Central Apnea Research Articles

Butyrate supplementation rescues sex‐specific deficits in respiratory plasticity and mean arterial pressure in adult offspring exposed to gestational intermittent hypoxia

Sleep disordered breathing (SDB) in pregnancy is increasing in parallel with the obesity epidemic, and is linked to adverse perinatal outcomes in the offspring. Consequences of maternal SDB during pregnancy on the adult offspring are not well‐understood. Preliminary data indicate that adult male, but not female, offspring of dams exposed to intermittent hypoxia during gestation (GIH ‐ gestational intermittent hypoxia), a rat model of SDB during pregnancy, have elevated mean arterial pressure (MAP), increased neuroinflammation, inflammation‐induced impairment of homeostatic plasticity in the respiratory control system, and gut dysbiosis. Specifically, adult male GIH offspring have decreased relative abundance of gut bacteria that produce butyrate, a short‐chain fatty acid that has potent anti‐inflammatory properties and regulates immune function in the central nervous system. Since literature suggests that gut dysbiosis, neuroinflammation, and hypertension exist in a complicated vicious cycle, we treated male GIH offspring with tributyrin, a butyrate prodrug. Prior to tributyrin treatment, MAP in male GIH offspring was 96±3 mmHg, versus 76±1 mmHg in control rats receiving gestational intermittent normoxia (GNX). Similarly, male GIH offspring exhibited deficits in respiratory plasticity in response to recurrent central apneas (3.6±6.8% plasticity), when compared to GNX offspring (59.3±4.8% plasticity). GIH offspring exhibited evidence of elevated neuroinflammation in brain regions underlying cardiorespiratory control (e.g., IL‐1β expression 1.6±0.2‐fold higher than GNX controls (1.0±0.2)). Following three weeks of tributyrin treatment, MAP had normalized (80±2 mmHg), neuroinflammation was reduced to control levels, and the ability to express respiratory neuroplasticity was rescued (78±30%). These data indicate that gut dysbiosis may contribute to sex‐specific impairments induced by maternal exposure to intermittent hypoxia during gestation that can be rescued in adulthood by supplementing with butyrate.

Effects of sacubitril-valsartan on central and obstructive apneas in heart failure patients with reduced ejection fraction

ObjectiveThis study aimed to evaluate the effect of sacubitril-valsartan (SV) on central apneas (CA) and obstructive apneas (OA) in patients with heart failure with reduced ejection fraction (HFrEF).MethodsIn patients with HFrEF, SV initiation was titrated to the highest tolerable dosage. Patients were evaluated with portable apnea monitoring, echocardiography, and cardiopulmonary exercise testing at baseline and 3 months later.ResultsOf a total of 18 patients, 9 (50%) had OA, 7 (39%) had CA, and 2 (11%) had normal breathing. SV therapy was related to a reduction in NT-pro BNP and an improvement in LV function after 3 months. Portable apnea monitoring revealed a significant decrease of the respiratory event index (REI) after treatment with SV (20 ± 23 events/h to 7 ± 7 events/h, p = 0.003). When subgrouping according to type of apneas, REI, and time spent below 90% saturation (T90) decreased in patients with CA and OA (all p < 0.05).ConclusionIn this prospective study, SV treatment for 3 months in patients with CA and OA is associated with a significant decrease in REI.

Serotonin transporter in the temporal lobe, hippocampus and amygdala in SUDEP.

