Nocturnal hypoxemic burden in patients with heart failure: Emerging prognostic role of its nonspecific component.

BACKGROUND: Nocturnal hypoxemic burden has been shown to be a robust, independent predictor of all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to occur in a severe form even in patients with low or negligible frequency of respiratory events (apneas/hypopneas). This suggests the existence of two components of hypoxemic burden: one unrelated to respiratory events and the other related. The aim of this study was to characterize these two components and to evaluate their prognostic value. METHODS: Nocturnal hypoxemic burden was assessed in a cohort of 280 patients with HFrEF by measuring the percentage of sleep with an oxygen saturation (SpO2) <90% (T90), and the area of the SpO2 curve below 90% (Area90). Both indices were also recalculated within the sleep segments associated with respiratory events (event-related component: T90Eve, Area90Eve) and outside these segments (nonspecific component: T90Nspec, Area90Nspec). The outcome of the survival analysis (Cox regression) was all-cause mortality. RESULTS: During a median follow-up of 60 months, 87 patients died. T90, Area90, and their components were significant in univariate analysis (P < .05 all). However, when these indices were adjusted for known risk factors, T90, T90Nspec, Area90, and Area90Nspec remained statistically significant (P = .018, hazard ratio (HR)=1.12, 95%CI=(1.02, 1.23); P = .007, HR=1.20, 95% CI = [1.05, 1.37]; P = .020, HR = 1.05, 95% CI = [1.01, 1.10]; P = .0006, HR = 1.15, 95% CI = [1.06, 1.25]), whereas T90Eve and Area90Eve did not (P = .27, P = .28). These results were internally validated using bootstrap resampling. CONCLUSIONS: By demonstrating a significant independent association of nonspecific hypoxemic burden with all-cause mortality, this study suggests that this component of total nocturnal hypoxemic burden may play an important prognostic role in patients with HFrEF.

Effect of lateral position on rostral fluid shift and relationship to severity of Cheyne-Stokes respiration in heart failure patients.

PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.

CARDIAC chronotropic effects of sleep-disordered breathing in patients with heart failure.

It is still not known whether the oscillation in heart rate (HR) induced by sleep-disordered breathing (SDB) in patients with heart failure entails significant chronotropic effects. We hypothesised that since cyclical changes in ventilation and arterial blood gases during SDB affect HR through multiple and complexly interacting mechanisms characterised by large inter-subject variability, chronotropic effects may change from patient to patient. A total of 42 patients with moderate-to-severe chronic heart failure with systolic dysfunction underwent an in-hospital sleep study. Chronotropic effects of SDB were quantified by comparing the distribution of instantaneous HR during SDB with that during periods without SDB (noSDB) within the same night in each patient. Based on distribution changes from noSDB to SDB, 12, nine, 11, and 10 patients showed a significant tachycardic, bradycardic, tachycardic and bradycardic, and neither significant tachycardic nor significant bradycardic effect, respectively. Tachycardic and bradycardic effects were primarily due to an increase in the rate rather than in the magnitude of cyclical HR elevations and reductions, and were more prevalent and severe in patients with dominant obstructive and central events, respectively. The apnea-hypopnea index did not differ between groups. Conversely, the time spent with an oxygen saturation of <90% was greater in the tachycardic and tachycardic-bradycardic groups compared to the bradycardic group. These findings indicate that HR distribution changes induced by SDB can vary from patient to patient revealing four distinct and well-characterised chronotropic effects. These effects are related to the degree of hypoxic burden brought about by SDB and are affected by the type of sleep apnea (central/obstructive).

Quantitative assessment of the quality of home sleep studies: A computer-assisted approach.

