Effects of adaptive servo-ventilation on ventricular arrhythmias in patients with stable congestive heart failure and sleep-disordered breathing

Background

Congestive heart failure patients with reduced left ventricular ejection fraction (HFrEF) and sleep-disordered breathing (SDB) are at an increased risk of nocturnal cardiac arrhythmias. SDB can be effectively treated with adaptive servo-ventilation (ASV). Therefore, we tested the hypothesis that ASV therapy reduces nocturnal arrhythmias and heart rate in patients with HFrEF and SDB.

Methods

In a non-prespecified subanalysis of a multicenter randomized controlled trial (ISRCTN04353156), 20 consecutive patients with stable HFrEF (age 67 ± 9 years; left ventricular ejection fraction, LVEF 32 ± 7?%) and SDB (apnea–hypopnea index, AHI 48 ± 20/h) were randomized to either an ASV therapy (n = 10) or an optimal medical treatment alone group (controls, n = 10). Polysomnography (PSG) with blinded centralized analysis and scoring was performed at baseline and at 12 weeks. The electrocardiograms (ECG) of the PSGs were analyzed with long-term (24-h) Holter ECG software (QRS-Card? Cardiology Suite; Pulse Biomedical Inc., King of Prussia, PA, USA).

Results

There was a decrease in ventricular extrasystoles (VES) per hour of recording time in the ASV group compared to the control group (?8.1 ± 42.4 versus +9.8 ± 63.7/h, p = 0.356). ASV reduced the number of ventricular couplets and nonsustained ventricular tachycardias (nsVT) compared to the control group (?2.3 ± 6.9 versus +2.1 ± 12.7/h, p = 0.272 and ?0.1 ± 0.5 versus +0.1 ± 1.1/h, p = 0.407, respectively). Mean nocturnal heart rate decreased in the ASV group compared to the controls (?2.0 ± 2.7 versus +3.9 ± 11.5/min, p = 0.169). The described changes were not significantly different between the groups.

Conclusion

In HFrEF patients with SDB, ASV treatment may reduce nocturnal VES, couplets, nsVT, and mean nocturnal heart rate. The findings of the present pilot study underscore the need for further analyses in larger studies.

     

Model based analysis of sleep disordered breathing in congestive heart failure

We employed a computational model of the respiratory control system to examine which of several factors, in isolation and in combination, can contribute to or explain the development of Cheyne-Stokes breathing (CSB). Our approach uses a graphical method for stability analysis similar, in concept, to the phase plane. The results from the computer simulations indicate that a postulated three-fold increase in the chemosensitivity of the central chemoreflex (CCR) loop may, by itself, explain development of CSB. By contrast, a similar increase in the chemosensitivity of the peripheral chemoreflex (PCR) loop cannot, by itself, account for CSB. The analysis reveals that the system is more readily destabilized by increasing the gain of only one chemoreflex loop than by a combined increase in gain of both loops. Reduction in the cardiac output or cardiomegaly decreases the size of the stability region. We conclude that development of CSB is the result of a complex interaction between CCR and PCR loops which may, in turn, interact with decreased cardiac output and cardiomegaly.     

Detection of exercise periodic breathing using thermal flowmeter in patients with heart failure

Exercise periodic breathing (EPB) is associated with exercise intolerance and poor prognosis in patients with heart failure (HF). However, EPB detection during cardiopulmonary exercise test (CPET) is difficult. The present study investigated the use of a wireless monitoring device to record the EPB during CPET and proposed quantization parameter estimates for the EPB. A total of 445 patients with HF were enrolled and underwent exercise tests. The ventilation data from the wearable device were compared with the data obtained during the CPET and were analyzed based on professional opinion and on 2 automated programs (decision tree [DT] and oscillatory pattern methods). The measurement accuracy was greater with the DT method (89 %) than with the oscillatory pattern method (75 %). The cutoffs for EPB recognition using the DT method were (1) an intercept of the regression line passing through the minute ventilation rate vs. the time curve during the recovery phase ≥64.63, and (2) an oscillatory phase duration to total exercise time ratio ≥0.5828. The wearable device was suitable for the assessment of EPB in patients with HF, and our new automated analysis system using the DT method effectively identified the EPB pattern.     

