Dual-energy lattice-tip ablation system for persistent atrial fibrillation: a randomized trial.

Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency.

Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial.

Background: Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications.

Methods: The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation.

Effect of contact force on pulsed field ablation lesions in porcine cardiac tissue.

Introduction: Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed field ablation (PFA) is a field-based ablation technology for which limited evidence on the impact of contact force on lesion size is available.

Methods: Porcine hearts (n = 6) were perfused using a modified Langendorff set-up.

Effects of Electrode-Tissue Proximity on Cardiac Lesion Formation Using Pulsed Field Ablation.

Background: Pulsed field ablation (PFA) is a novel energy modality for treatment of cardiac arrhythmias. The impact of electrode-tissue proximity on lesion formation by PFA has not been conclusively assessed. The objective of this investigation was to evaluate the effects of electrode-tissue proximity on cardiac lesion formation with a biphasic, bipolar PFA system.

Characterization of Phrenic Nerve Response to Pulsed Field Ablation.

Background: Phrenic nerve palsy is a well-known complication of cardiac ablation, resulting from the application of direct thermal energy. Emerging pulsed field ablation (PFA) may reduce the risk of phrenic nerve injury but has not been well characterized.

Methods: Accelerometers and continuous pacing were used during PFA deliveries in a porcine model.

First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial.

Background: Pulsed field ablation (PFA) is a novel form of ablation using electrical fields to ablate cardiac tissue. There are only limited data assessing the feasibility and safety of this type of ablation in humans.

Methods: PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; https://www.

Safety and chronic lesion characterization of pulsed field ablation in a Porcine model.

Background: Pulsed field ablation (PFA) has been identified as an alternative to thermal-based ablation systems for treatment of atrial fibrillation patients. The objective of this Good Laboratory Practice (GLP) study was to characterize the chronic effects and safety of overlapping lesions created by a PFA system at intracardiac locations in a porcine model.

Methods: A circular catheter with nine gold electrodes was used for overlapping low- or high-dose PFA deliveries in the superior vena cava (SVC), right atrial appendage (RAA), and right superior pulmonary vein (RSPV) in six pigs.

Reduction in Pulmonary Vein Stenosis and Collateral Damage With Pulsed Field Ablation Compared With Radiofrequency Ablation in a Canine Model.

Background: Pulmonary vein (PV) stenosis is a highly morbid condition that can result after catheter ablation for PV isolation. We hypothesized that pulsed field ablation (PFA) would reduce PV stenosis risk and collateral injury compared with irrigated radiofrequency ablation (IRF).

Methods: IRF and PFA deliveries were randomized in 8 dogs with 2 superior PVs ablated using one technology and 2 inferior PVs ablated using the other technology.

βIV-Spectrin regulates STAT3 targeting to tune cardiac response to pressure overload.

Heart failure (HF) remains a major source of morbidity and mortality in the US. The multifunctional Ca2+/calmodulin-dependent kinase II (CaMKII) has emerged as a critical regulator of cardiac hypertrophy and failure, although the mechanisms remain unclear. Previous studies have established that the cytoskeletal protein βIV-spectrin coordinates local CaMKII signaling.

Ca/calmodulin-dependent kinase II-dependent regulation of atrial myocyte late Na current, Ca cycling, and excitability: a mathematical modeling study.

Atrial fibrillation (AF) affects more than three million people per year in the United States and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca/calmodulin-dependent protein kinase II (CaMKII) in the regulation of persistent "late" Na current ( I) has been identified.

: A cardiac electrophysiology simulation platform.

Mathematical modeling has been used for over half a century to advance our understanding of cardiac electrophysiology and arrhythmia mechanisms. Notably, computational studies using mathematical models of the cardiac action potential (AP) have provided important insight into the fundamental nature of cell excitability, mechanisms underlying both acquired and inherited arrhythmia, and potential therapies. Ultimately, an approach that tightly integrates mathematical modeling and experimental techniques has great potential to accelerate discovery.

Two-Pore K+ Channel TREK-1 Regulates Sinoatrial Node Membrane Excitability.

Background: Two-pore K(+) channels have emerged as potential targets to selectively regulate cardiac cell membrane excitability; however, lack of specific inhibitors and relevant animal models has impeded the effort to understand the role of 2-pore K(+) channels in the heart and their potential as a therapeutic target. The objective of this study was to determine the role of mechanosensitive 2-pore K(+) channel family member TREK-1 in control of cardiac excitability.

Methods And Results: Cardiac-specific TREK-1-deficient mice (αMHC-Kcnk(f/f)) were generated and found to have a prevalent sinoatrial phenotype characterized by bradycardia with frequent episodes of sinus pause following stress.

Modeling CaMKII in cardiac physiology: from molecule to tissue.

Post-translational modification of membrane proteins (e.g., ion channels, receptors) by protein kinases is an essential mechanism for control of excitable cell function.

Cycle length restitution in sinoatrial node cells: a theory for understanding spontaneous action potential dynamics.

Normal heart rhythm (sinus rhythm) is governed by the sinoatrial node, a specialized and highly heterogeneous collection of spontaneously active myocytes in the right atrium. Sinoatrial node dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, is associated with cardiovascular disease (e.g.

β(IV)-Spectrin regulates TREK-1 membrane targeting in the heart.

Aims: Cardiac function depends on the highly regulated and co-ordinate activity of a large ensemble of potassium channels that control myocyte repolarization. While voltage-gated K(+) channels have been well characterized in the heart, much less is known about regulation and/or targeting of two-pore K(+) channel (K(2P)) family members, despite their potential importance in modulation of heart function.

Methods And Results: Here, we report a novel molecular pathway for membrane targeting of TREK-1, a mechano-sensitive K(2P) channel regulated by environmental and physical factors including membrane stretch, pH, and polyunsaturated fatty acids (e.

Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling.

Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility.

Microfluidic labeling of biomolecules with radiometals for use in nuclear medicine.

Radiometal-based radiopharmaceuticals, used as imaging and therapeutic agents in nuclear medicine, consist of a radiometal that is bound to a targeting biomolecule (BM) using a bifunctional chelator (BFC). Conventional, macroscale radiolabeling methods use an excess of the BFC-BM conjugate (ligand) to achieve high radiolabeling yields. Subsequently, to achieve maximal specific activity (minimal amount of unlabeled ligand), extensive chromatographic purification is required to remove unlabeled ligand, often resulting in longer synthesis times and loss of imaging sensitivity due to radioactive decay.

Epimorphin deletion protects mice from inflammation-induced colon carcinogenesis and alters stem cell niche myofibroblast secretion.

Epithelial-mesenchymal interactions regulate normal gut epithelial homeostasis and have a putative role in inflammatory bowel disease and colon cancer pathogenesis. Epimorphin is a mesenchymal and myofibroblast protein with antiproliferative, promorphogenic effects in intestinal epithelium. We previously showed that deletion of epimorphin partially protects mice from acute colitis, associated with an increase in crypt cell proliferation.