Men-Tzung Lo

The Prognostic Value of Non-Linear Analysis of Heart Rate Variability in Patients with Congestive Heart Failure—A Pilot Study of Multiscale Entropy

Aims The influences of nonstationarity and nonlinearity on heart rate time series can be mathematically qualified or quantified by multiscale entropy (MSE). The aim of this study is to investigate the prognostic value of parameters derived from MSE in the patients with systolic heart failure. Methods and Results Patients with systolic heart failure were enrolled in this study. One month after clinical condition being stable, 24-hour Holter electrocardiogram was recording. MSE as well as other standard parameters of heart rate variability (HRV) and detrended fluctuation analysis (DFA) were assessed. A total of 40 heart failure patients with a mea age of 56±16 years were enrolled and followed-up for 684±441 days. There were 25 patients receiving β-blockers treatment. During follow-up period, 6 patients died or received urgent heart transplantation. The short-term exponent of DFA and the slope of MSE between scale 1 to 5 were significantly different between patients with or without β-blockers (p = 0.014 and p = 0.028). Only the area under the MSE curve for scale 6 to 20 (Area6–20) showed the strongest predictive power between survival (n = 34) and mortality (n = 6) groups among all the parameters. The value of Area6–20 21.2 served as a significant predictor of mortality or heart transplant (p = 0.0014). Conclusion The area under the MSE curve for scale 6 to 20 is not relevant to β-blockers and could further warrant independent risk stratification for the prognosis of CHF patients.

Suprachiasmatic neuron numbers and rest–activity circadian rhythms in older humans

The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day–night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age‐matched controls is correlated with the number of vasoactive intestinal peptide–expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging‐ and AD‐related circadian disturbances. Ann Neurol 2015;78:317–322

Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma.

CONTEXT Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and is associated with more prominent vascular stiffness and atherosclerosis. However, the effect of adrenalectomy on reversibility of vascular damage is unclear. OBJECTIVE Our objective was to investigate the vascular changes and possibility of reversibility after adrenalectomy in PA patients. METHODS We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that received adrenalectomy from October 2006 to December 2008 and 21 patients with essential hypertension (EH) were enrolled as the control group. Carotid intima media thickness (CIMT) measurement by B-mode ultrasound of the right common carotid arteries and pulse wave velocity (PWV) measurement including brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV) were performed in both groups. The follow-up measurements were performed one-year after adrenalectomy in APA group. RESULTS APA patients had significantly higher diastolic blood pressure, plasma aldosterone concentration (PAC) and aldosterone-renin ratio (ARR), but lower serum potassium level and plasma renin activity (PRA) than EH patients. APA patients had significantly higher CIMT (0.64±0.13 vs. 0.53±0.10 mm, p=0.006), higher baPWV (1589±296 vs. 1405±187 cm/s, p=0.024) and haPWV (1095±150 vs. 987±114 cm/s, p=0.013) comparing with EH patients. One-year after adrenalectomy, CIMT reduced significantly from 0.64±0.13 mm to 0.59±0.14 mm (p=0.014), and baPWV and haPWV also showed significant reduction (baPWV, 1589±296 to 1463±188 cm/s, p=0.035; haPWV, 1095±150 to 1017±109 cm/s, p=0.019). CONCLUSION APA patients have higher degree of early atherosclerosis and vascular stiffness. Adrenalectomy not only corrects the high blood pressure and biochemical parameters but also reverse adverse vascular change in APA patients.

