RT Journal Article
SR Electronic
T1 Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 1821
OP 1829
DO 10.1136/heartjnl-2016-311079
VO 103
IS 22
A1 Lazzerini, Pietro Enea
A1 Laghi-Pasini, Franco
A1 Bertolozzi, Iacopo
A1 Morozzi, Gabriella
A1 Lorenzini, Sauro
A1 Simpatico, Antonella
A1 Selvi, Enrico
A1 Bacarelli, Maria Romana
A1 Finizola, Francesco
A1 Vanni, Francesca
A1 Lazaro, Deana
A1 Aromolaran, Ademuyiwa
A1 El Sherif, Nabil
A1 Boutjdir, Mohamed
A1 Capecchi, Pier Leopoldo
YR 2017
UL http://heart.bmj.com/content/103/22/1821.abstract
AB Objective Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population.Methods Forty consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), interleukin-1 (IL-1)) were compared with patients with active rheumatoid arthritis (RA), comorbidity or healthy controls. An additional 46 patients with different inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12; others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled, and corrected QT (QTc) and cytokine levels were measured during active disease and after a CRP decrease of >75% subsequent to therapy.Results In the TdP cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a definite inflammatory disease identifiable in 18/40 cases (acute infections, n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but not TNFα and IL-1, was ~15–20 times higher than in controls, and comparable to RA patients. In the inflammatory cohort, where QTc prolongation was common (mean values: 456.6±30.9 ms), CRP reduction was associated with IL-6 level decrease and significant QTc shortening (−22.3 ms).Conclusion The data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy.