Cheyne-stokes respiration in children with heart failure.

Cheyne-Stokes respiration (CSA-CSR) is a form of central sleep apnea characterized by alternating periods of hyperventilation and central apneas or hypopneas. CSA-CSR develops following a cardiac insult resulting in a compensatory increase in sympathetic activity, which in susceptible patients causes hyperventilation and destabilizes respiratory control. The physiological changes that occur in CSA-CSR include hyperventilation, a reduced blood gas buffering capacity, and circulatory delay. In adults, 25% to 50% of patients with heart failure are reported to have CSA-CSR. The development of CSA-CSR in this group of patients is considered a poor prognostic sign. The prevalence, progression, and treatment outcomes of CSA-CSR in children remain unclear with only 11 children being described in the literature. The lack of data is possibly not due to the paucity of children with severe heart failure and CSA-CSR but because they may be under-recognized, compounded by the absence of routine polysomnographic assessment of children with moderate to severe heart failure. Building on much broader experience in the diagnosis and management of CSA-CSR in adult sleep medicine and our limited experience in a pediatric quaternary center, this paper will discuss the prevalence of CSA-CSR, its' treatment options, outcomes in children, and the potential future direction for research in this understudied area of pediatric sleep medicine.

CPAP telemonitoring can track Cheyne-Stokes respiration and detect serious cardiac events: The AlertApnée Study.

BACKGROUND AND OBJECTIVE: Case reports have suggested that continuous positive airway pressure (CPAP) telemonitoring can detect the onset of acute cardiac events such as decompensated heart failure (HF) or atrial fibrillation through an increase in the apnoea-hypopnoea index (AHI) and onset of Cheyne-Stokes Respiration (CSR). This study addressed whether long-term remote CPAP treatment telemonitoring revealing CSR can help detect serious cardiac events (SCEs) in obstructive sleep apnoea (OSA) patients. METHODS: This monocentric prospective cohort study included adults receiving CPAP therapy for OSA with daily telemonitoring. Any sudden increase in AHI generated an alert for the home healthcare provider to download CPAP data to identify CSR. A medical consultation was scheduled if CSR was detected. RESULTS: We included 555 adults (412 men; 57% with known cardiovascular comorbidities). During the 1-year follow-up, 78 CSR episodes were detected in 74 patients (CSR+). The main conditions associated with incident CSR were HF (24 patients [30.8%]), ventilatory instability (21, 26.9%), leaks (13, 16.7%), medications inducing central apnoeas (baclofen, ticagrelor, opioids) (7, 9.0%), arrhythmias (6, 7.7%) and renal failure (2, 2.6%). Fifteen (20.3%) CSR+ patients had a confirmed SCE. In univariable analysis, a CSR episode increased the risk of an SCE by 13.8-fold (5.7-35.6) (p < 0.0001), with an adjusted OR of 5.7 (2.0-16.8) in multivariable analysis. CONCLUSION: Long-term telemonitoring of patients on CPAP treatment can alert CSR episodes and allows early detection of SCEs in patients with or without known cardiac comorbidities.

Treatment of Cheyne-Stokes Respiration in Heart Failure with Adaptive Servo-Ventilation: An Integrative Model.

The SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) multicenter trial found a small but significant increase in all-cause and cardiovascular mortality in patients assigned to adaptive servo-ventilation (ASV) versus guideline-based medical treatment. To better understand the physiological underpinnings of this clinical outcome, we employ an integrative computer model to simulate congestive heart failure with Cheyne-Stokes respiration (CHF-CSR) in subjects with a broad spectrum of underlying pathogenetic mechanisms, as well as to determine the in silico changes in cardiopulmonary and autonomic physiology resulting from ASV. Our simulation results demonstrate that while the elimination of CSR through ASV can partially restore cardiorespiratory and autonomic physiology toward normality in the vast majority of CHF phenotypes, the degree of restoration can be highly variable, depending on the combination of CHF mechanisms in play. The group with the lowest left ventricular ejection fraction (LVEF) appears to be most vulnerable to the potentially adverse effects of ASV, but the level of pulmonary capillary wedge pressure (PCWP) plays an important role in determining the nature of these effects.

