Predominant Central Sleep Apnea Research Articles

O070 Prevalence of central sleep apnoea in people with tetraplegic spinal cord injury: a retrospective analysis of research and clinical data

Abstract Study Objectives Over 80% of people with tetraplegia have sleep disordered breathing, but whether this is predominantly obstructive or central is unclear. This study aimed to estimate the prevalence of central sleep apnoea (CSA) in tetraplegia and the contributions of central, obstructive and hypopnoea respiratory events to sleep disordered breathing summary indices in tetraplegia. Methods Research and clinical data from 606 individuals with tetraplegia and full overnight polysomnography were collated. The proportions of different respiratory event types were calculated; overall and for mild, moderate, and severe disease. The prevalence of Predominant CSA (central apnoea index 5 and more central than obstructive apnoeas) and Any CSA (central apnoea index  5) was estimated. Prevalence of sleep-related hypoventilation was estimated in a clinical sub-cohort. Results Respiratory events were primarily hypopnoeas (71%), followed by obstructive (23%), central (4%) and mixed apnoeas (2%). As severity increased, the relative contribution of hypopnoeas and central apnoeas decreased, while that of obstructive apnoeas increased. The prevalence of Predominant CSA and Any CSA were 4.3% (26/606) and 8.4% (51/606) respectively. Being male, on opiates and having a high tetraplegic spinal cord injury were associated with CSA. Sleep-related hypoventilation was identified in 26% (26/113) of the clinical sub-cohort. Conclusions This is the largest study to characterize sleep disordered breathing in tetraplegia. It provides strong evidence that obstructive sleep apnoea is the predominant sleep disordered breathing type; 9-18 times more prevalent than CSA. The prevalence of CSA was estimated to be 4-8%, significantly lower than previously reported.

Prevalence of central sleep apnea in people with tetraplegic spinal cord injury: a retrospective analysis of research and clinical data.

Over 80% of people with tetraplegia have sleep-disordered breathing (SDB), but whether this is predominantly obstructive or central is unclear. This study aimed to estimate the prevalence of central sleep apnea (CSA) in tetraplegia and the contributions of central, obstructive, and hypopnea respiratory events to SDB summary indices in tetraplegia. Research and clinical data from 606 individuals with tetraplegia and full overnight polysomnography were collated. The proportions of different respiratory event types were calculated; overall and for mild, moderate, and severe disease. The prevalence of Predominant CSA (Central Apnea Index [CAI] ≥ 5 and more central than obstructive apneas) and Any CSA (CAI ≥ 5) was estimated. Prevalence of sleep-related hypoventilation (SRH) was estimated in a clinical sub-cohort. Respiratory events were primarily hypopneas (71%), followed by obstructive (23%), central (4%), and mixed apneas (2%). As severity increased, the relative contribution of hypopneas and central apneas decreased, while that of obstructive apneas increased. The prevalence of Predominant CSA and Any CSA were 4.3% (26/606) and 8.4% (51/606) respectively. Being male, on opiates and having a high tetraplegic spinal cord injury were associated with CSA. SRH was identified in 26% (26/113) of the clinical sub-cohort. This is the largest study to characterize SDB in tetraplegia. It provides strong evidence that obstructive sleep apnea is the predominant SDB type; 9-18 times more prevalent than CSA. The prevalence of CSA was estimated to be 4%-8%, significantly lower than previously reported.

FACE study: 2-year follow-up of adaptive servo-ventilation for sleep-disordered breathing in a chronic heart failure cohort

BackgroundSleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF) and is associated with worse prognosis. ObjectivesThis study evaluated the effects of adaptive servo-ventilation (ASV) on morbidity and mortality in a large heterogeneous population of HF patients with different etiologies/phenotypes. MethodsConsecutive HF patients with predominant central sleep apnea (± obstructive sleep apnea) indicated for ASV were included; the control group included patients who refused or stopped ASV before three months follow-up. Six homogenous clusters were determined using the latent class analysis (LCA) method. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of chronic HF). ResultsOf 503 patients at baseline, 324 underwent 2-year follow-up. Compared to control group, 2-year primary endpoint event-free survival was significantly greater in patients in ASV group only in univariable analysis (1.67, 95% [1.12–2.49]; p = 0.01). Secondary endpoints, event-free of cardiovascular death or heart failure-related hospitalization and all-cause death or all-cause hospitalization were positively impacted by ASV (univariate and multivariable analysis). LCA identified two groups, with preserved and mid-range left ventricular ejection fraction (LVEF) and severe hypoxia, in whom ASV increase prognosis benefit. ConclusionsPatients with HF and SDB are a highly heterogeneous group identified using LCA. Systematic deep phenotyping is essential to ensure that ASV is prescribed to those benefit from therapy, as ASV use in patients with severe hypoxic burden and those with HFpEF was associated with a significant reduction in cardiovascular events and mortality. Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01831128.

P047 Rehabilitation-led management of sleep disordered breathing: adapting a model of care for a rehabilitation centre in Australia

Abstract Introduction Sleep disordered breathing (SDB) is highly prevalent in tetraplegia, yet most remain undiagnosed and untreated for the disorder. We have described the care models of three international SCI rehabilitation centres that are independently diagnosing and treating SDB, and distilled their common pathways into the SCISTAR (SCI Sleep disordered breathing Treatment & Assessment in Rehabilitation) model. The aim of this project was to adapt the SCISTAR model to suit the Royal Rehab Spinal Injuries Unit, and to prepare for the implementation of this new model of care. Methods A clinical advisory group, consisting of researchers, rehabilitation and respiratory health professionals, met six times over eight months to: • identify the multidisciplinary SDB clinical team, • adapt the SCISTAR model, • develop parameters for safe clinical practice, • identify education needs, • identify and acquire the necessary equipment. Results The SDB clinical team consists of two rehabilitation consultants, two physiotherapists and four nurses. All patients with SCI will be assessed for SDB following admission. Assessments will include symptoms, spirometry and sniff nasal inspiratory pressure, and a Level 3 overnight sleep study (ResMed ApneaLink). Patients diagnosed with un-complicated SDB will be prescribed CPAP, which will be initiated and progressed on the ward. Screening for hypoventilation and predominant central sleep apnoea will occur throughout the pathway and if identified, patients will be referred to a specialist respiratory service. Comprehensive education and equipment has been provided. Conclusions The new care model is currently being piloted for 12 months. A comprehensive evaluation has been developed.

Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study.

Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA. HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea-hypopnoea index (AHI) ≥15 events·h-1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed. 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h-1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min-1 at baseline to 44.6±11.2 bursts·min-1; ASV group: 43.0±9.0 bursts·min-1 at baseline to 42.74±9.45 bursts·min-1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective. Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

Effect of adaptive servo ventilation on central sleep apnea and sleep structure in systolic heart failure patients: polysomnography data from the SERVE-HF major sub study.

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94-103 in the control group, 77-99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p=0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p=0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk.

Sleep Breathing Disorders in Heart Failure.

Sleep-disordered breathing (SDB), including obstructive sleep apnea, central sleep apnea (CSA), and Cheyne-Stokes respiration, is common in patients with heart failure (HF) and associated with lower left ventricular ejection fraction (EF), increased arrhythmia burden, and increased mortality. Continuous positive airway pressure therapy improves short-term and long-term outcomes in HF patients. Adaptive servoventilation (ASV) therapy in patients with low-EF HF with predominant CSA is not recommended. Ongoing trials are evaluating whether ASV will have a role in SDB treatment. Phrenic nerve stimulation is an emerging treatment option that has shown promising outcomes. All HF patients should be screened for SDB.

Treatment of Cheyne-Stokes Respiration in Heart Failure with Adaptive Servo-Ventilation: An Integrative Model.

The SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) multicenter trial found a small but significant increase in all-cause and cardiovascular mortality in patients assigned to adaptive servo-ventilation (ASV) versus guideline-based medical treatment. To better understand the physiological underpinnings of this clinical outcome, we employ an integrative computer model to simulate congestive heart failure with Cheyne-Stokes respiration (CHF-CSR) in subjects with a broad spectrum of underlying pathogenetic mechanisms, as well as to determine the in silico changes in cardiopulmonary and autonomic physiology resulting from ASV. Our simulation results demonstrate that while the elimination of CSR through ASV can partially restore cardiorespiratory and autonomic physiology toward normality in the vast majority of CHF phenotypes, the degree of restoration can be highly variable, depending on the combination of CHF mechanisms in play. The group with the lowest left ventricular ejection fraction (LVEF) appears to be most vulnerable to the potentially adverse effects of ASV, but the level of pulmonary capillary wedge pressure (PCWP) plays an important role in determining the nature of these effects.

Adaptive servo ventilation for sleep apnoea in heart failure: the FACE study 3-month data

RationaleAdaptive servo ventilation (ASV) is contraindicated in patients with systolic heart failure (HF) who have a left ventricular ejection fraction (LVEF) below 45% and predominant central sleep apnoea (CSA). However,...

828 Challenges of artifact in Polysomnography-An LVAD Story

Abstract Introduction Congestive heart failure and sleep-disordered breathing frequently coexist. Many of these patients are referred for polysomnography(PSG). Left ventricular assist device (LVAD) is increasingly used as a destination therapy or as a bridge to transplant. This can lead to artifacts in EEG and EKG. The artifact can mask pathological waves or over-reading of pathology. We present a case report of a patient who underwent a PSG on LVAD. Report of case(s) Sixty-six-year old male with severe heart failure with reduced ejection fraction (EF) of 15 % presented with snoring and witnessed apnea. The patient was diagnosed with predominant central sleep apnea (92%) but never initiated BPAP/ST due to an unstable heart. He was placed on LVAD (HeartMate III LVAD, oscillatory speed of 5300 rpm/83.3Hz) as the heart status deteriorated. Repeat polysomnography was done for persistent snoring but improved witnessed apneas revealed a newly appearing artifact. EEG showed a diffuse low amplitude,6–7 Hz frequency waves, and a regularly appearing high voltage sharp-peaked wave. The morphology of alpha wave, K wave, spindles, and delta waves could not be appreciated and hence was unable to perform sleep staging. EKG had electrical artifacts. All troubleshooting maneuvers were unsuccessful in eliminating artifacts. The artifact is generated by the impeller rotational speed of LVAD that ranges from 2400 rpm to 10,00 rpm(oscillation frequencies of 40 Hz to 166.7 Hertz,1Hz == 60 rpm). The device’s artificial pulse causes additional minor peaks. EEG artifact can be improved by moving the amplifier away from the heart and repositioning the patient. Adjusting the low-frequency filter can affect the nasal pressure tracing, delta waves, and stage 3 recognition. Reducing the high-frequency filter frequency by 10 from the LVAD oscillation frequency improves the EKG signal. But this may cut off the frequency component of pathologies like left ventricular hypertrophy. Conclusion The LVAD has been increasingly used in the United States. It is important to improve awareness regarding the artifacts among sleep techs and physicians. Unresolved artifacts may lead to missing serious pathologies in EEG and EKG and also can lead to misreading the waves as pathological leading to unnecessary treatment. Support (if any) An image of EEG and EKG

