Cardiac Arrest Risk During Acute Infections: Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-mediated Effects on Potassium Channel Expression.

Cardiac Arrest Risk During Acute Infections: Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-mediated Effects on Potassium Channel Expression.

Publication date: Jul 13, 2020

Background – During acute infections the risk of malignant ventricular arrhythmias (VA) is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K-channels expression. Methods – We evaluated: (1) the frequency of QTc prolongation, and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes (TdP); (3) the relationship between K-channels mRNA levels in ventricles and peripheral blood mononuclear cells (PBMC), and their changes in patients with acute infection over time. Results – In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged, but rapidly normalized in parallel to C-reactive protein (CRP) and cytokine levels reduction. Consistently in the TdP cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K-channel expression in PBMC, which strongly correlated to that in ventricles, inversely associated to CRP and interleukin-1 changes in acute infection patients. Conclusions – During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodelling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening VA in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease-19 pandemic (COVID-19), in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs.

Concepts Keywords
Antimicrobial QTc acute infections
Blood Concomitant acute infections
Cardiac Arrest Cytokines cardiac arrhythmias
Cardiac Arrhythmias Prevalence acute infections
Cohort Branches of biology
Coronavirus Medical specialties
Cytokine Cardiac arrhythmia
Cytokines Medicine
Frequency RTT
Infection Immunology
Inflammation Cardiac electrophysiology
Interleukin 1 QT interval
Malignant Drug-induced QT prolongation
MRNA Torsades de pointes
Normalized Long QT syndrome
Pandemic Inflammation
QTc Interval
Remission
Repolarization
TdP
Transpose
Ventricles
Ventricular
Ventricular Arrhythmias

Semantics

Type Source Name
disease MESH Cardiac Arrest
disease MESH Infections
disease MESH Inflammation
drug DRUGBANK Potassium
disease MESH Torsades de Pointes
drug DRUGBANK Thiocolchicoside
disease IDO acute infection
disease IDO antimicrobial
disease MESH cardiac arrhythmias

Original Article

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