Mutsuko Sangawa

Abnormal transmural repolarization process in patients with Brugada syndrome

BACKGROUND Repolarization abnormality, especially during bradycardia, might be critical for initiation of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS), but the contribution of the rate-dependent repolarization dynamics to the occurrence of VF is still unknown. OBJECTIVE The aim of our study was to determine the differences in rate-dependent repolarization dynamics between BrS with and without spontaneous VF and between BrS with and without SCN5A mutation. METHODS The subjects were 37 BrS patients with VF (VF(+) group: 10 male subjects) and without VF (VF(-) group: 27 male subjects) and 20 control subjects. Genetic analysis of SCN5A was performed in all 37 BrS patients. The relationships between QT, QTp, Tp-e, and RR intervals were obtained from Holter recordings as first linear regression lines, and the slopes of QT/RR, QTp/RR, and Tp-e/RR linear regression lines as the sensitivity of rate-dependent repolarization dynamics were compared. RESULTS QT/RR and Tp-e/RR slopes showed loss of a rate-dependent property in the VF(+) group compared with those in the VF(-) and control groups. There was no significant difference in QTp/RR slope among the VF(+), VF(-) and control groups. The Tp-e interval had a negative correlation with the RR interval in the VF(+) group and a positive correlation with the RR interval in the VF(-) and control groups. There was no significant difference in QT/RR, QTp/RR, and Tp-e/RR slopes between BrS patients with SCN5A mutation and those without SCN5A mutation. CONCLUSIONS Loss of rate-dependent QT dynamics may be associated with occurrence of VF in BrS.

Intense response of heart rate with pronounced suppression of high-frequency power of heart rate variability to early morning exercise with high-intensity load

Autonomic nerve activity shows circadian variation. Therefore, we put forward the hypothesis that the responses of heart rate (HR) and high-frequency (HF) power of HR variability to exercise would be different between early morning and daytime exercise. We performed ergometer constant load exercise tests [50 watts (low), 100 watts (high load)] in the early morning and during the day in 6 healthy volunteers. The HR response was fitted to an exponential hyperbolic sine function: HR= alpha*e(-beta*t) *sinh(omega*t)+gamma. In this equation, the beta/omega ratio was inversely correlated with the intensity of the HR response. HF power was determined using a recently developed algorithm with high time-resolution power. There were no significant differences in HR, HF power or systolic blood pressure (BP) pressure before exercise between early morning and daytime exercise with either the 50 or 100 watt loads. During exercise, there were no significant differences in maximal HR or maximal systolic BP between early morning and daytime exercise with either 50 or 100 watt loads. For high-load exercise, the beta/omega ratio was significantly lower in early morning exercise (mean +/- SD, 0.945 +/- 0.02) than in daytime exercise (0.987 +/- 0.03). Similarly, for 100 watt exercise, HF power of HR variability was significantly lower in early morning exercise (0.94 +/- 0.52 msec/Hz 1/2) than in daytime exercise (1.26 +/- 0.74 msec/Hz 1/2). In conclusion, the present study demonstrated that a lower beta/omega ratio in the HR response was associated with lower HF power of HR variability in early morning high-load exercise compared to that in daytime exercise, indicating that the heart rate responded more intensely to early morning exercise than to daytime exercise with a high load due, at least partly, to pronounced suppression of parasympathetic nerve activity.