Magnetic field-induced interactions between phones containing magnets and cardiovascular implantable electronic devices: Flip it to be safe?

BACKGROUND: Recent case reports and small studies have reported activation of the magnet-sensitive switches in cardiovascular implantable electronic devices (CIED) by the new iPhone 12 series, initiating asynchronous pacing in pacemakers and suspension of anti-tachycardia therapies in ICDs. OBJECTIVE AND METHODS: We performed a prospective single-center observational study to quantify the risk of magnetic field interactions of the iPhone 12 with CIEDs. A representative model of each CIED series from all manufacturers was tested ex vivo. Incidence and minimum distance necessary for magnet mode triggering were analyzed in 164 CIED patients with either the front or the back of the phone facing the device. The magnetic field of the iPhone 12 was analyzed using a 3-axis hall probe. RESULTS: Ex vivo, magnetic interferences occurred in 84.6% with the back compared to 46.2% with the front of the iPhone 12 facing the CIED. In vivo, activation of the magnet-sensitive switch occurred in 30 CIED patients (18.3%; 21 pacemaker, 9 ICDs) when the iPhone 12 was placed in close proximity over the CIED pocket and the back of the phone was facing the skin. Multiple binary logistic regression analysis identified the implantation depth (95% confidence interval [CI], 0.02 to 0.24) as independent predictor of magnet-sensitive switch activation. CONCLUSION: Magnetic field interactions occur only in close proximity, and with precise alignment of the iPhone 12 and CIEDs. It is important to advise CIED patients to not put the iPhone 12 directly on the skin above the CIED. Further recommendations are not necessary

COVID19-associated cardiomyocyte dysfunction, arrhythmias and the effect of Canakinumab

BACKGROUND: Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. AIMS AND METHODS: We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1β antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. RESULTS: Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca(2+) transient amplitudes and altered baseline [Ca(2+)] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca(2+) release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca(2+) release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca(2+) release or Ca(2+) signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. CONCLUSION: Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca(2+) signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca(2+) imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein

Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1(IS) and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.</p

A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR

Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by diff

G(q)-mediated arrhythmogenic signaling promotes atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is promoted by various stimuli like angiotensin II, endothelin-1, epinephrine/norepinephrine, vagal activation, or mechanical stress, all of which activate receptors coupled to G-proteins of the Ga(q)/Ga(11)-family (G(q)). Besides pro-fibrotic and pro-inflammatory effects, G(q)-mediated signaling induces inositol trisphosphate receptor (IP(3)R)-mediated intracellular Ca(2+) mobilization related to delayed after-depolarisations and AF. However, direct evidence of arrhythmogenic G(q)-mediated signaling is absent. METHODS AND RESULTS: To define the role of G(q) in AF, transgenic mice with tamoxifen-inducible, cardiomyocyte-specific Ga(q)/Ga(11)-deficiency (G(q)-KO) were created and exposed to intracardiac electrophysiological studies. Baseline electrophysiological properties, including heart rate, sinus node recovery time, and atrial as well as AV nodal effective refractory periods, were comparable in G(q)-KO and control mice. However, inducibility and mean duration of AF episodes were significantly reduced in G(q)-KO mice-both before and after vagal stimulation. To explore underlying mechanisms, left atrial cardiomyocytes were isolated from G(q)-KO and control mice and electrically stimulated to study Ca(2+)-mobilization during excitation-contraction coupling using confocal microscopy. Spontaneous arrhythmogenic Ca(2+) waves and sarcoplasmic reticulum content-corrected Ca(2+) sparks were less frequent in G(q)-KO mice. Interestingly, nuclear but not cytosolic Ca(2+) transient amplitudes were significantly decreased in G(q)-KO mice. CONCLUSION: G(q)-signaling promotes arrhythmogenic atrial Ca(2+)-release and AF in mice. Targeting this pathway, ideally using G(q)-selective, biased receptor ligands, may be a promising approach for the treatment and prevention of AF. Importantly, the atrial-specific expression of the G(q)-effector IP(3)R confers atrial selectivity mitigating the risk of life-threatening ventricular pro-arrhythmic effects

G_q-Mediated Arrhythmogenic Signaling Promotes Atrial Fibrillation

Background: Atrial fibrillation (AF) is promoted by various stimuli like angiotensin II, endothelin-1, epinephrine/norepinephrine, vagal activation, or mechanical stress, all of which activate receptors coupled to G-proteins of the Gαq/Gα11-family (Gq). Besides pro-fibrotic and pro-inflammatory effects, Gq-mediated signaling induces inositol trisphosphate receptor (IP3R)-mediated intracellular Ca2+ mobilization related to delayed after-depolarisations and AF. However, direct evidence of arrhythmogenic Gq-mediated signaling is absent. Methods and results: To define the role of Gq in AF, transgenic mice with tamoxifen-inducible, cardiomyocyte-specific Gαq/Gα11-deficiency (Gq-KO) were created and exposed to intracardiac electrophysiological studies. Baseline electrophysiological properties, including heart rate, sinus node recovery time, and atrial as well as AV nodal effective refractory periods, were comparable in Gq-KO and control mice. However, inducibility and mean duration of AF episodes were significantly reduced in Gq-KO mice—both before and after vagal stimulation. To explore underlying mechanisms, left atrial cardiomyocytes were isolated from Gq-KO and control mice and electrically stimulated to study Ca2+-mobilization during excitation–contraction coupling using confocal microscopy. Spontaneous arrhythmogenic Ca2+ waves and sarcoplasmic reticulum content-corrected Ca2+ sparks were less frequent in Gq-KO mice. Interestingly, nuclear but not cytosolic Ca2+ transient amplitudes were significantly decreased in Gq-KO mice. Conclusion: Gq-signaling promotes arrhythmogenic atrial Ca2+-release and AF in mice. Targeting this pathway, ideally using Gq-selective, biased receptor ligands, may be a promising approach for the treatment and prevention of AF. Importantly, the atrial-specific expression of the Gq-effector IP3R confers atrial selectivity mitigating the risk of life-threatening ventricular pro-arrhythmic effects