Youkou Tominaga

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.

Inverse Correlation Between Seasonal Changes in Home Blood Pressure and Atmospheric Temperature in Treated-Hypertensive Patients

We examined the relationships between home blood pressure (BP) and atmospheric temperature in 20 treated-hypertensive patients. A significant correlation between morning and evening BP and atmospheric temperature was found. For morning systolic blood pressure (SBP), the maximal seasonal difference was 13.2 mmHg with 25.5°C temperature difference. Morning SBP increased by approximately 0.41 mmHg with a 1°C decrease in atmospheric temperature. A similar but weaker correlation with temperature was observed for morning diastolic, evening systolic and diastolic blood pressure (DBP). The present study provides important information in respect to BP changes with atmospheric temperature that should be taken into account in the analysis and treatment of hypertension.

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 Augmentation Index of the Radial Pressure Waveform in Patients with Paroxysmal Atrial Fibrillation

Objective: The augmentation index, a marker of wave reflection, has been reported to reflect vascular properties and to determine left ventricular (LV) characteristics. We investigated the relationship between the augmentation index and paroxysmal atrial fibrillation (AF). Methods: A total of 244 outpatients (122 patients with paroxysmal AF and 122 age-, and gender-matched controls without paroxysmal AF) were examined during sinus rhythm. The augmentation index was calculated from the radial arterial waveform using applanation tonometry methods. Results: After adjusting for age, gender, heart rate, and medications, the augmentation index was significantly higher in patients with paroxysmal AF than in subjects without paroxysmal AF (means ± SE: 88.9 ± 1.0 and 81.8 ± 1.0%, respectively; p < 0.001). In all subjects, an increase in the augmentation index was significantly correlated with LV hypertrophy and left atrial enlargement. Multiple logistic analysis revealed that an increase in the augmentation index was significantly related with paroxysmal AF, and the adjusted odds ratio of paroxysmal AF was approximately 1.8 for each 10% augmentation index increase (p < 0.01). Conclusion: An increase in the augmentation index was independently associated with paroxysmal AF. This result suggests that enhanced wave reflection may be related to the development of AF.

Exponential-exponential cosine fitting of blood pressure decay induced by a long-acting calcium blocker, amlodipine, using home blood pressure measurement

Blood pressure (BP) decay data obtained from home BP measurements in six patients with uncomplicated essential hypertension treated with a calcium blocker, amlodipine, were fitted to an exponential–exponential cosine function to determine the characteristic BP‐lowering effects of amlodipine. An exponential–exponential cosine function fitted the morning and night systolic BP (sBP) decay data better than a simple exponential function. From the coefficients of the equation, the estimated BP lowering, time constant for BP decay and BP oscillation induced by amlodipine for morning and night sBP were approximately 23 and 25 mmHg, 10 and 6 days, and 12 and 12 mmHg, respectively. Diastolic BP showed a similar fitting though the fitting was weaker. The fitting results indicate that the BP decay, especially the sBP decay, induced by amlodipine occurred in an oscillative fashion, and the present analysis using home BP data may provide clinically useful information about the characteristic effects of amlodipine.

CORRELATION OF LORENZ SCATTERPLOTS WITH FREQUENCY-DOMAIN HEART RATE VARIABILITY

Heart rate (HR) variability is important with respect to disease prognosis and the effects of drugs. Lorenz scatterplots provide a simple way to evaluate HR variability visually. The relation of Lorenz scatterplots to frequency-domain HR variability was examined in 75 Holter recordings and in simulated HR trends. The length of Lorenz scatterplots was double-exponentially correlated with total frequency and very-low frequency powers, with correlation coefficients (r) of 0.88. The width of Lorenz scatterplots was highly correlated with the high frequency power (r = 0.98). The sum of the width and length of Lorenz scatterplots was highly correlated with the total frequency power (r = 0.92). Identical results were obtained when simulated HR trends were used. In conclusion, Lorenz scatterplots provide a simple way to estimate the frequency-domain HR variability.

Effects of Cilostazol on Heart Rate and Its Variability in Patients with Sick Sinus Syndrome

ObjectiveHeart rate (HR) variability is an important factor for the prognosis of heart disease. We examined the effects of cilostazol, a quinolone derivative, on HR and HR variability in patients with sick sinus syndrome.DesignNon-blind sequential single-group study.Patients12 patients, aged 53 to 84 years, with type I or II sick sinus syndrome classified according to the Rubenstein system.MethodsPatients received cilostazol (100 or 200 mg/day) orally for at least 2 months, and 24-hour ambulatory electrocardiogram monitoring was performed before and after the start of cilostazol administration. Plasma atrial natriuretic polypeptide (ANP) levels and cardiothoracic ratio were also measured as markers of heart failure. Twelve age- and gender-matched volunteers were used for control measurements of HR variability.ResultsThe mean HR and minimum HR were significantly increased, by an average of 15 and 10 beats/min, respectively, at 8.6 ± 2.5 weeks (mean ± SD) after the start of cilostazol treatment. The number of pauses (defined as an RR interval >2.5 sec) was significantly decreased. The circadian variation of HR, determined by cosine fitting, was increased by cilostazol treatment and was not different from that of the controls. The time-domain and frequency-domain variability of HR were changed to within or closer to within the control ranges. Plasma ANP level and cardiothoracic ratio were significantly decreased after the initiation of cilostazol treatment.ConclusionCilostazol improved the slow HR in patients with sick sinus syndrome and ameliorated the HR variability, indicating that cilostazol has therapeutic utility for the treatment of the slow HR associated with sick sinus syndrome.

Comparable effect of aliskiren or a diuretic added on an angiotensin II receptor blocker on augmentation index in hypertension: a multicentre, prospective, randomised study

Background The effects of antihypertensive drug combination therapy on central blood pressure (BP) and augmentation index (AI) have not been fully elucidated. We investigated the effects of the direct renin inhibitor, aliskiren, or a diuretic added to an angiotensin II receptor blocker on AI in patients with essential hypertension. Methods A 24-week, prospective, multicentre, randomised, open-label study enrolled 103 patients already treated with valsartan. Participants were randomly allocated to receive either valsartan with aliskiren (V+A), or valsartan with trichlormethiazide (V+T). The primary outcome was the change in AI derived from radial artery tonometry. Secondary outcome measures included systolic and diastolic BP, cardio-ankle vascular index (CAVI, which reflects arterial stiffness) and urinary 8-hydroxydeoxyguanosine concentration. Results After 24 weeks, systolic and diastolic BP were significantly reduced in both groups to a broadly comparable extent. There was no significant difference in AI at the end of the study between the V+A group and the V+T group (between-group difference: −2.3%, 95% CI −6.9% to 2.2%, p=0.31). Central BP at the end of the study also did not differ between the two groups (p=0.62). There was no significant difference in the CAVI between the groups at the end of the study. Urinary 8-hydroxydeoxyguanosine concentration was significantly lower in the V+A group than in the V+T group (p<0.01), suggesting that V+A attenuated oxidative stress more than V+T. Conclusion The combination of valsartan and aliskiren had an effect on AI comparable with that of the combination of valsartan and trichlormethiazide. UMIN Clinical Trial Registration number UMIN000005726.