Key result
Inward rectifier blockade plus PVI prevents AF induction despite severe fibrosis in 3D atrial models.
Why the study?
Inhibitors of IKACh suppress AF experimentally but have not been evaluated clinically, prompting in silico testing of whether inward rectifier current inhibition alone or combined with PVI reduces AF inducibility.
Does the combination of inward rectifier current blockade and pulmonary vein isolation reduce atrial fibrillation inducibility in a 3D computer model of human atria?
Does the combination of inward rectifier current blockade and pulmonary vein isolation reduce atrial fibrillation inducibility in a 3D computer model of human atria?
In a 3D computer model of human atria, combining inward rectifier current blockade with pulmonary vein isolation synergistically prevented atrial fibrillation induction across varying degrees of fibrosis.
Answers are grounded in this paper and cite their sources.
May warrant preclinical testing of inward rectifier blockade as PVI adjunct in fibrotic atria; leaves open translation to clinical AF management.
AIMS: Recent clinical studies showed that antiarrhythmic drug (AAD) treatment and pulmonary vein isolation (PVI) synergistically reduce atrial fibrillation (AF) recurrences after initially successful ablation. Among newly developed atrial-selective AADs, inhibitors of the G-protein-gated acetylcholine-activated inward rectifier current (IKACh) were shown to effectively suppress AF in an experimental model but have not yet been evaluated clinically. We tested in silico whether inhibition of inward rectifier current or its combination with PVI reduces AF inducibility. METHODS AND RESULTS: We simulated the effect of inward rectifier current blockade (IK blockade), PVI, and their combination on AF inducibility in a detailed three-dimensional model of the human atria with different degrees of fibrosis. IK blockade was simulated with a 30% reduction of its conductivity. Atrial fibrillation was initiated using incremental pacing applied at 20 different locations, in both atria. IK blockade effectively prevented AF induction in simulations without fibrosis as did PVI in simulations without fibrosis and with moderate fibrosis. Both interventions lost their efficacy in severe fibrosis. The combination of IK blockade and PVI prevented AF in simulations without fibrosis, with moderate fibrosis, and even with severe fibrosis. The combined therapy strongly decreased the number of fibrillation waves, due to a synergistic reduction of wavefront generation rate while the wavefront lifespan remained unchanged. CONCLUSION: Newly developed blockers of atrial-specific inward rectifier currents, such as IKAch, might prevent AF occurrences and when combined with PVI effectively supress AF recurrences in human.
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Gharaviri et al. (2020) studied Atrial fibrillation. Inward rectifier current blockade (IK blockade) combined with pulmonary vein isolation (PVI) vs. IK blockade alone or PVI alone was evaluated on Atrial fibrillation inducibility. In a 3D computer model of human atria, combining inward rectifier current blockade with pulmonary vein isolation prevented atrial fibrillation induction even in the presence of severe fibrosis.
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