Mansukhani, Meghna P.

Abstract Background The implications of poor sleep for cardiovascular disease risk are increasingly recognised. Although previous research has focused on clinical sleep disorders, emerging evidence highlights the relevance of subclinical sleep aspects for cardiovascular health. Sleep midpoint, an index of sleep timing and a proxy of circadian phase, has been shown to be associated with markers of cardiometabolic risk, including obesity, in the general population. Purpose We aimed to assess whether sleep midpoint was related to body composition measures in patients with coronary heart disease enrolled in cardiac rehabilitation (CR). Methods Study participants were recruited from the patient population referred to our CR center for acute coronary syndrome or coronary revascularisation. Shift work was exclusionary. Participants underwent sleep testing prior to entering the CR program, including completion of one week of wrist actigraphy and sleep log. Using actigraphy-derived sleep metrics, sleep midpoint was calculated as the middle time (hh:mm) between bedtime and wake up time for each individual night, and averaged across the monitoring week. Based on the median sleep midpoint of the sample, participants were categorised as having early (before 2:42) or late (after 2:42) sleep midpoint. Body composition and regional fat distribution were determined by whole-body dual-energy absorptiometry (DEXA). Between-group characteristics were compared using independent t-test, Mann-Whitney U test and Chi-square statistics as appropriate. Linear regression was used to test the association between sleep midpoint and body fat measures. Results Thirty-one participants (26 males, 64.7±12.5 years) completed both actigraphy and DEXA assessments. Demographics, lifestyle, and clinical characteristics were similar between patients with early sleep midpoint (n=15; sleep midpoint, hh:mm: 2:00, range 0:57 to 2:41) and patients with late sleep midpoint (n=16; sleep midpoint 3:18, range 2:42 to 4:17). Despite comparable body mass index between groups (p=0.21), patients with late sleep midpoint had significantly higher total body fat percentage (p=0.017), android fat percentage (p=0.015), and gynoid fat percentage (p=0.045). Late sleep midpoint remained significantly associated with adiposity measures in age- and sex-adjusted analysis (total body fat percentage, beta = 0.371, 95% CI 0.063 to 0.68; android fat percentage, beta = 0.394, 95% CI 0.078 to 0.71; gynoid fat percentage, beta = 0.301, 95% CI 0.007 to 0.596). Conclusions Late sleep midpoint was associated with excess adiposity in patients with coronary heart disease enrolled in CR. These findings support the predictive value of sleep timing for cardiometabolic risk and emphasise the importance of objective sleep assessment for secondary prevention.

Over 37% of pregnant women report excessive daytime sleepiness or hypersomnia during the first trimester, and commonly throughout the remaining trimesters of pregnancy and the postpartum period. The clinical presentation and symptoms of central disorders of hypersomnolence (CDH) such as narcolepsy, idiopathic hypersomnia, or excessive daytime sleepiness secondary to shift work or obstructive sleep apnea may be confounded by physiological changes in sleep architecture and hormonal fluctuations occurring during pregnancy. These overlapping features may cause delays in diagnosis and treatment, impacting quality of life, maternal functioning, and overall health. Management of CDH during pregnancy and lactation requires careful consideration of maternal benefits, potential side effects of medications and fetal and neonatal safety. Here, we present a case of idiopathic hypersomnia and detail management and outcomes during pregnancy and lactation. We briefly review the existing literature on prevalence, pathophysiological mechanisms, diagnostic challenges, objective findings, and risks posed by CDH in pregnancy and lactation. In this narrative review for primary care clinicians, we also summarize currently available evidence regarding the efficacy, teratogenic and other risks of pharmacologic agents used in the treatment of CDH in pregnancy and lactation. Lastly, we provide a clinical algorithm for management of CDH during pregnancy and lactation.