Event-related potentials in patients with insomnia and sleep-related breathing disorders: evening-to-morning changes

STUDY OBJECTIVES: The relationship between event-related potentials (ERPs) and sleep alterations in patients with sleep disorders is still controversial. Whether the ERP alterations are affected by sleep loss and sleep discontinuity can be addressed by studying presleep-to-postsleep changes in ERPs. We investigated if presleep-to-postsleep ERP latencies and amplitudes differ in patients with insomnia and sleep-related breathing disorders and whether these changes are affected by the degree of subjective and objective sleep alterations. METHODS: Fifteen patients with a diagnosis of insomnia, 45 patients with sleep-related breathing disorders, and 13 healthy controls were examined. Auditory ERPs were measured in the evening before sleep and in the morning after polysomnography. Subjective sleepiness and sleep quality were assessed by the Epworth Sleepiness Scale and the Saint Mary's Hospital Quality of Sleep Questionnaire. RESULTS: Analysis of evening-to-morning ERP variations did not reveal significant between-group differences in N100 latency and amplitude or in P200 and P300 amplitudes. Patients with sleep-related breathing disorders had a significant lengthening of P200 and P300 latencies in the morning, compared with controls and insomniacs. A trend to delayed morning P300 was present in patients with insomnia but did not reach statistical significance. The evening-to-morning ERP differences were not significantly related to subjective sleep quality, indexes of sleep fragmentation, or total sleep time. CONCLUSIONS: ERPs are sufficiently sensitive to assess attention dysfunction in patients with sleep disorders when presleep-to-postsleep changes are considered. The lack of relationship between indexes of sleep loss and sleep fragmentation and presleep-to-postsleep ERP changes might suggest that other factors outside sleep alterations affect ERP deterioration in patients with sleep disorders.     

Adipokines in children with sleep disordered breathing

STUDY OBJECTIVE: Associations between SDB, the metabolic syndrome, and circulating levels of adipokines have emerged in adults but have not been examined in snoring children, who, in contradistinction to adults, display insulin resistance and lipid abnormalities as a function of adiposity rather than SDB. Therefore, we aimed to examine associations between circulating adipokines levels, insulin resistance, and measures of SDB in children. DESIGN: Prospective study. SETTING: Polysomnographic evaluation and assessment of plasma levels of leptin, adiponectin, resistin, glucose, insulin, and CRP. PARTICIPANTS: 130 children (mean age 8.2 +/- 2.8 years; 39% obese) were studied. MEASUREMENTS AND RESULTS: Log adiponectin levels were lower in obese than nonobese children (3.8 +/- 0.31 vs 4.0 +/- 0.30 corresponding to 8,381.4 +/- 5,841.0 vs 12,853.2 +/- 7,780.2 ng/ml, P < 0.0001) and were inversely correlated with BMI Z scores (r = -0.47, P < 0.0001) but not with log AHI. Log leptin concentrations were higher in the obese group than the nonobese group (4.2 +/- 0.32 vs 3.4 +/- 0.57 corresponding to 19,542.6 +/- 13,643.6 vs 5,875.5 +/- 8,425.7 pg/ml, P < 0.0001), correlated with BMI Z scores (r = 0.64, P < 0.0001), and were significantly lower in children with AHI < or = 1/hr than children with AHI > 1/hr (P = 0.006) and in children with SpO2 nadir > or = 90% than children with SpO2 nadir < 90%, even after controlling for BMI Z score (P < 0.03). No significant differences were found in log resistin levels as a function of obesity or AHI. Significant correlations between log adiponectin levels and log Insulin/Glucose (I/G) ratios (-0.28, P = 0.006) and between log leptin levels and log I/G ratios (r = 0.66, P < 0.0001) emerged. CONCLUSIONS: In close agreement with the absence of a measurable effect of SDB on insulin resistance in children, circulating adipokines levels are primarily attributable to the ponderal index. However, SDB and associated hypoxemia may contribute to the elevation of leptin levels.     

