Left atrial appendage occlusion in patients suffering from advanced chronic kidney disease (stage 4 and 5). Long-term follow-up.

INTRODUCTION AND OBJECTIVES: Advanced chronic kidney disease (A-CKD) combined with atrial fibrillation increases the risk of both thrombogenic and bleeding events. Left atrial appendage occlusion (LAAO) may be an alternative to oral anticoagulation to prevent thromboembolic events. We aimed to evaluate the outcomes of LAAO in patients with A-CKD. METHODS: Comparison at long-term follow-up of patients diagnosed with and without A-CKD (eGFR<30 mL/min/1.73 m2 ) who underwent LAAO between 2009 and May 2022. RESULTS: Five hundred seventy-three patients were included. Eighty-one (14%) were diagnosed with A-CKD. There were no differences in sex, age, and cardiovascular risk factors, except for diabetes which was more frequent in patients with A-CKD. The control group had higher rates of stroke, both ischemic and hemorrhagic. There were no differences in the CHA2 DS2 -VASc score, although A-CKD patients had a higher bleeding risk according to the HASBLED scale. Global procedural success was 99.1%. At follow-up, there were no differences in stroke rate: at 1-year (HR: 1.22, IC-95%: 0.14-10.42, p = 0.861); at 5-years (HR: 0.60, IC-95%: 0.08-4.58, p = 0.594). Although bleeding events were higher in the A-CKD group, no differences were found in major bleeding (defined BARC ≥ 3) at 1-year (HR: 1.34, IC-95%: 0.63-2.88, p = 0.464) or at 5-years follow-up (HR: 1.30, IC-95%: 0.69-2.48, p = 0.434). Mortality rate at 5 years was higher in the A-CKD patients (HR: 1.84, IC-95%: 1.18-2.87, p = 0.012). CONCLUSIONS: LAAO is an effective and safe treatment in A-CKD patients to prevent ischemic events and bleeding. This strategy could be an alternative to oral anticoagulation in this high-risk group of patients.

A deep learning model based on the combination of convolutional and recurrent neural networks to enhance pulse oximetry ability to classify sleep stages in children with sleep apnea.

Characterization of sleep stages is essential in the diagnosis of sleep-related disorders but relies on manual scoring of overnight polysomnography (PSG) recordings, which is onerous and labor-intensive. Accordingly, we aimed to develop an accurate deep-learning model for sleep staging in children suffering from pediatric obstructive sleep apnea (OSA) using pulse oximetry signals. For this purpose, pulse rate (PR) and blood oxygen saturation (SpO2) from 429 childhood OSA patients were analyzed. A CNN-RNN architecture fed with PR and SpO2 signals was developed to automatically classify wake (W), non-Rapid Eye Movement (NREM), and REM sleep stages. This architecture was composed of: (i) a convolutional neural network (CNN), which learns stage-related features from raw PR and SpO2 data; and (ii) a recurrent neural network (RNN), which models the temporal distribution of the sleep stages. The proposed CNN-RNN model showed a high performance for the automated detection of W/NREM/REM sleep stages (86.0% accuracy and 0.743 Cohen's kappa). Furthermore, the total sleep time estimated for each children using the CNN-RNN model showed high agreement with the manually derived from PSG (intra-class correlation coefficient = 0.747). These results were superior to previous works using CNN-based deep-learning models for automatic sleep staging in pediatric OSA patients from pulse oximetry signals. Therefore, the combination of CNN and RNN allows to obtain additional information from raw PR and SpO2 data related to sleep stages, thus being useful to automatically score sleep stages in pulse oximetry tests for children evaluated for suspected OSA.Clinical Relevance-This research establishes the usefulness of a CNN-RNN architecture to automatically score sleep stages in pulse oximetry tests for pediatric OSA diagnosis.

ECG-based convolutional neural network in pediatric obstructive sleep apnea diagnosis.

