Severe Central Sleep Apnea Research Articles

Gender-specific associations between sleep stages and cardiovascular risk factors.

Sleep characteristics are associated with cardiovascular disease (CVD) risk and both sleep and CVD risk vary by gender. Our objective was to examine associations between polysomnographic sleep characteristics and CVD risk after excluding moderate-severe sleep apnea, and whether gender modifies these associations. This was a cross-sectional study with at-home polysomnography in adults in Brazil (n= 1,102 participants with apnea-hypopnea index (AHI)<15 events/hour). Primary exposures were N3, REM, wake after sleep onset (WASO), arousal index (AI) and AHI, and outcomes were blood pressure (BP) and lipid levels. Associations between sleep and BP varied by gender. In women, more N3 was associated with lower systolic BP (-0.40 mmHg per 10 minutes, 95%CI -0.71, -0.09), lower diastolic BP (-0.29 mmHg per 10 minutes, 95%CI -0.50, -0.07), and lower odds of hypertension (OR 0.94, 95%CI 0.89, 0.98). In men, more WASO was associated with higher systolic BP (0.41 mmHg per 10 minutes, 95%CI 0.08, 0.74) and higher odds of hypertension (OR 1.07, 95%CI 1.01, 1.14). No interactions by gender were observed for lipids. More WASO was associated with lower total cholesterol (-0.71 per 10 minutes, 95%CI -1.37, -0.05). Higher AHI was associated with higher total cholesterol (+0.97 per event/hour, 95%CI 0.24, 1.70) and higher LDL (+0.84 per event/hour, 95%CI 0.04, 1.64). N3 is more strongly associated with BP in women, which is consistent with other studies demonstrating gender differences in BP control and CVD risk and adds a novel risk factor. Longitudinal and interventional studies are required to determine whether changes in N3 result in BP changes.

Posterior fossa decompression in patients with Chiari malformation type 1: effect on sleep apnea and follow-up outcomes.

Sleep apnea, posing significant health risks, is frequently associated with Chiari malformation (CM), characterized by cerebellar tonsil herniation through the foramen magnum. Central sleep apnea (CSA) in CM results from impaired brain-to-muscle signaling and requires treatment. Conversely, obstructive sleep apnea (OSA), arising from throat muscle relaxation, typically unrelated to CM, often coexists. This study evaluates the effectiveness of posterior fossa decompression (PFD) on sleep apnea. A retrospective chart review was conducted of pediatric patients with CM-1 and sleep apnea who underwent PFD between April 1, 2004, and September 30, 2022. Data collected included demographics, clinical characteristics, adenotonsillectomy status, PFD details, and sleep study parameters like the apnea-hypopnea index and respiratory disturbance index. Statistical analysis assessed the surgery's impact on sleep apnea severity. The study included eleven patients, predominantly male (63.6%). All had OSA (100%), with 63.6% also having CSA. Preoperative sleep studies classified OSA severity as 36.4% mild, 18.2% moderate, and 45.5% severe, with no change post-surgery. CSA severity initially included seven mild cases, which became three mild, one moderate, and three resolved cases post-surgery. Among seven patients who had adenotonsillectomy before decompression, five showed no improvement in OSA severity post-surgery. This study elucidates the complex relationship between CM-1, sleep apnea, and PFD. The findings show the persistence of sleep apnea in some patients and highlight the need for continuous monitoring of these patients in order to optimize their care after surgery.

Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea

Both obstructive and central sleep apnea (OSA and CSA) may contribute to nocturnal cardiac arrhythmias (NCA). Data on the prevalence of clinically important nocturnal atrial and ventricular arrythmias in patients with heart failure with reduced ejection fraction (HFrEF) and obstructive (OSA) or central sleep apnea (CSA) are scarce. In a cohort of patients with HFrEF, how does the prevalence of NCA compare among those with OSA, CSA and those with no to mild sleep apnea? Is the severity of OSA or CSA associated with atrial and ventricular NCA? This cross-sectional analysis is an ancillary study of the ADVENT-HF trial. We compared the prevalence of NCA (excessive supraventricular ectopic activity [ESVEA], defined as premature atrial complexes [PAC] ≥30/h or supraventricular tachycardia ≥20 beats); atrial fibrillation/flutter [AF]; and >10 premature ventricular complexes [PVC/h]) on ECGs from polysomnograms of HFrEF patients between those with OSA (apnea-hypopnea index [AHI≥15]), those with CSA (AHI≥15/h) and those with no to mild sleep apnea (AHI<15, control). Compared to controls (n=76), the prevalence of ESVEA was higher in patients with OSA (n=430) and CSA (n=150), 0%, 9% and 12%, respectively. The prevalences of AF in the control, OSA and CSA groups were 9%, 17% and 27%, and of >10 PVC/h 45%, 59% and 63%, respectively. In multivariable regression analyses PAC/h was associated with OSA severity (obstructive AHI) [22.4% increase per 10 events/h (95% confidence interval: 5.2; 42.3); p=0.009], but neither obstructive nor central AHI were associated with AF or >10 PVC/h. In patients with HFrEF, the prevalences of nocturnal ESVEA, AF and PVC >10/h were higher in those with, than in those without OSA or CSA, and OSA severity was related to the burden of nocturnal atrial ectopy. Severity of OSA or CSA were not significantly related to AF or >10 PVC/h.

