Author + information
- Received September 9, 2015
- Revision received November 20, 2015
- Accepted December 14, 2015
- Published online April 5, 2016.
- aCenter for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy
- bDepartment of Biomedical Informatics, University of Arizona College of Medicine, Phoenix, Arizona
- cAZCERT, Inc., Oro Valley, Arizona
- ↵∗Reprint requests and correspondence:
Dr. Peter J. Schwartz, IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, c/o Centro Diagnostico e di Ricerca S. Carlo, Via Pier Lombardo, 22, 20135 Milan, Italy.
Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and both syndromes can result in life-threatening torsades de pointes (TdP). Our understanding of their mechanistic and genetic similarities has led to their improved clinical management. However, our inability to prevent diLQTS has resulted in removal of many medicines from the market and from development. Genetic and clinical risk factors for diLQTS and TdP are well known and raise the possibility of TdP prevention. Clinical decision support systems (CDSS) can scan the patient’s electronic health records for clinical risk factors predictive of diLQTS and warn when a drug that can cause TdP is prescribed. CDSS have reduced prescriptions of QT-prolonging drugs, but these relatively small changes lack the power to reduce TdP. The growing genetic evidence linking diLQTS to cLQTS suggests that prevention of TdP in the future may require inclusion of both genetic and clinical predictors into CDSS.
This study was supported by U.S. Food and Drug Administration grant HHSF223201400189C. Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 9, 2015.
- Revision received November 20, 2015.
- Accepted December 14, 2015.
- 2016 American College of Cardiology Foundation
- Historical Background
- Cellular mechanism of TdP
- CredibleMeds risk categorization of drugs
- Epidemiology of TdP and Death Associated With QT-Prolonging Drugs
- Factors Contributing to Risk of TdP
- Drug-Induced LQTS Versus Congenital LQTS
- Future Opportunities for TdP Prevention: Potential Role of Genomics and CDSS