Obstructive sleep apnea (OSA) is a prevalent respiratory condition in children and is characterized by partial or complete obstruction of the upper airway during sleep. The respiratory events in OSA induce transient alterations of the cardiovascular system that ultimately can lead to increased cardiovascular risk in affected children. Therefore, a timely and accurate diagnosis is of utmost importance. However, polysomnography (PSG), the standard diagnostic test for pediatric OSA, is complex, uncomfortable, costly, and relatively inaccessible, particularly in low-resource environments, thereby resulting in substantial underdiagnosis. Here, we propose a novel deep-learning approach to simplify the diagnosis of pediatric OSA using raw electrocardiogram tracing (ECG). Specifically, a new convolutional neural network (CNN)-based regression model was implemented to automatically predict pediatric OSA by estimating its severity based on the apnea-hypopnea index (AHI) and deriving 4 OSA severity categories. For this purpose, overnight ECGs from 1,610 PSG recordings obtained from the Childhood Adenotonsillectomy Trial (CHAT) database were used. The database was randomly divided into approximately 60%, 20%, and 20% for training, validation, and testing, respectively. The diagnostic performance of the proposed CNN model largely outperformed the most accurate previous algorithms that relied on ECG-derived features (4-class Cohen's kappa coefficient of 0.373 versus 0.166). Specifically, for AHI cutoff values of 1, 5, and 10 events/hour, the binary classification achieved sensitivities of 84.19%, 76.67%, and 53.66%; specificities of 46.15%, 91.39%, and 98.06%; and accuracies of 75.92%, 86.96%, and 91.97%, respectively. Therefore, pediatric OSA can be readily identified by our proposed CNN model, which provides a simpler, faster, and more accessible diagnostic test that can be implemented in clinical practice.

Prediction of the Sleep Apnea Severity Using 2D-Convolutional Neural Networks and Respiratory Effort Signals.

The high prevalence of sleep apnea and the limitations of polysomnography have prompted the investigation of strategies aimed at automated diagnosis using a restricted number of physiological measures. This study aimed to demonstrate that thoracic (THO) and abdominal (ABD) movement signals are useful for accurately estimating the severity of sleep apnea, even if central respiratory events are present. Thus, we developed 2D-convolutional neural networks (CNNs) jointly using THO and ABD to automatically estimate sleep apnea severity and evaluate the central event contribution. Our proposal achieved an intraclass correlation coefficient (ICC) = 0.75 and a root mean square error (RMSE) = 10.33 events/h when estimating the apnea-hypopnea index, and ICC = 0.83 and RMSE = 0.95 events/h when estimating the central apnea index. The CNN obtained accuracies of 94.98%, 79.82%, and 81.60% for 5, 15, and 30 events/h when evaluating the complete apnea hypopnea index. The model improved when the nature of the events was central: 98.72% and 99.74% accuracy for 5 and 15 events/h. Hence, the information extracted from these signals using CNNs could be a powerful tool to diagnose sleep apnea, especially in subjects with a high density of central apnea events.

An explainable deep-learning model to stage sleep states in children and propose novel EEG-related patterns in sleep apnea.

Automatic deep-learning models used for sleep scoring in children with obstructive sleep apnea (OSA) are perceived as black boxes, limiting their implementation in clinical settings. Accordingly, we aimed to develop an accurate and interpretable deep-learning model for sleep staging in children using single-channel electroencephalogram (EEG) recordings. We used EEG signals from the Childhood Adenotonsillectomy Trial (CHAT) dataset (n = 1637) and a clinical sleep database (n = 980). Three distinct deep-learning architectures were explored to automatically classify sleep stages from a single-channel EEG data. Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable artificial intelligence (XAI) algorithm, was then applied to provide an interpretation of the singular EEG patterns contributing to each predicted sleep stage. Among the tested architectures, a standard convolutional neural network (CNN) demonstrated the highest performance for automated sleep stage detection in the CHAT test set (accuracy = 86.9% and five-class kappa = 0.827). Furthermore, the CNN-based estimation of total sleep time exhibited strong agreement in the clinical dataset (intra-class correlation coefficient = 0.772). Our XAI approach using Grad-CAM effectively highlighted the EEG features associated with each sleep stage, emphasizing their influence on the CNN's decision-making process in both datasets. Grad-CAM heatmaps also allowed to identify and analyze epochs within a recording with a highly likelihood to be misclassified, revealing mixed features from different sleep stages within these epochs. Finally, Grad-CAM heatmaps unveiled novel features contributing to sleep scoring using a single EEG channel. Consequently, integrating an explainable CNN-based deep-learning model in the clinical environment could enable automatic sleep staging in pediatric sleep apnea tests.

