title: Marked QTc Prolongation and Torsades de pointes in Patients with Chronic Inflammatory Arthritis.
abstract: Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about torsades de pointes (TdP) prevalence in CIA, and the few cases reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development. We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24 h from TdP/marked QTc prolongation occurrence, and levels of IL-6, TNFα, and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNFα and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other "classical" risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levelsviadirect electrophysiological effects on the heart. This fact should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Pietro Enea
authors.initials: PE
authors.lastname: Lazzerini
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.affiliation: Cardiology Intensive Therapy Unit, Department of Internal Medicine, Hospital of Carrara , Carrara , Italy.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Bertolozzi
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Morozzi
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Sauro
authors.initials: S
authors.lastname: Lorenzini
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Simpatico
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Selvi
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Maria Romana
authors.initials: MR
authors.lastname: Bacarelli
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Acampa
authors.affiliation: VA New York Harbor Healthcare System, SUNY Downstate Medical Center , New York, NY , USA.
authors.forename: Deana
authors.initials: D
authors.lastname: Lazaro
authors.affiliation: VA New York Harbor Healthcare System, SUNY Downstate Medical Center , New York, NY , USA.
authors.forename: Nabil
authors.initials: N
authors.lastname: El-Sherif
authors.affiliation: VA New York Harbor Healthcare System, SUNY Downstate Medical Center, New York, NY, USA; NYU School of Medicine, New York, NY, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boutjdir
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
keywords: chronic inflammatory arthritis; interleukin-6; psoriatic arthritis; rheumatoid arthritis; sudden death; systemic inflammation; torsades de pointes