Ventricular assist devices and sleep-disordered breathing-A mechanical heart stimulating a sleepy brain.

Sleep-disordered breathing, including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is common in severe heart failure (HF) patients. There is limited data on the effect of left ventricular assist devices (LVAD) on sleep apnea. We performed a retrospective review of 350 durable LVAD patients and found 5 with a history of pre- and post-LVAD sleep studies. All five patients had OSA, and three had concomitant CSA. We observed reduced apnea-hypopnea index following LVAD placement. This was due to a near abolishment of CSA in three mixed sleep apnea patients-as seen by a central apnea index improvement from an average of 25.9 ± 13.1 to 1.4 ± 2.5 events per hour (p = 0.063). LVAD placement was associated with an increase in thermodilution cardiac output from 2.7 ± 0.6 to 4.1 ± 1.1 L/min (p = 0.014). These findings support chemoreception physiology seen in patients with poor circulation and the effect of restoring this circulation with LVAD support.

Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study.

BACKGROUND: Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA. METHODS: HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea-hypopnoea index (AHI) ≥15 events·h-1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed. RESULTS: 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h-1). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min-1 at baseline to 44.6±11.2 bursts·min-1; ASV group: 43.0±9.0 bursts·min-1 at baseline to 42.74±9.45 bursts·min-1). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective. CONCLUSIONS: Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.

Circulating miR-133a-3p defines a low-risk subphenotype in patients with heart failure and central sleep apnea: a decision tree machine learning approach.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes. OBJECTIVE: To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA. METHODS: The study included patients with HFrEF and CSA from the SERVE-HF trial. A three-step protocol was applied: microRNA (miRNA) screening (n = 20), technical validation (n = 60), and biological validation (n = 587). The primary outcome was either death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of heart failure, whatever occurred first. MiRNA quantification was performed in plasma samples using miRNA sequencing and RT-qPCR. RESULTS: Circulating miR-133a-3p levels were inversely associated with the primary study outcome. Nonetheless, miR-133a-3p did not improve a previously established clinical prognostic model in terms of discrimination or reclassification. A customized regression tree model constructed using the Classification and Regression Tree (CART) algorithm identified eight patient subphenotypes with specific risk patterns based on clinical and molecular characteristics. MiR-133a-3p entered the regression tree defining the group at the lowest risk; patients with log(NT-proBNP) ≤ 6 pg/mL (miR-133a-3p levels above 1.5 arbitrary units). The overall predictive capacity of suffering the event was highly stable over the follow-up (from 0.735 to 0.767). CONCLUSIONS: The combination of clinical information, circulating miRNAs, and decision tree learning allows the identification of specific risk subphenotypes in patients with HFrEF and CSA.

Unexplained Significant Central Sleep Apnea in Infants: Clinical Presentation and Outcomes.

OBJECTIVE: Unexplained significant central sleep apnea in term infants presents as central apneas with associated oxygen desaturations requiring respiratory support and monitoring for prolonged periods. However, there is a paucity of literature describing idiopathic central sleep apnea (ICSA) in term or near-term infants. Our aim was to describe the clinical manifestations, polysomnography data, interventions, and trajectory of ICSA in infants. DESIGN: This is a retrospective study of infants (gestational age ≥ 35 weeks) who presented with significant central apneas and were subsequently diagnosed with ICSA following polysomnography and clinical investigations between January 2011 and April 2021 at a tertiary care hospital in Canada. Polysomnography data, clinical investigations, and treatments were documented. RESULTS: Eighteen infants (male, 78%; median gestational age 38 weeks) with ICSA were included. Initial polysomnograms were completed at a median (interquartile range [IQR]) age of 1.2 (0.6-1.6) months (n = 18) and follow-up polysomnograms at 12.4 (10.6-14.0) months (n = 13). Compared to baseline diagnostic polysomnograms, at follow-up there was a significant reduction in the median (IQR) central apnea-hypopnea index (26.1 [18.2-52.9] versus 4.2 [2.6-7.2] events/hour; p = 0.001), desaturation index (30.9 [12.2-57.4] versus 3.9 [3.0-7.9] events/hour; p = 0.002), average transcutaneous carbon dioxide (41.9 [40.1-47.3 versus 39.4 [37.5-42.7] mmHg; p = 0.025), and improved nadir oxygen saturation (79.8 [69.1-83.0] versus 85.5 [83.2-87.8]%; p = 0.033), respectively. Prescribed treatments included supplemental oxygen (14/18, 78%), caffeine (5/18, 28%), and noninvasive ventilation (1/18, 6%). CONCLUSIONS: Infants with significant unexplained ICSA have a favorable clinical trajectory over time. Further research is needed to understand the etiology of this rare disorder.

