Severe Central Sleep Apnea Research Articles

Transvenous Phrenic Nerve Stimulation is Safe and Effective in Patients with Heart Failure and Cheyne-stokes Respiration

Introduction The most common type of central sleep apnea (CSA) breathing pattern in patients with heart failure (HF) is Cheyne-Stokes respiration (CSR). CSR manifests as a cyclical pattern of apnea and hyperventilation, with absence of airflow and respiratory effort followed by hyperventilation in a crescendo-decrescendo pattern. CSR may be a predictor of negative clinical outcomes in HF patients. Purpose Examine the response to transvenous phrenic nerve stimulation (TPNS) in patients with HF and different amounts of CSR. Methods Patients with CSA and HF who participated in the remedē System Pivotal Trial were divided into clinically relevant subgroups based on percentage of sleep in CSR (%CSR: 50%) during their baseline polysomnogram. The subgroups were analyzed for efficacy and safety by randomized group (TPNS vs control [no TPNS]). Epworth sleepiness scale (ESS) was also collected. Results At baseline, higher percentage CSR subgroups had lower left ventricular ejection fraction (median 45% for CSR 50%). Baseline apnea-hypopnea index (AHI) indicated severe CSA in all subgroups. All CSR subgroups receiving TPNS therapy had more than 50% of patients achieve ≥50% reduction in AHI at 6 months (see Table); control response rates were ≤11% in each CSR subgroup. The AHI decreased by ≥21 events/hour in each CSR subgroup on therapy while Control subgroups had little or no improvement. The central apnea index decreased to median ≤3 events/hour in each TPNS CSR subgroup; each control subgroup had median 22-24 events/hour remaining at 6 months. Baseline daytime sleepiness was worse in lower %CSR subgroups, however improved in all subgroups. No apparent relationship existed between %CSR and cardiovascular death in patients using TPNS therapy through 6 months, with the only death being in the 20-50% CSR subgroup; the death was determined not related to device, therapy or procedure by the clinical events committee. Further, 2/22 control subjects with CSR>50% experienced a cardiovascular death compared to 0/12 in the TPNS treated subgroup. Conclusions Transvenous phrenic nerve stimulation can treat CSA in HF patients regardless of the percentage of sleep in CSR and no signal of increased mortality was observed.

Transvenous Phrenic Nerve Stimulation Improves Central Sleep Apnea in Heart Failure Patients

Introduction Central sleep apnea (CSA) and heart failure (HF) often present with similar symptoms. Treatment of CSA primarily focuses on management of CSA-related symptoms such as frequent night-time awakenings or arousals, daytime sleepiness and reduced quality of life (QoL). Transvenous phrenic nerve stimulation (TPNS) has demonstrated improvements in sleep metrics and patient reported outcomes (PROs). Hypothethis To identify symptoms experienced by patients with HF and CSA and determine what types of improvements occur in the most symptomatic patients using TPNS. Methods Post-hoc analysis of baseline and 12-month data collected from patients (N = 75) with HF and moderate to severe CSA from the remedē System Pivotal Trial. Responses to questions pertaining to PROs (Epworth Sleepiness Scale [ESS] and Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and clinical symptoms were analyzed to assess impact of TPNS therapy. Results Baseline clinical symptoms including nocturia (72%), reduced exercise capacity (61%), fatigue or weakness (69%), daytime sleepiness (77%), difficulty falling or staying asleep (52%), snoring (56%) and insomnia/fragmented sleep (51%) were reported by over half of the patients. By 12 months, 24%, 41%, 44%, 45%, 51%, 60% and 66% of the patients, respectively, no longer reported these specific clinical symptoms. On the baseline ESS, > = 50% of patients with HF reported moderate to high (2-3 on the scale) chance of dozing while sitting and reading (55%), watching television (56%) and lying down to rest in the afternoon (68%). For these patients with > = moderate at baseline, 71%, 52% and 35%, respectively, improved to less than moderate chance at 12 months. On the MLHFQ, 6/21 questions had > = 50% of subjects report that HF prevented them from living as they wanted moderately to very much (3-5 on the scale). Following 12 months of TPNS therapy, 33% to 71% of subjects improved from > = moderate at baseline to below moderate (Figure). NYHA functional class improved or remained stable in 89% (67/75) of subjects. Conclusion In the most symptomatic patients with CSA and HF, TPNS may improve symptoms and QoL, specifically related to sleep, sleepiness and fatigue. Heart failure patients with these symptoms may benefit from screening and subsequent treatment of CSA with TPNS.

