Instantaneous response of the QT interval to heart rate change in patients with type-1 long QT syndrome

Genotyping is considered the most reliable tool to identify the presence of the long QT syndrome (LQTS) but genetic testing captures only 75% of phenotypically affected LQTS individuals, and negative test in a phenotype-positive patient does not rule out the presence of the syndrome. Also, these tests do not fully capture an individual risk to life-threatening arrhythmias that is modulated by exogenous factors. The surface electrocardiogram (ECG) is an investigational tool that could provide insights into the integrated functional defects associated with LQTS mutations. We designed a method to visualize and quantify the dynamic features of the QT interval that is known to play a crucial role in the triggering of arrhythmias in these patients. The method is applied to a set of 24-hour Holter recordings acquired in 195 healthy individuals and 68 genotyped LQTS patients from the Telemetric and Holter ECG Warehouse (THEW) project. The technique provides a three dimensional representation of the instantaneous adaptation of the QT interval across heart rate and across the spectrum of autonomic states recorded during the ambulatory Holter ECG. Our results provide a description of the “normal” range of values of instantaneous response of QT to HR changes and confirm the presence of abnormal regulation of the QT interval in LQT-1 patients which revealed to be specific to the location of their mutation in the KCNQ1 channel.