Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF.

AIMS: Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodeling and atrial fibrillation is frequently observed in HFpEF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial antiarrhythmic effects. We tested if isolated human atrial cardiomyocytes from patients with HFpEF exhibit an increased Na influx, which is known to cause atrial arrhythmias, and if that is responsive to treatment with the SGTL2i empagliflozin. METHODS AND RESULTS: Cardiomyocytes were isolated from atrial biopsies of 124 patients (82 with HFpEF) undergoing elective cardiac surgery. Na influx was measured with the Na-dye Asante Natrium Green-2 AM (ANG-2). Compared to patients without heart failure (NF), Na influx was doubled in HFpEF patients (NF vs HFpEF: 0.21±0.02 vs 0.38±0.04 mmol/L/min (N=7 vs 18); p=0.0078). Moreover, late INa (measured via whole-cell patch clamp) was significantly increased in HFpEF compared to NF. Western blot and HDAC4 pulldown assay indicated a significant increase in CaMKII expression, CaMKII autophosphorylation, CaMKII activity, and CaMKII-dependent NaV1.5 phosphorylation in HFpEF compared to NF, whereas NaV1.5 protein and mRNA abundance remained unchanged. Consistently, increased Na influx was significantly reduced by treatment with the CaMKII inhibitor autocamtide-2 related inhibitory peptide (AIP), late INa inhibitor tetrodotoxin (TTX) but also with NHE1 inhibitor cariporide. Importantly, empagliflozin abolished both increased Na influx and late INa in HFpEF. Multivariate linear regression analysis, adjusting for important clinical confounders, revealed HFpEF to be an independent predictor for changes in Na handling in atrial cardiomyocytes. CONCLUSION: We show for the first time increased Na influx in human atrial cardiomyocytes from HFpEF patients, partly due to increased late INa and enhanced NHE1-mediated Na influx. Empagliflozin inhibits Na influx and late INa, which could contribute to antiarrhythmic effects in patients with HFpEF.

Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease.

INTRODUCTION: Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. METHODS: Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. RESULTS: 48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. CONCLUSION: Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.

[Guideline for Long-Term Oxygen Therapy - S2k-Guideline Published by the German Respiratory Society]. / Leitlinie zur Langzeit-Sauerstofftherapie.

Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.

Sleep-Disordered Breathing Is Associated with Metabolic Syndrome in Outpatients with Diabetes Mellitus Type 2.

BACKGROUND: Metabolic syndrome (MS) and sleep-disordered breathing (SDB) are highly prevalent in patients with diabetes mellitus type 2 (DM2). The present study examined whether there is an independent association between SDB and MS in a sample of outpatients with DM2. METHODS: MS was determined in 679 patients of the DIACORE-SDB substudy, a study of outpatients with DM2. According to the National Cholesterol Education Program (NCEP) criteria, MS is defined by at least three of the following five criteria: waist circumference of >102 cm (men)/>88 cm (women), blood pressure of ≥130/85 mmHg, a fasting triglyceride level of >150 mg/dl, high-density lipoprotein (HDL) of <40 mg/dl (men)/<50 mg/dl (women), and a fasting glucose level of ≥110 mg/dl. The apnea-hypopnea index (AHI) was assessed with a 2-channel ambulatory monitoring device and used to define the severity of SDB (AHI < 15.0: no/mild SDB; AHI 15.0-29.9: moderate SDB; AHI ≥ 30.0: severe SDB). RESULTS: 228 (34%) of the 679 participants (mean age 66 years, mean body mass index (BMI) 31.2 kg/m2, and mean AHI 14/hour) had SDB. MS was significantly more frequent in patients with more severe SDB (no/mild SDB vs. moderate SDB vs. severe SDB: 72% vs. 79% vs. 85%, respectively, p = 0.038). Logistic regression analysis adjusted for sex, age, obesity (BMI ≥ 30 kg/m2), and the HOMA index showed a significant association between the AHI and the presence of MS (OR (95%CI) = 1.039 (1.011; 1.068); p = 0.007). Further, male sex, obesity, and the HOMA index were significantly associated with MS. CONCLUSION: SDB is significantly and independently associated with MS in outpatients with DM2.

Sex Differences in the Prevalence and Modulators of Sleep-Disordered Breathing in Outpatients with Type 2 Diabetes.

