Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

BACKGROUND: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. METHODS: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. RESULTS: The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. CONCLUSION: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice.

Entropy Measures as Descriptors to Identify Apneas in Rheoencephalographic Signals.

Rheoencephalography (REG) is a simple and inexpensive technique that intends to monitor cerebral blood flow (CBF), but its ability to reflect CBF changes has not been extensively proved. Based on the hypothesis that alterations in CBF during apnea should be reflected in REG signals under the form of increased complexity, several entropy metrics were assessed for REG analysis during apnea and resting periods in 16 healthy subjects: approximate entropy (ApEn), sample entropy (SampEn), fuzzy entropy (FuzzyEn), corrected conditional entropy (CCE) and Shannon entropy (SE). To compute these entropy metrics, a set of parameters must be defined a priori, such as, for example, the embedding dimension m, and the tolerance threshold r. A thorough analysis of the effects of parameter selection in the entropy metrics was performed, looking for the values optimizing differences between apnea and baseline signals. All entropy metrics, except SE, provided higher values for apnea periods (p-values < 0.025). FuzzyEn outperformed all other metrics, providing the lowest p-value (p = 0.0001), allowing to conclude that REG signals during apnea have higher complexity than in resting periods. Those findings suggest that REG signals reflect CBF changes provoked by apneas, even though further studies are needed to confirm this hypothesis.

Refined Multiscale Entropy Using Fuzzy Metrics: Validation and Application to Nociception Assessment.

The refined multiscale entropy (RMSE) approach is commonly applied to assess complexity as a function of the time scale. RMSE is normally based on the computation of sample entropy (SampEn) estimating complexity as conditional entropy. However, SampEn is dependent on the length and standard deviation of the data. Recently, fuzzy entropy (FuzEn) has been proposed, including several refinements, as an alternative to counteract these limitations. In this work, FuzEn, translated FuzEn (TFuzEn), translated-reflected FuzEn (TRFuzEn), inherent FuzEn (IFuzEn), and inherent translated FuzEn (ITFuzEn) were exploited as entropy-based measures in the computation of RMSE and their performance was compared to that of SampEn. FuzEn metrics were applied to synthetic time series of different lengths to evaluate the consistency of the different approaches. In addition, electroencephalograms of patients under sedation-analgesia procedure were analyzed based on the patient's response after the application of painful stimulation, such as nail bed compression or endoscopy tube insertion. Significant differences in FuzEn metrics were observed over simulations and real data as a function of the data length and the pain responses. Findings indicated that FuzEn, when exploited in RMSE applications, showed similar behavior to SampEn in long series, but its consistency was better than that of SampEn in short series both over simulations and real data. Conversely, its variants should be utilized with more caution, especially whether processes exhibit an important deterministic component and/or in nociception prediction at long scales.

Comparison of the qCON and qNOX indices for the assessment of unconsciousness level and noxious stimulation response during surgery.

The objective of this work is to compare the performances of two electroencephalogram based indices for detecting loss of consciousness and loss of response to nociceptive stimulation. Specifically, their behaviour after drug induction and during recovery of consciousness was pointed out. Data was recorded from 140 patients scheduled for general anaesthesia with a combination of propofol and remifentanil. The qCON 2000 monitor (Quantium Medical, Barcelona, Spain) was used to calculate the qCON and qNOX. Loss of response to verbal command and loss of eye-lash reflex were assessed during the transition from awake to anesthetized, defining the state of loss of consciousness. Movement as a response to laryngeal mask (LMA) insertion was interpreted as the response to the nociceptive stimuli. The patients were classified as movers or non-movers. The values of qCON and qNOX were statistically compared. Their fall times and rise times defined at the start and at the end of the surgery were calculated and compared. The results showed that the qCON was able to predict loss of consciousness such as loss of verbal command and eyelash reflex better than qNOX, while the qNOX has a better predictive value for response to noxious stimulation such as LMA insertion. From the analysis of the fall and rise times, it was found that the qNOX fall time (median: 217 s) was significantly longer (p value <0.05) than the qCON fall time (median: 150 s). At the end of the surgery, the qNOX started to increase in median at 45 s before the first annotation related to response to stimuli or recovery of consciousness, while the qCON at 88 s after the first annotation related to response to stimuli or recovery of consciousness (p value <0.05). The indices qCON and qNOX showed different performances in the detection of loss of consciousness and loss of response to stimuli during induction and recovery of consciousness. Furthermore, the qCON showed faster decrease during induction. This behaviour is associated with the hypothesis that the loss of response to stimuli (analgesic effect) might be reached after the loss of consciousness (hypnotic effect). On the contrary, the qNOX showed a faster increase at the end of the surgery, associated with the hypothesis that a higher probability of response to stimuli might be reached before the recovery of consciousness.