Sleep Outcomes From AWAKE-HF: A Randomized Clinical Trial of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Heart failure and sleep-disordered breathing have been increasingly recognized as co-occurring conditions. Their bidirectional relationship warrants investigation into whether heart failure therapy improves sleep and sleep-disordered breathing. We sought to explore the effect of treatment with sacubitril/valsartan on sleep-related endpoints from the AWAKE-HF study. METHODS AND RESULTS: AWAKE-HF was a randomized, double-blind study conducted in 23 centers in the United States. Study participants with heart failure with reduced rejection fraction and New York Heart Association class II or III symptoms were randomly assigned to receive treatment with either sacubitril/valsartan or enalapril. All endpoints were assessed at baseline and after 8 weeks of treatment. Portable sleep-monitoring equipment was used to measure the apnea-hypopnea index, including obstructive and central events. Total sleep time, wake after sleep onset and sleep efficiency were exploratory measures assessed using wrist actigraphy. THE RESULTS WERE AS FOLLOWS: 140 patients received treatment in the double-blind phase (sacubitril/valsartan, n = 70; enalapril, n = 70). At baseline, 39% and 40% of patients randomly assigned to receive sacubitril/valsartan or enalapril, respectively, presented with undiagnosed, untreated, moderate-to-severe sleep-disordered breathing (≥ 15 events/h), and nearly all had obstructive sleep apnea. After 8 weeks of treatment, the mean 4% apnea-hypopnea index changed minimally from 16.3/h to 15.2/h in the sacubitril/valsartan group and from 16.8/h to 17.6/h in the enalapril group. Mean total sleep time was long at baseline and decreased only slightly in both treatment groups at week 8 (-14 and -11 minutes for sacubitril/valsartan and enalapril, respectively), with small changes in wake after sleep onset and sleep efficiency in both groups. CONCLUSIONS: In a cohort of patients with heart failure with reduced rejection fraction who met prescribing guidelines for sacubitril/valsartan, one-third had undiagnosed moderate-to-severe obstructive sleep apnea. The addition of sacubitril/valsartan therapy did not significantly improve sleep-disordered breathing or sleep duration or efficiency. Patients who meet indications for treatment with sacubitril/valsartan should be evaluated for sleep-disordered breathing.

Adaptive servo-ventilation in patients with chronic heart failure and sleep disordered breathing: predictors of usage.

PURPOSE: Adaptive servo-ventilation (ASV) is a therapy designed for patients with central sleep apnea (CSA) and Cheyne Stokes respiration. The aim of this study was to find predictors of ASV usage in patients with CSA in a routine sleep clinic cohort. METHODS: In this retrospective study, consecutive patients in whom ASV therapy was initiated at the University Hospital Regensburg between 2011 and 2015, were analyzed. Analysis included polysomnographies of diagnostic and ASV initiation nights, a phone questionnaire on ASV usage, readout of the ASV device 1 month after initiation ("early ASV usage," 1 month after ASV initiation), and the readout of the last month before a reappointment date set in 2015 ("late ASV usage," median 17 months after ASV initiation). RESULTS: In 69 consecutive patients, the mean early and late ASV usage per night was 4.8 ± 2.5 h and 4.1 ± 3.0 h, respectively. Seventeen months after initiation, 57% of patients used the device ≥ 4 h per night, and of those 91% reported a subjective benefit from ASV therapy. Early ASV usage was significantly associated with late ASV usage (univariable regression: Beta 0.8, 95%CI [0.6; 1.0] p < 0.001). In multivariable regression analysis, short duration of slow wave sleep (N3) during diagnostic polysomnography (Beta - 6.2, 95%CI [- 11.0; - 1.5]; p = 0.011) and subjective benefit from ASV (Beta 174.0, 95%CI [68.6; 279.5]; p = 0.002) were significantly associated with longer late ASV usage. CONCLUSION: Early ASV usage predicts late ASV usage. In addition, low slow wave sleep before ASV initiation and subjective benefit from ASV may contribute to higher late ASV usage.

