Central Sleep-disordered Breathing Research Articles

Sleep-disordered breathing on respiratory polygraphy in neonates with spina bifida.

Studies have shown a high prevalence of sleep-disordered breathing (SDB) in children with spina bifida. International standards for regular testing for SDB in this population are lacking. While there are studies investigating the prevalence of SDB in children with spina bifida, there are close to no studies in neonates. To evaluate if routine respiratory polygraphy (RPG) testing is indicated for neonates with spina bifida and if yes, with what therapeutic consequence. We conducted a retrospective cohort study of all neonates with spina bifida at the University (Children's) Hospital Zurich after fetal spina bifida repair born between 2017 and 2022, who had undergone at least 1 RPG evaluation during hospitalization on the neonatal ward. RPG were evaluated by a blinded group of experienced pediatric pulmonologists. Based on the neonatal RPG results and pediatric pulmonologist's recommendation for caffeine therapy the spina bifida cohort was divided into two groups. Neonatal baseline RPG and follow-up RPG at the age of the 3 months were evaluated. 48 neonates with RPG were included. Compared to the standard values in healthy neonates, the RPG results of this spina bifida cohort showed findings of SDB with central apnea and hypopnea. 22 (45.8%) neonatal RPG evaluations detected central SDB, prompting caffeine therapy. Follow-up RPG conducted after 3 months showed significant improvement of SDB with (almost) no need for continuation of caffeine. We recommend the implementation of routine RPG testing in neonates with spina bifida to detect SDB and facilitate early targeted treatment.

Influence of Obstructive Apnea Index on Persistent Left Ventricular Dysfunction in Patients with ST-Segment Elevation Myocardial Infarction.

Background: We retrospectively investigated the effects of the severity and classification of sleep-disordered breathing (SDB) on left ventricular (LV) function in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 115 patients with STEMIs underwent a sleep study using a multichannel frontopolar electroencephalography recording device (Sleep Profiler) one week after STEMI onset. We evaluated LV global longitudinal strain (LV-GLS) using two-dimensional echocardiography at one week and seven months. Patients were classified as no SDB (AHI < 5 events/h), obstructive SDB (over 50% of apnea events are obstructive), and central SDB (over 50% of apnea events are central). Due to the device's limitations in distinguishing obstructive from central hypopnea, SDB classification was based on apnea index percentages. Results: The obstructive apnea index (OAI) was significantly associated with LV-GLS at one week (r = 0.24, p = 0.027) and seven months (r = 0.21, p = 0.020). No such correlations were found for the central apnea index and SDB classification. Multivariable regression analysis showed that the OAI was independently associated with LV-GLS at one week (β = 0.24, p = 0.002) and seven months (β = 0.20, p = 0.008). Conclusions: OAI is associated with persistent LV dysfunction assessed by LV-GLS in STEMI.

Prevalence of central sleep apnea among veterans and response rate to continuous positive airway pressure therapy.

Sleep-disordered breathing (SDB) is common in the Veteran population. In this retrospective study, we investigated the prevalence of comorbid central and obstructive SDB and the response rate to PAP among Veterans. Veterans were screened from a single VA medical center who had polysomnography (PSG) study from 2017 to 2021 to ascertain the presence, severity, and type of SDB by measuring the apnea-hypopnea index (AHI) and central apnea index (CAI). Patients were excluded if they did not have complete studies (diagnostic and PAP titration studies). The inclusion criteria for these analyses were central sleep apnea (CSA) defined as AHI ≥ 10 events/hour and CAI ≥ 5 events/hour. Diagnostic "CSA only" was defined as AHI ≥ 10 events/hour and CAI ≥ 50% of AHI. "OSA only" was defined if AHI ≥ 10 events/hour and CAI < 5 events/hour. Comorbid central and obstructive sleep apnea (COSA) was defined if AHI ≥ 10 events/hour and CAI > 5 events/hour but < 50% of AHI. The responsiveness to PAP therapy was determined based on the CAI < 5 events/hour on the titration study. A total of 90 patients met the inclusion criteria and from those 64 Veterans were found to have COSA (71%), 18 (20%) were CSA only, and 8 (9%) were OSA only. A total of 22 (24.4%) Veterans diagnosed with CSA or COSA were responsive to PAP therapy. Sixty days after treatment initiation, both responsive and nonresponsive groups had significant decreases in AHI and CAI (p < 0.05). Comorbid central and obstructive SDB is common among Veterans. The response to PAP therapy is suboptimal but improves over time.