Prevalence, Characteristics, Mapping, and Catheter Ablation of Potential Rotors in Nonparoxysmal Atrial Fibrillation

Background— Identification of critical atrial substrates in patients with nonparoxysmal atrial fibrillation (AF) failing to respond to pulmonary vein isolation is important. This study investigated the signal characteristics, substrate nature, and ablation results of rotors during AF. Methods and Results— In total, 53 patients (age=55±8), 31 with persistent AF and 22 with long-lasting AF, underwent pulmonary vein isolation and substrate modification of complex fractionated atrial electrograms. Small-radius-reentrant rotors were identified from signal analyses of the dominant frequency and fractionation interval and nonlinear analyses (newly developed, beat-to-beat nonlinear measurement of the repetitiveness of the electrogram morphology >6 seconds). In 15% of the patients, activation maps demonstrated occurrences of rotor-like small-radius reentrant circuits (n=9; 1.1 per patient; cycle length=110±21 ms; diameter=11±6 mm) with fibrillation occurring outside these areas. Rotors were identified by conventional point-by-point mapping and signal analyses and were subsequently eradicated by catheter ablation in these patients. Persistent AF for <1 year, a smaller left atrial size, substrates with higher mean voltages and shorter total activation durations predicted a higher incidence of rotors (all P<0.05). In the multivariable model, areas of reentrant circuits exhibited a higher dominant frequency, kurtosis, and higher degree of a beat-to-beat electrogram similarity than areas without or outside the rotors (all P<0.05). Conclusions— Rotor-like re-entry with fibrillatory conduction was found in a limited number of patients with nonparoxysmal AF after pulmonary vein isolation. Those areas were characterized by rapid repetitive activity with a high degree of electrogram similarity.

Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimers disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients.

Revealing the brain's adaptability and the transcranial direct current stimulation facilitating effect in inhibitory control by multiscale entropy

The abilities to inhibit impulses and withdraw certain responses are critical for humans survival in a fast-changing environment. These processes happen fast, in a complex manner, and sometimes are difficult to capture with fMRI or mean electrophysiological brain signal alone. Therefore, an alternative measure that can reveal the efficiency of the neural mechanism across multiple timescales is needed for the investigation of these brain functions. The present study employs a new approach to analyzing electroencephalography (EEG) signal: the multiscale entropy (MSE), which groups data points with different timescales to reveal any occurrence of repeated patterns, in order to theoretically quantify the complexity (indicating adaptability and efficiency) of neural systems during the process of inhibitory control. From this MSE perspective, EEG signals of successful stop trials are more complex and information rich than that of unsuccessful stop trials. We further applied transcranial direct current stimulation (tDCS), with anodal electrode over presupplementary motor area (preSMA), to test the relationship between behavioral modification with the complexity of EEG signals. We found that tDCS can further increase the EEG complexity of the frontal lobe. Furthermore, the MSE pattern was found to be different between high and low performers (divided by their stop-signal reaction time), where the high-performing group had higher complexity in smaller scales and less complexity in larger scales in comparison to the low-performing group. In addition, this between-group MSE difference was found to interact with the anodal tDCS, where the increase of MSE in low performers benefitted more from the anodal tDCS. Together, the current study demonstrates that participants who suffer from poor inhibitory control can efficiently improve their performance with 10min of electrical stimulation, and such cognitive improvement can be effectively traced back to the complexity within the EEG signals via MSE analysis, thereby offering a theoretical basis for clinical intervention via tDCS for deficits in inhibitory control.

Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism.

Objective: Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. However, the reversibility of cardiac fibrosis is still unclear. Our objective was to investigate myocardial fibrosis in primary aldosteronism patients and its change after surgery. Method: We prospectively analyzed 20 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008 and 20 patients with essential hypertension were enrolled as the control group. Plasma carboxy-terminal propeptide of procollagen type I (PICP) determination and echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS) were performed in both groups and 1 year after operation in the APA group. Results: APA patients had significantly higher SBP and DBP, higher plasma aldosterone concentration (PAC), higher aldosterone–renin ratio (ARR), lower serum potassium levels, and lower plasma renin activity (PRA) than patients with essential hypertension. In echocardiography, APA patients had a higher left ventricular mass index than essential hypertension patients. APA patients had significantly lower CVIBS (6.2 ± 1.5 vs. 8.7 ± 2.0 dB, P < 0.001) and higher plasma PICP levels (107 ± 27 vs. 85 ± 24 &mgr;g/l, P = 0.009) than essential hypertension patients. In the correlation study, CVIBS is correlated with log-transformed PRA and log-transformed ARR and PICP is correlated with log-transformed PRA, log-transformed PAC, and log-transformed ARR. One year after adrenalectomy, CVIBS increased significantly (6.2 ± 1.5 to 7.3 ± 1.7 dB, P = 0.033) and plasma PICP levels decreased (107 ± 27 vs. 84 ± 28 &mgr;g/l, P = 0.026). Conclusion: Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy.

