Treatment of sleep apnoea early after myocardial infarction with adaptive servo-ventilation - a proof-of-concept randomised controlled trial.

INTRODUCTION: Sleep-disordered breathing has been associated with less myocardial salvage and smaller infarct size reduction after acute myocardial infarction (AMI). The Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation (TEAM-ASV I) trial investigated the effects of adding adaptive servo-ventilation (ASV) for sleep-disordered breathing (SDB) to standard therapy on myocardial salvage index (MSI) and change in infarct size within 12 weeks after AMI. METHODS: In this multicentre, randomised, open-label trial, patients with AMI and successful percutaneous coronary intervention within 24 h after symptom onset plus SDB (apnoea-hypopnoea index ≥15/h) were randomised to standard medical therapy alone (control) or plus ASV (starting 3.6±1.4 days post-AMI). The primary outcome was MSI at 12 weeks post-AMI. Cardiac magnetic resonance (CMR) imaging was performed at ≤5 days and 12 weeks after AMI. RESULTS: Seventy-six individuals were enrolled from February 2014 to August 2020; 39 had complete CMR data for analysis of the primary endpoint. MSI was significantly higher in the ASV versus control group (difference 14.6% of left ventricular mass [LVM]; 95% confidence interval 0.14-29.1; p=0.048). At 12 weeks, absolute [interquartile range] (6.6 [4.8-8.5] versus 2.8 [0.9-4.8] %LVM; p=0.003) and relative (44 [30-57] versus 21 [6-35] % of baseline; p=0.013) reductions in infarct size were greater in the ASV versus control group. No serious treatment-related adverse events occurred. CONCLUSIONS: Early treatment of SDB with ASV improved the MSI and decreased the infarct size at 12 weeks after AMI. Larger randomised trials are required to confirm these findings.

Inflammation and Fibrosis in Sleep-Disordered Breathing after Acute Myocardial Infarction.

BACKGROUND: After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB. METHODS AND RESULTS: This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h-1). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP (p = 0.028). Similarly, only SDB was independently associated with PIIINP (p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP (p = 0.012) and PIIINP (p = 0.006) levels. CONCLUSIONS: The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

Measurement of peripheral arterial tone to detect sleep-disordered breathing in patients with heart failure.

PURPOSE: Sleep-disordered breathing is highly prevalent in patients with heart failure and is related to increased mortality and morbidity. The gold standard for sleep diagnostic is polysomnography in a sleep laboratory. Measurement of peripheral arterial tone with a wrist-worn diagnostic device is a promising method to detect sleep-disordered breathing without major technical effort. METHODS: We prospectively enrolled patients with heart failure with reduced ejection fraction for measurement of the peripheral arterial tone and polysomnography simultaneously during one night in the sleep laboratory. Raw data of polysomnography was analyzed blindly by sleep core lab personnel and compared with automatic algorithm-based sleep results of measurement of the peripheral arterial tone. RESULTS: A total of 25 patients provided comparable sleep results. All patients had sleep-disordered breathing and were identified by measurement of the peripheral arterial tone. The comparison of apnea-hypopnea index between peripheral arterial tone 38.8 ± 17.4/h and polysomnography 44.5 ± 17.9/h revealed a bias of - 5.7 ± 9.8/h with limits of agreement of ± 19.2/h in Bland-Altman analysis but showed high and significant Pearson correlation (r = 0.848, p < 0.001). CONCLUSION: The findings suggest that measurement of the peripheral arterial tone may be useful to identify sleep-disordered breathing in patients with heart failure with reduced ejection fraction.

Early identification of heart failure deterioration through respiratory monitoring with adaptive servo-ventilation.