842 PAP Therapy in a Pandemic: Management of Severe Mixed Apnea Predominant OSA &amp; CSA during the COVID-19 Pandemic

IntroductionIntroduction/Background: A new protocol and standard of care was created amidst the COVID-19 Pandemic that began in 2020. Traditional split night studies fell out of favor and were replaced by solely diagnostic studies with placement on Auto-PAP therapy if treatment of sleep disordered breathing was required. Some patients, however, required a more tailored approach if diagnostic polysomnogram (PSG) was particularly concerning. Our case report describes the treatment of a patient with severe Mixed Apnea Predominant Obstructive Sleep Apnea (OSA) with accompanying Central Sleep Apnea (CSA) using COVID-19 Precautions.Report of case(s)Case Description: A 48 year old AAM patient with a PMH of HTN, pre-diabetes, GERD, obesity and tobacco abuse initially presented to Sleep Medicine in late January 2020 with complaints of snoring, witnessed apneas, waking up gasping, excessive daytime sleepiness, fatigue, and non-restorative sleep for many years with ESS 24 and FSS 48 on initial evaluation. Diagnostic PSG showed AHI 76.9 with O2 desaturation to 59% and demonstrated the presence of severe Mixed Apnea predominant OSA and CSA with worsening during REM sleep. Because of the severity, he underwent a PAP titration in August 2020 using the AASM COVID-19 sleep study precautions which included use of a negative pressure room. Optimal control of snoring, apneic respiratory events and oxygen desaturations was achieved at 14 cm H2O in the supine body position during REM sleep. Follow up with Sleep Medicine in October and December 2020 showed objective compliance over a 30 day period not completely at goal due to issues with mask desensitization and sleep hygiene, however the patient subjectively reported that he noticed great improvement in snoring, excessive daytime sleepiness and fatigue.Conclusion: Discussion/ConclusionWith a diagnosis of Severe Mixed Apnea Predominant OSA as well as CSA noted during the study, the differential diagnosis included CHF, Chiari malformation, opioid abuse and idiopathic CSA as the cause. Despite a dangerous pandemic, appropriate therapy for certain patients must still be attained. Special protocols developed during the COVID-19 Pandemic allowed for our patient to receive adequate treatment, while ensuring the safety of all involved.Support (if any)References COVID 19: FAQs for Sleep Clinicians. AASM official website. https://aasm.org/covid-19-resources/covid-19-faq/

Sleep-Disordered Breathing and Nocturnal Hypoxemia in Precapillary Pulmonary Hypertension: Prevalence, Pathophysiological Determinants, and Clinical Consequences

Background and objective: The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood. Methods: Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34). Results: Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to <15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO₂] <90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO₂, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = −0.39; p = 0.03) and end-systolic (r = −0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO₂ but not with measures of OSA severity or daytime clinical variables. Conclusion: OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO₂, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.

0731 Obstructive Sleep Apnea with Predominant Respiratory Effort Related Arousals: Theta Power in C3- M2 And C4-M1 Derivation Comparison in Male And Female

Abstract Introduction Theta power in electroencephalography has been studied as a correlate to REM sleep. An increase in theta power during REM sleep has been observed in patients during recovery sleep after sleep deprivation. Emotional memories appear to be processed and consolidated during REM sleep.The role of hippocampal theta wave activity during REM sleep on emotional memory processing is limited. The importance of theta power has not been well characterized in patients with obstructive sleep apnea (OSA) with predominant respiratory Effort Related Arousals (RERAs). This report aims to study the theta power in patients with OSA with predominant Respiratory Effort Related Arousals (RERAs) with an apnea-hypopnea index (AHI) of &amp;lt; 5. Methods We have identified 38 patients with baseline polysomnograms performed from December 2019 to July 2019 with AHI &amp;lt; 5 and a Respiratory Disturbance Index (RDI) of at least 5 or greater. Patients with chronic hypoxemic respiratory failure, hypoventilation and predominant central sleep apnea were excluded from the study. Total power of frequency in bands was obtained for theta waves (4-8 Hz) and total waves (1-30 Hz). Relative theta power was calculated on the last REM sleep using C3-M2 and C4-M1 derivations. Paired two-tailed t-Test was performed on the theta power in C3-M2 and C4-M1 in both the sexes. Results Initial analysis was performed in 38 patients out of which 20 were male and 18 female. Among males, (Mean ± SEM) age was 52.3 (±2.9); Epworth Sleepiness Scale (ESS) of 6.6 (±1.1), AHI of 2.1 (±0.3), and RDI of 7.3 (±0.3).Whereas in female (Mean ± SEM) age was 46.8 (± 2.8), ESS of 7.7 (±1.4), AHI of 2.3 (±0.35), and RDI of 6.9 (±0.4). Statistically significant difference was noted in the theta power between the C3-M2 and C4-M1 derivations with P value of 0.03 and 0.04 in male and female respectively. However, no significant difference was found when C3-M2 and C4 -M1 was compared between male and female. Further, statistical analysis will be performed after gathering data from a larger sample size. Conclusion There was significant difference between C3-M2 and C4-M1;overall no difference was found between sexes. Support none

