Effect of lateral position on rostral fluid shift and relationship to severity of Cheyne-Stokes respiration in heart failure patients.

PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.

Central Sleep Apnea.

Central sleep apnea (CSA) is characterized by intermittent repetitive cessation and/or decreased breathing without effort caused by an abnormal ventilatory drive. Although less prevalent than obstructive sleep apnea, it is frequently encountered. CSA can be primary (idiopathic) or secondary in association with Cheyne-Stokes respiration, drug-induced, medical conditions such as chronic renal failure, or high-altitude periodic breathing. Risk factors have been proposed, including gender, age, heart failure, opioid use, stroke, and other chronic medical conditions. This article discusses the prevalence of CSA in the general population and within each of these at-risk populations, and clinical presentation, diagnostic methods, and treatment.

Detection of pathological mechano-acoustic signatures using precision accelerometer contact microphones in patients with pulmonary disorders.

Monitoring pathological mechano-acoustic signals emanating from the lungs is critical for timely and cost-effective healthcare delivery. Adventitious lung sounds including crackles, wheezes, rhonchi, bronchial breath sounds, stridor or pleural rub and abnormal breathing patterns function as essential clinical biomarkers for the early identification, accurate diagnosis and monitoring of pulmonary disorders. Here, we present a wearable sensor module comprising of a hermetically encapsulated, high precision accelerometer contact microphone (ACM) which enables both episodic and longitudinal assessment of lung sounds, breathing patterns and respiratory rates using a single integrated sensor. This enhanced ACM sensor leverages a nano-gap transduction mechanism to achieve high sensitivity to weak high frequency vibrations occurring on the surface of the skin due to underlying lung pathologies. The performance of the ACM sensor was compared to recordings from a state-of-art digital stethoscope, and the efficacy of the developed system is demonstrated by conducting an exploratory research study aimed at recording pathological mechano-acoustic signals from hospitalized patients with a chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia, and acute decompensated heart failure. This unobtrusive wearable system can enable both episodic and longitudinal evaluation of lung sounds that allow for the early detection and/or ongoing monitoring of pulmonary disease.

A signal demodulation-based method for the early detection of Cheyne-Stokes respiration.

Cheyne-Stokes respiration (CSR) is a sleep-disordered breathing characterized by recurrent central apneas alternating with hyperventilation exhibiting a crescendo-decrescendo pattern of tidal volume. This respiration is reported in patients with heart failure, stroke or damage in respiratory centers. It increases mortality for patients with severe heart failure as it has adverse impacts on the cardiac function. Early stage of CSR, also called periodic breathing, is often undiagnosed as it only provokes hypopneas instead of apneas, which are much more difficult to detect. This paper demonstrates the proof of concept of a new method devoted to the early detection of CSR. The proposed approach relies on a signal demodulation technique applied to ventilation signals measured on 15 patients with chronic heart failure whose respiration goes from normal to severe CSR. Based on a modulation index and its instantaneous frequency, oscillation zones are detected and classified into three categories: CSR, periodic breathing and no abnormal pattern. The modulation index is used as an efficient indicator to quantify the degree of certainty of the pathology for each patient. Results show high correlation with experts' annotations with sensitivity and specificity values of 87.1% and 89.8% respectively. A final decision leads to a classification which is confirmed by the experts' conclusions.

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.

Effect of Treatment of Central Sleep Apnea/Cheyne-Stokes Respiration on Left Ventricular Ejection Fraction in Heart Failure: A Network Meta-Analysis.