Several lines of evidence link deficient serotonin function and SUDEP. Chronic treatment with serotonin reuptake inhibitors (SRIs) reduces ictal central apnoea, a risk factor for SUDEP. Reduced medullary serotonergic neurones, modulators of respiration in response to hypercapnia, were reported in a SUDEP post‐mortem series. The amygdala and hippocampus have high serotonergic innervation and are functionally implicated in seizure‐related respiratory dysregulation. We explored serotonergic networks in mesial temporal lobe structures in a surgical and post‐mortem epilepsy series in relation to SUDEP risk. We stratified 75 temporal lobe epilepsy patients with hippocampal sclerosis (TLE/HS) into high (N = 16), medium (N = 11) and low risk (N = 48) groups for SUDEP based on generalised seizure frequency. We also included the amygdala in 35 post‐mortem cases, including SUDEP (N = 17), epilepsy controls (N = 10) and non‐epilepsy controls (N = 8). The immunohistochemistry labelling index (LI) and axonal length (AL) of serotonin transporter (SERT)‐positive axons were quantified in 13 regions of interest with image analysis. SERT LI was highest in amygdala and subiculum regions. In the surgical series, higher SERT LI was observed in high risk than low risk cases in the dentate gyrus, CA1 and subiculum (p < 0.05). In the post‐mortem cases higher SERT LI and AL was observed in the basal and accessory basal nuclei of the amygdala and peri‐amygdala cortex in SUDEP compared to epilepsy controls (p < 0.05). Patients on SRI showed higher SERT in the dentate gyrus (p < 0.005) and CA4 (p < 0.05) but there was no difference in patients with or without a psychiatric history. Higher SERT in hippocampal subfields in TLE/HS cases with SUDEP risk factors and higher amygdala SERT in post‐mortem SUDEP cases than epilepsy controls supports a role for altered serotonergic networks involving limbic regions in SUDEP. This may be of functional relevance through reduced 5‐HT availability.

Unexplained Significant Central Sleep Apnea in Infants: Clinical Presentation and Outcomes.

Unexplained significant central sleep apnea in term infants presents as central apneas with associated oxygen desaturations requiring respiratory support and monitoring for prolonged periods. However, there is a paucity of literature describing idiopathic central sleep apnea (ICSA) in term or near-term infants. Our aim was to describe the clinical manifestations, polysomnography data, interventions, and trajectory of ICSA in infants. This is a retrospective study of infants (gestational age ≥ 35weeks) who presented with significant central apneas and were subsequently diagnosed with ICSA following polysomnography and clinical investigations between January 2011 and April 2021 at a tertiary care hospital in Canada. Polysomnography data, clinical investigations, and treatments were documented. Eighteen infants (male, 78%; median gestational age 38weeks) with ICSA were included. Initial polysomnograms were completed at a median (interquartile range [IQR]) age of 1.2 (0.6-1.6) months (n = 18) and follow-up polysomnograms at 12.4 (10.6-14.0) months (n = 13). Compared to baseline diagnostic polysomnograms, at follow-up there was a significant reduction in the median (IQR) central apnea-hypopnea index (26.1 [18.2-52.9] versus 4.2[2.6-7.2] events/hour; p = 0.001), desaturation index (30.9 [12.2-57.4] versus 3.9[3.0-7.9] events/hour; p = 0.002), average transcutaneous carbon dioxide (41.9 [40.1-47.3 versus 39.4[37.5-42.7] mmHg; p = 0.025), and improved nadir oxygen saturation (79.8 [69.1-83.0] versus 85.5[83.2-87.8]%; p = 0.033), respectively. Prescribed treatments included supplemental oxygen (14/18, 78%), caffeine (5/18, 28%), and noninvasive ventilation (1/18, 6%). Infants with significant unexplained ICSA have a favorable clinical trajectory over time. Further research is needed to understand the etiology of this rare disorder.

Diagnosis and management of cardiopulmonary events in very low birth weight infants close to discharge: a quality improvement initiative.