Phrenic nerve stimulation for central sleep apnea: a single institution experience

PurposePhrenic nerve stimulation (PNS) was approved by the Food and Drug Administration (FDA) to treat moderate to severe central sleep apnea. We report here, results of a retrospective study regarding our institutional outcomes at one year. In this study we evaluated the change in the apnea hypopnea index, epworth sleepiness score, and functional outcomes of sleep score at one year post implant.MethodsThis is a retrospective analysis of patients ≥ 18 years of age who had PNS implanted for moderate to severe CSA at the Ohio State University Wexner Medical Center apnea between Feb 1, 2018 to July 1, 2021. Sleep disordered breathing parameters and objective sleepiness as measured by the Epworth Sleepiness Scale (ESS) scores, and Functional Outcomes of Sleep Questionnaire (FOSQ) scores were assessed at baseline and one-year post-implant.ResultsTwenty-two patients were implanted with PNS at OSU between February 1, 2018 and May, 31, 2022. The AHI showed a statistically significant decrease from a median of 40 events/hour at baseline to 18 at follow-up (p-value = 0.003). The CAI decreased from 16 events/hour to 2 events/hour (p-value of 0.001). The obstructive apnea index, mixed apnea index, and hypopnea index did not significantly change. The ESS scores had a statistically significant improvement from a median score of 12 to 9 (p-value = 0.028). While the FOSQ showed a trend to improvement from 15.0 to 17.8, it was not statistically significant (p-value of 0.086).ConclusionOur study found that PNS therapy for moderate to severe CSA improves overall AHI and CAI. Objective sleepiness as measured by the ESS also improved at one-year post implant.

Wireless wearable sensors can facilitate rapid detection of sleep apnea in hospitalized stroke patients.

To evaluate wearable devices and machine learning for detecting sleep apnea in patients with stroke at an acute inpatient rehabilitation facility (IRF). A total of 76 individuals with stroke wore a standard home sleep apnea test (ApneaLink Air), a multimodal, wireless wearable sensor system (ANNE), and a research-grade actigraphy device (ActiWatch) for at least one night during their first week after IRF admission as part of a larger clinical trial. Logistic regression algorithms were trained to detect sleep apnea using biometric features obtained from the ANNE sensors and ground truth apnea rating from the ApneaLink Air. Multiple algorithms were evaluated using different sensor combinations and different apnea detection criteria based on the Apnea-Hypopnea Index (AHI≥5, AHI≥15). Seventy-one (96%) participants wore the ANNE sensors for multiple nights. In contrast, only forty-eight participants (63%) could be successfully assessed for OSA by ApneaLink; 28 (37%) refused testing. The best-performing model utilized photoplethysmography (PPG) and finger temperature features to detect moderate-severe sleep apnea (AHI≥15), with 88% sensitivity and a positive likelihood ratio (LR+) of 44.00. This model was tested on additional nights of ANNE data achieving 71% sensitivity (10.14 LR+) when considering each night independently and 86% accuracy when averaging multi-night predictions. This research demonstrates the feasibility of accurately detecting moderate-severe sleep apnea early in the stroke recovery process using wearable sensors and machine learning techniques. These findings can inform future efforts to improve early detection for post-stroke sleep disorders, thereby enhancing patient recovery and long-term outcomes.

