Pietro Enea Lazzerini 1 , Franco Laghi-Pasini 1 , Iacopo Bertolozzi 2 , Gabriella Morozzi 1 , Sauro Lorenzini 1 , Antonella Simpatico 1 , Enrico Selvi 1 , Maria Romana Bacarelli 1 , Francesco Finizola 1 , Francesca Vanni 1 , Deana Lazaro 3 , Ademuyiwa Aromolaran 3 , Nabil El Sherif 3 , Mohamed Boutjdir 3,4 , Pier Leopoldo Capecchi 1 Show Affiliations »
Abstract
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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Entities: Chemical
Disease
Gene
Species
Keywords:
Torsades de pointes; interleukin-6.; sudden death; systemic inflammation
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Year: 2017
PMID： 28490617 DOI： 10.1136/heartjnl-2016-311079
Source DB: PubMed Journal: Heart ISSN： 1355-6037 Impact factor: 5.994