Cardiopulmonary events (CPE) have a central, obstructive, or mixed etiology. Lack of standardized diagnosis and management of CPE may prolong the length of stay (LOS). To increase the accuracy of CPE diagnosis and decrease LOS by 10% for preterm infants over a 12-month period. Develop an evidence-based algorithm to identify type of CPE, determine management approach, and evaluate cardio-respiratory monitors output. Apply model for improvement and statistical process control charts to determine special cause variation. Identification of central apnea increased from 15 to 39% (p < 0.01). LOS decreased 26% from 52.6 days to 39.2 days, with an estimated cost savings of $13,119 per each of the 225 infants in the initiative. After implementing an evidence-based algorithm for management of neonatal CPE, a significant increase in the accuracy of the diagnosis of central apnea and cost savings associated with a decrease in LOS were observed.

Prevalence and clinical characteristics of sleep-disordered breathing in patients with heart failure of different left ventricular ejection fractions.

The prevalence of sleep-disordered breathing (SDB) is high in patients with heart failure (HF), while the prevalence of SDB in HF with different left ventricular ejection fractions (LVEF) has rarely been reported. We aimed to explore the prevalence and clinical characteristics of SDB in patients withHF having different LVEF. Patients with stable HF were consecutively enrolled. All patients underwent portable overnight cardiorespiratory polygraphy and echocardiography. According to their LVEF, the patients were divided into the HFrEF (HF with reduced EF, EF < 40%), HFmrEF (HF with mid-range EF, 40 ≤ EF < 50), and HFpEF groups (HF with preserved EF, EF ≥ 50%). The prevalence and clinical data of SDB among the 3 groups were then compared. A total of 252 patients, including 134 men, were enrolled in the study. The prevalence of SDB inpatients with HF was 70%. Obstructive sleep apnea (OSA) was diagnosed in48% and central sleep apnea (CSA) in 22%. The prevalence of SDB in the HFrEE, HFmrEF, and HFpEF groups was 86%, 86%, and 62%, respectively (P = 0.001). The prevalence of OSA among the 3 groups was 42%, 47%, and 49%, respectively (P = 0.708), while the prevalence of CSA among the 3 groups was 44%, 40%, and 13% (P < 0.001). Logistic regression analysis revealed that age and BMI were independent risk factors for OSA in patientswith HF, while LVEF and smoking were independent risk factors for CSA in patientswith HF. Correlational analyses revealed that LVEF was negatively correlated with apnea-hypopnea index (AHI) (r = -0.309, P < 0.001) and central apnea index (CAI) ( r = -0.558, P < 0.001), while there was no significant correlation with obstructive apnea index (OAI). The ROC curve revealed that LVEF could predict the occurrence of CSA and SDB, with AUC = 0.683 (95%CI 0.600-0.767, P < 0.001) and AUC = 0.630 (95%CI 0.559-0.702, P = 0.001), but not of OSA. SDB was highly common in HF, and the prevalence of SDB was different in HF with different LVEF, mainly due to the difference in cardiac functions. The prevalence and severity of SDB in HFrEF and HFmrEF were significantly higher than those in HFpEF, which was mainly related to the increase in CSA. When HFmrEF was similar to HFrEF in cardiac functions, the prevalence, type, and severity of SDB were similar between the two groups. Changes in LVEF had a significant impact on CAI, but not on OAI. LVEF can predict the occurrence of CSA and SDB to a certain extent.

Mandibular Movements are a Reliable Noninvasive Alternative to Esophageal Pressure for Measuring Respiratory Effort in Patients with Sleep Apnea Syndrome.