Sindrom kongenitalne centralne hipoventilacije - heterogenost kliničke prezentacije, modaliteti ventilatorne potpore i ishodi

Introduction/aim: Central congenital hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by autonomic dysregulation and alveolar hypoventilation with ventilatory support being the cornerstone of long-term survival. The aim was to present different ventilatory strategies in CCHS. Material and methods: The study included retrospectively analyzed medical records of five patients diagnosed with CCHS in a national pediatric center. Alveolar hypoventilation was evidenced by noninvasive continuous transcutaneous capnometry and central sleep-disordered breathing documented by polygraphy. Clinical evaluation included cardiac evaluation, rectal biopsies, and urinalysis of catecholamine levels. Life-threatening cardiac arrhythmias were indications for pacemaker implantation. Genetic analyses of alanine residues in paired-like homeobox 2B gene (PHOX2B) confirmed the diagnosis. Results: A range of pathogenic changes in the PHOX2B gene resulted in varying clinical outcomes. 3/4 (75%) of patients with an early onset were ventilated continuously through a tracheostomy tube, while one patient was successfully treated with noninvasive ventilation (NIV) as the preferred option. Additionally, NIV was applied in one child with early-onset disease after decannulation. Finally, NIV was also feasible in a case with late-onset disease presented by the time of four years with symptoms of pulmonary hypertension. There were no serious side effects of ventilation, and one patient died due to cardiac arrhythmias. Conclusion: Invasive mechanical ventilation remains the treatment of choice in most children with early-onset disease. However, the indications for NIV have been widened from overnight ventilation in the late-onset course to selected cases with early-onset disease. The timely switch from IMV to NIV has been popularized in recent years worldwide.

Sleep-disordered breathing in patients with Chiari malformation type II: a case-control study and review of the literature.

The main aim was to evaluate the prevalence of sleep-disordered breathing (SDB) in patients with Chiari II malformation (CM-II). The secondary objectives were to evaluate the association between SDB, morphological abnormalities, and neurological symptoms and to review the literature on patients with SDB and CM-II. The study has a cross-sectional, case-control design. Patients with CM-II (patients) were compared to control patients referred for clinical polysomnography in the Sleep Medicine Unit, matched for age and sex. All patients underwent brain and spinal cord magnetic resonance imaging, and polysomnography was conducted for all participants. A review of the literature about SDB in patients with CM-II was performed. Forty patients were included (20 patients vs 20 control patients). SDB was identified in 45% of patients, a significantly higher prevalence compared to control patients. Three patients presented with purely obstructive SDB, 3 patients with purely central SDB, and 3 patients with both obstructive and central SDB. Compared with control patients, patients with CM-II showed a higher oxygen desaturation index (median: CM-II, 3.7; interquartile range, 1.6-19.5; control patients: 1.1; interquartile range, 0.3-3.2) and obstructive apnea-hypopnea index (median: CM-II, 1.5; interquartile range, 0.5-5.1; control patients, 0.1; interquartile range, 0.0-0.7). A logistic regression showed that the risk of developing SDB in patients affected by CM-II was 14.7 times higher than in the control population. Our study and literature review showed a high prevalence of SDB in patients with CM-II. These patients are often asymptomatic at diagnosis, suggesting that PSG should be routinely provided in this population. Lazzareschi I, Curatola A, Massimi L, etal. Sleep-disordered breathing in patients with Chiari malformation type II: a case-control study and review of the literature. J Clin Sleep Med. 2022;18(9):2143-2154.

Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing.

RationaleDetermining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment.ObjectivesHere we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies.MethodsFrom five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs.Measurements and Main ResultsA total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93].ConclusionsUsing nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea.

Sleep-disordered breathing in Australian children with Prader-Willi syndrome following initiation of growth hormone therapy.