In patients with type 2 diabetes, sleep-disordered breathing is a widespread cause of deteriorated quality of life. However, robust prevalence estimates for sleep-disordered breathing in patients with type 2 diabetes are limited due to scarce data. We investigated sex differences in sleep-disordered breathing prevalence and its modulators in the DIACORE SDB substudy, a sample of outpatient type 2 diabetes. 721 participants were tested for sleep-disordered breathing using a two-channel sleep apnoea monitoring device. Patients were stratified according to the severity of sleep-disordered breathing, defined as an apnoea-hypopnoea index < 15, ≥15 to 29, and ≥30 events per hour as no/mild, moderate, and severe sleep-disordered breathing, respectively. In the 679 analysed patients (39% women, age 66 ± 9 years, body mass index 31.0 ± 5.4 kg/m2), the prevalence of sleep-disordered breathing was 34%. The prevalence of sleep-disordered breathing was higher in men than in women (41% versus 22%, p < 0.001) and increased with age (15%, 21%, and 30% in women and 35%, 40%, and 47% in men in those aged 18-59, 60-69, or ≥70, respectively; age trend p = 0.064 in women and p = 0.15 in men). In linear regression analysis, age, BMI, and waist-hip ratio were associated with apnoea-hypopnoea index. Modulators for higher apnoea-hypopnoea index seem to be similar in men and women.

[Comorbidities of heart failure: sleep apnea]. / Schlafapnoe als Komorbidität bei Herzinsuffizienz.

BACKGROUND: Since sleep apnea often occurs in heart failure, physicians regularly need to decide whether further diagnostic procedures and/or treatment are required. OBJECTIVES: Which types of sleep apnea occur in heart failure patients? When is treatment needed? Which treatments and treatment goals are appropriate? MATERIALS AND METHODS: Clinical trials and guidelines as well as their implementation in clinical practice are discussed. RESULTS: At least 40% of patients with heart failure, both with reduced and preserved left ventricular ejection fraction (HFrEF and HFpEF, respectively), suffer from relevant sleep apnea. In heart failure patients both obstructive and central sleep apnea are associated with increased mortality. In HFrEF as well as in HFpEF patients with obstructive sleep apnea, treatment with continuous positive airway pressure (CPAP) achieves symptomatic and functional improvements. In patients with HFpEF, positive airway pressure treatment of central sleep apnea may be beneficial. In patients with HFrEF and left ventricular ejection fraction ≤45%, adaptive servoventilation is contraindicated. CONCLUSIONS: Sleep apnea is highly prevalent in heart failure patients and its treatment in specific patient groups can improve symptoms and functional outcomes. Thus, testing for sleep apnea is recommended.

Whom are we treating with adaptive servo-ventilation? A clinical post hoc analysis.

BACKGROUND: Recent evidence has shown that adaptive servo-ventilation (ASV) is contraindicated in patients with predominant central sleep apnea (CSA) and reduced left ventricular ejection fraction (LVEF ≤45%). The objective of this study was to assess the clinical usage of ASV in patients at the time-point of the release of a safety warning by type of SDB, breathing pattern and LVEF. METHODS: Patients of a cardiac and a respirology sleep center, both in Germany, who received ASV therapy were contacted between May and October 2015. Retrospective analyses included diagnostic polysomnography, polysomnography with continuous positive airway pressure prior to ASV initiation and echocardiography. Treatment emergent CSA was diagnosed after an appropriate treatment period on CPAP. RESULTS: 285 patients receiving ASV therapy (91 in the cardiac and 194 in the respirology setting) underwent diagnostic polysomnography. 233 (82%) patients had severe SDB, 94 (33%) predominant CSA, and 185 (65%) periodic breathing. 20% (n = 52) of patients had an LVEF of ≤45%. The most common indications for ASV were CSA in heart failure (41%) in the cardiac setting and treatment emergent CSA (80%) diagnosed after an appropriate period on CPAP in the respirology setting. The proportion of patients in whom ASV was contraindicated (CSA and LVEF ≤45%) was 16% in the cardiac setting and 9% in the respirology setting. CONCLUSION: Clinical usage of ASV changed for a small subgroup of patients after release of the SERVE-HF results. Nevertheless, ASV treatment should be monitored and evaluated with diligence in the reminder indications.

[Consensus paper on the diagnosis and treatment of sleep disordered breathing]. / Konsensuspapier zur Diagnostik und Therapie schlafbezogener Atmungsstörungen bei Erwachsenen.