A Novel Measurement of Loop Gain Via Voluntary End-Expiratory Breath Holds During Acclimatization to High Altitude: Relationship to Central Sleep Apnea

Central sleep apnea (CSA) is universal at high altitude (HA; hypobaric hypoxia), with a high degree of variability. CSA increases in incidence and severity with ascent above 3,000m and with increased time spent at HA, due in part to increases in chemoreflex sensitivity (i.e., loop gain; LG) resulting from ventilatory acclimatization (VA). CSA is characterized by alternating reductions (hypopnea) or complete absence of airflow (apnea) during sleep, separated by intermittent periods of hyperventilation, and is thought to be associated with a LG ratios &gt;1.0. In HA fieldwork expeditions, testing respiratory chemoreflex sensitivity using traditional lab-based steady-state methods may not be relevant to CSA, nor feasible to predict those susceptible to CSA with ascent to HA. While CSA is universal with ascent to HA, it remains unclear how the incidence and severity of CSA may be related to LG with early ascent, given the high between-individual variability. Before (1400m; Day 0) and during early acclimatization to HA (4300m; days 6-8) in 11 healthy participants, we aimed to characterize a novel breath-holding protocol to quantify LG and assess the relationship between LG and CSA severity. We hypothesized that (a) LG will be &lt;1.0 before ascent, and subsequently will be &gt;1.0 with early incremental ascent to 4300m, suggesting VA and susceptibility for CSA, and (b) there will be an increase in the incidence and severity of CSA with ascent to HA, which will be correlated with LG, within-individual. In both locations, we used a series of five ~10-sec voluntary end-expiratory breath holds (EEBHs) separated by a ~60-sec recovery period to quantify LG. Following the breath-hold protocol, we utilized portable sleep monitors to assess the incidence and severity of CSA via the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) during sleep. AHI and ODI increased significantly compared to 1400m (p&lt;0.0001), indicating CSA. LG using the 1st breath following apnea (LG1) was significantly larger at 4300m (1.54±0.75 a.u.) than 1400m (0.89±0.73 a.u.; P=0.04, ES=0.88). Calculating LG using an average of the 1st and 2nd breaths following apnea (LG1+2) was also significantly larger at 4300m (1.09±0.51 a.u.) than 1400m (0.62±0.39 a.u.; P=0.022, ES=1.04). LG1 was strongly correlated with AHI (r=0.76, P=0.007) and moderately correlated with ODI (r=0.66, P=0.029). LG1+2 was strongly correlated with both AHI (r=0.78, P=0.004) and ODI (r=0.7, P=0.017). These data suggest that this EEBH protocol is well-suited to quantifying chemoreflex LG during VA to HA, and may have utility for predicting the incidence and severity of CSA in individuals in the context of HA fieldwork. MRU, NSERC, NSF. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prevalences of sleep-related breathing disorders and severity factors in chronic spinal cord injury and abled-bodied individuals undergoing rehabilitation: a comparative study.

The objective of this study was to discern distinguishing characteristics of sleep-related breathing disorders in individuals with chronic spinal cord injury (CSCI) compared with participants without CSCI. Additionally, the study investigated factors associated with sleep-related breathing disorder severity. This is a cross-sectional analysis of 123 individuals without CSCI, 40 tetraplegics, and 48 paraplegics who underwent attended or partially supervised full polysomnography for suspected sleep-related breathing disorders in a rehabilitation center. Polysomnographic, transcutaneous capnography, and clinical data were collected and compared between the groups. Among tetraplegics, apnea-hypopnea index ≥ 30 events/h (67.5%, P = .003), central apnea (17.5%, P = .007), and higher oxygen desaturation index (80.0%, P = .01) prevailed. Sleep-related hypoventilation was present in 15.4% of tetraplegics and 15.8% of paraplegics, compared with 3.2% in participants without CSCI (P = .05). In the group without CSCI and the paraplegic group, snoring and neck circumference were positively correlated with obstructive sleep apnea (OSA) severity. A positive correlation between waist circumference and OSA severity was identified in all groups, and multivariate logistic regression analysis showed that loud snoring and waist circumference had the greatest impact on OSA severity. Severe OSA and central sleep apnea prevailed in tetraplegic participants. Sleep-related hypoventilation was more common in tetraplegics and paraplegics than in participants without CSCI. Loud snoring and waist circumference had an impact on OSA severity in all groups. We recommend the routine implementation of transcutaneous capnography in individuals with CSCI. We underscore the significance of conducting a comprehensive sleep assessment in the rehabilitation process for individuals with CSCI. Souza Bastos P, Amaral TLD, Yehia HC, Tavares A. Prevalences of sleep-related breathing disorders and severity factors in chronic spinal cord injury and abled-bodied individuals undergoing rehabilitation: a comparative study. J Clin Sleep Med. 2024;20(7):1119-1129.

