The present study demonstrated that the QTVI is correlated with autonomic nerve activity in prepubescent healthy children aged 0–7 years. Namely, QTVI showed a significant positive correlation with LF/HF ratio reflecting sympathetic nerve activity and negative correlation with HF/(LF +HF) ratio, reflecting vagal nerve activity. QTVI showed a significant negative correlation with SDNN reflecting the sympatho-vagal nervous balance and negative correlation with rMSSD, reflecting vagal nerve activity.
Berger et al. [
2] proposed that temporal variations in the QT interval—instability in myocardial repolarization—could serve as an electrophysiological indicator. QT interval is affected by the heart rate; larger HRV could induce larger QT interval variability, whereas smaller HRV could induce smaller QT interval variability. Either overestimation or underestimation of QT variability might occur without considering the degree of HRV. Therefore, the authors proposed the formula: QTVI = log
10 (QTv/QTm
2)/(HRv/HRm
2)] taking into account the effects of HRV. In fact, this formula has been evaluated in clinical studies and proved to be useful in distinguishing patients with high risk for sudden cardiac death in hypertrophic cardiomyopathy and patients with a history of ventricular fibrillation [
11]. Although all studies did not always present data of the numerator (QTVN: QT variance/QTmean
2) and denominator (HRVN: HR variance/HRmean
2), increased QTVN rather than decreased HRVN might usually be the cause of QTVI to increase. Dobson suggested that evaluating both QTVN and HRVN is important in assessing the pathophysiology of QTVI. [
6] As previously shown, HRVN changes with age; however, QTVN was not affected by age and remained stable without sex-related differences in children [
7]. Thus, increase in QTVI might not necessarily indicate increase in QTVN, but could be due to decrease in HRVN. Actually, our analysis revealed a significant relationship between LF/HF and HF/(LF + HF) with log
10HRVN; however, only weak relationship was observed with log
10QTVN. Therefore, it might be possible that increased sympathetic nerve activity reduces RR interval variability but has no marked effect on the QT interval variability. Schmidt M and colleagues showed that QTV was increased in rapid eye movement sleep, reflective of high sympathetic drive and predicts death from cardiovascular disease [
12]. However, HRV was not assessed in the paper. Likewise, augmented vagal nerve activity increases RR interval variability and could decrease QTVI, but its effect on QTVN is not clear. Further studies are required to evaluate the relationship between autonomic nerve balance and QTVN.
Potential Clinical Implication
Sudden Infant Death Syndrome (SIDS) is one of the leading causes of death in infants. Although the exact mechanisms contributing SIDS have not been fully elucidated until now, it is estimated that dysfunction of the autonomic nervous system regulation either respiratory or cardiovascular systems might play a part. The advantage of this study is that QTVI, which reflects myocardial repolarization variability, calculated from short-term ECG recording, can be used to assess the degree of autonomic tone. Thus, QTVI could be potentially used for predicting lethal arrhythmias, including SIDS. This should be explored in the future studies.