Abstract
Introduction The role of the right atrium (RA) in atrial fibrillation (AF) has long been overlooked. Computer models of the atria can aid in assessing how the RA influences arrhythmia vulnerability and in studying the role of RA drivers in the induction of AF, both aspects challenging to assess in living patients. It remains unclear if incorporating the RA influences the reentry inducibility of the model. As personalized ablation strategies rely on non-inducibility criteria, the adequacy of left atrium (LA)-only models for developing such ablation tools is uncertain.
Aim To evaluate the effect of incorporating the RA in 3D patient-specific computer models on arrhythmia vulnerability.
Methods Imaging data from 8 subjects were obtained to generate patient-specific computer models. We created 2 models for each subject: a monoatrial with only the LA and a biatrial with both the RA and LA. We considered 3 different states of substrate remodeling: healthy (H), mild (M), and severe (S). The Courte-manche et al. cellular model was modified from control conditions to a setup representing AF-induced remodeling with 0 %, 50 %, and 100 % changes for H, M, and S, respectively. Conduction velocity was set to 1.2, 1.0, and 0.8 m/s for each remodeling state. Fibrosis extent corresponded to Utah 2 (5-20 %) and Utah 4 (>35 %) stages for M and S, while the H state was modeled without fibrosis. Arrhythmia vulnerability was assessed by virtual S1S2 pacing from different points separated by 2cm using openCARP. A point was classified as inducing arrhythmia if reentry was maintained for at least 1 s. The vulnerability ratio was defined as the number of inducing points divided by the number of stimulation points. The mean tachycardia cycle length (TCL) was assessed at the stimulation site. We compared LA vulnerability ratios in monoatrial and biatrial models.
Results Incorporating the RA increased the mean LA vulnerability ratio by 115.8 % (0.19 ± 0.13 to 0.41 ± 0.22, p = 0.033) in state M and 29.0 % in state S (0.31 ± 0.14 to 0.40 ± 0.15, p = 0.219). No arrhythmia was induced in the H models. RA inclusion increased the TCL of LA reentries by 5.5 % (186.9 ± 13.3 ms to 197.2 ± 18.3 ms, p = 0.006) in scenario M and decreased it by 7.2 % (224.3 ± 27.6 ms to 208.2 ± 34.8 ms, p = 0.010) in scenario S. RA inclusion increased LA inducibility revealing 5.5 ± 3.0 new points per patient in the LA for the biatrial model, which did not induce reentry in the monoatrial model.
Conclusions LA reentry vulnerability in a biatrial model is higher than in a monoatrial model. Incorporating the RA in patient-specific computational models unmasked potential inducing points in the LA. The RA had a substrate-dependent effect on reentry dynamics, altering the TCL of LA-induced reentries. Our results provide evidence for an important role of the RA in the maintenance and induction of arrhythmia in patient-specific computational models, thus suggesting the use of biatrial models.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860974. This work was supported by the Leibniz ScienceCampus "Digital Transformation of Research" with funds from the programme "Strategic Networking in the Leibniz Association". The authors acknowledge support by the state of Baden-Württemberg through bwHPC.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Subjects provided written informed consent and the study protocol was reviewed and approved by the ethical committee of Guy's Hospital, London, UK, and University Hospital Heidelberg, Heidelberg, Germany
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Data Availability
A carputils bundle containing the openCARP experiment is publicly available https://dx.doi.org/10.35097/1830