Effects of nitric oxide inhalation on periodic breathing in awake patients with chronic heart disease

BACKGROUND: Periodic breathing, an abnormal pattern of respiration consisting of alternating hyperpnea and hypopnea, has been recognized in patients with heart failure. Although fluctuations in pulmonary blood flow have been considered as a possible cause of this type of breathing, its patho-physiological mechanisms are not fully understood. In this study, we sought to determine whether inhaled nitric oxide (NO), a selective pulmonary vasodilator, attenuates periodic breathing. METHODS: Eight cardiac patients who exhibited clear oscillatory ventilation while awake (age: 62 +/- 16 years, left ventricular ejection fraction: 48 +/- 20%) were enrolled in the study. After breathing room air (RA) for 15 min, the subjects inhaled air containing 30 ppm of NO for 15 min. Respiratory gas variables including minute ventilation (VE) were measured on a breath-by-breath basis throughout the test. RESULTS: There were no differences in VE (10.7 +/- 1.5 vs. 11.0 +/- 1.7 l/min) or among any of the other hemodynamic or respiratory gas variables studied in the control and NO tests, with the exception of the end-tidal CO(2) partial pressure (5.0 +/- 0.4 vs. 4.8 +/- 0.5%; p = 0.018). The % magnitude of oscillation (i.e., the difference between the peak and nadir of oscillating VE, divided by the mean VE) was 40.0 +/- 22.4% in RA and not influenced by inhaled NO (43.9 +/- 20.8%, p = 0.57). CONCLUSION: Inhaled NO at a concentration of 30 ppm did not attenuate periodic breathing in awake patients with mild heart failure.     

Chest wall regional volume in heart failure patients during inspiratory loaded breathing

Were evaluated individuals divided into two groups: we studied chronic heart failure (CHF) (19 patients with CHF plus cardiomegaly) and control (12 healthy volunteers) during performance of inspiratory loaded breathing (ILB). We evaluated: spirometry, functional capacity through the six-minute walk test (6MWT), and distribution of thoracoabdominal volumes via optoelectronic plethysmography (OEP), namely volume variations of pulmonary rib cage (Vrc,p), abdominal rib cage (Vrc,a), and abdomen (Vab). In each compartment, the percentage contributions of right and left sides were also calculated. During ILB, patients with heart failure were characterized by a significant reduction of the Vrc,a volume variations compared to the control group. Correlations were found between left %Vrc,a on the left side measured during ILB and left ventricular ejection fraction (r=0.468; p=0.049), and dyspnea after the 6MWT (r=-0.878; p<0.01).Then, patients with CHF and cardiomegaly are characterized by a reduced mobility in left part of the lower part of the rib cage, that contributes leading to increased perception of dyspnea during submaximal exercise.     

The effects of adaptive servo ventilation on cerebral vascular reactivity in patients with congestive heart failure and sleep-disordered breathing

STUDY OBJECTIVE: Hypercapnic cerebral vascular reactivity (HCVR) is reduced in patients with congestive heart failure (CHF) and sleep-disordered breathing (SDB); this may be associated with an increased risk of stroke. We tested the hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation (ASV) would increase morning HCVR. DESIGN: Interventional, cross-over clinical study. SETTING: Research sleep laboratory. PATIENTS: Ten CHF patients with SDB, predominantly obstructive sleep apnea. INTERVENTIONS: The HCVR was measured from the change in middle cerebral artery velocity, using pulsed Doppler ultrasound. HCVR was determined during the evening (before) and morning (after) 1 night of sleep on ASV and 1 night of spontaneous sleep (control). MEASUREMENTS AND RESULTS: Compared with the control situation, ASV decreased the apnea-hypopnea index (group mean +/- SEM, control: 48 +/- 12, ASV: 4 +/- 1 events per hour). HCVR was 23% lower in the morning, compared with the evening, on the control night (evening: 1.3 +/- 0.2, morning: 1.0 +/- 0.2 cm/sec per mm Hg, P < 0.05) and 27% lower following the ASV night (evening: 1.5 +/- 0.2, morning: 1.1 +/- 0.2 cm/sec per mm Hg, P < 0.05). The effect of ASV on the evening-to-morning reduction in HCVR was not significant, compared with the control night (0.02 cm/sec per mm Hg, 95% confidence interval: -0.28, 0.32 P = 0.89). CONCLUSIONS: In CHF patients with SDB, HCVR was reduced in the morning compared with the evening. However, removal of SDB for 1 night did not reverse the reduced HCVR. The relatively low morning HCVR could be linked with an increased risk of stroke.     

