Oscillatory Breathing Pattern Research Articles

P3523Cardiac contractility modulation provides improved ventilatory efficiency and reduces oscillatory breathing pattern

Abstract Introduction Cardiac Contractility Modulation (CCM) is a treatment for patients with heart failure with reduced ejection fraction (HFrEF) providing improved myocardial molecular and biochemical characteristics and thus improved exercise tolerance and quality of life by application of electrical signals during the absolute refractory period. Cardiopulmonary exercise testing is an integrative method to assess exercise tolerance in heart failure patients providing insights in circulatory, respiratory and metabolic reactions during exercise. The VE/VCO2-Slope (minute ventilation/carbon dioxide production) and an oscillatory breathing pattern have widely been demonstrated to have strong prognostic value for patients with chronic heart failure. Methods Between February 2017 and January 2019 15 patients (mean age 64.4±7.9 years, NYHA 2.93±0.58) with standard indication for CCM-therapy have been enrolled in a single center in Germany. Prior to implantation of the Optimizer Smart System, symptom-limited cardiopulmonary exercise testing was performed using a bicycle ramp protocol (25W+10W/min). The Follow-up was conducted 6 weeks post implantation. The control group consisted of 45 patients (mean age 64.8±7.9 years, NYHA 2.2±0.72) with stable systolic heart failure and reduced ejection fraction. Statistical Analysis was performed by paired and unpaired t tests. Results 6 weeks after CCM-implantation the VE/VCO2-Slope showed a significant decrease (39.6±11.1 vs. 36.6±8.9, p<0.05) showing changes in ventilatory efficiency whereas the control-group showed stable measurements with even an increasing tendency (33.6±7.4 vs. 34.2±7.4, p=0.43). The absolute change of the VE/VCO2-Slope between the CCM-group and control-group highlights the improvement after the intervention (−2.99±5.07 vs. 0.63±4.79, p<0.05). The number of patients presenting an oscillatory breathing pattern markedly decreased with CCM-therapy (11 of 15 vs. 6 of 15, p<0.05), whereas even one additional patient of the control group showed an oscillatory breathing pattern at follow up (15 of 45 vs. 16 of 45). In contrast, subjects showed no significant changes in watt-measurements (72.67 W ± 19.2 W vs. 76.57 W ± 18.5 W) or maximal oxygen uptake (1034 ml/min ± 247 ml/min vs. 1104 ml/min ± 256 ml/min) compared to baseline. Similarly, the control-group showed stable measurements for external load (79.9 W ± 16.4 W vs. 77.1 W ± 17.5 W) and peak oxygen uptake (1097 ml/min ± 225 ml/min vs. 1116 ml/min ± 330 ml/min). Conclusion Cardiac Contractility Modulation provides improved ventilatory efficiency measures by VE/VCO2-slope and reduces oscillatory breathing pattern during exercise at follow up. As the low ventilatory efficiency observed in patients with heart failure constitutes an important predictor of cardiovascular mortality these results provide an interesting insight of therapeutic effects of Cardiac Contractility Modulation apart from VO2-measurements.

P317Improvement of ventilatory efficiency and reduction of oscillatory breathing pattern by cardiac contractility modulation

P317Improvement of ventilatory efficiency and reduction of oscillatory breathing pattern by cardiac contractility modulation

Enhanced carotid body chemoreflex function drives respiratory‐sympathetic coupling in systolic heart failure

