mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions.

A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway.

Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.

A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet been proven in humans.We used ELISA for serial measurements of SARS-CoV-2 neutralizing Ab (anti-S) and anti-PEG IgG/IgM Ab levels before and after the first and subsequent booster vaccinations with mRNA-LNP vaccines in a total of 291 blood donors.

History of the Plague: An Ancient Pandemic for the Age of COVID-19.

During the fourteenth century, the bubonic plague or Black Death killed more than one third of Europe or 25 million people. Those afflicted died quickly and horribly from an unseen menace, spiking high fevers with suppurative buboes (swellings). Its causative agent is Yersinia pestis, creating recurrent plague cycles from the Bronze Age into modern-day California and Mongolia.

Recommendations regarding dietary intake and caffeine and alcohol consumption in patients with cardiac arrhythmias: what do you tell your patients to do or not to do?

The etiology of arrhythmias including atrial fibrillation is multifactorial. Most arrhythmias are associated with comorbid illnesses like hypertension, diabetes, thyroid disease, or advanced age. Although it is tempting to blame a stimulant like caffeine as a trigger for arrhythmias, the literature does not support this idea.

Short-term secondhand smoke exposure decreases heart rate variability and increases arrhythmia susceptibility in mice.

Exposure to secondhand smoke (SHS), a major indoor air pollutant, is linked to increased cardiovascular morbidity and mortality, including cardiac arrhythmias. However, the mechanisms underlying the epidemiological findings are not well understood. Impaired cardiac autonomic function, indexed by reduced heart rate variability (HRV), may represent an underlying cause.

Inductionless or limited shock testing is possible in most patients with implantable cardioverter- defibrillators/cardiac resynchronization therapy defibrillators: results of the multicenter ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations).

Background: Implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators have relied on multiple ventricular fibrillation (VF) induction/defibrillation tests at implantation to ensure that the device can reliably sense, detect, and convert VF. The ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations) is the first large, multicenter, prospective trial comparing vulnerability safety margin testing versus defibrillation safety margin testing with a single VF induction/defibrillation.

Methods And Results: A total of 426 patients receiving an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator underwent vulnerability safety margin or defibrillation safety margin screening at 14 J in a randomized order.

Implantable cardioverter-defibrillators: a new preventive medical option.

Implantable cardioverter-defibrillator (ICD or defibrillator) therapy has revolutionized the fields of cardiology and electrophysiology. Hundreds of thousands of patients at risk for sudden cardiac death receive them each year. The devices are not much larger than a pacemaker, and they have full pacemaker capabilities in addition to being able to shock patients out of life-threatening ventricular arrhythmias.

Ratio of late to early T-wave peak amplitude in 24-h electrocardiographic recordings as indicator of symptom history in patients with long-QT Syndrome types 1 and 2.

Unlabelled: We reviewed 24-h electrocardiographic recordings from 214 genotyped subjects--97 with long-QT syndrome type 1 (LQT1), 62 with LQT2, and 55 unaffected--to record maximal diurnal amplitude ratios between late and early T-wave peaks. Maximal amplitude ratios between late and early T-wave peaks were higher in symptomatic than in asymptomatic patients both in LQT1 (3.2 +/- 1.

Functional roles of Cav1.3(alpha1D) calcium channels in atria: insights gained from gene-targeted null mutant mice.

Background: Previous data suggest that L-type Ca2+ channels containing the Cav1.3(alpha(1D)) subunit are expressed mainly in neurons and neuroendocrine cells, whereas those containing the Cav1.2(alpha1C) subunit are found in the brain, vascular smooth muscle, and cardiac tissue.

Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes.

Small-conductance Ca2+-activated K+ channels (SK channels, KCa channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ with membrane potential. We recently reported for the first time the functional existence of SK2 (KCa2.2) channels in human and mouse cardiac myocytes.

Pregnancy in postural orthostatic tachycardia syndrome.

Introduction: Postural orthostatic tachycardia syndrome (POTS) is a rare disease characterized by syncope, sinus tachycardia, and orthostasis due to autonomic dysfunction.

Methods And Results: Two women aged 26 and 24 years with severe POTS became pregnant. Both women experienced hyperemesis gravidarum with subsequent marked improvement in their POTS symptoms until 6 months gestation, when their syncope and sinus tachycardia caused clinical decompensation.

Use of ibutilide in cardioversion of patients with atrial fibrillation or atrial flutter treated with class IC agents.

Objectives: We sought to assess the efficacy and safety of ibutilide cardioversion for those with atrial fibrillation (AF) or atrial flutter (AFL) receiving long-term treatmentwith class IC agents.

Background: Attenuation of ibutilide-induced QT prolongation has been observed in a small number of patients pretreated with class IC agents. The clinical significance of the interaction between ibutilide and class IC agents is unknown.

Retrograde cycle length alternans during supraventricular tachycardia: an unusual tachycardia mechanism.

Cycle length alternans is occasionally seen during supraventricular tachycardia due to oscillations in the antegrade atrioventricular nodal (AVN) refractoriness. However, alternans due to retrograde variation in AVN conduction has not been reported. This report describes the case of a 36-year-old man with atypical AVN reentry tachycardia (AVNRT) whose episodes of tachycardia were characterized by continuous oscillations in retrograde AVN conduction.

Characterization of a KCNQ1/KVLQT1 polymorphism in Asian families with LQT2: implications for genetic testing.

Congenital long QT syndrome (LQTS) is a genetic disease that predisposes affected individuals to arrhythmias, syncope, and sudden death. Mutations in several ion channel genes have been discovered in different families with LQTS: KCNQ1 (KVLQT1, LQT1), KCNH2 (HERG, LQT2), SCN5A (LQT3), KCNE1 (minK, LQT5), and KCNE2 (MiRP1, LQT6). Previously, the P448R-KVLQT1 missense mutation has been reported as an LQT1-causing mutation.

Effectiveness of sotalol treatment in symptomatic Brugada syndrome.

We describe a 53-year-old man with recurrent syncopal events and a malignant family history who was treated for 13 years with sotalol drug therapy with no further occurrence of Brugada syndrome symptoms. Genetic testing revealed that he carried a Brugada syndrome sodium channel SCN5A mutation (4189delT). This finding suggests that sotalol may be of therapeutic benefit in such patients.

Molecular identification and functional roles of a Ca(2+)-activated K+ channel in human and mouse hearts.

The repolarization phase of cardiac action potential is prone to aberrant excitation that is common in cardiac patients. Here, we demonstrate that this phase is markedly sensitive to Ca2+ because of the surprising existence of a Ca2+-activated K+ currents in cardiac cells. The current was revealed using recording conditions that preserved endogenous Ca2+ buffers.

Mechanism of conversion of atypical right atrial flutter to atrial fibrillation.

The purpose of this study was to explore the mechanisms of conversion from atypical atrial flutter (AFL) to atrial fibrillation (AF), and the long-term results of cavotricuspid isthmus ablation in these patients. We retrospectively reviewed the records of 221 patients with typical AFL referred to our hospital for ablation. A total of 25 patients had atypical AFL, and cavotricuspid isthmus ablation was performed in 23 with isthmus-dependent atypical AFL, as well as in 180 patients with typical counterclockwise and/or clockwise AFL.