Accelerated Pacing in Patients Undergoing Pace-and-ablate Strategy With LBBAP: a Randomized Controlled Pilot Trial (PACE-AF)

Accelerated PACing for Improved Quality of lifE in Symptomatic Atrial Fibrillation Patients Undergoing Pace-and-ablate Strategy With Left Bundle Branch Area Pacing: a Randomized Controlled Pilot Trial: PACE-AF

The goal of this clinical trial is to determine the effect of accelerated pacing (pacemaker lower rate programmed to 80bpm) compared to pacing at the standard programmed lower rate of 60bpm in symptomatic atrial fibrillation patients undergoing pace-and-ablate strategy with LBBAP.

The main question it aims to answer is:

- To determine the effect of accelerated pacing on health-related quality of life compared to the current standard of care.

Secondary questions it aims to answer are:

• To study the acute hemodynamic effect of different (accelerated) pacing rates on pulmonary capillary wedge pressure, cardiac output and arterial blood pressure among atrial fibrillation patients undergoing pace-and-ablate strategy.
• To study the long-term effects (at 6 months) of accelerated pacing compared to the current standard of care among atrial fibrillation patients undergoing pace-and-ablate strategy on:
• NT pro BNP levels
• device detected atrial fibrillation burden and daily activity
• echocardiographic measurements (LVEF, left ventricular ejection fraction; LVEDD, left ventricular end- diastolic diameter; LVESD, left ventricular end-systolic diameter; LAVI left atrial volume index; diastolic parameters; strain

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation; Pacemaker DDD; Paroxysmal Atrial Fibrillation; Persistent Atrial Fibrillation; Permanent Atrial Fibrillation
• Intervention / Treatment: Device: Accelerated pacing; Device: Current standard of care

Detailed Description

Rationale:

Permanent pacemaker implantation combined with atrioventricular node ablation (AVNA) reduces symptoms and improves health-related quality of life (HRQoL) in patients with symptomatic atrial fibrillation (AF). A high percentage of conventional right ventricular pacing increases the risk for pacing-induced cardiomyopathy, a risk which is presumably minimised by a form of conduction system pacing, termed left bundle branch area pacing (LBBAP). LBBAP attempts to recreate the normal physiologic activation of the heart through stimulation of the heart's own natural conduction system, thereby maintaining ventricular synchrony. This strategy may be particularly important in patients with heart failure with preserved ejection fraction (HFpEF), a diagnosis that frequently coexists with AF. The long-term programming of a patient undergoing a "pace-and-ablate strategy" (pacemaker implantation and AVNA), is such that the lower rate of the pacemaker is routinely set to 60 bpm. Previous studies have shown that accelerated pacing (ie. programming the pacemaker to a lower rate of 80bpm) may improve HRQoL in a subset of patients with HFpEF. It is therefore hypothesized that accelerated pacing will improve HRQoL in patients with symptomatic AF undergoing a pace and ablate strategy, when compared to pacing at 60 bpm, which is standard of care.

Objective:

Primary objective: To determine the effect of accelerated pacing (lower programmed rate of 80 bpm) compared to pacing at the standard programmed rate of 60 bpm on HRQoL in symptomatic AF patients undergoing pace-and-ablate strategy with LBBAP.

Secondary objectives:

• To study, in a subset of participants who give informed consent, the acute hemodynamic effect of accelerated pacing rates on pulmonary capillary wedge pressure (PCWP), cardiac output and arterial blood pressure, among AF patients undergoing a pace-and-ablate strategy with LBBAP.
• To study the long-term (6 months) effects of accelerated pacing among AF patients undergoing a pace-and-ablate strategy with LBBAP by measuring NT-proBNP levels, device detected AF-burden and daily activity, by evaluating HRQoL questionnaires (SF-36), and by assessing echocardiographic measurements (LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; LAVI left atrial volume index; diastolic parameters; strain) compared to pacing at the standard of care lower rate of 60bpm.
• To investigate whether participants experience symptoms of accelerated pacing (such as palpitations), based on the Atrial Fibrillation Effect on Quality-of-life (AFEQT) questionnaire, compared to standard of care.

Study design:

Randomized, single center, prospective, single blinded, parallel group, pilot-trial.

Study population:

Patients ≥ 18 years with symptomatic AF undergoing pace-and-ablate strategy.

Intervention:

- 1:1 randomization to a lower rate of DDDR 80 bpm (intervention) or a lower rate of DDDR 60 bpm (control). Duration of the study is 6 months.

In a subset of participants:

- Right heart catheterisation and invasive blood pressure measurements will be conducted to evaluate acute hemodynamic effects of different (accelerated) ventricular pacing rates during the standard of care AV node ablation.

Main study parameters/endpoints:

Primary endpoint:

Difference in HRQoL between a lower rate of 80 bpm and a lower rate of 60 bpm, based on the Minnesota Living with Heart Failure Questionnaire (MLHFQ), determined at 6 months follow-up.

