Publications

CCBY Intermittent hypoxia (IH) produces autonomic dysfunction that promotes the development of arrhythmia and hypertension in patients with obstructive sleep apnea (OSA). This paper investigated different heart rate variability (HRV) indices in the context of IH using a rat model for OSA. Linear and non-linear HRV parameters were assessed from ultra-short (15-s segments) and short-term (5 min) analyses of heartbeat time-series. Transient changes observed from pre-apnea segments to hypoxia episodes were evaluated, besides the relative and global impact of IH, as a function of its severity. Results showed an overall increase in ultra-short HRV markers as immediate response to hypoxia: standard deviation of normal RR intervals, SDNN=1.2 ms (IQR: 1.1-2.1) vs 1.4 ms (IQR: 1.2-2.2), p=0.015; root mean square of the successive differences, RMSSD=1.7 ms (IQR: 1.5-2.2) vs 1.9 ms (IQR: 1.6-2.4), p=0.031. The power in the very low frequency (VLF) band also showed a significant increase: 0.09 ms2 (IQR: 0.05-0.20) vs 0.16 ms2 (IQR: 0.12-0.23), p=0.016, probably associated with the potentiation of the carotid body chemo-sensory response to hypoxia. Moreover, a clear link between severity of IH and short-term HRV measures was found in VLF and LF power, besides their progressive increase seen throughout the experiment after each apnea sequence. However, only those markers quantifying fragmentation levels in RR series were significantly affected when the experiment ended, as compared to baseline measures: percentage of inflection points, PIP=49% (IQR: 45-51) vs 53% (IQR: 47-53), p=0.031; percentage of short (≥3 RR intervals) accelerated/decelerated segments, PSS=75% (IQR: 51-81) vs 87% (IQR: 51-90), p=0.046. These findings suggest a significant deterioration of cardiac rhythm with a more erratic behavior beyond the normal sinus arrhythmia, that may lead to a future cardiac condition.

JTD Keywords: artificial intelligence, atmospheric modeling, electrocardiography, heart rate variability, hypoxia rat model, intermittent hypoxia, obstructive apneas, protocols, radio access technologies, Artificial intelligence, Atmospheric modeling, Electrocardiography, Heart rate variability, Hypoxia rat model, Intermittent hypoxia, Obstructive apneas, Protocols, Radio access technologies, Rats

In this work, we evaluated a non-linear approach to estimate morphological variations in ECG depolarization, in the context of intermittent hypoxia (IH). Obstructive apnea sequences were provoked for 15 minutes in anesthetized Sprague-Dawley rats, alternating with equal periods of normal breathing, in a recurrent obstructive sleep apnea (OSA) model. Each apnea episode lasted 15 s, while the frequency used for each sequence was randomly selected. Average heartbeats obtained before the start and at the end of each episode, were delineated to extract only the QRS wave. Then, the segmented QRS waves were non-linearly aligned using the dynamic time warping (DWT) algorithm. Morphological QRS changes in both the amplitude and temporal domains were estimated from this alignment procedure. The hypoxic and basal segments were analyzed using ECG (lead I) recordings acquired during the experiment. To assess the effects of IH over time, the changes relative to the basal QRS wave were determined, in the intervals prior to each successive events until the end of the experiment. The results showed a progressive increase in the amplitude and time-domain morphological markers of the QRS wave along the experiment, which were strongly correlated with the changes in traditional QRS markers (r ≈ 0.9). Significant changes were found between pre-apnea and hypoxic measures only for the time-domain analysis (p<0.001), probably due to the short duration of the simulated apnea episodes.Clinical relevance Increased variability in ECG depolarization morphology during recurrent hypoxic episodes would be closely related to the expression of cardiovascular dysfunction in OSA patients.

