Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study.

BACKGROUND: Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA. METHODS: HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea-hypopnoea index (AHI) ≥15 events·h-1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed. RESULTS: 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h-1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min-1 at baseline to 44.6±11.2 bursts·min-1; ASV group: 43.0±9.0 bursts·min-1 at baseline to 42.74±9.45 bursts·min-1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective. CONCLUSIONS: Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

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.

[Effects of Outpatient Compact Rehabilitation on Physical Performance and Quality of Life in Patients with Work-Related Lung Diseases]. / Effekte einer ambulanten Kompaktrehabilitation auf körperliche Leistungsfähigkeit und Lebensqualität bei Patienten mit Berufskrankheiten der Lunge.

In Germany, pulmonary rehabilitation (PR) traditionally takes place in rehabilitation clinics. According to the current German guideline "Diagnostics and assessment of asbestos-related occupational diseases", PR can also be offered as outpatient program with the essential elements of inpatient PR (compact rehabilitation [CR]). Our project investigated the effects of CR regarding acceptance, physical performance, and quality of life of patients with occupational lung diseases. CR included 24 units of 90 minutes each with physiotherapy and breathing therapy as well as device-supported strength and endurance training. The aim of our study was to investigate the effects of CR in subjects with occupational diseases of the respiratory system and a legally anchored right to PR. Randomization was therefore not planned. A total of 148 insured persons with a confirmed occupational disease of the respiratory system were invited to participate by the employers' liability insurance association; 126 patients (85 %) accepted the invitation, and 78 participants (mean age: 71 years) completed the entire program (53 %). Benign asbestos-related diseases (plaques, pleural thickening, asbestosis) dominated with around 80 %. Ailments, depression, and dementia were typical obstacles. No adverse events occurred with strict observance of the chosen inclusion and exclusion criteria and training conditions. The measurement results at enrolment were compared with those at completion of the CR. CR led to a significant (p < 0.01) improvement in all parameters of physical performance: 6-minute walking test: + 36 m, ergometer test: + 9 watts, hand dynamometry: + 29 N, quadriceps strength test: + 84 MKI. The inspiratory capacity of the respiratory muscles (Pimax: + 1.1 kPa) also improved (p < 0.01). The SF-36 showed an improvement in quality of life (p < 0.05) in the subdomains "mental well-being" (+ 3.7) and "physical role function" (+ 4.2). Therefore, CR proves to be a safe therapy if the inclusion and exclusion criteria are adhered to. CR is widely accepted by patients without severe comorbidities and achieves positive effects comparable to those that have been demonstrated in rehabilitation clinics. Outpatient CR is therefore suitable for eliminating the lack of structured and certified rehabilitation and training offers in rehabilitation clinics and for preserving the effects achieved there for insured patients with work-related respiratory and lung diseases.

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.

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.).

Association between the time after transplantation and different immunosuppressive medications with dental and periodontal treatment need in patients after solid organ transplantation.

OBJECTIVE: The aim of this study was to investigate the association of time after transplantation and different immunosuppressive medications with dental and periodontal treatment needs in patients after solid organ transplantation (SOT). METHODS: After lung, liver, or kidney transplantation, patients were included and divided into subgroups based on the time after SOT (0-1, 1-3, 3-6, 6-10, and >10 years) and immunosuppression (tacrolimus, cyclosporine, mycophenolate, glucocorticoids, sirolimus, and monotherapy vs combination). Dental treatment need was determined by the presence of carious lesions, while periodontal treatment need was diagnosed based on a Periodontal Screening index score of 3-4. The overall treatment need included both the dental and/or periodontal treatment needs. Statistical analysis was performed using the Kruskal-Wallis test and chi-squared test (P < .05). RESULTS: A total of 169 patients were included after SOT. A dental treatment need of 44%, a periodontal treatment need of 71%, and an overall treatment need of 84% were detected in the total cohort. Only patients with >10 years after SOT had a lower dental treatment need compared to the other groups (P = .02). All other comparisons of dental, periodontal, and overall treatment needs were comparable between subgroups depending on time since SOT. Furthermore, no statistically significant differences were found in terms of the dental, periodontal, or overall treatment needs following the administration of different immunosuppressive medications. CONCLUSION: The high treatment need of patients after SOT, irrespective of the time since transplantation, suggests insufficient dental and periodontal treatment before and maintenance after organ transplantation. Furthermore, immunosuppressive medication was not associated with the treatment need.

