Carotid body chemoreceptors: physiology, pathology, and implications for health and disease.

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 and pH, eliciting reflex ventilatory, cardiovascular, and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiological responses, and its role in maintaining health and potentiating disease. Emphasis is placed on 1) transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ion channels; 2) synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; 3) integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological, or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and 4) the contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension, and metabolic diseases and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.

The Role of Sleep in Cardiovascular Disease.

PURPOSE OF REVIEW: Sleep is an important component of cardiovascular (CV) health. This review summarizes the complex relationship between sleep and CV disease (CVD). Additionally, we describe the data supporting the treatment of sleep disturbances in preventing and treating CVD. RECENT FINDINGS: Recent guidelines recommend screening for obstructive sleep apnea in patients with atrial fibrillation. New data continues to demonstrate the importance of sleep quality and duration for CV health. There is a complex bidirectional relationship between sleep health and CVD. Sleep disturbances have systemic effects that contribute to the development of CVD, including hypertension, coronary artery disease, heart failure, and arrhythmias. Additionally, CVD contributes to the development of sleep disturbances. However, more data are needed to support the role of screening for and treatment of sleep disorders for the prevention of CVD.

Sleep-Disordered Breathing and Cardiac Arrhythmias in Adults: Mechanistic Insights and Clinical Implications: A Scientific Statement From the American Heart Association.

Sleep-disordered breathing (SDB), characterized by specific underlying physiological mechanisms, comprises obstructive and central pathophysiology, affects nearly 1 billion individuals worldwide, and is associated with excessive cardiopulmonary morbidity. Strong evidence implicates SDB in cardiac arrhythmogenesis. Immediate consequences of SDB include autonomic nervous system fluctuations, recurrent hypoxia, alterations in carbon dioxide/acid-base status, disrupted sleep architecture, and accompanying increases in negative intrathoracic pressures directly affecting cardiac function. Day-night patterning and circadian biology of SDB-induced pathophysiological sequelae collectively influence the structural and electrophysiological cardiac substrate, thereby creating an ideal milieu for arrhythmogenic propensity. Cohort studies support strong associations of SDB and cardiac arrhythmia, with evidence that discrete respiratory events trigger atrial and ventricular arrhythmic events. Observational studies suggest that SDB treatment reduces atrial fibrillation recurrence after rhythm control interventions. However, high-level evidence from clinical trials that supports a role for SDB intervention on rhythm control is not available. The goals of this scientific statement are to increase knowledge and awareness of the existing science relating SDB to cardiac arrhythmias (atrial fibrillation, ventricular tachyarrhythmias, sudden cardiac death, and bradyarrhythmias), synthesizing data relevant for clinical practice and identifying current knowledge gaps, presenting best practice consensus statements, and prioritizing future scientific directions. Key opportunities identified that are specific to cardiac arrhythmia include optimizing SDB screening, characterizing SDB predictive metrics and underlying pathophysiology, elucidating sex-specific and background-related influences in SDB, assessing the role of mobile health innovations, and prioritizing the conduct of rigorous and adequately powered clinical trials.

Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy-Associated Putative Pathogenic Gene Variants in UK Biobank Participants.

BACKGROUND: There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features. METHODS: UK Biobank participants who had undergone whole exome sequencing, ECG, and cardiovascular magnetic resonance imaging were selected for study. Three variant-calling strategies (1 primary and 2 secondary) were used to identify participants with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded DCM (clinical or cardiovascular magnetic resonance diagnosis); early DCM features, including arrhythmia or conduction disease, isolated ventricular dilation, and hypokinetic nondilated cardiomyopathy; or phenotype-negative. RESULTS: Among 18 665 individuals included in the study, 1463 (7.8%) possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and cardiovascular magnetic resonance analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in an additional 15.9% of individuals with putative pathogenic variants. Arrhythmias or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic nondilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all 3 variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes as compared with those with variants in moderate/limited evidence genes. CONCLUSIONS: In the UK Biobank, ≈1 of 6 of adults with putative pathogenic variants in DCM genes exhibited early DCM features potentially associated with DCM genotype, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction.

Association of obstructive sleep apnoea with cardiovascular events in women and men with acute coronary syndrome.