Cardiac decompensation is associated with worse prognosis in patients with heart failure. Reliable methods to predict cardiac decompensation events are not yet available. Sleep-disordered breathing (SDB) is a frequent comorbidity in heart failure, and it has been shown to correlate with heart failure severity. This prospective observational trial investigated SDB characteristics in patients with heart failure with the aim to identify patterns that may predict early cardiac decompensation. Patients with heart failure with diagnosed SDB and hospitalised for cardiac decompensation were prospectively enrolled and treated with adaptive servo-ventilation (ASV). SDB characteristics, daily body weight and clinical cardiac decompensation events were collected over a 1-year follow-up. Clinical events were categorised by an independent clinical event committee. A total of 43 patients were enrolled (81% male, mean [SD] age 71 [11] years, body mass index 30 kg/m2 , 95% New York Heart Association function class III or IV, mean [SD] left ventricular ejection fraction 37% [11%], median apnea-hypopnoea index [AHI] of 37 events/h). A total of 48 cardiac decompensation events were recorded during the 1-year study period. Respiratory rate was found to be significantly lower in patients with cardiac decompensation. The AHI and applied inspiratory pressure ASV-device support were significantly increased 10 days before a clinical cardiac decompensation event. Device usage was also found to be significantly decreased 2 nights before cardiac decompensation. Device-derived respiratory data in ASV therapy devices for SDB may therefore serve as a monitoring tool to predict early clinical cardiac decompensation events. Prediction and avoidance of cardiac decompensation, in turn, may attenuate serious health consequences in patients with heart failure.

Prevalence and predictors of sleep-disordered breathing in chronic heart failure: the SchlaHF-XT registry.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing prevalence. Sleep-disordered breathing (SDB) is an important co-morbidity in HFpEF. The SchlaHF-XT registry evaluated the sex-specific prevalence and predictors of SDB, including obstructive (OSA) and central sleep apnoea, in patients with HFpEF compared with heart failure with mildly reduced (HFmrEF) or reduced (HFrEF) ejection fraction. METHODS AND RESULTS: Consecutive adults with chronic heart failure treated according to current guidelines were enrolled. The presence of moderate-to-severe SDB (apnoea-hypopnoea index ≥15/h) was determined using Type 3 polygraphic devices. Of 3289 patients included, 2032 had HFpEF, 559 had HFmrEF, and 698 had HFrEF, of whom 34, 21, 23, and 42%, respectively, were female. Prevalence of SDB in HFpEF was high, but significantly lower than in HFmrEF or HFrEF (36% vs. 41 and 48%, respectively). Rates of SDB in males and females were 41 and 28% in HFpEF, 44 and 30% in HFmrEF, and 50 and 40% in HFrEF. The proportion of males and females with SDB who had OSA was significantly greater in those with HFpEF vs. HFrEF. Male sex, older age, higher body mass index, and New York Heart Association functional Class III/IV were significant predictors of moderate-to-severe SDB in HFpEF patients. CONCLUSIONS: Prevalence of SDB in HFpEF was high, but lower than in patients with HFmrEF or HFrEF. Moderate-to-severe SDB occurred more frequently in males than in females across the whole spectrum of heart failure. In both sexes, the proportion of OSA in SDB patients with HFpEF was higher than in those with HFrEF.

Occurrence of Coronary Collaterals in Acute Myocardial Infarction and Sleep Apnea.

Background In patients with acute myocardial infarction (MI), cardioprotective effects of obstructive sleep apnea are postulated on account of hypoxemic preconditioning. The aim of this single-center substudy was to investigate a potential association between obstructive sleep apnea and the presence of coronary collaterals in patients with first-time acute MI who have been enrolled in an ongoing, multicenter clinical trial. Methods and Results In TEAM-ASV I (Treatment of Sleep Apnea Early After Myocardial Infarction With Adaptive Servo-Ventilation Trial; NCT02093377) patients with first acute MI who received a coronary angiogram within 24 hours after onset of symptoms underwent polygraphy within the first 3 days. Coronary collaterals were classified visually by assigning a Cohen-Rentrop Score (CRS) ranging between 0 (no collaterals) and 3. Of 94 analyzed patients, 14% had significant coronary collaterals with a CRS ≥2. Apnea-Hypopnea Index (AHI) score was significantly higher in patients with CRS ≥2 compared with those with CRS <2 (31/hour [11-54] versus 13/hour [4-27]; P=0.032). A multivariable regression model revealed a significant association between obstructive AHI and CRS ≥2 that was independent of age, sex, body mass index, and culprit lesion left anterior descending artery (odds ratio [OR], 1.06; 95% CI, 1.01-1.12; P=0.023), but no significant association between coronary collaterals and central AHI (OR, 1.02; 95% CI, 0.97-1.08; P=0.443). Conclusions Patients with first-time acute MI had more extensive coronary collateralization with an increased AHI or rather an increased obstructive AHI. This finding supports the hypothesis that obstructive sleep apnea exerts potential cardioprotective effects, in addition to its known deleterious effects, in patients with acute MI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02093377.

