Computer based method for identification of fibrotic scars from electrograms and local activation times on the epi- and endocardial surfaces of the ventricles.

Cardiac fibrosis stands as one of the most critical conditions leading to lethal cardiac arrhythmias. Identifying the precise location of cardiac fibrosis is crucial for planning clinical interventions in patients with various forms of ventricular and atrial arrhythmias. As fibrosis impedes and alters the path of electrical waves, detecting fibrosis in the heart can be achieved through analyzing electrical signals recorded from its surface. In current clinical practices, it has become feasible to record electrical activity from both the endocardial and epicardial surfaces of the heart. This paper presents a computational method for reconstructing 3D fibrosis using unipolar electrograms obtained from both surfaces of the ventricles. The proposed method calculates the percentage of fibrosis in various ventricular segments by analyzing the local activation times and peak-to-peak amplitudes of the electrograms. Initially, the method was tested using simulated data representing idealized fibrosis in a heart segment; subsequently, it was validated in the left ventricle with fibrosis obtained from a patient with nonischemic cardiomyopathy. The method successfully determined the location and extent of fibrosis in 204 segments of the left ventricle model with an average error of 0.0±4.3% (N = 204). Moreover, the method effectively detected fibrotic scars in the mid-myocardial region, a region known to present challenges in accurate detection using electrogram amplitude as the primary criterion.

Directed Graph Mapping exceeds Phase Mapping for the detection of simulated 2D meandering rotors in fibrotic tissue with added noise.

Cardiac arrhythmias such as atrial fibrillation (AF) are recognised to be associated with re-entry or rotors. A rotor is a wave of excitation in the cardiac tissue that wraps around its refractory tail, causing faster-than-normal periodic excitation. The detection of rotor centres is of crucial importance in guiding ablation strategies for the treatment of arrhythmia. The most popular technique for detecting rotor centres is Phase Mapping (PM), which detects phase singularities derived from the phase of a signal. This method has been proven to be prone to errors, especially in regimes of fibrotic tissue and temporal noise. Recently, a novel technique called Directed Graph Mapping (DGM) was developed to detect rotational activity such as rotors by creating a network of excitation. This research aims to compare the performance of advanced PM techniques versus DGM for the detection of rotors using 64 simulated 2D meandering rotors in the presence of various levels of fibrotic tissue and temporal noise. Four strategies were employed to compare the performances of PM and DGM. These included a visual analysis, a comparison of F2-scores and distance distributions, and calculating p-values using the mid-p McNemar test. Results indicate that in the case of low meandering, fibrosis and noise, PM and DGM yield excellent results and are comparable. However, in the case of high meandering, fibrosis and noise, PM is undeniably prone to errors, mainly in the form of an excess of false positives, resulting in low precision. In contrast, DGM is more robust against these factors as F2-scores remain high, yielding F2≥0.931 as opposed to the best PM F2≥0.635 across all 64 simulations.

High-frequency pacing of scroll waves in a three-dimensional slab model of cardiac tissue.

Vortices in excitable media underlie dangerous cardiac arrhythmias. One way to eliminate them is by stimulating the excitable medium with a period smaller than the period of the vortex. So far, this phenomenon has been studied mostly for two-dimensional vortices known as spiral waves. Here we present a first study of this phenomenon for three-dimensional vortices, or scroll waves, in a slab. We consider two main types of scroll waves dynamics: with positive filament tension and with negative filament tension and show that such elimination is possible for some values of the period in all cases. However, in the case of negative filament tension for relatively long stimulation periods, three-dimensional instabilities occur and make elimination impossible. We derive equations of motion for the drift of paced filaments and identify a bifurcation parameter that determines whether the filaments orient themselves perpendicular to the impeding wave train or not.

Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability.

Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to understand and define the conditions underlying Cx43 hemichannel activation in ventricular cardiomyocytes, their contribution to diastolic Ca2+ release from the sarcoplasmic reticulum, and their impact on electrical stability. We showed that Cx43 hemichannels were activated during diastolic Ca2+ release in single ventricular cardiomyocytes and cardiomyocyte cell pairs from mice and pigs. This activation involved Cx43 hemichannel Ca2+ entry and coupling to Ca2+ release microdomains at the intercalated disc, resulting in enhanced Ca2+ dynamics. Hemichannel opening furthermore contributed to delayed afterdepolarizations and triggered action potentials. In single cardiomyocytes, cardiomyocyte cell pairs, and arterially perfused tissue wedges from failing human hearts, increased hemichannel activity contributed to electrical instability compared with nonfailing rejected donor hearts. We conclude that microdomain coupling between Cx43 hemichannels and Ca2+ release is a potentially novel, targetable mechanism of cardiac arrhythmogenesis in heart failure.