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.

Ventilation Parameters under Adaptive Servo Ventilation: A Comparison on Behalf of CSA-Pattern, BNP/NT-pro-BNP, and Ejection Fraction.

BACKGROUND: The SERVE-HF study has raised questions concerning the higher mortality under adaptive servoventilation. The ventilatory mode was discussed as a possible aggravating factor. OBJECTIVES: We wondered if the data recorded by the adaptive servo-ventilation (ASV)-devices in heart failure patients with CSA-CSR ± OSA are different in terms of respiratory parameters and therapeutic pressures compared to patients with CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP. METHODS: Patients were included, if ASV had normalized respiratory disturbance index in the first night of application and after at least 6 weeks. ASV-device data were analyzed in terms of respiratory rate (RR), min ventilation (MV), endexpiratory (EEP), peak inspiratory pressure (Ppeak) and median pressure. RESULTS: Compared to CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP (n = 25), CSA-CSR- (n = 13) CSA-CSR+OSA-patients (n = 32) with elevated BNP/NT-pro-BNP had higher RR (p < 0.01) in the first night of ASV therapy and during follow-up (15.3 ± 1.3 vs. 17.3 ± 2.4/min) with similar MV (6.5 ± 1.3 vs. 6.6 ± 1.3 L), resulting in significantly lower tidal volumes. EEP (5.6 ± 1.1 vs. 5.5 ± 1.1 hPa), Pmedian and Ppeak (9.8 ± 1.5 vs. 9.7 ± 1.2 hPa) were comparable. Ventilatory parameters were not different between LVEF < 40, 40-49, and ≥50%, neither within the whole group nor the group of CSA-CSR ± OSA and heart failure. CONCLUSION: Patients with heart failure and CSA-CSR ± OSA have higher RRs but similar MV under ASV-therapy than patients with CSA and normal BNP. This indicates higher dead space ventilation. EF was not found to have an influence on the ventilatory parameters.

Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure.

RATIONALE: In patients with chronic heart failure, daytime oscillatory breathing at rest is associated with a high risk of mortality. Experimental evidence, including exaggerated ventilatory responses to CO2 and prolonged circulation time, implicates the ventilatory control system and suggests feedback instability (loop gain > 1) is responsible. However, daytime oscillatory patterns often appear remarkably irregular versus classic instability (Cheyne-Stokes respiration), suggesting our mechanistic understanding is limited. OBJECTIVES: We propose that daytime ventilatory oscillations generally result from a chemoreflex resonance, in which spontaneous biological variations in ventilatory drive repeatedly induce temporary and irregular ringing effects. Importantly, the ease with which spontaneous biological variations induce irregular oscillations (resonance "strength") rises profoundly as loop gain rises toward 1. We tested this hypothesis through a comparison of mathematical predictions against actual measurements in patients with heart failure and healthy control subjects. METHODS: In 25 patients with chronic heart failure and 25 control subjects, we examined spontaneous oscillations in ventilation and separately quantified loop gain using dynamic inspired CO2 stimulation. MEASUREMENTS AND MAIN RESULTS: Resonance was detected in 24 of 25 patients with heart failure and 18 of 25 control subjects. With increased loop gain-consequent to increased chemosensitivity and delay-the strength of spontaneous oscillations increased precipitously as predicted (r = 0.88), yielding larger (r = 0.78) and more regular (interpeak interval SD, r = -0.68) oscillations (P < 0.001 for all, both groups combined). CONCLUSIONS: Our study elucidates the mechanism underlying daytime ventilatory oscillations in heart failure and provides a means to measure and interpret these oscillations to reveal the underlying chemoreflex hypersensitivity and reduced stability that foretells mortality in this population.