Validation of a non-contact screening device for the combination of sleep-disordered breathing and periodic limb movements in sleep.

PURPOSE: Recent studies found that the non-contact screening device SleepMinder (ResMed Sensor Technologies, Dublin, Ireland) detects sleep-disordered breathing (SDB) with high diagnostic accuracy in cohorts suspected of this disorder. However, it was reported that in patients with periodic limb movement in sleep (PLMS), this non-contact device overestimates the apnea-hypopnea index (AHI). We aimed to overcome this limitation by introducing the novel sleep disorder index (SDI) which is sum of the AHI and the period limb movement index (PLMI). METHODS: Between January 2011 and December 2013, we studied a mixed cohort of 57 patients (31 OSA, 19 PLMS). The easy-to-use non-contact device emits a very weak electromagnetic radiation and detects body movement by measuring the Doppler effect. We interpreted the device-generated movement index as the SDI and validated the diagnostic accuracy against simultaneous application of the gold-standard polysomnography (PSG). RESULTS: We found that the SDI of the non-contact device correlated well with the sum of AHI and PLMI derived from PSG (r = 0.79, p = 0.01). For PSG-derived SDI cutoff ≥ 15/h, we obtained a sensitivity of 92.2% and a specificity of 95.8%. Positive likelihood ratio was 23.3 and negative likelihood ratio 0.03. CONCLUSIONS: The studied non-contact screening device detects accurately the combination of the sleep disorders SDB and/or PLM. However, further testing is required in order to specify the nature of the underlying sleep disorder. At the current stage of algorithm development, the clinical strength is that the studied non-contact device can be used as a rule-out screening device for SDB and PLM.

Predictors of positive airway pressure therapy termination in the first year: analysis of big data from a German homecare provider.

BACKGROUND: There is a lack of robust data about factors predicting continuation (or termination) of positive airway pressure therapy (PAP) for sleep apnea. This analysis of big data from a German homecare provider describes patients treated with PAP, analyzes the therapy termination rate over the first year, and investigates predictive factors for therapy termination. METHODS: Data from a German homecare service provider were analyzed retrospectively. Patients who had started their first PAP therapy between September 2009 and April 2014 were eligible. Patient demographics, therapy start date, and the date of and reason for therapy termination were obtained. At 1 year, patients were classified as having compliance-related therapy termination or remaining on therapy. These groups were compared, and significant predictors of therapy termination determined. RESULTS: Of 98,329 patients included in the analysis, 11,702 (12%) terminated PAP therapy within the first year (after mean 171 ± 91 days). There was a U-shaped relationship between therapy termination and age; therapy termination was higher in the youngest (< 30 years, 15.5%) and oldest (≥ 80 years, 19.8%) patients, and lower in those aged 50-59 years (9.9%). Therapy termination was significantly more likely in females versus males (hazard ratio 1.48, 95% confidence interval 1.42-1.54), in those with public versus private insurance (1.75, 1.64-1.86) and in patients whose first device was automatically adjusting or fixed-level continuous positive airway pressure versus bilevel or adaptive servo-ventilation (1.28, 1.2-1.38). CONCLUSIONS: This analysis of the largest dataset investigating PAP therapy termination identified a number of predictive factors. These can help health care providers chose the most appropriate PAP modality, identify specific patient phenotypes at higher risk of stopping PAP and target interventions to support ongoing therapy to these groups, as well as allow them to develop a risk stratification tool.

Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis.

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial.Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias).The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased.On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies.

Cardiovascular risk in patients with alpha-1-antitrypsin deficiency.

BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a rare inherited condition caused by mutations of the SERPINA1 gene that is associated with the development of a COPD like lung disease. The comorbidities in patients with AATD-related lung diseases are not well defined. The aim of this study was to analyze the clinical phenotype of AATD patients within the German COPD cohort study COSYCONET ("COPD and SYstemic consequences-COmorbidities NETwork") cohort focusing on the distribution of comorbidities. METHOD AND RESULTS: The data from 2645 COSYCONET patients, including 139 AATD patients (110 with and 29 without augmentation therapy), were analyzed by descriptive statistics and regression analyses. We found significantly lower prevalence of cardiovascular comorbidities in AATD patients as compared to non-AATD COPD patients. After correction for age, pack years, body mass index, and sex, the differences were still significant for coronary artery disease (p = 0.002) and the prevalence of peripheral artery disease as determined by an ankle-brachial-index <= 0.9 (p = 0.035). Also the distribution of other comorbidities such as bronchiectasis differed between AATD and non-deficient COPD. CONCLUSION: AATD is associated with a lower prevalence of cardiovascular disease, the underlying mechanisms need further investigation.

Decreased Hypercapnic Ventilatory Response in Long-Term Lung Transplant Recipients is Associated with Exercise Impairment.

PURPOSE: Bilateral lung transplantation results in complete denervation of the lung and might impair hypercapnic ventilatory response (HCVR). However, experimental and clinical findings are scarce and conflicting. Therefore, this study investigated the relationship between HCVR and exercise capacity after long-term bilateral lung transplantation. METHODS: This cross-sectional analysis enrolled 46 bilateral lung transplant recipients between October 2011 and July 2012 who underwent cardiopulmonary exercise testing to evaluate maximum workload, and carbon dioxide (CO2) rebreathing. CO2 rebreathing was also evaluated in 35 control subjects. RESULTS: In lung transplant recipients age was 54 ± 11 years, body mass index (BMI) 25.4 ± 4.1 kg/m(2), and time after transplantation 4.5 ± 2.5 years (range 9 months to 10 years). Controls were aged 41 ± 12 years and had a BMI of 24.9 ± 4.0 kg/m(2). There were significant differences between lung transplant recipients and controls in forced expiratory volume in 1 s (76 ± 22 vs. 94 ± 12 % predicted, p < 0.001) and inspiratory vital capacity (91 ± 20 vs. 105 ± 14 % predicted, p = 0.001). Blood gases did not differ significantly in patients versus controls. HCVR in lung transplant recipients was 1.44 ± 1.07 L/min/mmHg compared with 2.09 ± 1.14 L/min/mmHg in controls (p = 0.001). Exercise capacity in lung transplant recipients (73 ± 24 W) was 49 % predicted. Linear regression analysis showed that exercise capacity was significantly associated with HCVR. A 1 L/min/mmHg decrease in HCVR decreased exercise capacity by 50 W. CONCLUSION: HCVR is reduced in long-term bilateral lung transplant recipients and this might explain the observed impairment of exercise capacity.

Association of short-term ozone and temperature with sleep disordered breathing.

Scarce evidence suggests that ambient air pollution and temperature might play a role in incidence and severity of sleep disordered breathing (SDB). We investigated the association of short-term exposure to fine particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10)), ozone and temperature with SDB in the general population. Between 2006 and 2008, 1773 participants (aged 50-80 years) of the Heinz Nixdorf Recall study underwent screening for SDB, as defined by the apnoea-hypopnoea index (AHI). We assessed daily exposure to PM10, ozone, temperature and humidity. We used multiple linear regression to estimate associations of daily PM10, ozone levels and temperature on the day of screening, adjusting for relative humidity, season, age, sex, body mass index, education, smoking habits, alcohol consumption and physical activity. In the study population, the mean±sd AHI was 11.2±11.4 events·h(-1). Over all seasons, an interquartile range increase in temperature (8.6°C) and ozone (39.5 µg·m(-3)) was associated with a 10.2% (95% CI 1.2-20.0%) and 10.1% (95% CI 2.0-18.9%) increase in AHI, respectively. Associations for temperature were stronger in summer, yielding a 32.4% (95% CI 0.0-75.3%) increase in AHI per 8.6°C (p-value for season-temperature interaction 0.08). We observed that AHI was not associated with PM10. This study suggests that short-term variations in ozone concentration and temperature are associated with SDB.

Determining the prevalence and predictors of sleep disordered breathing in patients with chronic heart failure: rationale and design of the SCHLA-HF registry.