Home monitoring is the most practical means of collecting sleep data in large-scale research investigations. Because the portion of recording time with poor-quality data is higher than in attended polysomnography, a quantitative assessment of the quality of each signal should be recommended. Currently, only qualitative or semi-quantitative assessments are carried out, likely because of the lack of computer-based applications to carry out this task efficiently. This paper presents an innovative computer-assisted procedure designed to perform a quantitative quality assessment of standard respiratory signals recorded by Type 2 and Type 3 portable sleep monitors. The proposed system allows to assess the quality (good versus bad) of consecutive 1-min segments of thoraco-abdominal movements, oronasal, nasal airflow and oxygen saturation through an automatic classifier. The performance of the classifier was evaluated in a sample of 30 unattended polysomnography recordings, comparing the computer output with the consensus of two expert scorers. The difference (computer versus scorers) in the percentage of good-quality segments was on average very small, ranging from -3.1% (abdominal movements) to 0.8% (nasal flow), with an average total classification accuracy from 90.2 (oronasal flow) to 94.9 (nasal flow), a Sensitivity from 0.93 (oronasal flow) to 0.98 (nasal flow), and a Specificity from 0.74 (nasal flow) to 0.86 (abdominal movements). In practical applications, the scorer can run a check-and-edit procedure, further improving the classification accuracy. Considering a sample of 270 unattended polysomnography recordings (recording time: 545 ± 44 min), the average time taken for the check-and-edit procedure of each recording was 6.9 ± 2.1 min for all respiratory signals.

Sleep-wake fluctuations and respiratory events during Cheyne-Stokes respiration in patients with heart failure.

Fluctuations in sleep-wake state are thought to contribute to the respiratory instability of Cheyne-Stokes respiration in patients with heart failure by promoting the rhythmic occurrence of central apnea and ventilatory overshoot. There are no data, however, on the relationship between vigilance state and respiratory events. In this study we used a novel method to detect the occurrence of state transitions (time resolution: 0.25 s, minimum duration of state changes: 2 s) and to assess their time relationship with apnoeic events. We also evaluated whether end-apnoeic arousals are associated with a ventilatory overshoot. A polysomnographic, daytime laboratory recording (25 min) was performed during Cheyne-Stokes respiration in 16 patients with heart failure. Automatic state classification included wakefulness and non-rapid eye movement sleep stages 1-2. As a rule, wakefulness occurred during hyperpnoeic phases, and non-rapid eye movement sleep occurred during apnoeic events. Ninety-two percent of the observed central apneas (N = 272) were associated with a concurrent wakefulness → non-rapid eye movement sleep → wakefulness transition. The delay between wakefulness → non-rapid eye movement sleep transitions and apnea onset was -0.3 [-3.1, 3.0] s [median (lower quartile, upper quartile); P = 0.99 testing the null hypothesis: median delay = 0], and the delay between non-rapid eye movement sleep â†’ wakefulness transitions and apnea termination was 0.2 [-0.5, 1.2] s (P = 0.7). A positive/negative delay indicates that the state transition occurred before/after the onset or termination of apnea. Non-rapid eye movement sleep â†’ wakefulness transitions synchronous with apnea termination were associated with a threefold increase in tidal volume and a twofold increase in ventilation (all P < 0.001), indicating ventilatory overshoot. These findings highlight that wakefulness â†’ non-rapid eye movement sleep → wakefulness transitions parallel apnoeic events during Cheyne-Stokes respiration in patients with heart failure. The relationships between state changes and respiratory events are consistent with the notion that state fluctuations promote ventilatory instability.

Can cardiorespiratory polygraphy replace portable polysomnography in the assessment of sleep-disordered breathing in heart failure patients?

PURPOSE: Portable polysomnography (PSG) and cardiorespiratory polygraphy are increasingly being used in the assessment of sleep-disordered breathing (SDB) in heart failure patients. Scoring of SDB from cardiorespiratory polygraphy recordings is based only on respiratory signals, while electroencephalographic, electrooculographic and electromyographic channels are taken into account when using PSG recordings. The aim of this study was to assess the agreement between these two scoring methods. METHODS: An overnight sleep study was performed in 67 heart failure patients using a standard portable polysomnograph. Each recording was scored twice, once using all acquired signals (PSG mode) and, after a median of 64 days, using only respiratory signals (cardiorespiratory mode). Agreement was assessed by Bland-Altman analysis and Cohen's kappa. RESULTS: We found that (1) more respiratory events were detected using cardiorespiratory analysis [median (25th percentile, 75th percentile), 75 (39, 200) events] compared to analysis of portable PSG [69 (29, 173) events, p < 0.0001], the extra events being, for the vast majority, central in origin; (2) the apnea/hypopnea index (AHI) estimated by cardiorespiratory polygraphy [11.9 (5.7, 30.8)/h] showed a negligible negative bias relative to portable PSG [15.1 (5.7, 33.6)/h; bias, -0.8 (-2.9, 0.4)/h, p = 0.0002]; (3) limits of agreement between the two systems (-6.2/h, 1.7/h) were much smaller than those previously observed between two nights using the same scoring modality; and (4) the kappa coefficient using categorised AHI was 0.89 (95% confidence interval (CI) 0.82, 0.96). CONCLUSIONS: We found a high degree of agreement between the AHIs obtained from the two scoring methods, thus suggesting that cardiorespiratory polygraphy may be used as an alternative to portable PSG in the assessment of SDB in heart failure patients.