Enhanced carotid body (CB) chemoreflex sensitivity in systolic heart failure (HF) has been linked to oscillatory breathing patterns and autonomic imbalance. Importantly, breathing pattern alterations and heightened chemoreflex‐mediated sympathetic nerve activity are both associated with higher morbidity and mortality in HF. Therefore, the objective of this study was to determine whether CB denervation (CBD) would improve respiratory stability and decrease sympathetic drive in HF. In rabbits with pacing‐induced HF, we measured resting breathing and renal sympathetic nerve activity (RSNA), before and after CBD. In addition, we assessed respiratory‐sympathetic coupling using power spectral analysis and the magnitude of the peak coherence function between tidal volume (Vt) and RSNA frequency spectra. Minute ventilation and RSNA responses to acute hypoxia were significantly augmented in HF compared to controls and were abolished by CBD. Resting RSNA was greater in HF compared to control animals (43 ± 5% max vs. 23 ± % max, p<0.05). HF animals after CBD displayed resting RSNA levels similar to control animals. HF animals displayed altered breathing patterns characterized by oscillatory breathing and increases in the incidence of apneas/hypopneas. Remarkably, CBD totally normalized oscillatory breathing patterns in HF animals. Peak coherence between RSNA and Vt signals was increased in HF animals (control 0.49 ± 0.05; HF 0.79 ± 0.06), and was significantly attenuated by CBD (0.59 ± 0.05, p<0.05 for all comparisons). Our data show that enhanced CB‐mediated chemoreflex drive contributes to tonic elevations in RSNA and breathing instability in HF. Additionally, a tonic increase in CB afferent discharge may also play an important role in strengthening a link between respiratory and sympathetic neural outflow in HF.Support or Funding InformationSupported by Fondecyt 1140275, NIH PO1‐HL62222 and NIH F32 HL108592‐01A1.

A model of the effects of fluid variation due to body position on Cheyne-Stokes respiration.

Cheyne-Stokes respiration is a distinct breathing pattern consisting of periods of hyperpnea followed by apnoeas, with unknown aetiology. One in two patients with congestive heart failure suffers from this condition. Researchers hypothesize that key factors in CSR are the fluid shift from the standing to supine position and the differences between genders. A mathematical model of the cardiorespiratory system was constructed using parameter values from real data. Hopf bifurcation analysis was used to determine regions of steady versus oscillatory breathing patterns. In the model, Cheyne-Stokes respiration is more likely to occur while in the supine position and males are more likely to develop Cheyne-Stokes than females. These findings, which are in agreement with clinical experience, suggest that both gender and fluid shift contribute to the pathogenesis of Cheyne-Stokes respiration and that physical quantities such as blood volumes and neural feedback may be sufficient to explain the observations of CSR.

Central role of carotid body chemoreceptors in disordered breathing and cardiorenal dysfunction in chronic heart failure.

Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. Elimination of CB afferents in experimental models of CHF has been shown to reduce OB, respiratory-sympathetic coupling, and renal SNA, and to improve autonomic balance in the heart. The CB chemoreceptors may play an important role in progression of CHF by contributing to respiratory instability and OB, which in turn further exacerbates tonic and chemoreflex-evoked increases in SNA to the heart and kidney.

Pathophysiology of oscillatory breathing during sleep and exercise in heart failure patients (1132.12)

Background: There is OB during sleep and exercise in HF. However, mechanism is unclear. Since 2011, we reported new theory system of integrated control/regulation of respiration-circulation. For breath, the next breath is dominantly initiated by this breath, by magnitude of oscillatory PaO2, PaCO2 and [H+] via fast peripheral chemical receptors (PCR); and its gain/sensitivity is adjusted by slow central chemical receptors (CCR) with long time delay (~30s). It appears to be clear to explain mechanism of OB. Pathophysiology: 1.Ventricle Mixed Effect: It decreased oscillatory signals in blood which dominantly effected by LVEF. The poor ventricle function (lower LVEF) , the lower oscillatory magnitude from pulmonary vein o artery. The normal breath signals, via HF ventricle, only generate smaller next breath; and so on襃 the final breath should be very small or disappeared (apnea). 2. Time Phase difference: Then delayed averaged/mean signal arrived at central chemical receptors will change gain to adjust the sensitivity to make larger breath襃 There is a time phase difference between PCR (close to lung) and CCR, i.e. PCR-lung hyperventilation with CCR hypoventilation and PCR-lung hypoventilation with CCR hyperventilation. Combined two of Ventricle Mixed Effect and Time Phase Difference, HF patients should have oscillatory breathing pattern. Grant Funding Source: Chinese National High Technology Research and Development Program (863 Program) Project 2012AA021009

Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

In congestive heart failure (CHF), carotid body (CB) chemoreceptor activity is enhanced and is associated with oscillatory (Cheyne-Stokes) breathing patterns, increased sympathetic nerve activity (SNA) and increased arrhythmia incidence. We hypothesized that denervation of the CB (CBD) chemoreceptors would reduce SNA, reduce apnoea and arrhythmia incidence and improve ventricular function in pacing-induced CHF rabbits. Resting breathing, renal SNA (RSNA) and arrhythmia incidence were measured in three groups of animals: (1) sham CHF/sham-CBD (sham-sham); (2) CHF/sham-CBD (CHF-sham); and (3) CHF/CBD (CHF-CBD). Chemoreflex sensitivity was measured as the RSNA and minute ventilatory (VE) responses to hypoxia and hypercapnia. Respiratory pattern was measured by plethysmography and quantified by an apnoea-hypopnoea index, respiratory rate variability index and the coefficient of variation of tidal volume. Sympatho-respiratory coupling (SRC) was assessed using power spectral analysis and the magnitude of the peak coherence function between tidal volume and RSNA frequency spectra. Arrhythmia incidence and low frequency/high frequency ratio of heart rate variability were assessed using ECG and blood pressure waveforms, respectively. RSNA and VE responses to hypoxia were augmented in CHF-sham and abolished in CHF-CBD animals. Resting RSNA was greater in CHF-sham compared to sham-sham animals (43±5% max vs. 23 ± 2% max, P<0.05), and this increase was not found in CHF-CBD animals (25±1% max, P<0.05 vs. CHF-sham). Low frequency/high frequency heart rate variability ratio was similarly increased in CHF and reduced by CBD (P<0.05). Respiratory rate variability index, coefficient of variation of tidal volume and apnoea-hypopnoea index were increased in CHF-sham animals and reduced in CHF-CBD animals (P<0.05). SRC (peak coherence) was increased in CHF-sham animals (sham-sham 0.49±0.05; CHF-sham 0.79±0.06), and was attenuated in CHF-CBD animals (0.59±0.05) (P<0.05 for all comparisons). Arrhythmia incidence was increased in CHF-sham and reduced in CHF-CBD animals (213±58 eventsh(-1) CHF, 108±48 eventsh(-1) CHF-CBD, P<0.05). Furthermore, ventricular systolic (3.8±0.7 vs. 6.3±0.5ml, P<0.05) and diastolic (6.3±1.0 vs. 9.1±0.5ml, P<0.05) volumes were reduced, and ejection fraction preserved (41±5% vs. 54±2% reduction from pre-pace, P<0.05) in CHF-CBD compared to CHF-sham rabbits. Similar patterns of changes were observed longitudinally within the CHF-CBD group before and after CBD. In conclusion, CBD is effective in reducing RSNA, SRC and arrhythmia incidence, while improving breathing stability and cardiac function in pacing-induced CHF rabbits.

Treatment of Central Sleep Apnea in US Veterans

There are no standard therapies for the management of central sleep apnea (CSA). Either positive pressure therapy (PAP) or supplemental oxygen (O(2)) may stabilize respiration in CSA by reducing ventilatory chemoresponsiveness. Additionally, increasing opioid use and the presence of comorbid conditions in US veterans necessitates investigations into alternative titration protocols to treat CSA. The goal was to report on the effectiveness of titration with PAP, used alone or in conjunction with O(2), for the management of CSA associated with varying comorbidities and opioid use. This was a retrospective chart review over 3 years, performed at a VA sleep disorders center. The effects of CPAP, CPAP+O(2), and BPAP+O(2), used in a step-wise titration protocol, on consecutive patients diagnosed with CSA were studied. CSA was diagnosed in 162 patients. The protocol was effective in eliminating CSA (CAI ≤ 5/h) in 84% of patients. CPAP was effective in 48%, while CPAP+O(2) combination was effective in an additional 25%, and BPAP+O(2) in 11%. The remaining 16% were non-responders. Forty-seven patients (29%) were on prescribed opioid therapy for chronic pain, in whom CPAP, CPAP+O(2), or BPAP+O(2) eliminated CSA in 54%, 28%, and 10% cases, respectively. CPAP, CPAP+O(2), and BPAP+O(2) each produced significant declines in the AHI, CAI, and arousal index, and an increase in the SpO(2). The data demonstrate that using a titration protocol with CPAP and then PAP with O(2) effectively eliminates CSA in individuals with underlying comorbid conditions and prescription opioid use. Comparative studies with other therapeutic modalities are required.

