Shinji Toyonaga

Use of Plasma B-Type Natriuretic Peptide Level to Identify Asymptomatic Hypertensive Patients with Abnormal Diurnal Blood Pressure Variation Profiles: Nondippers, Extreme Dippers, and Risers

We examined the relationship between plasma B-type natriuretic peptide (BNP) level and diurnal variability pattern of blood pressure (BP). Twenty-four-hour ambulatory BP monitoring was performed in 98 patients with asymptomatic essential hypertension, and the patients were classified into four groups according to their circadian BP variation profiles: dippers (n=29), nondippers (n=36), extreme dippers (n=19), and risers (n=14). Plasma BNP was measured by enzyme immunoassay. Based on the distribution pattern of BNP values, the values were analyzed after logarithmic transformation. Significant differences in plasma BNP levels among the types of circadian BP variations were demonstrated by analysis of variance (p<0.0005). Nondippers and risers showed significantly higher plasma BNP levels (mean [range: −1 SD and +1 SD]: 16.1 [6.3, 41.6] pg/mL and 29.2 [15.9, 53.4] pg/mL, respectively) than dippers (8.4 [3.7, 19.1] pg/mL). The area under the receiver operating characteristics curve for distinguishing patients with abnormal circadian BP variation from those with normal variation was 0.72, indicating that plasma BNP levels were useful for distinguishing between these patients. Specificity of 69% and sensitivity of 72% were obtained with a cut-off value of 10.5 pg/mL (log plasma BNP, 1.02) for distinguishing the abnormal diurnal BP profile group from the normal group. In conclusion, hypertensive patients with abnormal diurnal BP variation patterns (nondippers, extreme dippers, and risers) showed higher plasma BNP levels than those with normal circadian BP variation (dippers). Plasma BNP level is clinically useful for the identification of hypertensive patients who have abnormal circadian BP variability, which increases the risk of cardiovascular events.

Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia.

Background: Heart-rate (HR) variability is an important predictor of mortality in patients with heart disease. We examined the effects of cilostazol, a quinolinone derivative, on HR and HR variability in patients with chronic atrial fibrillation associated with bradycardia episodes. Patients and Methods: Thirteen patients with chronic atrial fibrillation associated with bra dycardia episodes (minimal HR <40/min and/or pauses, ie, episodes with an RR interval > 2.5 sec) received cilostazol (100 or 200 mg/day) orally for at least 2 months and 24-hour Holter electrocardiography was performed before and after the start of cilostazol administration. Results: Minimal HR was significantly increased, by an average of 14 beats/min (bpm), at 3.3 ± 0.8 weeks (mean ± SD) after the start of cilostazol treatment. The number of pauses was significantly decreased. As a consequence, mean HR was increased by an average of 18 bpm. Maximal HR was also increased by an average of 19 bpm. The circadian variation of the HR, determined by cosine fitting, was not changed by cilostazol treatment. The time-domain HR variabilities, ie, the SD of the mean RR interval and the SD of the 5-minute mean RR intervals, were also unchanged. New York Heart Association functional class was signifi cantly improved and the plasma atrial natriuretic polypeptide level was significantly de creased after the initiation of cilostazol treatment. Conclusion: Cilostazol improves the slow HR episodes associated with chronic atrial fibril lation and maintains the HR circadian variation and time-domain variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with chronic atrial fibrillation.

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.

Association of augmentation index of radial pressure wave form with diurnal variation pattern of blood pressure in untreated patients with essential hypertension.