BACKGROUND: The impact of sex on the association of obstructive sleep apnoea (OSA) with recurrent cardiovascular events following acute coronary syndrome (ACS) remains uncertain. This study sought to examine the association between OSA and long-term cardiovascular outcomes in women and men with ACS. METHODS: In this prospective cohort study, we recruited 2160 ACS patients undergoing portable sleep monitoring between June 2015 and January 2020. The primary end-point was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischaemia-driven revascularisation or hospitalisation for unstable angina or heart failure. RESULTS: After exclusion of patients with failed sleep studies, central sleep apnoea, regular continuous positive airway pressure therapy and loss of follow-up, 1927 patients were enrolled. Among them, 298 (15.5%) were women and 1014 (52.6%) had OSA (apnoea-hypopnoea index ≥15 events·h-1). The prevalence of OSA was 43.0% and 54.4% in women and men, respectively. In 4339 person-years (median 2.9 years, interquartile range 1.5-3.6 years), the cumulative incidence of MACCE was significantly higher in OSA versus non-OSA groups in the overall population (22.4% versus 17.7%; adjusted hazard ratio (HR) 1.29, 95% CI 1.04-1.59; p=0.018). OSA was associated with greater risk of MACCE in women (28.1% versus 18.8%; adjusted HR 1.68, 95% CI 1.02-2.78; p=0.042), but not in men (21.6% versus 17.5%; adjusted HR 1.22, 95% CI 0.96-1.54; p=0.10). No significant interaction was noted between sex and OSA for MACCE (interaction p=0.32). The incremental risk in women was attributable to higher rates of hospitalisation for unstable angina and ischaemia-driven revascularisation. CONCLUSIONS: In hospitalised ACS patients, OSA was associated with increased risk of subsequent events, particularly among women. Female patients with ACS should not be neglected for OSA screening and dedicated intervention studies focusing on women with ACS and comorbid OSA should be prioritised.

Detecting Unique Analyte-Specific Radio Frequency Spectral Responses in Liquid Solutions-Implications for Non-Invasive Physiologic Monitoring.

With rising healthcare costs and the rapid increase in remote physiologic monitoring and care delivery, there is an increasing need for economical, accurate, and non-invasive continuous measures of blood analytes. Based on radio frequency identification (RFID), a novel electromagnetic technology (the Bio-RFID sensor) was developed to non-invasively penetrate inanimate surfaces, capture data from individual radio frequencies, and convert those data into physiologically meaningful information and insights. Here, we describe groundbreaking proof-of-principle studies using Bio-RFID to accurately measure various concentrations of analytes in deionized water. In particular, we tested the hypothesis that the Bio-RFID sensor is able to precisely and non-invasively measure and identify a variety of analytes in vitro. For this assessment, varying solutions of (1) water in isopropyl alcohol; (2) salt in water, and (3) commercial bleach in water were tested, using a randomized double-blind trial design, as proxies for biochemical solutions in general. The Bio-RFID technology was able to detect concentrations of 2000 parts per million (ppm), with evidence suggesting the ability to detect considerably smaller concentration differences.

Sex Differences in Neurovascular Control: Implications for Obstructive Sleep Apnea.

Patients with obstructive sleep apnea (OSA) have a heightened risk of developing cardiovascular diseases, namely hypertension. While seminal evidence indicates a causal role for sympathetic nerve activity in the hypertensive phenotype commonly observed in patients with OSA, no studies have investigated potential sex differences in the sympathetic regulation of blood pressure in this population. Supporting this exploration are large-scale observational data, as well as controlled interventional studies in healthy adults, indicating that sleep disruption increases blood pressure to a greater extent in females relative to males. Furthermore, females with severe OSA demonstrate a more pronounced hypoxic burden (i.e., disease severity) during rapid eye movement sleep when sympathetic nerve activity is greatest. These findings would suggest that females are at greater risk for the hemodynamic consequences of OSA and related sleep disruption. Accordingly, the purpose of this review is three-fold: (1) to review the literature linking sympathetic nerve activity to hypertension in OSA, (2) to highlight recent experimental data supporting the hypothesis of sex differences in the regulation of sympathetic nerve activity in OSA, and (3) to discuss the potential sex differences in peripheral adrenergic signaling that may contribute to, or offset, cardiovascular risk in patients with OSA.

Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure-intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.

Impact of intracardiac echocardiography on readmission morbidity and mortality following atrial fibrillation ablation.

INTRODUCTION: The use of intracardiac echocardiography (ICE) is beneficial during the ablation of atrial fibrillation (AF). Evidence is conflicting regarding the clinical impact of using ICE on arrhythmia recurrence and mortality. METHODS: Patients undergoing catheter ablation of AF during 2010-2017 were identified using the International Classification of Diseases-9th and 10th Revision-Clinical Modification (ICD-9-CM and ICD-10-CM) from the Nationwide Readmissions Database. Propensity matching was used to generate a control group. Patient demographics, Charlson comorbidity indexes, time from discharge to readmission, and the reason of readmission were extracted. RESULTS: From 2010 to 2017, 51 129 patients were included in the analysis out of which ICE was used in 8005 (15.7%) patients. The in-hospital mortality at readmission was significantly higher in the patients without ICE use (2.9% vs. 1.7%, p = .02). The length of stay (LOS) at readmission was significantly higher in non-ICE arm (median [interquartile range, IQR]: 3 [2-6] vs. 2 [3-5] days, p < .0001) with similar healthcare-associated cost (HAC) in both the groups (median [IQR]: US$7507.3 [4057.8-15 474.2] vs. 7339.4 [4024.8-15 191.6], p = .43). Freedom from readmission was 12% higher (hazard ratio [HR] [95% confidence interval, CI]: 0.88 [0.83-0.94], p < .0001) with the use of ICE at 90-day follow-up, which was driven by 24% reduction in heart failure (HF) at follow-up (HR [95% CI]: 0.76 [0.60-0.96], p = .02). CONCLUSIONS: ICE use during AF ablation procedure reduces readmissions at 90 days by 12%, driven by a 24% decrease in HF-related admissions. The non-ICE arm showed a significantly higher LOS which offsets marginally higher HAC in the ICE arm.

Metabolic dysfunction-associated fatty liver disease and implications for cardiovascular risk and disease prevention.

The newly proposed term "metabolic dysfunction-associated fatty liver disease" (MAFLD) is replacing the old term "non-alcoholic fatty liver disease" (NAFLD) in many global regions, because it better reflects the pathophysiology and cardiometabolic implications of this common liver disease. The proposed change in terminology from NAFLD to MAFLD is not simply a single-letter change in an acronym, since MAFLD is defined by a set of specific and positive diagnostic criteria. In particular, the MAFLD definition specifically incorporates within the classification recognized cardiovascular risk factors. Although convincing evidence supports a significant association between both NAFLD and MAFLD, with increased risk of CVD morbidity and mortality, neither NAFLD nor MAFLD have received sufficient attention from the Cardiology community. In fact, there is a paucity of scientific guidelines focusing on this common and burdensome liver disease from cardiovascular professional societies. This Perspective article discusses the rationale and clinical relevance for Cardiologists of the newly proposed MAFLD definition.

Effect of adaptive servo ventilation on central sleep apnea and sleep structure in systolic heart failure patients: polysomnography data from the SERVE-HF major sub study.

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94-103 in the control group, 77-99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk.

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

Background: 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.Methods: An international multidisciplinary group with expertise in sleep medicine, pulmonary medicine, heart failure, clinical research, and health outcomes was convened. The group met at the American Thoracic Society 2019 International Conference to determine research priority areas. A statement summarizing the findings of the group was subsequently authored using input from all members.Results: The workgroup identified 11 specific research priorities in several key areas: 1) control of breathing and pathophysiology leading to CSA, 2) variability across individuals and over time, 3) techniques to examine CSA pathogenesis and outcomes, 4) impact of device and pharmacological treatment, and 5) implementing CSA treatment for all individualsConclusions: Advancing care for patients with CSA in the context of heart failure will require progress in the arenas of translational (basic through clinical), epidemiological, and patient-centered outcome research. Given the increasing prevalence of heart failure and its associated substantial burden to individuals, society, and the healthcare system, targeted research to improve knowledge of CSA pathogenesis and treatment is a priority.

Demographic characteristics associated with circadian rest-activity rhythm patterns: a cross-sectional study.