STUDY OBJECTIVES: Patients who have experienced heart failure with central sleep apnea/Cheyne-Stokes respiration (CSA/CSR) have an impaired prognosis. Continuous positive airway pressure (CPAP) and adaptive servoventilation (ASV) as well as nocturnal oxygen (O2) are proposed treatment modalities of CSA/CSR. The goal of the study is to assess whether and how different treatments of CSA/CSR affect cardiac function. METHODS: Databases were searched up to December 2017 for randomized controlled trials (RCTs) comparing the effect of any combination of CPAP, ASV, O2 or an inactive control on left ventricular ejection fraction (LVEF) in patients with heart failure and CSA/CSR. A systematic review and network meta-analysis using multivariate random-effects meta-regression were performed. RESULTS: Twenty-four RCTs (1,289 patients) were included in the systematic review and data of 16 RCTs (951 patients; apnea-hypopnea-index 38 ± 3/h, LVEF 29 ± 3%) could be pooled in a network meta-analysis. Compared to an inactive control, both CPAP and ASV significantly improved LVEF by 4.4% (95% confidence interval 0.3-8.5%, P = 0.036) and 3.8% (95% confidence interval 0.6-7.0%, P = 0.025), respectively, whereas O2 had no effect on LVEF (P = 0.35). There was no difference in treatment effects on LVEF between CPAP and ASV (P = 0.76). The treatment effect of positive pressure ventilation was larger when baseline LVEF was lower in systolic heart failure. CONCLUSIONS: CPAP and ASV are effective in improving LVEF in patients with heart failure and CSA/CSR to a clinically relevant amount, whereas nocturnal O2 is not. There is no difference between CPAP and ASV in the comparative beneficial effect on cardiac function.

Contribution of the Lung to the Genesis of Cheyne-Stokes Respiration in Heart Failure: Plant Gain Beyond Chemoreflex Gain and Circulation Time.

Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ([Formula: see text]) and hypercapnia ([Formula: see text]) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91-0.99); the best-fitting curve to express the PG was a hyperbola ( R2≥0.98). Patients with CSR showed increased PG , [Formula: see text] (but not [Formula: see text]), and lung-to-finger circulation time, compared with patients without CSR (all P<0.05). PG was the only predictor of the daytime AHI ( R=0.56, P=0.01) and together with the [Formula: see text] also predicted the nighttime AHI ( R=0.81, P=0.0003) and the 24-hour AHI ( R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length ( R=0.82, P=0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.

Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure.

STUDY OBJECTIVES: In patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF), stroke volume (SV) falls during hyperpnea of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). We have identified two distinct patterns of hyperpnea: positive, in which end-expiratory lung volume (EELV) remains at or above functional residual capacity (FRC), and negative, in which EELV falls below FRC. The increase in expiratory intrathoracic pressure generated by the latter should have effects on the heart analogous to external chest compression. To test the hypotheses that in HFrEF patients, CSR-CSA with the negative pattern has an auto-resuscitation effect such that compared with the positive pattern, it is associated with a smaller fall in SV and a smaller increase in cardiac workload (product of heart rate and systolic blood pressure). METHODS: In 15 consecutive HFrEF patients with CSR-CSA during polysomnography, hemodynamic data derived from digital photoplethysmography during positive and negative hyperpneas were compared. RESULTS: Compared to the positive, negative hyperpneas were accompanied by reductions in the maximum and mean relative fall in SV of 30% (p = 0.002) and 10% (p = 0.031), respectively, and by reductions in the degree of increases in heart rate and rate pressure product during hyperpnea of 46% (p < 0.001) and 13% (p = 0.007), respectively. CONCLUSIONS: Our findings suggest the novel concept that the negative pattern of CSR-CSA may constitute a form of auto-resuscitation that acts as a compensatory mechanism to maintain SV in patients with severe HF.

Cheyne-Stokes respiration related oscillations in cardiopulmonary hemodynamics in patients with heart failure.

