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Archives of cardiovascular diseases
Volume 112, n° 11
pages 699-712 (novembre 2019)
Doi : 10.1016/j.acvd.2019.06.008
Received : 21 April 2019 ;  accepted : 18 June 2019
Clinical research

Clinical characterization of men with long QT syndrome and torsades de pointes associated with hypogonadism: A review and pharmacovigilance study
Caractérisation clinique des hommes avec syndrome du QT long et Torsade de Pointes associé à un hypogonadisme – Une étude de Pharmacovigilance
 

Joe-Elie Salem a, b, , Marie Bretagne a, Benedicte Lebrun-Vignes a, Xavier Waintraub c, Estelle Gandjbakhch c, Francoise Hidden-Lucet c, Paul Gougis a, Anne Bachelot d, Christian Funck-Brentano a

the French Network of Regional Pharmacovigilance Centres

a Inserm, UNICO-GRECO Cardio-Oncology Programme, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, Pitié-Salpêtrière Hospital, Sorbonne Université, AP–HP, 75013 Paris, France 
b Pharmacology and Cardio-Oncology Program, Departments of Medicine, Vanderbilt University Medical Center, 37232 Nashville, TN, USA 
c Inserm, ICAN, Rythmology Unit, Department of Cardiology, Pitié-Salpêtrière Hospital, Sorbonne Université, AP–HP, 75013 Paris, France 
d Department of Endocrinology and Reproductive Medicine, IE3M, centre de référence des maladies endocriniennes rares de la croissance et centre des pathologies gynécologiques rares, ICAN, Pitié-Salpêtrière Hospital, AP–HP, 75013 Paris, France 

Corresponding author: UF de Cardio-Oncologie, Centre d’investigation clinique Paris-Est, hôpital La Pitié-Salpêtrière, 47–83, boulevard de l’Hôpital, 75651 Paris, France.UF de Cardio-Oncologie, Centre d’investigation clinique Paris-Est, hôpital La Pitié-Salpêtrière47–83, boulevard de l’HôpitalParis75651France
Summary
Background

Long QT syndrome (LQTS) can cause the potentially fatal ventricular tachycardia torsades de pointes (TdP). QT interval corrected for heart rate (QTc) is shorter in men than in women, with testosterone contributing to shorten QTc. We recently described male hypogonadism as a reversible risk factor for acquired LQTS and TdP, but the clinical characteristics of such patients have not been characterized.

Aims

To describe the clinical characteristics of men with acquired LQTS or TdP associated with hypogonadism caused by endocrine conditions or androgen deprivation therapy (ADT), and to evaluate the relationship between testosterone concentrations and electrocardiographic changes.

Methods

We searched MEDLINE (to 04 January 2019) and the French pharmacovigilance database (to 09 August 2018) to identify male cases of acquired LQTS and TdP associated with endocrine hypogonadism or ADT; their narratives were gathered from reporting collaborators.

Results

We identified seven cases of TdP (one fatal) with endocrine hypogonadism, abnormally long QTc and morphologically abnormal T-wave notches. After reversion of low testosterone concentrations in the surviving patients (N =6), QTc shortened, T-wave morphology normalized and there was no TdP recurrence. Among these cases, none had mutation in the LQTS genes, three men required testosterone and three had reversible hypogonadism after resolution of a concurrent acute severe illness. We found an additional 27 reports of men with LQTS (N =6), TdP (N =9; 2/9 fatal) or sudden death (N =12; 10/12 fatal) suspected to be induced or favoured by ADT (24/27 for prostate cancer). Generally, after ADT withdrawal, QTc shortened and no TdP recurred.

Conclusion

We propose seeking for hypogonadism caused by endocrine conditions or ADT in men presenting with TdP. Caution is warranted when ADT is used in situations at risk of TdP. Testosterone may be useful to treat or prevent TdP.

The full text of this article is available in PDF format.
Résumé
Contexte

Le syndrome du QT long (SQTL) peut se compliquer de torsade-de-pointe (TdP) et de mort subite. L’intervalle QT corrigé sur la fréquence cardiaque (QTc) est influencé par les hormones sexuelles et notamment raccourci par la testostérone. Nous avons récemment décrit que l’hypogonadisme masculin est un facteur de risque réversible de SQTL et de TdP.

Objectifs

Description des caractéristiques cliniques des hommes avec un hypogonadisme endocrinien ou secondaire à un traitement anti-androgène (ADT) ayant présenté une TdP. Évaluation de la relation entre les taux de testostérone et des modifications électrocardiographiques.

Méthodes

Analyse des bases MEDLINE et de pharmacovigilance française.

Résultats

Des Tdp ont été identifiés chez 7 hommes hypogonadiques présentant un QTc allongé et des anomalies morphologiques de l’onde T (notches). Sur les 6 survivants, la correction de l’hypogonadisme s’est faite par administration de testostérone (n =3) ou par résolution de son origine étiologique (n =3). Cette correction a permis un raccourcissement du QTc, une normalisation de la morphologie de l’onde T et une absence de récidive des TdP. Aucune mutation des gènes SQTL n’a été retrouvée. La prise d’ADT a été reportée comme suspecte dans 27 autres cas de SQTL (n =6), de TdP (n =9 ; 2/9 décès) ou de mort subite (n =12 ; 10/12 décès). L’arrêt de l’ADT permettait un raccourcissement du QTc et une absence de récidive des TdP.

Conclusion

Un hypogonadisme est à rechercher chez les hommes présentant une TdP. Les ADT doivent être utilisés prudemment chez des hommes à risque de TdP. Nos données suggèrent l’utilisation de la testostérone dans la prise en charge des TdP.

The full text of this article is available in PDF format.

Keywords : Torsades de pointes, Hypogonadism, Long QT syndrome, Testosterone, Androgen deprivation therapy

Mots clés : Torsade-de-Pointes, Hypogonadisme, Syndrome du QT Long, Testostérone, Anti-androgène

Abbreviations : ADR, ADT, aLQTS, BNPV, ICD, LQTS, PVR, QTc, TdP




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