Pediatric sleep apnea: Characterization of apneic events and sleep stages using heart rate variability.

Heart rate variability (HRV) is modulated by sleep stages and apneic events. Previous studies in children compared classical HRV parameters during sleep stages between obstructive sleep apnea (OSA) and controls. However, HRV-based characterization incorporating both sleep stages and apneic events has not been conducted. Furthermore, recently proposed novel HRV OSA-specific parameters have not been evaluated. Therefore, the aim of this study was to characterize and compare classic and pediatric OSA-specific HRV parameters while including both sleep stages and apneic events. A total of 1610 electrocardiograms from the Childhood Adenotonsillectomy Trial (CHAT) database were split into 10-min segments to extract HRV parameters. Segments were characterized and grouped by sleep stage (wake, W; non-rapid eye movement, NREMS; and REMS) and presence of apneic events (under 1 apneic event per segment, e/s; 1-5 e/s; 5-10 e/s; and over 10 e/s). NREMS showed significant changes in HRV parameters as apneic event frequency increased, which were less marked in REMS. In both NREMS and REMS, power in BW2, a pediatric OSA-specific frequency domain, allowed for the optimal differentiation among segments. Moreover, in the absence of apneic events, another defined band, BWRes, resulted in best differentiation between sleep stages. The clinical usefulness of segment-based HRV characterization was then confirmed by two ensemble-learning models aimed at estimating apnea-hypopnea index and classifying sleep stages, respectively. We surmise that basal sympathetic activity during REMS may mask apneic events-induced sympathetic excitation, thus highlighting the importance of incorporating sleep stages as well as apneic events when evaluating HRV in pediatric OSA.

A 5-year clinical follow-up of the efficacy of proximal sealing in high caries risk children.

OBJECTIVE: The aim of the present study was to evaluate, after 5 years, the efficacy of proximal microinvasive sealing of permanent teeth on the risk for caries lesion development. METHODS: Children aged 8 to 10 y at baseline, at high caries risk, were studied. In the preventive (P) group the children had caries lesions on the distal surface of primary second molars (05d) but sound mesial surfaces of the approximating permanent first molars (6m). In the therapeutic (T) group the children had initial caries lesions on 6m that abutted lesions on 05d. Each child in the two groups had one 05d/6m pair. Using a split-mouth design, one 6m surface in each pair was randomly assigned to receive sealing while the other pair served as an unsealed control. RESULTS: Of the 61 children at baseline 42 could be blindly examined clinically and radiographically both at baseline and after 5 years. In the P group, 8 of 28 (28.6%) sealed and 15 of 28 (53.6 %) unsealed sound 6m surfaces had developed caries lesions (p = 0.04). In the T group, the progression of the carious lesions on 6m was observed in 4 of 14 sealed (28.6%) and 8 of 14 (57.1%) unsealed caries control surfaces (p = 0.29). Pooling the data from the two groups, the difference between sealed and non-sealed surfaces was significant (p = 0.013). CONCLUSION: Both preventive and therapeutic sealant to 6m adjacent to a lesion on 05d has effectiveness in caries reduction in high caries risk children CLINICAL SIGNIFICANCE: The beneficial effect of sealing is observed for at least 5 years after a single sealant treatment.

Covering the Gap Between Sleep and Cognition - Mechanisms and Clinical Examples.

