Clinical characterization of men with long QT syndrome and torsades de pointes associated with hypogonadism: A review and pharmacovigilance study

Abstract

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.

Keywords: Androgen deprivation therapy; Anti-androgène; Hypogonadism; Hypogonadisme; Long QT syndrome; Syndrome du QT Long; Testosterone; Testostérone; Torsade-de-Pointes; Torsades de pointes.