Discussion
The present study demonstrated that QTe/RR and QTa/RR slopes from entire 24-hour and daytime Holter recordings were significantly steeper in the LQT2 patients in contrary to LQT1 patients. A cutoff score of 0.211 of QTa/RR slope from entire 24-hour Holter recordings was most optimal to differentiate LQT1 from LQT2 (sensitivity, 80%; specificity, 75%). The identification of LQTS genotype is crucial because the treatment differ according to LQTS genotype. From an electrocardiographic point of view, broad-based prolonged T waves are commonly observed in the LQT1 syndrome, whereas low-amplitude T waves with a notched or bifurcated configuration are seen frequently in the LQT2 syndrome.9 Furthermore, the exercise-stress test and epinephrine infusion test have been proposed for differential diagnosis between LQT1 and LQT2.10,11 However, predicting the T wave pattern’s value is relatively low, the exercise-stress test and epinephrine infusion test are both provocative tests.
QT/RR relationship analyzed based on long-term Holter recordings can evaluate the QT adaptation to a changing heart rate. It has been demonstrated that the QT/RR slope was significantly increased in patients with structural heart disease.12-14 As for LQTS patients, a previous QT/RR relationship analysis showed a linear slope equal to 0.12 ± 0.04 in healthy subjects and a significantly higher slope in LQT1 and LQT2 carriers (QT slope > 0.17). However, no significant difference was observed at the QT/RR slope between LQT1 and LQT2 (0.17 ± 0.10 vs. 0.22 ± 0.16).15In contrast, Yamaguchi et al reported that QT/RR slope was significantly greater in LQT2 than in LQT1 patients (0.207 ± 0.032 vs. 0.163 ± 0.014, P < 0.05).16
In this multicenter study with all patients genetically identified, QTe/RR and QTa/RR slopes from entire 24-hour and daytime Holter recordings were significantly steeper in the LQT2 patients compared to the LQT1 patients. Our findings support previous studies suggesting that QT/RR relationship may be useful for differential diagnosis between LQT1 and LQT2. The steeper QT/RR slope in the LQT2 than that in the LQT1 is at least due to more significant QT prolongation at an increased heart rate in the LQT1 compared to the LQT2 patients, resulting in a more gradual QT/RR slope at an increased heart rate in the LQT1 patients. Our result may support this speculation that the QT/RR slope at daytime, when a sympathetic tone is higher, was significantly steeper in the LQT2, whereas that at night time, when a sympathetic tone is lower, was not different between the LQT1 and LQT2. The QT/RR slope is influenced by autonomic balance and has circadian variations.17Recently, Page et al. reported that LQT1 patients showed more frequent QTc prolongation during the day than night. In contrast, LQT2 patients showed less frequent QTc prolongation during the day than at night.18
QTe-QTa is considered to reflect transmural dispersion of repolarization (TDR) and possibly useful for differential diagnosis between LQT1 and LQT2. Our previous study from the body surface potential mapping showed that the QTe-QTa was more decreased in LQT1 than that in LQT2 patients after beta-blockade administration.19 This may explain the reason why beta-blockers are more effective in LQT1 than LQT2. In the present study, there were no significant differences in QTe-QTa/RR slope between the LQT1 and the LQT2, although the reason of this finding is unclear.