Impact of effective refractory period personalization on prediction of atrial fibrillation vulnerability
Authors: Martinez Diaz P , Goetz C , Dasi A , Unger L A , Haas A , Doessel O , Luik A , Loewe A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska- Curie grant agreement

Introduction
Although the effective refractory period (ERP) is one of the main electrophysiological properties governing atrial tachycardia (AT) maintenance, ERP personalization is rarely performed when creating patient-specific computer models of the atria to inform clinical decision making. State-of-the-art models usually do not consider physiological ERP gradients but assume a homogeneous ERP distribution. This assumption might have an influence on the ability to induce reentries in the model.

Aim
To evaluate the impact of incorporating clinical ERP measurements when creating in silico personalized models to predict vulnerability to atrial fibrillation (AF).

Methods
Clinical ERP measurements were obtained from three patients from multiple locations in the atria. The protocol for ERP identification consisted of trains of 7 S1 stimuli with a basic cycle length of 500ms followed by an S2 stimulus with a coupling interval between 300 and 200ms in decrements of 10ms until loss of capture. The atrial geometries from the electroanatomical mapping system were used to generate personalized atrial models. To reproduce patient-specific ERP, the established Courtemanche cellular model was gradually reparameterized from control conditions to a setup representing AF-induced remodeling. Three different approaches were studied: 1) a control scenario with no ERP personalization 2) a discrete split where each region had a single ERP value and 3) a continuous ERP distribution by interpolation of measured ERP data (Fig. 1). Arrhythmia vulnerability was assessed by virtual S1S2 pacing from different locations separated by 3cm. The number and location of inducing points and type of arrhythmia were determined for the three approaches. The mean conduction velocity was set to 0.7 m/s and the electrical propagation in the atria was modeled by the monodomain equation and solved with openCARP.

Results
Incorporating patient-specific ERP as a continuous distribution did not induce any reentrant activity. A summary of induced ATs is shown in Table 1. For patient A, AF was induced from 3 different locations with the control setup, whereas 9 ATs were induced with the regional method, of which 4 were AF and 5 macro reentries. For patient B, AF was induced from 1 point with the control setup; whereas with the regional approach, AF was induced at 4 points. For patient C, only one macro reentry was induced with the regional method.

Conclusion
Incorporation of patient-specific ERP values has an impact on the assessment of AF vulnerability. Furthermore, the type of personalization affects the likelihood of AF inducibility. The incorporation of more detailed ERP distributions may lead to a more accurate prediction of AF trigger points and could in the future inform patient-specific therapy planning. Larger cohorts need to follow to demonstrate the role of incorporating clinical patient-specific ERP values into personalized models for predicting AF vulnerability.