PurposeDifferentiation between obstructive and central apneas and hypopneas requires quantitative measurement of respiratory effort (RE) using esophageal pressure (PES), which is rarely implemented. This study investigated whether the sleep mandibular movements (MM) signal recorded with a tri-axial gyroscopic chin sensor (Sunrise, Namur, Belgium) is a reliable surrogate of PES in patients with suspected obstructive sleep apnea (OSA).Patients and MethodsIn-laboratory polysomnography (PSG) with PES and concurrent MM monitoring was performed. PSGs were scored manually using AASM 2012 rules. Data blocks (n=8042) were randomly sampled during normal breathing (NB), obstructive or central apnea/hypopnea (OA/OH/CA/CH), respiratory effort-related arousal (RERA), and mixed apnea (MxA). Analyses were evaluation of the similarity and linear correlation between PES and MM using the longest common subsequence (LCSS) algorithm and Pearson’s coefficient; description of signal amplitudes; estimation of the marginal effect for crossing from NB to a respiratory disturbance for a given change in MM signal using a mixed linear-regression.ResultsParticipants (n=38) had mild to severe OSA (median AH index 28.9/h; median arousal index 23.2/h). MM showed a high level of synchronization with concurrent PES signals. Distribution of MM amplitude differed significantly between event types: median (95% confidence interval) values of 0.60 (0.16–2.43) for CA, 0.83 (0.23–4.71) for CH, 1.93 (0.46–12.43) for MxA, 3.23 (0.72–18.09) for OH, and 6.42 (0.88–26.81) for OA. Mixed regression indicated that crossing from NB to central events would decrease MM signal amplitude by –1.23 (CH) and –2.04 (CA) units, while obstructive events would increase MM amplitude by +3.27 (OH) and +6.79 (OA) units (all p<10−6).ConclusionIn OSA patients, MM signals facilitated the measurement of specific levels of RE associated with obstructive, central or mixed apneas and/or hypopneas. A high degree of similarity was observed with the PES gold-standard signal.

Sleep-Related Breathing Disorders in Multiple Sclerosis: Prevalence, Features and Associated Factors.

BackgroundMultiple sclerosis (MS) represents a risk factor for sleep disorders, but there are conflicting results about the prevalence and severity of sleep-related breathing disorders (SRBD) in MS. Most available data come from self-administered questionnaires.ObjectiveTo conduct a polysomnographic study in MS focused on SRBD, compared to a group of healthy controls (HC), also considering the neuroimaging findings. To evaluate the impact of SRBD on vigilance, fatigue and depression in MS.MethodsIn this cross-sectional, observational, instrumental study, 67 MS patients (men/women: 20/47; mean age: 50.6±8.2 years) underwent PSG and maintenance of wakefulness test. Findings were compared to 67 age-, sex-, BMI-matched HC, by using parametric (Student’s t-test) and nonparametric statistics (chi-squared test). A subgroup analysis was then performed, evaluating the influence of brainstem (mesencephalic, pontine and medullary) lesions at neuroimaging on instrumental and clinical data: MS patients with at least one brainstem lesion vs MS patients without vs HC.ResultsThe frequency of SRBD was comparable in MS patients and HC. No MS patient had a central apnea index ≥2/h. The respiratory disturbance index (RDI) did not correlate to clinical parameters such as fatigue and depression. Patients with MS were drowsier than HC (47% vs 26%, p = 0.019) and showed a worse sleep pattern, in terms of duration, efficiency and architecture.ConclusionOur study does not provide evidence of an association between MS-specific symptoms such as fatigue, sleepiness, depression and central or obstructive apneas, even in the presence of brainstem lesions.

A cervical compartment syndrome impairs cerebral circulation in post-thyroidectomy hemorrhage: data from an animal model.