Prevalence of Sleep Disordered Breathing in Patients with Primary Mitral Regurgitation Undergoing Mitral Valve Surgery.

BACKGROUND: Sleep disordered breathing (SDB) is a frequent comorbidity in cardiac disease patients. Nevertheless, the prevalence and relationship between SDB and severe primary mitral regurgitation (PMR) has not been well investigated to date. METHODS: A cohort of 121 patients with significant PMR undergoing mitral valve surgery were prospectively enrolled and received a cardiorespiratory single night polygraphy screening using ApneaLink before surgery. Eighty-two of them underwent a follow-up examination including a follow-up single-night sleep study 3 months after surgery. RESULTS: The mean age of patients was 65.3 ± 12.0 years. Sixty patients (49.6%) were female. The mean EuroSCORE II was 2.5 ± 2.4%. Initially, 91 (75.2%) patients presented with SDB, among whom 50.4% (46 patients, 38.0% of total cohort) were classified as moderate to severe. These patients tended to require significantly longer postoperative intensive care and mechanical ventilation. Among the 82 patients who completed follow-up exams, mitral valve surgery led to a significant reduction in relevant SDB (20.7%). The apnea-hypopnea index (from 11/h [4;18] to 4/h [3;14] (p = 0.04)), the oxygenation-desaturation index (from 8/h [3;18] to 5/h [3;12] (p = 0.008)) as well as the saturation time below 90% (from 32 min [13;86] to 18 min [5;36] (p = 0.005)), were all shown to be improved significantly. CONCLUSION: The prevalence of SDB is very high in patients with severe primary mitral regurgitation and may contribute to postoperative complications and prolonged intensive care. A significantly reduced but still high prevalence of SDB was observed 3 months after mitral valve surgery, highlighting the bidirectional relationship between SDB and heart failure.

Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes.

BACKGROUND: The remede System Pivotal Trial was a prospective, multi-center, randomized trial demonstrating transvenous phrenic nerve stimulation (TPNS) therapy is safe and effectively treats central sleep apnea (CSA) and improves sleep architecture and daytime sleepiness. Subsequently, the remede System was approved by FDA in 2017. As a condition of approval, the Post Approval Study (PAS) collected clinical evidence regarding long-term safety and effectiveness in adults with moderate to severe CSA through five years post implant. METHODS: Patients remaining in the Pivotal Trial at the time of FDA approval were invited to enroll in the PAS and consented to undergo sleep studies (scored by a central laboratory), complete the Epworth Sleepiness Scale (ESS) questionnaire to assess daytime sleepiness, and safety assessment. All subjects (treatment and former control group) receiving active therapy were pooled; data from both trials were combined for analysis. RESULTS: Fifty-three of the original 151 Pivotal Trial patients consented to participate in the PAS and 52 completed the 5-year visit. Following TPNS therapy, the apnea-hypopnea index (AHI), central-apnea index (CAI), arousal index, oxygen desaturation index, and sleep architecture showed sustained improvements. Comparing 5 years to baseline, AHI and CAI decreased significantly (AHI baseline median 46 events/hour vs 17 at 5 years; CAI baseline median 23 events/hour vs 1 at 5 years), though residual hypopneas were present. In parallel, the arousal index, oxygen desaturation index and sleep architecture improved. The ESS improved by a statistically significant median reduction of 3 points at 5 years. Serious adverse events related to implant procedure, device or delivered therapy were reported by 14% of patients which include 16 (9%) patients who underwent a pulse generator reposition or lead revision (primarily in the first year). None of the events caused long-term harm. No unanticipated adverse device effects or related deaths occurred through 5 years. CONCLUSION: Long-term TPNS safely improves CSA, sleep architecture and daytime sleepiness through 5 years post implant. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01816776.

Sleep - the yet underappreciated player in cardiovascular diseases: A clinical review from the German Cardiac Society Working Group on Sleep Disordered Breathing.