Secondary endpoints:

• The acute hemodynamic effects of (accelerated) pacing at time of AVNA:

  • Pulmonary Capillary Wedge Pressure (PCWP)
  • Cardiac Output (CO)
  • Systemic arterial blood pressure

• The long-term effect of accelerated pacing on:

  • HRQoL, based on the MLHFQ and SF-36 questionnaires.
  • NT-proBNP levels
  • Device detected AF burden
  • Device detected daily activity comparing accelerated- vs control rate
  • Echocardiographic measurements (LVEF, LVEDD, LVESD, LAVI, LA strain)
• Symptoms experienced as a result of (accelerated) pacing based on the AFEQT questionnaire

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kevin Vernooy, MD, PhD; Phone Number: +31433877095; Email: kevin.vernooy@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults > 18 years of age
• Referred for pace-and-ablate strategy with LBBAP for symptomatic AF
• Left ventricular ejection fraction ≥ 40%.
• Willingness to participate, to understand the instructions and fill out the questionnaires, and ability to sign informed consent.

Exclusion Criteria:

• Infiltrative or constrictive cardiomyopathy (cardiac amyloidosis/sarcoidosis/ constrictive pericarditis)
• Severe Valvular heart disease (more than moderate valvular stenosis or regurgitation, aortic or mitral valve replacement)
• Patient participating in another interventional clinical trial
• Recent (< 3 months) Myocardial infarction (MI), Transient Ischemic Attack or Cerebro- Vascular Accident

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Accelerated pacing (lower rate pacemaker 80bpm); Patients in the experimental arm will have their pacemaker programmed to a lower rate of 80bpm.	Device: Accelerated pacing; The lower rate of the pacemaker will be programmed to 80 bpm in DDDR mode with mode switch to DDIR mode.
Active Comparator: Current standard of care (lower rate pacemaker 60bpm); Patients in the control arm will have their pacemaker programmed to a lower rate of 60bpm, which is the current standard of care.	Device: Current standard of care; The lower rate of the pacemaker will be programmed to the current standard of care which is 60 bpm in DDDR mode with mode switch to DDIR mode.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of accelerated pacing (lower programmed rate of 80 bpm) compared to pacing at the standard programmed rate of 60 bpm on health-related quality of life (HRQoL) in symptomatic AF patients undergoing pace-and-ablate strategy with LBBAP.	The primary endpoint of this study is the difference in HRQoL, measured with the Minnesota Living with Heart Failure Questionnaire (MLHFQ), between patients programmed to accelerated pacing with a lower rate of 80 bpm (intervention) compared to current standard of care with a lower rate of 60 bpm (control). The score in the MLHFQ can range between 0 to 105, with higher scores indicating more significant impairment in health-related quality of life.	6 months after the AV node ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The acute hemodynamic effects of different (accelerated) pacing rates on pulmonary capillary wedge pressure (PCWP).	The acute effect of various accelerated pacing rates on PCWP measured by a right heart catheterization during the AV node ablation procedure among AF patients undergoing a pace-and-ablate strategy with LBBAP.	At the AV node ablation
The acute hemodynamic effects of different (accelerated) pacing rates on cardiac output (CO).	The acute effect of various accelerated pacing rates on CO measured by a right heart catheterization during the AV node ablation procedure among AF patients undergoing a pace-and-ablate strategy with LBBAP.	At the AV node ablation
The acute hemodynamic effects of different (accelerated) pacing rates on arterial blood pressure.	The acute effect of various accelerated pacing rates on arterial blood pressure measured invasively in the femoral artery during the AV node ablation procedure among AF patients undergoing a pace-and-ablate strategy with LBBAP.	At the AV node ablation
The long-term effects of accelerated pacing on health-related quality of life based on the 36-item short form health survey (SF-36) among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on HRQoL measured by the SF-36 questionnaire.	6 months after the AV node ablation
The long-term effects of accelerated pacing on NTproBNP levels among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on NTproBNP levels.	6 months after the AV node ablation
The long-term effects of accelerated pacing on device detected AF burden among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on device detected AF burden.	6 months after the AV node ablation
The long-term effects of accelerated pacing on device detected daily activity among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on device detected daily activity.	6 months after the AV node ablation
The long-term effects of accelerated pacing on echocardiographic changes among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on LVEF.	6 months after the AV node ablation
The long-term effects of accelerated pacing on echocardiographic changes among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on LVEDD.	6 months after the AV node ablation
The long-term effects of accelerated pacing on echocardiographic changes among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on LVESD.	6 months after the AV node ablation
The long-term effects of accelerated pacing on echocardiographic changes among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on LAVI.	6 months after the AV node ablation
The long-term effects of accelerated pacing on echocardiographic changes among AF patients undergoing pace-and-ablate strategy.	The long-term (6 months) effects of accelerated pacing on LA-strain.	6 months after the AV node ablation
Palpitations experienced as a result of (accelerated) pacing.	Palpitations experienced as a result of (accelerated) pacing based on the AF effect on quality of life (AFEQT) questionnaire. Patients can score between 0 and 100, with a lower score meaning a worse outcome.	6 months after the AV node ablation

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: NL86643.068.24

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