BACKGROUND: Although Cheyne-Stokes respiration (CSR) is an oscillatory phenomenon, the direct effects of cyclical hyperventilation and apnea on cardiopulmonary hemodynamics have been poorly investigated. The aim of the study was to examine the echocardiographic changes associated with CSR phases in a group of patients with systolic heart failure (HF) and daytime CSR. METHODS: 14 HF patients (age 70 ±â€¯9 years, LVEF 24 ±â€¯5) underwent a thorough clinical evaluation, 24-h respiratory polygraphy, chemoreflex evaluation by rebreathing technique and neuro-hormonal assessment. Furthermore, they received a simultaneous echocardiographic and respiratory monitoring embedding the respiratory signal in the echocardiographic machine. RESULTS: All patients had daytime CSR (diurnal apnea-hypopnea index, AHI: 18.5, interquartile range: 15.3-39.5 events/h). Systolic pulmonary artery pressure and pulmonary vascular resistances (PVR) increased from hyperventilation to apnea (H 45.3 ±â€¯11.4 vs A 52.4 ±â€¯13.8 mmHg, p = 0.004, and H 3.3 ±â€¯2.5 vs A 5.1 ±â€¯3.2 Wood units, p = 0.0003, respectively), while acceleration time of the pulmonary artery decreased (H 110.1 ±â€¯19.8 vs A 92.0 ±â€¯19.9 ms, p = 0.001). During apnea a reduction of right and left ventricular outflow tract VTI (H 12.8 ±â€¯4.9 versus A 9.9 ±â€¯3.1, p = 0.002 and H 26.9 ±â€¯8.8 versus A 22.8 ±â€¯7.9 mm, p = 0.006, respectively), and a reduction in tricuspid annular plane systolic excursion (H 15.9 ±â€¯4.4 versus A 14.4 ±â€¯4.1 mm, p = 0.005) were also observed. Notably, PVR variation strongly correlated with chemosensitivity to hypercapnia (R = 0.89, p = 0.0004) and plasma norepinephrine level (R = 0.78, p = 0.003). CONCLUSIONS: In HF patients with CSR, an increase in pulmonary pressure and pulmonary vascular resistances was observed during apnea. Pulmonary vasoconstriction strongly correlated with chemosensitivity to hypercapnia and indexes of adrenergic activation.

ECG derived Cheyne-Stokes respiration and periodic breathing are associated with cardiorespiratory arrest in intensive care unit patients.

BACKGROUND: Cheyne-Stokes respiration and periodic breathing (CSRPB) have not been studied sufficiently in the intensive care unit setting (ICU). OBJECTIVES: To determine whether CSRPB is associated with adverse outcomes in ICU patients. METHODS: The ICU group was divided into quartiles by CSRPB (86 patients in quartile 1 had the least CSRPB and 85 patients in quartile 4 had the most CSRPB). Adverse outcomes (emergent intubation, cardiorespiratory arrest, inpatient mortality and the composite of all) were compared between patients with most CSRPB (quartile 4) and those with least CSRPB (quartile 1). RESULTS: ICU patients in quartile 4 had a higher proportion of cardiorespiratory arrests (5% versus 0%, (p=.042), and more adverse events over all (19% versus 8%, p=.041) as compared to patients in quartile 1. CONCLUSIONS: CSRPB can be measured in the ICU and it's severity is associated with adverse outcomes in critically ill patients.

Is dynamic desaturation better than a static index to quantify the mortality risk in heart failure patients with Cheyne-Stokes respiration?

Cheyne-Stokes respiration (CSR) is a periodic, highly dynamic, respiratory pattern and a known comorbidity in congestive heart failure (CHF) patients. It is generally seen as an indicator for a negative prognosis, even if no distinction in degree is known or understood. This paper aims to improve on existing attempts by creating a quantification of the behavior of the dynamic desaturation process of oxygen in the blood. We performed this work on a cohort of 11 subjects with CHF, reduced left ventricular ejection fraction, and CSR. The dynamic desaturation process was evaluated according to changes to peripheral capillary oxygenation S p O 2 resulting from highly nonlinear relationships in the ventilatory system perturbed by periodic breathing. Hypoxaemic burden expressed as a static index T 90 was compared to a novel relative desaturation index R D I , developed in this paper. While T 90 represents a single value calculated using a static cut-off value of 90 % S p O 2 , the R D I is more sensitive to dynamic influences as it uses the specific maximum change in saturation for each CSR episode. The threshold of T 90 = 22 min per night as suggested by Oldenburg et al. could not be confirmed to predict survival, but all central apneas resulting in a relative desaturation of S p O 2 above a cut-off value of 8 % were a 100 % positive predictor of mortality. The R D I proved sufficiently stable in intraindividual measurements across CSR epochs. Across the cohort, it showed a bimodal distribution for the deceased group, indicative of a possible aetiological difference. Hence, it is our conclusion that a dynamic approach to analyse desaturation of oxygen during Cheyne-Stokes respiration is to be strongly favoured over a static approach to analysis.

