In industrialized countries with aging populations, heart failure affects 0.3%-2% of the general population. The investigation of 24h-ECG recordings revealed the potential of nonlinear indices of heart rate variability (HRV) for enhanced risk stratification in patients with ischemic heart failure (IHF). However, long-term analyses are time-consuming, expensive and delay the initial diagnosis. The objective of this study was to investigate whether 30min short-term HRV analysis is sufficient for comparable risk stratification in IHF in comparison to 24h-HRV analysis. From 256 IHF patients (221 at low risk (IHFLR) and 35 at high risk (IHFHR)) a) 24h beat-to-beat time series b) the first 30min segment c) the 30min most stationary day segment and d) the 30min most stationary night segment were investigated. We calculated linear (time and frequency domain) and nonlinear HRV analysis indices. Optimal parameter sets for risk stratification in IHF were determined for 24 hours and for each 30min segment by applying discriminant analysis on significant clinical and non-clinical indices. Long- and short-term HRV indices from frequency domain and particularly from nonlinear dynamics revealed high univariate significances (p

Schizophrenia is a severe mental disorder associated with a significantly increased cardiovascular mortality rate. However, the underlying mechanisms leading to this cardiovascular disease (CVD) are not fully known. Therefore, the objective of this study was to characterize the cardiorespiratory influence by investigating heart rate, respiration and the causal strength and direction of cardiorespiratory coupling (CRC), based mainly on entropy measures. We investigated 23 non-medicated patients with schizophrenia (SZ), comparing them to 23 age- and gender-matched healthy controls (CO). A significantly reduced complexity was found for the heart rate and a significantly increased complexity in respiration and CRC in SZ patients when compared to corresponding measurements from CO (p < 0.001). CRC analyses revealed a clear coupling, with a driver-responder relationship from respiration to heart rate in SZ patients. Moreover, a slight driver-responder relationship from heart rate to respiration could be recognized. These findings lead to the assumption that SZ should be considered to be a high-risk group for CVD. We hypothesize that the varying cardiorespiratory regulation contributes to the increased risk for cardiac mortality. Therefore, regular monitoring of the cardiorespiratory status of SZ is suggested to identify autonomic regulation impairment at an early stage—to develop timely and effective treatment and intervention strategies.

The multivariate analysis of coupling pathways within physiological (sub)systems focusing on identifying healthy and diseased conditions. In this study, we investigated a part of the central-autonomic-network (CAN) in 17 patients suffering from schizophrenia (SZO) compared to 17 age–gender matched healthy controls (CON) applying linear and nonlinear causal coupling approaches (normalized short time partial directed coherence, multivariate transfer entropy). Therefore, from all subjects continuous heart rate (successive beat-to-beat intervals, BBI), synchronized maximum successive systolic blood pressure amplitudes (SYS), synchronized calibrated respiratory inductive plethysmography signal (respiratory frequency, RESP), and the power P_EEG of frontal EEG activity were investigated for 15 min under resting conditions. The CAN revealed a bidirectional coupling structure, with central driving towards blood pressure (SYS), and respiratory driving towards P_EEG. The central-cardiac, central-vascular, and central-respiratory couplings are more dominated by linear regulatory mechanisms than nonlinear ones. The CAN showed significantly weaker nonlinear central-cardiovascular and central-cardiorespiratory coupling pathways, and significantly stronger linear central influence on the vascular system, and on the other hand significantly stronger linear respiratory and cardiac influences on central activity in SZO compared to CON, and thus, providing better understanding of the interrelationship of central and autonomic regulatory mechanisms in schizophrenia might be useful as a biomarker of this disease.

Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDC_HR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDC_LR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDC_HR patients presented lowered HRV and increased BPV compared to both IDC_LR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDC_LR vs. IDC_HR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the aforementioned models, and achieved 94.4% accuracy. In conclusion, this study introduced a novel method for SCD risk stratification for IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We have uncovered some of the complex interactions within the autonomic regulation in this type of patient.

In this study, the linear method of extended partial directed coherence (ePDC) was applied to establish the temporal dynamic behavior of cardiovascular and cardiorespiratory interactions during orthostatic stress at a 70° head-up tilt (HUT) test on young age-matched healthy subjects and patients with orthostatic intolerance (OI), both male and female. Twenty 5-min windows were used to analyze the minute-wise progression of interactions from 5 min in a supine position (baseline, BL) until 18 min of the orthostatic phase (OP) without including pre-syncopal phases. Gender differences in controls were present in cardiorespiratory interactions during OP without compromised autonomic regulation. However in patients, analysis by ePDC revealed considerable dynamic alterations within cardiovascular and cardiorespiratory interactions over the temporal course during the HUT test. Considering the young female patients with OI, the information flow from heart rate to systolic blood pressure (mechanical modulation) was already increased before the tilt-up, the information flow from systolic blood pressure to heart rate (neural baroreflex) increased during OP, while the information flow from respiration to heart rate (respiratory sinus arrhythmia) decreased during the complete HUT test. Findings revealed impaired cardiovascular interactions in patients with orthostatic intolerance and confirmed the usefulness of ePDC for causality analysis.

Background: Newborn mammals suffering from moderate hypoxia during or after birth are able to compensate a transitory lack of oxygen by adapting their vital functions. Exposure to hypoxia leads to an increase in the sympathetic tone causing cardio-respiratory response, peripheral vasoconstriction and vasodilatation in privileged organs like the heart and brain. However, there is only limited information available about the time and intensity changes of the underlying complex processes controlled by the autonomic nervous system.Methods: In this study an animal model involving seven piglets was used to examine an induced state of circulatory redistribution caused by moderate oxygen deficit. In addition to the main focus on the complex dynamics occurring during sustained normocapnic hypoxia, the development of autonomic regulation after induced reoxygenation had been analysed. For this purpose, we first introduced a new algorithm to prove stationary conditions in short-term time series. Then we investigated a multitude of indices from heart rate and blood pressure variability and from bivariate interactions, also analysing respiration signals, to quantify the complexity of vegetative oscillations influenced by hypoxia.Results: The results demonstrated that normocapnic hypoxia causes an initial increase in cardiovascular complexity and variability, which decreases during moderate hypoxia lasting one hour (p < 0.004). After reoxygenation, cardiovascular complexity parameters returned to pre-hypoxic values (p < 0.003), however not respiratory-related complexity parameters.Conclusions: In conclusion, indices from linear and nonlinear dynamics reflect considerable temporal changes of complexity in autonomous cardio-respiratory regulation due to normocapnic hypoxia shortly after birth. These findings might be suitable for non-invasive clinical monitoring of hypoxia-induced changes of autonomic regulation in newborn humans.