Patients with a wide variety of cardiovascular diseases, including arterial and pulmonary hypertension, arrhythmia, coronary artery disease and heart failure, are more likely to report impaired sleep with reduced sleep duration and quality, and also, sometimes, sleep interruptions because of paroxysmal nocturnal dyspnoea or arrhythmias. Overall, objective short sleep and bad sleep quality (non-restorative sleep) and subjective long sleep duration are clearly associated with major cardiovascular diseases and fatal cardiovascular outcomes. Sleep apnoea, either obstructive or central in origin, represents the most prevalent, but only one, of many sleep-related disorders in cardiovascular patients. However, observations suggest a bidirectional relationship between sleep and cardiovascular diseases that may go beyond what can be explained based on concomitant sleep-related disorders as confounding factors. This makes sleep itself a modifiable treatment target. Therefore, this article reviews the available literature on the association of sleep with cardiovascular diseases, and discusses potential pathophysiological mechanisms. In addition, important limitations of the current assessment, quantification and interpretation of sleep in patients with cardiovascular disease, along with a discussion of suitable study designs to address future research questions and clinical implications are highlighted. There are only a few randomised controlled interventional outcome trials in this field, and some of the largest studies have failed to demonstrate improved survival with treatment (with worse outcomes in some cases). In contrast, some recent pilot studies have shown a benefit of treatment in selected patients with underlying cardiovascular diseases.

Automatic positive airway pressure for obstructive sleep apnea in heart failure with reduced ejection fraction.

BACKGROUND: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in heart failure patients with reduced left ventricular ejection fraction (HFrEF), and is associated with worsening cardiac function and increased mortality. OBJECTIVES: The automatic positive airway pressure (APAP) trial tested the impact of APAP treatment on changes for the pre-specified endpoints: changes in peak oxygen uptake (peak VO2), percent-predicted peak VO2 and oxygen uptake at anaerobic threshold (VO2-AT). METHODS: This randomized, controlled pilot study included patients with chronic, stable HFrEF who had moderate-to-severe OSA. Patients were randomized 1:1 to either APAP (AutoSet™, ResMed) or nasal strips (control) for 6 months. RESULTS: 76 patients have been randomized and 58 had complete data for final analysis. There was a statistically significant change in the APAP intervention arm for the primary endpoint percent-predicted peak VO2 in comparison to control (67 ± 17 to 73 ± 19%; p = 0.01). Additional primary endpoints peak VO2 and VO2-AT showed a trend in increase in the APAP group. Moreover, there were significant improvements within the APAP group for hypoxemia, left ventricular function and quality of life from baseline to 6 months, but not within the control group (p = 0.001 and p = 0.037, respectively). CONCLUSION: APAP intervention was shown to significantly improve outcome compared to control group, represented in percent-predicted peak VO2, an established surrogate marker for cardiovascular prognosis in HFrEF. APAP has additional beneficial effects on hypoxemia, cardiac function and quality of life.

Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea.

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remede System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden. Graphical Abstract.

Adaptive servo-ventilation therapy does not favourably alter sympatho-vagal balance in sleeping patients with systolic heart failure and central apnoeas: Preliminary data.

BACKGROUND: In contrast to continuous positive airway pressure (CPAP), the use of adaptive servo-ventilation (ASV) for treatment of central sleep apnoea (CSA) was associated with increased mortality in patients with chronic systolic heart failure (CHF). In order to characterize the interplay between sleep-disordered breathing, CHF and sympathovagal balance (SVB) this study investigated the effect of nocturnal CPAP and ASV on SVB in CSA patients with or without CHF. METHODS: Thirty-seven patients with ongoing positive airway pressure therapy (CPAP or ASV) for CSA (17 patients with systolic CHF - left ventricular ejection fraction <50% - and 20 patients with CSA but no CHF) underwent evaluation of SVB (spectral analysis of heart rate -HRV- and diastolic blood pressure variability) during full nocturnal polysomnography. The night was randomly split into equal parts including no treatment (NT), automatic CPAP and ASV. Data analysis was restricted to stable N2 sleep. RESULTS: In patients with CSA and systolic CHF, neither automatic CPAP nor ASV showed favourable effects on parameters reflecting SVB during N2 sleep (all p > 0.05). In contrast, in subjects with CSA without CHF automatic CPAP, but not ASV, favourably altered SVB by decreasing the low frequency and increasing the high frequency component of HRV (both p = 0.03). CONCLUSIONS: Effects of various modes of positive airway pressure therapy of CSA on SVB during sleep depend on the mode of pressure support and underlying cardiac function. Automatic CPAP but not ASV favourably influences SVB in subjects without CHF, whereas both interventions leave SVB unchanged in patients with CHF.