Phrenic nerve stimulation for the treatment of central sleep apnea in patients with heart failure.

OBJECTIVE: Central sleep apnea (CSA) is associated with increased morbidity and mortality in patients with heart failure (HF). We aimed to explore the effectiveness of phrenic nerve stimulation (PNS) on CSA in patients with HF. METHODS: This was a prospective and non-randomized study. The stimulation lead was inserted into the right brachiocephalic vein and attached to a proprietary neurostimulator. Monitoring was conducted during the implantation process, and all individuals underwent two-night polysomnography. RESULTS: A total of nine subjects with HF and CSA were enrolled in our center. There was a significant decrease in the apnea-hypopnea index (41 ± 18 vs 29 ± 25, p = 0.02) and an increase in mean arterial oxygen saturation (SaO2) (93% ± 1% vs 95% ± 2%, p = 0.03) after PNS treatment. We did not observe any significant differences of oxygen desaturation index (ODI) and SaO2 < 90% (T90) following PNS. Unilateral phrenic nerve stimulation might also categorically improve the severity of sleep apnea. CONCLUSION: In our non-randomized study, PNS may serve as a therapeutic approach for CSA in patients with HF.

The impact of sleep disordered breathing on cardiac troponin in acutely decompensated heart failure.

PURPOSE: Sleep disordered breathing in decompensated heart failure has physiological consequences (e.g., intermittent hypoxemia) that may predispose to subclinical myocardial injury, yet a temporal relationship between sleep apnea and troponin elevation has not been established. METHODS: We assessed the feasibility of performing respiratory polygraphy and measuring overnight high-sensitivity cardiac troponin T change in adults admitted to the hospital with acutely decompensated heart failure. Repeat sleep apnea tests (SATs) were performed to determine response to optimal medical heart failure therapy. Multivariable logistic regression was used to identify associations between absolute overnight troponin change and sleep apnea characteristics. RESULTS: Among the 19 subjects with acutely decompensated heart failure, 92% of SATs demonstrated sleep disordered breathing (apnea-hypopnea index [AHI] > 5 events/h). For those with repeat SATs, AHI increased in 67% despite medical management of heart failure. Overnight troponin increase was associated with moderate to severe sleep apnea (vs. no to mild sleep apnea, odds ratio (OR = 18.4 [1.51-224.18]), central apnea index (OR = 1.11 [1.01-1.22]), and predominantly central sleep apnea (vs. obstructive, OR = 22.9 [1.29-406.32]). CONCLUSIONS: Sleep apnea severity and a central apnea pattern may be associated with myocardial injury. Respiratory polygraphy with serial biomarker assessment is feasible in this population, and combining this approach with interventions (e.g., positive airway pressure) may help establish if a link exists between sleep apnea and subclinical myocardial injury.

Adaptive servo-ventilation and mortality in patients with systolic heart failure and central sleep apnea: a single-center experience.

BACKGROUND: Central sleep apnea (CSA) is associated with increased mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Treatment of CSA with a certain type of adaptive servo-ventilation (ASV) device that targets minute ventilation (ASVmv) was found to be harmful in these patients. A newer generation of ASV devices that target peak flow (ASVpf) is presumed to have different effects on ventilation and airway patency. We analyzed our registry of patients with HFrEF-CSA to examine the effect of exposure to ASV and role of each type of ASV device on mortality. METHODS: This is a retrospective cohort study in patients with HFrEF and CSA who were treated with ASV devices between 2008 and 2015 at a single institution. Mortality data were collected through the institutional data honest broker. Usage data were obtained from vendors' and manufacturers' servers. Median follow-up was 64 months. RESULTS: The registry included 90 patients with HFrEF-CSA who were prescribed ASV devices. Applying a 3-h-per-night usage cutoff, we found a survival advantage at 64 months for those who used the ASV device above the cutoff (n = 59; survival 76%) compared to those who did not (n = 31; survival 49%; hazard ratio 0.44; CI 95%, 0.20 to 0.97; P = 0.04). The majority (n = 77) of patients received ASVpf devices with automatically adjusting end-expiratory pressure (EPAP) and the remainder (n = 13) received ASVmv devices mostly with fixed EPAP (n = 12). There was a trend towards a negative correlation between ASVmv with fixed EPAP and survival. CONCLUSION: In this population of patients with HFrEF and CSA, there was no evidence that usage of ASV devices was associated with increased mortality. However, there was evidence of differential effects of type of ASV technology on mortality.