Meta-Analysis Comparing Outcomes of Therapies for Patients With Central Sleep Apnea and Heart Failure With Reduced Ejection Fraction

Patients with heart failure with reduced ejection fraction and predominant central sleep apnea pose treatment challenges. A system review and meta-analysis of randomized controlled trials (RCTs) were undertaken. Electronic searches of digital repositories, journals, specialty society and manufacturer websites, manual searches of reference sections of RCTs, and published clinical guidelines were performed. Studies were graded for bias. Meta-analytic random effects models were used. Outcomes of interest included: sleep, cardiovascular, mortality, and quality of life (QoL). Grading of recommendations assessment, development and evaluation was performed. Nineteen randomized studies were identified that met the inclusion criteria of apnea hypopnea index (AHI) ≥10, predominant central sleep apnea (CSA), and heart failure with reduced ejection fraction (HFrEF) ≤50%. Most trials examined adaptive servo ventilation (ASV) (8 studies) and continuous positive airway pressure (CPAP) (9 studies). Bias existed in that: 15 of 19 (79%) of the trials lacked blinding, 10 of 19 were manufacturer funded, and with attrition in 8 of 19 studies. In meta-analysis, ASV performed better than control on sleep but not on QoL or cardiovascular outcomes, including mortality. CPAP demonstrated positive short-term outcomes on sleep, cardiovascular, and QoL (3 months). Longer-term cardiovascular and mortality data did not show benefit. Drug therapies demonstrated a positive clinical effect short term on sleep outcomes only. Transvenous phrenic nerve stimulation (TPNS) demonstrated positive treatment outcomes on sleep and QoL at 6 months. Evidence suggests improvement in cardiovascular outcomes with TPNS. In conclusion, ASV and CPAP therapies improve sleep, but long-term QoL or cardiovascular benefit was lacking. TPNS exhibited positive outcomes on sleep and QoL at 6 months with positive trends in CV outcomes.

Sleep for Stroke Management and Recovery Trial (Sleep SMART): Rationale and methods.

Obstructive sleep apnea is common among patients with acute ischemic stroke and is associated with reduced functional recovery and an increased risk for recurrent vascular events. The Sleep for Stroke Management and Recovery Trial (Sleep SMART) aims to determine whether automatically adjusting continuous positive airway pressure (aCPAP) treatment for obstructive sleep apnea improves clinical outcomes after acute ischemic stroke or high-risk transient ischemic attack. A total of 3062 randomized subjects for the prevention of recurrent serious vascular events, and among these, 1362 stroke survivors for the recovery outcome. Sleep SMART is a phase III, multicenter, prospective randomized, open, blinded outcome event assessed controlled trial. Adults with recent acute ischemic stroke/transient ischemic attack and no contraindication to aCPAP are screened for obstructive sleep apnea with a portable sleep apnea test. Subjects with confirmed obstructive sleep apnea but without predominant central sleep apnea proceed to a run-in night of aCPAP. Subjects with use (≥4 h) of aCPAP and without development of significant central apneas are randomized to aCPAP plus usual care or care-as-usual for six months. Telemedicine is used to monitor and facilitate aCPAP adherence remotely. Two separate primary outcomes: (1) the composite of recurrent acute ischemic stroke, acute coronary syndrome, and all-cause mortality (prevention) and (2) the modified Rankin scale scores (recovery) at six- and three-month post-randomization, respectively. Sleep SMART represents the first large trial to test whether aCPAP for obstructive sleep apnea after stroke/transient ischemic attack reduces recurrent vascular events or death, and improves functional recovery.

Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE-HF trial.

AimsThe Treatment of Sleep‐Disordered Breathing with Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients with Heart Failure trial investigated the effects of adaptive servo‐ventilation (ASV) (vs. control) on outcomes of 1325 patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). The primary outcome (a composite of all‐cause death or unplanned HF hospitalization) did not differ between the two groups. However, all‐cause and cardiovascular (CV) mortality were higher in the ASV group. Circulating biomarkers may help in better ascertain patients' risk, and this is the first study applying a large set of circulating biomarkers in patients with both HFrEF and CSA.Methods and resultsCirculating protein‐biomarkers (n = 276) ontologically involved in CV pathways, were studied in 749 (57% of the trial population) patients (biomarker substudy), to investigate their association with the study outcomes (primary outcome, CV death and all‐cause death). The mean age was 69 ± 10 years, and > 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The “best” clinical prognostic model included male sex, systolic blood pressure < 120 mmHg, diabetes, loop diuretic, cardiac device, 6‐min walking test distance, and N‐terminal pro BNP as the strongest prognosticators. On top of the “best” clinical prognostic model, the biomarkers that significantly improved both the discrimination (c‐index) and the net reclassification index (NRI) of the model were soluble suppression of tumorigenicity 2 for the primary outcome; neurogenic locus notch homolog protein 3 (Notch‐3) for CV‐death and all‐cause death; and growth differentiation factor 15 (GDF‐15) for all‐cause death only.ConclusionsWe studied 276 circulating biomarkers in patients with HFrEF and central sleep apnoea; of these biomarkers, three added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch‐3 (CV and all‐cause death), and GDF‐15 (all‐cause death).

Association of serious adverse events with Cheyne-Stokes respiration characteristics in patients with systolic heart failure and central sleep apnoea: A SERVE-Heart Failure substudy analysis.

Increases in Cheyne-Stokes respiration (CSR) cycle length (CL), lung-to-periphery circulation time (LPCT) and time to peak flow (TTPF) may reflect impaired cardiac function. This retrospective analysis used an automatic algorithm to evaluate baseline CSR-related features and then determined whether these could be used to identify patients with systolic heart failure (HF) who experienced serious adverse events in the Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE-HF) substudy. A total of 280 patients had overnight diagnostic polysomnography data available; an automated algorithm was applied to quantify CSR-related features. Median baseline CL, LPCT and TTPF were similar in the control (n = 152) and adaptive servo-ventilation (ASV, n = 156) groups. In both groups, CSR-related features were significantly longer in patients who did (n = 129) versus did not (n = 140) experience a primary endpoint event (all-cause death, life-saving cardiovascular intervention or unplanned hospitalization for worsening HF): CL, 61.1 versus 55.1 s (P = 0.002); LPCT, 36.5 versus 31.5 s (P < 0.001); TTPF, 15.20 versus 13.35 s (P < 0.001), respectively. This finding was independent of treatment allocation. Patients with systolic HF and central sleep apnoea who experienced serious adverse events had longer CSR CL, LPCT and TTPF. Future studies should examine an independent role for CSR-related features to enable risk stratification in systolic HF.

Servo-Ventilation Therapy for Sleep-Disordered Breathing

As seen in this CME online activity (available at http://journal.cme.chestnet.org/sv-sleep-disorder), central sleep apnea (CSA) is associated with increased mortality in patients with heart failure (HF), and it has been thought that treatment of CSA may improve underlying HF. Positive airway pressure therapy, specifically auto-servoventilation (ASV), can not only suppress abnormal breathing patterns but has been reported to improve cardiac function in HF patients with CSA. In patients with HF and with CSA unsuppressed with CPAP, newer ASV use has been associated with significant CSA improvement; in addition, several studies have reported efficacy of ASV in the treatment of underlying cardiac dysfunction in HF patients with CSA. However, results from the large randomized Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo-Ventilation in Patients with Heart Failure (SERVE-HF) trial (Cowie MR, Woehrle H, Wegscheider K, etal. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. New Engl J Med. 2015;373[12]:1095-1105) showed no significant effect on the primary end point in patients with stable HF with reduced ejection fraction and predominantly CSA, but all-cause and cardiovascular mortality were both increased in the ASV arm. These results are surprising and inconsistent with earlier smaller studies reporting positive surrogate outcomes, and they require additional study and resolution. However, until this is done, there is an urgent educational need for review of the approved labeling and validated clinical use of ASV within the medical community. The purpose of this educational activity is to review the appropriate use of ASV for the treatment of sleep-disordered breathing, including Cheyne-Stokes respiration, treatment-emergent central apnea, and opioid-induced periodic breathing. Emphasis will be placed on proper patient and therapy selection, especially in patients with HF.

