Apnea Heart Failure Research Articles

A Long-Term Prognosis of Adaptive Servo Ventilation Therapy for Patients with Heart Failure -Consideration in Severity of Sleep-Disordered Breathing-

<p><strong>Background:</strong> Adaptive servo-ventilation (ASV) is used to treat sleep apnea in heart failure (HF). However, it is unclear whether ASV improves the long-term prognosis for all patients with HF, regardless of the severity of sleep-disordered breathing (SDB). We therefore aimed to estimate the long-term prognosis associated with ASV therapy for patients with HF by the severity of SDB.</p><p><strong>Methods:</strong> Sixty-one consecutive patients with HF (mean age ± standard deviation: 70 ± 10 years) were initiated on ASV therapy for HF treatment after polysomnography. Patients were then classified into the following three groups based on their apnea–hypopnea index (AHI): a severe group with an AHI of ≥40/h (n = 28); a moderate group with an AHI of ≥20/h but <40/h (n = 20); and a mild group with an AHI of <20/h (n = 13). To estimate long-term prognosis, we reviewed the 3-year follow-up data, including that concerning fatal cardiovascular events (death from myocardial infarction, cardioembolic stroke, and fatal cardiac arrhythmias).</p><p><strong>Results:</strong> No significant differences were observed between the three study groups in the risk of fatal cardiovascular events (p = 0.207).<strong></strong></p><p><strong>Conclusions:</strong> Our results suggest that ASV therapy is associated with a good prognosis and that ASV therapy is effective, regardless of the severity of SDB.</p><p> </p>

Novel Therapies for the Treatment of Central Sleep Apnea.

Neurophysiologically, central apnea is due to a temporary cessation of respiratory rhythmogenesis in medullary respiratory networks. Central apneas occur in several disorders and result in pathophysiological consequences, including arousals and desaturation. The 2 most common causes in adults are congestive heart failure and chronic use of opioids to treat pain. Under such circumstances, diagnosis and treatment of central sleep apnea may improve quality of life, morbidity, and mortality. This article discusses recent developments in the treatment of central sleep apnea in heart failure and opioids use.

Sleep Apnea and Left Atrial Phasic Function in Heart Failure With Reduced Ejection Fraction

BackgroundThe study aim was to determine whether phasic left atrial (LA) function of patients with heart failure with reduced ejection fraction differs between those with obstructive sleep apnea (OSA) and central sleep apnea (CSA). MethodsParticipation in the Adaptive Servo Ventilation for Therapy of Sleep Apnea in Heart Failure (ADVENT-HF) trial requires 2-dimensional echocardiographic documentation of left ventricular ejection fraction ≤ 45% and a polysomnographic apnea hypopnea index (AHI) ≥ 15 events per hour. Of initial enrollees, we identified 132 patients in sinus rhythm (82 with predominantly OSA and 50 with CSA). To determine LA reservoir (expansion index; EI), conduit (passive emptying index; PEI), and booster function (active emptying index), we blindly quantified maximum and minimum LA volume and LA volume before atrial contraction. ResultsEach of EI (P = 0.004), PEI (P < 0.001), and active emptying index (P = 0.045) was less in participants with CSA compared with those with OSA, whereas average left ventricular ejection fraction and LA and left ventricular volumes were similar. Multivariable analysis identified an independent relationship between central AHI and LA EI (P = 0.040) and PEI (P = 0.005). In contrast, the obstructive AHI was unrelated to any LA phasic index, and slopes relating central AHI to EI and PEI differed significantly from corresponding relationships with obstructive AHI (P = 0.018; P = 0.006). ConclusionsIn these ADVENT-HF patients with heart failure with reduced ejection fraction, all 3 components of LA phasic function (reservoir, conduit, and contractile) were significantly reduced in those with CSA compared with participants with OSA. The severity of CSA, but not OSA associated inversely and independently with LA reservoir and conduit function. Impaired LA phasic function might be consequent to or could exacerbate CSA.

Is Mixed Apnea Associated with Non-Rapid Eye Movement Sleep a Reversible Compensatory Sign of Heart Failure?