Central Sleep Apnea and Pacing-Induced Cardiomyopathy

The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was assessed by single-night polysomnography (PSG) in 54 PICM patients within 1 month after left ventricular lead implantation (with biventricular stimulation still not activated). CSA was diagnosed in half of patients (n = 27). Patients with moderate or severe CSA were randomized to cardiac resynchronization therapy (CRT) versus right ventricular pacing (RVP) in a double-blinded cross-over design and re-scheduled for a follow-up PSG within 3 to 5 months. After crossing-over of stimulation mode another PSG was conducted 3 to 5 months later. CRT led to a significant increase in left ventricular ejection fraction and significant reduction in left ventricular end systolic volumes and N-terminal pro brain natriuretic peptide plasma levels, whereas no significant effects were observed with ongoing RVP. CSA was significantly improved after 3.9 (3.2 to 4.4) months of CRT: apnea-hypopnea index decreased from 39.1 (32.1 to 54.0) events per hour at baseline to 22.2/h (10.9 to 36.7) by CRT (p <0.001). Central apnea index decreased from 27.1/h (17.7 to 36.1) at baseline to 6.8/h (1.1 to 14.4) after CRT activation (p <0.001). Ongoing RVP yielded only a minor improvement in apnea-hypopnea index and central apnea index. Pre-existent CSA did not affect structural response rate and had no impact on mid-term follow-up (median 2.8 years). In conclusion, CSA is highly prevalent in patients with PICM. CRT upgrading significantly improves CSA leading to a similar outcome in PICM patients without pre-existent CSA.

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

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

Transvenous Phrenic Nerve Stimulation and Automatic Positive Airway Pressure Therapy for Treating Central Sleep Apnea and Residual Obstructive Sleep Apnea

Central sleep apnea (CSA) is a neurological breathing disorder resulting from intermittent disruptions in the neural drive to breath. CSA and obstructive sleep apnea (OSA), caused by partial or complete airway blockage, sometimes occur together. The remede System (Respicardia, Minnetonka, MN) is an implantable device that delivers transvenous phrenic nerve stimulation therapy (TPNS) to treat CSA. A patient who failed previous Positive Airway Pressure (PAP) therapies presented with severe CSA and OSA with a baseline Apnea Hypopnea Index (AHI) of 98.1 events/hour. The patient was implanted with a TPNS device and titrated to maximum effectiveness. His CSA improved, but still had persistent OSA. PAP therapy was added to supplement the TPNS. With TPNS off, PAP therapy treated obstructive events but not the central events. TPNS alone treated the central events but not the obstructive events. With both therapies on, CSA and OSA were controlled and breathing was normalized (AHI=3.8). ClinicalTrials.gov Identifier: NCT01816776.

1265 Severe Central and Obstructive Sleep Apnea in Teenager with Severe Obesity, Tonsillar Hyper-trophy, and Maxillary Constriction

Abstract Introduction Obesity in children escalated in the past 50 years. For American children 2-19 years old, Obesi-ty(BMI &amp;gt;= 95th%) increased from 5% in 1971-4 to 19%(13.7 million children)2015-16. Severe Obesity(BMI &amp;gt;=120th% or &amp;gt;35) is less common with prevalences of 1% 1971-4 to 6% in 2015-16(1). Obesity increases risk for physical and mental illness. Sleep apnea risk factors include obesity, maxillary restriction(3), and adenotonsillar hypertro-phy(4). Report of Case 16 yo boy with snoring, gasping during sleep, witnessed apneas, mouth breathing, morning head-aches, EDS, and learning disability requiring an IEP. Past medical history of neonatal snoring, apneas, and reflux. Physical exam revealed severe obesity(BMI 45.3), high arched/narrow palate, Class II bite, large tongue, Mallampati IV, Grade 3-4 tonsils, CricoMental Space +1cm. Inattentive with mildly de-pressed affect. No cardiovascular, pulmonary or neurologic findings. PSG: CAI 31.2, OAHI 23.8. Average O2 sat 97% with 11 minutes&amp;lt;88%. End-tidal CO2 average 50 during sleep and wake. 51% of total sleep time with ETCO2&amp;gt;50 mmHg. CPAP titration: CAI 1.8, OAHI 10.4. Average O2 sat 96% with &amp;lt;1 minute&amp;lt;88%. Events improved with CPAP 14 cm H20 to OAHI 3.5 with &amp;gt;30 minutes of supine REM. Conclusion Severe Central Sleep Apnea with significant obstructive component associated with hypoxia and hypoventilation. With the diurnal hypoventilation, the likely etiology for central apneas is Obesity Hypoventilation Syndrome(5). The central apnea improved with CPAP. His management included CPAP therapy, ENT referral for adenotonsillectomy(5), bariatric referral, and further evaluation for learning/behavior concerns. In retrospect, earlier diagnosis/intervention on behalf of this teenage boy with a history of neonatal snoring presenting now with Severe Obesity, tonsillar hypertrophy and maxillary constriction may have made a significant difference for his cognitive/mental/physical health outcomes.