Type one chiari malformation as a cause of central sleep apnea and hypoventilation in children

ObjectivesChiari type 1 malformation (CM1) may occasionally lead to central sleep apnea (CSA). We studied, in a large clinical cohort of pediatric CM1 patients, the effect of CM1 on breathing during sleep. MethodsThis is a retrospective single pediatric pulmonology center study with a systematic evaluation of pediatric CM1 patients under age 18 with polysomnography (PSG) during 2008–2020. Children with syndromes were excluded. All patients had undergone head and spine magnetic resonance imaging. ResultsWe included 104 children with CM1 with a median age of 7 (interquartile range (IQR) 5–13) years. The median extent of tonsillar descent (TD) was 13 (IQR 10–18) mm. Syringomyelia was present in 19 children (18%). Of all children, 53 (51%) had normal PSG, 35 (34%) showed periodic breathing or central apnea and hypopnea index ≥5 h−1, and 16 (15%) displayed features of compensated central hypoventilation and end-tidal or transcutaneous carbon dioxide 99th percentile level above 50 mmHg. TD had the best predictive value for central breathing disorders. In a linear model, both age (61%) and TD (39%) predicted median breathing frequency (R = 0.33, p < 0.001). ConclusionsAlthough severe CSA is a rare complication of brainstem compression in pediatric patients with CM1, short arousal-triggered episodes of periodic breathing and mild compensated central hypoventilation are common. TD shows the best but still poor prediction of the presence of a central breathing disorder. This highlights the use of PSG in patient evaluation. Posterior fossa decompression surgery effectively treats central breathing disorders.

Loop gain response to increased cerebral blood flow at high altitude.

To compare loop gain (LG) before and during pharmacological increases in cerebral blood flow (CBF) at high altitude (HA). Loop gain (LG) describes stability of a negative-feedback control system; defining the magnitude of response to a disturbance, such as hyperpnea to an apnea in periodic breathing (PB). "Controller-gain" sensitivity from afferent peripheral (PCR) and central-chemoreceptors (CCR) plays a key role in perpetuating PB. Changes in CBF may have a critical role via effects on central chemo-sensitivity during sleep. Polysomnography (PSG) was performed on volunteers after administration of I.V. Acetazolamide (ACZ-10mg/kg) + Dobutamine (DOB-2-5 μg/kg/min) to increase CBF (via Duplex-ultrasound). Central sleep apnea (CSA) was measured from NREM sleep. The duty ratio (DR) was calculated as ventilatory duration (s) divided by cycle duration (s) (hyperpnea/hyperpnea + apnea), LG = 2π/(2πDR-sin2πDR). A total of 11 volunteers were studied. Compared to placebo-control, ACZ/DOB showed a significant increase in the DR (0.79 ± 0.21 vs 0.52 ± 0.03, P = 0.002) and reduction in LG (1.90 ± 0.23 vs 1.29 ± 0.35, P = 0.0004). ACZ/DOB increased cardiac output (CO) (8.19 ± 2.06 vs 6.58 ± 1.56L/min, P = 0.02) and CBF (718 ± 120 vs 526 ± 110ml/min, P < 0.001). There was no significant change in arterial blood gases, minute ventilation (VE), or hypoxic ventilatory response (HVR). However, there was a reduction of hypercapnic ventilatory response (HCVR) by 29% (5.9 ± 2.7 vs 4.2 ± 2.8 L/min, P = 0.1). Pharmacological elevation in CBF significantly reduced LG and severity of CSA. We speculate the effect was on HCVR "controller gain," rather than "plant gain," because PaCO2 and VE were unchanged. An effect via reduced circulation time is unlikely, as the respiratory-cycle length did not change.

Altered sleep architecture in diabetes and prediabetes: findings from the Baependi Heart Study.