A growing number of studies have shown the strong relationship between sleep and different cognitive processes, especially those that involve memory consolidation. Traditionally, these processes were attributed to mechanisms related to the macroarchitecture of sleep, as sleep cycles or the duration of specific stages, such as the REM stage. More recently, the relationship between different cognitive traits and specific waves (sleep spindles or slow oscillations) has been studied. We here present the most important physiological processes induced by sleep, with particular focus on brain electrophysiology. In addition, recent and classical literature were reviewed to cover the gap between sleep and cognition, while illustrating this relationship by means of clinical examples. Finally, we propose that future studies may focus not only on analyzing specific waves, but also on the relationship between their characteristics as potential biomarkers for multiple diseases.

Conventional Machine Learning Methods Applied to the Automatic Diagnosis of Sleep Apnea.

The overnight polysomnography shows a range of drawbacks to diagnose obstructive sleep apnea (OSA) that have led to the search for artificial intelligence-based alternatives. Many classic machine learning methods have been already evaluated for this purpose. In this chapter, we show the main approaches found in the scientific literature along with the most used data to develop the models, useful and large easily available databases, and suitable methods to assess performances. In addition, a range of results from selected studies are presented as examples of these methods. Very high diagnostic performances are reported in these results regardless of the approaches taken. This leads us to conclude that conventional machine learning methods are useful techniques to develop new OSA diagnosis simplification proposals and to act as benchmark for other more recent methods such as deep learning.

Airflow Analysis in the Context of Sleep Apnea.

The airflow (AF) is a physiological signal involved in the overnight polysomnography (PSG) that reflects the respiratory activity. This signal is able to show the particularities of sleep apnea and is therefore used to define apneic events. In this regard, a growing number of studies have shown the usefulness of employing the overnight airflow as the only or combined information source for diagnosing sleep apnea in both children and adults. Due to its easy acquisition and interpretation, this biosignal has been widely analyzed by means of different signal processing techniques. In this chapter, we review the main methodological approaches applied to characterize and extract relevant information from this signal. In view of the results, we can conclude that the overnight airflow successfully reflects the particularities caused by the occurrence of apneic and hypopneic events and provides useful information for obtaining relevant biomarkers that characterize this disease.

Oximetry Indices in the Management of Sleep Apnea: From Overnight Minimum Saturation to the Novel Hypoxemia Measures.

Obstructive sleep apnea (OSA) is a multidimensional disease often underdiagnosed due to the complexity and unavailability of its standard diagnostic method: the polysomnography. Among the alternative abbreviated tests searching for a compromise between simplicity and accurateness, oximetry is probably the most popular. The blood oxygen saturation (SpO2) signal is characterized by a near-constant profile in healthy subjects breathing normally, while marked drops (desaturations) are linked to respiratory events. Parameterization of the desaturations has led to a great number of indices of severity assessment commonly used to assist in OSA diagnosis. In this chapter, the main methodologies used to characterize the overnight oximetry profile are reviewed, from visual inspection and simple statistics to complex measures involving signal processing and pattern recognition techniques. We focus on the individual performance of each approach, but also on the complementarity among the great amount of indices existing in the state of the art, looking for the most relevant oximetric feature subset. Finally, a quick overview of SpO2-based deep learning applications for OSA management is carried out, where the raw oximetry signal is analyzed without previous parameterization. Our research allows us to conclude that all the methodologies (conventional, time, frequency, nonlinear, and hypoxemia-based) demonstrate high ability to provide relevant oximetric indices, but only a reduced set provide non-redundant complementary information leading to a significant performance increase. Finally, although oximetry is a robust tool, greater standardization and prospective validation of the measures derived from complex signal processing techniques are still needed to homogenize interpretation and increase generalizability.

Deep-Learning Model Based on Convolutional Neural Networks to Classify Apnea-Hypopnea Events from the Oximetry Signal.