Patient: Male, 24Final Diagnosis: Dilated cardiomyopathySymptoms: Biventricular heart failure • sleep apneaMedication: —Clinical Procedure: Heart transplantationSpecialty: CardiologyObjective:Unusual or unexpected effect of treatmentBackground:Sleep-disordered breathing is common in heart failure (HF), and prolonged circulation time and diminished pulmonary volume are considered the main possible causes of sleep apnea in these patients. However, the impact and interrelation between sleep apnea and HF development are unclear. We report the case of a patient with complete elimination of non-rapid-eye-movement (NREM) sleep-associated mixed apnea in HF after heart transplantation.Case Report:After unsuccessful 12-month conventional treatment with abrupt exacerbation of biventricular HF IV class (according to New York Heart Association Functional Classification), a 26-year-old man was admitted to the hospital. Based on a comprehensive examination including endomyocardial biopsy, dilated cardiomyopathy was diagnosed. Heart transplantation was considered the only possible treatment strategy. Polysomnography showed severe NREM sleep-associated mixed sleep apnea [apnea-hypopnea index 43/h, in rapid eye movement (REM) sleep 3.7/h, in NREM sleep 56.4/h, mean SatO2 93.9%], and periodic breathing. One-month post-transplantation polysomnography did not show sleep-disordered breathing (apnea-hypopnea index 1.0/h; in REM sleep − 2.8/h, in NREM sleep 0.5/h, mean SatO2 97.5%). The patient was discharged from the hospital in improved condition.Conclusions:NREM sleep-associated mixed apnea occurring in severe systolic HF due to dilated cardiomyopathy might be reversible in case of successful HF treatment. We suggest that mixed sleep apnea strongly associated with NREM sleep occurs in HF, when the brain centers regulating ventilation are intact, and successful HF compensation might be highly effective regarding sleep-breathing disorders without non-invasive ventilation. This is important to know, especially with regard to the recently published data of potentially unfavorable effects of adaptive servoventilation in systolic HF, and the lack of other treatment options.

Advanced Positive Airway Pressure Modalities

Auto-adjusting positive airway pressure (PAP) devices are increasingly becoming the first line treatment for obstructive sleep apnea (OSA). More complex sleep- disordered breathing such as Cheyne-Stokes respirations and central sleep apnea related to heart failure as well as complex sleep-disordered breathing related to chronic hypoventilation syndromes may require the use of advanced positive airway pressure modalities such as automated servo ventilation (ASV) and volume targeted pressure limited ventilation. Identifying patients with complex sleep-disordered breathing that will benefit from treatment with advanced modalities re- mains an area of active investigation. A recent and surprising development found ASV to be associated with an increased risk of sudden cardiac death when used to treat central sleep apnea in patients with symptomatic systolic heart failure and an ejection fraction less than 45 %. The optimal treatment of central sleep apnea in heart failure and the role of ASV are currently in question. The following chapter is intended to provide the clinician with a description of newer PAP modal- ities; a review of evidence supported indications for use as well as provide a framework for managing patients with ad- vanced positive airway pressure therapy.

Mechanisms and clinical consequences of untreated central sleep apnea in heart failure.

Central sleep apnea (CSA) is a highly prevalent, though often unrecognized, comorbidity in patients with heart failure (HF). Data from HF population studies suggest that it may present in 30% to 50% of HF patients. CSA is recognized as an important contributor to the progression of HF and to HF-related morbidity and mortality. Over the past 2 decades, an expanding body of research has begun to shed light on the pathophysiologic mechanisms of CSA. Armed with this growing knowledge base, the sleep, respiratory, and cardiovascular research communities have been working to identify ways to treat CSA in HF with the ultimate goal of improving patient quality of life and clinical outcomes. In this paper, we examine the current state of knowledge about the mechanisms of CSA in HF and review emerging therapies for this disorder.

