Seiichiro Sakata

Circadian rhythms of atrioventricular conduction properties in chronic atrial fibrillation with and without heart failure.

OBJECTIVES We examined the circadian variations in atrioventricular (AV) conduction properties during atrial fibrillation (AF) by a technique based on the Lorenz plot of successive ventricular response (VR) intervals and analyzed their relations with clinical features. BACKGROUND The VR interval in chronic AF shows circadian variation, which is attenuated in patients with an increased risk of death. Although the VR interval is determined by the dynamic processes in the AV node randomly stimulated by rapid atrial activity, the circadian variations of the AV conduction properties related to this mechanism are unknown. METHODS In 48 patients with chronic AF, Lorenz plots were generated on overlapping sequential segments of 512 VR intervals in 24-h ambulatory electrocardiograms. For each scatter plot, the 1.0-s intercept of the lower envelope (LE1.0) of the plot and the degree of scatter above the envelope (root mean square difference from the envelope [scattering index]) were measured for estimating AV node refractoriness and concealed AV conduction, respectively. RESULTS In all patients, a significant circadian rhythm was observed for the average VR interval, LE1.0 and scattering index, with an acrophase occurring at night. The mesor, amplitude and acrophase of LE1.0 and the scattering index closely and independently correlated with the corresponding rhythm variables of the average VR interval (partial r2 0.98, 0.86 and 0.68 for LE1.0 and 0.98, 0.92 and 0.92 for scattering index). The amplitudes of these measures were lower in patients with congestive heart failure (CHF) even after adjustment for the effects of age, duration of AF, medications, left atrial diameter and blood pressure (p < 0.01 for all). CONCLUSIONS These results suggest that 1) both AV node refractoriness and the degree of concealed AV conduction during AF may show a circadian rhythm; 2) the circadian rhythms of these properties may independently contribute to the circadian variation of the VR interval; and 3) these circadian rhythms may be attenuated in patients with CHF.

Critical Scale Invariance in a Healthy Human Heart Rate

We demonstrate the robust scale-invariance in the probability density function (PDF) of detrended healthy human heart rate increments, which is preserved not only in a quiescent condition, but also in a dynamic state where the mean level of the heart rate is dramatically changing. This scale-independent and fractal structure is markedly different from the scale-dependent PDF evolution observed in a turbulentlike, cascade heart rate model. These results strongly support the view that a healthy human heart rate is controlled to converge continually to a critical state.

Spectral characteristics of ventricular response to atrial fibrillation

To investigate the spectral characteristics of the fluctuation in ventricular response during atrial fibrillation (AF), R-R interval time series obtained from ambulatory electrocardiograms were analyzed in 45 patients with chronic AF and in 30 age-matched healthy subjects with normal sinus rhythm (SR). Although the 24-h R-R interval spectrum during SR showed a 1/f noise-like downsloping linear pattern when plotted as log power against log frequency, the spectrum during AF showed an angular shape with a breakpoint at a frequency of 0.005 +/- 0.002 Hz, by which the spectrum was separated into long-term and short-term components with different spectral characteristics. The short-term component showed a white noise-like flat spectrum with a spectral exponent (absolute value of the regression slope) of 0.05 +/- 0.08 and an intercept at 10(-2) Hz of 4.9 +/- 0.3 log(ms2/Hz). The long-term component had a 1/f noise-like spectrum with a spectral exponent of 1.26 +/- 0.40 and an intercept at 10(-4) Hz of 7.0 +/- 0.3 log(ms2/Hz), which did not differ significantly from those for the spectrum during SR in the same frequency range [spectral exponent, 1.36 +/- 0.06; intercept at 10(-4) Hz, 7.1 +/- 0.3 log(ms2/Hz)]. The R-R intervals during AF may be a sequence of uncorrelated values over the short term (within several minutes). Over the longer term, however, the R-R interval fluctuation shows the long-range negative correlation suggestive of underlying regulatory processes, and spectral characteristics indistinguishable from those for SR suggest that the long-term fluctuations during AF and SR may originate from similar dynamics of the cardiovascular regulatory systems.

Reduced Ventricular Response Irregularity Is Associated With Increased Mortality in Patients With Chronic Atrial Fibrillation

BACKGROUND-Variations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined. METHODS AND RESULTS-In 107 patients with chronic AF (age, 64+/-9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEn(b-b) and ApEn(m-m)]). During a follow-up period of 33+/-16 months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and 2 from malignancies. Reductions in all VRI variability and irregularity measures were associated with an increased risk for cardiac death but not for fatal stroke. A significant association with cardiac death was also found for ejection fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1% decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26. 3). After adjustment for these clinical variables, all irregularity measures except symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD decrement: Shannon entropy of histogram, 2. 03 [1.14 to 3.61]; ApEn(b-b), 1.72 [1.14 to 2.60]; and ApEn(m-m), 1. 90 [1.03 to 3.52]); however, the predictive power of variability measures was no longer significant. When the patients were stratified with the 33rd and 67th percentile values of ApEn(b-b) (1. 83 and 1.94, respectively), the 5-year cardiac mortality rates for the upper, middle, and lower tertiles were 0%, 13%, and 43%, respectively (log-rank test, P=0.04). CONCLUSIONS-Reduced VRI irregularity in a 24-hour ambulatory ECG has an independent prognostic value for cardiac mortality during long-term follow-up in patients with chronic AF.