Association between central sleep apnea and atrial fibrillation/flutter in Japanese-American men: The Kuakini Honolulu Heart Program (HHP) and Honolulu-Asia Aging Study (HAAS)

IntroductionWhile several studies have indicated that central sleep apnea (CSA) is associated with atrial fibrillation and atrial flutter (AF) in older populations, few studies have focused on older Asian populations. MethodsWe conducted a cross- sectional analysis using data from the 1999–2000, 7th exam cycle of the Kuakini Honolulu-Asia Aging Study. Participants were 718 Japanese-American men between 79 and 97 years old, who had overnight polysomnography. Obstructive Apnea-Hypopnea Index (OAHI) was the measure of the number of obstructive apneas and hypopneas with >4% oxygen desaturation. Additionally, the Central Apnea Index (CAI) was the measure of the number of central apneas. Obstructive sleep apnea (OSA) was categorized as none (OAHI <5), mild (OAHI 5–14), moderate (OAHI 15–29) and severe (OAHI ≥30). CSA was defined by CAI of 5 or more. Cheyne-Stokes Breathing (CSB) was defined as a minimum consecutive 5-minute period of a crescendo-decrescendo respiratory pattern associated with CSA. ResultsAF prevalence was 5.5% (39 of 709). The prevalence proportions of severe OSA, CSA, and CSB were 20.2% (143 of 709), 6.4% (43 of 673) and 3.2% (22 of 673), respectively. In multivariable-adjusted logistic regression models, CSA and CSB were significantly associated with AF prevalence: odds ratio (OR) 5.15, 95% confidential interval (CI), 2.21–12.52 and OR 6.26, 95% CI, 2.05–19.14, respectively. However, OSA was not significantly associated with AF prevalence. ConclusionAF prevalence is associated with CSA and CSB but not OSA in older Japanese-American men. This information could help target AF prevention strategies in this population.

Angiotensin II-Type I Receptor Antagonism Does Not Influence the Chemoreceptor Reflex or Hypoxia-Induced Central Sleep Apnea in Men.

Components of the renin-angiotensin system (RAS) situated within the carotid body or central nervous system may promote hypoxia-induced chemoreceptor reflex sensitization or central sleep apnea (CSA). We determined if losartan, an angiotensin-II type-I receptor (AT1R) antagonist, would attenuate chemoreceptor reflex sensitivity before or after 8 h of nocturnal hypoxia, and consequently CSA severity. In a double-blind, randomized, placebo-controlled, crossover protocol, 14 men (age: 25 ± 2 years; BMI: 24.6 ± 1.1 kg/m2; means ± SEM) ingested 3 doses of either losartan (50 mg) or placebo every 8 h. Chemoreceptor reflex sensitivity was assessed during hypoxic and hyperoxic hypercapnic ventilatory response (HCVR) tests and during six-20s hypoxic apneas before and after 8 h of sleep in normobaric hypoxia (FIO2 = 0.135). Loop gain was assessed from a ventilatory control model fitted to the ventilatory pattern of CSA recorded during polysomnography. Prior to nocturnal hypoxia, losartan had no effect on either the hyperoxic (losartan: 3.6 ± 1.1, placebo: 4.0 ± 0.6 l/min/mmHg; P = 0.9) or hypoxic HCVR (losartan: 5.3 ± 1.4, placebo: 5.7 ± 0.68 l/min/mmHg; P = 1.0). Likewise, losartan did not influence either the hyperoxic (losartan: 4.2 ± 1.3, placebo: 3.8 ± 1.1 l/min/mmHg; P = 0.5) or hypoxic HCVR (losartan: 6.6 ± 1.8, placebo: 6.3 ± 1.5 l/min/mmHg; P = 0.9) after nocturnal hypoxia. Cardiorespiratory responses to apnea and participants’ apnea hypopnea indexes during placebo and losartan were similar (73 ± 15 vs. 75 ± 14 events/h; P = 0.9). Loop gain, which correlated with CSA severity (r = 0.94, P < 0.001), was similar between treatments. In summary, in young healthy men, hypoxia-induced CSA severity is strongly associated with loop gain, but the AT1R does not modulate chemoreceptor reflex sensitivity before or after 8 h of nocturnal hypoxia.