Left Atrial Size, Chemosensitivity, and Central Sleep Apnea in Heart Failure

Central sleep apnea (CSA) is common among patients with heart failure (HF) and is promoted by elevated CO2 chemosensitivity. Left atrial size is a marker of the hemodynamic severity of HF. The aim of this study was to determine if left atrial size predicts chemosensitivity to CO2 and CSA in patients with HF. Patients with HF with left ventricular ejection fraction ≤ 35% underwent polysomnography for detection of CSA, echocardiography, and measurement of CO2 chemosensitivity. CSA was defined as an apnea-hypopnea index (AHI) ≥ 15/h with ≥ 50% central apneic events. The relation of clinical and echocardiographic parameters to chemosensitivity and CSA were evaluated by linear regression, estimation of ORs, and receiver operator characteristics. Of 46 subjects without OSA who had complete data for analysis, 25 had CSA. The only parameter that significantly correlated with chemosensitivity was left atrial volume index (LAVI) (r = 0.40, P < .01). LAVI was greater in those with CSA than those without CSA (59.2 mL/m2 vs 36.4 mL/m2, P < .001) and significantly correlated with log-transformed AHI (r = 0.46, P = .001). LAVI was the best predictor of CSA (area under the curve = 0.83). A LAVI ≤ 33 mL/m2 was associated with 22% risk for CSA, while LAVI ≥ 53 mL/m2 was associated with 92% risk for CSA. Increased LAVI is associated with heightened CO2 chemosensitivity and greater frequency of CSA. LAVI may be useful to guide referral for polysomnography for detection of CSA in patients with HF.

Transvenous phrenic nerve stimulation for central sleep apnoea in heart failure: chicken or egg?

This editorial refers to ‘Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure’, by P. Ponikowski et al. , doi:10.1093/eurheartj/ehr298 The prevalence of central sleep apnoea (CSA) is 100-fold greater in chronic heart failure (HF) due to impaired systolic function than in the general population.1 It afflicts principally elderly male patients who have atrial fibrillation, implanted pacemakers, low arterial PCO2 when awake, or high diuretic requirements.1 Its presence identifies HF patients with higher night- and day-time sympathetic nervous system activity,2 at increased of risk of malignant ventricular arrhythmias,3 whose survival is foreshortened.4 The primary abnormality in CSA is neither the upper airway collapse of obstructive sleep apnoea (OSA), which can be treated quite effectively with continuous positive airway pressure (CPAP), nor a paucity of ventilation, but rather the compromise of mechanisms that normally stabilize breathing due to the confluence of pulmonary congestion, circulatory delay, altered cerebrovascular blood flow, and enhanced central sensitivity to CO2, all predisposing to hyperventilation.4 Although the reality is more complex, to simplify, in HF the cyclical oscillations between hyperpnoea and apnoea, known commonly as Cheyne–Stokes respiration, are initiated by the hyperpnoea, which can be stimulated by spontaneous arousal from sleep, or by pulmonary congestion. During sleep, the latter is exacerbated both by fluid shifts from the periphery to the cardiopulmonary reservoir,5 and by pre-existing pulmonary–cardiac–chemoreceptor circulatory delay. Thus, when increases in pulmonary capillary and venous pressures stimulate pulmonary irritant receptors, triggering a bout of hyperpnoea, the already low PaCO2 is driven below the patient's apnoeic threshold. Central drive to the muscles of breathing pauses until the rising PaCO2 and falling PaO2 are sensed, eventually, by chemoreceptors, which then initiate a new cycle of hyperpnoea, hypocapnia, and apnoea. CSA is …

Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure

Periodic breathing with central sleep apnoea (CSA) is common in heart failure patients and is associated with poor quality of life and increased risk of morbidity and mortality. We conducted a prospective, non-randomized, acute study to determine the feasibility of using unilateral transvenous phrenic nerve stimulation for the treatment of CSA in heart failure patients. Thirty-one patients from six centres underwent attempted transvenous lead placement. Of these, 16 qualified to undergo two successive nights of polysomnography-one night with and one night without phrenic nerve stimulation. Comparisons were made between the two nights using the following indices: apnoea-hypopnoea index (AHI), central apnoea index (CAI), obstructive apnoea index (OAI), hypopnoea index, arousal index, and 4% oxygen desaturation index (ODI4%). Patients underwent phrenic nerve stimulation from either the right brachiocephalic vein (n = 8) or the left brachiocephalic or pericardiophrenic vein (n = 8). Therapy period was (mean ± SD) 251 ± 71 min. Stimulation resulted in significant improvement in the AHI [median (inter-quartile range); 45 (39-59) vs. 23 (12-27) events/h, P = 0.002], CAI [27 (11-38) vs. 1 (0-5) events/h, P≤ 0.001], arousal index [32 (20-42) vs. 12 (9-27) events/h, P = 0.001], and ODI4% [31 (22-36) vs. 14 (7-20) events/h, P = 0.002]. No significant changes occurred in the OAI or hypopnoea index. Two adverse events occurred (lead thrombus and episode of ventricular tachycardia), though neither was directly related to phrenic nerve stimulation therapy. Unilateral transvenous phrenic nerve stimulation significantly reduces episodes of CSA and restores a more natural breathing pattern in patients with heart failure. This approach may represent a novel therapy for CSA and warrants further study.