Post thyroidectomy hemorrhage is a potentially life-threatening complication. As the mechanism leading to hypoxemic brain damage and death is still unknown, our aim was to examine the underlaying pathophysiology in an animal model. A series of experiments was performed in our established model for post thyroidectomy hemorrhage in 6 pigs. First, post thyroidectomy hemorrhage was simulated with an artificial increase of cervical compartment pressure. Second, spontaneous bleeding into the cervical compartment was initiated. Primary outcome measure is the correlation between cerebral oxygenation and cervical compartment pressure. With an increase in cervical compartment pressure apnea could be detected in all experiments. A significant 24.2% (9.5-34.4%) decrease of cerebral oxygenation at time of apnea (47.0%; 38.0-65.0%) compared to baseline values (63.5%; 56.0-74.0%; P=0.043) occurred due increase of cervical compartment pressure concurrent with an impaired cerebral perfusion. Apnea occurred about 200 sec after a 10% decrease of cerebral oxygenation, but 35 sec before a 10% decrease of peripheral oxygenation. Spontaneous bleeding into the cervical compartment causes an increase of cervical compartment pressure reaching levels of the mean arterial blood pressure 56.0 (35.0-72.0) mmHg. Peripheral hypoxemia occurs with relevant delay in time after decrease of cerebral perfusion and cerebral hypoxemia, therefore cerebral hypoxemia seems to be causal for a central apnea. With this evidence of impaired cerebral perfusion and cerebral hypoxemia due to an increased cervical compartment pressure we can disprove the historic theory of tracheal collapse due to a compressive hematoma in post thyroidectomy hemorrhage. A cervical compartment syndrome seems to be causal, not only for brain hypoxemia but also an additional laryngo-pharyngeal mucosal edema.

Development of Central Sleep Apnea After Sleep Surgery

Central sleep apnea (CSA) is defined as an absence of breathing without respiratory drive during sleep. It can occur after treatment of obstructive sleep apnea (OSA), a phenomenon known as treatment-emergent central sleep apnea (TECSA). We present a case of a 23-year-old male who developed CSA after pharyngeal and nasal surgery for severe OSA. High loop gain and increased ventilations from frequent arousal are likely explanations for our patient’s central apnea, which resolved with positive airway pressure therapy that possibly alleviated residual airway obstruction and ventilatory instability. This case suggests that effectiveness of treatment for OSA should be based on careful long-term observation with multiple follow-up polysomnography tests, especially in patients at high risk of TECSA.

Effect of doxapram on the electrical activity of the diaphragm waveform pattern of preterm infants.

This study aimed to evaluate the change in the waveform pattern of the electrical activity of the diaphragm (Edi) following the administration of doxapram in extremely preterm infants ventilated with neurally adjusted ventilatory assist (NAVA). We conducted this retrospective cohort study in our neonatal intensive care unit between November 2019 and September 2021. The study participants were extremely preterm infants under the gestational age of 28 weeks who were ventilated with NAVA and administered doxapram. We collected the data of the Edi waveform pattern and calculated the proportion. To analyze the change in the proportion of the Edi waveform pattern, we compared the proportion of the data for 1 h before and after doxapram administration. Ten extremely preterm infants were included. Almost all the patients' respiratory condition improved after doxapram administration. The ventilatory parameters-Edi peak, Edi minimum, peak inspiratory pressure, time in backup ventilation, and number of switches to backup ventilation-did not change significantly. However, the proportion of phasic pattern significantly increased (before: 46% vs. after: 72%; p < 0.05), whereas the central apnea pattern significantly decreased after doxapram administration (before: 31% vs. after: 8.3%; p < 0.05). The proportion of irregular low-voltage patterns tended to decrease, albeit with no significant changes. Our results indicated that the proportion of Edi waveform patterns changed following doxapram administration. Edi waveform pattern analysis could be a sensitive indicator of effect with other intervention for respiratory conditions.

Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea.

Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnoticzolpidemon the frequency of respiratory-related arousals and central apneain patients withmoderate-to-severe SDB.We hypothesized thatzolpidemdecreasesthe severity of SDB by decreasingthe frequency ofrespiratory-related arousals. Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO2 reserve and the respiratory arousal threshold, were also compared. Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO2 reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmH2O, P = 0.41). Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO2 reserve or increase the arousal threshold. Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).

Incidence and Nature of Respiratory Events in Patients Undergoing Bronchoscopy Under Conscious Sedation.

