Potential depot medroxyprogesterone acetate–triggered torsades de pointes in a case of congenital type 2 long QT syndrome

Abstract

Congenital or acquired long QT syndrome (LQTS) stems from disordered myocardial repolarization and is characterized by a prolonged QT interval on an electrocardiogram and an increased risk of syncope and sudden death secondary to torsades de pointes (TdP). Female gender is an independent risk factor for the development of TdP in both forms of LQTS. 1 Makkar R.R. Fromm B.S. Steinman R.T. Meissner M.D. Lehmann M.H. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA. 1993; 270: 2590-2597 Crossref PubMed Scopus (814) Google Scholar , 2 Locati E.H. Zareba W. Moss A.J. et al. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation. 1998; 97: 2237-2244 Crossref PubMed Scopus (403) Google Scholar Furthermore, while women with congenital LQTS have a reduced risk of TdP-triggered cardiac events during pregnancy, the 9-month postpartum period represents a temporal window of increased arrhythmogenicity. 3 Seth R. Moss A.J. McNitt S. et al. Long QT syndrome and pregnancy. J Am Coll Cardiol. 2007; 49: 1092-1098 Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar Interestingly, these postpartum-timed cardiac events are more commonly observed in women with type 2 LQTS (LQT2), which stems from mutations in the KCNH2-encoded human ether-a-go-go–related gene (hERG/Kv11.1) cardiac potassium (K+) ion channel. 4 Khositseth A. Tester D.J. Will M.L. Bell C.M. Ackerman M.J. Identification of a common genetic substrate underlying postpartum cardiac events in congenital long QT syndrome. Heart Rhythm. 2004; 1: 60-64 Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar Although several studies suggest that sex-specific hormonal and autonomic differences that impact cardiac repolarization underlie the longer heart rate–corrected QT interval (QTc) and a higher incidence of TdP observed in postpubertal women with LQTS, the precise mechanisms underlying these differences remain poorly understood. 5 Jonsson M.K. Vos M.A. Duker G. Demolombe S. van Veen T.A. Gender disparity in cardiac electrophysiology: implications for cardiac safety pharmacology. Pharmacol Ther. 2010; 127: 9-18 Crossref PubMed Scopus (62) Google Scholar