Suitability of the Pericardiophrenic Veins for Phrenic Nerve Stimulation: An Anatomic Study

The objective of this study was to assess the potential of the pericardiophrenic veins (PPVs) as conduits for transvenous stimulation of the phrenic nerves. Modulating respiration with transvenous phrenic nerve stimulation via the PPVs might reduce or eliminate the adverse effects of central sleep apnea in heart failure. Forty-eight fixed cadavers were dissected to study the anatomic characteristics of the PPVs and related neurovascular structures. The right PPV, found in only 1 of 35 cadavers, was <0.5 mm diameter. The left PPV, located in all 48 cadavers, drained into the left brachiocephalic vein (BCV) directly or into the BCV via the superior intercostal vein (SICV). Mean ± SD SICV trunk diameter was 4 ± 2 mm. Mean ± SD left PPV diameter was 2 ± 1 mm. The length between the point of separation of the left PPV from the phrenic nerve to its junction with the BCV or SICV trunk ranged from 6 to 40 mm. The angle of approach, defined as the angle formed by the intersection of the longitudinal axis of the BCV and the longitudinal axis of the PPV or SICV trunk, and which represents the angle that would need to be navigated when inserting a stimulation lead into the PPV using a peripheral cannulation approach, was 99 ± 28 degrees. Valves were identified in 54% of left PPVs. Because of its extremely small size, the right PPV appears unsuitable for transvenous phrenic nerve stimulation. In contrast, the left PPV may be accessible via the left BCV using standard transvenous catheterization techniques; however, the small caliber of the left PPV and the frequent presence of valves within it might pose challenges in navigating the vessel to achieve transvenous phrenic nerve stimulation.

Echocardiography To Screen for Central Sleep Apnea in Heart Failure

Echocardiography To Screen for Central Sleep Apnea in Heart Failure

Real-Time Dynamic Carbon Dioxide Administration: A Novel Treatment Strategy for Stabilization of Periodic Breathing With Potential Application to Central Sleep Apnea

This study targeted carbon dioxide (CO(2)) oscillations seen in oscillatory ventilation with dynamic pre-emptive CO(2) administration. Oscillations in end-tidal CO(2) (et-CO(2)) drive the ventilatory oscillations of periodic breathing (PB) and central sleep apnea in heart failure (HF). Seven healthy volunteers simulated PB, while undergoing dynamic CO(2) administration delivered by an automated algorithm at different concentrations and phases within the PB cycle. The algorithm was then tested in 7 patients with HF and PB. In voluntary PB, the greatest reduction (74%, p < 0.0001) in et-CO(2) oscillations was achieved when dynamic CO(2) was delivered at hyperventilation; when delivered at the opposite phase, the amplitude of et-CO(2) oscillations increased (35%, p = 0.001). In HF patients, oscillations in et-CO(2) were reduced by 43% and ventilatory oscillations by 68% (both p < 0.05). During dynamic CO(2) administration, mean et-CO(2) and ventilation levels remained unchanged. Static CO(2) (2%, constant flow) administration also attenuated spontaneous PB in HF patients (p = 0.02) but increased mean et-CO(2) (p = 0.03) and ventilation (by 45%, p = 0.03). Dynamic CO(2) administration, delivered at an appropriate time during PB, can almost eliminate oscillations in et-CO(2) and ventilation. This dynamic approach might be developed to treat central sleep apnea, as well as minimizing undesirable increases in et-CO(2) and ventilation.

