Emerging risk factors for QT interval prolongation and torsades de pointes

Long QT syndrome (LQTS) is a cardiac electrical disorder which increases the risk for malignant ventricular arrhythmias, specifically torsades de pointes (TdP). LQTS can result from a large number of etiologic factors, congenital and acquired. Mutations, mainly in potassium or sodium channel genes, drugs, and electrolyte imbalances are the most recognized causes. Structural heart disease, bradyarrhythmias, endocrine and liver diseases, nervous system injuries, starvation, hypothermia, and toxins represent other well-documented causes for acquired LQTS. Nonetheless, the above “conventional” risk factors cannot explain all cases of LQTS/TdP. In the recent years, a number of novel “nonconventional” causes of LQTS have emerged in the literature, both acquired (inflammation, autoimmunity, human immunodeficiency virus infection, male hypogonadism, heart failure with preserved ejection fraction, QT interval-prolonging foods) and genetic (polygenic mutations), with a potentially significant impact on TdP prevalence in the general population. By integrating basic and clinical research, we here provide an updated overview on this topic, also discussing the clinical implications and perspectives.