Regional differences in extracellular volume increase arrhythmia vulnerability in aortic stenosis patients with and without diffuse fibrosis: a computational study

Abstract Background Extracellular volume (ECV) determined by magnetic resonance imaging (MRI) is considered a marker of myocardial fibrosis and a predictor of mortality. In addition to diffuse fibrosis, aortic stenosis (AS) patients present increased ECV. However, the impact of regional ECV differences on arrhythmia vulnerability in AS patients has not been assessed. Purpose To investigate regional ECV differences in AS patients and to determine their impact on ventricular arrhythmia vulnerability. Methods MRI was performed in 51 AS patients (32 males, 19 females) before and 3 months after aortic valve replacement (AVR). Regional differences in ECV were measured between mid-ventricular and basal planes. To investigate their impact on arrhythmia vulnerability, a computational biventricular model was developed from MRI data of the patient who presented the highest ECV difference between the planes in absence of a scar determined by late gadolinium enhancement (male 75y, post-AVR, ECV mid 25.5%, ECV base 31.3%, Figure A). The model was divided in two regions and extracellular conductivities (GE) were adjusted in each region as described previously (1), with additional GE reduction in the high ECV region representing increased interstitial fibrosis. This approach resulted in GE being 26.4% lower for ECV of 31.3% when compared to ECV of 25.5%. A model with uniform ECV of 25.5% was used as a control. Myocardial tissue was modelled with a cell radius of 16 micrometers, as reported in AS patients (2). The right ventricular apex was paced with S1=750 ms for 10 beats, followed by rapid pacing with different cycle lengths spanning the 20 ms window before the loss of stimulus capture to test arrhythmia inducibility. The simulations were repeated with an additional GE reduction by 30% and 60% in both regions to mimic conduction delays from diffuse fibrosis. Results Cardiac MRI showed significantly higher ECV in the basal plane of AS patients when compared to the mid-ventricular plane, both before and after AVR (Figure B), with the largest ECV found after AVR (mid-ventricular: p<0.0001; basal: p=0.0011). No sex-specific differences were found. Simulations in the model with patient-derived ECV showed slightly longer QRS and lower CV than the model with uniform ECV (Table). By contrast, myocardial fibrosis had a larger impact on CV slowing. Arrhythmia was inducible when either diffuse fibrosis was present or ECV at the ventricular base was increased (Table). Conclusion Regional differences in ECV were found in the ventricles of AS patients. Computer simulations suggest that these differences have a minimal effect on ventricular conduction when compared to diffuse fibrosis. However, they might increase arrhythmia vulnerability even in the absence of diffuse fibrosis. Additional studies are necessary to investigate the effects of each on arrhythmia maintenance and cardiac mechanics.