Effect of remote ischemic preconditioning on electrophysiological parameters in nonvalvular paroxysmal atrial fibrillation: The RIPPAF Randomized Clinical Trial

Background: Atrial fibrillation (AF) remains the most relevant arrhythmia with a prevalence of 2%. The treatment options are either highly invasive and cost-intensive or limited by potential side effects or insufficient efficacy. However, no direct means of prevention that could reduce the burden of AF have been tested.

Objective: The purpose of this study was to determine whether remote ischemic preconditioning (RIPC) has an impact on inducibility and sustainability of AF.

Methods: A total of 146 patients with paroxysmal AF undergoing electrophysiology study were randomized to receive either RIPC, performed by short episodes of forearm ischemia, or sham intervention (clinicaltrials.gov identifier: NCT02779660). Effective refractory periods, conduction times, velocities, and conduction delays measured were analyzed by pacing from the coronary sinus (CS). End points of the study were the inducibility and sustainability of AF after prespecified rapid pacing sequences.

Results: RIPC significantly reduces the inducibility (odds ratio 0.35; 95% confidence interval 0.17-0.71; P = .003) and sustainability (odds ratio 0.36; 95% confidence interval 0.16-0.81; P = .01) of AF. Furthermore, it decreased dispersion of atrial refractory periods (16.0 ± 14.0 ms vs 22.7 ± 19.0 ms; P = .021) as well as atrial conduction delays (49.2 ± 19.6 ms vs 56.2 ± 22.5 ms; P = .049 for proximal CS and 42.4 ± 16.6 ms vs 49.8 ± 22.2 ms; P = .029 for distal CS). In the whole cohort, longer atrial conduction delay (57.6 ± 22.2 ms vs 50.0 ± 20.5 ms; P = .044) and slower conduction velocity (1.74 ± 0.3 mm/ms vs 1.93 ± 0.5 mm/ms; P = .006) were associated with inducibility of AF whereas a wider dispersion of effective refractory periods (25.9 ± 18.3 ms vs 15.7 ± 11.6 ms; P = .028) maintained AF episodes.

Conclusion: RIPC reduces the inducibility and sustainability of AF, which is possibly mediated by changes in electrophysiological properties of the atria. It may be used as a simple noninvasive procedure to reduce AF burden.