AimIn children with Prader‐Willi syndrome (PWS), growth hormone (GH) improves height and body composition; however, may be associated with worsening sleep‐disordered breathing (SDB). Some studies have reported less SDB after GH initiation, but follow‐up with polysomnography is still advised in most clinical guidelines.MethodsThis retrospective, multicentre study, included children with PWS treated with GH at seven PWS treatment centres in Australia over the last 18 years. A paired analysis comparing polysomnographic measures of central and obstructive SDB in the same child, before and after GH initiation was performed with Wilcoxon signed‐rank test. The proportion of children who developed moderate/severe obstructive sleep apnoea (OSA) was calculated with their binomial confidence intervals.ResultsWe included 112 patients with available paired data. The median age at start of GH was 1.9 years (range 0.1–13.5 years). Median obstructive apnoea hypopnoea index (AHI) at baseline was 0.43/h (range 0–32.9); 35% had an obstructive AHI above 1.0/h. Follow‐up polysomnography within 2 years after the start of GH was available in 94 children who did not receive OSA treatment. After GH initiation, there was no change in central AHI. The median obstructive AHI did not increase significantly (P = 0.13), but 12 children (13%, CI95% 7–21%) developed moderate/severe OSA, with clinical management implications.ConclusionsOur findings of a worsening of OSA severity in 13% of children with PWS support current advice to perform polysomnography after GH initiation. Early identification of worsening OSA may prevent severe sequelae in a subgroup of children.

Mirtazapine reduces susceptibility to hypocapnic central sleep apnea in males with sleep-disordered breathing: a pilot study.

Studies in humans and animal models with spinal cord injury (SCI) have demonstrated that medications targeting serotonin receptors may decrease the susceptibility to central sleep-disordered breathing (SDB). We hypothesized that mirtazapine would decrease the propensity to develop hypocapnic central sleep apnea (CSA) during sleep. We performed a single-blind pilot study on a total of 10 men with SDB (7 with chronic SCI and 3 noninjured) aged 52.0 ± 11.2 yr. Participants were randomly assigned to either mirtazapine (15 mg at bedtime) or a placebo for at least 1 wk, followed by a 7-day washout period before crossing over to the other intervention. Split-night studies included polysomnography and induction of hypocapnic CSA using a noninvasive ventilation (NIV) protocol. The primary outcome was CO2 reserve, defined as the difference between eupneic and end of NIV end-tidal CO2 ([Formula: see text]) preceding induced hypocapneic CSA. Secondary outcomes included controller gain (CG), other ventilatory parameters, and SDB severity. CG was defined as the ratio of change in minute ventilation (V̇e) between control and hypopnea to the change in CO2 during sleep. CO2 reserve was significantly widened on mirtazapine than placebo (-3.8 ± 1.2 vs. -2.0 ± 1.5 mmHg; P = 0.015). CG was significantly decreased on mirtazapine compared with placebo [2.2 ± 0.7 vs. 3.5 ± 1.9 L/(mmHg × min); P = 0.023]. There were no significant differences for other ventilatory parameters assessed or SDB severity between mirtazapine and placebo trials. These findings suggest that the administration of mirtazapine can decrease the susceptibility to central apnea by reducing chemosensitivity and increasing CO2 reserve; however, considering the lack of changes in apnea-hypopnea index (AHI), further research is required to understand the significance of this finding.NEW & NOTEWORTHY To our knowledge, this research study is novel as it is the first study in humans assessing the effect of mirtazapine on CO2 reserve and chemosensitivity in individuals with severe sleep-disordered breathing. This is also the first study to determine the potential therapeutic effects of mirtazapine on sleep parameters in individuals with a spinal cord injury.

Sleep Studies in Children

Sleep-related breathing disorders (SRBD), also referred to as sleep-disordered breathing (SDB), are common sleep disorders in children. They can be broadly divided between central and obstructive sleep-disordered breathing with or without associated hypoventilation. In most cases, SRBD are associated with adenotonsillar hypertrophy (obstructive SDB) which are classified as simple. SRBD can co-exist with an underlying condition like obesity, genetic syndromes or neuromuscular disorders which are classified as complex. Polysomnography (PSG) is the gold standard for diagnosing sleep disorders. However, it is time-consuming and requires trained technician to acquire and interpret signals. Attended in-lab respiratory polygraphies are easier to conduct and provide respiratory data equivalent to a PSG. Similar to adult sleep services, overnight unattended home respiratory polygraphies are becoming more widely used. These require careful patient selection and good parental education programs to be most successful in children. Overnight oximetry has limitations but can be a useful tool for screening children with obstructive sleep apnea and prioritizing treatment. This review aims to discuss these various diagnostic methods to assess sleep disorders in children.