A hybrid approach for continuous detection of sleep‐wakefulness fluctuations: validation in patients with Cheyne–Stokes respiration

Fluctuations in sleep/wake state have been proposed as an important mechanism contributing to the development of oscillatory breathing patterns, including Cheyne-Stokes respiration in patients with heart failure. In order to properly assess the interactions between changes in state and changes in ventilatory parameters, a methodology capable of continuously and reliably detecting state transitions is needed. Traditional fixed-epoch analysis of polysomnographic recordings is not suitable for this purpose. Moreover, visual identification of changes in the dominant electroencephalogram activity at the transition from wakefulness to sleep and vice versa is often very subjective. We have therefore developed a hybrid approach--including both visual scoring and computer-based procedures--for continuous analysis of state transitions from polysomnographic recordings, specifically tailored for fluctuations between wakefulness and non-rapid eye movement-1 and -2 sleep. The overall analysis process comprises three major phases: (1) manual identification of relevant electroencephalogram/electrooculogram features and events, including a sample of unequivocal alpha and theta-delta activity; (2) automatic statistical discrimination of dominant electroencephalogram activity; and (3) state classification (wakefulness, non-rapid eye movement-1 and -2). The latter is carried out by merging information from visual scoring with the output of the discriminator. Validation has been carried out in 16 patients with heart failure during daytime Cheyne-Stokes respiration, using a training and testing set of electroencephalogram polysomnograms. The statistical discriminator correctly classified 99.1 ± 1.4% and 99.2 ± 1.1% of unequivocal alpha and theta-delta activity. This approach has therefore the potential to be used to reliably measure the incidence and location of sleep-wake transitions during abnormal breathing patterns, as well as their temporal relationship with major ventilatory events.

Oscillatory Breathing and Exercise Gas Exchange Abnormalities Prognosticate Early Mortality and Morbidity in Heart Failure

The goal of this study was to identify better predictors of early death in patients with chronic left ventricular heart failure (CHF). Potential predictors, derived from cardiopulmonary exercise testing, were compared with other commonly used cardiovascular measurements. The prediction of early death in patients with CHF remains challenging. Five hundred eight patients with CHF due to systolic dysfunction underwent resting cardiovascular measurements, 6-min walking tests, and cardiopulmonary exercise testing. The peak oxygen uptake (.VO(2)), peak oxygen pulse, anaerobic threshold, ratio of ventilation to carbon dioxide output (.VE/.VCO(2)), slope of .VE versus .VCO(2), and presence or absence of a distinctive oscillatory breathing pattern (OB) were ascertained. Outcomes were 6-month mortality and morbidity, the latter a sum of cardiac hospitalizations and deaths. The single best predictor of mortality was an elevated lowest .VE/.VCO(2) (> or =155% predicted). Adding OB on the basis of stepwise regression (optimal 2-predictor model), the odds ratio for mortality increased from 9.4 to 38.9 (p < 0.001). The slope of .VE versus .VCO(2) slope, peak .VO(2), peak oxygen pulse, and anaerobic threshold combined with OB were also strong predictors. OB also increased the odds ratio 2- to 3-fold for each of these (p < 0.01). Kaplan-Meier survival curves and area under the receiver-operating characteristic curve confirmed that lowest .VE/.VCO(2) and OB were superior. For morbidity, elevated lowest .VE/.VCO(2) or lower peak .VO(2) with OB were the best predictors. No nonexercise measurements discriminated mortality and morbidity. Cardiopulmonary exercise testing parameters are powerful prognosticators of early mortality and morbidity in patients with CHF, especially the optimal 2-predictor model of a combination of elevated lowest .VE/.VCO(2) and OB.

