Frequency Domain Heart Period and QT Interval Variability Markers Are Linked to Arrhythmic Risk in Long QT Syndrome Type 2

Vlasta Bari1, Giulia Girardengo2, Beatrice De Maria3, Beatrice Cairo4, Lia Crotti2, Peter J Schwartz5, Alberto Porta6
1Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, 2IRCCS Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, 3IRCCS Istituti Clinici Scientifici Maugeri, Milan, 4University of Milan,Department of Biomedical Sciences for Health, 5IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, 6Department of Biomedical Sciences for Health, University of Milan


The long QT syndrome type 2 (LQT2) is an inherited genetic disease affecting cardiac cell ion channels. Its main clinical sign is a prolonged QT interval (QT). LQT2 can lead to life-threatening arrhythmias and sudden death in response to a sudden sympathetic stimulus. We hypothesize that cardiac autonomic control, as inferred from heart period (HP) and QT variability analyses, could stratify the arrhythmic risk in LQT2 patients. Heart period (HP) and QT variability beat-to-beat time series were extracted from 24h Holter ECG recordings derived from 10 asymptomatic (ASYMP, age 39.0±11.0 yrs, 9 males) and 7 symptomatic (SYMP, age 41.7±12.8 yrs, 4 males) subjects. HP and QT sequences were analyzed during daytime (from 2:00 to 6:00 PM) and nighttime (from 12:00 to 4:00 AM) in time and frequency domains. In addition to mean and variance, we computed the HP power in high frequency (HF, from 0.15 to 0.5 Hz) band and the QT power in low frequency (LF, from 0.04 to 0.15 Hz) band. Markers were computed over 300 consecutive measures with 50% overlap. Median value of the distribution during daytime and nighttime was retained as the final marker. Results showed that HP and QT means exhibited significant day-night changes in both groups, with HP being longer in ASYMP subjects, leading them to have a shorter corrected QT interval. Furthermore, solely ASYMP group exhibited the expected increase of the HF power of RR during nighttime, thus indicating a more reactive vagal control than in SYMP subjects. On the contrary, SYMP subjects had a higher sympathetic modulation than ASYMP individuals during daytime, as suggested by the larger value of the QT variance. This work shows that LQT2 ASYMP and SYMP subjects have a different cardiac autonomic profile that might account for the diverse arrhythmic risk of the two groups.