Objectives The augmentation index of the radial pulse wave has been reported to be a sensitive aortic stiffness marker in relatively young but not in older individuals. We studied the relationship between augmentation index and the diurnal blood pressure profiles. Patients and methods Twenty-four-hour ambulatory blood pressure monitoring was performed in 90 untreated patients with uncomplicated essential hypertension. The patients were classified into four groups: dippers, extreme dippers, nondippers, and risers. Augmentation index was calculated as the percentage of the second systolic peak relative to the first systolic peak. Results No significant differences in the averaged whole 24-h systolic or diastolic blood pressure were observed in the whole set of patients or in subgroup patients with age 60 years or under. In the whole set of patients (58.7 ± 12.9 years), there were significant differences in augmentation index between patients with abnormal (other than dippers) and normal diurnal blood pressure profiles (dippers). In subgroup patients with age 60 years or below (49.1 ± 9.1 years, n = 48), the abnormal diurnal blood pressure profile group showed significantly higher augmentation index (89.6 ± 10.3%) than dippers (80.5 ± 11.8%). The area under the curve in the receiver operating characteristics curve for distinguishing between dippers than other dippers was 0.73 (P < 0.01). Multivariate analysis demonstrated that abnormal diurnal blood pressure profile was independently associated with increase in augmentation index. In contrast, these relationships were not significant in the over 60 years subgroup patients (69.8 ± 5.6 years old, n = 42). Conclusions The present study revealed that augmentation index was associated with dipping blood pressure patterns in untreated hypertensive patients aged 60 years or younger. Augmentation index determination would be useful for initial assessment in connection with possible abnormal diurnal blood pressure variability in patients with age 60 years or younger.

Double-Sector Lorenz Plot Scattering in an R-R Interval Analysis of Patients With Chronic Atrial Fibrillation Incidence and Characteristics of Vertices of the Double- Sector Scattering

Abstract Animal experiments have demonstrated that the minimum R-R interval during atrial fibrillation is proportional to the functional refractory period of the atrioventricular node. On Lorenz plots, atrial fibrillation is characterized by sector-shaped scattering; the vertex of the sector (ie, the minimum R-R interval) represents the functional refractory period. According to the atrioventricular nodal dual-pathway theory, it was hypothesized that the dual atrioventricular nodal pathways associated with chronic atrial fibrillation represent two vertices with two sectors. Detection of two-sector Lorenz plot scattering was attempted in 48 patients with chronic atrial fibrillation who underwent 24-hour ambulatory electrocardiography. Lorenz plot scattering was constructed by means of a computer. Two sectors, suggesting dual pathways, were detected in 19 (40%) of the 48 patients. The two vertices, located at 388 ± 61 ms (mean ± SD) and 580 ± 60 ms were considered to represent the functional refractory periods of the fast and slow pathways, respectively. The vertex indicating the fast pathway showed greater circadian variation than that indicating the slow pathway. In one patient with dual-sector Lorenz plot scattering, whose atrial fibrillation spontaneously converted to sinus rhythm, an electrophysiologic study demonstrated dual atrioventricular nodal pathways. Thus, the Lorenz plot analysis identified two sectors, indicating the dual pathways, in approximately 40% of the patients with chronic atrial fibrillation, and the characteristics of the functional refractory periods of both pathways were estimated from the characteristics of the vertices. Although this study did not provide direct evidence of the dual atrioventricular nodal pathways, the analysis of Lorenz plot scattering may be clinically useful for studying the effects of drugs and/or ablation on the ventricular response in patients with atrial fibrillation based on the dual atrioventricular nodal pathway theory.

Increased Blood Pressure Levels Relative to Subjective Feelings of Intensity of Exercise Determined with the Borg Scale in Male Patients with Hypertension

We examined the hemodynamic responses to exercise and symptoms in 37 male patients with untreated essential hypertension, and compared the findings with those in 32 age-matched healthy male volunteers by performing a graded symptom-limited exercise test using a bicycle ergometer. The subjective feeling of intensity of exercise was determined using the Borg scale. In the relationship between Borg scores and blood pressure (BP), patients with hypertension showed higher systolic BP and diastolic BP relative to the Borg scores than the controls. Consequently, patients with hypertension showed significantly higher systolic BP with Borg scores ≤ 3 (subjective symptoms ≤ moderately hard) than the controls (177.8 ± 27.0 vs. 143.7 ± 17.9 mmHg, p < 0.0001). Similarly, significantly higher diastolic BP with Borg scores ≤ 3 was observed in patients with hypertension than in the controls (101.6 ± 12.0 vs. 82.6 ± 11.6 mmHg, p < 0.0001). The pulse pressure with Borg scores ≤ 3 was also significantly higher in patients with hypertension than in the controls (76.2 ± 20.6 vs. 61.0 ± 13.6 mmHg, p < 0.0001). Hypertensive patients showed a decrease in the high-frequency power of heart rate variability at initial low-load exercise. In conclusion, the present study revealed that there was a greater BP response relative to the Borg score in patients with hypertension than in the controls. Autonomic nerve activity may contribute to some extent to these different relations. A determination of the relationship between the subjective feeling of intensity of the exercise and BP levels caused by a given intensity of load is essential before exercise training in patients, at least in males, with hypertension to avoid increasing the risk of cardiovascular events in association with excessive exercise training.