Background: Sleep regularity is emerging as an independent determinant of health. Multiple studies suggest a link between increased variability in sleep duration and timing and adverse cardiovascular, metabolic, and cognitive outcomes. There is, however, a lack of data on the implications of sleep regularity for aerobic capacity and physical endurance, particularly in patients with established cardiovascular disease. This study seeks to investigate the influence of irregularity in sleep duration on functional capacity in patients with coronary artery disease (CAD) undergoing cardiac rehabilitation (CR). Methods: We recruited a sample of patients with CAD who were referred to CR at Mayo Clinic Rochester. Participants completed a 6-minute walk test (6MWT) upon enrollment into CR. 6MWT variables included distance walked (meters), predicted distance walked (percentage) and estimated metabolic equivalents (METs). 24-hour objective sleep quality and quantity were assessed over a 7-day period by wrist actigraphy. Average standard deviation (SD) of sleep duration was used to define sleep regularity, with SD >60 minutes indicating irregular sleep. Chi-square test, independent samples t-test, and linear regression were used for statistical analysis. Results: Twenty-eight participants with valid actigraphy and 6MWT were included in this analysis (eight females; mean age 67.4 ± 11.6 years; body mass index 31.1 ± 5.8 kg/m 2 ). The average total sleep time was 7.1 ± 1.2 hours, and 10 participants (35.7%) exhibited sleep duration SD >60 minutes. Demographic, clinical and sleep characteristics were comparable between the regular and irregular sleep groups. Compared to patients with regular sleep, those with irregular sleep had poorer 6MWT, with shorter distance walked (406.2 ± 81.2 meters vs 338.8 ± 80.7 meters; p = 0.045), lower % of predicted distance walked (87.1 ± 18.7% vs 69.2 ± 11.4%; p = 0.011), and lower METS (2.99 ± 0.36 vs 2.63 ± 0.38; p = 0.022). Irregular sleep remained significantly associated with performance at the 6MWT after taking into account age and sex, with patients walking 14.4 meters fewer with every 10-minute increase in sleep variability (95% CI -28.1, -0.7; p 0.041). Conclusions: Increased day-to-day fluctuation in sleep duration is associated with reduced exercise capacity in patients with CAD undergoing CR. These findings add to the mounting body of evidence linking irregular sleep patterns to heightened cardiovascular risk, and support the integration of sleep monitoring in the CR practice to enhance risk stratification and outcome prediction. Funding Source: Sleep Number Corp. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Abstract Introduction Clinical hypnosis is among the limited treatment options currently available to mitigate the symptom burden associated with parasomnias; however, there is scant literature regarding its effectiveness. We conducted a retrospective cohort study to examine the efficacy of clinical hypnosis in treating parasomnias. Methods We included all adult patients with research authorization on file who were referred for clinical hypnosis for the management of parasomnias at the Mayo Clinic Center for Sleep Medicine. Data on demographics, type and frequency of parasomnia(s), number of hypnosis sessions, concurrent medication(s), and polysomnographic variables were extracted. Information about the efficacy of treatment, including patient reports of change in intensity and frequency was extracted where available. A Clinical Global Impression-Improvement (CGI-I) score was assigned based on review of the follow up note. Results A total of 134 patients received clinical hypnosis. A majority of the sample was female (65.67%) with a median age of 41.5 years. The most common indications were non-rapid eye movement (REM) parasomnia (33), REM sleep behavior disorder (27), nightmare disorder (24), parasomnia overlap disorder (11), and sleep-related eating disorder (8). Follow up data were available on 76 patients (56.71%). Of these, a total of 47/76 (61.84%) reported subjective improvement in parasomnias following hypnosis. The median CGI-I score was 3.07±1.22; a total of 23/76 (30.26%) reported substantial improvement and 19/76 (25.0%) reported some impovement based on the CGI scores. Conclusion A majority of patients reported improvement in symptoms. Clinical hypnosis was effective for both non-REM and REM parasomnias. Given its relative safety and minimal potential adverse effects, clinical hypnosis remains an effective first-line treatment option for parasomnias. Support (if any)

