Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico inter–subject variability study

Liberos, A; Bueno Orovio, A; Rodrigo, M; Ravens, U; Hernandez-Romero, I; Fernandez-Aviles, F; Guillem, M; Rodriguez, B; Climent, A

Journal article

Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico inter–subject variability study

Abstract:: Background

Atrial remodeling due to long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction of the efficacy of antiarrhythmic treatments.

Objective

To identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies.

Methods

A population of 173 mathematical models of remodeled human atrial tissue with realistic inter–subject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relation of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3D simulations.

Results

Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL (p<0.01), with no significant differences in the remaining currents. ICaL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors due to an increase in rotor meandering (1.71±2.01cm^2) and presented an increased efficacy in models with a depressed INa (p<0.01).

Conclusion

Mathematical simulations based on a population of models representing inter-subject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacological strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Liberos, A., Bueno Orovio, A., Rodrigo, M., Ravens, U., Hernandez-Romero, I., Fernandez-Aviles, F., Guillem, M., Rodriguez, B., & Climent, A. (2016). Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico inter–subject variability study. Heart Rhythm, 13(12), 2358–2365.

MLA Style

Liberos, A, et al. “Balance between Sodium and Calcium Currents Underlying Chronic Atrial Fibrillation Termination: An in Silico Inter–Subject Variability Study.” Heart Rhythm, vol. 13, no. 12, 2016, pp. 2358–65.

Chicago Style

Liberos, A, A Bueno Orovio, M Rodrigo, et al. 2016. “Balance between Sodium and Calcium Currents Underlying Chronic Atrial Fibrillation Termination: An in Silico Inter–Subject Variability Study.” Heart Rhythm 13 (12): 2358–65.
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