Development of the control of breathing: implications for sleep-related breathing disorders in infants

Abnormal development of the control of breathing has implications for the occurrence and severity of SDB during infancy. Prevention of prenatal insults such as nicotine exposure should be included in public health programs. Infants at risk for SDB or with symptoms of SDB should be investigated for peripheral and central chemoreceptor dysfunction. Peripheral chemoreceptor function can be assessed using either the hyperoxic test or the alternating breath test, and central chemoreceptor function using the rebreathing test. Optimal treatment of SDB in the developing infant is of central importance for preserving normal behavior and neurocognitive development. Oxygen supplementation and/or ventilatory support during sleep prevent uncontrolled episodes of hypoxemia, sleep fragmentation, and REM sleep reduction. Finally, alterations in homeostatic responses during development may have long-term effects on breathing during sleep in childhood and adulthood. In genetically-predisposed subjects, environmental conditions during the period of development of respiratory control mechanisms may add to the intrinsic vulnerability to SDB.     

Sleep-disordered breathing in heart failure: characteristics and implications

Sleep-disordered breathing, namely obstructive sleep apnea (OSA) and central sleep apnea (CSA), are both often encountered in the setting of heart failure (HF), and have distinct differences in terms of prevalence, pathophysiology and consequences. OSA is independently associated with an increased risk for cardiovascular disease and for congestive HF in the general population. It is conceivable that this breathing disorder may have particularly deleterious effects in patients with coexisting heart disease, especially in those with a failing heart. There are considerable data addressing the interaction between OSA and the cardiovascular system, which underscore the importance of an early detection of this breathing disorder, especially in patients with HF. CSA is generally considered a consequence rather than a cause of HF, and is correlated with the severity of hemodynamic impairment. However, when present, it is associated with increased arrhythmic risk and higher cardiac mortality. Potential mechanisms implicated in the genesis of this breathing pattern and the possible therapeutic options, which have been proven to be effective in the clinical setting, are discussed.     

Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 ± 12.3 years; LVEF, 33.5 ± 9.8%). SDB defined as AHI ≥15 h⁻¹ was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI ( r  =   0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5–30 h⁻¹) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.     

Sleep‐disordered breathing in children with pycnodysostosis

Upper airway obstruction is a common feature in pycnodysostosis and may cause obstructive sleep apnea (OSA). The aim of our study was to analyze sleep‐disordered breathing and respiratory management in children with pycnodysostosis. A retrospective review of the clinical charts and sleep studies of 10 consecutive children (three girls and seven boys) with pycnodysostosis seen over a time period of 10 years was performed. Six patients had severe OSA and/or nocturnal hypoventilation and were started on continuous positive airway pressure (CPAP) as a first treatment at a median age of 3.4 ± 2.6 years, because of the lack of indication of any surgical treatment. Three patients could be weaned after several years from CPAP after spontaneous improvement (two patients) or multiple upper airway surgeries (one patient). Three patients had upper airway surgery prior to their first sleep study with two patients still needing CPAP during their follow‐up. Only one patient never developed OSA. Patients with pycnodysostosis are at a high risk of severe OSA, underlying the importance of a systematic screening for sleep‐disordered breathing. Multidisciplinary care is mandatory because of the multilevel airway obstruction. CPAP is very effective and well accepted for treating OSA.     

Effects of helium and 40% O2 on graded exercise with self-contained breathing apparatus.

Maximal exercise performance is decreased when breathing from a self-contained breathing apparatus (SCBA), owing to a ventilatory limitation imposed by the increased expiratory resistance. To test the hypothesis that decreasing the density of the breathing gas would improve maximal exercise performance, we studied 15 men during four graded exercise tests with the SCBA. Participants breathed a different gas mixture during each test: normoxia (NOX; 21% O2, 79% N2), hyperoxia (HOX; 40% O2, 60% N2), normoxic helium (HE-OX; 21% O2, 79% He), and hyperoxic helium (HE-HOX; 40% O2, 60% He). Compared to NOX, power output at the ventilatory threshold and at maximal exercise significantly increased with both hyperoxic mixtures. Minute ventilation was increased at peak exercise with both helium mixtures, and maximal aerobic power (VO2max) was significantly increased by 12.9 +/- 5.6%, 10.2 +/- 6.3%, and 21.8 +/- 5.6% with HOX, HE-OX, and HE-HOX, respectively. At peak exercise, the expired breathing resistance imposed by the SCBA was significantly decreased with both helium mixtures, and perceived respiratory distress was lower with HE-HOX. The results show that HE-OX improved maximal exercise performance by minimizing the ventilation limitation. The performance-enhancing effect of HOX may be explained by increased arterial oxygen content. Moreover, HE-HOX appeared to combine the effects of helium and hyperoxia on VO2max.     