JTD Keywords: Electrocardiography, Rats, Heart rate variability, Sleep apnea, Protocols, Heuristic algorithms

Chronic obstructive pulmonary disease (COPD) patients exhibit impaired autonomic control which can be assessed by heart rate variability analysis. The study aims to evaluate the cardiac autonomic responses of COPD patients after completing a conventional six-minute walk test (6MWT). Fifty COPD patients were included in the study, for which an ECG signal (lead II) was acquired by a wearable device, before, during, and after the test. We used the heart rate (HR) time-series to assess the heart rate dynamic during recovery. The heart rate recovery (HRR) marker was evaluated every 5 s after the 6MWT and showed different dynamic trends among severity groups. We compared the HRR among patient groups classified according to the GOLD standard. Significantly larger normalized HRR values (nHRR) were found in mild COPD patients (n=23, GOLD={1,2}; nHRR 1 =14.B±7.5 %, nHRR 2 =18.6±8.1 %) compared to those with more disease severity (n=23, GOLD={3,4}; nHRR 1 =9.3±5.8 %, p=0.002; and nHRR 2 = 13.7±6.7%, p=0.041). The largest differences were observed around the first 30 s of the recovery phase (nHRR=10.8±6.6 % vs. nHRR=5.6±4 % p=0.001). Our results showed a slower recovery for the severest patients, suggesting that cardiac parameters like the ones we propose here, may provide valuable information for a better characterization of COPD severity.

JTD Keywords: Pulmonary diseases, Wearable computers, Electrocardiography, Market research, Cardiology, Heart rate variability

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 (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) 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. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR 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 IDCLR vs. IDCHR 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.

JTD Keywords: Idiopathic dilated cardiomyopathy, Heart rate variability, Blood pressure variability, Coupling analysis, Sudden cardiac death, Risk stratification

Hypoxia induced by obstructive sleep apnea (OSA) leads to the deregulation of the autonomic nervous system (ANS), resulting in an abnormally increased sympathetic activity. Since ANS modulation varies throughout the night, notably for each sleep stage, the hypno-gram and heart rate signals of 81 OSA patients were collected during a polysomnography. They were classified as mild-moderate (n=44) or severe (n=37) based on their apnea-hypopnea index (AHI). Spectral heart rate variability (HRV) series were extracted by a time-frequency approach. These series were then averaged for each sleep stage, in order to compare the sympathetic modulation of mild-moderate and severe patients at the following phases: rapid eye movement (REM), S1, S2 and SWS (slow wave sleep). According to normalized power at the low-frequency band (LFnu) values, severe OSA seems to be associated with an increased sympathetic modulation at non-REM sleep. Moreover, a decreased autonomic variability throughout the night may be related to a reduced adaptability of the cardiovascular system, characterizing a more advanced stage of the disease. These results provide further evidence for the role of autonomic alterations induced by hypoxia, suggesting the use of HRV analysis, together with AHI, for the study of OSA severity.

JTD Keywords: Sleep apnea, Heart rate variability, Modulation, Indexes, Standards

Assessment of the dynamic interactions between cardiovascular signals can provide valuable information that improves the understanding of cardiovascular control. Heart rate variability (HRV) analysis is known to provide information about the autonomic heart rate modulation mechanism. Using the HRV signal, we aimed to obtain parameters for classifying patients with and without chronic heart failure (CHF), and with periodic breathing (PB), non-periodic breathing (nPB), and Cheyne-Stokes respiration (CSR) patterns. An electrocardiogram (ECG) and a respiratory flow signal were recorded in 36 elderly patients: 18 patients with CHF and 18 patients without CHF. According to the clinical criteria, the patients were classified into the follow groups: 19 patients with nPB pattern, 7 with PB pattern, 4 with Cheyne-Stokes respiration (CSR), and 6 non-classified patients (problems with respiratory signal). From the HRV signal, parameters in the time and frequency domain were calculated. Frequency domain parameters were the most discriminant in comparisons of patients with and without CHF: P_Tot (p = 0.02), P_LF (p = 0.022) and fp_HF (p = 0.021). For the comparison of the nPB vs. CSR patients groups, the best parameters were RMSSD (p = 0.028) and SDSD (p = 0.028). Therefore, the parameters appear to be suitable for enhanced diagnosis of decompensated CHF patients and the possibility of developed periodic breathing and a CSR pattern.

