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Heart failure (HF) is a major cardiovascular disease worldwide, and the early detection and diagnosis remain challenges. Recently, heart rhythm complexity analysis, derived from non-linear heart rate variability (HRV) analysis, has been proposed as a non-invasive method to detect diseases and predict outcomes. In this study, we aimed to investigate the diagnostic value of heart rhythm complexity in HF patients. We prospectively analyzed 55 patients with symptomatic HF with impaired left ventricular ejection fraction and 97 participants without HF symptoms and normal LVEF as controls. Traditional linear HRV parameters and heart rhythm complexity including detrended fluctuation analysis (DFA) and multiscale entropy (MSE) were analyzed. The traditional linear HRV, MSE parameters and DFAα1 were significantly lower in HF patients compared with controls. In regression analysis, DFAα1 and MSE scale 5 remained significant predictors after adjusting for multiple clinical variables. Among all HRV parameters, MSE scale 5 had the greatest power to differentiate the HF patients from the controls in receiver operating characteristic curve analysis (area under the curve: 0.844). In conclusion, heart rhythm complexity appears to be a promising tool for the detection and diagnosis of HF.

Pulmonary hypertension is a fatal disease, however reliable prognostic tools are lacking. Heart rhythm complexity analysis is derived from non-linear heart rate variability (HRV) analysis and has shown excellent performance in predicting clinical outcomes in several cardiovascular diseases. However, heart rhythm complexity has not previously been studied in pulmonary hypertension patients. We prospectively analyzed 57 patients with pulmonary hypertension (31 with pulmonary arterial hypertension and 26 with chronic thromboembolic pulmonary hypertension) and compared them to 57 age- and sex-matched control subjects. Heart rhythm complexity including detrended fluctuation analysis (DFA) and multiscale entropy (MSE) and linear HRV parameters were analyzed. The patients with pulmonary hypertension had significantly lower mean RR, SDRR, pNN20, VLF, LF, LF/HF ratio, DFAα1, MSE slope 5, scale 5, area 1–5 and area 6–20 compared to the controls. Receiver operating characteristic curve analysis showed that heart rhythm complexity parameters were better than traditional HRV parameters to predict pulmonary hypertension. Among all parameters, scale 5 had the greatest power to differentiate the pulmonary hypertension patients from controls (AUC: 0.845, P

Measures characterizing the complexity of heart rate (HR) dynamics have been informative in predicting age- and disease-related decline in cardiovascular health, but few studies have evaluated whether mind-body exercise can impact HR complexity. This study evaluated the effects of long-term Tai Chi (TC) practice on the complexity of HR dynamics using an observational comparison of TC experts and age- and gender-matched TC-naïve individuals. Shorter-term effects of TC were assessed by randomly assigning TC-naïve participants to either TC group to receive six months of TC training or to a waitlist control group. 23 TC experts (age = 63.3 ± 8.0 y; 24.6 ± 12.0 y TC experience) and 52 TC-naïve (age = 64.3 ± 7.7 y) were enrolled. In cross-sectional analyses, TC experts had a higher overall complexity index (CI, p = 0.004) and higher entropy at multiple individual time scales (p

Abdominal aorta calcification (AAC) has been associated with clinical outcomes in peritoneal dialysis (PD) patients. Heart rhythm complexity analysis has been shown to be a promising tool to predict outcomes in patients with cardiovascular disease. In this study, we aimed to analyze the association between heart rhythm complexity and AAC in PD patients. We prospectively analyzed 133 PD patients. Heart rhythm complexity including detrended fluctuation analysis and multiscale entropy was performed. In linear analysis, the patients in the higher AAC group (AAC ≥15%) had a significantly lower standard deviation of normal RR intervals, very low frequency, low frequency, high frequency and low/high frequency ratio. In non-linear analysis, DFAα1, slope 1–5, scale 5 and area 6–20 were significantly lower in the patients with higher AAC. Receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power to differentiate these two groups. Multivariate logistic regression analysis showed that DFAα1 and HbA1c were significantly associated with higher AAC ratio. Adding DFAα1 significantly improved the discriminatory power of the linear parameters in both net reclassification improvement and integrated discrimination improvement models. In conclusion, DFAα1 is highly associated with AAC and a potential cardiovascular marker in PD patients.