People with diabetes and prediabetes are more likely to have sleep-disordered breathing (SDB), but few studies examined sleep architecture in people with diabetes or prediabetes in the absence of moderate-severe SDB, which was the aim of our cross-sectional study. This cross-sectional sample is from the Baependi Heart Study, a family-based cohort of adults in Brazil. About 1074 participants underwent at-home polysomnography (PSG). Diabetes was defined as fasting glucose >125 mg/dL or HbA1c > 6.4 mmol/mol or taking diabetic medication, and prediabetes was defined as HbA1c ≥ 5.7 & <6.5 mmol/mol or fasting glucose ≥ 100 & ≤125 mg/dl. We excluded participants with an apnea-hypopnea index (AHI) ≥ 30 in primary analyses and ≥ 15 in secondary analysis. We compared sleep stages among the 3 diabetes groups (prediabetes, diabetes, neither). Compared to those without diabetes, we found shorter REM duration for participants with diabetes (-6.7 min, 95%CI -13.2, -0.1) and prediabetes (-5.9 min, 95%CI -10.5, -1.3), even after adjusting for age, gender, BMI, and AHI. Diabetes was also associated with lower total sleep time (-13.7 min, 95%CI -26.8, -0.6), longer slow-wave sleep (N3) duration (+7.6 min, 95%CI 0.6, 14.6) and higher N3 percentage (+2.4%, 95%CI 0.6, 4.2), compared to those without diabetes. Results were similar when restricting to AHI < 15. People with diabetes and prediabetes had less REM sleep than people without either condition. People with diabetes also had more N3 sleep. These results suggest that diabetes and prediabetes are associated with differences in sleep architecture, even in the absence of moderate-severe sleep apnea.

Analysis by sex of safety and effectiveness of transvenous phrenic nerve stimulation

PurposeLittle is known about sex differences in the treatment of central sleep apnea (CSA). Our post hoc analysis of the remedē System Pivotal Trial aimed to determine sex-specific differences in the safety and effectiveness of treating moderate to severe CSA in adults with transvenous phrenic nerve stimulation (TPNS).MethodsMen and women enrolled in the remedē System Pivotal Trial were included in this post hoc analysis of the effect of TPNS on polysomnographic measures, Epworth Sleepiness Scale, and patient global assessment for quality of life.ResultsWomen (n = 16) experienced improvement in CSA metrics that were comparable to the benefits experienced by men (n = 135), with central apneas being practically eliminated post TPNS. Women experienced improvement in sleep quality and architecture that was comparable to men post TPNS. While women had lower baseline apnea hypopnea index than men, their quality of life was worse at baseline. Additionally, women reported a 25-percentage point greater improvement in quality of life compared to men after 12 months of TPNS therapy. TPNS was found to be safe in women, with no related serious adverse events through 12 months post-implant, while men had a low rate of 10%.ConclusionAlthough women had less prevalent and less severe CSA than men, they were more likely to report reduced quality of life. Transvenous phrenic nerve stimulation may be a safe and effective tool in the treatment of moderate to severe CSA in women. Larger studies of women with CSA are needed to confirm our findings.Clinical trial registrationClinicalTrials.gov NCT01816776; March 22, 2013.

0975 Severe Central Sleep Apnea After Bilateral Lung Transplantation

Abstract Introduction Central sleep apnea (CSA) is characterized by repetitive disruptions in airflow during sleep due to impaired central respiratory drive. Multiple studies have described an increased incidence of sleep disordered breathing after lung transplantation. However, these studies implicate obstructive sleep apnea as the primary sleep disturbance related to post-transplant weight gain, increased neck circumference, and fluid retention from immunosuppressive therapy. We report an uncommon presentation of new onset severe central predominant sleep apnea in a bilateral lung transplant recipient. Report of case(s) A 61-year-old female with a history of end stage COPD with chronic hypoxic respiratory failure status post bilateral lung transplantation in 2020 presented to sleep medicine clinic with several months of witnessed apneic episodes, excessive daytime sleepiness, morning headaches, and insomnia. Physical exam was notable for an increased body mass index (BMI) of 35 kg/m² from pre-transplant BMI of 29 kg/m². Epworth Sleepiness Scale was 15, compared to 4 prior to transplant. Polysomnogram showed an apnea hypopnea index (AHI) of 94.5 events/hour with central AHI of 54.6, consistent with severe central predominant sleep apnea. Titration on CPAP at 5 cmH2O and 7 cmH2O improved the AHI to 13.3 and 20.3, respectively, with residual central hypopneas. On follow-up, downloaded therapy data revealed a residual AHI of 23.3 on CPAP at 5 cmH2O and 1.5 L/min O2, suggesting the need for a BiPAP/ASV titration study if control remains suboptimal. Conclusion Common etiologies of CSA include heart failure with Cheyne-Stokes respirations, neurologic disease, high altitude, and the use of centrally acting medications. This patient did not have clearly identifiable risk factors. Pre- and post-transplant echocardiograms showed preserved left ventricular function with no regional wall motion abnormalities. She lacks history of neurologic disease or narcotic use, and her current immunosuppressive regimen has not been linked to worsened sleep apnea. Proposed pathogenesis of CSA in lung transplant recipients include abnormalities in respiratory mechanics due to pulmonary denervation and altered chemoreceptor sensitivity. Prompt diagnosis and treatment of sleep disordered breathing is crucial in organ transplant recipients to prevent adverse cardiovascular outcomes. Thus, further investigation is warranted to better characterize the changes in respiratory parameters that occur after lung transplantation. Support (if any)

