2-Hydroxybenzylamine (2-HOBA) to Prevent Early Recurrence of Atrial Fibrillation After Catheter-based Ablation
Status:
Recruiting
Trial end date:
2024-05-15
Target enrollment:
Participant gender:
Summary
The proposed studies will test this hypothesis by randomizing patients with AF to 2-HOBA or
placebo 7 days prior to AF ablation to allow 2-HOBA to reach steady-state levels. We
hypothesize that tissue injury from AF ablation causes a large release of ROS that react with
lipids to generate IsoLGs (Figure 2). In the absence of 2-HOBA, IsoLGs will react within
seconds to form IsoLG-macromolecule adducts in atrial tissue, promoting early recurrence of
AF. In the presence of 2-HOBA, IsoLGs will rapidly react to form IsoLG-macromolecule adducts
in atrial tissue, promoting early recurrence of AF. In the presence of 2-HOBA, IsoLG will
preferentially bind to and therefore be inactivated by 2-HOBA thereby sparing injury to the
atrial tissue caused by oxidative stress and its contribution to early recurrence of AF.
Early recurrence of AF will be measured by ECGs that are recorded once per day by a
smartwatch (Apple Watch, Apple Inc., Cupertino, CA) with additional ECGs recorded by the
participant if they experience symptoms of AF, or if the smartwatch alerts the participant of
a possible AF episode via its auto-detection AF monitoring algorithm. The Apple Watch's AF
algorithm is based on sampling of heart rate and variability and will give an audible alarm
if those parameters indicate a possible episode of AF. The smartwatch records a single-lead
ECG if the participant touches the watch with their contralateral hand. The day and time of
the episode is also stored by the smartwatch. At the end of the 28-day follow-up period,
study personnel will review the stored ECGs. Blood will be drawn prior to ablation and on
post-procedure Day 1 for measurement of IsoLG-adduct levels. DNA will be extracted to explore
a pharmacogenomic interaction with haplotypes at the chromosome 4q25 AF risk locus, which: 1)
is strongly associated with the development of AF and the early recurrence of AF after
ablation27; and 2) has been reported to be a regulator of an anti-oxidant gene program in
response to cardiac injury.