Defibrillation effectiveness and safety of the shock waveform used in a contemporary wearable cardioverter defibrillator: Results from animal and human studies.

Introduction: The wearable cardioverter defibrillator (WCD) is used to protect patients at risk for sudden cardiac arrest. We examined defibrillation efficacy and safety of a biphasic truncated exponential waveform designed for use in a contemporary WCD in three animal studies and a human study.

Methods: Animal (swine) studies: #1: Efficacy comparison of a 170J BTE waveform (SHOCK A) to a 150J BTE waveform (SHOCK B) that approximates another commercially available waveform.

Molecular remodeling of Cx43, but not structural remodeling, promotes arrhythmias in an arrhythmogenic canine model of nonischemic heart failure.

Background: Both gap junctional remodeling and interstitial fibrosis have been linked to impaired electrical conduction velocity (CV) and fatal ventricular arrhythmias in nonischemic heart failure (HF). However, the arrhythmogenic role of the ventricular gap junctional Cx43 in nonischemic HF remains in debate. Here, we assessed this in a newly developed arrhythmogenic canine model of nonischemic HF.

Left atrial appendage electrical isolation and concomitant device occlusion: A safety and feasibility study with histologic characterization.

Background: Left atrial appendage (LAA) electrical isolation is reported to improve atrial fibrillation ablation outcomes. However, loss of mechanical function may increase thromboembolic risk.

Objective: The aim of this study was to evaluate the feasibility and safety of LAA occlusion after electrical isolation in a canine model.

Chymase inhibition prevents fibronectin and myofibrillar loss and improves cardiomyocyte function and LV torsion angle in dogs with isolated mitral regurgitation.

Background: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.

Mast cell stabilization decreases cardiomyocyte and LV function in dogs with isolated mitral regurgitation.

Background: Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog.

Methods And Results: MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months.

Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model.

Background: The roles of Purkinje fibers (PFs) and focal wave fronts, if any, in the maintenance of ventricular fibrillation (VF) are unknown. If PFs are involved in VF maintenance, it should be possible to map wave fronts propagating from PFs into the working ventricular myocardium during VF. If wave fronts ever arise focally during VF, it should be possible to map them appearing de novo.

Quantification of activation patterns during ventricular fibrillation in open-chest porcine left ventricle and septum.

Background: A single stationary mother rotor has been hypothesized to be responsible for maintenance of ventricular fibrillation (VF) in the guinea pig. Previous studies have pointed to the ventricular septum as a possible location for a mother rotor in the pig heart.

Objectives: The purpose of this study was to test the hypothesis that a mother rotor is located in the septum.

Regional differences in ventricular fibrillation in the open-chest porcine left ventricle.

It has been hypothesized that during ventricular fibrillation (VF), the fastest activating region, the dominant domain, contains a stable reentrant circuit called a mother rotor. This hypothesis postulates that the mother rotor spawns wavefronts that propagate to maintain VF elsewhere and implies that the ratio of wavefronts propagating off a region to those propagating onto it (propoff/propon) should be >1 for the dominant domain but <1 elsewhere. To test this prediction in the left ventricular (LV) epicardium of a large animal, most of the LV free wall was mapped with 1008 electrodes in 7 pigs.

Left ventricular resynchronization therapy in a canine model of left bundle branch block.

Positive responses to left (LV) and biventricular (BV) stimulation observed in heart failure patients with left bundle branch block (LBBB) suggest a possible mechanism of LV resynchronization. An anesthetized canine LBBB model was developed using radio frequency ablation. Before and after ablation, LV pressure derivative over time (dP/dt) and aortic pulse pressure (PP) were assessed during normal sinus rhythm with right ventricle (RV), LV, or BV stimulation combined with four atrioventricular delays in six dogs.