Applicability of an unsupervised cluster model developed on first wave COVID-19 patients in second/third wave critically ill patients.

OBJECTIVE: To validate the unsupervised cluster model (USCM) developed during the first pandemic wave in a cohort of critically ill patients from the second and third pandemic waves. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adult patients admitted with COVID-19 and respiratory failure during the second and third pandemic waves. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. To validate our original USCM, we assigned a phenotype to each patient of the validation cohort. The performance of the classification was determined by Silhouette coefficient (SC) and general linear modelling. In a post-hoc analysis we developed and validated a USCM specific to the validation set. The model's performance was measured using accuracy test and area under curve (AUC) ROC. RESULTS: A total of 2330 patients (mean age 63 [53-82] years, 1643 (70.5%) male, median APACHE II score (12 [9-16]) and SOFA score (4 [3-6]) were included. The ICU mortality was 27.2%. The USCM classified patients into 3 clinical phenotypes: A (n = 1206 patients, 51.8%); B (n = 618 patients, 26.5%), and C (n = 506 patients, 21.7%). The characteristics of patients within each phenotype were significantly different from the original population. The SC was -0.007 and the inclusion of phenotype classification in a regression model did not improve the model performance (0.79 and 0.78 ROC for original and validation model). The post-hoc model performed better than the validation model (SC -0.08). CONCLUSION: Models developed using machine learning techniques during the first pandemic wave cannot be applied with adequate performance to patients admitted in subsequent waves without prior validation.

Assessment of autonomic control of the heart during transient myocardial ischemia.

INTRODUCTION: In the presence of coronary artery obstruction, complex cardiovascular reflexes may lead to changes in heart rate and even to the precipitation of malignant arrhythmias. The autonomic nervous system (ANS) has traditionally been considered to be "balanced" between continuously interacting sympathetic and parasympathetic outflows. The purpose of this study was to assess ANS control of the heart during prolonged coronary balloon occlusion procedures of one of the major coronary arteries. METHODS: R-R intervals were obtained from continuous electrocardiographic data of 90 patients undergoing selective percutaneous coronary interventions (PCI) with balloon inflation periods ranging from 3 to 10 minutes (4.7 ± 1.1 minutes). Three 3-minute stages were chosen: (1) preinflation (baseline), (2) from the start of occlusion (PCI), and (3) immediately post deflation. The dynamics of the ANS was evaluated by heart rate variability analysis using standard time and frequency domain indices and the short-term fractal-like index (α(1)). RESULTS: During PCI, time and frequency domain measures related to vagal control decreased significantly with respect to baseline (significantly in left anterior descending [LAD] artery occlusions). During the postdeflation stage, heart rate variability and high-frequency power increased (P < .01) in the group with right coronary artery occlusions, whereas a marked sympathetic increase, as assessed by an increase (P < .01) of normalized low-frequency power and the low/high-frequency ratio was observed in the LAD group after balloon deflation. Fractal index α(1) decreased during the PCI period but increased significantly after balloon deflation. CONCLUSIONS: Significant changes in autonomic control of heart rate that were a function of the affected artery occurred during and after coronary artery occlusions. Occlusion of the LAD resulted in a significant reduction of vagal activity and a decrease of the short-term fractal index during PCI and a marked sympathetic response after postdeflation. However, a marked increment of vagal activity between the occlusion stage and postdeflation period was found in the right coronary artery group. These results may relate the site of the occlusion and lack of blood supply to different parts of the left ventricle.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

MISS: a non-linear methodology based on mutual information for genetic association studies in both population and sib-pairs analysis.

MOTIVATION: Finding association between genetic variants and phenotypes related to disease has become an important vehicle for the study of complex disorders. In this context, multi-loci genetic association might unravel additional information when compared with single loci search. The main goal of this work is to propose a non-linear methodology based on information theory for finding combinatorial association between multi-SNPs and a given phenotype. RESULTS: The proposed methodology, called MISS (mutual information statistical significance), has been integrated jointly with a feature selection algorithm and has been tested on a synthetic dataset with a controlled phenotype and in the particular case of the F7 gene. The MISS methodology has been contrasted with a multiple linear regression (MLR) method used for genetic association in both, a population-based study and a sib-pairs analysis and with the maximum entropy conditional probability modelling (MECPM) method, which searches for predictive multi-locus interactions. Several sets of SNPs within the F7 gene region have been found to show a significant correlation with the FVII levels in blood. The proposed multi-site approach unveils combinations of SNPs that explain more significant information of the phenotype than their individual polymorphisms. MISS is able to find more correlations between SNPs and the phenotype than MLR and MECPM. Most of the marked SNPs appear in the literature as functional variants with real effect on the protein FVII levels in blood. AVAILABILITY: The code is available at http://sisbio.recerca.upc.edu/R/MISS_0.2.tar.gz

Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU: A multicentre retrospective cohort study.