Severity of Central Sleep Apnea Does Not Improve Sleeping Oxygen Saturation During Ascent to High Altitude

Central sleep apnea (CSA) is characterized by intermittent periods of apnea (no breathing) and hyperventilation (over breathing) with associated fluctuations in blood oxygen saturation. CSA is universal at high altitude (&gt;3000m), increasing in severity with ascent and/or time spent at high altitude. Although there is a large degree of variability in CSA severity, factors that increase susceptibility to CSA at altitude include: (a) hypoxia, (b) hypoxic ventilatory response‐mediated hypocapnia and (c) increases in chemoreflex responsiveness via ventilatory acclimatization. Whether CSA is adaptive or maladaptive at altitude is unknown. Notwithstanding the brief periods of desaturation associated with apnea, the subsequent relative intermittent hyperventilation may increase oxygen reserves during sleep, protecting overall mean saturation. We hypothesized that CSA protects mean sleeping oxygen saturation during acclimatization to high altitude. In two groups of Diamox‐free native lowlanders, we characterized the effects of increasing CSA severity on night‐time sleeping oxygen saturation during two separate high altitude ascent profiles: (I) incremental ascent to 5160m over 10 days/nights in the Nepal Himalaya (n=21) and (II) rapid ascent to and residing at 3800m over 10 days/nights in the Sierra Nevada mountains, CA, USA (n=21). Using portable polysomnographs and scoring software (ResMed ApneaLink; AASM criteria), we assessed apnea‐hypopnea index (AHI), oxygen desaturation index (ODI), and baseline, mean and nadir oxygen saturation (SpO2) during sleep at each altitude. During sleep across both ascent profiles, AHI and ODI increased in severity, and baseline, mean and nadir SpO2 decreased significantly, suggesting both altitude‐ and sleep apnea‐associated hypoxia. During incremental ascent to 5160m over 10 days/nights (Part I), AHI and ODI increased from 3.9±4.1 and 9.8±7.8 (1045m) to 37.5±32.8 and 54.4±24.8 events/hour, respectively (P&lt;0.001). In addition, baseline, mean and nadir SpO2 decreased from 96.0±2.0, 94.3±1.6 and 87.1±3.7% (1045m) to 78.9±3.6, 73.5±4.2 and 63.7±6.6%, respectively (P&lt;0.0001). After 10 days/nights following rapid ascent to 3800m (Part II), AHI and ODI increased from 3.4±3.5 and 6.8±5.3 (1045m) to 23.2±21.2 and 38.0±24.4 events/hour, respectively (P&lt;0.001). In addition, baseline, mean and nadir SpO2 decreased from 95.3±1.9, 93.7±2.1 and 86.0±5.1% (1045m) to 85.6±1.8, 84.0±2.4 and 74.1±6.2%, respectively (P&lt;0.0001). There were no significant correlations between AHI nor ODI and mean nor nadir SpO2 during sleep at 5160m (night 9/10; Part I; r&gt;−0.35, P&gt;0.2) and 3800m (night 9/10; Part II; r&gt;−0.45, P&gt;0.05). We conclude that the severity of CSA following acclimatization to high altitude does not play a role in improving oxygen saturation. However, the relative hyperventilation between apneas likely protects against the apnea‐mediated oxygen desaturations during sleep at altitude.Support or Funding InformationAlberta Government Student Temporary Employment Program, Alberta Innovates Health Solutions, Natural Sciences and Engineering Research Council of Canada.

Central Sleep Apnea Alters Neuronal Excitability and Increases the Randomness in Sleep-Wake Transitions.

While most studies on Central Sleep Apnea (CSA) have focused on breathing and metabolic disorders, the neuronal dysfunction that causes CSA remains largely unknown. Here, we investigate the underlying neuronal mechanism of CSA by studying the sleep-wake dynamics as derived from hypnograms. We analyze sleep data of seven groups of subjects: healthy adults (n=48), adults with obstructive sleep apnea (OSA) (n=29), adults with CSA (n=25), healthy children (n=40), children with OSA (n=18), children with CSA (n=73) and CSA children treated with CPAP (n=10). We calculate sleep-wake parameters based on the probability distributions of wake-bout durations and sleep-bout durations. We compare these parameters with results obtained from a neuronal model that simulates the interplay between sleep- and wake-promoting neurons. We find that sleep arousals of CSA patients show a characteristic time scale (i.e., exponential distribution) in contrast to the scale-invariant (i.e., power-law) distribution that has been reported for arousals in healthy sleep. Furthermore, we show that this change in arousal statistics is caused by triggering more arousals of similar durations, which through our model can be related to a higher excitability threshold in sleep-promoting neurons in CSA patients. We propose a neuronal mechanism to shed light on CSA pathophysiology and a method to discriminate between CSA and OSA. We show that higher neuronal excitability thresholds can lead to complex reorganization of sleep-wake dynamics. The derived sleep parameters enable a more specific evaluation of CSA severity and can be used for CSA diagnosis and monitor CSA treatment.

