Why Ablation of Sites With Purkinje Activation Is Antiarrhythmic: The Interplay Between Fast Activation and Arrhythmogenesis

Ablation of sites showing Purkinje activity is antiarrhythmic in some patients with idiopathic ventricular fibrillation (iVF). The mechanism for the therapeutic success of ablation is not fully understood. We propose that deeper penetrance of the Purkinje network allows faster activation of the ventricles and is proarrhythmic in the presence of steep repolarization gradients. Reduction of Purkinje penetrance, or its indirect reducing effect on apparent propagation velocity may be a therapeutic target in patients with iVF.

3D magnetization transfer (MT) for the visualization of cardiac free-running Purkinje fibers: an ex vivo proof of concept

Objectives We investigate the possibility to exploit high-field MRI to acquire 3D images of Purkinje network which plays a crucial role in cardiac function. Since Purkinje fibers (PF) have a distinct cellular structure and are surrounded by connective tissue, we investigated conventional contrast mechanisms along with the magnetization transfer (MT) imaging technique to improve image contrast between ventricular structures of differing macromolecular content. Methods Three fixed porcine ventricular samples were used with free-running PFs on the endocardium. T1, T2*, T2, and M0 were evaluated on 2D slices for each sample at 9.4 T. MT parameters were optimized using hard pulses with different amplitudes, offset frequencies and durations. The cardiac structure was assessed through 2D and 3D T1w images with isotropic resolutions of 150 µm. Histology, immunofluorescence, and qPCR were performed to analyze collagen contents of cardiac tissue and PF. Results An MT preparation module of 350 ms duration inserted into the sequence with a B1 = 10 µT and frequency offset = 3000 Hz showed the best contrast, approximately 0.4 between PFs and myocardium. Magnetization transfer ratio (MTR) appeared higher in the cardiac tissue (MTR = 44.7 ± 3.5%) than in the PFs (MTR = 25.2 ± 6.3%). Discussion MT significantly improves contrast between PFs and ventricular myocardium and appears promising for imaging the 3D architecture of the Purkinje network.

A Two-Stage Purkinje Network for More Accurate ECG Representations

In this manuscript we propose a method to generate Purkinje networks that are anatomically and physiologically plausible, for use with in-silico modeling. Purkinje networks play a fundamental role in shaping cardiac electrical activation patterns and their corresponding clinical electrocardiograms (ECGs). Despite a known variability in ventricular activation sequences, certain sites of early activation within the left and right ventricles have been identified in the literature for normal electrical excitation patterns. Nevertheless, in-vivo imaging of Purkinje networks cannot at present yield detailed information on their structure, so there is a genuine need for in-silico models that can construct Purkinje networks that are both anatomically and physiologically plausible, in particular networks that can exhibit correctly situated early activation sites in the ventricles. Of special interest to this manuscript is the method of representation of Purkinje networks by line-like electrical elements that are generated by means of a fractal-tree algorithm (1–3) to overlay the irregular endocardial surfaces. A known drawback to a direct implementation of this approach in complex geometries relates to its incorrect modeling of clinically observed ECGs and electrical activation sequences for a human heart (4). Our aim was thus to correct this deficiency by generating Purkinje networks that leverage a pre-knowledge of the location of early activation sites. At every such site we first generate a Purkinje sub-network. These sub-networks are linked together and to the bundle of His, setting up our first stage of the Purkinje network. Subsequently, we spawn a second stage to the Purkinje network from one or more tips of any given sub-network, to cover the full endocardial surface with Purkinje elements. Our resulting activation sequences and ECGs compare favorably to those of a population of 39 healthy male individuals (the PTB diagnostic database), and our corresponding mechanical markers of cardiac function also match well with the literature.

A comparison between different Purkinje network generation methods

Heart diseases are the major cause of deaths worldwide and within this context, the most common disease is cardiac arrhythmia. There is some evidence that the generation and maintenance of those arrhythmias might be related to the properties of the Purkinje system. Mostly because of its complex structure, which is thought to be the source of reentry activity, one of the precursors of dangerous arrhythmias. The objective of this work is to investigate how the morphology and properties of the Purkinje fibers of the heart may affect the electrical activation of the tissue. In order to build the Purkinje networks of this project, three different algorithms were used and their responses in activating the ventricular walls were compared. The monodomain equation was used to mathematically model the electrical activation and a parallel solver was used to speed up the numerical solution of the problem. The results of this work show that together with the geometry of the Purkinje network, properties of the coupling between the terminals of the network and the ventricular tissue also affect the electrical activation by leading to conduction blocks.