Sleep‐disordered breathing in children with mucolipidosis

Mucolipidosis (ML) is a rare lysosomal storage disorder with a wide spectrum of disease severity according to the type. Sleep‐disordered breathing is recognized as a characteristic feature of ML but objective data are scarce. The aim of the study was to describe sleep data and medical management in children with ML α/β. All patients with ML α/β followed at a national reference center of ML were included. Five patients had ML II, one patient had ML III and one patient had ML II‐III. One patient was started on noninvasive ventilation (NIV) to allow extubation after prolonged invasive mechanical ventilation. The six other patients underwent sleep study at a median age of 1.8 years (range 4 months–17.4 years). Obstructive sleep apnea (OSA) was observed in all patients with a median apnea‐hypopnea index (AHI) of 36 events/hr (range 5–52) requiring continuous positive airway pressure (CPAP) or NIV. CPAP/NIV resulted in an improvement of nocturnal gas exchange and was continued in all patients with an excellent compliance. Two patients died. Systematic sleep studies are recommended at time of diagnosis in ML. CPAP or NIV are effective treatments of OSA, well tolerated, and may contribute to improve the quality of life of patients and caregivers.     

Apnea and heart rate detection from tracheal body sounds for the diagnosis of sleep-related breathing disorders

Sleep apnea is one of the most common sleep disorders. Here, patients suffer from multiple breathing pauses longer than 10 s during the night which are referred to as apneas. The standard method for the diagnosis of sleep apnea is the attended cardiorespiratory polysomnography (PSG). However, this method is expensive and the extensive recording equipment can have a significant impact on sleep quality falsifying the results. To overcome these problems, a comfortable and novel system for sleep monitoring based on the recording of tracheal sounds and movement data is developed. For apnea detection, a unique signal processing method utilizing both signals is introduced. Additionally, an algorithm for extracting the heart rate from body sounds is developed. For validation, ten subjects underwent a full-night PSG testing, using the developed sleep monitor in concurrence. Considering polysomnography as gold standard the developed instrumentation reached a sensitivity of 92.8% and a specificity of 99.7% for apnea detection. Heart rate measured with the proposed method was strongly correlated with heart rate derived from conventional ECG (r ² = 0.8164). No significant signal losses are reported during the study. In conclusion, we demonstrate a novel approach to reliably and noninvasively detect both apneas and heart rate during sleep.     

Age and QT variability index during free breathing, controlled breathing and tilt in patients with chronic heart failure and healthy control subjects

The QT variability index (QTVI) indicates temporal dispersion in myocardial repolarization, and a high QTVI is associated with a propensity for sudden death from malignant ventricular arrhythmias in subjects at high risk. In this study, the authors assessed the effects of free breathing, controlled breathing, and sympathetic stress (tilt) on the QTVI in patients with chronic heart failure (CHF) and healthy control subjects. The authors also examined the influence of age on the same variables. To obtain normative data, they calculated 95% confidence intervals for healthy subjects grouped according to age. Under all experimental conditions, the QTVI was larger in the CHF group overall and in the age subsets than in controls. In patients and controls, the QTVI increased significantly during tilt, although no differences were found between the QTVI measured during free and controlled breathing. In healthy controls, the following variables correlated significantly with the QTVI: age and baseline heart rate (P < 0.001). In patients with CHF, aging had no influence on the QTVI. Conclusion: Age, sympathetic stress, and CHF all tend to increase the QTVI and could potentially induce sudden death. Further studies should assess the usefulness of the QTVI as a marker predicting sudden cardiac death under the various conditions of risk.