Temporal relationship between arousals and Cheyne-Stokes respiration with central sleep apnea in heart failure patients.

OBJECTIVE: The interplay between arousals and respiratory events during Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF) patients is still not fully understood. We investigated the temporal relationship between arousals and CSR-CSA. METHODS: Episodes of CSR-CSA during sleep stages N1-N2 were analyzed in 22 HF patients with an apnea-hypopnea index ≥15/h, dominant CSA and central apnea index ≥5/h. For each CSR-CSA cycle (apnea + hyperpnea), we determined the onset (ARonset, relative to hyperpnea onset) and duration of detected arousals. RESULTS: Arousals (N = 2348) mostly occurred within the first half of the hyperpneic phase (42.6%, ARonset = 10.6 ±â€¯2.1 s; duration = 10.6 ±â€¯5.2 s) or close to hyperpnea onset (21.5%, ARonset = -0.1 ±â€¯0.6 s; duration = 13.9 ±â€¯5.4 s). Within-apnea arousals were less frequent (12.4%, ARonset = -16.0 ±â€¯4.7 s; duration = 3.8 ±â€¯1.4 s). The proportion of CSR-CSA cycles without any hyperpnea-related arousal was 27.5 ±â€¯18.2%. Hyperpnea-related arousability (total number of hyperpneic arousals/total duration of hyperpneas) and apnea-related arousability were 63.4 ±â€¯21.0/h and 23.8 ±â€¯16.9/h, respectively (p < 0.0001). CONCLUSION: During CSR-CSA, a significant proportion of arousals occur at hyperpnea onset, indicating a low arousal threshold. Hyperpneic arousals are not essential for CSR-CSA. Arousability markedly increases during hyperpneas, likely due to the concurrent increase in chemoreceptor stimulation. SIGNIFICANCE: This study extends current knowledge on the interplay between sleep instability and respiratory events during CSR-CSA.

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.

Central Sleep Apnea with Cheyne-Stokes Breathing in Heart Failure - From Research to Clinical Practice and Beyond.

Characterized by periodic crescendo-decrescendo pattern of breathing alternating with central apneas, Central sleep apnea (CSA) with Cheyne-Stokes Breathing represents a highly prevalent, yet underdiagnosed comorbidity in chronic heart failure (CHF). A diverse body of evidence demonstrates increased morbidity and mortality in the presence of CSB. CSB has been described in both CHF patients with preserved and reduced ejection fraction, regardless of drug treatment. Risk factors for CSB are older age, male gender, high BMI, atrial fibrillation and hypocapnia.The pathophysiology of CSB has been explained by the loop gain theory, where a controller (the respiratory center) and a plant (the lungs) are operating in a reciprocal relationship (negative feedback) to regulate a key parameter (partial pressure of carbon dioxide (pCO2)). The temporal interaction between these elements is dependent on the circulatory delay. Increased chemosensitivity/chemoresponsiveness of the respiratory center and/or augmented ascending non- CO2 stimuli from the C-fibers in the lungs (interstitial pulmonary edema), overly efficient ventilation when breathing at low volumes and prolonged circulation time are involved. An alternative hypothesis of CSB being an adaptive response of the failing heart has its merits as well. The clinical manifestation of CSB is usually poor, lacking striking symptoms and complaints. Witnessed apneas and snoring are infrequently reported by the sleep partner. Sometimes patients may report poor sleep quality with frequent awakenings, paroxysmal nocturnal dyspnea and frequent urination at night. Standard instrumental and laboratory studies, performed in CHF patients, may present clues to the presence of CSB. Concentric remodeling of the left ventricle and dilated left atrium (echocardiography), high BNP and C-reactive protein levels, increased ventilation-carbon dioxide output (VEVCO2) and lower end-tidal CO2 (cardiopulmonary exercise testing), reduced diffusion capacity (pulmonary function testing) and hypocapnia (blood-gas analysis) may indicate the presence of CSB.CSB and cardiovascular disease are probably linked through bidirectional causality. Cyclic variations in heart rate, blood pressure, respiratory volume, partial pressure of arterial oxygen (pO2) and pCO2 lead to sympathetic-adrenal activation. The latter worsens ventricular energetism and survival of cardiomyocytes and exerts antiarhythmogenic effects. It causes cardiac remodeling, potentiating the progression and the lethal outcome in CHF patients. Several treatment modalities have been proposed in CSB. The most commonly used are continuous positive airway pressure (CPAP), adaptive servoventilation (ASV) and nocturnal home oxygen therapy (HOT). Novel therapies like nocturnal supplemental CO2 and phrenic nerve stimulation are being tested recently. The current treatment recommendations (by the American Academy of Sleep Medicine) are for CPAP and HOT as standard therapies, while ASV is an option only in patients with EF > 45%. BPAP (bilevel device) remains an option only when there is no adequate response to previous modes of treatment. Acetazolamide and theophylline are options only after failing the above modalities and if accompanied by a close follow-up.

