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.
|disease||MESH||Torsades de Pointes|