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We investigate the properties of static mechanical and dynamic electro‐mechanical models for the deformation of the human heart. Numerically this is realized by a staggered scheme for the coupled partial/ordinary differential equation (PDE‐ODE) system. First, we consider a static and purely mechanical benchmark configuration on a realistic geometry of the human ventricles. Using a penalty term for quasi‐incompressibility, we test different parameters and mesh sizes and observe that this approach is not sufficient for lowest order conforming finite elements. Then, we compare the approaches of active stress and active strain for cardiac muscle contraction. Finally, we compare in a coupled anatomically realistic electro‐mechanical model numerical Newmark damping with a visco‐elastic model using Rayleigh damping. Nonphysiological oscillations can be better mitigated using viscosity. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AFib) and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2 + macrophages secrete osteopontin (encoded by Spp1 ), a matricellular signaling protein that engenders fibrosis and AFib. Here we show that silencing Spp1 in TREM2 + cardiac macrophages with an antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib in mice, thus offering a new immunotherapy for the most common arrhythmia., Competing Interests: Competing interests: S.S. received speaker fees or honoraria from Astra Zeneca, Novartis, Berlin-Chemie, Daiichi Sankyo, Bristol Myers Squibb, Pfizer, Boehringer Ingelheim, and Lilly. P.T.E. receives sponsored research support from Bayer AG, IBM Research, Bristol Myers Squibb, Pfizer, and Novo Nordisk; he has also served on advisory boards or consulted for Bayer AG. D.G.A is a founder of oRNA Tx, Verseau Tx, Combined Tx, and Souffle Tx. M.N. has received funds or material research support from Alnylam, Biotronik, CSL Behring, GlycoMimetics, GSK, Medtronic, Novartis, and Pfizer, as well as consulting fees from Biogen, Gimv, IFM Therapeutics, Molecular Imaging, Sigilon, Verseau Therapeutics, and Bitterroot. N.M., A.R., I.L., M.J.S., D.G.A., K.N, M.N., and M.H. are inventors on U.S. Provisional Patent applications no. 63/501,286 and 63/525,135 regarding the role of and modulating stromal and immune cells in atrial disease. The other authors declare no competing interests.

Background: Acute stimulation of the late sodium current (I NaL ) as pharmacologically induced by Anemonia toxin II (ATX-II) results in Na + -dependent Ca 2+ overload and enhanced formation of reactive oxygen species (ROS). This is accompanied by an acute increase in the amplitude of the systolic Ca 2+ transient. Ca 2+ transient amplitude is determined by L-type Ca 2+ -mediated transsarcolemmal Ca 2+ influx (I Ca ) into the cytosol and by systolic Ca 2+ release from the sarcoplasmic reticulum (SR). Type-1 protein kinase A (PKARIα) becomes activated upon increased ROS and is capable of stimulating I Ca , thereby sustaining the amplitude of the systolic Ca 2+ transient upon oxidative stress., Objectives: We aimed to investigate whether the increase of the systolic Ca 2+ transient as acutely induced by I NaL (by ATX-II) may involve stimulation of I Ca through oxidized PKARIα., Methods: We used a transgenic mouse model in which PKARIα was made resistant to oxidative activation by homozygous knock-in replacement of redox-sensitive Cysteine 17 with Serine within the regulatory subunits of PKARIα (KI). ATX-II (at 1 nmol/L) was used to acutely enhance I NaL in freshly isolated ventricular myocytes from KI and wild-type (WT) control mice. Epifluorescence and confocal imaging were used to assess intracellular Ca 2+ handling and ROS formation. A ruptured-patch whole-cell voltage-clamp was used to measure I NaL and I Ca . The impact of acutely enhanced I NaL on RIα dimer formation and PKA target structures was studied using Western blot analysis., Results: ATX-II increased I NaL to a similar extent in KI and WT cells, which was associated with significant cytosolic and mitochondrial ROS formation in both genotypes. Acutely activated Ca 2+ handling in terms of increased Ca 2+ transient amplitudes and elevated SR Ca 2+ load was equally present in KI and WT cells. Likewise, cellular arrhythmias as approximated by non-triggered Ca 2+ elevations during Ca 2+ transient decay and by diastolic SR Ca 2+ -spark frequency occurred in a comparable manner in both genotypes. Most importantly and in contrast to our initial hypothesis, ATX-II did not alter the magnitude or inactivation kinetics of I Ca in neither WT nor KI cells and did not result in PKARIα dimerization (i.e., oxidation) despite a clear prooxidant intracellular environment., Conclusions: The inotropic and arrhythmogenic effects of acutely increased I NaL are associated with elevated ROS, but do not involve oxidation of PKARIα., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Gissibl, Stengel, Tarnowski, Maier, Wagner, Feder and Sag.)