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.

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity, cardiac function, exercise capacity, and symptom in patients with chronic heart failure and Cheyne-Stokes respiration.

PURPOSE: Adaptive servo-ventilation (ASV) therapy has been reported to be effective for improving central sleep apnea (CSA) and chronic heart failure (CHF). The purpose of this study was to clarify whether ASV is effective for CSA, cardiac sympathetic nerve activity (CSNA), cardiac symptoms/function, and exercise capacity in CHF patients with CSA and Cheyne-Stokes respiration (CSR-CSA). METHODS: In this study, 31 CHF patients with CSR-CSA and a left ventricular ejection fraction (LVEF) ≤ 40% were randomized into an ASV group and a conservative therapy (non-ASV) group for 6 month. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. CSNA was evaluated by 123I-MIBG imaging, with the delayed heart/mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). RESULTS: The ASV group had significantly better (P < .05) results than the non-ASV group with respect to the changes of AHI (-20.8 ± 14.6 vs -0.5 ± 8.1), TDS (-7.9 ± 4.3 vs 1.4 ± 6.0), and H/M(0.16 ± 0.16 vs -0.04 ± 0.10) on 123I-MIBG imaging, as well as the changes of LVEF (5.3 ± 3.9% vs 0.7 ± 32.6%), SAS (1.6 ± 1.4 vs 0.3 ± 0.7), and NYHA class (2.2 ± 0.4 vs 2.7 ± 0.5) after 6-month therapy. CONCLUSIONS: Performing ASV for 6 months achieved improvement of CSR-CSA, CSNA, cardiac symptoms/function, and exercise capacity in CHF patients with CSR-CSA.

Resolution of Cheyne-Stokes Respiration after Treatment of Heart Failure with Sacubitril/Valsartan: A First Case Report.

Sleep-disordered breathing (SDB) is highly prevalent in patients with heart failure (HF), and is known to be associated with a worse prognosis. The severity of central sleep apnea is thought to mirror cardiac dysfunction. The novel angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril has been shown to improve HF, but a relationship between treatment with ARNi and the severity of SDB has not yet been investigated. We report the case of a 71-year-old male with HF and SDB. Treatment with sacubitril/valsartan was associated with improved cardiac function, as shown by a reduction in the level of N-terminal prohormone of brain natriuretic peptide from 3,249 to 1,720 pg/mL, and an improvement in left-ventricular ejection fraction from 30 to 35%. This was accompanied by a marked reduction in the apnea-hypopnea index (from 41 to 19/h). To the best of our knowledge, this is the first case to document parallel improvements in HF and SDB after the initiation of ARNi treatment.

Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment.

BACKGROUND: Sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) are associated with shorter survival in patients with heart failure. A novel treatment method for this patient group is unilateral phrenic nerve stimulation by the remede® system (Respicardia Inc., Minnetonka, MN, USA), a transvenously implantable neurostimulation device, which has recently been studied in a large randomized, controlled trial. Previous literature has shown efficacy and safety of the treatment with this first-generation device, but hardly any data are available on long-term clinical parameters, the remede® device's battery lifetime, device exchangeability, lead position stability, surgical accessibility, and manageability. METHODS: We performed remede® device replacements in consecutive patients for battery depletion, and documented clinical parameters, longevity, operation procedure, complications, and difficulties. RESULTS: All patients were on neurostimulation treatment by phrenic nerve neurostimulation when device replacement became necessary. Apnea-hypopnea index (from 45 ± 4/h to 9 ± 4/h), oxygen-desaturation index (from 35 ± 7/h to 7 ± 6/h), and time spent with oxygen saturation of <90% (T < 90% from 5 ± 7% to 0 ± 0%) were improved and improvements remained constant throughout the 4-year follow-up. Mean battery life was 4.2 ± 0.2 years and mean replacement procedure time was 25 ± 5.1 minutes. Apart from conventional X-ray documentation of stable lead positions in a long-term setting, no radiation or contrast dye usage was needed and no major complications occurred. In addition, clinical exercise capacity and sleepiness symptoms improved. CONCLUSIONS: Novel remede® device shows sustained therapy efficacy and safety in terms of stable lead positions over 4 years. Long-term phrenic nerve neurostimulation therapy for central SDB/CSR appears feasible in a clinical routine setting.

