Salem J-E, Waintraub X, Courtillot C, et al. Hypogonadism as a Reversible Cause of Torsades de Pointes in Men. Circulation 2018;138:110. Hypogonadism as a Reversible Cause of Torsades de Pointes in Men
Long QT intervals corrected for rate (QTc) >480 to 500 milliseconds predispose to the polymorphic ventricular tachycardia torsades de pointes (TdP). Because QTc is shorter and TdP is less frequent in men than in women and because testosterone shortens ventricular repolarization, we examined the effect of hypogonadism and androgen deprivation therapy (ADT) on QTc and TdP risk.
We prospectively evaluated testosterone and related plasma levels in each man seen with TdP (n=7) over 19 months at a single university hospital (Hôpital Pitié-Salpétrière, Paris, France, Commission nationale de l’informatique et des libertés No. 1491960v0, patients’ informed consent obtained). We then analyzed the European pharmacovigilance database (up to June 2017, URL: https://clinicaltrials.gov, Unique identifier: NCT03193138) searching for QTc/TdP adverse drug reactions (Medical Dictionary for Regulatory Activities terms: long-QT syndrome [LQT], ECG QT-prolonged, and TdP) associated with ADT, and we performed a cross-sectional analysis of the association between the International Classification of Diseases revisions 9 and 10 codes for LQT/TdP and hypogonadism in 1.1 million men in a US electronic health record cohort (up to November 2017, Vanderbilt University Medical Center, Institutional Review Board approval no. 171796).3
Hypogonadism was diagnosed in 7 of 7 cases of TdP. After correction of low testosterone levels, QTc shortened and there was no TdP recurrence. Three patients had spontaneous reversal of hypogonadism after resolution of a severe critical illness; 3 patients needed testosterone supplementation for chronic hypogonadism; and 1 patient died. LQT genetic screening was negative in 6 of the 6 tested patients.
Long QT intervals corrected for rate (QTc) >480 to 500 milliseconds predispose to the polymorphic ventricular tachycardia torsades de pointes (TdP). Because QTc is shorter and TdP is less frequent in men than in women and because testosterone shortens ventricular repolarization, we examined the effect of hypogonadism and androgen deprivation therapy (ADT) on QTc and TdP risk.
We prospectively evaluated testosterone and related plasma levels in each man seen with TdP (n=7) over 19 months at a single university hospital (Hôpital Pitié-Salpétrière, Paris, France, Commission nationale de l’informatique et des libertés No. 1491960v0, patients’ informed consent obtained). We then analyzed the European pharmacovigilance database (up to June 2017, URL: https://clinicaltrials.gov, Unique identifier: NCT03193138) searching for QTc/TdP adverse drug reactions (Medical Dictionary for Regulatory Activities terms: long-QT syndrome [LQT], ECG QT-prolonged, and TdP) associated with ADT, and we performed a cross-sectional analysis of the association between the International Classification of Diseases revisions 9 and 10 codes for LQT/TdP and hypogonadism in 1.1 million men in a US electronic health record cohort (up to November 2017, Vanderbilt University Medical Center, Institutional Review Board approval no. 171796).3
Hypogonadism was diagnosed in 7 of 7 cases of TdP. After correction of low testosterone levels, QTc shortened and there was no TdP recurrence. Three patients had spontaneous reversal of hypogonadism after resolution of a severe critical illness; 3 patients needed testosterone supplementation for chronic hypogonadism; and 1 patient died. LQT genetic screening was negative in 6 of the 6 tested patients.