1035 Joubert Syndrome and severe central sleep apnea treated with noninvasive ventilation: A case report

Abstract Introduction Joubert syndrome is an autosomal recessive heterogenous ciliopathy characterized by cerebellar vermis hypoplasia resulting in ataxia, hypotonia, developmental delay, neonatal respiratory dysregulation, and abnormal eye movements. It is typically accompanied by the pathognomonic “molar tooth sign” on brain MRI. Primary central sleep apnea has been described in case reports about this condition, however given the rarity of this disease, there are very few studies conducted on these patients. Our goal is to share our treatment approaches for the sleep disturbances seen in these patients. Report of case(s) A 6-year-old female from Kuwait with a history of Joubert syndrome and global development delay presented at UCMC for evaluation of sleep issues. During the history taking, patient’s mother reported that the patient was born with acute respiratory failure shortly and required CPAP therapy in the NICU. She later developed tachypnea and cyanosis during feedings, which prompted further evaluation. A subsequent brain MRI demonstrated a molar tooth sign consistent with Joubert Syndrome. Patient required supplemental oxygenation due to nocturnal desaturations found on pulse oximetry. Due to persistent apneas and chokings during sleep, the patient underwent a repeat diagnostic polysomnogram with an electroencephalogram at our institution demonstrating severe central sleep apnea most predominant during NREM sleep. An extended montage of the EEG did not show any epileptiform discharge. This was followed by a mask de-sensitization and an inpatient PAP titration study during which BPAP therapy ST mode with a backup rate of 8 breath/minute successfully treated the patient’s primary central sleep apnea. Patient also underwent a multidisciplinary consultation with PM&amp;R, speech therapy and ophthalmology due to her ataxia, speech delay, and need to assess for retinal dystrophy, respectively. Conclusion Sleep disordered breathing in the neonatal period is an early presentation in Joubert syndrome with central sleep apnea being the primary sleep disordered breathing. Fortunately, the clinical course of sleep disordered breathing does improve with treatment overtime, as in our case. Treatment options include conservative treatment, oxygen supplementation or PAP therapy. In our case, BPAP with ST mode was the most effective modality despite the need for mask desensitization and initial hesitation with using a PAP device. Support (if any)

0992 Reversible Pediatric Central Sleep Apnea in Hyperhomocysteinemia and Cerebral Sinus Venous Thrombosis

Abstract Introduction Pediatric central sleep apnea (CSA) rarely initially presents in adolescent age groups, being more commonly diagnosed in infants. CSA may result from a multitude of neurological insults, such as stroke and brain masses. It may also less often present in metabolic and non-ischemic thrombotic disorders. Report of case(s) A 12-year-old female with history of global developmental delay of unclear etiology, chronic headaches, insulin resistance, and early morning tremors was referred for initial evaluation of possible narcolepsy. Severe daytime sleepiness had acutely worsened over the previous month. She was unable to stay awake during school, despite sleeping 13 hours per 24 hours. Central hypersomnia was suspected and polysomnogram with MSLT was scheduled. The patient presented to the Emergency Department 10 days later for worsening headaches and new oral aversion with 12-pound weight loss. Examination showed ataxic gait and dysarthria. Brain MRI revealed non-occlusive cerebral sinus venous thrombosis (CSVT) involving the superior sagittal sinus, right transverse sinus, right sigmoid sinus, right jugular bulb/vein, and cortical veins overlying both cerebral hemispheres with no stroke. Anticoagulation with enoxaparin was initiated and thrombophilia work-up commenced. Polysomnogram demonstrated a central AHI of 49.9/hr with significant periodic breathing and no obstructive sleep apnea. Oxygen titration sleep study failed to significantly improve CSA and BPAP was initiated. Thrombophilia work-up revealed severe hyperhomocysteinemia. Genetic analysis was consistent with autosomal recessive severe methylenetetrahydrofolate reductase (MTHFR) deficiency. The patient was begun on metabolic treatment with betaine, pyridoxine, hydroxocobalamin, and vitamin C, and transitioned to oral rivaroxaban. At 4 months, blood levels had normalized, and MRI demonstrated resolution of CSVT. Family endorsed BPAP compliance and complete resolution of all sleep symptoms. In addition, there was significant improvement in cognition, interpersonal skills, and abstract thought. Follow up polysomnogram 10 months after presentation demonstrated no CSA nor periodic breathing. Conclusion To our knowledge, this is the first report of MTHFR deficiency and CSVT resulting in severe CSA. While it is difficult to ascertain which entity ultimately caused the CSA, MTHFR deficiency can produce significant neurologic impairment through white matter disease and defective myelination, while CSVT can provoke venous hypertension, venous stasis, or hypoxia. Support (if any)