Automated analysis of the blood oxygen saturation (SpO2) signal from nocturnal oximetry has shown usefulness to simplify the diagnosis of obstructive sleep apnea (OSA), including the detection of respiratory events. However, the few preceding studies using SpO2 recordings have focused on the automated detection of respiratory events versus normal respiration, without making any distinction between apneas and hypopneas. In this sense, the characteristics of oxygen desaturations differ between obstructive apnea and hypopnea episodes. In this chapter, we use the SpO2 signal along with a convolutional neural network (CNN)-based deep-learning architecture for the automatic identification of apnea and hypopnea events. A total of 398 SpO2 signals from adult OSA patients were used for this purpose. A CNN architecture was trained using 30-s epochs from the SpO2 signal for the automatic classification of three classes: normal respiration, apnea, and hypopnea. Then, the apnea index (AI), the hypopnea index (HI), and the apnea-hypopnea index (AHI) were obtained by aggregating the outputs of the CNN for each subject (AICNN, HICNN, and AHICNN). This model showed a promising diagnostic performance in an independent test set, with 80.3% 3-class accuracy and 0.539 3-class Cohen's kappa for the classification of respiratory events. Furthermore, AICNN, HICNN, and AHICNN showed a high agreement with the values obtained from the standard PSG: 0.8023, 0.6774, and 0.8466 intra-class correlation coefficients (ICCs), respectively. This suggests that CNN can be used to analyze SpO2 recordings for the automated diagnosis of OSA in at-home oximetry tests.

Slow EEG Oscillation to Characterize Pediatric Sleep Apnea and Associated Cognitive Impairments.

Previous studies have suggested that the typical slow oscillations (SO) characteristics during sleep could be modified in the presence of pediatric obstructive sleep apnea (OSA). Here, we evaluate whether these modifications are significant and if they may reflect cognitive deficits. We recorded the overnight electroencephalogram (EEG) of 294 pediatric subjects (5-9 years old) using eight channels. Then, we divided the cohort in three OSA severity groups (no OSA, mild, and moderate/severe) to characterize the corresponding SO using the spectral maximum in the slow wave sleep (SWS) band δ1: 0.1-2 Hz (Maxs o), as well as the frequency where this maximum is located (FreqMaxso). Spectral entropy (SpecEn) from δ1 was also included in the analyses. A correlation analysis was performed to evaluate associations of these spectral measures with six OSA-related clinical variables and six cognitive scores. Our results indicate that Maxso could be used as a moderate/severe OSA biomarker while providing useful information regarding verbal and visuo-spatial impairments, and that FreqMaxso emerges as an even more robust indicator of visuospatial function. In addition, we uncovered novel insights regarding the ability of SpecEn in δ1 to characterize OSA-related disruption of sleep homeostasis. Our findings suggest that the information from SO may be useful to automatically characterize moderate/severe pediatric OSA and its cognitive consequences. Clinical Relevance- This study contributes towards reaching an objective quantifiable and automated assessment of the potential cognitive consequences of pediatric sleep apnea.

A 2D convolutional neural network to detect sleep apnea in children using airflow and oximetry.

The gold standard approach to diagnose obstructive sleep apnea (OSA) in children is overnight in-lab polysomnography (PSG), which is labor-intensive for clinicians and onerous to healthcare systems and families. Simplification of PSG should enhance availability and comfort, and reduce complexity and waitlists. Airflow (AF) and oximetry (SpO2) signals summarize most of the information needed to detect apneas and hypopneas, but automatic analysis of these signals using deep-learning algorithms has not been extensively investigated in the pediatric context. The aim of this study was to evaluate a convolutional neural network (CNN) architecture based on these two signals to estimate the severity of pediatric OSA. PSG-derived AF and SpO2 signals from the Childhood Adenotonsillectomy Trial (CHAT) database (1638 recordings), as well as from a clinical database (974 recordings), were analyzed. A 2D CNN fed with AF and SpO2 signals was implemented to estimate the number of apneic events, and the total apnea-hypopnea index (AHI) was estimated. A training-validation-test strategy was used to train the CNN, adjust the hyperparameters, and assess the diagnostic ability of the algorithm, respectively. Classification into four OSA severity levels (no OSA, mild, moderate, or severe) reached 4-class accuracy and Cohen's Kappa of 72.55% and 0.6011 in the CHAT test set, and 61.79% and 0.4469 in the clinical dataset, respectively. Binary classification accuracy using AHI cutoffs 1, 5 and 10 events/h ranged between 84.64% and 94.44% in CHAT, and 84.10%-90.26% in the clinical database. The proposed CNN-based architecture achieved high diagnostic ability in two independent databases, outperforming previous approaches that employed SpO2 signals alone, or other classical feature-engineering approaches. Therefore, analysis of AF and SpO2 signals using deep learning can be useful to deploy reliable computer-aided diagnostic tools for childhood OSA.

