Data_Sheet_1_A Reproducible Protocol to Assess Arrhythmia Vulnerability in silico: Pacing at the End of the Effective Refractory Period.PDF

In both clinical and computational studies, different pacing protocols are used to induce arrhythmia and non-inducibility is often considered as the endpoint of treatment. The need for a standardized methodology is urgent since the choice of the protocol used to induce arrhythmia could lead to contrasting results, e.g., in assessing atrial fibrillation (AF) vulnerabilty. Therefore, we propose a novel method—pacing at the end of the effective refractory period (PEERP)—and compare it to state-of-the-art protocols, such as phase singularity distribution (PSD) and rapid pacing (RP) in a computational study. All methods were tested by pacing from evenly distributed endocardial points at 1 cm inter-point distance in two bi-atrial geometries. Seven different atrial models were implemented: five cases without specific AF-induced remodeling but with decreasing global conduction velocity and two persistent AF cases with an increasing amount of fibrosis resembling different substrate remodeling stages. Compared with PSD and RP, PEERP induced a larger variety of arrhythmia complexity requiring, on average, only 2.7 extra-stimuli and 3 s of simulation time to initiate reentry. Moreover, PEERP and PSD were the protocols which unveiled a larger number of areas vulnerable to sustain stable long living reentries compared to RP. Finally, PEERP can foster standardization and reproducibility, since, in contrast to the other protocols, it is a parameter-free method. Furthermore, we discuss its clinical applicability. We conclude that the choice of the inducing protocol has an influence on both initiation and maintenance of AF and we propose and provide PEERP as a reproducible method to assess arrhythmia vulnerability.

在临床与计算研究中，学界常采用不同的起搏方案诱发心律失常，而无法诱发心律失常常被视为治疗的终点。由于诱发心律失常的起搏方案选择可能导致结果相悖——例如在评估心房颤动（Atrial Fibrillation, AF）易感性时，亟需一套标准化的研究方法。为此，我们提出一种全新的起搏方案——有效不应期末起搏（Pacing at the End of the Effective Refractory Period, PEERP），并在一项计算研究中将其与当前主流的起搏方案进行对比，例如相位奇点分布（Phase Singularity Distribution, PSD）与快速起搏（Rapid Pacing, RP）。所有测试方案均通过在两种双心房几何模型中，以1cm的点间距在心内膜均匀分布的位点进行起搏来验证。本研究共构建7种不同的心房模型：5种未出现特异性AF诱导重构，但整体传导速度逐渐降低；另外2种为持续性AF模型，其纤维化程度逐渐升高，模拟不同的心房基质重构阶段。相较于PSD与RP方案，PEERP可诱发更多样的心律失常复杂度，且平均仅需2.7个额外刺激脉冲与3秒的模拟时长即可触发折返活动。此外，与RP相比，PEERP与PSD两种方案可揭示出更多能够维持稳定持久折返活动的易感区域。最后，PEERP无需任何参数设置，相较于其余起搏方案，更有助于推动研究的标准化与可重复性。此外，我们还探讨了该方案的临床应用前景。本研究最终证实，诱发方案的选择对AF的启动与维持均存在影响，并提出并提供PEERP作为一种可重复的心律失常易感性评估方案。