Patients with Cheyne-Stokes respiration and heart failure: patient tolerance after three-month discontinuation of treatment with adaptive servo-ventilation.

The recent SERVE HF study concluded that patients with chronic heart failure (CHF) and Cheyne-Stokes respiration (CSR) have increased mortality when treated with adaptive servo-ventilation (ASV). We, therefore, wanted to explore if these patients tolerated discontinuation of ASV treatment. The study was a prospective post-ASV treatment observational design with a 3-month follow-up period. 14 patients from our outpatient clinic, all male, were originally diagnosed with CHF and Cheyne-Stokes respiration, which is a clinical form of central sleep apnea. Left ventricular ejection fraction (LVEF) was ≤45% when ASV treatment was initiated. Median machine use was 68 (42-78) months when the patients were instructed to terminate ASV treatment. The patients were then followed during conventional CHF treatment for 3 months. Study baseline was set the last ASV treatment day. Sleep data were collected from the machine the last day of use. Apnea-hypopnea index (AHI), LVEF, 6-min walk test and 24-h ambulatory electrocardiogram recordings were performed at baseline and at study end. Life quality data were obtained using The Minnesota Living with Heart Failure Questionaire (MLHFQ). New York Heart Association Functional Classification (NYHA) was registered. An ambulatory sleep screening was performed at study end. AHI increased significantly after 3 months without ASV treatment [from 1.6 (0.8-3.2) to 39.2 (24.3-44.1, p = 0.001)]. Quality of life (QOL) decreased significantly: 30 (13-54) at discontinuation of ASV vs. 46 (24-67) (MLHFQ) at study end, p = 0.04. Though there was no significant change in NYHA functional class, patients especially reported increased shortness of breath, reduced concentration and reduced memory after discontinuation of ASV treatment. There were no significant differences in LVEF, heart rhythm data and physical capacity. Left ventricular function was preserved indicating that discontinuation of ASV in heart failure patients does not affect cardiac capacity. There was a significant decrement in QOL that must be considered in further treatment of these patients.

Cheyne-stokes respiration during wakefulness in patients with chronic heart failure.

PURPOSE: Cheyne-Stokes respiration (CSR) during sleep has been studied extensively in patients with chronic heart failure (CHF). Prevalence and prognostic significance of CSR during wakefulness in CHF, however, are largely unknown. METHODS: CSR during wakefulness with an apnea-hypopnea cut-off ≥5/h and moderate to severe CSR with an apnea-hypopnea cutoff ≥15/h were analyzed using polysomnographic recordings in 267 patients with stable CHF with reduced left ventricular (LV) ejection fraction at our institution. Primary endpoint during follow-up was heart transplant-free survival. RESULTS: Fifty of 267 patients (19%) had CSR during wakefulness and 73 of 267 patients (27%) had CSR during sleep. CSR during wakefulness was associated with advanced age, atrial fibrillation, decreased LV ejection fraction, increased LV end-diastolic diameter, brain natriuretic peptide, New York Heart Failure class, and CSR during sleep. During 43 months mean follow-up, 67 patients (25%) died and 4 patients (1%) underwent heart transplantation. Multivariate Cox analysis identified age, male gender, chronic kidney disease, and LV ejection fraction as predictors of reduced transplant-free survival. CSR during wakefulness with an apnea-hypopnea cutoff ≥5/h as well as moderate to severe CSR while awake using an apnea-hypopnea cutoff ≥15/h did not predict reduced transplant-free survival independently from confounding factors. CONCLUSION: CSR during wakefulness appears to be a marker of heart failure severity.