Hypercapnic ventilatory response in heart failure patients with central sleep-disordered breathing

Abstract Background Sleep-disordered breathing (SDB) is a highly common comorbidity in heart failure (HF) patients and appears mainly as obstructive SDB, or central SDB. SDB has been shown to deteriorate quality of life in HF patients, but its presence is also associated with worse prognosis. SDB severity has been shown to mirror HF level and hereby hypercapnic ventilatory response (HCVR) depicts ventilation instability which furthermore expresses HF severity. But HCVR direct correlation with HF to predict HF severity has not been sufficiently studied yet. Methods and results We included 501 HF patients that received multichannel cardiorespiratory polygraphy, clinical workup for HF and HCVR in our center. The degree of SDB was graded with apnea-hypopnea-index (AHI) with guideline recommendation for treatment at an AHI &amp;gt;15/h. NT-Pro-BNP was obtained for HF quantification. Mean age was 66.4±11 years, body mass index (BMI) 30.7±5 kg/m2 and mean HCVR was 2.56±1.18. 136 (27.2%) patients had central SDB with a proportion of 124 (24.8%) having moderate to severe SDB (AHI &amp;gt;15/h). 345 (68.9%) had obstructive SDB with moderate to severe SDB in 296 (59.1%) patients. Differences were detected for HCVR and HF in the central SDB group with a HCVR of 2.78±1.4 and NT-Pro-BNP of 2835.88±10536.4 pg/ml, while the OSA group shows a HCVR of 2.5±1 and NT-Pro-BNP of 929.9±1781. Linear regression identified HCVR (p=0.045) and NT-Pro-BNP (p=0.034) to independently correlate with central SDB and in addition HCVR was also significantly associated with NT-Pro-BNP (p=0.007). Conclusion HF severity is closely linked to both NT-Pro-BNP and central SDB. HCVR seems to have the potential to predict manifestation of central SDB and increased NT-Pro-BNP values in HF. HCVR may be an easily obtainable parameter to identify both HF severity and presence of central SDB in HF patients. Funding Acknowledgement Type of funding source: None

The influence of opioids and nonopioid central nervous system active medications on central sleep apnea: a case-control study.

Opioids are known to contribute to central sleep apnea (CSA), but the influence of nonopioid central nervous system active medications (CNSAMs) on CSA remains unclear. In light of the hypothesized impact of nonopioid CNSAMs on respiration, we examined the relationships between the use of opioids only, nonopioid CNSAMs alone, and their combination with CSA. Among all adults who underwent polysomnography testing at the University of Michigan's sleep laboratory between 2013 and 2018 (n = 10,606), we identified 212 CSA cases and randomly selected 300 controls. Participants were classified into four groups based on their medication use: opioids alone, nonopioid CNSAMs only, their combination, and a reference group, including those who did not use any of these medications. We defined CSA as a binary outcome and as a continuous variable using central apnea index data. Logistic and linear regression were used to examine associations between medication use, CSA diagnosis, and central apnea index. Study participants included 58% men, and mean age was 50 (± 14 standard deviation years. Nearly half of the study participants did not use opioids or nonopioid CNSAMs, 6% used opioids alone, 27% nonopioid CNSAMs alone, and 16% used a combination of these medications. In adjusted analyses, opioids-only users had a nearly twofold increase in CSA odds, whereas those who used a combination of opioids and nonopioid CNSAMs had fivefold higher odds of CSA relative to the reference group. In contrast, the use of nonopioid CNSAMs alone had protective associations with CSA. This report showed increased odds of CSA, particularly among patients with sleep complaints who were prescribed opioids in combination with nonopioid CNSAMs compared with those who did not use any of these medications.

Effect of acetazolamide on susceptibility to central sleep apnea in chronic spinal cord injury.