1/f scaling in heart rate requires antagonistic autonomic control

We present systematic evidence for the origins of 1/f -type temporal scaling in human heart rate. The heart rate is regulated by the activity of two branches of the autonomic nervous system: the parasympathetic (PNS) and the sympathetic (SNS) nervous systems. We examine alterations in the scaling property when the balance between PNS and SNS activity is modified, and find that the relative PNS suppression by congestive heart failure results in a substantial increase in the Hurst exponent H towards random-walk scaling 1/ f(2) and a similar breakdown is observed with relative SNS suppression by primary autonomic failure. These results suggest that 1/f scaling in heart rate requires the intricate balance between the antagonistic activity of PNS and SNS.

Aging and spectral characteristics of the nonharmonic component of 24-h heart rate variability

To examine whether heart rate variability (HRV) during daily life shows power law behavior independently of age and interindividual difference in the total power, log-log scaled coarse-graining spectra of the nonharmonic component of 24-h HRV were studied in 62 healthy men (age 21-79 yr). The spectra declined with increasing frequency in all subjects, but they appeared as broken lines slightly bending downward, particularly in young subjects with a large total power. Regression of the spectrum by a broken line with a single break point revealed that the spectral exponent (β) was greater in the region below than above the break point (1.63 ± 0.23 vs. 0.96 ± 0.21, P < 0.001). The break point frequency increased with age ( r = 0.51, P < 0.001) and β correlated with age negatively below the break point ( r = 0.39) and positively above the break point ( r = 0.70). The contribution to interindividual difference in total power was greater from the differences in the power spectral density at frequencies closer to both ends of the frequency axis and minimal from that at -3.25 log(Hz), suggesting hingelike movement of the spectral shape at this frequency with the difference in total power. These characteristics of the 24-h HRV spectrum were simulated by an artificial signal generated by adding two noises with different β values. Given that the power law assumption is fundamental to the analysis of dynamics through the log-log scaled spectrum, our observations are substantial for physiological and clinical studies of the heartbeat dynamic during daily life and suggest that the nonharmonic component of HRV in normal subjects during daily life may include at least two 1/ f β fluctuations that differ in dynamics and age dependency.To examine whether heart rate variability (HRV) during daily life shows power law behavior independently of age and interindividual difference in the total power, log-log scaled coarse-graining spectra of the nonharmonic component of 24-h HRV were studied in 62 healthy men (age 21-79 yr). The spectra declined with increasing frequency in all subjects, but they appeared as broken lines slightly bending downward, particularly in young subjects with a large total power. Regression of the spectrum by a broken line with a single break point revealed that the spectral exponent (beta) was greater in the region below than above the break point (1.63 +/- 0. 23 vs. 0.96 +/- 0.21, P < 0.001). The break point frequency increased with age (r = 0.51, P < 0.001) and beta correlated with age negatively below the break point (r = 0.39) and positively above the break point (r = 0.70). The contribution to interindividual difference in total power was greater from the differences in the power spectral density at frequencies closer to both ends of the frequency axis and minimal from that at -3.25 log(Hz), suggesting hingelike movement of the spectral shape at this frequency with the difference in total power. These characteristics of the 24-h HRV spectrum were simulated by an artificial signal generated by adding two noises with different beta values. Given that the power law assumption is fundamental to the analysis of dynamics through the log-log scaled spectrum, our observations are substantial for physiological and clinical studies of the heartbeat dynamic during daily life and suggest that the nonharmonic component of HRV in normal subjects during daily life may include at least two 1/fbeta fluctuations that differ in dynamics and age dependency.