Rationale and design of the randomised Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation trial (TEAM-ASV I).

AIMS: In acute myocardial infarction (AMI), impaired myocardial salvage and large infarct size result in residual heart failure, which is one of the most important predictors of morbidity and mortality after AMI. Sleep-disordered breathing (SDB) is associated with reduced myocardial salvage index (MSI) within the first 3 months after AMI. Adaptive servo-ventilation (ASV) can effectively treat both types of SDB (central and obstructive sleep apnoea). The Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation trial (TEAM-ASV I) will investigate the effects of ASV therapy, added to percutaneous coronary intervention (PCI) and optimal medical management of AMI, on myocardial salvage after AMI. METHODS/DESIGN: TEAM ASV-I is a multicentre, randomised, parallel-group, open-label trial with blinded assessment of PCI outcomes. Patients with first AMI and successful PCI within 24 h after symptom onset and SDB (apnoea-hypopnoea index ≥ 15/h) will be randomised (1:1 ratio) to PCI and optimal medical therapy alone (control) or plus ASV (with stratification of randomisation by infarct location; left anterior descending (LAD) or no LAD lesion). The primary outcome is the MSI, assessed by cardiac magnetic resonance imaging. Key secondary outcomes are change of infarct size, left ventricular ejection fraction and B-type natriuretic peptide levels and disease-specific symptom burden at 12 weeks. CONCLUSION: TEAM ASV-I will help to determine whether treatment of SDB with ASV in the acute phase after myocardial infarction contributes to more myocardial salvage and healing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02093377. Registered on March 21, 2014.

Sleep duration and architecture during ASV for central sleep apnoea in systolic heart failure.

BACKGROUND: Adaptive servoventilation (ASV) effectively treats nocturnal respiratory events in patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA), but increased mortality has been reported. This study investigated changes in sleep architecture during ASV treatment in HFrEF patients. METHODS: A retrospective analysis of polysomnographic datasets for 30 ASV-treated patients with stable HFrEF and moderate-to-severe CSA was performed, including blinded analyses of total sleep time (TST), and percentage of REM and non-REM sleep (stages N1-N3). RESULTS: Follow-up was 109 ±â€¯32 days; mean device usage was 6.0 ±â€¯1.1 h/day. During ASV there was reduction of N1 (34 ±â€¯20%/TST to 13 ±â€¯5%/TST, p < 0.001) and N3 sleep (4 ±â€¯6%/TST to 1 ±â€¯4%/TST, p = 0.020), and increase of N2 (44 ±â€¯14%/TST to 62 ±â€¯7%/TST, p < 0.001) and REM-sleep (18 ±â€¯8%/TST to 24 ±â€¯6%/TST, p = 0.002). CONCLUSIONS: Disturbances of sympatho-vagal balance during ASV might help explain increased mortality during ASV. Since sympathetic tone is highest in REM-sleep and vagal predominance occurs during N3 sleep, these findings generate new hypotheses for the increased mortality seen in SERVE-HF.

APAP therapy does not improve impaired sleep quality and sympatho-vagal balance: a randomized trial in patients with obstructive sleep apnea and systolic heart failure.

