Increased interleukin-6 levels are associated with atrioventricular conduction delay in severe COVID-19 patients.

Background: Severely ill patients with coronavirus disease 2019 (COVID-19) show an increased risk of new-onset atrioventricular blocks (AVBs), associated with high rates of short-term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)-6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL-6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID-19.

Life-Threatening Arrhythmias in Patients With Takotsubo Syndrome: Insights Into Pathophysiology and Treatment Innovations.

Takotsubo syndrome (TTS) is a reversible form of acute myocardial injury due to a neurocardiogenic mechanism associated with a relevant risk for life-threatening ventricular arrhythmias, occurring in up to 25% of all patients and including both ventricular arrhythmias (especially) in the context of QT prolongation and atrial tachy- or bradyarrhythmias. The pathogenetic mechanisms of TTS-related arrhythmic complications are not completely understood, and there are no randomized clinical trials addressing the pharmacologic and nonpharmacologic management in this specific setting. In this narrative review, the authors provide an overview of the pathogenesis and the therapeutic management of arrhythmic complications in patients with TTS, along with the future perspectives and the remaining knowledge gaps in this field.

Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans.

Background: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects.

Fir(e)ing the Rhythm: Inflammatory Cytokines and Cardiac Arrhythmias.

Inflammatory activation is increasingly recognized as a nonconventional risk factor for arrhythmias, and experimental studies provided robust evidence that this association is mediated by direct arrhythmogenic effects of proinflammatory cytokines on cardiac cells. Additionally, inflammatory cytokines can favor arrhythmias indirectly through multiple systemic effects. Accumulating data confirm the clinical relevance of these mechanisms; the largest evidence being available for atrial fibrillation, acquired long-QT syndrome, and ventricular arrhythmias.

Anti-Ro/SSA Antibodies Blocking Calcium Channels as a Potentially Reversible Cause of Atrioventricular Block in Adults.

Background: In ∼50% of severe atrioventricular blocks (AVBs) occurring in adults <50 years, the underlying etiology remains unknown. Preliminary evidence from case reports suggests that autoimmunity, specifically the presence of circulating anti-Ro/SSA antibodies in the patient (acquired form), in the patient's mother (late-progressive congenital form), or in both (mixed form), could be involved in a fraction of idiopathic AVBs in adults by possibly targeting the L-type calcium channel (Ca1.2) and inhibiting the related current (I).

Surveillance of Influenza and Other Airborne Transmission Viruses during the 2021/2022 Season in Hospitalized Subjects in Tuscany, Italy.

Winter in the northern hemisphere is characterized by the circulation of influenza viruses, which cause seasonal epidemics, generally from October to April. Each influenza season has its own pattern, which differs from one year to the next in terms of the first influenza case notification, the period of highest incidence, and the predominant influenza virus subtypes. After the total absence of influenza viruses in the 2020/2021 season, cases of influenza were again recorded in the 2021/2022 season, although they remained below the seasonal average.

Contribution of cytokine-mediated prolongation of QTc interval to the multi-hit theory of Torsade de Pointes.

Background: Torsade de pointes is a potentially lethal polymorphic ventricular tachyarrhythmia that can occur in the setting of long QT syndrome (LQTS). LQTS is multi-hit in nature and multiple factors combine their effects leading to increased arrhythmic risk. While hypokalemia and multiple medications are accounted for in LQTS, the arrhythmogenic role of systemic inflammation is increasingly recognized but often overlooked.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

Background: Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms.

Inflammatory cytokines and cardiac arrhythmias: the lesson from COVID-19.

Although inflammatory cytokines are implicated in the pathogenesis of cardiac arrhythmias, inflammation is still largely overlooked in the current management of heart rhythm disorders. Now, COVID-19, a systemic inflammatory disease, causes an unexpectedly high prevalence of arrhythmic events, emphasizing the relevance of inflammation in the pathogenesis of cardiac arrhythmias.

Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases.

Inflammatory diseases including COVID-19 are associated with a cytokine storm characterized by high interleukin-6 (IL-6) titers. In particular, while recent studies examined COVID-19 associated arrhythmic risks from cardiac injury and/or from pharmacotherapy such as the combination of azithromycin (AZM) and hydroxychloroquine (HCQ), the role of IL-6 per se in increasing the arrhythmic risk remains poorly understood. The objective is to elucidate the electrophysiological basis of inflammation-associated arrhythmic risk in the presence of AZM and HCQ.

Transient Hypogonadism Is Associated With Heart Rate-Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men.

Background Systemic inflammation and male hypogonadism are 2 increasingly recognized "nonconventional" risk factors for long-QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate-corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men.

Epidemiological and virological surveillance of Severe Acute Respiratory Infections in the 2019/2020 season in Siena, Tuscany, Italy.

Background: Influenza is a major public health issue. Indeed, in Italy there were 7.6 million symptomatic cases of influenza in the 2019/2020 influenza season (from October 2019 to April 2020).

Unravelling Atrioventricular Block Risk in Inflammatory Diseases: Systemic Inflammation Acutely Delays Atrioventricular Conduction via a Cytokine-Mediated Inhibition of Connexin43 Expression.

Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap-junctions containing connexin43 coupling cardiomyocytes and inflammation-related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms.

Anti-Ro/SSA Antibodies and the Autoimmune Long-QT Syndrome.

Autoimmunity is increasingly recognized as a novel pathogenic mechanism for cardiac arrhythmias. Several arrhythmogenic autoantibodies have been identified, cross-reacting with different types of surface proteins critically involved in the cardiomyocyte electrophysiology, primarily ion channels (autoimmune cardiac channelopathies). Specifically, some of these autoantibodies can prolong the action potential duration leading to acquired long-QT syndrome (LQTS), a condition known to increase the risk of life-threatening ventricular arrhythmias, particularly Torsades de Pointes (TdP).

Proton Pump Inhibitors Directly Block hERG-Potassium Channel and Independently Increase the Risk of QTc Prolongation in a Large Cohort of US Veterans.

[Figure: see text].

Surveillance for Severe Acute Respiratory Infections among Hospitalized Subjects from 2015/2016 to 2019/2020 Seasons in Tuscany, Italy.

In Italy, the influenza season lasts from October until April of the following year. Influenza A and B viruses are the two viral types that cocirculate during seasonal epidemics and are the main causes of respiratory infections. We analyzed influenza A and B viruses in samples from hospitalized patients at Le Scotte University Hospital in Siena (Central Italy).

Drug-Associated QTc Prolongation in Geriatric Hospitalized Patients: A Cross-Sectional Study in Internal Medicine.

Objective: The primary objectives of this prospective cross-sectional study were to estimate the prevalence of drug-related long QT syndrome (LQTS) and the prevalence of use of QT-prolonging drugs in older patients admitted to an internal medicine unit.

Methods: We screened consecutive patients hospitalized in an internal medicine unit over a 2-year period. A 12-lead electrocardiogram using an electrocardiograph with automated measurement of QT interval was recorded.