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.

Development of an automatic Doppler flow signal detection system: variability of pulmonary and aortic peak flow velocity

PurposeAutomatic Doppler flow signal detection systems can provide beat-to-beat information for large blood vessels. We have developed new equipment for automatic measurement of Doppler flow signals. The reliability of the system was examined, and the variability of aortic and pulmonary peak flow velocity was determined.MethodsWe measured peak flow velocity using a newly developed system in healthy volunteers and patients with atrial fibrillation. Analysis of variability of peak flow velocity was performed with maximal entropy methods.ResultsIn Bland–Altman plots, the mean and standard deviation (SD) of differences in aortic peak flow velocities between the automatic and manual measurements were 0.22 ± 0.75 cm/s and 0.85 ± 0.38 cm/s, respectively, in five normal volunteers. Moreover, less than 5% of the plotted points were beyond ± 2 SD of the differences. Furthermore, good reproducibility was demonstrated using Bland–Altman plots and Pearsons correlation analysis. Identical reliability was obtained in patients with atrial fibrillation. The same results were obtained for pulmonary peak flow velocity. In five healthy subjects, aortic and pulmonary peak flow showed standard deviations of 7.2 ± 2.4 and 3.8 ± 0.6 cm/s, respectively, and coefficients of variation of 6.1% ± 1.0% and 5.1% ± 1.1%, respectively, in time-domain variability. Similarly, frequency-domain variability was obtained for both peak flow velocities.ConclusionThe present study demonstrated the reliability of a newly developed automatic Doppler flow signal detection system. Using this system, the present study demonstrated for the first time aortic and pulmonary peak flow velocity variability. The present analytical methods may have considerable potential for studying aortic and/or pulmonary flow variability in connection with cardiac performance and prognosis of cardiac disease.

Effect of cilnidipine on normal to marginally elevated urine albumin-creatinine ratio in asymptomatic non-diabetic hypertensive patients: an exponential decay curve analysis.

AbstractBackground: High-normal urinary albumin excretion has been reported to have clinical significance with respect to progression of proteinuria and hypertension. Objective: We analysed the effect of cilnidipine (10 mg/day) on morning systolic blood pressure (SBP) and urine albumin-creatinine ratio (UACR) in 16 non-diabetic hypertensive patients with a normal to marginally elevated UACR (mean ± SD 29.4 ± 21.7; range 7.5–72.9 mg/g creatinine). Methods: Sequential home BP and UACR data were fitted to a simple exponential function as follows: y = α · e−t/β+ γ, where y is SBP (mmHg) or UACR (mg/g creatinine); α is the extent of the SBP (mmHg)- or UACR (mg/g creatinine)-lowering effect; β (days) is the time-constant for SBP or UACR decrease; t is the number of days after the start of cilnidipine administration; and γ is the finally stabilized SBP (mmHg) or UACR (mg/g creatinine). Results: Mean ± SD morning SBP and UACR decreased by 20.4 ±11.4mmHg and 15.2±13.1 mg/g creatinine, respectively, as determined by coefficient a. The mean ± SD time-constant for UACR decrease was significantly longer than that for BP decrease (43.5 ± 22.9 vs 15.4 ± 7.1 days). UACR reduction correlated with pre-treatment UACR values (correlation coefficient [R] = 0.88, p < 0.01) but not with BP decrease. Conclusions: The present study demonstrated that cilnidipine reduced UACR in hypertensive patients with normal to marginally elevated UACR independent of its BP-lowering effect.