Impact of optimized transcutaneous auricular vagus nerve stimulation on cardiac autonomic profile in healthy subjects and heart failure patients.

Objective.To determine the optimal frequency and site of stimulation for transcutaneous vagus nerve stimulation (tVNS) to induce acute changes in the autonomic profile (heart rate (HR), heart rate variability (HRV)) in healthy subjects (HS) and patients with heart failure (HF).Approach.We designed three single-blind, randomized, cross-over studies: (1) to compare the acute effect of left tVNS at 25 Hz and 10 Hz (n= 29, age 60 ± 7 years), (2) to compare the acute effect of left and right tVNS at the best frequency identified in study 1 (n= 28 age 61 ± 7 years), and (3) to compare the acute effect of the identified optimal stimulation protocol with sham stimulation in HS and HF patients (n= 30, age 59 ± 5 years, andn= 32, age 63 ± 7 years, respectively).Main results.In study 1, left tragus stimulation at 25 Hz was more effective than stimulation at 10 Hz in decreasing HR (-1.0 ± 1.2 bpm,p< 0.001 and -0.5 ± 1.6 bpm, respectively) and inducing vagal effects (significant increase in RMSSD, and HF power). In study 2, the HR reduction was greater with left than right tragus stimulation (-0.9 ± 1.5 bpm,p< 0.01 and -0.3 ± 1.4 bpm, respectively). In study 3 in HS, left tVNS at 25 Hz significantly reduced HR, whereas sham stimulation did not (-1.1 ± 1.2 bpm,p< 0.01 and -0.2 ± 2.9 bpm, respectively). In HF patients, both active and sham stimulation produced negligible effects.Significance.Left tVNS at 25 Hz is effective in acute modulation of cardiovascular autonomic control (HR, HRV) in HS but not in HF patients (NCT05789147).

A hybrid approach for continuous detection of sleep-wakefulness fluctuations: validation in patients with Cheyne-Stokes respiration.

Fluctuations in sleep/wake state have been proposed as an important mechanism contributing to the development of oscillatory breathing patterns, including Cheyne-Stokes respiration in patients with heart failure. In order to properly assess the interactions between changes in state and changes in ventilatory parameters, a methodology capable of continuously and reliably detecting state transitions is needed. Traditional fixed-epoch analysis of polysomnographic recordings is not suitable for this purpose. Moreover, visual identification of changes in the dominant electroencephalogram activity at the transition from wakefulness to sleep and vice versa is often very subjective. We have therefore developed a hybrid approach--including both visual scoring and computer-based procedures--for continuous analysis of state transitions from polysomnographic recordings, specifically tailored for fluctuations between wakefulness and non-rapid eye movement-1 and -2 sleep. The overall analysis process comprises three major phases: (1) manual identification of relevant electroencephalogram/electrooculogram features and events, including a sample of unequivocal alpha and theta-delta activity; (2) automatic statistical discrimination of dominant electroencephalogram activity; and (3) state classification (wakefulness, non-rapid eye movement-1 and -2). The latter is carried out by merging information from visual scoring with the output of the discriminator. Validation has been carried out in 16 patients with heart failure during daytime Cheyne-Stokes respiration, using a training and testing set of electroencephalogram polysomnograms. The statistical discriminator correctly classified 99.1 ± 1.4% and 99.2 ± 1.1% of unequivocal alpha and theta-delta activity. This approach has therefore the potential to be used to reliably measure the incidence and location of sleep-wake transitions during abnormal breathing patterns, as well as their temporal relationship with major ventilatory events.

Effect of Algorithmic Music Listening on Cardiac Autonomic Nervous System Activity: An Exploratory, Randomized Crossover Study.