JTD Keywords: cardiovascular system, diseases, electrocardiography, frequency-domain analysis, geriatrics, medical signal processing, patient diagnosis, pneumodynamics, signal classification, Cheyne-Stokes respiration patterns, ECG, autonomic heart rate modulation mechanism, cardiovascular control, cardiovascular signals, chronic heart failure, decompensated CHF patients, dynamic interaction assessment, elderly patients, electrocardiogram, enhanced diagnosis, frequency domain parameters, heart rate variability analysis, patient classification, periodic breathing, respiratory flow signal recording, Electrocardiography, Frequency modulation, Frequency-domain analysis, Heart rate variability, Senior citizens, Standards

This work investigates the very low frequency (VLF) modulation of QRS slopes and heart rate variability (HRV). Electrocardiogram (ECG) and respiratory flow signal were acquired from patients with dilated cardiomyopathy and ischemic cardiomyopathy. HRV as well as the upward QRS slope (I_US) and downward QRS slope (I_DS) were extracted from the ECG. The relation between HRV and QRS slopes in the VLF band was measured using ordinary coherence in 5-minute segments. Partial coherence was then used to remove the influence that respiration simultaneously exerts on HRV and QRS slopes. A statistical threshold was determined, below which coherence values were considered not to represent a linear relation. 7 out of 276 segments belonging to 5 out of 29 patients for I_US and 10 segments belonging to 5 patients for I_DS presented a VLF modulation in QRS slopes, HRV and respiration. In these segments spectral coherence was statistically significant, while partial coherence decreased, indicating that the coupling HRV and QRS slopes was related to respiration. 4 segments had a partial coherence value below the threshold for I_US, 3 segments for I_DS. The rest of the segments also presented a notable decrease in partial coherence, but still above the threshold, which means that other non-linearly effects may also affect this modulation.

JTD Keywords: diseases, electrocardiography, feature extraction, medical signal processing, pneumodynamics, statistical analysis, ECG, QRS slopes, cardiomyopathy patients, dilated cardiomyopathy, electrocardiogram, feature extraction, heart rate variability, ischemic cardiomyopathy, ordinary coherence, partial coherence value, respiration, respiratory flow signal acquisition, spectral coherence, statistical threshold, time 5 min, very low frequency modulation, Coherence, Educational institutions, Electrocardiography, Frequency modulation, Heart rate variability

Rat model of Obstructive Sleep Apnea (OSA) is a realistic approach for studying physiological mechanisms involved in sleep. Rats are usually anesthetized and autonomic nervous system (ANS) could be blocked. This study aimed to assess the effect of anesthesia on ANS activity during OSA episodes. Seven male Sprague-Dawley rats were anesthetized intraperitoneally with urethane (1g/kg). The experiments were conducted applying airway obstructions, simulating 15s-apnea episodes for 15 minutes. Five signals were acquired: respiratory pressure and flow, SaO2, ECG and photoplethysmography (PPG). In total, 210 apnea episodes were studied. Normalized power spectrum of Pulse Rate Variability (PRV) was analyzed in the Low Frequency (LF) and High Frequency (HF) bands, for each episode in consecutive 15s intervals (before, during and after the apnea). All episodes showed changes in respiratory flow and SaO₂ signal. Conversely, decreases in the amplitude fluctuations of PPG (DAP) were not observed. Normalized LF presented extremely low values during breathing (median=7,67%), suggesting inhibition of sympathetic system due to anesthetic effect. Subtle increases of LF were observed during apnea. HRV and PPG analysis during apnea could be an indirect tool to assess the effect and deep of anesthesia.

JTD Keywords: electrocardiography, fluctuations, medical disorders, medical signal detection, medical signal processing, neurophysiology, photoplethysmography, pneumodynamics, sleep, ECG, SaO₂ flow, SaO₂ signal, airway obstructions, amplitude fluctuations, anesthesia effects, anesthetized nervous system, autonomic evaluation, autonomic nervous system, breathing, heart rate variability, high-frequency bands, low-frequency bands, male Sprague-Dawley rats, normalized power spectrum, obstructive sleep apnea, photoplethysmography, physiological mechanisms, pulse rate variability, rat model, respiratory flow, respiratory pressure, signal acquisition, sympathetic system inhibition, time 15 min, time 15 s, Abstracts, Atmospheric modeling, Computational modeling, Electrocardiography, Rats, Resonant frequency