BACKGROUND: The objective of the SCHLA-HF registry is to investigate the prevalence of sleep-disordered breathing (SDB) in patients with chronic heart failure with reduced left ventricular systolic function (HF-REF) and to determine predictors of SDB in such patients. METHODS: Cardiologists in private practices and in hospitals in Germany are asked to document patients with HF-REF into the prospective SCHLA-HF registry if they meet predefined inclusion and exclusion criteria. Screening was started in October 2007 and enrolment was completed at the end of May 2013. After enrolment in the registry, patients are screened for SDB. SDB screening is mainly undertaken using the validated 2-channel ApneaLink™ device (nasal flow and pulse oximetry; ResMed Ltd., Sydney, Australia). Patients with a significant number of apneas and hypopneas per hour recording time (AHI ≥15/h) and/or clinical symptoms suspicious of SDB will be referred to a cooperating sleep clinic for an attended in-lab polysomnography with certified scoring where the definite diagnosis and, if applicable, the differentiation between obstructive and central sleep apnea will be made. Suggested treatment will be documented. DISCUSSION: Registries play an important role in facilitating advances in the understanding and management of cardiovascular disease. The SCHLA-HF registry will provide consistent data on a large group of patients with HF-REF that will help to answer questions on the prevalence, risk factors, gender differences and stability of SDB in these patients by cross-sectional analyses. Further insight into the development of SDB will be gained by extension of the registry to include longitudinal data.

Inhalation treatment with glutathione in patients with cystic fibrosis. A randomized clinical trial.

RATIONALE: Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF). OBJECTIVES: We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease. METHODS: This randomized, double-blind, placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40-90% of predicted. Subjects were randomized to receive 646 mg glutathione in 4 ml (n = 73) or placebo (n = 80) via an investigational eFlow nebulizer every 12 hours for 6 months. MEASUREMENTS AND MAIN RESULTS: FEV1 (absolute values), both as pre-post differences (P = 0.180) and as area under the curves (P = 0.205), were the primary efficacy endpoints, and were not different between the glutathione group and the placebo group over the 6-month treatment period. Exploratory analysis showed an increase of FEV1 from baseline over placebo of 100 ml or 2.2% predicted; this was significant at 3 months, but not later. Subjects receiving glutathione had neither fewer pulmonary exacerbations, nor better scores for quality of life. Whereas increased glutathione and metabolites in sputum demonstrated significant delivery to the lungs, there was no indication of diminished oxidative stress to proteins or lipids, and no evidence for anti-inflammatory or antiproteolytic actions of glutathione supplemented to the airways. The adverse event incidence was similar between glutathione and placebo. CONCLUSIONS: Inhaled glutathione in the dose administered did not demonstrate clinically relevant improvements in lung function, pulmonary exacerbation frequency, or patient-reported outcomes. Glutathione delivery to the airways was not associated with changes in markers of oxidation, proteolysis, or inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT00506688) and https://eudract.ema.europa.eu/index.html (EudraCT 2005-003870-88).

The effects of controlled breathing during pulmonary rehabilitation in patients with COPD.

BACKGROUND: Conventional pulmonary rehabilitation programs improve exercise tolerance but have no effect on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The role of controlled breathing using respiratory biofeedback during rehabilitation of patients with COPD remains unclear. OBJECTIVES: To compare the effects of a conventional 4-week pulmonary rehabilitation program with those of rehabilitation plus controlled breathing interventions. METHODS: A randomized controlled trial was performed. Pulmonary function (FEV1), exercise capacity (6-min walking distance, 6 MWD), health-related quality of life (chronic respiratory questionnaire, CRQ) and cardiac autonomic function (rMSSD) were evaluated. RESULTS: Forty COPD patients (mean±SD age 66.1±6.4, FEV1 45.9±17.4% predicted) were randomized to rehabilitation (n=20) or rehabilitation plus controlled breathing (n=20). There were no statistically significant differences between the two groups regarding the change in FEV1 (mean difference -0.8% predicted, 95% CI -4.4 to 2.9% predicted, p=0.33), 6 MWD (mean difference 12.2 m, 95% CI -37.4 to 12.2 m, p=0.16), CRQ (mean difference in total score 0.2, 95% CI -0.1 to 0.4, p=0.11) and rMSSD (mean difference 2.2 ms, 95% CI -20.8 to 25.1 ms, p=0.51). CONCLUSIONS: In patients with COPD undergoing a pulmonary rehabilitation program, controlled breathing using respiratory biofeedback has no effect on exercise capacity, pulmonary function, quality of life or cardiac autonomic function.

