UNASSIGNED: Sleep disordered breathing (SDB) may trigger nocturnal cardiac arrhythmias (NCA) in patients with heart failure with reduced ejection fraction (HFrEF). The NCA ancillary study of the ADVENT-HF trial will test whether, in HFrEF-patients with SDB, peak-flow-triggered adaptive servo-ventilation (ASVpf) reduces NCA. To this end, accurate scoring of NCA from polysomnography (PSG) is required.
UNASSIGNED: To develop a method to detect NCA accurately from a single-lead electrocardiogram (ECG) recorded during PSG and assess inter-observer agreement for NCA detection.
UNASSIGNED: Quality assurance of ECG analysis included training of the investigators, development of standardized technical quality, guideline-conforming semi-automated NCA-scoring via Holter-ECG software and implementation of an arrhythmia adjudication committee. To assess inter-observer agreement, the ECG was analysed by two independent investigators and compared for agreement on premature ventricular complexes (PVC) /h, premature atrial complexes/h (PAC) as well as for other NCA in 62 patients from two centers of the ADVENT-HF trial.
UNASSIGNED: The intraclass correlation coefficients for PVC/h and PAC/h were excellent: 0.99 (95%- confidence interval [CI]: 0.99-0.99) and 0.99 (95%-CI: 0.97-0.99), respectively. No clinically relevant difference in inter-observer classification of other NCA was found. The detection of non-sustained ventricular tachycardia (18% versus 19%) and atrial fibrillation (10% versus 11%) was similar between the two investigators. No sustained ventricular tachycardia was detected.
UNASSIGNED: These findings indicate that our methods are very reliable for scoring NCAs and are adequate to apply for the entire PSG data set of the ADVENT-HF trial.

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund\'s SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.

Most preclinical sleep studies are conducted in nocturnal rodents that have fragmented sleep in comparison to humans who are primarily diurnal, typically with a consolidated sleep period. Consequently, we sought to define basal sleep characteristics, sleep/wake architecture and electroencephalographic (EEG) activity in a diurnal non-human primate (NHP) to evaluate the utility of this species for pharmacological manipulation of the sleep/wake cycle. Adult, 9-11 y.o. male cynomolgus macaques (n = 6) were implanted with telemetry transmitters to record EEG and electromyogram (EMG) activity and Acticals to assess locomotor activity under baseline conditions and following injections either with vehicle or the caffeine (CAF; 10 mg/kg, i.m.) prior to the 12 h dark phase. EEG/EMG recordings (12-36 h in duration) were analyzed for sleep/wake states and EEG spectral composition. Macaques exhibited a sleep state distribution and architecture similar to previous NHP and human sleep studies. Acute administration of CAF prior to light offset enhanced wakefulness nearly 4-fold during the dark phase with consequent reductions in both NREM and REM sleep, decreased slow wave activity during wakefulness, and increased higher EEG frequency activity during NREM sleep. Despite the large increase in wakefulness and profound reduction in sleep during the dark phase, no sleep rebound was observed during the 24 h light and dark phases following caffeine administration. Cynomolgus macaques show sleep characteristics, EEG spectral structure, and respond to CAF in a similar manner to humans. Consequently, monitoring EEG/EMG by telemetry in this species may be useful both for basic sleep/wake studies and for pre-clinical assessments of drug-induced effects on sleep/wake.

The neuropeptides orexin and melanin-concentrating hormone (MCH), as well as the neurotransmitters GABA (γ-Aminobutyric acid) and glutamate are chief modulators of the sleep-wake states in the posterior hypothalamus. To investigate co-expression of vesicular GABA transporter (VGAT, a marker of GABA neurons) and the vesicular glutamate transporter-2 (VGLUT2, a marker of glutamate neurons) in orexin and MCH neurons, we generated two transgenic mouse lines. One line selectively expressed the reporter gene EYFP in VGAT+ neurons, whereas the other line expressed reporter gene tdTomato in VGLUT2+ neurons. Co-localization between these genetic reporters and orexin or MCH immunofluorescent tags was determined using 3D computer reconstructions of Z stacks that were acquired using a multiphoton laser confocal microscope. Our results demonstrated that MCH neurons expressed neither VGAT nor VGLUT2, suggesting MCH neurons are a separate cluster of cells from VGAT+ GABAergic neurons and VGLUT2+ glutamatergic neurons. Moreover, most orexin neurons expressed VGLUT2, indicating these neurons are glutamatergic. Our data suggested that in the posterior hypothalamus there are four major distinct groups of neurons: VGAT+, orexin+/VGLUT2+, orexin-/VGLUT2+, and MCH neurons. This study facilitated our understanding of the role of these neurotransmitters and neuropeptides in relation to sleep/wake regulation.

Parasomnias with sexual behavior or sexsomnias are considered a subtype of NREM parasomnias. Obstructive sleep apnea/hypopnea (OSAH) has been described as a known triggering factor for parasomnias including sexsomnia. Nasal continuous positive airway pressure (nCPAP) has been the standard of treatment for OSAH but mandibular advancement devices (MAD) are becoming an important treatment alternative. We present the case of a patient with mild OSAH and sexsomnia who had resolution of both conditions with a MAD. This patient had the added uniqueness of having REM-predominant OSAH.

Here our goal was to determine the magnitude of sleep-related motor skill enhancement. Performance on the finger tapping task (FTT) was evaluated after a 90 min daytime nap (n=15) or after quiet wakefulness (n=15). By introducing a slight modification in the formula used to calculate the offline gains we were able to refine the estimated magnitude of sleep׳s effect on motor skills. The raw value of improvement after a nap decreased after this correction (from ~15% to ~5%), but remained significantly higher than the control. These results suggest that sleep does indeed play a role in motor skill consolidation.