Six-Minute Walk Test and Cardiopulmonary Exercise Testing in Patients With Chronic Heart Failure

Background— The six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) are the 2 testing modalities most broadly used for assessing functional limitation in patients with heart failure (HF). A comprehensive comparison on clinical and prognostic validity of the 2 techniques has not been performed and is the aim of the present investigation. Methods and Results— Two hundred fifty-three patients diagnosed with systolic (n=211) or diastolic (n=42) HF (age: 61.9�10.1 years; New York Heart Association Class: 2.2�0.78) underwent a 6MWT and a symptom-limited CPET evaluation and were prospectively followed up. During the 4-year tracking period, there were 43 cardiac-related deaths with an annual cardiac mortality rate of 8.7%. The 6MWT distance correlated with CPET-derived variables (ie, peak V o 2 , V o 2 at anaerobic threshold, and V e /V co 2 slope) and was significantly reduced in proportion with lower peak V o 2 and higher V e /V co 2 slope classes and presence of an exercise oscillatory breathing (EOB) pattern ( P &lt;0.01). However, no significant differences were observed in distance covered between survivors and nonsurvivors (353.2�95.8 m versus 338.5�76.4 m; P =NS). At univariate and multivariate Cox proportional analyses, the association of the 6MWT distance with survival was not significant either as a continuous or dicotomized variable (≤300 m). Conversely, CPET-derived variables emerged as prognostic with the strongest association found for EOB (systolic HF) and V e /V co 2 slope (entire population with HF and patients with a 6MWT≤300 m). Conclusions— The 6MWT is confirmed to be a simple and reliable first-line test for quantification of exercise intolerance in patients with HF. However, there is no supportive evidence for its use as a prognostic marker in alternative to or in conjunction with CPET-derived variables.

Theoretical rationale and practical recommendations for cardiopulmonary exercise testing in patients with chronic heart failure

The syndrome of chronic heart failure (CHF) becomes increasingly prevalent in older patients, and while mortality rates are declining in most cardiovascular diseases, both prevalence and mortality in CHF remain high. The heart is unable to meet the demands of the skeletal musculature, and symptoms manifest as dyspnoea and signs of fatigue during exercise. The cardiopulmonary exercise test (CPET) can provoke symptoms which may be useful in improving the accuracy of diagnosis in CHF in a non-invasive setting. CPET also provides important information on the pathophysiology of exercise limitation, risk stratification and can establish exercise-training protocols. The information provided by the CPET allows suitable pharmacological or device-based adjustments to be considered in the management of CHF, which can be crucial in maintaining a patient's quality of life. This manuscript provides a useful insight into the theoretical rationale and practical recommendations for CPET in patients with CHF. Prior to CPET, it is important to consider the mode of exercise, as cycle ergometry or treadmill protocols will yield different outcomes in patients with CHF. We discuss how pre-CPET set-up procedures should be conducted and also the significance of electrocardiographic abnormalities found in CHF patients, and how these should be interpreted. The assessment of lung function is integral to the underlying pathophysiological basis of exercise limitation and we explain how this should be performed. CHF patients display the following abnormal exercise responses which can be identified by CPET: peak oxygen uptake ( [Formula: see text] peak), anaerobic threshold (AT), DeltaVO(2)/Delta work rate (WR), peak oxygen pulse, estimated peak stroke volume and predicted peak heart rate are reduced. The [Formula: see text] slope is abnormally high and the breathing reserve is normal or high. An immediate post-exercise increase in O(2) pulse is evident, and/or a regular oscillatory breathing pattern has been observed at lower exercise intensities in some CHF patients. Symptoms of breathlessness, fatigue, and/or leg pain occur earlier during CPET and may cause the CPET to be aborted early. We explain the significance of the 9-panelled array, and how it can help to determine the underlying pathophysiology of exercise intolerance in these patients.

Effect of oscillatory breathing on the variability of the RR Intervals and its prognostic importance in individuals with left ventricular global systolic dysfunction.

To assess the effect of the oscillatory breathing on the variability of RR intervals (VRR) and on prognostic significance after one year follow-up in subjects with left ventricular global systolic dysfunction. We studied 76 subjects, whose age ranged from 40 to 80 years, paired for age and gender, divided into two groups: group I - 34 healthy subjects; group II - 42 subjects with left ventricular global systolic dysfunction (ejection fraction < or = 0.40). The ECG signals were acquired during 600s in supine position, and analyzed the variation of the thoracic amplitude and the VRR. Clinical and V-RR variables were applied into a logistic multivariate model to foretell survival after one year follow-up. Oscillatory breathing was detected in 35.7% of subjects in vigil state of group II, with a concentration of the spectral power in the very low frequency band, and was independent of the presence of diabetes, functional class, ejection fraction, cause of ventricular dysfunction and survival after one year follow-up. In the logistic regression model, ejection fraction was the only independent variable to predict survival. 1). Oscillatory breathing pattern is frequent during wakefulness in the left ventricular global systolic dysfunction and concentrates spectral power in the very low band of V-RR; 2). it does not relate to severity and cause of left ventricular dysfunction; 3). ejection fraction is the only independent predictive variable for survival in this group of subjects.