BACKGROUND: Rest-activity rhythm (RAR), a manifestation of circadian rhythms, has been associated with morbidity and mortality risk. However, RAR patterns in the general population and specifically the role of demographic characteristics in RAR pattern have not been comprehensively assessed. Therefore, we aimed to describe RAR patterns among non-institutionalized US adults and age, sex, and race/ethnicity variation using accelerometry data from a nationally representative population. METHODS: This cross-sectional study was conducted using the US National Health and Nutrition Examination Survey (NHANES) 2011-2014. Participants aged ≥20 years who were enrolled in the physical activity monitoring examination and had at least four 24-h periods of valid wrist accelerometer data were included in the present analysis. 24-h RAR metrics were generated using both extended cosinor model (amplitude, mesor, acrophase and pseudo-F statistic) and nonparametric methods (interdaily stability [IS] and intradaily variability [IV]). Multivariable linear regression was used to assess the association between RAR and age, sex, and race/ethnicity. RESULTS: Eight thousand two hundred participants (mean [SE] age, 49.1 [0.5] years) were included, of whom 52.2% were women and 67.3% Whites. Women had higher RAR amplitude and mesor, and also more robust (pseudo-F statistic), more stable (higher IS) and less fragmented (lower IV) RAR (all P trend < 0.001) than men. Compared with younger adults (20-39 years), older adults (≥ 60 years) exhibited reduced RAR amplitude and mesor, but more stable and less fragmented RAR, and also reached their peak activity earlier (advanced acrophase) (all P trend < 0.001). Relative to other racial/ethnic groups, Hispanics had the highest amplitude and mesor level, and most stable (highest IS) and least fragmented (lowest IV) RAR pattern (P trend < 0.001). Conversely, non-Hispanic blacks had the lowest peak activity level (lowest amplitude) and least stable (lowest IS) RAR pattern (all P trend < 0.001). CONCLUSIONS: In the general adult population, RAR patterns vary significantly according to sex, age and race/ethnicity. These results may reflect demographic-dependent differences in intrinsic circadian rhythms and may have important implications for understanding racial, ethnic, sex and other disparities in morbidity and mortality risk.

CPAP adherence reduces cardiovascular risk among older adults with obstructive sleep apnea.

STUDY OBJECTIVES: To examine (1) the impact of adherence to continuous positive airway pressure (CPAP) therapy on risk for cardiovascular (CVD) events among a nationally representative sample of older adults with obstructive sleep apnea (OSA), and (2) the heterogeneity of this effect across subgroups defined by race, sex, and socioeconomic status. METHODS: We conducted a retrospective cohort study among Medicare beneficiaries aged ≥ 65 years with OSA (2009-2013). Monthly indicators of CPAP adherence (charges for machines, masks, or supplies) were summed over 25 months to create a CPAP adherence variable. New CVD events (ischemic heart disease, cardiac and peripheral procedures) were modeled as a function of CPAP adherence using generalized estimating equations. Heterogeneity of the effect of CPAP on new CVD events was evaluated based on race, sex, and socioeconomic status. RESULTS: Among 5024 beneficiaries diagnosed with OSA who initiated CPAP, 1678 (33%) demonstrated new CVD events. Following adjustment for demographic and clinical characteristics, CPAP adherence was associated with reduced risk of new CVD events (hazard ratio 0.95; 95% confidence interval 0.94, 0.96) over 25 months. When analyses were stratified by time since the first CPAP charge, the protective effect remained significant for the 12- and 6-month, but not 3-month, outcome models. No significant differences were observed in the protective effect of CPAP based on race, sex, or socioeconomic status. CONCLUSIONS: In this national study of older adult Medicare beneficiaries with OSA, CPAP adherence was associated with greatly reduced risk for CVD events. This risk reduction was consistent across race, sex, and socioeconomic subgroups.

Mitigation of Exercise Oscillatory Ventilation Score by Cardiac Resynchronization Therapy.