Prevalence, risk factors, and type of sleep apnea in patients with paroxysmal atrial fibrillation

BackgroundRecent studies have suggested an association between sleep apnea (SA) and atrial fibrillation (AF). We aimed to study the prevalence, characteristics, risk factors and type of sleep apnea (SA) in ablation candidates with paroxysmal AF. Methods/ResultsWe prospectively studied 579 patients with paroxysmal AF, including 157 women (27.1%) and 422 men (72.9%). Mean age was 59.9 ± 9.6 years and mean body mass index (BMI) 28.5 ± 4.5 kg/m2. SA was diagnosed using polygraphy for two nights at home. The Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire, and Berlin Questionnaire (BQ) assessed the degree of SA symptoms. A total of 479 (82.7%) patients had an apnea-hypopnea index (AHI) ≥ 5, whereas moderate-severe SA (AHI ≥ 15) was diagnosed in 244 patients (42.1%). The type of SA was predominantly obstructive, with a median AHI of 12.1 (6.7–20.6) (range 0.4–85.8). The median central apnea index was 0.3 (0.1–0.7). AHI increased with age, BMI, waist and neck circumference, body and visceral fat. Using the Atrial Fibrillation Severity Scale and the SF-36, patients with more severe SA had a higher AF burden, severity and symptom score and a lower Physical-Component Summary score. Age, male gender, BMI, duration of AF, and habitual snoring were independent risk factors in multivariate analysis (AHI ≥ 15). We found no association between ESS and AHI (R2 = 0.003, p = 0.367). ConclusionsIn our AF population, SA was highly prevalent and predominantly obstructive. The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. None of the screening questionnaires predicted SA reliably.

Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea: A Pooled Cohort Analysis.

Early evidence with transvenous phrenic nerve stimulation (PNS) demonstrates improved disease severity and quality of life (QOL) in patients with central sleep apnea (CSA). The goal of this analysis is to evaluate the complete prospective experience with PNS in order to better characterize its efficacy and safety, including in patients with concomitant heart failure (HF). Using pooled individual data from the pilot (n = 57) and pivotal (n = 151) studies of the remedē System in patients with predominant moderate to severe CSA, we evaluated 12-month safety and 6- and 12-month effectiveness based on polysomnography data, QOL, and cardiac function. Among 208 combined patients (June 2010 to May 2015), a remedē device implant was successful in 197 patients (95%), 50/57 pilot study patients (88%) and 147/151 pivotal trial patients (97%). The pooled cohort included patients with CSA of various etiologies, and 141 (68%) had concomitant HF. PNS reduced apnea-hypopnea index (AHI) at 6 months by a median of -22.6 episodes/h (25th and 75th percentile; -38.6 and -8.4, respectively) (median 58% reduction from baseline, P < .001). Improvement in sleep variables was maintained through 12 months of follow-up. In patients with HF and ejection fraction ≤ 45%, PNS was associated with improvement in systolic function from 27.0% (23.3, 36.0) to 31.1% (24.0, 41.5) at 12 months (P = .003). In the entire cohort, improvement in QOL was concordant with amelioration of sleep measures. Transvenous PNS significantly improves CSA severity, sleep quality, ventricular function, and QOL regardless of HF status. Improvements, which are independent of patient compliance, are sustained at 1 year and are associated with acceptable safety.