JS3-4 Pathogenesis and Treatment of Sleep Apnoea in Heart Failure

JS3-4 Pathogenesis and Treatment of Sleep Apnoea in Heart Failure

Alleviation of Pulmonary Hypertension by Cardiac Resynchronization Therapy is Associated with Improvement in Central Sleep Apnea

Recent studies have demonstrated that cardiac resynchronization therapy (CRT) reduces sleep apnea in heart failure (HF); however, the mechanism of benefit remains unclear. Overnight polysomnography (PSG) was performed in consecutive HF patients who were scheduled for CRT implant. Patients with sleep apnea defined by an apnea-hypopnea index (AHI) of >10/hour were recruited and underwent echocardiogram examination at baseline and 3 months after CRT. Among 37 HF patients screened, 20 patients (54%) had sleep apnea and 15 of them consented for the study. After 3 months of CRT, there was a significant improvement in New York Heart Association functional class (3.1+/-0.1 vs 2.1+/-0.1, P<0.01), quality-of-life (QoL) score (62.9+/-3.3 vs 56.1+/-4.5, P=0.02), left ventricular ejection fraction (LVEF, 28.8+/-2.5% vs 38.1+/-2.3%, P<0.01), and reduction in pulmonary artery systolic pressure (PASP, 41.0+/-2.7 vs 28.6+/-2.2 mmHg; P<0.01) compared with baseline. Repeated PSG after CRT demonstrated a reduction in the duration of arterial oxygen desaturation<or=95% (251.2+/-36.7 vs 141.0+/-37.1 minutes), AHI (27.5+/-4.7 vs 18.1+/-3.0, P=0.05), and number of central sleep apnea (CSA) (7.8+/-2.6 vs 3.0+/-1.3/hour, P=0.03), but not number of obstructive sleep apnea (OSA, 8.6+/-3.3 vs 7.2+/-2.3/hour, P=0.65) compared to baseline. Percentage change in PASP was significantly correlated with percentage changes in LVEF (r=-0.57, P=0.04), AHI (r=0.5, P=0.05), and number of CSA episodes (r=0.55, P=0.02). The results demonstrated that CRT significantly reduces CSA in patients with HF. Importantly, we have noted a decrement of PASP correlated to drop in CSA which maybe one of the mechanisms explaining this observation. Future studies are required to confirm our finding and elucidate other possible mechanisms in this regard.

Central Sleep Apnea in Heart Failure: Clinical Implications,Recognition, and Management

Central sleep apnea (CSA) is characterized by a lack of respiratory drive during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime breathing disturbances can lead to daytime impairment and poor cardiovascular outcomes. There are several types of CSA, including idiopathic CSA, high altitude-induced periodic breathing, obesity hypoventilation syndrome, drug-induced central apnea, and Cheyne-Stokes breathing pattern. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA varies greatly. Among them, CSA associated with heart failure is well-studied in the respect of clinical impact and management strategy. Through this article, I will summarize the underlying pathophysiology, clinical impacts, and potential treatment of CSA occurring in subjects with heart failure.

Sleep apnea in heart failure in heart failure. Effects of continuous positive airway pressure on cardiovascular outcomes

Sleep apnea in heart failure in heart failure. Effects of continuous positive airway pressure on cardiovascular outcomes

Treatment of obstructive and central sleep apnoea in heart failure: practical options: Table 1—

Sleep apnoea, both central and obstructive disordered breathing, commonly occurs in patients with heart failure.Obstructive sleep apnoea occurs both in systolic and diastolic heart failure and is best treated with nasal positive airway pressure devices.Central sleep apnoea occurs primarily in systolic heart failure and therapeutic options are evolving.Optimal therapy of systolic heart failure, nocturnal use of supplemental oxygen, theophylline, acetazolamide and positive airway pressure devices have been shown to improve central sleep apnoea. Among these therapeutic modalities only continuous positive airway pressure has been studied in a long-term trials; unfortunately, it failed to improve survival.

