Nocturnal Oxygen Therapy for Central Sleep Apnea in Patients with Heart Failure: A Multi-site, Double-blind, Sham-controlled Randomized Clinical Trial (LOFT-HF).

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF, but has not been rigorously studied. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.

Determinants of transvenous phrenic nerve stimulation-induced improvements in left ventricular function in central sleep apnea and heart failure.

Study Objectives: Central sleep apnea (CSA) is common in heart failure (HF) patients, but its treatment's impact on cardiac function is unclear. Transvenous phrenic nerve stimulation (TPNS) is an emerging CSA therapy that may improve long-term left ventricular systolic function (LVEF) in HF. Given that the cardiovascular risk of sleep apnea appears contingent on respiratory event-related heart rate surges ("high ∆HR"), we hypothesized that TPNS treatment may preferentially improve LVEF in CSA patients with high ∆HR.

Central sleep apnea and cardiovascular disease state-of-the-art.

Central sleep apnea, a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke, and use of certain cardiac-related medications. Polysomnographic findings of central sleep apnea with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, central sleep apnea is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose-dependent relationship between nocturnal desaturation and mortality.

Treatment of OSA and its Impact on Cardiovascular Disease, Part 2: JACC State-of-the-Art Review.

Many studies have shown an association of obstructive sleep apnea (OSA) with incident cardiovascular diseases, particularly when comorbid with insomnia, excessive sleepiness, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease. Randomized controlled trials (RCTs) have demonstrated that treatment of OSA with positive airway pressure devices (CPAP) improves systemic hypertension, particularly in those with resistant hypertension who are adherent to CPAP. However, large RCTs have not shown long-term benefits of CPAP on hard cardiovascular outcomes, but post hoc analyses of these RCTs have demonstrated improved hard outcomes in those who use CPAP adequately.

Interactions of Obstructive Sleep Apnea With the Pathophysiology of Cardiovascular Disease, Part 1: JACC State-of-the-Art Review.

The American Heart Association considers sleep health an essential component of cardiovascular health, and sleep is generally a time of cardiovascular quiescence, such that any deviation from normal sleep may be associated with adverse cardiovascular consequences. Many studies have shown that both impaired quantity and quality of sleep, particularly with obstructive sleep apnea (OSA) and comorbid sleep disorders, are associated with incident cardiometabolic consequences. OSA is associated with repetitive episodes of altered blood gases, arousals, large negative swings in intrathoracic pressures, and increased sympathetic activity.

Cardiovascular Risks in People With Narcolepsy: Expert Panel Consensus Recommendations.

Background: Observational and retrospective studies suggest that people with narcolepsy may have an increased prevalence of cardiovascular and cardiometabolic comorbidities and may be at greater risk for future cardiovascular events. An expert consensus panel was formed to establish agreement on the risk of hypertension and cardiovascular/cardiometabolic disease in people with narcolepsy and to develop strategies to mitigate these risks.

Methods And Results: Experts in sleep medicine and cardiology were selected to participate in the panel.

Medication-induced central sleep apnea: a unifying concept.

Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing.

Relevance of cortical arousals for risk stratification in sleep apnea: a 3 cohort analysis.

Study Objectives: There is uncertainty on best approaches for defining apnea-hypopnea events. To clarify the contributions of desaturation vs arousal to defining hypopneas, we examined the associations of events with desaturation (≥ 3%) but not arousal (apnea-hypopnea index [AHI]) vs events with arousals but no desaturation (AHI) with obstructive sleep apnea-related comorbidities and incident cardiovascular disease across multiple cohorts.

Methods: In the Sleep Heart Health Study (n = 5,473), the Multi-Ethnic Study of Atherosclerosis (n = 1,904), and the Osteoporotic Fractures in Men Study (n = 2,685), we examined the independent associations of AHI and AHI with hypertension, diabetes, and daytime sleepiness, and incident cardiovascular disease.

Autonomic and respiratory consequences of altered chemoreflex function: clinical and therapeutic implications in cardiovascular diseases.

The importance of chemoreflex function for cardiovascular health is increasingly recognized in clinical practice. The physiological function of the chemoreflex is to constantly adjust ventilation and circulatory control to match respiratory gases to metabolism. This is achieved in a highly integrated fashion with the baroreflex and the ergoreflex.

Distinguishing central from obstructive hypopneas on a clinical polysomnogram.