Diagnosis and treatment of sleep disordered breathing (SDB) undergo substantial changes, both in terms of increasing scientific knowledge and also in terms of patient provision and socio-economic aspects. Increasing evidence shows the relevance of SDB on morbidity and mortality of affected patients. The precise differentiation of different phenotypes of SDBs has improved substantially in recent years. These proceedings influence the approach to the patients suspected of suffering from SDB. The scientific advances on the one hand are facing intentions to simplify diagnostical processes and treatment initiation and intentions to translate duties of physicians to non-medical personnel on the other hand. This consensus paper presents the principals of diagnosis, treatment initiation and provision, including the role of different participants of the healthcare system, and compares different treatment options. Major aspects include the differentiation of the diagnostical process in screening, affirmation of diagnosis and differential diagnosis. In addition, it focusses on the relevance of the pretest probability and describes a therapeutical algorithm.

[COPD and heart disease]. / COPD und Herzerkrankung.

Cardiovascular diseases are highly prevalent in patients with chronic obstructive pulmonary disease (COPD). Approximately one out of three patients with COPD dies of cardiovascular disease. Overlap syndrome (COPD and obstructive sleep apnea), pulmonary hypertension and lung hyperinflation have a further impact on cardiovascular function in patients with COPD.

Six-minute walk distance target in elderly patients with idiopathic pulmonary arterial hypertension - consideration of predicted values.

BACKGROUND: The number of elderly patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) is increasing. A 6-min walk distance (6MWD) > 380 m on therapy is associated with improved survival in IPAH. As exercise capacity is naturally decreasing with age, treatment goals for elderly patients might be different from those established for younger patients. METHODS: Consecutive adult patients diagnosed with IPAH between 1/2005 and 7/2012 were retrospectively included. We analysed the prognostic value of 6MWD targets (in metres and % predicted) with respect to age at diagnosis. RESULTS: The mean (± SD) 6MWD in 23 patients aged > 65 years at diagnosis compared with 22 younger patients was significantly lower at baseline (262 ± 69 vs. 356 ± 128 m; p = 0.011) and first follow up (310 ± 75 vs. 377 ± 137 m; p = 0.045), while the corresponding % predicted values were similar (62 ± 16% vs. 63 ± 21%; p = 0.854, and 74 ± 16% vs. 68 ± 21%; p = 0.267). The established treatment target of > 380 m 6MWD was met by only 13% of elderly compared with 46% of younger patients (p = 0.016), while the corresponding 6MWD of 78% predicted was exceeded by similar proportions (48% and 46%, respectively; p = 0.873). Survival of patients walking > 380 m or 78% predicted on first follow up was significantly better compared with patients not exceeding the respective threshold (100% vs. 72% and 95% vs. 67% at the end of follow up, respectively; p < 0.05 each). CONCLUSION: Expression of the 6MWD target as % predicted equalises age-related differences and has similar prognostic power compared with absolute values in patients with IPAH. As elderly patients are less likely to reach the absolute 6MWD threshold, the use of % predicted could be helpful in their individual assessment and adaption of targeted therapy.

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin-treated rats.

AIM: Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo. METHODS: Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests. RESULTS: Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups. CONCLUSIONS: Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

[Sleep-disordered breathing in patients with chronic heart failure: epiphenomenon or bidirectional relationship]. / Schlafbezogene Atmungsstörungen bei Patienten mit Herzinsuffizienz: Epiphänomen oder wechselseitige Krankheitsbeeinflussung.

Sleep-disordered breathing (SDB) constitutes a highly prevalent comorbidity in patients with chronic heart failure (HF, approximately 45%). Both diseases are related in a bidirectional way: Obstructive sleep apnoea (OSA) can contribute to the development of HF via multiple mechanisms. Apnoea-related acute rise of cardiac afterload as well as manifest hypertension may contribute to the development of myocardial hypertrophy and thus HF. In addition, OSA increases the risk for myocardial infarction and impaired recovery of cardiac function after the event. Impaired cardiac function itself may contribute to the development of obstructive and central sleep apnoea (SA). Therefore, optimal medical management of HF is part of the therapy of SDB in such patients. Treatment of SDB with different modes of positive airway pressure suppresses apnoeas and hypopnoeas, improves sleep and may improve related symptoms and cardiac function of affected patients. Considering the high coincidence of SDB and HF, the adequate diagnosis of SDB and evaluation of indication for therapy of SDB performed in a specialised centre is advised.