P2833 Association of oscillatory breathing patterns during wakefulness with long-term prognosis in patients with chronic heart failure

P2833 Association of oscillatory breathing patterns during wakefulness with long-term prognosis in patients with chronic heart failure

Oscillatory breathing patterns during wakefulness in patients with chronic heart failure: clinical implications and role of augmented peripheral chemosensitivity.

Oscillatory breathing patterns characterized by rises and falls in ventilation with apnea (Cheyne-Stokes respiration [CSR]) or without apnea (periodic breathing [PB]) commonly occur during the daytime in chronic heart failure (CHF). We have prospectively characterized patients with cyclical breathing in terms of clinical characteristics, indices of autonomic control, prognosis, and the role of peripheral chemosensitivity. To determine cyclical breathing pattern, power spectral analysis was applied to 30-minute recordings of respiration in 74 stable CHF patients. Analyses of heart rate variability and baroreflex sensitivity were used to assess autonomic balance. Peripheral chemosensitivity was assessed with the transient hypoxia method. We also determined whether the suppression of peripheral chemoreceptor activity (hyperoxia or dihydrocodeine) would influence the respiratory pattern. Cyclical respiration was found in 49 (66%) patients (22 [30%] CSR, 27 [36%] PB) and was associated with more advanced CHF symptoms, impaired autonomic balance, and increased chemosensitivity (0.80 and 0.75 versus 0.34 L. min(-1). %SaO(2)(-1), P<0.001, for CSR and PB versus normal breathing, respectively). Transient hyperoxia abolished oscillatory breathing in 7 of 8 patients. Dihydrocodeine administration decreased chemosensitivity by 42% (P=0.05), which correlated with improvement in respiratory pattern. Cyclical breathing predicted poor 2-year survival (relative risk 9.41, P<0.01, by Cox proportional hazards analysis), independent of peak oxygen consumption (P=0.04). An oscillatory breathing pattern during the daytime is a marker of impaired autonomic regulation and poor outcome. Augmented activity of peripheral chemoreceptors may be involved in the genesis of this respiratory pattern. Modulation of peripheral chemosensitivity can reduce or abolish abnormal respiratory patterns and may be an option in the management of CHF patients with oscillatory breathing.

Expiratory and arterial partial pressure relations under different ventilation-perfusion conditions.

Inert tracer gas exchange across the human respiratory system is simulated in an asymmetric lung model for different oscillatory breathing patterns. The momentary volume-averaged alveolar partial pressure (PA), the expiratory partial pressure (PE), the mixed expiratory partial pressure (PE), the end-tidal partial pressure (PET), and the mean arterial partial pressure (Pa), are calculated as functions of the blood-gas partition coefficient (lambda) and the diffusion coefficient (D) of the tracer gas. The lambda values vary from 0.01 to 330.0 inclusive, and four values of D are used (0.5, 0.22, 0.1, and 0.01). Three ventilation-perfusion conditions corresponding to rest and mild and moderate exercise are simulated. Under simulated exercise conditions, we compute a reversed difference between PET and Pa compared with the rest condition. This reversal is directly reflected in the relation between the physiological dead space fraction (1--PE/Pa) and the Bohr dead space fraction (1--PE/PET). It is argued that the difference (PET--Pa) depends on the lambda of the tracer gas, the buffering capacity of lung tissue, and the stratification caused by diffusion-limited gas transport in the gas phase. Finally some determinants for the reversed difference (PET--Pa) and the significance for conventional gas analysis are discussed.

Oscillatory breathing patterns leading to apneic spells in infants.

Oscillatory breathing patterns leading to apneic spells in infants.