Difficulty initiating sleep in patients with heart failure: Impact of left atrial pressure.

BACKGROUND: Patients with heart failure (HF) often complain of sleep discomfort. Previous reports described that difficulty initiating sleep increased the cardiovascular risk in the general population. However, the association between difficulty initiating sleep and cardiac function in patients with HF remains unclear. This study aimed to investigate the associations between difficulty initiating sleep and clinical characteristics and cardiac function in patients with HF. METHODS: Eighty-seven patients with HF who underwent overnight polysomnography for suspected sleep-disordered breathing were included. Patients were divided into two groups of the longer sleep latency (SL) group (SL ≥14 min, n = 44) and the shorter SL group (SL <14 min, n = 43). The median value of SL was defined as the time from lights-off to falling asleep. We compared the patients' characteristics, laboratory data, and polysomnographic and echocardiographic indices between the two groups. RESULTS: The patients' median age was 67 years, and 85.1 % were men. There was lower beta blocker use [25 (56.8 %) vs. 34 (79.1 %), p = 0.046] and a higher peak mitral early filling velocity to mitral annular velocity ratio (E/e') [16.5 (14.2-21.7) vs. 13.7 (10.9-16.2), p = 0.005] in the longer SL group than in the shorter SL group. In multivariate logistic analysis, E/e' (odds ratio: 1.10, 95 % confidence interval: 1.01 to 1.19; p = 0.032) and systolic blood pressure before sleeping (odds ratio: 1.05, 95 % confidence interval: 1.00 to 1.10; p = 0.033) were significantly associated with a longer SL in patients with HF. CONCLUSIONS: Increased left atrial pressure suggested by increased E/e' and increased systolic blood pressure before sleeping is independently associated with difficulty initiating sleep in patients with HF. Management of these hemodynamic imbalances is required to improve difficulty initiating sleep in patients with HF.

Hyperthyroidism in Graves Disease Causes Sleep Disorders Related to Sympathetic Hypertonia.

CONTEXT: It is well known that Graves disease (GD) causes sleep disorders (SDs). However, the characteristics and associated factors of SD and its clinical course post hyperthyroidism normalization remain unclear. OBJECTIVE: To clarify the characteristics and associated factors of subjective SD and its clinical course after GD treatment. METHODS: From November 2017 to October 2020, we enrolled 72 participants (22 newly diagnosed with GD with untreated hyperthyroidism, 20 previously diagnosed with GD with normal thyroid function, and 30 normal controls) with no other underlying SD-related diseases. We compared the groups at enrollment and conducted prospective observations after 12 months of treatment on participants with newly diagnosed GD. Main outcome measures were differences and changes in the Pittsburgh Sleep Quality Index (PSQI) global and component sleep quality scores. RESULTS: PSQI global sleep quality scores (P = .036) and sleep disturbance scores (P = .011) were significantly different among the 3 groups, and were highest in the untreated hyperthyroidism group. Multiple regression analysis demonstrated that free thyroxine level, which was positively correlated with sympathetic tone (ST) as evaluated by pulse rate, and urinary total metanephrines was associated with poorer PSQI global sleep quality scores independently of other factors (P = .006). Prospective observation showed that PSQI global sleep quality scores (P = .018) and sleep disturbance scores (P = .011) significantly improved with thyroid function normalization and ST attenuation. CONCLUSION: Hyperthyroidism caused by GD augmented ST and exacerbated subjective SD. Normalization of hyperthyroidism caused by GD improved subjective SD.

Effect of Serotonin 1A Agonists and Selective Serotonin Reuptake Inhibitors on Behavioral and Nighttime Respiratory Symptoms in Rett Syndrome.

BACKGROUND: Rett syndrome is characterized by psychomotor regression during early childhood, autistic-like behaviors, and aberrant breathing patterns. Dysfunction of the serotonergic system has been postulated to play a role in the pathophysiology of these symptoms. PATIENT DESCRIPTION: We present an 11-year-old girl with Rett syndrome who exhibited marked respiratory symptoms, including frequent apneic events during sleep. She had been treated for these respiratory symptoms using noninvasive positive pressure ventilation since age six years. Treatment with serotonin 1A receptor agonist was initiated at age eight years, whereas treatment using a selective serotonin reuptake inhibitor began at age nine years. Noninvasive positive pressure ventilation therapy was effective in reducing symptoms of sleep apnea, and administration of serotonergic agents resulted in amelioration of sleep apneic events even in the absence of noninvasive positive pressure ventilation. In addition, improvements in hand stereotypy and social skills were observed after initiation of serotonin-based therapy. DISCUSSION: The respiratory difficulties our patient experienced during non-rapid eye movement (REM) sleep are characteristic of post-sigh central apnea. Exaggerated activity of expiratory neurons during such apneic events has been observed in mouse models of Rett syndrome. We suggest that prescribed serotonergic agents might serve to inhibit such activity, attenuating the imbalance between inspiratory and expiratory neurons. These agents might also be useful in the treatment of autistic-like behaviors caused by impaired serotonergic transmission in the brain.