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Original research article
Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes
  1. Pietro Enea Lazzerini1,
  2. Franco Laghi-Pasini1,
  3. Iacopo Bertolozzi2,
  4. Gabriella Morozzi1,
  5. Sauro Lorenzini1,
  6. Antonella Simpatico1,
  7. Enrico Selvi1,
  8. Maria Romana Bacarelli1,
  9. Francesco Finizola1,
  10. Francesca Vanni1,
  11. Deana Lazaro3,
  12. Ademuyiwa Aromolaran3,
  13. Nabil El Sherif3,
  14. Mohamed Boutjdir3,4,
  15. Pier Leopoldo Capecchi1
  1. 1 Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
  2. 2 Cardiology Intensive Therapy Unit, Department of Internal Medicine, Hospital of Carrara, Carrara, Italy
  3. 3 VA New York Harbor Healthcare System, SUNY Downstate Medical Center, Brooklyn, New York, USA
  4. 4 NYU School of Medicine, New York, New York, USA
  1. Correspondence to Pietro Enea Lazzerini, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy; lazzerini7{at}unisi.it

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.

  • Torsades de pointes
  • sudden death
  • systemic inflammation
  • interleukin-6.

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Footnotes

  • Contributors All the authors have directly contributed to (1) conception and design or analysis and interpretation of data, or both; (2) drafting of the manuscript or revising it critically for important intellectual content; and (3) final approval of the manuscript submitted.

  • Funding This work has received funding from FAS-Salute ToRSADE project (FAS Salute 2014, Regione Toscana).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Local ethical committee (Comitato Etico Regione Toscana Area Vasta Sud Est).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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