Cardiac autonomic function and cardiovascular response to exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. OBJECTIVE: To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. METHODS: Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. RESULTS: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV(1) %predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV(1) and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV(1) were independent predictors of exercise capacity in patients with COPD. CONCLUSIONS: In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.

Prevalence and predictors of sleep-disordered breathing in chronic heart failure: the SchlaHF-XT registry.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing prevalence. Sleep-disordered breathing (SDB) is an important co-morbidity in HFpEF. The SchlaHF-XT registry evaluated the sex-specific prevalence and predictors of SDB, including obstructive (OSA) and central sleep apnoea, in patients with HFpEF compared with heart failure with mildly reduced (HFmrEF) or reduced (HFrEF) ejection fraction. METHODS AND RESULTS: Consecutive adults with chronic heart failure treated according to current guidelines were enrolled. The presence of moderate-to-severe SDB (apnoea-hypopnoea index ≥15/h) was determined using Type 3 polygraphic devices. Of 3289 patients included, 2032 had HFpEF, 559 had HFmrEF, and 698 had HFrEF, of whom 34, 21, 23, and 42%, respectively, were female. Prevalence of SDB in HFpEF was high, but significantly lower than in HFmrEF or HFrEF (36% vs. 41 and 48%, respectively). Rates of SDB in males and females were 41 and 28% in HFpEF, 44 and 30% in HFmrEF, and 50 and 40% in HFrEF. The proportion of males and females with SDB who had OSA was significantly greater in those with HFpEF vs. HFrEF. Male sex, older age, higher body mass index, and New York Heart Association functional Class III/IV were significant predictors of moderate-to-severe SDB in HFpEF patients. CONCLUSIONS: Prevalence of SDB in HFpEF was high, but lower than in patients with HFmrEF or HFrEF. Moderate-to-severe SDB occurred more frequently in males than in females across the whole spectrum of heart failure. In both sexes, the proportion of OSA in SDB patients with HFpEF was higher than in those with HFrEF.

Effects of Adaptive Servo-Ventilation on Nocturnal Ventricular Arrhythmia in Heart Failure Patients With Reduced Ejection Fraction and Central Sleep Apnea-An Analysis From the SERVE-HF Major Substudy.

Background: The SERVE-HF trial investigated the effect of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with heart failure with reduced ejection fraction (HFrEF). Objective: The aim of the present ancillary analysis of the SERVE-HF major substudy (NCT01164592) was to assess the effects of ASV on the burden of nocturnal ventricular arrhythmias as one possible mechanism for sudden cardiac death in ASV-treated patients with HFrEF and CSA. Methods: Three hundred twelve patients were randomized in the SERVE-HF major substudy [no treatment of CSA (control) vs. ASV]. Polysomnography including nocturnal ECG fulfilling technical requirements was performed at baseline, and at 3 and 12 months. Premature ventricular complexes (events/h of total recording time) and non-sustained ventricular tachycardia were assessed. Linear mixed models and generalized linear mixed models were used to analyse differences between the control and ASV groups, and changes over time. Results: From baseline to 3- and 12-month follow-up, respectively, the number of premature ventricular complexes (control: median 19.7, 19.0 and 19.0; ASV: 29.1, 29.0 and 26.0 events/h; p = 0.800) and the occurrence of ≥1 non-sustained ventricular tachycardia/night (control: 18, 25, and 18% of patients; ASV: 24, 16, and 24% of patients; p = 0.095) were similar in the control and ASV groups. Conclusion: Addition of ASV to guideline-based medical management had no significant effect on nocturnal ventricular ectopy or tachyarrhythmia over a period of 12 months in alive patients with HFrEF and CSA. Findings do not further support the hypothesis that ASV may lead to sudden cardiac death by triggering ventricular tachyarrhythmia.