[Relationship between obstructive sleep apnea and coronary artery stenosis, myocardial injury and cardiac structure and function in coronary heart disease patients].

Objective: To further investigate the relationship between sleep apnea and coronary heart disease. Obstructive sleep apnea (OSA) is associated with various cardiovascular diseases including coronary heart disease. Moderate to severe OSA patients are prone to more severe coronary stenosis. We combined the serological indicators, echocardiography and coronary angiography all together to further investigate the relationship between sleep apnea and coronary heart disease. Methods: A total of 110 coronary heart disease patients who underwent coronary angiography and overnight polysomnography during hospitalization were enrolled, including 97 males and 13 females aged 27-85 years. Data of baseline characteristics, biochemical measurements, echocardiography, coronary angiography and polysomnography were collected. The differences in cardiovascular indicators of different degrees of OSA were compared by t-test and nonparametric test. Logistic regression was used to analyze the risk factors for OSA and coronary stenosis. Results: The median age of the enrolled 110 patients was 56 years. Totally, 88.2% patients were male and 84.5% suffered from OSA. Patients with moderate to severe OSA had a greater degree of heart rate variation during sleep, a wider proximal ascending aorta, and were more prone to abnormal right heart structure, however, no significant difference was found in myocardial injury. Patients with more severe coronary stenosis were more likely to have OSA, and they often had higher apnea-hypopnea index (AHI) and more central sleep apnea. Hypertension was independently associated with coronary stenosis and moderate to severe OSA after adjustment (OR=3.88, P=0.035; OR=2.95, P=0.046). Conclusions: Patients with more severe coronary stenosis had higher prevalence of OSA and more central sleep apnea affairs. Coronary heart disease patients with moderate to severe sleep apnea were more likely to develop aortic widening and abnormal right heart structure. Hypertension was an independent risk factor for severe coronary stenosis and moderate to severe OSA, respectively.

Sleep-disordered breathing and ventilatory chemosensitivity in first ischaemic stroke patients: a prospective cohort study.

RATIONALE: Sleep-disordered breathing (SDB) is highly prevalent after stroke. The clinical and ventilatory chemosensitivity characteristics of SDB, namely obstructive, central and coexisting obstructive and central sleep apnoea (coexisting sleep apnoea) following stroke are poorly described. OBJECTIVE: To determine the respective clinical and ventilatory chemosensitivity characteristics of SDB at least 3 months after a first ischaemic stroke. METHODS: Cross-sectional analysis of a prospective, monocentric cohort conducted in a university hospital. 380 consecutive stroke or transient ischaemic attack patients were screened between December 2016 and December 2019. MEASUREMENTS AND MAIN RESULTS: Full-night polysomnography, and hypercapnic ventilatory response were performed at a median (Q1; Q3) time from stroke onset of 134.5 (97.0; 227.3) days. 185 first-time stroke patients were included in the analysis. 94 (50.8%) patients presented no or mild SDB (Apnoea-Hypopnoea Index <15 events/hour of sleep) and 91 (49.2%) moderate to severe SDB, of which 52 (57.1%) presented obstructive sleep apnoea and 39 (42.9%) coexisting or central sleep apnoea. Obstructive sleep apnoea patients significantly differed regarding their clinical presentation from patients with no or mild SDB, whereas there was no difference with coexisting and central sleep apnoea patients. The latter presented a higher frequency of cerebellar lesions along with a heightened hypercapnic ventilatory response compared with no or mild SDB patients. CONCLUSION: SDB in first-time stroke patients differ in their presentation by their respective clinical traits and ventilatory chemosensitivity characteristics. The heightened hypercapnic ventilatory response in coexisting and central sleep apnoea stroke patients may orientate them to specific ventilatory support.