ResCSRF: Algorithm to Automatically Extract Cheyne-Stokes Respiration Features From Respiratory Signals.

OBJECTIVE: Cheyne-Stokes respiration (CSR) related features are significantly associated with cardiac dysfunction. Scoring of these features is labor intensive and time-consuming. To automate the scoring process, an algorithm (ResCSRF) has been developed to extract these features from nocturnal measurement of respiratory signals. METHODS: ResCSRF takes four signals (nasal flow, thorax, abdomen, and finger oxygen saturation) as input. It first detects CSR cycles and then calculates the respiratory features (cycle length, lung-to-periphery circulation time, and time to peak flow). It outputs nightly statistics (mean, median, standard deviation, and percentiles) of these features. It was developed and blindly tested on a group of 49 chronic heart failure patients undergoing overnight in-home unattended respiratory polygraphy recordings. RESULTS: The performance of ResCSRF was evaluated against manual expert scoring (ES) (consensus between two independent sleep scorers). In terms of percentage of CSR per recording, the mean difference [reproducibility coefficient (RPC)] between ResCSRF and ES was 0.5(6.4) and 0.5(8.1) for development and test set, respectively. The nightly statistics of CSR-related features output by ResCSRF showed high correlation with ES on the blind test set with the mean difference of less than 3 s and RPC of less than 7 s. CONCLUSIONS: These results indicate that ResCSRF is capable of automating the scoring of CSR-related features and could potentially be implemented into a remote monitoring system to regularly monitor patients' cardiac function.

Microstructural cerebral lesions are associated with the severity of central sleep apnea with Cheyne-Stokes-respiration in heart failure and are modified by PAP-therapy.

This study investigated the association of microstructural cerebral lesions with central sleep apnea with Cheyne-Stokes-respiration (CSA-CSR) in heart failure (HF) patients and the effect of positive airway pressure therapy (PAP) of CSA-CSR on these lesions. PAP-therapy was initiated in patients with HF with midrange and with reduced ejection fraction (NYHA≥II; left ventricular ejection fraction <50%) and proven CSA-CSR. Cerebral magnetic resonance imaging (MRI) scans at 3T including diffusion tensor imaging were obtained before and after 4 months of PAP-therapy. Cerebral MRI scans revealed microstructural lesions in all 11 patients with HF with midrange or reduced ejection fraction and CSA-CSR (64±8years, 82% male, left ventricular ejection fraction 37±11%) that were focussed on the brainstem and frontal cerebral regions. This microstructural damage correlated with the severity of CSA-CSR and 4 months of PAP-therapy lead to voxel clusters of altered fiber integrity in these lesions. Microstructural cerebral lesions might contribute to the pathophysiology of CSA-CSR in HF. In these patients PAP-therapy induces neuronal plasticity.