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Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men

BACKGROUND: Systemic inflammation and male hypogonadism are 2 increasingly recognized “nonconventional” risk factors for long‐QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate–corrected QT interval (QTc) via direct ele...

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Autores principales: Lazzerini, Pietro Enea, Cantara, Silvia, Bertolozzi, Iacopo, Accioli, Riccardo, Salvini, Viola, Cartocci, Alessandra, D’Errico, Antonio, Sestini, Fausta, Bisogno, Stefania, Cevenini, Gabriele, Capecchi, Matteo, Laghi‐Pasini, Franco, Castagna, Maria Grazia, Acampa, Maurizio, Boutjdir, Mohamed, Capecchi, Pier Leopoldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075210/
https://www.ncbi.nlm.nih.gov/pubmed/34935398
http://dx.doi.org/10.1161/JAHA.121.023371
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author Lazzerini, Pietro Enea
Cantara, Silvia
Bertolozzi, Iacopo
Accioli, Riccardo
Salvini, Viola
Cartocci, Alessandra
D’Errico, Antonio
Sestini, Fausta
Bisogno, Stefania
Cevenini, Gabriele
Capecchi, Matteo
Laghi‐Pasini, Franco
Castagna, Maria Grazia
Acampa, Maurizio
Boutjdir, Mohamed
Capecchi, Pier Leopoldo
author_facet Lazzerini, Pietro Enea
Cantara, Silvia
Bertolozzi, Iacopo
Accioli, Riccardo
Salvini, Viola
Cartocci, Alessandra
D’Errico, Antonio
Sestini, Fausta
Bisogno, Stefania
Cevenini, Gabriele
Capecchi, Matteo
Laghi‐Pasini, Franco
Castagna, Maria Grazia
Acampa, Maurizio
Boutjdir, Mohamed
Capecchi, Pier Leopoldo
author_sort Lazzerini, Pietro Enea
collection PubMed
description BACKGROUND: Systemic inflammation and male hypogonadism are 2 increasingly recognized “nonconventional” risk factors for long‐QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate–corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. METHODS AND RESULTS: We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C‐reactive protein and interleukin‐6 levels. Reduction of testosterone levels, which also inversely correlated with 17‐β estradiol over time, significantly contributed to inflammation‐induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C‐reactive protein, testosterone, and 17‐β estradiol levels; in these patients, increased C‐reactive protein and reduced testosterone were associated with a worse short‐term outcome of the arrhythmia. CONCLUSIONS: During systemic inflammatory activation, interleukin‐6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen‐to‐estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long‐QT syndrome/TdP risk in men.
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spelling pubmed-90752102022-05-10 Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men Lazzerini, Pietro Enea Cantara, Silvia Bertolozzi, Iacopo Accioli, Riccardo Salvini, Viola Cartocci, Alessandra D’Errico, Antonio Sestini, Fausta Bisogno, Stefania Cevenini, Gabriele Capecchi, Matteo Laghi‐Pasini, Franco Castagna, Maria Grazia Acampa, Maurizio Boutjdir, Mohamed Capecchi, Pier Leopoldo J Am Heart Assoc Original Research BACKGROUND: Systemic inflammation and male hypogonadism are 2 increasingly recognized “nonconventional” risk factors for long‐QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate–corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. METHODS AND RESULTS: We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C‐reactive protein and interleukin‐6 levels. Reduction of testosterone levels, which also inversely correlated with 17‐β estradiol over time, significantly contributed to inflammation‐induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C‐reactive protein, testosterone, and 17‐β estradiol levels; in these patients, increased C‐reactive protein and reduced testosterone were associated with a worse short‐term outcome of the arrhythmia. CONCLUSIONS: During systemic inflammatory activation, interleukin‐6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen‐to‐estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long‐QT syndrome/TdP risk in men. John Wiley and Sons Inc. 2021-12-22 /pmc/articles/PMC9075210/ /pubmed/34935398 http://dx.doi.org/10.1161/JAHA.121.023371 Text en © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Lazzerini, Pietro Enea
Cantara, Silvia
Bertolozzi, Iacopo
Accioli, Riccardo
Salvini, Viola
Cartocci, Alessandra
D’Errico, Antonio
Sestini, Fausta
Bisogno, Stefania
Cevenini, Gabriele
Capecchi, Matteo
Laghi‐Pasini, Franco
Castagna, Maria Grazia
Acampa, Maurizio
Boutjdir, Mohamed
Capecchi, Pier Leopoldo
Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men
title Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men
title_full Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men
title_fullStr Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men
title_full_unstemmed Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men
title_short Transient Hypogonadism Is Associated With Heart Rate–Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men
title_sort transient hypogonadism is associated with heart rate–corrected qt prolongation and torsades de pointes risk during active systemic inflammation in men
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075210/
https://www.ncbi.nlm.nih.gov/pubmed/34935398
http://dx.doi.org/10.1161/JAHA.121.023371
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