BACKGROUND: Exercise oscillatory ventilation (EOV) is a consequence of ventilatory control system instability and is commonly observed in patients with advanced heart failure (HF); it is associated with adverse prognosis. The goal of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) on oscillatory ventilation as quantified by a proposed EOV score. METHODS AND RESULTS: Consecutive patients with HF (N = 35) who underwent clinically indicated CRT, cardiopulmonary exercise testing and carbon dioxide (CO2) chemosensitivity by rebreathe before and 4-6 months after CRT were included in this post hoc analysis. With CRT, EOV scores improved in 22 patients (63%). In these patients, left ventricular ejection fraction, left atrial volume, brain natriuretic peptide concentration, and CO2 chemosensitivity significantly improved after CRT (P < 0.05). Furthermore, minute ventilation per unit CO2 production significantly decreased, and end-tidal CO2 increased at rest and at peak exercise post-CRT. Multiple regression analysis showed only the change of CO2 chemosensitivity to be significantly associated with the improvement of the EOV score (b = 0.64; F = 11.3; P = 0.004). In the group without EOV score improvement (n = 13), though left ventricular ejection fraction significantly increased with CRT (P = 0.015), no significant changes in ventilation or gas exchange were observed. CONCLUSION: The EOV score was mitigated by CRT and was associated with decreased CO2 chemosensitivity.

Association of serious adverse events with Cheyne-Stokes respiration characteristics in patients with systolic heart failure and central sleep apnoea: A SERVE-Heart Failure substudy analysis.

BACKGROUND AND OBJECTIVE: Increases in Cheyne-Stokes respiration (CSR) cycle length (CL), lung-to-periphery circulation time (LPCT) and time to peak flow (TTPF) may reflect impaired cardiac function. This retrospective analysis used an automatic algorithm to evaluate baseline CSR-related features and then determined whether these could be used to identify patients with systolic heart failure (HF) who experienced serious adverse events in the Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE-HF) substudy. METHODS: A total of 280 patients had overnight diagnostic polysomnography data available; an automated algorithm was applied to quantify CSR-related features. RESULTS: Median baseline CL, LPCT and TTPF were similar in the control (n = 152) and adaptive servo-ventilation (ASV, n = 156) groups. In both groups, CSR-related features were significantly longer in patients who did (n = 129) versus did not (n = 140) experience a primary endpoint event (all-cause death, life-saving cardiovascular intervention or unplanned hospitalization for worsening HF): CL, 61.1 versus 55.1 s (P = 0.002); LPCT, 36.5 versus 31.5 s (P < 0.001); TTPF, 15.20 versus 13.35 s (P < 0.001), respectively. This finding was independent of treatment allocation. CONCLUSION: Patients with systolic HF and central sleep apnoea who experienced serious adverse events had longer CSR CL, LPCT and TTPF. Future studies should examine an independent role for CSR-related features to enable risk stratification in systolic HF.

Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study.

Recent population-based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general, and incidence in particular, are lacking. We examined trends in NAFLD incidence in a U.S. community and the impact of NAFLD on incident metabolic comorbidities (MCs), cardiovascular (CV) events, and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate were calculated. The impact of NAFLD on incident MCs, CV events, and mortality was studied using a multistate model, with a 4:1 age- and sex-matched general population as a reference. We identified 3,869 NAFLD subjects (median age, 53; 52% women) and 15,209 controls; median follow-up was 7 (1-20) years. NAFLD incidence increased 5-fold, from 62 to 329 in 100,000 person-years. The increase was highest (7-fold) in young adults, aged 18-39 years. The 10-year mortality was higher in NAFLD subjects (10.2%) than controls (7.6%; P < 0.0001). NAFLD was an independent risk factor for incident MCs and death. Mortality risk decreased as the number of incident MCs increased: relative risk (RR) = 2.16 (95% confidence [CI], 1.41-3.31), 1.99 (95% CI, 1.48-2.66), 1.75 (95% CI, 1.42-2.14), and 1.08 (95% CI, 0.89-1.30) when 0, 1, 2, or 3 MCs were present, respectively. The NAFLD impact on CV events was significant only in subjects without MCs (RR = 1.96; 95% CI = 1.35-2.86). NAFLD reduced life expectancy by 4 years, with more time spent in high metabolic burden. CONCLUSION: Incidence of NAFLD diagnosis in the community has increased 5-fold, particularly in young adults. NAFLD is a consequence, but also a precursor of MC. Incident MC attenuates the impact of NAFLD on death and annuls its impact on CV disease. (Hepatology 2018;67:1726-1736).

Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure.

BACKGROUND: Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. METHODS: We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. RESULTS: In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006). CONCLUSIONS: Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.).