This study determined the impact of subcutaneous implantable cardioverter-defibrillator (S-ICD) coil and generator position on defibrillation threshold (DFT). S-ICD implantation can occasionally result in unacceptably high DFT. Implant position characteristics associated with high DFTs in S-ICD patients have not been fully elucidated. A 3.8-million-element computer model built from magnetic resonance images was used to simulate the electric fields that occur during defibrillation. Generator positions were tested from posterior to anterior in 4-cm increments. The left parasternal coil was tested with 0, 5, and 10 mm of underlying subcutaneous fat and the generator with 20 mm of underlying fat. The estimated DFT for the S-ICD was defined as the energy delivered when producing an electric field of 4 volts/cm in at least 95% of the ventricular myocardium. Estimated DFTs were 22, 29, 64, and 135 joules for posterior, standard (lateral), mid-anterior, and anterior generator locations, respectively. Defibrillation thresholds were 29, 58, and 95 joules with 0, 5, and 10 mm subcoil fat, respectively, and 45 joules with 20 mm subgenerator fat. Combining anterior generator position with subcoil fat resulted in a very high DFT (379 joules). Shock impedance increased with both subcoil and subgenerator fat but was minimally affected by anterior/posterior generator position. The model suggests that an S-ICD implantation strategy involving posterior generator location and coil and generator directly over the fascia without underlying fat is likely to markedly lower DFTs with the S-ICD and assist in troubleshooting of patients with unacceptably high DFTs.

Stimulation of cells by Ca(2+)-linked signaling agents increases Ca2+ levels within both the cell cytosol and nucleus. The multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) family, consisting of CaM kinases I, II and IV, have all been detected within the nucleus and each may serve as a mediator of nuclear Ca2+ signals. Certain isoforms of the large multimeric CaM kinase II are targeted to the nucleus as a result of an alternatively spliced nuclear localization signal. By contrast, CaM kinases I and IV are monomeric and likely gain nuclear access by passive diffusion through nuclear pores. These kinases have activation properties which may allow them to discriminate between Ca2+ signals which differ in their spike frequency, amplitude and duration. In addition, these kinases have the ability to control gene expression through the phosphorylation of key regulatory sites on nuclear transcription factors. CaM kinases may thus serve to decode Ca2+ signals to the nucleus in order to produce a multitude of cellular responses including control of cell cycle, apoptosis and synaptic efficacy.

Introduction: Various catheter designs are appearing for Pulsed Field Ablation (PFA). It is unclear if they differ in terms of safety and efficiency. PFA studies have reported hemolysis, kidney injury, high troponin, among other side effects.Methods: Using a CT‐derived computer model, we compared catheter designs using two metrics: (1) efficiency: power delivered to an atrial wall target, expressed as a percent of total generator power; and (2) safety: electric current to achieve 90% transmurality (since more energy causes more collateral effects), as well as the corresponding electrode current density (ECD), a heat and bubble metric. The following catheter designs were compared: penta‐spline basket, Nitinol spheres (focal 9 mm and large 1‐shot), circular, balloon, and flex‐circuit. Target was a 6 × 47 mm circumferential segment of atrial wall at LPV antrum. Transmurality was defined as percent of target having >600 volts per centimeter (V/cm) electric field needed for electroporation.Results: Efficiency was 0.9, 1.4, 2.7, 5.9, 10, and 12% for the large 1‐shot and 9 mm Nitinol spheres, penta‐spline, circular, flex spline, and balloon catheters, respectively. Regarding safety, currents for 90% transmurality were 70, 39,36,12.5, 5.3, and 4 Amps for the same respective catheters, with less being safer. ECD was 124, 25, 74, 83, 41, and 31 A/cm², respectively.Conclusion: Computer models demonstrated a remarkable range in efficiency among catheters studied. Those having less atrial blood exposure had the highest efficiencies, with factors of up to 13X more efficiency compared to exposed ones. Higher efficiency designs have less collateral current and are safer. Confirmatory in‐vivo studies are required.