Discussion
The major findings of this study are that low dose colchicine was
associated with a significant reduction in AF recurrence after AF
ablation. There was a 22% reduction in AF recurrence in the entire
cohort and a 29% reduction in the PSM subgroup. Our results suggest
that low dose colchicine may be useful to reduce long-term AF recurrence
after AF ablation.
Catheter ablation has been validated as the most effective therapy for
atrial fibrillation. The 12-month and 62-month success rate for
pulmonary vein isolation for paroxysmal AF has been demonstrated to be
as high as 78% and 59%, respectively 5. Adjunctive
approaches to achieve more durable AF ablation efficacy continue to be
explored. Deftereos et al reported that 0.5mg colchicine twice
daily for 3 months was associated with a significant reduction in AF
recurrence at 12 months after de novo ablation in paroxysmal AF
patients (31.1% vs. 49.5%).9 However, there were
frequent reported side effects with a treatment discontinuation rate of
10.8%. Agarwal et al reported that 0.6mg colchicine twice daily
was associated with reduction of AF recurrence at 12
months19. In the Post Ablation Pericarditis Reduction
Study (PAPERS ) trial 20, patients were
randomized on the day of the procedure to receive 0.6 mg of colchicine
twice daily for 7 days. Significant side effects were reported in the
treatment group (47%) with no difference in pericarditis rates. All of
these studies used higher doses of colchicine than we employed in the
present study. To our knowledge, our study is the first to report the
effect of short term (1 month), low dose (0.6 mg daily) colchicine use
on long-term AF recurrence after AF ablation. We hypothesize that the
efficacy of the low dose, short-term colchicine regimen that we used is
attributable to less treatment discontinuation, although this could not
be tested due to inconsistent reporting in the medical record. Short
term colchicine administration may improve compliance without
compromising efficacy, as AF incidence was reduced to a similar extent
after cardiac surgery with 1 month and 3 month treatment
durations.22 It is notable that colchicine was
associated with a long-term reduction in AF recurrence despite a higher
incidence of persistent AF and more extensive substrate ablation in the
colchicine group, which would be expected to increase AF recurrence.
Colchicine has historically been used to treat gout and other
inflammatory conditions including pericarditis 1.
Colchicine inhibits the assembly and activation of the NLRP3
inflammasome as well as the release of neutrophil enzymes that activate
inflammatory interleukins 1ß and 18 5, 18. The NLRP3
inflammasome has cardiac specific effects, and plays a role in the
secretion of cytokines while also promoting ectopic firing and adverse
atrial remodeling 5. In the immediate-term, reducing
neutrophil activation by microtubule inhibition may attenuate
inflammatory responses that could precipitate
arrhythmogenesis5. The NLRP3 inflammasome has been
found to promote upregulation of RYR2 receptors and subsequent
Ca2+ release from the sarcoplasmic reticulum21, which promotes ectopic firing through delayed
afterdepolarizations. Additionally, through Caspase1-mediated
pyroptosis, an inflammatory cascade ultimately leads to recruitment of
inflammatory mediators that promote formation of fibrosis and the atrial
substrate that ultimately facilitates AF5.
Furthermore, colchicine reduces serum inflammatory biomarkers after
ablation, including C-reactive protein (CRP) and interleukin-6 (IL-6)9, 10.
It is unclear how short-term colchicine use prevents long-term AF
recurrence. Colchicine reduces early AF recurrence and pericarditis,
which could decrease the risk of long-term AF
recurrence.13 However, amiodarone reduced early, but
not long-term AF recurrence.23 Colchicine has been
associated with reduced myocardial fibrosis in animal studies, which
could influence long-term AF recurrence.24