Accelerated Pacing for Improved Quality of Life in Symptomatic Atrial Fibrillation Patients undergoing Pace-and-Abate Strategy with Left Bundle Branch Area Pacing: a Randomized Controlled Pilot Trial: PACE-AF

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
sys-tem 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 sys-tem, thereby maintaining ventricular
synchrony. This strategy may be particularly important in pa-tients with heart
failure with preserved ejection fraction (HFpEF), a diagnosis that frequency
coex-ists 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 under-going a pace and ablate strategy, when compared to pacing
at 60 bpm, which is standard of care.

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 undergo-ing 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.

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

- 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.

The additional burden for participating in the study comprises of completing
questionnaires at three occasions. There are no additional risks with regards
to the pacemaker implantation and AV-NA procedure, as these are standard of
care and not part of the study. Pacing with moderately elevated lower rates
has not been associated with an increased risk for heart failure in HFpEF
patients.

The (optional, in patients who give additional informed consent) right heart
catheterisation is part of the study and will be performed during the same
session as AVNA, for which an additional femoral vein puncture is required. The
most reported serious complication is pulmonary artery damage, which occurs in
< 0.5%. In addition, there is a low risk of pacemaker lead dislodgement during
right heart catheterisation. Local vascular complications of the venous
puncture like bleed-ing, infection or damage to the vessel wall may occur but
are rare.

Additional invasive arterial blood pressure measurements are performed by
placing a sheath in the femoral artery which is not routine care during AVNA.
Local vascular complications of the arterial puncture like bleeding, infection
or damage to the vessel wall may occur but are rare.