It is proven that music listening can have a therapeutic impact in many clinical fields. However, to assume a curative value, musical stimuli should have a therapeutic logic. This study aimed at assessing short-term effects of algorithmic music on cardiac autonomic nervous system activity. Twenty-two healthy subjects underwent a crossover study including random listening to relaxing and activating algorithmic music. Electrocardiogram (ECG) and non-invasive arterial blood pressure were continuously recorded and were later analyzed to measure Heart Rate (HR) mean, HR variability and baroreflex sensitivity (BRS). Statistical analysis was performed using a general linear model, testing for carryover, period and treatment effects. Relaxing tracks decreased HR and increased root mean square of successive squared differences of normal-to-normal (NN) intervals, proportion of interval differences of successive NN intervals greater than 50 ms, low-frequency (LF) and high-frequency (HF) power and BRS. Activating tracks caused almost no change or an opposite effect in the same variables. The difference between the effects of the two stimuli was statistically significant in all these variables. No difference was found in the standard deviation of normal-to-normal RR intervals, LFpower in normalized units and LFpower/HFpower variables. The study suggests that algorithmic relaxing music increases cardiac vagal modulation and tone. These results open interesting perspectives in various clinical areas.

Night-to-night repeatability of measurements of nocturnal breathing disorders in clinically stable chronic heart failure patients.

BACKGROUND: Portable sleep apnea monitors are often used to screen for sleep-disordered breathing in chronic heart failure patients (CHF), but night-to-night repeatability of obtained measurements of nocturnal breathing disorders has not been fully assessed. METHODS: Fifty-six stable, moderate-to-severe CHF patients [male, 87%; age, 57 ± 9 years; NYHA class, 2.6 ± 0.6; left ventricular ejection fraction (LVEF), 32% ± 9%] underwent an unattended in-hospital cardiorespiratory recording using a portable sleep apnea monitor during two consecutive nights. The apnea/hypopnea index (AHI), apnea index (AI), oxygen desaturation index (ODI), and periodic breathing (PB) duration were computed. Intra-subject night-to-night variability was assessed by the 95% limits of random variation (LoV). We also estimated the contribution of intra-rater variability to the overall intra-subject variability. Dichotomizing the AHI and PB duration according to conventional cutoffs of, respectively, ≥5 events per hour, ≥15 events per hour, and ≥120 min, the percentage of patients concordantly classified by the two measurements was finally computed. RESULTS: The 95% LoV were ±10.6, ±7.7, ±11.3 events per hour for AHI, AI and ODI, and ±63.2 min for PB duration, respectively. The contribution of intra-rater variability to total intra-subject variability was 1.7%, 1.4%, 2.5%, and 1.3% for AHI, AI, ODI, and PB duration, respectively. Most patients (85%, 82%, and 95% for AHI ≥ 5, AHI ≥ 15, and PB duration, respectively) were classified concordantly by the two measurements. CONCLUSIONS: In patients with heart failure, measurements of severity of sleep-disordered breathing derived from portable sleep apnea monitors show significant night-to-night intra-subject variation with a negligible contribution from intra-rater variability; however, using the same measurements for classification purposes, as commonly performed in clinical practice to screen patients for sleep-disordered breathing, very stable results are obtained.

Interaction Between Arousals and Ventilation During Cheyne-Stokes Respiration in Heart Failure Patients: Insights From Breath-by-Breath Analysis.

Study Objectives: Arousals from sleep during the hyperpneic phases of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure are thought to cause ventilatory overshoot and a consequent longer apnea, thereby sustaining and exacerbating ventilatory instability. However, data supporting this model are lacking. We investigated the relationship between arousals, hyperpnea and post-hyperpnea apnea length during CSR-CSA. Methods: Breath-by-breath changes in ventilation associated with the occurrence of arousal were evaluated in 18 heart failure patients with CSR-CSA, apnea-hypopnea index ≥15/h and central apnea index ≥5/h. The change in apnea length associated with the presence of arousal during the previous hyperpnea was also evaluated. Potential confounding variables (chemical drive, sleep stage) were controlled for. Results: Arousals were associated with a large increase in ventilation at the beginning of the hyperpnea (+76 ± 35%, p < 0.0001), that rapidly declined during its crescendo phase. Around peak hyperpnea, the change in ventilation was -8 ± 26% (p = 0.14). The presence of arousal during the hyperpnea was associated with a median increase in the length of the subsequent apnea of +4.6% (Q1, Q2: -0.7%, 20.5%; range: -8.5%, 36.2%) (p = 0.021). The incidence of arousals occurring at the beginning of hyperpnea and mean ventilation in the region around its peak were independent predictors of the change in apnea length (p = 0.004 and p = 0.015, respectively; R2 = 0.78). Conclusions: Arousals from sleep during CSR-CSA in heart failure patients are associated with a rapidly decreasing ventilatory overshoot at the beginning of the hyperpnea, followed by a tendency toward a slight ventilatory undershoot around its peak. On average, arousals are also associated with a modest increase in post-hyperpnea apnea length; however, large increases in apnea length (>20%) occur in about a quarter of the patients.

