Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks

Abstract

Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic. In this study, we sought to investigate how electric fields from implanted devices interact with the highly trabeculated human endocardial surface to better understand shock success in order to help optimise future clinical protocols. A bi-ventricular human computational model was constructed from high resolution (350 μm) ex-vivo MR data, including anatomically accurate endocardial structures. Monophasic shocks were applied between a basal right ventricular catheter and an exterior ground. Shocks of varying strengths were applied with both anodal [positive right ventricle (RV) electrode] and cathodal (negative RV electrode) polarities at different states of tissue refractoriness and during induced arrhythmias. Anodal shocks induced isolated positive VEs at the distal side of “detached” trabeculations, which rapidly spread into hyperpolarised tissue on the surrounding endocardial surfaces following the shock. Anodal shocks thus depolarised more tissue 10 ms after the shock than cathodal shocks where the propagation of activation from VEs induced on the proximal side of “detached” trabeculations was prevented due to refractory endocardium. Anodal shocks increased arrhythmia complexity more than cathodal shocks during failed anti-arrhythmia shocks. In conclusion, multiple detached trabeculations in the human ventricle interact with anodal stimuli to induce multiple secondary sources from VEs, facilitating more rapid shock-induced ventricular excitation compared to cathodal shocks. Such a mechanism may help explain inter-species differences in response to shocks and help to develop novel defibrillation strategies.

Conceptual Intra-Cardiac Electrode Configurations That Facilitate Directional Cardiac Stimulation for Optimal Electrotherapy

“…The governing equations used neglect all physical nonlinearities [53] occurring at the interface between the electrode surfaces and the colloidal electrolyte (blood), although it is thought that the influence of these effects will not change the structure of the electric fields generated. While we intentionally chose to use the simplified Oxford rabbit [43] to highlight the effects of the directional stimulation electrodes, this geometry does not include the papillary muscles [54] and the coronary vasculature [55], [24] which are known to create additional VE sources upon field stimulation. It is thought that break excitations [56], [54] near hyperpolarized boundaries may reduce the directional efficacy of the bipole arrangement, however this is thought to be of lesser significance for the bipole Halbach arrangement, due to the theoretically lower virtual-electrode magnitudes created in the non-augmented directions by the Halbach configuration.…”

“…While we intentionally chose to use the simplified Oxford rabbit [43] to highlight the effects of the directional stimulation electrodes, this geometry does not include the papillary muscles [54] and the coronary vasculature [55], [24] which are known to create additional VE sources upon field stimulation. It is thought that break excitations [56], [54] near hyperpolarized boundaries may reduce the directional efficacy of the bipole arrangement, however this is thought to be of lesser significance for the bipole Halbach arrangement, due to the theoretically lower virtual-electrode magnitudes created in the non-augmented directions by the Halbach configuration. This is in contrast to the bipole arrangement, where all points (apart from where the field is tangent to the heart surface) experience a similar current-density.…”

Ventricular anatomical complexity and sex differences impact predictions from electrophysiological computational models

“…To date, there have been a few computational models studying the influences of the position and amount of both trabeculae and False Tendons (FTs) FTs on the overall cardiac electrophysiology (Bishop et al [ 5 ], Bordas et al [ 6 ], Lange et al [ 7 ], Connolly et al [ 8 ] and Galappaththinge et al [ 9 ]).…”

“…The main limitations to their work, were the omissions of other anatomical details; e.g., the two LV PMs and RV anatomies were not included. More recently, [ 8 ] investigated the response of human heart trabeculations to low-energy monophasic shocks. They reported how induced shocks, generated local regions of depolarization on the distal side of trabeculations, became entirely detached from the endocardial surfaces, relative to the electrode position.…”

Ventricular anatomical complexity and gender differences impact predictions from computational models

“…To date, there have been a few computational models studying the influences of the position and amount of both trabeculae and FTs on the overall cardiac electrophysiology (Bishop et al [5], Bordas et al [6], Lange et al [7], Connolly et al [8] and Galappaththinge et al [9]). Nevertheless, none of these previous works explore their effect on ventricular tachycardia simulations and the reentry channel locations as related to gender-specific risk prediction.…”