ON HILBERT SPECTRAL REPRESENTATION: A TRUE TIME-FREQUENCY REPRESENTATION FOR NONLINEAR AND NONSTATIONARY DATA

As the original definition on Hilbert spectrum was given in terms of total energy and amplitude, there is a mismatch between the Hilbert spectrum and the traditional Fourier spectrum, which is defined in terms of energy density. Rigorous definitions of Hilbert energy and amplitude spectra are given in terms of energy and amplitude density in the time-frequency space. Unlike Fourier spectral analysis, where the resolution is fixed once the data length and sampling rate is given, the time-frequency resolution could be arbitrarily assigned in Hilbert spectral analysis (HSA). Furthermore, HSA could also provide zooming ability for detailed examination of the data in a specific frequency range with all the resolution power. These complications have made the conversion between Hilbert and Fourier spectral results difficult and the conversion formula is elusive until now. We have derived a simple relationship between them in this paper. The conversion factor turns out to be simply the sampling rate for the full resolution cases. In case of zooming, there is another additional multiplicative factor. The conversion factors have been tested in various cases including white noise, delta function, and signals from natural phenomena. With the introduction of this conversion, we can compare HSA and Fourier spectral analysis results quantitatively.

Detrended fluctuation analysis predicts successful defibrillation for out-of-hospital ventricular fibrillation cardiac arrest

AIMS Repeated failed shocks for ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OOHCA) can worsen the outcome. It is very important to rapidly distinguish between early and late VF. We hypothesised that VF waveform analysis based on detrended fluctuation analysis (DFA) can help predict successful defibrillation. METHODS Electrocardiogram (ECG) recordings of VF signals from automated external defibrillators (AEDs) were obtained for subjects with OOHCA in Taipei city. To examine the time effect on DFA, we also analysed VF signals in subjects who experienced sudden cardiac death during Holter study from PhysioNet, a publicly accessible database. Waveform parameters including root-mean-squared (RMS) amplitude, mean amplitude, amplitude spectrum analysis (AMSA), frequency analysis as well as fractal measurements including scaling exponent (SE) and DFA were calculated. A defibrillation was regarded as successful when VF was converted to an organised rhythm within 5s after each defibrillation. RESULTS A total of 155 OOHCA subjects (37 successful and 118 unsuccessful defibrillations) with VF were included for analysis. Among the VF waveform parameters, only AMSA (7.61+/-3.30 vs. 6.30+/-3.13, P=0.028) and DFAalpha2 (0.38+/-0.24 vs. 0.49+/-0.24, P=0.013) showed significant difference between subjects with successful and unsuccessful defibrillation. The area under the curves (AUCs) for AMSA and DFAalpha2 was 0.63 (95% confidence interval (CI)=0.52-0.73) and 0.65 (95% CI=0.54-0.75), respectively. Among the waveform parameters, only DFAalpha2, SE and dominant frequency showed significant time effect. CONCLUSIONS The VF waveform analysis based on DFA could help predict first-shock defibrillation success in patients with OOHCA. The clinical utility of the approach deserves further investigation.

Influence of Non-Alcoholic Fatty Liver Disease on Autonomic Changes Evaluated by the Time Domain, Frequency Domain, and Symbolic Dynamics of Heart Rate Variability

Background Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown. Methods Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured. Results Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms2, 4.49 vs 5.21 ms2, respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF). Conclusions NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.