Fluctuations of the fractal dimension of the electroencephalogram during periodic breathing in heart failure patients.

The physiological mechanisms responsible for periodic breathing (PB) in heart failure (HF) patients are still debated. A role for rhythmic shifts in the level of wakefulness has been suggested, but their existence has never been proven. In this study we investigated the existence of an oscillation in EEG activity during PB in these patients and assessed its relationship with the ventilatory oscillation. EEG activity was measured by the fractal dimension (FD) and by a spectral technique (weighted mean frequency, WMF) in 17 stable HF patients (mean age +/- SD: 57+/-10 yrs, NYHA class: 2.6 +/- 0.4, LVEF: 24 +/- 6%), with sustained PB during supine rest. The relationship between minute ventilation (MV) signal and FD and WMF was assessed by coherence analysis. Most patients (10/17) showed a well defined oscillation in FD and WMF at the frequency of PB closely linked (coherence > 0.7) with the oscillation of MV. In the remaining patients, neither FD nor WMF showed a clear oscillatory pattern synchronous with MV. Overall, the two EEG-derived parameters showed the same coherence with the ventilatory oscillation (mean coherence +/- SD: 0.65 +/- 0.25 vs 0.66 +/- 0.23, for FD and WMF respectively, p = 0.44). Our results provide evidence that during PB in HF patients, EEG activity often, but not always, fluctuates synchronously with the ventilatory oscillation. These fluctuations can be effectively detected by the fractal dimension, but classical spectral methods provide substantially the same information. Other mechanisms, particularly chemical instability in the respiratory control system, are likely to play a role in the genesis of PB.

Pathophysiological and clinical relevance of simplified monitoring of nocturnal breathing disorders in heart failure patients.

AIMS: Nocturnal breathing disorders in the form of periodic breathing (PB) are very common in heart failure (HF) patients. There is an increasing interest in simple and affordable tools to screen patients and monitor these disorders at home on a long-term basis. We aimed to assess the pathophysiological and clinical relevance of a simplified method for monitoring of PB suitable to be self-managed by the patient at home. METHODS AND RESULTS: A night-time respiratory recording was performed in 397 optimally treated HF patients (age 60 +/- 11 years, NYHA class 2.4 +/- 0.6, left ventricular ejection fraction 29 +/- 7%) and the duration of PB (PB(Dur)) automatically computed. Patients were followed-up for 1 year and the prognostic value of PB(Dur) evaluated. In 45 patients, we assessed the association between PB(Dur) and severity of oxygen desaturations (number of desaturations >3%). Twenty six of the 397 patients died of cardiac causes. A PB(Dur) > or =2 h was significantly associated with an increased risk of cardiac death after adjustment for major clinical predictors [hazard ratio (95% CI): 3.5 (1.6-7.9), P = 0.002]. The correlation between PB(Dur) and severity of desaturations was 0.94 (P < 0.0001). CONCLUSION: Relevant pathophysiological and clinical information can be obtained from simplified monitoring of breathing disorders managed by the patient. These results provide new perspectives in the investigation of the clinical impact of abnormal breathing in HF patients.

Arterial oxygen saturation during Cheyne-Stokes respiration in heart failure patients: does measurement site matter?

