Border zone fibrosis affects in-silico arrhythmia vulnerability of structural heart disease patients

Background

Myocardial fibrosis is the most important factor accounting for ventricular tachycardia (VT) in structural heart disease, both ischemic and non-ischemic.

In-silico electrophysiological modeling is emerging as an innovative tool not only for procedural planning and guidance, but also to deepen the understanding of the pathophysiological mechanism of arrhythmias. Existing in silico studies often overlook border zone fibrosis when assessing structural arrhythmia vulnerability.

Purpose

To assess the effect of border zone fibrosis on arrhythmia vulnerability in 3D patient-specific computational models of structural heart disease patients.

Methods

Seven consecutive patients prospectively enrolled in the VOYAGE clinical trial for CMR aided/guided VT ablation at our referral center were retrospectively analyzed. Multidetector computed tomography (MDCT), and LGE-CMR were acquired before the procedure. LGE-CMR was segmented with ADAS3D for scar characterization using custom pixel signal intensity (PSI) thresholds under expert supervision. For each patient, we generated five computational models with different average percentages of fibrotic tissue (i.e., 0,10,30,50,70) in the border zone (Figure 1). The density of border zone fibrosis was modulated according to the PSI, increasing close to the core scar. The fibrosis tissue percentage ranges used were 0-0% (i.e., without fibrosis), 0-20%, 20-40%, 40-60%, and 60-80%. Arrhythmia vulnerability was assessed for each model using a standardized protocol (S1 600 ms x 6, S2 350 ms, S3 300 ms, S4 280 ms) pacing from all 17 segments of the left ventricle. All the 595 3D simulations were set up and carried out with CardioMat, a monodomain cardiac electrophysiology simulator developed by our group. A simulation was considered an arrhythmia if the reentry induced by the pacing protocol was maintained for 4 seconds.

Results

A total of 72 sustained ventricular arrhythmias were induced, 49 of which were obtained with average fibrosis density equal to 50% (Figure 2). The number of events decreased very fast when border zone fibrosis density was reduced. Without considering fibrosis in the border zone, only one arrhythmic event was induced, whereas 4 were obtained in a single patient with average fibrosis density equal to 10%. Similarly, by increasing the fibrosis tissue percentages in the range 60-80% the number of events reduced to 7. The number of VT induced is significantly higher for border zone fibrosis percentage in the range 40-60% (p<0.001).

Conclusion

In-silico arrhythmia vulnerability in structural heart disease patients is significantly affected by border zone fibrosis. Our results demonstrate that arrhythmia vulnerability is maximum when the border zone includes important structural remodeling with an average fibrosis density of 50%. Our study also highlights the major role played by border zone fibrosis in the arrhythmogenesis of structural heart disease.Figure 1Figure 2