During diagnostic bronchoscopies, conscious sedation improves patient tolerance, but it can contribute to hypercapnia and hypoxia by various mechanisms including depression of ventilatory drive. This prospective study was undertaken to determine the frequency of respiratory events and associated oxygen desaturations during bronchoscopy with conscious sedation. The Nox-T3 monitoring system was placed before starting the bronchoscopy and remained in place for 30 minutes following the procedure. The primary endpoint was the occurrence of obstructive and central apneic events during bronchoscopy under conscious sedation. Obstructive events (apnea and hypopnea) occurred in 100% of patients (n=31), and central apneas occurred in 58% of patients (n=18) during the procedure with a median of 9 and 2 events per patient, respectively. During recovery, a significant proportion of patients had detectable obstructive (86%) and central (36%) events. Higher body mass index was associated with oxygen desaturation to <90% and with the need for escalation of care. Furthermore, a conscious sedation regimen that included propofol was significantly associated with central apneic events. Respiratory events are common during and immediately postprocedure after conscious sedation for bronchoscopy. Most events are obstructive, and the use of propofol predisposes to central apneas during the procedure. Both types of events are associated with a higher body mass index. Oxygen desaturation to <90% triggers escalation of care. A further prospective study will be required to determine the clinical significance of these apneic events and whether alleviating these events will improve the safety and outcomes of bronchoscopic procedures performed under conscious sedation.

Factors associated with treatment outcomes after use of auto-titrating CPAP therapy in adults with obstructive sleep apnea.

To determine factors that are associated with OSA therapy outcomes with auto-titrating positive airway pressure (APAP). We sequentially grouped patients from a retrospective cohort based on APAP efficacy (sufficiently vs. insufficiently treated; insufficiently treatment defined as residual AHI of ≥ 5), therapy adherence (adherent vs. non-adherent, non-adherence defined as < 70% usage for ≥ 4h/night), and therapy outcomes (optimal vs. non-optimal and non-optimal outcomes defined as non-adherent and/or insufficiently treated). We subsequently compared each group. The insufficiently treated were older (68.4 ± 12.5 vs. 60.4 ± 13.1years, p < 0.01) and had lower BMI (31.9 ± 6.3 vs. 37.9 ± 9.1kg/m2, p < 0.01). They had higher baseline central apnea indices (CAI), longer leaks, higher peak pressures, and were less compliant. The non-adherent were younger (61.1 ± 12.6 vs. 65.5 ± 13.2years, p = 0.03) and comprised more females (56.1 vs. 43.9%, p = 0.04). The leak duration per usage hour was higher in the non-compliant (median: 1.5; IQR 7.9 vs. median: 0.3; IQR 1.9min/h; p < 0.01). The non-optimally treated had lower BMI, longer leaks, and less nightly usage. Multivariate analyses showed that leak duration was the common factor associated with treatment effectiveness and optimal therapy outcomes. Various demographic and clinical factors were associated with treatment efficacy and adherence. However, leak duration was the common factor related to treatment efficacy and overall optimal therapy outcomes.

Effect of Opium Versus Methadone on Polysomnographic Characteristics of Patients With Obesity Hypoventilation Syndrome.

There are studies about polysomnographic (PSG) characteristics of patients with either obesity hypoventilation syndrome (OHS) or addiction. We aimed to investigate the PSG characteristics of obstructive sleep apnea (OSA) patients with opium addiction, those on methadone maintenance treatment (MMT), and non-addicts for the treatment of addiction. In this cross-sectional study, we enrolled 75 patients with OHS in the Bamdad Respiratory and Sleep Research Center affiliated with the Isfahan University of Medical Sciences between January 2020 and February 2021. The patients were categorized into three groups: Opium addicts (OA), MMT, and non-addicts (NA). All patients completed screening questionnaires for OSA. This included the Epworth sleepiness scale (ESS), stop-bang questionnaire, and Berlin questionnaire and the data analyzed by SPSS software, version 24. A total of 75 OHS patients (54 men [72%] and 21 women [28%]) were studied in three groups, including OA (n=30), MMT (n=15), and NA (n=30). The apnea hypopnea index was not significantly different between the three groups. The longest apnea duration was higher in the OA than in other groups (P=0.001). Central apnea index (P=0.01), longest hypopnea duration (P=0.04), PaCO2 (P=0.04), and time with SpO2<90% (T90) (P=0.009) were higher in the MMT than in other groups. Furthermore, the minimum SpO2 was lower in the MMT than in other groups (P=0.03). Some of the sleep disturbances were worse in the MMT than in the OA group. This suggests the need for further studies to compare the effects of opium and methadone on sleep in OHS patients.

