Andrey V. Zinchuk

Polysomnographic phenotypes and their cardiovascular implications in obstructive sleep apnoea

Background Obstructive sleep apnoea (OSA) is a heterogeneous disorder, and improved understanding of physiologic phenotypes and their clinical implications is needed. We aimed to determine whether routine polysomnographic data can be used to identify OSA phenotypes (clusters) and to assess the associations between the phenotypes and cardiovascular outcomes. Methods Cross-sectional and longitudinal analyses of a multisite, observational US Veteran (n=1247) cohort were performed. Principal components-based clustering was used to identify polysomnographic features in OSA’s four pathophysiological domains (sleep architecture disturbance, autonomic dysregulation, breathing disturbance and hypoxia). Using these features, OSA phenotypes were identified by cluster analysis (K-means). Cox survival analysis was used to evaluate longitudinal relationships between clusters and the combined outcome of incident transient ischaemic attack, stroke, acute coronary syndrome or death. Results Seven patient clusters were identified based on distinguishing polysomnographic features: ‘mild’, ‘periodic limb movements of sleep (PLMS)’, ‘NREM and arousal’, ‘REM and hypoxia’, ‘hypopnoea and hypoxia’, ‘arousal and poor sleep’ and ‘combined severe’. In adjusted analyses, the risk (compared with ‘mild’) of the combined outcome (HR (95% CI)) was significantly increased for ‘PLMS’, (2.02 (1.32 to 3.08)), ‘hypopnoea and hypoxia’ (1.74 (1.02 to 2.99)) and ‘combined severe’ (1.69 (1.09 to 2.62)). Conventional apnoea–hypopnoea index (AHI) severity categories of moderate (15≤AHI<30) and severe (AHI ≥30), compared with mild/none category (AHI <15), were not associated with increased risk. Conclusions Among patients referred for OSA evaluation, routine polysomnographic data can identify physiological phenotypes that capture risk of adverse cardiovascular outcomes otherwise missed by conventional OSA severity classification.

The Association between Nocturnal Cardiac Arrhythmias and Sleep-Disordered Breathing: The DREAM Study.

STUDY OBJECTIVES To determine whether sleep-disordered breathing (SDB) is associated with cardiac arrhythmia in a clinic-based population with multiple cardiovascular comorbidities and severe SDB. METHODS This was a cross-sectional analysis of 697 veterans who underwent polysomnography for suspected SDB. SDB was categorized according to the apnea-hypopnea index (AHI): none (AHI < 5), mild (5 ≥ AHI < 15), and moderate-severe (AHI ≥ 15). Nocturnal cardiac arrhythmias consisted of: (1) complex ventricular ectopy, (CVE: non-sustained ventricular tachycardia, bigeminy, trigeminy, or quadrigeminy), (2) combined supraventricular tachycardia, (CST: atrial fibrillation or supraventricular tachycardia), (3) intraventricular conduction delay (ICD), (4) tachyarrhythmias (ventricular and supraventricular), and (5) any cardiac arrhythmia. Unadjusted, adjusted logistic regression, and Cochran-Armitage testing examined the association between SDB and cardiac arrhythmias. Linear regression models explored the association between hypoxia, arousals, and cardiac arrhythmias. RESULTS Compared to those without SDB, patients with moderate-severe SDB had almost three-fold unadjusted odds of any cardiac arrhythmia (2.94; CI 95%, 2.01-4.30; p < 0.0001), two-fold odds of tachyarrhythmias (2.16; CI 95%,1.47-3.18; p = 0.0011), two-fold odds of CVE (2.01; 1.36-2.96; p = 0.003), and two-fold odds of ICD (2.50; 1.58-3.95; p = 0.001). A linear trend was identified between SDB severity and all cardiac arrhythmia subtypes (p value linear trend < 0.0001). After adjusting for age, BMI, gender, and cardiovascular diseases, moderate-severe SDB patients had twice the odds of having nocturnal cardiac arrhythmias (2.24; 1.48-3.39; p = 0.004). Frequency of obstructive respiratory events and hypoxia were strong predictors of arrhythmia risk. CONCLUSIONS SDB is independently associated with nocturnal cardiac arrhythmias. Increasing severity of SDB was associated with an increasing risk for any cardiac arrhythmia.

Synchronous Pulmonary Malignancies: Atypical Presentation of Mantle Cell Lymphoma Masking a Lung Malignancy.

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

Prevalence, associated clinical features, and impact on continuous positive airway pressure use of a low respiratory arousal threshold among male United States veterans with obstructive sleep apnea

STUDY OBJECTIVES Determine the prevalence of, and clinical features associated with, a low respiratory arousal threshold (ArTH) among patients with obstructive sleep apnea (OSA), and to assess whether a low ArTH is associated with reduced long-term CPAP use. METHODS Cross-sectional and longitudinal analyses were performed in an observational study conducted among 940 male Veterans with OSA. Data for clinical characteristics, polysomnography characteristics, and long-term (5 ± 2 years) CPAP use were obtained from clinical records. Logistic regression was used to assess the associations between low ArTH and clinical features, including regular CPAP use. RESULTS A low ArTH was observed in 38% of participants overall, and was more common among nonobese (body mass index < 30 kg/m2) patients (55%). In adjusted analyses, increasing body mass index (per 5 kg/m2) and antihypertensive medication use were negatively associated with low ArTH, with odds ratio (OR) (95% confidence interval [CI]) of 0.77 (0.69, 0.87) and 0.69 (0.49, 0.98), respectively. Conversely, increasing age (per 10 years) and antidepressant use-OR (95% CI) 1.15 (1.01,1.31) and 1.54 (1.14,1.98), respectively-were positively associated with low ArTH. Nonobese patients with low ArTH were less likely to be regular CPAP users-OR (95% CI) 0.38 (0.20, 0.72)-in an adjusted model. CONCLUSIONS Low ArTH is a common trait among Veterans with OSA and is more frequent among those who are older and nonobese and those taking antidepressants, but is less frequent among patients taking antihypertensive medications. A marked reduction of long-term CPAP use in nonobese patients with low ArTH highlights the importance of understanding a patients physiologic phenotype for OSA management, and suggests potential targets to improve CPAP adherence. COMMENTARY A commentary on this article appears in this issue on page 713.

Erratum to: The Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study: design, rationale, and methods (Sleep and Breathing, DOI: 10.1007/s11325-015-1254-3)

1 Department of Neurology, Yale University, New Haven, CT, USA 2 Department of Neurology, Connecticut Veterans Affairs Health System, West Haven, CT, USA 3 Department of Pulmonary, Critical Care, and Sleep Medicine, Yale University, New Haven, CT, USA 4 Department of Pulmonary, Critical Care, and Sleep Medicine, Connecticut Veterans Affairs Health System, West Haven, CT, USA 5 Department of Pulmonary, Critical Care, and Sleep Medicine, Mayo Clinic, Rochester, MN, USA 6 Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA 7 Division of Acute Care/Health Systems, Yale School of Nursing, New Haven, CT, USA 8 Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA Sleep Breath (2016) 20:901 DOI 10.1007/s11325-016-1329-9