Sleep apnea in heart failure increases heart rate variability and sympathetic dominance.

Sleep disordered breathing (SDB) is common in heart failure and ventilation is known to influence heart rate. Our aims were to assess the influence of SDB on heart rate variability (HRV) and to determine whether central sleep apnea (CSA) and obstructive sleep apnea (OSA) produced different patterns of HRV. Overnight polysomnography was performed in 21 patients with heart failure and SDB. Two 10-minute segments each of SDB and stable breathing from each patient were visually identified and ECG signal exported for HRV analysis. SDB increased total power (TP) with very low frequency (VLF) power accounting for the greatest increase (1.89+/-0.54 vs 2.96+/-0.46 ms2, P <0.001); LF/HF ratio increased during SDB (1.2+/-1.0 vs 2.7+/-2.1, P <0.001). Compared to OSA, CSA was associated with lower absolute LF (2.10+/-0.47 vs 2.52+/-0.55 ms2, P = 0.049) and HF power (1.69+/-0.41 vs 2.34+/-0.58 ms2, P = 0.004), increased VLF% (78.9%+/-13.4% vs 60.9%+/-19.2%, P = 0.008), decreased HF% (6.9%+/-7.8% vs 16.0%+/-11.7%, P = 0.046) with a trend to higher LF/HF ratio. SDB increases HRV in the setting of increased sympathetic dominance. HRV in CSA and OSA have unique HRV patterns which are likely to reflect the different pathophysiological mechanisms involved.

Treating Central Sleep Apnea in Heart Failure

A recent enhanced appreciation of sleep–cardiovascular interactions, particularly in patients with congestive heart failure (CHF), has prompted careful consideration of the relevance of sleep-disordered breathing to CHF pathophysiology, progression, and treatment.1 Sleep-disordered breathing may be broadly classified as either obstructive sleep apnea (OSA) or central sleep apnea (CSA).1 The former is characterized by repetitive collapse of the upper airway, whereas in patients with CHF, the latter is most often due to periodic alternation of diminished ventilatory drive and compensatory hyperventilation typical of Cheyne-Stokes respiration (Figure 1). CSA is likely a consequence rather than a cause of CHF. Although the mechanisms that underlie CSA/Cheyne-Stokes respiration in patients with CHF are not well understood, pulmonary congestion with increased lung J-receptor stimulation and greater chemosensitivity may play a role in the genesis of the periodic breathing that characterizes this disorder.1,2 Figure 1. Ventilation during sleep from a patient with CHF and CSA. The ventilatory pattern is characteristic of Cheyne-Stokes respiration: apnea followed by crescendo-decrescendo breathing followed by apnea. The cycle may be repeated throughout sleep. Article p 3173 Of 5 million North Americans with CHF, an estimated 50% may have coexistent sleep apnea. Although the prevalence of OSA is much higher than CSA in the general population,3 it appears that this relationship may be reversed among patients with systolic heart failure. Case series have reported frequencies of CSA exceeding 40% for stable, ambulatory patients with CHF in a ratio >2:1 relative to the frequency of OSA. Indeed, the frequency of OSA in these same series was similar to that observed in the general population, whereas the frequency of CSA was strikingly higher.4,5 Furthermore, in patients with CHF, CSA has been associated with increased morbidity and mortality,5–7 increased neurohormonal activation,1 increased ventricular arrhythmia,8 decreased exercise capacity, …

Autonomic Abnormalities in Congestive Heart Failure Patients With Sleep-Disordered Breathing

The increasing prevalence of chronic heart failure is affecting patients' longevity, quality of life, and health resources, despite advances in management. Recognizing and treating comorbid illnesses is critical. Risk factors such as hypertension and diabetes are treated, but less importance is placed on the role of sleep apnea in heart failure. There is a discrepancy between the growing evidence on the potential adverse influence of sleep apnea on heart failure (and vice versa) and incorporating its treatment as part of the management strategy for chronic heart failure. Apneic episodes during sleep can lead to profound disturbances to the sympathetic and parasympathetic nervous system. This review explores the impact of sleep disordered breathing in patients with chronic heart failure, focusing on the autonomic nervous system.