PO-04-076 PHRENIC NERVE STIMULATOR LEAD MIGRATION RESULTING IN ATRIAL DYSRHYTHMIA

The phrenic nerve stimulator (PNS) is a novel treatment for central sleep apnea (CSA). The device (Remede, Respicardia Inc) consists of a pulse generator and a lead positioned in the left pericardiophrenic or right brachiocephalic vein. This stimulates the phrenic nerve during sleep resulting in diaphragmatic contraction to restore normal breathing. We report a case of PNS lead migration into the right atrium resulting in atrial dysrhythmias during device stimulation. N/A An 83 year old female with history of ischemic cardiomyopathy status post primary prevention ICD, and severe CSA underwent PNS placement two years ago with the pacing lead in the right brachiocephalic vein. Due to ongoing dyspnea and LBBB she had an upgrade to CRT-D using an epicardial LV lead. Post operatively she developed palpitations with several recorded episodes of wide complex tachycardia (image 1a). Interrogation of her CRT showed nocturnal atrial arrhythmias with aberrancy seemingly triggered by rhythmic electrical interference on her atrial marker channels (image 1b). There were no recorded daytime episodes. When interrogating the CRT-D with the PNS turned on, atrial arrhythmias were reproduced by periods of phrenic nerve stimulation, and ceased with the PNS turned off. A chest X-ray obtained showed migration of the PNS lead below the superior vena cava (SVC)-right atrial junction, possibly stimulating myocardial tissue (image 1c). She was treated by reprogramming the PNS device to pace from the proximal poles of the lead still within the SVC, thereby preventing future atrial arrhythmias. This is the first reported case of PNS lead migration into the right atrium causing atrial dysrhythmias.

Sex-related Differences in Loop Gain during High-Altitude Sleep-disordered Breathing.

Rationale: Central sleep apnea (CSA) is pervasive during sleep at high altitude, disproportionately impacting men and associated with increased peripheral chemosensitivity. Objectives: We aimed to assess whether biological sex affects loop gain (LGn) and CSA severity during sleep over 9-10 days of acclimatization to 3,800 m. We hypothesized that CSA severity would worsen with acclimatization in men but not in women because of greater increases in LGn in men. Methods: Sleep studies were collected from 20 (12 male) healthy participants at low altitude (1,130 m, baseline) and after ascent to (nights 2/3, acute) and residence at high altitude (nights 9/10, prolonged). CSA severity was quantified as the respiratory event index (REI) as a surrogate of the apnea-hypopnea index. LGn, a measure of ventilatory control instability, was quantified using a ventilatory control model fit to nasal flow. Linear mixed models evaluated effects of time at altitude and sex on respiratory event index and LGn. Data are presented as contrast means with 95% confidence intervals. Results: REI was comparable between men and women at acute altitude (4.1 [-9.3, 17.5] events/h; P = 0.54) but significantly greater in men at prolonged altitude (23.7 [10.3, 37.1] events/h; P = 0.0008). Men had greater LGn than did women for acute (0.08 [0.001, 0.15]; P = 0.047) and prolonged (0.17 [0.10, 0.25]; P < 0.0001) altitude. The change in REI per change in LGn was significantly greater in men than in women (107 ± 46 events/h/LGn; P = 0.02). Conclusions: The LGn response to high altitude differed between sexes and contributed to worsening of CSA over time in men but not in women. This sex difference in acclimatization appears to protect females from high altitude-related CSA. Thesedata provide fundamental sex-specific physiological insightinto high-altitude acclimatization in healthy individuals and may help to inform sex differences in sleep-disordered breathing pathogenesis in patients with cardiorespiratory disease.