Effect of adaptive servo ventilation on central sleep apnea and sleep structure in systolic heart failure patients: polysomnography data from the SERVE-HF major sub study.

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94-103 in the control group, 77-99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk.

The Pathogenesis of Central and Complex Sleep Apnea.

PURPOSE: The purpose of this article is to review the recent literature on central apnea. Sleep disordered breathing (SDB) is characterized by apneas (cessation in breathing), and hypopneas (reductions in breathing), that occur during sleep. Central sleep apnea (CSA) is sleep disordered breathing in which there is an absence or diminution of respiratory effort during breathing disturbances while asleep. In obstructive sleep apnea (OSA), on the other hand, there is an absence of flow despite ongoing ventilatory effort. RECENT FINDINGS: Central sleep apnea is a heterogeneous disease with multiple clinical manifestations. OSA is by far the more common condition; however, CSA is highly prevalent among certain patient groups. Complex sleep apnea (CompSA) is defined as the occurrence/emergence of CSA upon treatment of OSA. Similarly, there is considerable overlap between CSA and OSA in pathogenesis as well as impacts. Thus, understanding sleep disordered breathing is important for many practicing clinicians.

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.

Adaptive support ventilation as an effective treatment option for central sleep apnea in an older adult with heart failure with preserved ejection fraction: a case report.

BACKGROUND: Adaptive support ventilation (ASV) is a proposed treatment option for central sleep apnea (CSA). Although the effectiveness of ASV remains unclear, some studies have reported promising results regarding the use of ASV in patients with heart failure with preserved ejection fraction (HfpEF). To illustrate the importance of suspecting and diagnosing sleep-disordered breathing (SDB) in older adults unable to recognize symptoms, we discuss a case in which ASV was effective in a patient with CSA and HfpEF, based on changes in the Holter electrocardiogram (ECG). CASE PRESENTATION: An 82-year-old man presented to our hospital with vomiting on April 19, 2021. Approximately 10 years before admission, he was diagnosed with type 1 diabetes mellitus and recently required full support from his wife for daily activities due to cognitive dysfunction. Two days before admission, his wife was unable to administer insulin due to excessively high glucose levels, which were displayed as "high" on the patient's glucose meter; therefore, we diagnosed the patient with diabetic ketoacidosis. After recovery, we initiated intensive insulin therapy for glycemic control. However, the patient exhibited excessive daytime sleepiness, and numerous premature ventricular contractions were observed on his ECG monitor despite the absence of hypoglycemia. As we suspected sleep-disordered breathing (SDB), we performed portable polysomnography (PSG), which revealed CSA. PSG revealed a central type of apnea and hypopnea due to an apnea-hypopnea index of 37.6, which was > 5. Moreover, the patient had daytime sleepiness; thus, we diagnosed him with CSA. We performed ASV and observed its effect using portable PSG and Holter ECG. His episodes of apnea and hypopnea were resolved, and an apparent improvement was confirmed through Holter ECG. CONCLUSION: Medical staff should carefully monitor adult adults for signs of or risk factors for SDB to prevent serious complications. Future studies on ASV should focus on older patients with arrhythmia, as the prevalence of CSA may be underreported in this population and determine the effectiveness of ASV in patients with HfpEF, especially in older adults.

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.

Abnormalities of the Vertebrobasilar Arterial System Leading to Sleep Disorders.