Positive Airway Pressure for Sleep-Related Breathing Disorders in Heart Failure—Overview and Discussion of Potential Mechanisms of Harm

The impact of positive airway pressure (PAP) therapies on cardiovascular outcome in obstructive sleep apnea (OSA) and central sleep apnea (CSA) is currently under debate. The goal of this review is to critically analyze the current findings and discuss hypotheses on benefits or even harm in patients with heart failure (HF). While PAP sufficiently improves OSA, symptoms and cardiac parameters, the SAVE trial failed to show survival benefits. However, it was limited due to low adherence, non-sleepy population and maximal cardiac pre-treatment. SERVE-HF showed increased mortality in secondary analysis in patients with severe systolic HF with predominant CSA under adaptive servo-ventilation (ASV). Criticism of the trial emanated from high crossover, low compliance, use of older devices, and contradictory beneficial results in other studies. As sudden cardiac deaths was the reported main cause of mortality, influences of pre-medication and methods of pressure support on cardiac instability may have contributed to the pathogenesis. OSA and CSA are main risk factors for poor outcome in cardiovascular disease. However, the effect of CPAP and ASV on cardiovascular comorbidities and prognosis requires further evaluation. Further insights from ongoing trials are urgently needed to clarify benefits and risk.

Adaptive servo-ventilation to treat central sleep apnea in heart failure with reduced ejection fraction: the BadOeynhausen prospective ASV registry.

Central sleep apnea (CSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HF-REF). The Bad Oeynhausen Adaptive Servo-ventilation (ASV) registry (NCT01657188) was designed to investigate whether treatment of CSA with ASV improved survival in HF-REF patients; the effects of ASV on symptoms and cardiopulmonary performance were also investigated. From January 2004 to October 2013, the registry prospectively enrolled HF-REF patients [NYHA class ≥ II, left ventricular ejection fraction (LVEF) ≤ 45%] with moderate to severe predominant CSA [apnea-hypopnea index (AHI) ≥ 15/h]. ASV-treated patients were followed up at 3, 6, 12 and 24months, including natriuretic peptide concentrations, blood gas analyses, echocardiography, 6-min walk distance (6MWD), and cardiopulmonary exercise (CPX) testing. 550 patients were included [age 67.7 ± 10 years, 90% male, 52% in NYHA class ≥ III, LVEF 29.9 ± 8%, AHI 35.4 ± 13.6/h, and time with nocturnal oxygen saturation < 90% (T < 90%) 58 ± 73min]; ASV was prescribed to 224 patients. Over a median follow-up of 6.6years, 109 (48.7%) ASV-treated patients and 191 (58.6%) controls died (adjusted Cox modelling hazard ratio of 0.95, 95% confidence interval 0.68-1.24; p = 0.740); older age, lower LVEF, impaired renal function, low sodium concentration, and nocturnal hypoxemia were significant predictors of mortality. Patient reported NYHA functional class improved in the ASV group, but LVEF, CPX, 6MWD, natriuretic peptides and blood gases remained unchanged. Long-term ASV treatment of predominant CSA in HF-REF patients included in our registry had no statistically significant effect on survival. ASV improved HF symptoms, but had no significant effects on exercise capacity, LVEF, natriuretic peptide concentrations or blood gases during follow-up as compared to control patients.