Background: During acute infections, the risk of malignant ventricular arrhythmias 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+channel 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; (3) the relationship between K+channel mRNA levels in ventricles and peripheral blood mononuclear cells 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 CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes 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 peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. Conclusions: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs.

Lazzerini, P.E., Acampa, M., Laghi-Pasini, F., Bertolozzi, I., Finizola, F., Vanni, F., et al. (2020). Cardiac arrest risk during acute infections: systemic inflammation directly prolongs QTc interval via cytokine-mediated effects on potassium channel expression. CIRCULATION. ARRHYTHMIA AND ELECTROPHYSIOLOGY, 13(8), 842-856 [10.1161/CIRCEP.120.008627].

Cardiac arrest risk during acute infections: systemic inflammation directly prolongs QTc interval via cytokine-mediated effects on potassium channel expression

Lazzerini P. E.
;
Acampa M.;Finizola F.;Vanni F.;Natale M.;Cevenini G.;Cartocci A.;Giabbani B.;Migliacci N.;D'Errico A.;Dokollari A.;Maccherini M.;Capecchi P. L.
2020-01-01

Abstract

Background: During acute infections, the risk of malignant ventricular arrhythmias 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+channel 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; (3) the relationship between K+channel mRNA levels in ventricles and peripheral blood mononuclear cells 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 CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes 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 peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. Conclusions: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs.
2020
Lazzerini, P.E., Acampa, M., Laghi-Pasini, F., Bertolozzi, I., Finizola, F., Vanni, F., et al. (2020). Cardiac arrest risk during acute infections: systemic inflammation directly prolongs QTc interval via cytokine-mediated effects on potassium channel expression. CIRCULATION. ARRHYTHMIA AND ELECTROPHYSIOLOGY, 13(8), 842-856 [10.1161/CIRCEP.120.008627].
File in questo prodotto:
File Dimensione Formato  
cardiac-arrest-risk-during-acute-infections-Lazzerini-2020.pdf

non disponibili

Descrizione: articolo
Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.62 MB
Formato Adobe PDF
1.62 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1122870