Unlabelled: Among sleep-related disordered breathing events, hypopneas are the most frequent. Like obstructive and central apneas, hypopneas may be obstructive or central (reduced drive) in origin. Nevertheless, unlike apneas, categorizing hypopneas as either "obstructive" or "central" is often difficult or ambiguous.

The Association between Low CO Production and Central Sleep Apnea in Men with Heart Failure.

Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) is prevalent in some patients with heart failure with reduced ejection fraction (HFrEF). Theoretical models of Hunter-Cheyne-Stokes breathing predict that a low metabolic rate (MR) predisposes one to CSA. In this study, we examined the role of MR in the pathogenesis of CSA.

Chronic Opioid Use and Sleep Disorders.

Opioid medications are considered a significant component in the multidisciplinary management of chronic pain. In the past two decades, the use of opioid medications has dramatically risen in part because of an increased awareness by health care providers to treat chronic pain more effectively. In addition, patients are encouraged to seek treatment.

Chemoreflex and Baroreflex Sensitivity Hold a Strong Prognostic Value in Chronic Heart Failure.

Background: Novel treatments targeting in baroreflex sensitivity (BRS) and chemoreflex sensitivity (CRS) heart failure (HF) are grounded on small prognostic studies, partly performed in the pre-beta-blockade era.

Objectives: This study assesses the clinical/prognostic significance of BRS and CRS in a large cohort of patients with chronic HF on modern treatments.

Methods: Outpatients with chronic HF with either reduced (≤40%) or mildly reduced left ventricular ejection fraction (LVEF) (41% to 49%) underwent BRS (SD method) and CRS to hypoxia and hypercapnia (rebreathing technique) assessment and were followed up for a composite endpoint of cardiac death, implantable cardioverter-defibrillator shock, or HF hospitalization.

Sleep and breathing disorders in heart failure.

Sleep disorders are prevalent in heart failure and include insomnia, poor sleep architecture, periodic limb movements and periodic breathing, and encompass both obstructive (OSA) and central sleep apnea (CSA). Polysomnographic studies show excess light sleep and poor sleep efficiency particularly in those with heart failure. Multiple studies of consecutive patients with heart failure show that about 50% of patients suffer from either OSA or CSA.

Obstructive Sleep Apnea in Heart Failure: Current Knowledge and Future Directions.

Obstructive sleep apnea (OSA) is highly prevalent among patients with asymptomatic left ventricular systolic and diastolic dysfunction and congestive heart failure, and if untreated may contribute to the clinical progression of heart failure (HF). Given the health and economic burden of HF, identifying potential modifiable risk factors such as OSA and whether appropriate treatment improves outcomes is of critical importance. Identifying the subgroups of patients with OSA and HF who would benefit most from OSA treatment is another important point.

Central sleep apnea: pathophysiologic classification.

Central sleep apnea is not a single disorder; it can present as an isolated disorder or as a part of other clinical syndromes. In some conditions, such as heart failure, central apneic events are due to transient inhibition of ventilatory motor output during sleep, owing to the overlapping influences of sleep and hypocapnia. Specifically, the sleep state is associated with removal of wakefulness drive to breathe; thus, rendering ventilatory motor output dependent on the metabolic ventilatory control system, principally PaCO2.

Obstructive sleep apnea and stroke: The mechanisms, the randomized trials, and the road ahead.

When considered separately from cardiovascular disease, stroke is the third leading cause of death in the U.S. and is the leading cause of long-term disability in adults.

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome.

Study Objectives: Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.

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

Background: The remedē 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 remedē 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.

In patients with heart failure, enhanced ventilatory response to exercise is associated with severe obstructive sleep apnea.

Study Objectives: Patients with congestive heart failure (CHF) frequently exhibit an elevated ratio of minute ventilation over CO output (VE/VCO slope) while undergoing exercise tests. One of the factors contributing to this elevated slope is an increased chemosensitivity to CO in that this slope significantly correlates with the slope of the ventilatory response to CO rebreathing at rest. A previous study in patients with CHF and central sleep apnea showed that the highest VE/VCO slope during exercise was associated with the most severe central sleep apnea.

Research Priorities for Patients with Heart Failure and Central Sleep Apnea. An Official American Thoracic Society Research Statement.

Central sleep apnea (CSA) is common among patients with heart failure and has been strongly linked to adverse outcomes. However, progress toward improving outcomes for such patients has been limited. The purpose of this official statement from the American Thoracic Society is to identify key areas to prioritize for future research regarding CSA in heart failure.