palacios IF, Sakhuja R, Passeri JJ, Inglessis I, Elmariah S. Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients. J Am Coll Cardiol. 2019 Sep 24;74(12):1532-1540. doi: 10.1016/j.jacc.2019.06.076.
• Auffret V, Lefevre T, Van Belle E, Eltchaninoff H, Iung B, Koning R, Motreff P, Leprince P, Verhoye JP, Manigold T, Souteyrand G, Boulmier D, Joly P, Pinaud F, Himbert D, Collet JP, Rioufol G, Ghostine S, Bar O, Dibie A, Champagnac D, Leroux L, Collet F, Teiger E, Darremont O, Folliguet T, Leclercq F, Lhermusier T, Olhmann P, Huret B, Lorgis L, Drogoul L, Bertrand B, Spaulding C, Quilliet L, Cuisset T, Delomez M, Beygui F, Claudel JP, Hepp A, Jegou A, Gommeaux A, Mirode A, Christiaens L, Christophe C, Cassat C, Metz D, Mangin L, Isaaz K, Jacquemin L, Guyon P, Pouillot C, Makowski S, Bataille V, Rodes-Cabau J, Gilard M, Le Breton H; FRANCE TAVI Investigators. Temporal Trends in Transcatheter Aortic Valve Replacement in France: FRANCE 2 to FRANCE TAVI. J Am Coll Cardiol. 2017 Jul 4;70(1):42-55. doi: 10.1016/j.jacc.2017.04.053.
• van Rosendael PJ, Delgado V, Bax JJ. Pacemaker implantation rate after transcatheter aortic valve implantation with early and new-generation devices: a systematic review. Eur Heart J. 2018 Jun 1;39(21):2003-2013. doi: 10.1093/eurheartj/ehx785.
• Cerrato E, Nombela-Franco L, Nazif TM, Eltchaninoff H, Sondergaard L, Ribeiro HB, Barbanti M, Nietlispach F, De Jaegere P, Agostoni P, Trillo R, Jimenez-Quevedo P, D'Ascenzo F, Wendler O, Maluenda G, Chen M, Tamburino C, Macaya C, Leon MB, Rodes-Cabau J. Evaluation of current practices in transcatheter aortic valve implantation: The WRITTEN (WoRldwIde TAVI ExperieNce) survey. Int J Cardiol. 2017 Feb 1;228:640-647. doi: 10.1016/j.ijcard.2016.11.104. Epub 2016 Nov 9.
• Rodes-Cabau J, Ellenbogen KA, Krahn AD, Latib A, Mack M, Mittal S, Muntane-Carol G, Nazif TM, Sondergaard L, Urena M, Windecker S, Philippon F. Management of Conduction Disturbances Associated With Transcatheter Aortic Valve Replacement: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Aug 27;74(8):1086-1106. doi: 10.1016/j.jacc.2019.07.014.
• Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, Goldschlager NF, Hamilton RM, Joglar JA, Kim RJ, Lee R, Marine JE, McLeod CJ, Oken KR, Patton KK, Pellegrini CN, Selzman KA, Thompson A, Varosy PD. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol. 2019 Aug 20;74(7):932-987. doi: 10.1016/j.jacc.2018.10.043. Epub 2018 Nov 6. No abstract available. Erratum In: J Am Coll Cardiol. 2019 Aug 20;74(7):1014-1016.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Estimated): February 25, 2024
• Study Completion (Estimated): February 25, 2025

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Right bundle branch block; atrioventricular block; left bundle branch block; intraventricular conduction delay; complete heart block; high-degree atrioventricular block; Permanent pacemaker implantation
• Other Study ID Numbers: PROMOTE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No