Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford OX1 3QD, UK.
Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Europace. 2024 Jun 3;26(6). doi: 10.1093/europace/euae150.
Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials.
A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient's ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant.
In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.
尽管进行了肺静脉隔离（PVI），但仍有 50%的持续性心房颤动（AF）患者复发，目前尚无针对继发性治疗的共识。我们的 i-STRATIFICATION 研究旨在通过计算机模拟试验，为 PVI 后 AF 复发患者分层提供最佳药物和消融治疗的证据。
开发了一个包含 800 名虚拟患者的队列，这些患者的心房解剖结构、电生理和组织结构（低电压区，LVAs）存在变异性，并根据离子电流到心电图的临床数据进行了验证。经 PVI 后出现 AF 的虚拟患者接受了 12 种继发性治疗。PVI 后 522 名虚拟患者发生持续性 AF。单独进行左房消融的第二次消融手术有效率为 55%，仅对小右房（<60ml）有效。当考虑额外的腔静脉峡部消融时，Marshall-PLAN 就足够了（有效率为 66%），适用于小左房（<90ml）。对于较大的左心房，需要更积极的消融方法，如前二尖瓣线（有效率为 75%）或后侧壁隔离加二尖瓣峡部消融（有效率为 77%）。左、右心房存在 LVA 的虚拟患者，LVA 消融获益极大（有效率为 100%）。相反，在不存在 LVA 的情况下，协同消融和药物治疗可以终止 AF。在不存在消融的情况下，患者的离子电流基质调节了对抗心律失常药物的反应，内向电流对胺碘酮或 vernakalant 的最佳分层至关重要。
计算机模拟试验根据虚拟患者的特征确定了 AF 治疗的最佳策略，证明了人体建模和模拟作为临床辅助工具的强大功能。