Sleep-related breathing disorders in patients with heart failure with reduced and mildly reduced ejection fraction: main types and their dependence on heart failure etiology

Aim. To identify and study the nature of sleep-related breathing disorders (SBDs) in a cohort of hospitalized patients with heart failure (HF) with reduced and mildly reduced ejection fraction (EF), as well as to clarify the relationship between SBD type, etiology and severity of HF.Material and methods. The study included 117 patients with HF with reduced and mildly reduced ejection fraction hospitalized at the National Medical Research Center for Therapy and Preventive Medicine from 2019 to 2021. All patients underwent clinical and paraclinical examination, including cardiorespiratory sleep study. Patients were divided into three groups according to the type and severity of SBD: no or mild SBD, predominantly with obstructive sleep apnea (OSA) and predominantly with central sleep apnea (CSA). Severity of SBD and clinical data were compared between these groups.Results. A total of 5 patients (4,27%) did not have any SBDs, while 47 (40,17%) were diagnosed with CSA, and 65 (55,56%) — OSA of varying severity. The proportions of patients with moderate and severe CSA and OSA differed insignificantly and amounted to 35,9% (n=42) and 44,4% (n=52), respectively. There were following proportions of diseases related to HF: coronary artery disease (41,88%), nonischemic cardiomyopathy (26,5%), arrhythmogenic cardiomyopathy (15,38%) and other causes (16,24%) (hypertension, myocarditis, heart defects). We found that reduced EF &lt;40%, end-diastolic volume &gt;210 ml, and ventricular ectopy (&gt;300 extrasystoles/day) were associated with CSA, and body mass index &gt;30 kg/m2 was traditionally associated with OSA.Conclusion. More than half of HF patients with reduced and mildly reduced EF have SBDs. Decreased LVEF and ventricular ectopic activity are associated with CSA, while increased body mass index is associated with OSA. Consideration of SBD risk factors may improve patient phenotyping for individualized therapy.

SÍNDROME DA HIPOVENTILAÇÃO CENTRAL CONGÊNITA ASSOCIADA À DOENÇA DE HIRSCHSPRUNG: A IMPORTÂNCIA DO DIAGNÓSTICO DIFERENCIAL E PRECOCE

Congenital central hypoventilation syndrome (CCHS, OMIM #209880), also known as Ondine's curse is characterized by episodes of central apnea, which is a dysfunction of the autonomic nervous system (ANS), occurring soon after birth or in the first month of life. Mutations in the PHOX2B gene, located on chromosome 4p12, are responsible for the development of the CCHS. This study reports the case of a newborn with recurrent episodes of apnea, diagnosed with CCHS associated with Hirschsprung's disease. Female patient, 10 years old, born at preterm, after birth presented episodes of apnea and oxygen saturation fall, which required positive pressure ventilation and admission to a pediatric intensive care unit. The patient was kept in Continuous Positive Airway Pressure (CPAP) during the first 24 h of life to treat the apnea, and after that, presented hypercapnia being submitted to intubation. She also had intestinal constipation and abdominal distension. Several tests were carried out without elucidation of the diagnostic, therefore the patient was follow-up with a geneticist, and after a genetic research using DNA sequencing, she was diagnosed with congenital central hypoventilation syndrome associated to Hirschsprung's disease. CCHS is a rare syndrome, but underdiagnosed. Clinical manifestations in the acute and chronic hypoventilation include apnea and hypoventilation at birth, oxygen desaturation and cyanosis, severe central sleep apnea, acquired pulmonary hypertension, and delayed recovered from anaesthesia or opioids are. Early recognition of the clinical features previously described is indispensable to the diagnostic, as well as access to genetic testing in order to corroborate CCHS.

Correction to: 0849 Baclofen-induced severe central sleep apnea.

Correction to: 0849 Baclofen-induced severe central sleep apnea.

TRANSVENOUS PHRENIC NERVE STIMULATION EFFECTIVELY TREATS CENTRAL SLEEP APNEA DURING BOTH RAPID AND NONRAPID EYE MOVEMENT SLEEP

TRANSVENOUS PHRENIC NERVE STIMULATION EFFECTIVELY TREATS CENTRAL SLEEP APNEA DURING BOTH RAPID AND NONRAPID EYE MOVEMENT SLEEP