Journal Article

Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes

Vanni, Francesca, Bacarelli, Maria Romana, Lazzerini, Pietro Enea, Bertolozzi, Iacopo, Lorenzini, Sauro, Aromolaran, Ademuyiwa, Morozzi, Gabriella, Laghi-Pasini, Franco, Finizola, Francesco, Capecchi, Pier Leopoldo, Selvi, Enrico, Simpatico, Antonella, El Sherif, Nabil, Lazaro, Deana, Boutjdir, Mohamed

2017

Overview

ObjectiveIncreasing 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.MethodsForty 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.ResultsIn 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).ConclusionThe 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.

• Publisher: BMJ Publishing Group LTD
• Subject: Age / Aged / Aged, 80 and over / Biomarkers - blood / C-Reactive Protein - analysis / Cardiac arrhythmia / Cardiovascular disease / Case-Control Studies / Congenital diseases / Cytokines / Electrocardiography / Electrolytes / Female / Heart failure / HIV / Human immunodeficiency virus / Humans / Inflammation / Inflammation - blood / Inflammation - complications / Inflammation - diagnosis / Inflammation Mediators - blood / Inflammatory diseases / Interleukin-1 - blood / Interleukin-6 - blood / Laboratories / Long QT syndrome / Male / Middle Aged / Patients / Potassium / Predictive Value of Tests / Prospective Studies / Rheumatoid arthritis / Risk Factors / Rodents / TNF inhibitors / Torsades de Pointes - blood / Torsades de Pointes - diagnosis / Torsades de Pointes - etiology / Torsades de Pointes - physiopathology / Tumor Necrosis Factor-alpha - blood / Tumor necrosis factor-TNF / Up-Regulation