INTRODUCTION: The abnormalities in the vertebrobasilar arterial system such as enlarged, tortuous or dilated arteries and aneurysms can generate pressure and distortion of brain structures especially in the medulla and pons. This brainstem compression by abnormal arteries can lead to various sleep disorders such as sleep related hypoventilation, central sleep apnea, obstructive sleep apnea, and positional sleep apnea. AIM: To highlight brainstem compression due to vascular abnormalities as a cause of sleep disordered breathing. METHODS: Manuscripts were identified using the National Institutes of Health PubMed literature search system. Search terms included sleep disorders, vertebrobasilar dolichoectasia, tortuous vertebral arteries, vertebrobasilar aneurysms, vascular compression and brainstem compression. Inclusion criteria required that the articles were written in English, highlighted both a sleep disorder and a vascular abnormality. RESULTS: The literature search resulted in 10 case reports where vascular abnormalities were leading to sleep disorders. Out of these: four patients had central sleep apnea; three had sleep related hypoventilation; one had positional central sleep apnea; one had positional central apnea along with obstructive sleep apnea; and one had obstructive sleep apnea. The various vascular lesions identified were: megadolichobasilar artery; dolichoectatic vertebral artery; fusiform vertebrobasilar aneurysm; tortuous and elongated vertebral arteries; calcified vertebral artery and medullary telangiectasia. CONCLUSIONS: Arterial compression of the respiratory centers in the pons and medulla can lead to central sleep apnea. Obstructive sleep apnea can also result from vascular compression of the medulla. The proposed mechanism is compression of nucleus ambiguus which controls pharyngeal tone. Pressure on cranial nerves IX and X can lead to pharyngeal dysfunction leading to occlusive apnea.

Sleep-related breathing disorders and pulmonary hypertension.

Sleep-related breathing disorders (SBDs) include obstructive apnoea, central apnoea and sleep-related hypoventilation. These nocturnal events have the potential to increase pulmonary arterial pressure (PAP) during sleep but also in the waking state. "Pure" obstructive sleep apnoea syndrome (OSAS) is responsible for a small increase in PAP whose clinical impact has not been demonstrated. By contrast, in obesity hypoventilation syndrome (OHS) or overlap syndrome (the association of chronic obstructive pulmonary disease (COPD) with obstructive sleep apnoea (OSA)), nocturnal respiratory events contribute to the development of pulmonary hypertension (PH), which is often severe. In the latter circumstances, treatment of SBDs is essential in order to improve pulmonary haemodynamics.Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are at risk of developing SBDs. Obstructive and central apnoea, as well as a worsening of ventilation-perfusion mismatch, can be observed during sleep. There should be a strong suspicion of SBDs in such a patient population; however, the precise indications for sleep studies and the type of recording remain to be specified. The diagnosis of OSAS in patients with PAH or CTEPH should encourage treatment with continuous positive airway pressure (CPAP). The presence of isolated nocturnal hypoxaemia should also prompt the initiation of long-term oxygen therapy. These treatments are likely to avoid worsening of PH; however, it is prudent not to treat central apnoea and Cheyne-Stokes respiration (CSR) with adaptive servo-ventilation in patients with chronic right-heart failure because of a potential risk of serious adverse effects from such treatment.In this review we will consider the current knowledge of the consequences of SBDs on pulmonary haemodynamics in patients with and without chronic respiratory disease (group 3 of the clinical classification of PH) and the effect of treatments of respiratory events during sleep on PH. The prevalence and consequences of SBDs in PAH and CTEPH (groups 1 and 4 of the clinical classification of PH, respectively), as well as therapeutic options, will also be discussed.

Central Apnea of Prematurity: Does Sex Matter?

OBJECTIVE: Apnea is common among infants in the neonatal intensive care unit (NICU). Our group previously developed an automated algorithm to quantitate central apneas with associated bradycardia and desaturation (ABDs). Sex differences in lung disease are well described in preterm infants, but the influence of sex on apnea has not been established. STUDY DESIGN: This study includes infants < 34 weeks' gestation admitted to the University of Virginia NICU from 2009 to 2014 with at least 1 day of bedside monitor data available when not on mechanical ventilation. Waveform and vital sign data were analyzed using a validated algorithm to detect ABD events of low variance in chest impedance signal lasting at least 10 seconds with associated drop in heart rate to < 100 beats/minute and drop in oxygen saturation to < 80%. Male and female infants were compared for prevalence of at least one ABD event during the NICU stay, treatment with caffeine, occurrence of ABDs at each week of postmenstrual age, and number of events per day. RESULTS: Of 926 infants studied (median gestational age 30 weeks, 53% male), median days of data analyzed were 19 and 22 for males and females, respectively. There was no sex difference in prevalence of at least one ABD event during the NICU stay (males 62%, females 64%, p = 0.47) or in the percentage of infants treated with caffeine (males 64%, females 67%, p = 0.40). Cumulative prevalence of ABDs from postmenstrual ages 24 to 36 weeks was comparable between sexes. Males had 18% more ABDs per day of data, but this difference was not statistically significant (p = 0.16). CONCLUSION: In this large cohort of infants < 34 weeks' gestation, we did not detect a sex difference in prevalence of central ABD events. There was a nonsignificant trend toward a greater number of ABDs per day in male infants. KEY POINTS: · Central apnea is pervasive among preterm infants in the NICU, but potential disparities between males and females have not been thoroughly studied.. · Identification of risk factors for central apnea can lead to improved treatment protocols.. · The rate and prevalence of central apnea events accompanied by bradycardia and desaturation does not significantly differ between male and female preterm infants..