Reliability of machine learning to diagnose pediatric obstructive sleep apnea: Systematic review and meta-analysis.

BACKGROUND: Machine-learning approaches have enabled promising results in efforts to simplify the diagnosis of pediatric obstructive sleep apnea (OSA). A comprehensive review and analysis of such studies increase the confidence level of practitioners and healthcare providers in the implementation of these methodologies in clinical practice. OBJECTIVE: To assess the reliability of machine-learning-based methods to detect pediatric OSA. DATA SOURCES: Two researchers conducted an electronic search on the Web of Science and Scopus using term, and studies were reviewed along with their bibliographic references. ELIGIBILITY CRITERIA: Articles or reviews (Year 2000 onwards) that applied machine learning to detect pediatric OSA; reported data included information enabling derivation of true positive, false negative, true negative, and false positive cases; polysomnography served as diagnostic standard. APPRAISAL AND SYNTHESIS METHODS: Pooled sensitivities and specificities were computed for three apnea-hypopnea index (AHI) thresholds: 1 event/hour (e/h), 5 e/h, and 10 e/h. Random-effect models were assumed. Summary receiver-operating characteristics (SROC) analyses were also conducted. Heterogeneity (I 2 ) was evaluated, and publication bias was corrected (trim and fill). RESULTS: Nineteen studies were finally retained, involving 4767 different pediatric sleep studies. Machine learning improved diagnostic performance as OSA severity criteria increased reaching optimal values for AHI = 10 e/h (0.652 sensitivity; 0.931 specificity; and 0.940 area under the SROC curve). Publication bias correction had minor effect on summary statistics, but high heterogeneity was observed among the studies.

Heart rate variability as a potential biomarker of pediatric obstructive sleep apnea resolution.

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) affects cardiac autonomic regulation, altering heart rate variability (HRV). Although changes in classical HRV parameters occur after OSA treatment, they have not been evaluated as reporters of OSA resolution. Specific frequency bands (named BW1, BW2, and BWRes) have been recently identified in OSA. We hypothesized that changes with treatment in these spectral bands can reliably identify changes in OSA severity and reflect OSA resolution. METHODS: Four hundred and four OSA children (5-9.9 years) from the prospective Childhood Adenotonsillectomy Trial were included; 206 underwent early adenotonsillectomy (eAT), while 198 underwent watchful waiting with supportive care (WWSC). HRV changes from baseline to follow-up were computed for classical and OSA-related frequency bands. Causal mediation analysis was conducted to evaluate how treatment influences HRV through mediators such as OSA resolution and changes in disease severity. Disease resolution was initially assessed by considering only obstructive events, and was followed by adding central apneas to the analyses. RESULTS: Treatment, regardless of eAT or WWSC, affects HRV activity, mainly in the specific frequency band BW2 (0.028-0.074 Hz). Furthermore, only changes in BW2 were specifically attributable to all OSA resolution mediators. HRV activity in BW2 also showed statistically significant differences between resolved and non-resolved OSA. CONCLUSIONS: OSA treatment affects HRV activity in terms of change in severity and disease resolution, especially in OSA-related BW2 frequency band. This band allowed to differentiate HRV activity between children with and without resolution, so we propose BW2 as potential biomarker of pediatric OSA resolution. CLINICAL TRIAL REGISTRATION: Childhood Adenotonsillectomy Trial, NCT00560859, https://sleepdata.org/datasets/chat.