Abstract Introduction Observational studies have reported associations between hypnotic use and increased risk of cognitive decline. These findings may reflect confounding from insomnia severity, healthcare utilization, and comorbidity burden. We evaluated whether hypnotic exposure is independently associated with incident mild cognitive impairment (MCI) or dementia after rigorous adjustment, including a comprehensive propensity score (PS) and Apolipoprotein E (APOE) ε4 status. Methods We conducted a retrospective cohort study using a biobank sample with linked electronic health records and genetic data. Hypnotic exposure was derived from orders data and categorized as unexposed (n=27,055), single prescription (n=4243), shorter-term use (n=3999), long-term use (≥6 orders for ≥1 year; n=3214), and by drug class: benzodiazepines (n=376), Z-drugs (n=6222), trazodone (n=2395), and mixed exposure (≥2 classes; n=2435). Incident MCI/dementia diagnoses (ICD-9/10) occurring ≥12 months after initial prescription constituted outcomes. The PS modeled likelihood of receiving hypnotics based on demographics; sleep-related conditions; healthcare utilization (record length, visit frequency, diagnostic burden); psychiatric comorbidities; alcohol use and chronic pain. Hypnotic users were 1:2 matched to unexposed individuals on age, sex, healthcare utilization, and PS. Cox proportional hazards models with a 60-month lag tested associations of exposure category, duration, and class with outcomes. Models adjusted for all PS covariates, cardiovascular risk score, and APOE ε4 status. Results Matched but unadjusted analyses suggested slightly higher hazards of MCI/dementia among hypnotic users versus unexposed (HR=1.08; CI=0.99–1.18). However, after PS adjustment and APOE ε4 inclusion, hypnotic users showed significantly lower hazards (HR=0.81; CI=0.74–0.89). Class-specific analyses indicated reduced hazards for Z-drugs (HR=0.83; CI=0.74–0.93), trazodone (HR=0.71; CI=0.60–0.86), and mixed users (HR=0.79; CI=0.68–0.91), with all classes showing lower hazards than benzodiazepine-only users. Long-term hypnotic use was associated with lower hazards than no prescription (HR=0.69; CI=0.61–0.80), single prescription (HR=0.81; CI=0.68–0.97), or short-term use (HR=0.76; CI=0.65–0.90). Conclusion The elevated cognitive risk among hypnotic users appears largely attributable to underlying clinical/utilization factors rather than hypnotic exposure itself. After comprehensive confounding control, all hypnotic classes except benzodiazepines demonstrated lower risk of MCI/dementia. These findings underscore the need for rigorous adjustment in studies of insomnia pharmacotherapy and suggest potential protective effects of certain hypnotics that warrant further investigation. Support (if any) None

Importance Sleep disordered breathing (SDB) is a well-established contributor to cardiovascular morbidity, mediated by intermittent hypoxemia, autonomic dysregulation, and endothelial dysfunction. Patients with hypertrophic cardiomyopathy (HCM) may be especially at risk for SDB, but the clinical impact of SDB in this population remains unclear. Objective To define the prevalence and subtypes of SDB in HCM and examine their association with echocardiographic parameters and cardiac biomarker expression. Design, Setting, and Participants A prospective cohort study was conducted between April 18, 2018, and January 15, 2024, at a single tertiary referral center specializing in HCM care. Adults with HCM (left ventricular wall thickness ≥15 mm or pathogenic variants) were recruited from an institutional registry. Patients diagnosed with SDB or current pregnancy were excluded. Patients underwent polysomnography, with comparative assessment of echocardiographic, electrocardiographic, and biomarker indices. Observers were blinded to polysomnographic results. Data analysis was performed from April 11, 2024, to July 25, 2024. Exposures SDB classified via polysomnography using apnea-hypopnea index thresholds, with subtypes including obstructive sleep apnea and central sleep apnea and with event severity, hypoxemia, and sleep architecture disruption quantified. Main Outcomes and Measures Echocardiographic indices, cardiac biomarker expression, functional status, apnea-hypopnea index, and overnight hypoxemia. Results Among 154 patients (median [IQR] age, 60 [48-68] years; 102 [66.2%] male), 91 (59.1%) were diagnosed with SDB. Those with SDB, compared with those without SDB, had higher left ventricular mass index (median [IQR], 128 [107-161] vs 109 [96-134] g/m 2 ; P = .03), E/e′ ratio (median [IQR], 12.5 [10.0-15.0] vs 10.0 [8.3-14.5]; P = .04), and baseline troponin-T level (median [IQR], 0.013 [0.009-0.022] vs 0.011 [0.007-0.015] ng/mL [to convert to micrograms per liter, multiply by 1]; P = .04) and greater overnight troponin-T level increases (change in median [IQR], 0.0021 [−0.0029 to 0.0062] vs 0.0002 [−0.0022 to 0.0026] ng/mL; P = .02). New York Heart Association class II or III symptoms were more common in those with SDB (48 [52.7%] vs 17 [27.0%]; P = .005). Hypertension and diabetes were more prevalent among patients with SDB than without SDB (hypertension: 67 [73.6%] vs 36 [57.1%]; P = .03; diabetes: 14 [15.4%] vs 3 [4.8%]; P = .04), whereas rates of atrial fibrillation and prior myectomy did not differ significantly between groups. Conclusions and Relevance This study suggests that undiagnosed SDB is highly prevalent in patients with HCM and that SDB is associated with adverse myocardial remodeling, greater diastolic dysfunction, and elevated troponin-T levels, indicating subclinical myocardial injury. SDB may contribute to HCM pathophysiology and symptom burden, supporting the rationale for randomized clinical trials to determine the impact of treating SDB on symptoms and clinical outcomes in patients with HCM.