BACKGROUND: It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. FINDINGS: As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p<0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p<0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p<0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p<0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. INTERPRETATION: Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. FUNDING: Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYUC.

Mutual information between heart rate variability and respiration for emotion characterization.

OBJECTIVE: Interest in emotion recognition has increased in recent years as a useful tool for diagnosing psycho-neural illnesses. In this study, the auto-mutual and the cross-mutual information function, AMIF and CMIF respectively, are used for human emotion recognition. APPROACH: The AMIF technique was applied to heart rate variability (HRV) signals to study complex interdependencies, and the CMIF technique was considered to quantify the complex coupling between HRV and respiratory signals. Both algorithms were adapted to short-term RR time series. Traditional band pass filtering was applied to the RR series at low frequency (LF) and high frequency (HF) bands, and a respiration-based filter bandwidth was also investigated ([Formula: see text]). Both the AMIF and the CMIF algorithms were calculated with regard to different time scales as specific complexity measures. The ability of the parameters derived from the AMIF and the CMIF to discriminate emotions was evaluated on a database of video-induced emotion elicitation. Five elicited states i.e. relax (neutral), joy (positive valence), as well as fear, sadness and anger (negative valences) were considered. MAIN RESULTS: The results revealed that the AMIF applied to the RR time series filtered in the [Formula: see text] band was able to discriminate between the following: relax and joy and fear, joy and each negative valence conditions, and finally fear and sadness and anger, all with a statistical significance level p -value [Formula: see text] 0.05, sensitivity, specificity and accuracy higher than 70% and area under the receiver operating characteristic curve index AUC [Formula: see text]0.70. Furthermore, the parameters derived from the AMIF and the CMIF allowed the low signal complexity presented during fear to be characterized in front of any of the studied elicited states. SIGNIFICANCE: Based on these results, human emotion manifested in the HRV and respiratory signal responses could be characterized by means of the information-content complexity.

Human Emotion Characterization by Heart Rate Variability Analysis Guided by Respiration.

Developing a tool that identifies emotions based on their effect on cardiac activity may have a potential impact on clinical practice, since it may help in the diagnosing of psycho-neural illnesses. In this study, a method based on the analysis of heart rate variability (HRV) guided by respiration is proposed. The method was based on redefining the high frequency (HF) band, not only to be centered at the respiratory frequency, but also to have a bandwidth dependent on the respiratory spectrum. The method was first tested using simulated HRV signals, yielding the minimum estimation errors as compared to classic and respiratory frequency centered at HF band based definitions, independently of the values of the sympathovagal ratio. Then, the proposed method was applied to discriminate emotions in a database of video-induced elicitation. Five emotional states, relax, joy, fear, sadness, and anger, were considered. The maximum correlation between HRV and respiration spectra discriminated joy versus relax, joy versus each negative valence emotion, and fear versus sadness with p-value ≤ 0.05 and AUC ≥ 0.70. Based on these results, human emotion characterization may be improved by adding respiratory information to HRV analysis.

Poincaré plot analysis of cerebral blood flow signals: Feature extraction and classification methods for apnea detection.

OBJECTIVE: Rheoencephalography is a simple and inexpensive technique for cerebral blood flow assessment, however, it is not used in clinical practice since its correlation to clinical conditions has not yet been extensively proved. The present study investigates the ability of Poincaré Plot descriptors from rheoencephalography signals to detect apneas in volunteers. METHODS: A group of 16 subjects participated in the study. Rheoencephalography data from baseline and apnea periods were recorded and Poincaré Plot descriptors were extracted from the reconstructed attractors with different time lags (τ). Among the set of extracted features, those presenting significant differences between baseline and apnea recordings were used as inputs to four different classifiers to optimize the apnea detection. RESULTS: Three features showed significant differences between apnea and baseline signals: the Poincaré Plot ratio (SDratio), its correlation (R) and the Complex Correlation Measure (CCM). Those differences were optimized for time lags smaller than those recommended in previous works for other biomedical signals, all of them being lower than the threshold established by the position of the inflection point in the CCM curves. The classifier showing the best performance was the classification tree, with 81% accuracy and an area under the curve of the receiver operating characteristic of 0.927. This performance was obtained using a single input parameter, either SDratio or R. CONCLUSIONS: Poincaré Plot features extracted from the attractors of rheoencephalographic signals were able to track cerebral blood flow changes provoked by breath holding. Even though further validation with independent datasets is needed, those results suggest that nonlinear analysis of rheoencephalography might be a useful approach to assess the correlation of cerebral impedance with clinical changes.