Sodium Oxybate as a Possible Cause of Emergent Central Apneas: Cheyne-Stokes Type.

Sodium Oxybate as a Possible Cause of Emergent Central Apneas: Cheyne-Stokes Type.

Central Apneas Are More Detrimental in Female Than in Male Patients With Heart Failure.

BackgroundCentral apneas (CA) are a frequent comorbidity in patients with heart failure (HF) and are associated with worse prognosis. The clinical and prognostic relevance of CA in each sex is unknown.Methods and ResultsConsecutive outpatients with HF with either reduced or mildly reduced left ventricular ejection fraction (n=550, age 65±12 years, left ventricular ejection fraction 32%±9%, 21% women) underwent a 24‐hour ambulatory polygraphy to evaluate CA burden and were followed up for the composite end point of cardiac death, appropriate implantable cardioverter‐defibrillator shock, or first HF hospitalization. Compared with men, women were younger, had higher left ventricular ejection fraction, had lower prevalence of ischemic etiology and of atrial fibrillation, and showed lower apnea‐hypopnea index (expressed as median [interquartile range]) at daytime (3 [0–9] versus 10 [3–20] events/hour) and nighttime (10 [3–21] versus 23 [11–36] events/hour) (all P<0.001), despite similar neurohormonal activation and HF therapy. Increased chemoreflex sensitivity to either hypoxia or hypercapnia (evaluated in 356 patients, 65%, by a rebreathing test) was less frequent in women (P<0.001), but chemoreflex sensitivity to hypercapnia was a predictor of apnea‐hypopnea index in both sexes. At adjusted survival analysis, daytime apnea‐hypopnea index ≥15 events/hour (hazard ratio [HR], 2.70; 95% CI, 1.06–7.34; P=0.037), nighttime apnea‐hypopnea index ≥15 events/hour (HR, 2.84; 95% CI, 1.28–6.32; P=0.010), and nighttime CA index ≥10 events/hour (HR, 5.01; 95% CI, 1.88–13.4; P=0.001) were independent predictors of the primary end point in women but not in men (all P>0.05), also after matching women and men for possible confounders.ConclusionsIn chronic HF, CA are associated with a greater risk of adverse events in women than in men.

Abnormalities of the Vertebrobasilar Arterial System Leading to Sleep Disorders

IntroductionThe abnormalities in the vertebrobasilar arterial system such as enlarged, tortuous or dilated arteries and aneurysms can generate pressure and distortion of brain structures especially in the medulla and pons. This brainstem compression by abnormal arteries can lead to various sleep disorders such as sleep related hypoventilation, central sleep apnea, obstructive sleep apnea, and positional sleep apnea. AimTo highlight brainstem compression due to vascular abnormalities as a cause of sleep disordered breathing. MethodsManuscripts were identified using the National Institutes of Health PubMed literature search system. Search terms included sleep disorders, vertebrobasilar dolichoectasia, tortuous vertebral arteries, vertebrobasilar aneurysms, vascular compression and brainstem compression. Inclusion criteria required that the articles were written in English, highlighted both a sleep disorder and a vascular abnormality. ResultsThe literature search resulted in 10 case reports where vascular abnormalities were leading to sleep disorders. Out of these: four patients had central sleep apnea; three had sleep related hypoventilation; one had positional central sleep apnea; one had positional central apnea along with obstructive sleep apnea; and one had obstructive sleep apnea. The various vascular lesions identified were: megadolichobasilar artery; dolichoectatic vertebral artery; fusiform vertebrobasilar aneurysm; tortuous and elongated vertebral arteries; calcified vertebral artery and medullary telangiectasia. ConclusionsArterial compression of the respiratory centers in the pons and medulla can lead to central sleep apnea. Obstructive sleep apnea can also result from vascular compression of the medulla. The proposed mechanism is compression of nucleus ambiguus which controls pharyngeal tone. Pressure on cranial nerves IX and X can lead to pharyngeal dysfunction leading to occlusive apnea.