Metabolic syndrome (MetS) has been associated with chronic damage to the cardiovascular system. This study aimed to evaluate early stage cardiac autonomic dysfunction with electrocardiography (ECG)-based measures in MetS subjects. During 2012–2013, 175 subjects with MetS and 226 healthy controls underwent ECG recordings of at least 4 hours starting in the morning with ambulatory one-lead ECG monitors. MetS was diagnosed using the criteria defined in the Adult Treatment Panel III, with a modification of waist circumference for Asians. Conventional heart rate variability (HRV) analysis, and complexity index (CI1–20) calculated from 20 scales of entropy (multiscale entropy, MSE), were compared between subjects with MetS and controls. Compared with the healthy controls, subjects with MetS had significantly reduced HRV, including SDNN and pNN20 in time domain, VLF, LF and HF in frequency domain, as well as SD2 in Poincaré analysis. MetS subjects have significantly lower complexity index (CI1–20) than healthy subjects (1.69 ± 0.18 vs. 1.77 ± 0.12, p 1–20 (r = −0.27, p

Drug resistance caused by excessive and indiscriminate antibiotic usage has become a serious public health problem. The need of finding new antibacterial drugs is more urgent than ever before. Tyrosyl-tRNA synthase was proved to be a potent target in combating drug-resistant bacteria. In silico methodologies including molecular docking and 3D-QSAR were employed to investigate a series of newly reported tyrosyl-tRNA synthase inhibitors of furanone derivatives. Both internal and external cross-validation were conducted to obtain high predictive and satisfactory CoMFA model (q2 = 0.611, r2 pred = 0.933, r2 m = 0.954) and CoMSIA model (q2 = 0.546, r2 pred = 0.959, r2 m = 0.923). Docking results, which correspond with CoMFA/CoMSIA contour maps, gave the information for interactive mode exploration. Ten new molecules designed on the basis of QSAR and docking models have been predicted more potent than the most active compound 3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (15) in the literatures. The results expand our understanding of furanones as inhibitors of tyrosyl-tRNA synthase and could be helpful in rationally designing of new analogs with more potent inhibitory activities.

Heart rhythm complexity analysis has been shown to have good prognostic power in patients with cardiovascular disease. The aim of this study was to analyze serial changes in heart rhythm complexity from the acute to chronic phase of acute myocardial infarction (MI). We prospectively enrolled 27 patients with anterior wall ST segment elevation myocardial infarction (STEMI) and 42 control subjects. In detrended fluctuation analysis (DFA), the patients had significantly lower DFAα2 in the acute stage (within 72 hours) and lower DFAα1 at 3 months and 12 months after MI. In multiscale entropy (MSE) analysis, the patients had a lower slope 5 in the acute stage, which then gradually increased during the follow-up period. The areas under the MSE curves for scale 1 to 5 (area 1–5) and 6 to 20 (area 6–20) were lower throughout the chronic stage. Area 6–20 had the greatest discriminatory power to differentiate the post-MI patients (at 1 year) from the controls. In both the net reclassification improvement and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of the linear parameters to differentiate the post-MI patients from the controls. In conclusion, the patients with STEMI had serial changes in cardiac complexity.

Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1–5) and 6 to 20 (area 6–20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.

Complexity in physiological outputs is believed to be a hallmark of healthy physiological control. How to accurately quantify the degree of complexity in physiological signals with outliers remains a major barrier for translating this novel concept of nonlinear dynamic theory to clinical practice. Here we propose a new approach to estimate the complexity in a signal by analyzing the irregularity of the sign time series of its coarse-grained time series at different time scales. Using surrogate data, we show that the method can reliably assess the complexity in noisy data while being highly resilient to outliers. We further apply this method to the analysis of human heartbeat recordings. Without removing any outliers due to ectopic beats, the method is able to detect a degradation of cardiac control in patients with congestive heart failure and a more degradation in critically ill patients whose life continuation relies on extracorporeal membrane oxygenator (ECMO). Moreover, the derived complexity measures can predict the mortality of ECMO patients. These results indicate that the proposed method may serve as a promising tool for monitoring cardiac function of patients in clinical settings.