Background: Sleep disordered breathing (SDB) is frequently observed in patients with cardiovascular disease, and is associated with intermittent hypoxia, sympathetic activation, oxidative stress, and endothelial dysfunction, all of which may facilitate the development and progression of cardiovascular disease. Objectives: We sought to determine the prevalence, subtypes, and clinical implications of comorbid SDB in patients with hypertrophic cardiomyopathy (HCM). Methods: In this prospective observational study, patients with HCM without prior diagnosis of SDB were recruited to undergo inpatient polysomnography between May 1 st 2018 and October 31 st 2022. Electrocardiographic and echocardiographic parameters, cardiac biomarkers, and symptoms were comparatively assessed in patients with and without comorbid SDB. Patients were assessed for the development of major adverse cardiovascular events (MACE) during follow-up (median 29, range 3-57 months). Results Among 154 participants, 91 (59.1%) were diagnosed with SDB of whom 38 (41.8%) had mild, 22 (24.2%) moderate, 18 (19.8%) severe obstructive sleep apnea, and 13 (14.3%) had central sleep apnea. SDB was associated with greater left ventricular mass (median [IQR]) (128 [107, 161] vs. 109 [96, 134] g/m 2 , p =0.034) and E/e’ ratio (12.5 [10, 15] vs. 10.0 [8.3, 14.5], p =0.039). Patients with HCM over the age of 50 years, with body mass index ≥ 30kg/m 2 , who described their sleep as “poor” were at particularly high risk of having comorbid SDB, as were those who were diabetic, hypertensive, or described greater exertional limitation (NYHA Class ≥II 53% vs. 27%, p =0.005). Importantly, subjects with SDB had elevated baseline Troponin T levels (14 ng/L vs 11 ng/L, p =0.030), and further substantial overnight troponin increases following untreated apneic sleep (2.1ng/L vs 0.2ng/L, p =0.009). Finally, patients with comorbid SDB experienced a significantly higher proportion of incident adverse cardiovascular events (MACE hazard ratio 5.3, 95% CI, 1.6, 17.2, p =0.006) than those without SDB. Conclusions: We report a particularly high burden of previously undiagnosed SDB in patients with HCM, particularly in older, heavier, male patients. Undiagnosed SDB in HCM is not benign and is associated with symptom progression, comorbidity, and a poorer prognosis, particularly in the case of central sleep apnea. These important new findings provide rationale for heightened vigilance and routine screening for SDB in patients with HCM.

Introduction: Sleep duration is now recognized as an important determinant of cardiovascular (CV) health. Recently, the CV implications of day-to-day variability in sleep duration have become apparent, with irregular sleep duration associated with increased risk of CV disease, including hypertension. However, the relationship between sleep duration variability and ambulatory blood pressure (BP) patterns in the general population or in patients with CV disease is unknown. Research Questions: We sought to investigate whether irregular sleep duration is associated with aberrant ambulatory BP or heart rate (HR) profiles in patients undergoing cardiac rehabilitation (CR). Methods: We recruited a sample of 42 patients with coronary artery disease enrolled in CR at Mayo Clinic Rochester. Participants underwent 24-hour ambulatory BP monitoring and sleep assessment including one week of wrist actigraphy and sleep diary prior to entering CR. Twenty-four hour, awake, and asleep averages were calculated for systolic BP, diastolic BP, and HR. Nocturnal dipping and morning surge were also computed for BP and HR. Sleep regularity was quantified by SD of actigraphy-derived sleep duration and irregular sleep duration was defined as SD >1 hour. Chi-square tests and Mann-Whitney U tests were used to compare groups. Results: Thirty-six participants (22% females, median age [25 th ,75 th IQR] 66.5 [61,75.8] years, body mass index 31.7 [26.9,35.1] kg/m 2 ) had valid actigraphy and ambulatory BP recordings. We found sleep duration SD >1 hour in 36% of them. Demographics and average sleep duration were similar between those with irregular and regular sleep duration (all Ps>0.11). Twenty-four-hour, awake and asleep HR values were comparable between groups (all Ps>0.26). Participants with irregular sleep duration exhibited lower nocturnal HR dipping (9.2 [3.1,11.6] % vs 12.9 [8.9,18.2] %, P=0.019) than their counterparts with regular sleep. Morning HR surge was also attenuated in patients with irregular sleep duration (3 [-1,9] bpm vs 10 [7,14] bpm, P=0.006). Ambulatory SBP and DBP measures did not differ significantly between groups (all Ps>0.17). Conclusions: High day-to-day variability in sleep duration is linked to blunted nocturnal dipping and morning surge in HR in patients with coronary artery disease enrolled in CR. Because altered ambulatory HR profile predicts unfavorable CV outcomes, evaluation of sleep patterns in the CR setting may yield important prognostic information.