Time-frequency Features for Impedance Cardiography Signals During Anesthesia Using Different Distribution Kernels.

OBJECTIVE: This works investigates the time-frequency content of impedance cardiography signals during a propofol-remifentanil anesthesia. MATERIALS AND METHODS: In the last years, impedance cardiography (ICG) is a technique which has gained much attention. However, ICG signals need further investigation. Time-Frequency Distributions (TFDs) with 5 different kernels are used in order to analyze impedance cardiography signals (ICG) before the start of the anesthesia and after the loss of consciousness. In total, ICG signals from one hundred and thirty-one consecutive patients undergoing major surgery under general anesthesia were analyzed. Several features were extracted from the calculated TFDs in order to characterize the time-frequency content of the ICG signals. Differences between those features before and after the loss of consciousness were studied. RESULTS: The Extended Modified Beta Distribution (EMBD) was the kernel for which most features shows statistically significant changes between before and after the loss of consciousness. Among all analyzed features, those based on entropy showed a sensibility, specificity and area under the curve of the receiver operating characteristic above 60%. CONCLUSION: The anesthetic state of the patient is reflected on linear and non-linear features extracted from the TFDs of the ICG signals. Especially, the EMBD is a suitable kernel for the analysis of ICG signals and offers a great range of features which change according to the patient's anesthesia state in a statistically significant way.

Detrended fluctuation analysis of EEG as a measure of depth of anesthesia.

For several decades, a number of methods have been developed for the noninvasive assessment of the level of consciousness during general anesthesia. In this paper, detrended fluctuation analysis is used to study the scaling behavior of the electroencephalogram as a measure of the level of consciousness. Three indexes are proposed in order to characterize the patient state. Statistical analysis demonstrates that they allow significant discrimination between the awake, sedated and anesthetized states. Two of them present a good correlation with established indexes of depth of anesthesia. The scaling behavior has been found related to the depth of anesthesia and the methodology allows real-time implementation, which enables its application in monitoring devices.

Changes of autonomic information flow due to idiopathic dilated cardiomyopathy.

Risk stratification of patients with idiopathic dilated cardiomyopathy (IDC) is an epidemiologically relevant question. But the results based on conventional heart rate variability (HRV) analysis are still unsatisfactory. The adjustments within the cardiovascular system incorporate nonlinear and complex mechanisms of information exchange which may have additional prognostic value. It is an objective of the present work to evaluate the prognostic value of autonomic information flow (AIF) measures in IDC patients compared to conventional HRV measures in a first explorative study. Holter recordings of 32 patients with idiopathic dilated cardiomyopathy (IDC) and 12 normal subjects (NRM) were analyzed. The IDC patients consisted of two groups: 10 high risk (HR) patients, after aborted sudden cardiac death (SCD); 22 low risk (LR) patients, without SCD. Sensitivity, specificity, positive predictive value, negative predictive value and ROC characteristics of a comprehensive set of AIF measures, organized according to the conventional HRV standards, and conventional HRV measures were investigated. The significant risk predictors were evaluated by Spearman's rank correlation. While the only traditional HRV measure discriminating IDC patients from NRM was ln(LF) most of the AIF measures had a discriminatory value. Concerning the prognosis of the IDC patients by conventional HRV we found that SDNN and all frequency band measures (lnHF, lnLF, lnVLF) significantly discriminated HR from LR. Among the AIF measures the time shift related peak decay (PD(dHF)) reflecting the HF band information flow had a prognostic value. PD(dHF) was identified as a promising candidate which might improve the predictive value of traditional HRV analysis, predominantly represented by SDNN. A subsequent comprehensive clinical study is necessary to validate this hypothesis.

Relation of heart rate turbulence to severity of heart failure.