OBJECTIVE: Despite the fact that the ear is the site to monitor arterial oxygen saturation by pulse oximetry (SpO2) closest to carotid chemoreceptors, sleep studies almost invariably use finger probes. This study aimed to assess the timing and morphological differences between SpO2 signals at the ear and finger during Cheyne-Stokes respiration (CSR) in heart failure (HF) patients. METHODS: We studied 21 HF patients with CSR during a 40-min in-laboratory resting recording. SpO2 was recorded by: (1) two identical bedside pulse-oximeters with an ear (SpO2_Ear) and a finger probe (SpO2_Finger), and (2) a standard polysomnograph with a finger probe (SpO2_PSG). We estimated the delays between signals and, for each signal, computed the mean and minimum SpO2, the magnitude of cyclic desaturations and the overall time spent with SpO2<90% (T90%). RESULTS: The SpO2_Finger signal was significantly delayed [bias: 12.7 s (95% limits of agreement: 2.2, 23.0 s)] and slightly but not significantly downward-shifted with respect to SpO2_Ear. SpO2_PSG was almost synchronous with SpO2_Finger; however, a further significant downward shift was observed relative to the latter. In particular, minimum SpO2_PSG was significantly lower [-2.1% (- 4.8, 0.6%)], and desaturations and T90% were significantly higher than SpO2_Finger [1.2% (-1.3, 3.7%), and 13.9% (-12.3, 40.0%), respectively]. CONCLUSION: During CSR in HF patients, the marked delay between SpO2_Ear and SpO2_Finger makes the interpretation of the timing relationship between peripheral chemoreceptor stimulation and ventilatory events rather difficult. The observed discrepancies between SpO2_PSG and SpO2_Finger, which may be due to differences in the processing of raw SpO2 signals, call for a standardization of processing algorithms.

Nocturnal cardiac arrhythmia in patients with obstructive sleep apnea.

BACKGROUND AND PURPOSE: Nocturnal cardiac arrhythmias occur in patients with obstructive sleep apnea (OSA), reportedly as a consequence of the autonomic effects of recurrent apnea with subsequent oxygen desaturation. We have investigated whether different patterns of OSA are associated with specific arrhythmia during sleep. PATIENTS AND METHODS: Electrocardiographic (ECG) data recorded during polysomnography (PSG) were analysed in 257 consecutive OSA patients to determine the prevalence of cardiac rhythm disturbances, and to relate these to breathing pattern (normal, apnea/hypopnea, recovering ventilation, snoring) and oxygen saturation. RESULTS: Arrhythmias were found in 18.5% of patients. Patients with nocturnal bradyarrhythmia (BA) had higher values of ventilatory disturbance (apnea-hypopnea index [AHI] 58.8+/-36.8 vs 37.2+/-30.3, p=0.02), mean desaturation amplitude (8.9+/-4 vs 5.9+/-3.4%, p=0.03), and a lower SaO(2) nadir (69% vs 77%, p=0.003) than those without arrhythmia. The prevalence of BA in patients with AHI>or=30/h was significantly higher than that observed in those with AHI<30/h (7.8% vs 1.5%, respectively; chi(2)=5.61, p=0.01). In contrast, patients with tachyarrhythmia (TA) had no significant differences in AHI, mean desaturation amplitude or SaO(2) nadir than those without arrhythmia. No associations were found between arrhythmia and the presence of comorbidity or concomitant medical therapy, except for an association between tachyarrhythmia and chronic obstructive pulmonary disease (COPD) (odds ratio 2.53; 95% confidence intervals 1.1-5.8, p=0.03). CONCLUSIONS: We conclude that while BA during sleep is associated with OSA severity, concomitant COPD or beta(2)-treatment may play a role in the development of TA during sleep.

Temporal relationship between arousals and Cheyne-Stokes respiration with central sleep apnea in heart failure patients.

OBJECTIVE: The interplay between arousals and respiratory events during Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF) patients is still not fully understood. We investigated the temporal relationship between arousals and CSR-CSA. METHODS: Episodes of CSR-CSA during sleep stages N1-N2 were analyzed in 22 HF patients with an apnea-hypopnea index ≥15/h, dominant CSA and central apnea index ≥5/h. For each CSR-CSA cycle (apnea + hyperpnea), we determined the onset (ARonset, relative to hyperpnea onset) and duration of detected arousals. RESULTS: Arousals (N = 2348) mostly occurred within the first half of the hyperpneic phase (42.6%, ARonset = 10.6 ±â€¯2.1 s; duration = 10.6 ±â€¯5.2 s) or close to hyperpnea onset (21.5%, ARonset = -0.1 ±â€¯0.6 s; duration = 13.9 ±â€¯5.4 s). Within-apnea arousals were less frequent (12.4%, ARonset = -16.0 ±â€¯4.7 s; duration = 3.8 ±â€¯1.4 s). The proportion of CSR-CSA cycles without any hyperpnea-related arousal was 27.5 ±â€¯18.2%. Hyperpnea-related arousability (total number of hyperpneic arousals/total duration of hyperpneas) and apnea-related arousability were 63.4 ±â€¯21.0/h and 23.8 ±â€¯16.9/h, respectively (p < 0.0001). CONCLUSION: During CSR-CSA, a significant proportion of arousals occur at hyperpnea onset, indicating a low arousal threshold. Hyperpneic arousals are not essential for CSR-CSA. Arousability markedly increases during hyperpneas, likely due to the concurrent increase in chemoreceptor stimulation. SIGNIFICANCE: This study extends current knowledge on the interplay between sleep instability and respiratory events during CSR-CSA.

