Ultra-Short Beat-to-Beat Repolarization Variability Predicts Cardiovascular Events in Individuals Without Cardiovascular Disease

The beat-to-beat variability of the QT interval (QTV) is thought to be a measure of sympathetic activity directed to the heart and it has predictive value in cardiac patients, but its predictive value in the general population is unclear. This study aimed to determine the association between ultra-short QTV from 15-second ECGs and future major adverse cardiovascular events (MACE) in a large cohort of middled aged individuals without previous cardiovascular disease. QTV was measured using the QTV index (QTVI), and the short-term QTV (STVQT) in n=55, 765 UK Biobank participants (54% female, 56.6±8.2 years old). The temporal variability of Q-Tpeak and Tpeak-Tend intervals was also assessed, and heart rate variability (RMSSD) was estimated for comparison. After a median follow-up of 12.5 years, n=2,542 (4.6%) MACE occurred. QTVI and STVQTV were associated with MACE and the association remained significant after adjusting for age, sex, bmi, diabetes, hypertension, smoking, betablockers, and, for STVQTV only, QT interval, resting heart rate, heart rate variability. QTVI showed the higher hazard ratio (1.10 (1.06, 1.15), p<0.01) and it was associated with MACE also when based on Q-Tpeak and Tpeak-Tend intervals. This study demonstrates for the first time that in the general population ultra-short repolarization variability from 15-sec ECG predicts MACE independently of traditional risk factors.