The aim of this study was to evaluate the association between heart rate turbulence (HRT) parameters and clinical, biochemical, echocardiographic, and electrocardiographic measures of heart failure (HF) in a large, prospectively enrolled population of patients with HF to determine whether HRT could be considered a marker of HF advancement and progression, giving insight into hemodynamic changes as well as changes of the autonomic nervous system. In 487 patients with HF (mean age 63 years), the following tests were performed: 12-lead surface electrocardiography, echocardiography, chest x-rays, N-terminal-pro-brain natriuretic peptide levels, and 24-hour Holter monitoring for HRT and heart rate variability analyses. Most patients were in New York Heart Association class II (82%) and had a mean left ventricular (LV) ejection fraction of 37 +/- 14%. Both HRT parameters, but especially turbulence slope, were significantly correlated with clinical indexes of HF (the third heart sound, peripheral edemas, jugular distension, and pulmonary congestion). Patients in New York Heart Association class III had significantly lower turbulence slopes and greater turbulence onset values than those in class II. Significant correlations were found between HRT parameters and the LV ejection fraction as well as with LV diameters. HRT parameters were significantly correlated with N-terminal-pro-brain natriuretic peptide levels (r = -0.47, p <0.001 for turbulence slope). Multivariate analyses showed that abnormal HRT parameters were independent predictors of HF severity measured by New York Heart Association class III and a LV ejection fraction <40%. In conclusion, the findings indicate that in patients with HF, HRT reflects well the severity of HF and associated LV dysfunction, which were verified in this study by a series of established clinical, echocardiographic, and biochemical parameters.

Non-linear dynamic analysis of the cardiac rhythm during transient myocardial ischemia.

Coronary artery occlusions related to myocardial ischemia drive cardiac control system reactions that may lead to heart failure. The purpose of this study was to assess the autonomic nervous system (ANS) response during prolonged percutaneous transluminal coronary angioplasty (PTCA). Continuous ECG data were acquired from 50 patients before and during PTCA, with occlusions in the left anterior descending, left circumflex or right coronary artery. Heart rate variability (HRV) was analyzed for 3-min segments of the R-R interval signal obtained from ECG data. The ANS behavior was evaluated by HRV analysis using fractal-like indices. The fractal scalar exponent alpha(1) and power-law slope beta decreased considerably during PTCA. This indicates that significant reactions of autonomic control of the heart rate occurred during coronary artery occlusions, with a reduction in complexity of the ANS.

Compression entropy contributes to risk stratification in patients with cardiomyopathy.

Sudden cardiac death (SCD) is a leading cause of mortality with an incidence of 3 million cases per year worldwide. Therapies for patients who have survived an SCD episode or have a high risk of developing lethal ventricular arrhythmia are well established and depend mainly on risk stratification. In this study we investigated the suitability of the non-linear measure compression entropy (Hc) for improved risk prediction in cardiac patients. We recorded 24-h Holter ECG for 300 patients with congestive heart failure (CHF). During a mean follow-up period of 12 months, 32 patients died due to a cardiac event. Hc depends on the compression parameters window length w and buffer length b, which were optimised by analysing a subgroup of patients. Compression entropies based on the beat-to-beat interval (BBI) were subsequently calculated and compared with standard heartrate variability parameters. Statistical analysis revealed significant differences between high- and low-risk CHF patients in standard HRV measures, as well as compression entropy based on the BBI (cardiac death, p = 0.005; SCD, p = 0.02). In conclusion, the implementation of non-linear compression entropy analysis in multivariate analysis seems to be useful for enhanced risk stratification of cardiac death, especially SCD, in ischaemic cardiomyopathy patients.

Complex autonomic dysfunction in cardiovascular, intensive care, and schizophrenic patients assessed by autonomic information flow.

BACKGROUND: The cardiovascular control system is mediated by mechanisms acting at different time scales, such as heart period, vagal, sympathetic, and other slower controllers. Since these elements are interrelated in a complex manner, classical control theory fails and information-based description, based on autonomic information flow (AIF) functions, is appropriate. We investigated the hypothesis that AIF functions of typical time scales specifically characterize autonomic dysfunction and prognosis. MATERIALS AND METHODS: Holter recordings of patients with multiple organ dysfunction syndrome (MODS) (26 survivors, 10 non-survivors), heart failure (13 low risk, 13 high risk of cardiac arrest), idiopathic dilated cardiomyopathy (IDC) (26 low risk, 11 high risk), after abdominal aorta surgery (AAS) [32 with length of stay in hospital (LOS) >7 days; 62 with LOS < or =7 days] or with schizophrenia (n=20) were assessed and compared to 20 control subjects. RESULTS: We found different AIF time scales discriminating risk. AIF measures of heart beat period had predominant prognostic value in heart failure patients, those of vagal communication in MODS and IDC, and those of long-term communication after AAS. Schizophrenic patients were discriminated from controls by vagally mediated communication. CONCLUSION: Different time scales of AIF represent specific pathophysiological aspects of altered complex autonomic control (communication) and consequently have predictive implications.