Endocardial repolarization dispersion in BrS: A novel automatic algorithm for mapping activation recovery interval.

INTRODUCTION: Repolarization dispersion in the right ventricular outflow tract (RVOT) contributes to the type-1 electrocardiographic (ECG) phenotype of Brugada syndrome (BrS), while data on the significance and feasibility of mapping repolarization dispersion in BrS patients are scarce. Moreover, the role of endocardial repolarization dispersion in BrS is poorly investigated. We aimed to assess endocardial repolarization patterns through an automated calculation of activation recovery interval (ARI) estimated on unipolar electrograms (UEGs) in spontaneous type-1 BrS patients and controls; we also investigated the relation between ARI and right ventricle activation time (RVAT), and T-wave peak-to-end interval (Tpe) in BrS patients. METHODS: Patients underwent endocardial high-density electroanatomical mapping (HDEAM); BrS showing an overt type-1 ECG were defined as OType1, while those without (latent type-1 ECG and LType1) received ajmaline infusion. BrS patients only underwent programmed ventricular stimulation (PVS). Data were elaborated to obtain ARI corrected with the Bazett formula (ARIc), while RVAT was derived from activation maps. RESULTS: 39 BrS subjects (24 OType1 and 15 LTtype1) and 4 controls were enrolled. OType1 and post-ajmaline LType1 showed longer mean ARIc than controls (306 ± 27.3 ms and 333.3 ± 16.3 ms vs. 281.7 ± 10.3 ms, p = .05 and p < .001, respectively). Ajmaline induced a significant prolongation of ARIc compared to pre-ajmaline LTtype1 (333.3 ± 16.3 vs. 303.4 ± 20.7 ms, p < .001) and OType1 (306 ± 27.3 ms, p < .001). In patients with type-1 ECG (OTtype1 and post-ajmaline LType1) ARIc correlated with RVAT (r = .34, p = .04) and Tpec (r = .60, p < .001), especially in OType1 subjects (r = .55, p = .008 and r = .65 p < .001, respectively). CONCLUSION: ARIc mapping demonstrates increased endocardial repolarization dispersion in RVOT in BrS. Endocardial ARIc positively correlates with RVAT and Tpec, especially in OType1.

A smoothed boundary bidomain model for cardiac simulations in anatomically detailed geometries.

This manuscript presents a novel finite difference method to solve cardiac bidomain equations in anatomical models of the heart. The proposed method employs a smoothed boundary approach that represents the boundaries between the heart and the surrounding medium as a spatially diffuse interface of finite thickness. The bidomain boundary conditions are implicitly implemented in the smoothed boundary bidomain equations presented in the manuscript without the need of a structured mesh that explicitly tracks the heart-torso boundaries. We reported some significant examples assessing the method's accuracy using nontrivial test geometries and demonstrating the applicability of the method to complex anatomically detailed human cardiac geometries. In particular, we showed that our approach could be employed to simulate cardiac defibrillation in a human left ventricle comprising fiber architecture. The main advantage of the proposed method is the possibility of implementing bidomain boundary conditions directly on voxel structures, which makes it attractive for three dimensional, patient specific simulations based on medical images. Moreover, given the ease of implementation, we believe that the proposed method could provide an interesting and feasible alternative to finite element methods, and could find application in future cardiac research guiding electrotherapy with computational models.

A transmurally heterogeneous model of the ventricular tissue and its application for simulation of Brugada Syndrome.

We present a transmurally heterogeneous phe-nomenological model of ventricular tissue that is designed to reproduce the most important features of action potential prop-agation of endocardial, midmyocardial, and epicardial tissue. Our model consists of only 3 variables and 20 parameters. Therefore, it is highly computational efficient and easy to fit to experimental data. We exploited our myocyte model to simulate action potential propagation in a 3D slab of cardiac tissue both in healthy conditions and in presence of Brugada syndrome. The results show that our model can accurately reproduce the transmural heterogeneity of the ventricular wall and the main characteristics of electrocardiographic pattern both in healthy and pathological conditions.

Low cardiac frequency associated with higher number of extrasistoles in a computational model of Brugada Syndrome.

Brugada Syndrome is a form of idiopathic ventricular fibrillation, to date there is no definitive theory about how ventricular fibrillation is initiated or its substrate. Starting from the clinical observation that cardiac episodes are more frequent at rest, we developed a model in order to study the effect of cardiac frequency on reentrant activity. Our results suggest that the combination of arrhythmic substrate and cardiac frequency has a role in the insurgence of cardiac arrhythmia.

Diffuse fibrosis and repolarization disorders explain ventricular arrhythmias in Brugada syndrome: a computational study.

In this work, we reported a computational study to quantitatively determine the individual contributions of three candidate arrhythmic factors associated with Brugada Syndrome. In particular, we focused our analysis on the role of structural abnormalities, dispersion of repolarization, and size of the diseased region. We developed a human phenomenological model capable of replicating the action potential characteristics both in Brugada Syndrome and in healthy conditions. Inspired by physiological observations, we employed the phenomenological model in a 2D geometry resembling the pathological RVOT coupled with healthy epicardial tissue. We assessed the insurgence of sustained reentry as a function of electrophysiological and structural abnormalities. Our computational study indicates that both structural and repolarization abnormalities are essential to induce sustained reentry. Furthermore, our results suggest that neither dispersion of repolarization nor structural abnormalities are sufficient on their own to induce sustained reentry. It should be noted how our study seems to explain an arrhythmic mechanism that unifies the classic repolarization and depolarization hypotheses of the pathophysiology of the Brugada Syndrome. Finally, we believe that this work may offer a new perspective on the computational and clinical investigation of Brugada Syndrome and its arrhythmic behaviour.