Neural Control of Heart Rate Is an Arrhythmia Risk Modifier in Long QT Syndrome

Neural Control of Heart Rate Is an Arrhythmia Risk Modifier in Long QT Syndrome Peter J. Schwartz, Emilio Vanoli, Lia Crotti, Carla Spazzolini, Chiara Ferrandi, Althea Goosen, Paula Hedley, Marshall Heradien, Sara Bacchini, Annalisa Turco, Maria Teresa La Rovere, Antonella Bartoli, Alfred L. George, Jr, Paul A. Brink There is high clinical heterogeneity in long QT syndrome (LQTS). We tested our hypothesis that autonomic responses could modulate arrhythmic risk in long QT syndrome type 1 (LQT1) patients. In an LQT1 population segregating KCNQ1 -A341V, we correlated cardiac events to heart rate (HR) and baroreflex sensitivity (BRS). In 56 mutation carriers, HR and BRS were lower among asymptomatic patients (p < 0.05). A BRS in the lower tertile was associated with a lower probability of being symptomatic (odds ratio 0.13, 95% confidence interval 0.02 to 0.96, p < 0.05). Higher BRS values were more frequent (45% vs. 8%, p < 0.05) in carriers of polymorphisms predicting enhanced adrenergic responses. We have identified a first physiological modifier of LQTS, which might itself be genetically determined.