Evidence map›Paper›PMID 31423933›Full record

ArticleJournal of the American Heart Association2019

Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin-6-Mediated Changes in Connexin Expression.

Pietro Enea Lazzerini, Franco Laghi-Pasini, Maurizio Acampa, Ujala Srivastava, Iacopo Bertolozzi, Beatrice Giabbani, Francesco Finizola, Francesca Vanni, Aleksander Dokollari, Mariarita Natale and 6 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Heart Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06095791 (Identification of Immunomodulators Associated With Atrial Fibrillation Reporting), which is not on this map. Cited by 121 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 4 pooled it
12.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06095791 completednot on this mapstarted 2022, after this paper: background citation

Identification of Immunomodulators Associated With Atrial Fibrillation Reporting: Analysis of the WHO Pharmacovigilance Database

TypeobservationalSponsorUniversity Hospital, CaenRan2022 to 2022Enrolled4,000,000ConditionsAtrial FibrillationArmsImmunomodulators with FDA approval on the 1st January 2023.
3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 4 syntheses or guidelines pooled it, 181 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Pooled it
  4. Pooled it
  5. Article
  6. Article
  7. Article
  8. Observational
  9. Incident atrial fibrillation and pyoderma gangrenosum: long-term thromboembolic, heart failure, and mortality risk.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
    Article
  10. Review
  11. Observational
  12. Review
  13. Article
  14. Article
  15. Observational
  16. Article
  17. Review
  18. Modifiable Risk Factors in Atrial Fibrillation: Clinical Implications and Pathophysiological Insights.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026
    Review
  19. Article
  20. Review

61 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 3 countries.

Pietro Enea LazzeriniDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Franco Laghi-PasiniDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Maurizio AcampaStroke Unit University Hospital of Siena Italy.
Ujala SrivastavaCardiovascular Research Program VA New York Harbor Healthcare System Brooklyn, New York NY.
Iacopo BertolozziCardiology Intensive Therapy Unit Department of Internal Medicine Hospital of Carrara Italy.
Beatrice GiabbaniDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Francesco FinizolaDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Francesca VanniDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Aleksander DokollariDepartment of Cardiac Surgery University Hospital of Siena Italy.
Mariarita NataleDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Gabriele CeveniniDepartment of Medical Biotechnologies University of Siena Italy.
Enrico SelviDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Nicola MigliacciDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
Massimo MaccheriniDepartment of Cardiac Surgery University Hospital of Siena Italy.
Mohamed BoutjdirCardiovascular Research Program VA New York Harbor Healthcare System Brooklyn, New York NY.
Pier Leopoldo CapecchiDepartment of Medical Sciences, Surgery and Neurosciences University of Siena Italy.
University of Siena · ITVA NY Harbor Healthcare System · USAccademia di Belle Arti di Carrara · ITUniversity of Toronto · CA

Funding

BLRD VA I01 BX002137
6 · The paper itself

Abstract

Background Systemic inflammation is a strong predictor of atrial fibrillation. A key role for electrical remodeling is increasingly recognized, and experimental data suggest that inflammatory cytokines can directly affect connexins resulting in gap-junction dysfunction. We hypothesized that systemic inflammation, regardless of its origin, promotes atrial electric remodeling in vivo, as a result of cytokine-mediated changes in connexin expression. Methods and Results Fifty-four patients with different inflammatory diseases and elevated C-reactive protein were prospectively enrolled, and electrocardiographic P-wave dispersion indices, cytokine levels (interleukin-6, tumor necrosis factor-α, interleukin-1, interleukin-10), and connexin expression (connexin 40, connexin 43) were measured during active disease and after reducing C-reactive protein by >75%. Moreover, peripheral blood mononuclear cells and atrial tissue specimens from an additional sample of 12 patients undergoing cardiac surgery were evaluated for atrial and circulating mRNA levels of connexins. Finally, in vitro effects of interleukin-6 on connexin expression were studied in HL-1 mouse atrial myocytes. In patients with active inflammatory diseases, P-wave dispersion indices were increased but rapidly decreased within days when C-reactive protein normalizes and interleukin-6 levels decline. In inflammatory disease patients, both P-wave dispersion indices and interleukin-6 changes were inversely associated with circulating connexin levels, and a positive correlation between connexin expression in peripheral blood mononuclear cells and atrial tissue was demonstrated. Moreover, interleukin-6 significantly reduced connexin expression in HL-1 cells. Conclusions Our data suggest that regardless of specific etiology and organ localization, systemic inflammation, via interleukin-6 elevation, rapidly induces atrial electrical remodeling by down-regulating cardiac connexins. Although transient, these changes may significantly increase the risk for atrial fibrillation and related complications during active inflammatory processes.

Indexed as

AdultAgedAged, 80 and overAnimalsAnti-Bacterial AgentsAnti-Inflammatory AgentsArthritis, RheumatoidAtrial RemodelingCardiac Surgical ProceduresConnexin 43ConnexinsC-Reactive ProteinElectrocardiographyFemaleGap Junction alpha-5 ProteinGene Expression RegulationAnti-Bacterial AgentsAnti-Inflammatory AgentsConnexin 43ConnexinsC-Reactive ProteinGap Junction alpha-5 ProteinGJA1 protein, humanGJA1 protein, mouseIL10 protein, humanIL6 protein, humanInterleukin-1Interleukin-10Interleukin-6RNA, MessengerTNF protein, humanTumor Necrosis Factor-alphaatrial electrical remodelingatrial fibrillationconnexinsinterleukin‐6P‐wave indicessystemic inflammation

Identifiers

PMID31423933
PMCPMC6759884
OpenAlexW2969562629

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.