Spinal cord injury (SCI) is an established risk factor for central sleep apnea. Acetazolamide (ACZ), a carbonic anhydrase inhibitor, has been shown to decrease the frequency of central apnea by inducing mild metabolic acidosis. We hypothesized that ACZ would decrease the propensity to develop hypocapnic central apnea and decrease the apneic threshold. We randomized 16 participants with sleep-disordered breathing (8 SCI and 8 able-bodied controls) to receive ACZ (500 mg twice a day for 3 days) or placebo with a 1-wk washout before crossing over to the other drug arm. Study nights included polysomnography and determination of the hypocapnic apneic threshold and CO2 reserve using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal Pco2 () before and after. Steady-state plant gain, the response of end-tidal Pco2 to changes in ventilation, was calculated from and V̇e ratio during stable sleep. Controller gain, the response of ventilatory drive to changes in end-tidal Pco2, was defined as the ratio of change in V̇e between control and hypopnea to the ΔCO2 during stable non-rapid eye movement sleep. Treatment with ACZ for three days resulted in widening of the CO2 reserve (-4.0 ± 1.2 vs. -3.0 ± 0.7 mmHg for able-bodied, -3.4 ± 1.9 vs. -2.2 ± 2.2 mmHg for SCI, P < 0.0001), and a corresponding decrease in the hypocapnic apnea threshold (28.3 ± 5.2 vs. 37.1 ± 5.6 mmHg for able-bodied, 29.9 ± 5.4 vs. 34.8 ± 6.9 mmHg for SCI, P < 0.0001), respectively. ACZ significantly reduced plant gain when compared with placebo (4.1 ± 1.7 vs. 5.4 ± 1.8 mmHg/L min for able-bodied, 4.1 ± 2.0 vs. 5.1 ± 1.7 mmHg·L-1·min for SCI, P < 0.01). Acetazolamide decreased apnea-hypopnea index (28.8 ± 22.9 vs. 39.3 ± 24.1 events/h; P = 0.05), central apnea index (0.6 ± 1.5 vs. 6.3 ± 13.1 events/h; P = 0.05), and oxyhemoglobin desaturation index (7.5 ± 8.3 vs. 19.2 ± 15.2 events/h; P = 0.01) compared with placebo. Our results suggest that treatment with ACZ decreases susceptibility to hypocapnic central apnea due to decreased plant gain. Acetazolamide may attenuate central sleep apnea and improve nocturnal oxygen saturation, but its clinical utility requires further investigation in a larger sample of patients.NEW & NOTEWORTHY Tetraplegia is a risk factor for central sleep-disordered breathing (SDB) and is associated with narrow CO2 reserve (a marker of susceptibility to central apnea). Treatment with high-dose acetazolamide for 3 days decreased susceptibility to hypocapnic central apnea and reduced the frequency of central respiratory events during sleep. Acetazolamide may play a therapeutic role in alleviating central SDB in patients with cervical spinal cord injury, but larger clinical trials are needed.

The Effect of Positive Airway Pressure Treatment of Obstructive and Central Sleep Apnea on the Recurrence of Atrial Fibrillation/Flutter Postintervention.

A strong association between sleep-disordered breathing (SDB) and atrial fibrillation and/or atrial flutter (AF) has consistently been observed in epidemiologic and interventional studies. The effect of positive airway pressure (PAP) on AF recurrence is inconclusive. This study sought to evaluate the effectiveness of PAP therapy for SDB on AF recurrence. This was a single-center, retrospective study conducted at a tertiary referral center. All adult patients who had SDB on polysomnography and underwent AF intervention (ablation or cardioversion) following polysomnography from January 1992-December 2014 were analyzed. Primary outcome was time to first-documented recurrence of AF after AF intervention by Kaplan-Meier estimates. Among 30,188 patients with obstructive and central SDB, 429 had this diagnosis before AF intervention; 269 were "PAP-adherent users," the remaining 160 were "PAP-nonusers." Patients in both groups had similar age, sex, body mass index (BMI), ejection fraction, left atrial volume index (LAVI), antiarrhythmic medications, diabetes mellitus, systemic hypertension, and heart failure diagnoses. Time to recurrence of AF postintervention was no different in PAP-adherent users and nonusers (4.8 and 4.1 months respectively, P = .7). Cardioversion (compared to catheter ablation) was the strongest independent predictor of recurrent AF (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.39-2.94, P < .001). BMI and LAVI were also significant predictors of recurrence in adjusted analyses (HR 1.01, 95% CI 1.003-1.023, P = .10 and HR 1.01, 95% CI 1.001-1.019, P = .024 respectively). Our study found no effect of PAP treatment of SDB on time to recurrence of AF post-AF intervention. Increased risk of recurrent AF was associated with high BMI and LAVI. These findings may affect the clinical management of AF.