Qualitative echocardiography parameters for prediction of pulmonary hypertension.

BACKGROUND: Current guidelines recommend echocardiography as the preferred screening method for pulmonary hypertension (PH). The probability of PH is primarily assessed by estimating the right ventricular systolic pressure while the value of qualitative parameters is uncertain. The aim of our study was to evaluate the diagnostic yield of qualitative and quantitative parameters from routine echocardiography reports for PH diagnosis. METHODS: Consecutive patients with suspected PH who received right heart catheterisation and echocardiography within 2 weeks between April 2003 and September 2008 were retrospectively included. PH was diagnosed by a mean pulmonary artery pressure of ≥ 25 mmHg on right heart catheterisation. Qualitative and quantitative parameters from echocardiography reports were analysed with respect to their predictive value for PH diagnosis. RESULTS: Inclusion criteria were met by 272 patients. Diagnosis of PH was confirmed in 172 and excluded in 100 patients. Qualitative and quantitative information about the right ventricle was available in 93% and 85% of the echocardiography reports respectively. Qualitative descriptions of the right ventricle to be dilated predicted PH with sensitivity, specificity, negative and positive predictive value of 89%, 63%, 78% and 80% respectively. An estimated right ventricular systolic pressure of ≥ 50 mmHg on echocardiography predicted PH with sensitivity, specificity, negative and positive predictive value of 84%, 69%, 68% and 84% respectively. CONCLUSION: Qualitative parameters are frequently described in routine echocardiography reports and are valuable for the prediction of PH with a similar diagnostic accuracy as the estimation of right ventricular systolic pressure.

Endobronchial ultrasound-guided transbronchial needle aspiration in routine care - plenty of benign results and follow-up tests.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widespread technique for tissue sampling from hilar and mediastinal lymph nodes (LN). The diagnostic yield of this method is reported to be very high even outside clinical trials. We aimed to assess the diagnostic accuracy of EBUS-TBNA after its implementation at a University hospital. METHODS: We analysed the first 100 consecutive patients who underwent an EBUS-TBNA procedure at our institution with respect to indication and cytological results. Sensitivity and negative predictive value (NPV) were calculated on the basis of histological confirmation or follow-up. RESULTS: From 03/2007 to 03/2008, EBUS-TBNA of 218 LNs was performed on the basis of chest computed tomography. The primary indication for EBUS-TBNA was lymphadenopathy of unknown cause with (44%) or without (37%) pulmonary nodule(s). Only 19% of patients had known cancer and underwent the procedure for (re-)staging. In 73% of patients a non-diagnostic cytology was reported. A diagnosis could be established in only 27% by EBUS-TBNA including four patients with sarcoidosis. Sensitivity and NPV were low with 61.4% and 76.7%, respectively. Diagnostic yield increased over time and was better in cancer patients than in patients with incidental lymphadenopathy. CONCLUSION: Although EBUS-TBNA is reported to have a very high diagnostic yield in selected patients, the predominant finding in routine care, depending on the patient population, can be a non-diagnostic cytology result with the need for surgical procedures or follow-up studies. This should be considered in the approach to patients with mediastinal or hilar lymphadenopathy.

Polysomnography underestimates altered cardiac autonomic control in patients with obstructive sleep apnea.

BACKGROUND: Repetitive nocturnal sympathetic activation during episodes of apnea and postapneic hyperventilation increases cardiovascular risk. The effects of hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea on sympathico-vagal balance have not been assessed yet. HYPOTHESIS: Hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea cause increased sympathetic activity when compared to normal respiration in nonREM stages 2­4. METHODS: A total of 34 patients were studied using in-laboratory polysomnography including continuous ECG recording. Absolute spectral power of heart rate variability in the very low (VLF), low (LF), and high frequency (HF) bands and low frequency to high frequency power ratio (LF/HF ratio) were analyzed during apnea, hypopnea, and during the pre- and post-phases of such respiratory episodes and compared to spectral powers during normal respiration in nonREM sleep 2­4. RESULTS: Patients with hypopnea and/or obstructive apnea showed higher power of VLF and the LF/HF ratio in intervals of hypopnea/apnea and in non-apneic, non-hypopneic intervals before and after hypopnea/apnea compared to normal respiration in nonREM stages 2­4. CONCLUSION: The effect of sleep-disordered breathing on alteration of autonomic tone in patients with hypopnea and obstructive apnea is more severe than estimated by conventional polysomnographic assessment of apnea and hypopnea. Patients with sleep apnea show a sympathetic overdrive not only during phases of hypopnea and obstructive apnea but also in non-apnea, non-hypopnea intervals before and after hypopnea, and obstructive apnea.