Phrenic Nerve Stimulation in an LVAD Patient with Severe Sleep Apnea

Introduction Central sleep apnea (CSA) occurs in approximately 35% of patients with heart failure, thought to be an acquired pattern of respiratory control instability related in part to elevated sympathetic nervous system activation. Studies show that CSA is an independent risk factor for morbidity and mortality in these patients. A newer approach to treatment involves implantation of a unilateral, transvenous phrenic nerve stimulator to restore a physiological breathing pattern during sleep. We present a case of a patient with heart failure and CSA who underwent placement of a phrenic nerve stimulator and subsequently a left ventricular assist device (LVAD). Case A 62 year-old male with NYHA III, ACC/AHA C heart failure (EF 15%), paroxysmal ventricular tachycardia with biventricular pacing and ICD placement who had polysomnography (PSG) that revealed severe CSA. He underwent placement of a transvenous phrenic nerve stimulation system. He subsequently reported improved symptoms, with less daytime sleeping and increased duration of daily exercise. His apnea hypopnea index decreased from 46.3 events/hour at baseline to 6.9 events/hour 18 months post-therapy, and his central apnea index decreased from 42.6 events/hour to 0.2 events/hour. Two years after device implant he underwent placement of an LVAD in the setting of worsening heart failure symptoms and refractory ventricular arrhythmias. Prior to surgery his device was placed in monitor mode. After successful LVAD implantation, despite normalization of cardiac output, he reported return of excessive daytime fatigue; PSG confirmed severe CSA. With device adjustment, the biventricular pacing leads, phrenic nerve stimulator system, and LVAD were able to run concurrently without artifact or interference. Subsequent PSG confirmed successful treatment of CSA along with improvement in symptoms. Discussion CSA is common in patients with heart failure, thought to be related to elevated sympathetic nervous system activation and hemodynamic perturbations. Medical treatment of heart failure has shown limited success in improving CSA, and small studies have shown that optimization of hemodynamics and end-organ function with LVAD implantation does not reverse CSA. We report the first case of a patient with successful implantation of both a transvenous phrenic nerve stimulator and an LVAD. Despite normalization of cardiac output after LVAD implantation, severe CSA persisted, consistent with prior case reports. Conclusion Phrenic nerve stimulation is an option for patients with heart failure and moderate to severe CSA, including LVAD patients.

Phrenic Nerve Stimulation and Automatic Positive Airway Pressure Therapy for Treating Central Sleep Apnea and Residual Obstructive Sleep Apnea: A Case Study

Introduction Central sleep apnea (CSA) is a neurological breathing disorder resulting from intermittent disruptions in the neural drive to breath. CSA and obstructive sleep apnea (OSA), caused by partial or complete blockage of the airway, frequently occur together. The remedē System (Respicardia, Minnetonka, MN) is an implantable device that delivers phrenic nerve stimulation therapy (PNS) to treat moderate to severe CSA. A remedē System pivotal trial patient presented following failure with mask-based therapies with baseline (BL) Apnea Hypopnea Index (AHI) 98.1 events/hour; Central Apnea Index (CAI)=60.8/Obstructive Apnea Index (OAI)=13.4/Mixed Apnea Index (MAI)=5.4/Hypopnea Index (HI)=18.4). The patient has a complex cardiovascular history including heart failure and classic sleep apnea symptoms. Hypothesis The combination of PNS and APAP for patients with CSA and residual OSA is feasible. Methods Patient was implanted with the PNS device and titrated to maximum effectiveness. Follow-up polysomnograms (PSG) were completed every 6 months. Results At the 6 month PSG, the patient transitioned from CSA into an OSA/OSA hypopnea pattern; Central Sleep Apnea Index (CAI)=1.4/Obstructive Apnea Index (OAI)=28.3/Mixed Apnea Index (MAI)=0.1/ Hypopnea Index (HI)=44.1 with Obstructive Hypopnea Index (OHI)=43.7 and this continued at the 12 month PSG. Mask-based therapy (APAP) was then added to supplement the PNS and the combination therapy was assessed during a routine PSG. Final APAP pressures of 6cmH2O-12cmH2O were well tolerated. The PSG demonstrated that with PNS off, APAP therapy treated the obstructive (apnea/hypopnea) events but did not treat the central events. PNS alone treated the CSA but did not resolve OSA (apnea/hypopnea) events. With both PNS and PAP therapy on, CSA and OSA were controlled and breathing was normalized (AHI 3.8). PSG testing at 18 months with PNS and APAP showed the AHI was reduced by 90% including a reduction in all AHI components; Central Apnea Index (CAI)=0.0/Obstructive Apnea Index (OAI)=3.9/Mixed Apnea Index (MAI)=0.0/Hypopnea Index (HI)=6.1). Epworth Sleepiness Scale improved (BL=14/6mo=4/9mo=5/12mo=6). PSG testing at 24 months with PNS on and APAP therapy off showed residual presence of hypopnic OSA and continued successful treatment of CSA; Central Apnea Index (CAI)=0.4/Obstructive Apnea Index (OAI)=0.8/Mixed Apnea Index (MAI)=0.0/Hypopnea Index (HI)=47.5 with Obstructive Hypopnea Index (OHI)=39.9). Patient remains treated with both PNS and APAP and sleeping well. Conclusion PNS effectively treated CSA. APAP therapy alone did not treat the CSA but did resolve obstructive apnea/hypopnea. Combination PNS and APAP safely and successfully treated both CSA and OSA.