Life-threatening cardiac arrhythmias in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients are at risk for life-threatening cardiac arrhythmias, and presentation is dependent on their PHOX2B gene mutation. We describe the presentation of life-threatening arrhythmias in our cohort of CCHS patients. We reviewed the records of 72 CCHS patients seen at CHLA from 2004 to 2018. Data collected included demographics, PHOX2B genotype, ventilatory support, clinical symptoms, ambulatory cardiac monitoring results, and presence of cardiac pacemaker. Sixteen of 72 patients had evidence of potential life-threatening cardiac arrhythmias. PHOX2B genotypes were 20/25 polyalanine repeat expansion mutation (PARM), 20/26 PARM, 20/27 PARM, 20/32 PARM, and c.245C > T non-polyalanine repeat mutation. 11/16 patients were ventilated during sleep only. Symptoms included syncope, dizziness, chest pain, tingling in the left arm, and palpitations. 15/16 patients had recorded ambulatory cardiac monitoring. 5/16 patients were symptomatic without significant sinus pauses. 12/16 patients had implantation of cardiac pacemakers. 9/12 had significant sinus pauses on ambulatory monitoring, and 7/12 patients were symptomatic.Conclusion: CCHS patients have potential life-threatening arrhythmias requiring cardiac pacemaker implantation. Many of these patients are symptomatic with significant sinus pauses on ambulatory monitoring. However, some symptomatic patients with no significant pauses on ambulatory monitoring may still require cardiac pacemaker implantation.What is Known:• CCHS patients are at risk for life-threatening sinus pauses and require cardiac pacemaker implantation.What is New:• CCHS patients regardless of PHOX2B genotype are at risk for significant sinus pauses. Many CCHS patients with significant sinus pause on ambulatory cardiac monitoring are symptomatic and most present with syncope. Some symptomatic patients do not have significant sinus pauses but may still require cardiac pacemaker implantation.

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.

Interventional techniques to increase implantation success of transvenous phrenic nerve stimulation for central sleep apnea treatment.

PURPOSE: Central sleep apnea (CSA) is a highly common comorbidity in heart failure (HF) patients and is known to deteriorate quality of life and prognosis. Effective treatment options are scarce. Transvenous phrenic nerve stimulation (PNS) has been shown to be effective and safe in CSA treatment in HF. However, lead implantation may be difficult or fail due to anatomical or technical challenges. We report novel and innovative approaches applying different interventional techniques to enhance PNS implantation success, allowing otherwise missing CSA treatment. METHODS: Twenty-seven consecutive HF patients (86% male, mean age: 69 ± 11 years; reduced left ventricular ejection fraction in 16 patients (57%)) were included in this study who were unable to tolerate or had contraindications for mask-based therapy. We evaluated PNS total implantation success, procedural characteristics, and feasibility and success rates of intravascular interventions to facilitate PNS lead implantation in otherwise ineffective procedures. RESULTS: Seven lead implantation attempts (24%) required additional intravascular interventional action to facilitate successful implantation, mainly consisting of balloon angioplasties to allow optimal PNS lead placement. Two procedures remained unsuccessful and two patients underwent a second procedure due to stimulation side effects and lead fracture respectively. All over, no complications resulted from application of interventional techniques to achieve a 93% implantation success rate. CONCLUSION: Transvenous PNS lead placement for CSA treatment can be difficult and challenging. However, interventional intravascular techniques markedly increase implantation success and thereby allow application of this therapy for effective CSA treatment in most patients without additional complications.