Quality of life improves in patients with chronic heart failure and Cheyne-Stokes respiration treated with adaptive servo-ventilation in a nurse-led heart failure clinic.

AIMS AND OBJECTIVES: The aim of this study was to investigate if quality of life improved in chronic heart failure patients with Cheyne-Stokes respiration treated with adaptive servo-ventilation in nurse-led heart failure clinic. BACKGROUND: Cheyne-Stokes respiration is associated with decreased quality of life in patients with chronic heart failure. Adaptive servo-ventilation is introduced to treat this sleep-disordered breathing. DESIGN: Randomised, controlled design. METHODS: Fifty-one patients (ranging from 53-84 years), New York Heart Association III-IV and/or left ventricular ejection fraction ≤40% and Cheyne-Stokes respiration were randomised to an intervention group who received adaptive servo-ventilation or a control group. Minnesota Living with Heart Failure Questionnaire was used to assess quality of life at randomisation and after three months. Both groups were followed in the nurse-led heart failure clinic. RESULT: Adaptive servo ventilation improved quality of life-scores both in a per protocol analysis and in an intention to treat analysis. Twenty-one patients dropped out of the study, nine in the control and 12 in the intervention group. CONCLUSION: Use of adaptive servo-ventilation improved quality of life in chronic heart failure patients with Cheyne-Stokes respiration. However, the drop-out rate was high. RELEVANCE TO CLINICAL PRACTICE: Chronic heart failure patients come regularly to the nurse-led heart failure clinic. The heart failure nurses' competency has to include knowledge of equipment to provide support and continuity of care to the patients.

Current and future developments in the field of central sleep apnoea.

Central sleep apnoea (CSA) occurs in ∼30-50% of patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and in as much as in 18-30% of patients with preserved LVEF. In HF patients, it is characterized by periodic breathing also known as the Cheyne-Stokes respiration followed by pauses of breathing. Central sleep apnoea remains often unrecognized due to its chronic and insidious incidences. Patients may report excessive daytime somnolence, poor sleep quality, nocturnal angina, recurrent arrhythmias, refractory HF symptoms, or demonstrate abnormal respiratory pattern or apnoeas. The pathogenesis of CSA remains incompletely understood, but changes in CO2 above and below the apnoea threshold play a major role in its pathogenesis. The presence of CSA in patients with HF is associated with some neurohumoral and haemodynamic responses that are detrimental to the failing heart including increased morbidity and mortality. The development of successful therapies targeting CSA and its harmful downstream effects is therefore important. Several different therapies from medications to implantable devices have been tested with varying effects and primarily in small non-randomized and/or single-centre studies. Large studies to date have been disappointing, but therapeutic options targeting the physiology of the disease may herald a new era in understanding and treating CSA.

Heterogenous haemodynamic effects of adaptive servoventilation therapy in sleeping patients with heart failure and Cheyne-Stokes respiration compared to healthy volunteers.

This study investigated the haemodynamic effects of adaptive servoventilation (ASV) in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) versus healthy controls. Twenty-seven HF patients with CSR and 15 volunteers were ventilated for 1 h using a new ASV device (PaceWave™). Haemodynamics were continuously and non-invasively recorded at baseline, during ASV and after ventilation. Prior to the actual study, a small validation study was performed to validate non-invasive measurement of Stroke volume index (SVI). Non-invasive measurement of SVI showed a marginal overall difference of -0.03 ± 0.41 L/min/m(2) compared to the current gold standard (Thermodilution-based measurement). Stroke volume index (SVI) increased during ASV in HF patients (29.7 ± 5 to 30.4 ± 6 to 28.7 ± 5 mL/m(2), p < 0.05) and decreased slightly in volunteers (50.7 ± 12 to 48.6 ± 11 to 47.9 ± 12 mL/m(2)). Simultaneously, 1 h of ASV was associated with a trend towards an increase in parasympathetic nervous activity (PNA) in HF patients and a trend towards an increase in sympathetic nervous activity (SNA) in healthy volunteers. Blood pressure (BP) and total peripheral resistance response increased significantly in both groups, despite marked inter-individual variation. Effects were independent of vigilance. Predictors of increased SVI during ASV in HF patients included preserved right ventricular function, normal resting BP, non-ischaemic HF aetiology, mitral regurgitation and increased left ventricular filling pressures. This study confirms favourable haemodynamic effects of ASV in HF patients with CSR presenting with mitral regurgitation and/or increased left ventricular filling pressures, but also identified a number of new predictors. This might be mediated by a shift towards more parasympathetic nervous activity in those patients.