Randomized Clinical Trial on the Effect of an Aerobic Exercise Program in Patients With Moderate-severe Sleep Apnea

Randomized Clinical Trial on the Effect of an Aerobic Exercise Program in Patients With Moderate-severe Sleep Apnea

Does Kidney Transplantation Affect Sleep and Fatigue in Patients With Kidney Disease?

Sleep disorders and fatigue are highly prevalent in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients but there is limited evidence on the effect of kidney transplant (KTx) on these. In a prospective cohort study of patients with advanced CKD (estimated glomerular filtration rate<30 mL/min/1.73 m2) or ESKD, polysomnography and patient-reported symptom assessments were conducted. Pre- and post-KTx changes in sleep apnea (SA) severity (measured by apnea hypopnea index [AHI]) were analyzed and compared with patients who did not receive KTx. Regression models were used to examine predictors of SA severity. Among 77 patients (mean age 51 y, BMI 29 kg/m2, 66% males, 23% ESKD), 61% had SA at baseline. Among 39 KTx recipients, 56% had SA, with 39% having moderate-severe SA after 10 ± 5.6 months post-KTx. There was no difference in AHI in either the KTx (median 6 versus 8; P = 0.37) or no-KTx (median 15 versus 16; P = 0.61) groups after an average of 19.9 ± 8.9 months. KTx led to significant clinically meaningful improvements in fatigue and health-related quality of life (adjusted effect size 0.3-0.6). In multivariable regression, baseline AHI was the only significant predictor of SA severity (adjusted β = 3.6/5 units, 95% confidence interval 2.1, 5.2) after adjusting for KTx status, age, sex, and body mass index. More than half of the KTx recipients had SA. There was no significant change in SA severity with KTx. Clinically meaningful moderate size improvements in patient-reported fatigue and health-related quality of life may be seen with KTx.

1072 OSA and IPF Exacerbations: A Deadly Duo

Obstructive sleep apnea (OSA) is common in Idiopathic Pulmonary Fibrosis (IPF) patients. IPF Patients with poorly controlled OSA appear to have worse in quality of life and possibly higher mortality than those with well controlled OSA. The role of OSA in IPF exacerbation is currently unknown. A 71 y/o man with PMH of IPF and OSA (on nocturnal BIPAP 16/4) presented to the ER with worse cough, dyspnea, and hypoxia. He was admitted to the ICU with a diagnosis of IPF exacerbation. He was restarted on his home BIPAP settings. His dyspnea improved, but did not quite return to baseline. An inpatient BIPAP titration study showed that the patient had significant obstructive hypopneas, as well as hypoxia and tachycardia, until his BIPAP was titrated up to 22/10 cm. At this pressure, his tachycardia, hypoxia, and hypopneas resolved. The patient’s BIPAP was adjusted to the new settings. Over the next few days, his dyspnea improved, and he was discharged. About six weeks after discharge, the patient returned to the sleep clinic for follow up. Review of his BIPAP machine data showed that he had developed new central apneas (27 per hour; none previously noted). The patient was diagnosed with severe treatment-emergent central sleep apnea. BIPAP settings were reduced to 13/7. Non-adherence to nocturnal BIPAP may be a risk factor for hospital admission in patients with OSA and IPF. Patients experiencing an acute exacerbation of IPF may temporarily require higher BIPAP settings. However, continued use of higher pressures after resolution of the exacerbation may lead to emergence of central sleep apnea. o Bosi M et al. “OSA and Prolonged Oxygen Desaturation During Sleep are Strong Predictors of Poor Outcome in IPF.” Lung (2017) 195:643–651. o Mermigkis C et al. “Obstructive sleep apnea should be treated in patients with idiopathic pulmonary fibrosis.” Sleep Breath (2015) 19:385–391. o Kim JS et al. “Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA).” Ann Am Thorac Soc Vol 14, No 12, pp 1786–1795, Dec 2017.