Loss of Fractal Heart Rate Dynamics in Depressive Hemodialysis Patients

Objective: To assess the relationship between depression, reduced heart rate (HR) variability, and altered HR dynamics among patients with end-stage renal disease who are receiving hemodialysis (HD) therapy. Methods: We analyzed the 24-hour electrocardiograms of 119 outpatients receiving chronic HD. HR variability was quantified with the standard deviation of normal-to-normal R-R intervals, the triangular index, and the powers of the high- (HF), low- (LF), very-low (VLF), and ultra-low frequency (ULF) components. Nonlinear HR dynamics was assessed with the short-term (α1) and long-term (α2) scaling exponents of the detrended fluctuation analysis and approximate entropy. The depression level was assessed using the Beck Depression Inventory, Second Edition (BDI-II). HR variability and dynamics measurements were compared by gender, diabetes, and depression with adjustment for age and serum albumin concentration. Results: Most indices of HR variability and dynamics were negatively correlated with age, serum albumin concentration, depression score, and were lower in women and patients with diabetes. The α2 was inversely associated with these variables. Depressed men had significantly lower HF, LF, VLF, and marginally lower ULF than nondepressed persons after adjustment for diabetes and other covariates; no difference in depression was observed in women. The α2 showed marginally significant difference in depression independent from gender and diabetes. Conclusions: Among the patients who received HD, depression is associated with reduced HR variability and loss of fractal HR dynamics. However, the influence of depression on HR variability may vary by gender and physiological backgrounds. Further prospective studies are necessary to confirm their association with poor prognosis. CHD = coronary heart disease; HR = heart rate; DFA = detrended fluctuation analysis; ApEn = approximate entropy; HD = hemodialysis; ESRD = end-stage renal disease; NKC = Nagoya Kidney Center; AMI = acute myocardial infarction; ECG = electrocardiography; PCR = protein catabolic rate; SDNN = standard deviation of normal-to-normal R-R intervals; HF = high-frequency band; LF = low-frequency band; VLF = very-low-frequency band; ULF = ultra-low-frequency band; SD = standard deviation; mNN = mean normal-to-normal R-R intervals; BDI = Beck Depression Inventory; DSM = Diagnostic and Statistical Manual of Mental Disorders; ANCOVA = analysis of covariance; GLM = general linear model.

Circadian rhythm of atrioventricular conduction predicts long-term survival in patients with chronic atrial fibrillation

The R–R interval of the electrocardiogram during atrial fibrillation (AF) appears absolutely irregular. However, the Poincaré plot of the R–R interval reveals a sector shape of distribution that is unique to AF. Furthermore, the height of lower envelope (LE1.0) of the distribution and the degree of scatter above the envelope (scattering index) may reflect the refractoriness and concealment of atrioventricular (AV) conduction, respectively. We previously observed that both the LE1.0 and scattering index show clear circadian rhythms in patients with chronic AF and that the rhythms are blunted in those with congestive heart failure and chronic AF. In the present study, we examined if the blunted circadian rhythm of the AV conduction has prognostic value in patients with chronic AF. We studied a retrospective cohort of 120 patients who underwent 24h Holter monitoring at baseline. During an observation period of 33±16 mon, there were 25 deaths (21%) including 13 cardiac and 8 stroke deaths. All patients showed significant circadian rhythms in both LE1.0 and scattering index with acrophases occurring at night; however, patients dying subsequently from cardiac causes, but not those from fatal stroke were blunted in the circadian rhythms (the amplitudes were <55% of those in surviving patients). Furthermore, the reduced circadian amplitude of scattering index was an increased risk for cardiac death even after adjustment of coexisting cardiovascular risks [adjusted relative risk (95% confidence interval) per 1-SD decrement, 4.24 (1.54–11.6)]. When patients were divided by the circadian amplitude of the scattering index of 36.5 msec (mean minus 1-SD), the 5yr cardiac mortality below and above the cutoff was 57 and 6%, respectively (log-rank test, p<0.001). We conclude that the blunted circadian rhythm of AV conduction is an independent risk for cardiac death in patients with chronic AF.

Dual Antagonistic Autonomic Control Necessary for 1/f Scaling in Heart Rate

Although the phenomenon of 1/f noise in heart rate has been known for more than two decades, ours has been the first systematic study showing the importance of antagonistic dynamics between the two branches of the autonomic nervous system

745 ESTIMATING AUTONOMIC NERVE ACTIVITY USING ABPM IN PATIENTS WITH CKD

Objectives: We have studied circadian blood pressure (BP) rhythm in patients with CKD using the night/day ratio of BP obtained by 24-h ABPM, and postulated that impaired renal sodium excretion causes insidious sodium-fluid retention to promote night-time hypertension. Emerging evidences suggest that, in addition to sodium-fluid retention and hyperactivity of the renin-angiotensin-aldosterone system, increased autonomic nervous system activity contributes to the genesis of hypertension in CKD. Methods: study 1. Relationship between the heart rate variability (HRV) obtained by Holter ECG (e.g., LF/HF, HF) and variables obtained by ABPM [e.g., day/night HR ratio, coefficient of variation (CV) of HR] were investigated.study 2. We examined the relationship between day/night ratios of HR and HF, as well as CV, before and during 8 week treatment with angiotensin II receptor blocker (ARB), which are known to suppress the sympathetic nerve activity (olmesartan 2.5-40 mg/day) in 45 CKD patients. Results: study 1. 24-h HF, ln(ms2) directly correlated with day/night HR ratio and CV of HR. study 2. ARB increased the day/night HR ratio (1.17 to 1.21, p = 0.04), and CV of HR (16 to 17%, NS). Day/night ratio of (HR/MAP) correlated inversely with the GFR (p = 0.04). This correlation did not persist during the treatment with ARB. Conclusions: The present study demonstrated that the increase in the CV and day/night ratio of HR provided by ABPM indicate the elevated parasympathetic activity shown by Holter ECG, and that autonomic nervous system activityis activated as renal function deteriorates, and ARB may suppress its activation.