PURPOSE: In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown. METHODS: In this randomized controlled trial (6 months of APAP vs. nasal strips as control), sleep quality and SVB in patients with HFrEF and OSA were monitored. The distinction was made between different breathing conditions (5-min segments of OSA or normal breathing [NB] during stable N2 sleep) at baseline (T0), APAP initiation (T1), and 6 months of successful APAP treatment (T2). RESULTS: Of 75 patients enrolled, 61 were men with average age of 65 ± 12 years and LVEF of 31 ± 9%; 37 patients were randomized into the APAP and 38 into the control (nasal strips only) group. At T0, OSA was associated with a 17% increase in the low-frequency/high-frequency component ratio of heart rate variability (LF/HF) versus baseline, suggesting an increase in sympathetic drive (SVB) with OSA compared with normal breathing. Respiratory indices and oxygen saturation all significantly improved at both T1 and T2, but at 6 months, APAP had no clinically relevant effect on objective sleep quality versus control. In fact, in patients with HFrEF (n = 23 with data suitable for HRV analysis), there was even a trend (p = 0.097) towards an additional 17% increase in LF/HF at T2 in the therapy group, suggesting (undesired) increased SVB in the APAP group. CONCLUSION: Treatment of OSA in patients with systolic HF improves respiratory indices but does not have a favorable effect on sleep quality. While OSA per se was associated with an increase in sympathetic drive, APAP treatment was not associated with a reduction in sympathetic drive. After 6 months of treatment, there was even a trend towards additional increases in sympathetic drive in the APAP group.

Long-term efficacy and safety of phrenic nerve stimulation for the treatment of central sleep apnea.

STUDY OBJECTIVE: To evaluate long-term efficacy and safety of phrenic nerve stimulation (PNS) in patients with moderate-to-severe central sleep apnea (CSA) through 3 years of therapy. METHODS: Patients in the remede System Pivotal Trial were observed every 3 months after implant until US Food and Drug Administration approval. At the time of approval and study closure, all patients completed 24 months of follow-up; 33 patients had not reached the 36-month visit. Sleep metrics (polysomnography) and echocardiographic parameters are reported at baseline, 12, 18, and 24 months, in addition to available 36-month sleep results from polygraphy. Safety was assessed through 36 months; however, analysis focused through 24 months and available 36-month results are provided. RESULTS: Patients were assessed at 24 (n = 109) and 36 (n = 60) months. Baseline characteristics included mean age 64 years, 91% male, and mean apnea-hypopnea index 47 events per hour. Sleep metrics (apnea-hypopnea index (AHI), central apnea index, arousal index, oxygen desaturation index, rapid eye movement sleep) remained improved through 24 and 36 months with continuous use of PNS therapy. At least 60% of patients in the treatment group achieved at least 50% reduction in AHI through 24 months. Serious adverse events (SAEs) related to the remede System implant procedure, device, or therapy through 24 months were reported by 10% of patients, no unanticipated adverse device effects or deaths, and all events resolved. No additional related SAEs were reported between 24 and 36 months. CONCLUSION: These data suggest beneficial effects of long-term PNS in patients with CSA appear to sustain through 36 months with no new safety concerns. TRIAL REGISTRATION: NCT01816776.

Auto positive airway pressure therapy reduces pulmonary pressures in adults admitted for acute heart failure with pulmonary hypertension and obstructive sleep apnea. The ASAP-HF Pilot Trial.

OBJECTIVES: Pulmonary hypertension (PH) is extremely common in acute decompensated heart failure (ADHF) patients and predicts increased mortality. Obstructive sleep apnea (OSA), highly prevalent in congestive heart failure patients, may contribute to further elevated pulmonary pressures. This study evaluates the impact of positive airway pressure (PAP) therapy on PH in patients admitted for ADHF with OSA. METHODS: A two-center randomized control trial comparing standard of care (SOC) therapy for ADHF versus addition of PAP therapy in patients with concomitant OSA. RESULTS: Twenty-one consecutive patients were enrolled with 1:1 randomization to SOC versus SOC plus 48-hour PAP therapy protocol. In the intervention arm, the mean pulmonary artery systolic pressure (PASP) difference before therapy and after 48 hours of PAP therapy was -15.8 ± 3.2 (58.6 ± 2.5 mm Hg to 42.8 ± 2.7) versus the SOC arm where the mean PASP difference was -5.2 ± 2.6 (62.7 ± 3.3 mm Hg reduced to 57.5 ± 3.9) (p = 0.025). In addition, ejection fraction in the intervention arm improved (3.4 ± 1.5% versus -0.5 ± 0.5 %) (p = 0.01). Significant improvement was also noted in tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic area in the intervention arm but not in NT-pro-BNP or 6-minute walk distance. CONCLUSIONS: In patients with ADHF and OSA, addition of 48 hours of PAP therapy to SOC treatment significantly reduced PH. In addition, PAP therapy was able to improve right and left ventricular function. ClinicalTrials.gov identifier: NCT02963597.