Chronic thromboembolic pulmonary hypertension: Reversal of pulmonary hypertension but not sleep disordered breathing following pulmonary endarterectomy.

BACKGROUND: It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors. METHODS: Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients. RESULTS: Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ±â€¯3.9 vs 7.0 ±â€¯4.5 vs 9.7 ±â€¯4.3 mm Hg (p = 0.054), mPAP: 39 ±â€¯12 vs 48 ±â€¯11 vs 51 ±â€¯16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized. CONCLUSIONS: Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH.

Clinical relevance of short-term day-time breathing disorders in chronic heart failure patients.

BACKGROUND: Periodic Breathing (PB, waxing and waning of tidal volume in which hyperventilation alternates with periods of apnoea or hypopnoea), is common during sleep and wakefulness in patients with Heart Failure (HF) and may increase mortality. AIM: To assess the effect of short-term, day-time PB on prognosis, in HF patients. METHODS: We prospectively studied 380 consecutive HF referrals who had a 10 min, supine day-time respiratory recording. We related PB (adjusted for known predictors) to total cardiac mortality, during a median follow-up of 41 months. RESULTS: Day-time PB occurred in 145/380 patients who had more severe HF and more compromised left ventricular function (p<0.005). Survival curves began to separate after 10 months and diverged steadily over the next 4 years with a cumulative risk of 41% (PB) vs 26% (No-PB), p=0.002. PB was independently predictive of increased cardiac mortality when entered into a clinical prognostic model (including NYHA Class, LVEF, LVEDD, Systolic Arterial Pressure, beta-blocker treatment, peak VO2 and blood urea) with a RR: 1.8, 95% CI 1.20-2.81. CONCLUSION: In advanced HF the presence of PB during a short day-time recording adds to known predictors of cardiac mortality. This may have practical implications for trials of HF therapy.

Differential impact of body position on the severity of disordered breathing in heart failure patients with obstructive vs. central sleep apnoea.

AIMS: Obstructive (OSA) and central sleep apnoea (CSA) are a common comorbidity in patients with heart failure. The purpose of this study was to assess and compare the impact of body position on the severity of sleep apnoea in these two groups of patients. METHODS AND RESULTS: Standard polysomnography was performed in consecutive, clinically stable, optimally treated patients with moderate-to-severe heart failure and systolic dysfunction. Patients with an apnoea-hypopnoea index (AHI) ≥15/h (n = 120) were included in the study. The severity of sleep-disordered breathing was quantified by the AHI, the mean value of oxygen desaturations (O2 desat) and the apnoea ratio. Data from the right and left positions were combined into a single lateral position. Positional sleep apnoea was defined as a >50% reduction in the AHI between the supine and the lateral position. Twenty-nine and 91 subjects had dominant OSA and CSA, respectively. The AHI markedly decreased from the supine to the lateral position in both groups [OSA: (median [q1,q3]) 50.3 [36.9, 67.6]/h vs. 10.4 [7.0, 18.5]/h, P < 0.0001; CSA: 47.4 [37.6, 56.0]/h vs. 19.3 [11.9, 33.3]/h]. The reduction was greater in OSA patients (p = 0.027). Similarly, O2 desat and the apnoea ratio decreased in the lateral position (P < 0.0001). Positional sleep apnoea was observed in 76% of OSA and 53% of CSA patients (P = 0.028). CONCLUSION: This study demonstrates that the lateral sleeping position has a major beneficial effect on the severity of sleep-disordered breathing in heart failure patients, and that this improvement is greater in subjects with OSA than in those with CSA.