The effect of continuous positive airway pressure on heart rate variability during the night in patients with chronic heart failure and central sleep apnoea.

Continuous positive airway pressure (CPAP) improves autonomic activity in patients with chronic heart failure (CHF) and central sleep apnoea (CSA), but its effect on heart rate variability (HRV) during therapy has not been reported. We hypothesized that CPAP may decrease HRV, despite its beneficial effects on sympathetic overactivation, due to the expected stabilization of breathing. Sixty-seven CHF patients underwent polysomnography (PSG). Ten of them presented with CSA (age 66.1±8.5 years, apnoea-hypopnea index [AHI]=57.6±23.3, central AHI [cAHI]=41.6±24.6 [mean±SD]) and were subjected to a second PSG with manual CPAP titration. Beat-to-beat heart intervals for a 6-hour period of sleep were extracted from each recording and HRV was analysed. CPAP significantly reduced AHI (AHI=23.1±18.3 P=.004). Standard deviation of normal-normal interbeat interval (SDNN) (61.5±29.0 vs 49.5±19.3 ms, P=.021), root mean square of successive differences (RMSSD) (21.8±9.2 vs 16.4±7.1 ms, P=.042), total power (lnTP=7.8±1.1 vs 7.4±0.8 ms2 , P=.037), low frequency power (lnLF=5.5±1.5 vs 5.0±1.4 ms2 , P=.003) and high frequency power (lnHF=4.6±1.0 vs 4.0±1.0 ms2 , P=.024) were decreased. There was a strong correlation between the decrease in AHI and the decrease in lnHF (Spearman's ρ=.782). CPAP leads to a decrease in spectral and time domain parameters of HRV during therapy in CHF patients with CSA. These changes are best explained by the effect which CPAP-influenced breathing pattern and lowered AHI exert on HRV.

Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure-a randomized, controlled, double-blind, crossover trial.

OBJECTIVES: This randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF). METHODS: Twenty-one consecutive patients with CHF and CSR (apnea-hypopnea index [AHI] ≥15/h) underwent right heart catheterization with titration of intravenous (IV) glyceryltrinitrate (GTN) to a maximum tolerable dosage and inhalation of iloprost 10 µg/mL after a washout phase. Maximum tolerable dosages of GTN and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with IV or inhaled sodium chloride (NaCl) 0.9 %, respectively. RESULTS: GTN (6.2 ± 1.5 mg/h) and iloprost significantly lowered \mean pulmonary artery pressure (20.1 ± 9.0 to 11.6 ± 4.2 mmHg, p < 0.001 and 16.9 ± 7.9 to 14.2 ± 6.4 mmHg, p < 0.01, respectively). Pulmonary capillary wedge pressure was only reduced by GTN (14.0 ± 5.6 to 7.2 ± 3.9 mmHg, p < 0.001), and there was no significant change in the cardiac index. Sleep studies revealed no significant improvement in markers of CSR severity, including AHI, central apnea index, and CSR cycle length following GTN or iloprost treatment. Significant decreases in blood pressure, mean oxygen saturation, and S3 sleep were documented during GTN infusion. CONCLUSIONS: Acute improvement of pulmonary congestion by GTN had no immediate impact on CSR severity. Future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure. TRIAL REGISTRATION: German Clinical Trial Registry-ID:DRKS00000467 ( www.germanctr.de ).