Key result
Pulsed field ablation drives extensive peripheral cardiomyocyte apoptosis, peaking at ~37% by day 3.
Why the study?
Following transient AF recurrence observed after pulsed field ablation in clinical trials, this study tested the hypothesis that myocardial cell apoptosis contributes to AF recurrence after PFA.
Does pulsed field ablation (PFA) induce delayed cardiomyocyte apoptosis in a healthy canine model?
Does pulsed field ablation (PFA) induce delayed cardiomyocyte apoptosis in a healthy canine model?
PFA causes immediate cardiomyocyte death centrally but delayed apoptosis peripherally peaking at 3 days, providing a mechanistic explanation for transient acute AF recurrences seen clinically post-PFA.
Answers are grounded in this paper and cite their sources.
May explain early post-PFA AF recurrences via delayed apoptosis; hypothesis-generating in canines, requires human validation.
Background: The development of pulsed field ablation (PFA) as a new technique for pulmonary vein isolation (PVI) has been advancing rapidly in recent years. My team's previous work has shown the safety and long-term efficacy of bipolar asymmetric pulses in animal experiments. However, in ongoing clinical trials, we have observed that atrial fibrillation (AF) recurs in some patients after surgery, but the rhythm returns to normal without surgical intervention after seven days, and there is no recurrence in the follow-up.Based on this observation, we have proposed the hypothesis that myocardial cell apoptosis may play a role in AF recurrence after PFA. Our team has designed animal experiments to verify this hypothesis and further investigate the process of PFA-induced cardiomyocyte apoptosis. Methods: Pulse field ablation was performed on 15 dogs and the animals were dissected at various time points after the operation (immediately, 3 days, 7 days, 30 days, and 150 days). To obtain ablation voltage maps, electroanatomic mapping was performed before and after ablation and before dissection. The ablation area was also subjected to HE and TUNEL staining to analyze apoptosis and pathological results. Results: The edge area of the ablation in the pulmonary vein (PV) demonstrated continuous dynamic changes from 0 to 2 h after the operation and a slight expansion of the ablation range was observed in the long-term follow-up. Myocardial intima hyperplasia was observed from 0 to 7 days. Local apoptosis was detected from 0 to 2 h and massive, concentrated apoptosis was observed at 3 days. No recurrence of apoptosis was seen at 7 days, 30 days, and 150 days. Conclusions: The results of this study showed that after pulse field ablation (PFA), the central ablation area of the canine heart experienced immediate cardiomyocyte death. Meanwhile, cardiomyocytes in the edge ablation area underwent apoptosis, which began from 0 to 2 h post-operation and ended between 3 and 7 days. This process occurred simultaneously with intimal thickening.In the long-term follow-up group, there was no recovery of isolation and no recurrence of cardiomyocyte apoptosis, and no change was observed in the endomyocardial intima.
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Fan et al. (2023) studied Healthy canines (animal model for pulsed field ablation) (n=15). Pulsed field ablation (PFA) was evaluated on Cardiomyocyte apoptosis rate at Day 3 (p=< 0.01). Pulsed field ablation induced massive cardiomyocyte apoptosis in the peripheral ablation zone, peaking at 36.5% on day 3 compared to 1.6% immediately post-operation.
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