P1767Prevalence and clinical significance of sleep-disordered breathing in patients with hypertrophic cardiomyopathy

Abstract Background Despite major advances in knowledge on hypertrophic cardiomyopathy (HCM) at the genetic and molecular levels, the understanding of essential clinical aspects remains limited. The aim of this study is to identify the prevalence and clinical significance of Sleep-disordered Breathing (SDB) in a large patient population. Methods 201 patients (78 women, age 64±15 years) with HCM were screened for obstructive (OSA) or central (CSA) sleep-disordered breathing using multichannel cardiorespiratory polygraphy. Additionally, patients received a spiroergometric examination and echocardiography. SDB was defined as apnea-hypopnea index (AHI) ≥5/h and OSA/CSA differentiated after the majority of events. Results SDB was documented in 60% of all patients. OSA was diagnosed in 71 patients (35.3%) and CSA in 44 (21.9%) patients. SDB requiring treatment was found in 106 (52.7%) patients. In patients with AHI ≥15/h NYHA class was increased (2.1 vs. 2.39, p=0.04) and maximal O2 uptake during exercise was lower (20.1 vs. 16.1 p&lt;0.001). Also left atrial diameter was significantly larger (46.9 mm vs. 50.41 mm, p=0.01) and rate of atrial fibrillation was increased (0.5 vs. 0.72 p=0.03). CSA pts had a larger left atrial diameter compared to pts with OSA (52.13 mm vs. 47.82 mm, p=0.02). Conclusion There is a high prevalence of SDB in HCM patients. Patients with moderate to severe SDB showed increased atrial fibrillation incidence and reduced cardiopulmonary performance. Whether the SDB has an independent prognostic relevance in patients with HCM needs to be elucidated.

CON: Persistent Central Sleep Apnea/Hunter-Cheyne-Stokes Breathing, Despite Best Guideline-Based Therapy of Heart Failure With Reduced Ejection Fraction, Is Not a Compensatory Mechanism and Should Be Suppressed.

CON: Persistent Central Sleep Apnea/Hunter-Cheyne-Stokes Breathing, Despite Best Guideline-Based Therapy of Heart Failure With Reduced Ejection Fraction, Is Not a Compensatory Mechanism and Should Be Suppressed.

P6173Impairment of pulmonary diffusion capacity correlates with hypoxemic burden in heart failure patients with central sleep-disordered breathing

P6173Impairment of pulmonary diffusion capacity correlates with hypoxemic burden in heart failure patients with central sleep-disordered breathing

Sleepiness and activity in heart failure patients with reduced ejection fraction and central sleep-disordered breathing

ObjectivePatients with heart failure (HF) and sleep disordered breathing (SDB) are typically not sleepy, unlike patients without heart failure. Previous work in HF patients with obstructive SDB suggested that sleepiness was associated with a reduction in daytime activity. The consequences of predominately central SDB on sleepiness in HF are less well understood. The aim of this study was to test the hypothesis that subjective sleepiness is associated with reduced daytime activity in HF patients with central SDB, compared to those without SDB. MethodsThe Epworth Sleepiness Scale (ESS), nocturnal polysomnography, and 14 days of wrist watch actigraphy were used to assess subjective daytime sleepiness, nocturnal sleep and breathing, and 24-h activity levels, respectively. ResultsA total of 54 patients with HF were studied, nine had obstructive SDB and were removed from further analysis. Of the patients, 23 had HF with predominantly central SDB (HF-CSA; apnea–hypopnea index (AHI) median 20.6 (IQR 12.9–40.2)/h), and 22 had noSDB (HF-noSDB; AHI 3.7 (2.5–5.9)/h). The median patient age was 68 years (range 59–73 years). There were no significant differences either in ESS score (HF-CSA; 8 [4–10] vs. HF-noSDB; 8 (6–12); p = 0.49) or in duration of daytime activity (HF-CSA 14.5 (14.1–15.2) and HF-noSDB 15.1 (14.4–15.3) hours; p = 0.10) between the groups. ConclusionHF patients with predominately central SDB are not subjectively sleepy compared to those without SDB, despite reduced sleep quality. We speculate that the lack of sleepiness (based on ESS score) may be due to increased sympathetic nerve activity, although further studies are needed due to the small number (n = 5) of sleepy HF-CSA patients. Daytime activity was not different between HF-noSDB and HF-CSA patients.

Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery.

Background:Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) are highly prevalent in stroke patients. Recent studies suggest that they represent both a risk factor and a consequence of stroke and affect stroke recovery, outcome, and recurrence.Methods:Review of literature.Results:Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in TIA and stroke patients are recommended in view of the very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of obstructive SDB with continuous positive airway pressure is recommended given the strength of the increasing evidence in support of a positive effect on outcome (Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB. Recently, both reduced and increased sleep duration, as well as hypersomnia, insomnia, and restless legs syndrome (RLS), were also suggested to increase stroke risk. Mainly experimental studies found that SWD may in addition impair neuroplasticity processes and functional stroke recovery. Treatment of SWD with hypnotics and sedative antidepressants (insomnia), activating antidepressants or stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias) are based on single case observations and should be used with caution.Conclusions:SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome. Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units.

Central Sleep-disordered Breathing Predicts Incident Atrial Fibrillation in Older Men.

Although research supports a sleep-disordered breathing and atrial fibrillation association, prospective data examining sleep-disordered breathing predicting incident atrial fibrillation are lacking. To investigate sleep-disordered breathing indices as predictors of incident atrial fibrillation. A cohort (n = 843) of ambulatory older men without prevalent atrial fibrillation was assessed for baseline sleep indices: apnea-hypopnea index, central sleep apnea (central apnea index, ≥5 vs. <5), central sleep apnea or Cheyne-Stokes respiration, obstructive apnea-hypopnea index, and percentage of sleep time with less than 90% oxygen saturation. Incident clinically symptomatic adjudicated or self-reported atrial fibrillation outcome was ascertained (mean follow-up, 6.5 ± 0.7 yr). We used logistic regression models adjusted for age, race, body mass index, cardiopulmonary disease, alcohol use, pacemaker, cholesterol, cardiac medications, and alternate apnea type for obstructive and central apnea. Age interaction terms and median age-stratified analyses were performed. Central sleep apnea (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.18-5.66) and Cheyne-Stokes respiration with central sleep apnea (OR, 2.27; 95% CI, 1.13-4.56), but not obstructive apnea or hypoxemia, predicted incident atrial fibrillation. Central apnea, Cheyne-Stokes respiration, and sleep-disordered breathing-age interaction terms were significant (P < 0.05). Unlike the case with younger participants, among participants aged 76 years or older (albeit with small atrial fibrillation counts), atrial fibrillation was related to central apnea (OR, 9.97; 95% CI, 2.72-36.50), Cheyne-Stokes respiration with central apnea (OR, 6.31; 95% CI, 1.94-20.51), and apnea-hypopnea index (OR, 1.22; 95% CI, 1.08-1.39 [per 5-unit increase]). In older men, central apnea and Cheyne-Stokes respiration predicted increased atrial fibrillation risk, with findings being strongest in older participants in whom overall sleep-disordered breathing also increased atrial fibrillation risk.

Current and Future Use of Adaptive Servo-Ventilation

Adaptive servo-ventilation (ASV) is a form of non-invasive positive airway pressure (PAP) therapy that differs from other PAP devices. It includes features to overcome both obstructive and central sleep-disordered breathing (SDB) events. In the Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo-Ventilation in Patients with Heart Failure (SERVE-HF) study, ASV significantly reduced SDB events in patients with systolic heart failure (HF) and predominant central sleep apnoea (CSA), but did not improve outcomes, and there was increased mortality risk in the ASV group. Although the SERVE-HF results represent a paradigm shift for ASV, they are only applicable to a small subset of ASV-treated patients, and there is no evidence suggesting that ASV use should stop altogether. There are a number of other indications and patient groups for whom ASV may be useful, effective and safe, including patients with treatment-emergent CSA, central apnoeas associated with long-term opioid therapy without alveolar hypoventilation, idiopathic Cheyne-Stokes respiration, after ischaemic stroke and those with HF with preserved ejection fraction. Additional research is required to better define the mechanism of increased risk associated with ASV identified in SERVE-HF and to more clearly characterise the specific patient phenotypes who benefit from ASV therapy.