Abstract P274: Association Between Atrial Fibrillation and Central Sleep Apnea in Older Japanese-American Men

Introduction: Several studies have indicated that central sleep apnea (CSA) is associated with atrial fibrillation (AF) in older populations. However, there are few studies of this association in older Asian populations. Hypothesis: The hypothesis being tested is that there is an association between AF and CSA in older Japanese-American men. Methods: The Kuakini Honolulu-Asia Aging Study is a longitudinal cohort study of Japanese-American men living in Hawaii. We did a cross- sectional analysis using data from the 1999- 2000 7th exam cycle. Participants were 718 Japanese-American men between 79 and 97 years old, who had overnight polysomnography (PSG) conducted in their homes using criteria established by the large multicenter Sleep Heart Health Study. Obstructive Apnea-Hypopnea Index (OAHI) was the measure of the number of obstructive apneas and hypopneas with &gt;4% oxygen desaturation. Additionally, the Central Apnea Index (CAI) was the measure of the number of central apneas. Obstructive sleep apnea (OSA) was categorized as none (OAHI &lt;5), mild (OAHI 5-14), moderate (OAHI 15-29) and severe (OAHI 30 or more). CSA was defined by CAI of 5 or more. Cheyne-Stokes Breathing (CSB) was defined as a minimum consecutive 10-minute period of a crescendo-decrescendo respiratory pattern associated with CSA. A board-certified physician confirmed AF by single lead electrocardiography of PSG. Results: The mean age of participants was 83.2±0.2 years. The prevalence of AF was 5.5% (39 of 709). The prevalence proportions of severe OSA, CSA, and CSB were 20.5% (145 of 709), 6.3% (43 of 681) and 3.2%, (22 of 681) respectively. In multivariable-adjusted logistic regression models, CSA and CSB were significantly associated with AF prevalence [Odds Ratio (OR) 4.78; 95% Confidential interval (CI), 1.91-11.95] and [OR 5.48; 95% CI, 1.70-17.66], respectively. In contrast, OSA was not significantly associated with AF prevalence (severe OSA [OR 1.17; 95% CI, 0.44-3.11], moderate OSA [OR 0.72; 95% CI, 0.26-2.05], mild OSA [OR 0.97; 95% CI, 0.39-2.44]). Conclusion: There is an association of AF prevalence with CSA and CSB in older Japanese-American Men. In older Japanese men, screening for CSA and CSB might be important to prevent AF.

Phrenic nerve stimulation to treat patients with central sleep apnoea and heart failure.

AimsThe presence of central sleep apnoea (CSA) is associated with poor prognosis in patients with heart failure (HF). The aim of this analysis was to evaluate if using phrenic nerve stimulation to treat CSA in patients with CSA and HF was associated with changes in HF‐specific metrics.Methods and resultsAll patients randomized in the remedē System Pivotal Trial and identified at baseline with HF were included (n = 96). Effectiveness data from treatment and former control groups were pooled based on months since therapy activation. Changes from baseline to 6 and 12 months in sleep metrics, Epworth Sleepiness Scale, patient global assessment health‐related quality of life, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and echocardiographic parameters are reported. HF hospitalization, cardiovascular death, and the composite of HF hospitalization or cardiovascular death within 6 months are reported by the original randomized group assignment for safety assessment. Sleep metrics and quality of life improved from baseline to 6 and 12 months. At 12 months, MLHFQ scores changed by –6.8 ± 20.0 (P = 0.005). The 6‐month rate of HF hospitalization was 4.7% in treatment patients (standard error = 3.3) and 17.0% in control patients (standard error = 5.5) (P = 0.065). Reported adverse events were as expected for a transvenous implantable system.ConclusionsPhrenic nerve stimulation reduces CSA severity in patients with HF. In parallel, this CSA treatment was associated with benefits on HF quality of life.

Case Report of Pediatric Channelopathies With UNC80 and KCNJ11 Mutations Having Abnormal Respiratory Control Treated With Positive Airway Pressure Therapy

There have been no published reports of central respiratory control abnormalities in pediatric patients with UNC80 or KCNJ11 mutations which cause neurologic channelopathies. We describe an 8-year-old male with a pathogenic UNC80 mutation, intellectual disability, hypotonia and epilepsy with severe central sleep apnea (213.5 events/h) on polysomnography (PSG). We also describe a 20-month-old female with a KCNJ11 mutation, neonatal diabetes and developmental delay who had severe central sleep apnea (131.1 events/h). Both patients had irregular respiratory patterns during sleep and wakefulness and were placed on empiric bilevel positive airway pressure therapy, which was well tolerated with resolution of abnormal respiratory control and hypercapnia. Patients with UNC80 and KCNJ11 gene mutations may have abnormal respiratory rhythm during sleep and wakefulness, mirroring animal models. We recommend routine PSG tests and further investigation into the respiratory control of patients with pediatric channelopathies involved in chemoreceptor function or central integration of respiratory control.