Lung ultrasound allows for earlier diagnosis of bronchiolitis than auscultation: an animal experiment and human case series.

Early diagnosis of bronchiolitis in infants allows for risk stratification for central apnea, and, when available, the timely initiation of antiviral treatment. An animal model could demonstrate if earlier diagnosis is possible with ultrasound than with clinical exam. Even if possible, translating this to pediatrics would require observations from undifferentiated human infants. We used serial daily clinical and lung ultrasound exams in a bovine calf model (Bos taurus) of respiratory syncytial virus bronchiolitis. Ultrasound and clinical examiners were blinded to each other's findings and the treatments used in 24 calves. Time to diagnosis was compared using Kaplan-Meier curves. A case series of human infants with upper respiratory tract infections, without clinical signs of bronchiolitis, and in whom lung ultrasound was performed, was extracted from hospital records. In the bovine model, lung ultrasound findings emerged earlier and lasted later than auscultatory findings. Relying on auscultation, 5/24 (21%) of animals were diagnosed by post-inoculation day 5 whereas 24/24 (100%) were diagnosed by ultrasound. We identified seven infants in whom lung ultrasound was used to diagnose bronchiolitis before adventitial lung sounds emerged. Three of these subsequently developed typical clinical findings of bronchiolitis in the hospital. Two had alternative explanations for their abnormal lung ultrasounds (both required surgical intervention). Two were discharged and required no further medical attention. Lung ultrasound allowed earlier diagnosis of bronchiolitis than clinical exam in the bovine model. In the human case series this was also true, but alternative causes of abnormal ultrasound were frequent.

Normal Neonatal Sleep Defined: Refining Patient Selection and Interpreting Sleep Outcomes for Mandibular Distraction

Background:Although polysomnography is paramount when evaluating neonatal airway obstruction, “normal” published references do not exist. We present normative polysomnography data for newborns age 0–1 month. We compare this reference to pre and postoperative sleep data from infants undergoing mandibular distraction osteogenesis (MDO) at this same age.Methods:Following IRB approval, normative subjects were recruited from our neonatal intensive care unit to undergo nap polysomnography. One blinded sleep physician read all studies. From 2016 to 2019, we prospectively collected sleep data for newborns undergoing MDO.Results:In total, 22 neonates without airway obstruction provided normative sleep data. Median total apnea-hypopnea index (AHI), obstructive apnea-hypopnea index (OAHI), and central apnea index (CAI) were 7.3, 4.9, and 0.7 events/hour. Median O2 nadir was 91%. Polysomnography for 13 neonates before MDO and during consolidation showed median preoperative AHI was 38.3, OAHI was 37.0, CAI was 1.9, and median O2 nadir was 83%. Following MDO, median AHI was 6.1, OAHI was 4.0, CAI was 1.3, and median O2 nadir was 92.5%. Paired t-tests confirmed significant improvements in all indices; when comparing the postoperative group with the normative group, there was no difference in oxygenation nor any respiratory index.Conclusions:“Normal” neonates have more obstructive events and lower oxygenation nadirs than previously appreciated. We provide normative nap polysomnography values for this age group and encourage centers with multidisciplinary MDO teams to utilize this data to calibrate patient selection algorithms, inform treatment discussions, and better understand surgical outcomes. Limitations include a small sample size and single institution study.