Housekeeping health care workers have the highest risk for tuberculin skin test conversion.

BACKGROUND: Not all health care workers (HCWs) are at the same risk for tuberculin skin test (TST) conversion, indicating latent tuberculosis (TB) infection. OBJECTIVE: To identify risk factors for TST conversion among HCWs. METHODS: A retrospective cohort study conducted at a tertiary university medical centre included every HCW who had had a negative two-step TST at work entry and at least one consecutive TST in the period 2005-2009 (mean follow-up period 55 months). Binomic logistic regression analysis was used to identify risk factors for TST conversion. Potential risk factors such as age, health care profession, patient exposure profile, workplace division and history of bacille Calmette-Guérin vaccination were entered in the model. RESULTS: A total of 450 subjects met the inclusion criteria, of whom 93 had TST conversion. The highest annual rates of TST conversion occurred in workers who worked as housekeeping staff (6.9%). Older age, a work environment with high patient turnover and employment in maintenance departments were significant risk factors (adjusted odds ratios 2.05, 5.2 and 8.4 respectively). CONCLUSION: Housekeeping staff, older age workers and health care professionals working in an environment of high patient turnover are at increased risk for latent TB infection.

[Influence of adaptive servoventilation on B-type natriuretic petide in patients with Cheyne-Stokes respiration and mild to moderate systolic and diastolic heart failure]. / Einfluss der Adaptiven Servoventilation auf das BNP bei Patienten mit Cheyne-Stokes-Atmung und leicht- bis mittelgradiger systolischer und diastolischer Herzinsuffizienz.

BACKGROUND: CPAP therapy has a variable effect on central sleep apnea with Cheyne-Stokes respiration (CSA-CSR). Adaptive servoventilation (ASV) is more effective in normalising breathing in patients with heart failure. We hypothesised that, by normalising AHI, ASV reduces elevated BNP levels in patients with mild systolic and diastolic heart failure. METHODS: From April 2004 to October 2006, patients with CSA-CSR with and without concomitant obstructive sleep apnea (OSA), clinical evidence of heart failure, regardless EF, and elevated BNP levels (> 100 pg/mL) were selected for treatment with ASV, unless CPAP therapy had reduced AHI to < 15 per hour of sleep. Follow-up polysomnographies and BNP analyses were performed after 6 weeks. RESULTS: 15-male patients (AHI 48.3 +/- 14.6/h) fulfilled all inclusion criteria; 7 patients had CSA-CSR + OSA, 8 had CSA-CSR. After 6 weeks of ASV, BNP decreased from 415 +/- 196 pg/mL to 264 +/- 146 pg/mL (p = 0.0009). There was only a significant BNP reduction in the CSA-CSR+OSA subgroup (p = 0.0002). CONCLUSION: ASV can normalise AHI in patients with mild systolic and diastolic heart failure and CSA-CSR +/- OSA, thus leading to a significant reduction of BNP levels. These findings suggest that effective suppression of sleep apnoea in such heart failure patients improves cardiac function.

Shift in sleep apnoea type in heart failure patients in the CANPAP trial.

In patients with heart failure (HF), the predominant type of sleep apnoea can change over time in association with alterations in circulation time. The aim of this study was to determine whether, in some patients with HF, a spontaneous shift from mainly central (>50% central events) to mainly obstructive (>50% obstructive events) sleep apnoea (CSA and OSA, respectively) over time coincides with improvement in left ventricular ejection fraction (LVEF). Therefore, sleep studies and LVEFs of HF patients with CSA from the control arm of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure (CANPAP) trial were examined to determine whether some converted to mainly OSA and, if so, whether this was associated with an increase in LVEF. Of 98 patients with follow-up sleep studies and LVEFs, 18 converted spontaneously to predominantly OSA. Compared with those in the nonconversion group, those in the conversion group had a significantly greater increase in the LVEF (2.8% versus -0.07%) and a significantly greater fall in the lung-to-ear circulation time (-7.6 s versus 0.6 s). In patients with HF, spontaneous conversion from predominantly CSA to OSA is associated with an improvement in left ventricular systolic function. Future studies will be necessary to further examine this relationship.