Care of Patients With Heart FailureThe effect of adaptive servo ventilation (ASV) on objective and subjective outcomes in Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF): A systematic review
Introduction
Heart failure (HF) is considered as a major public health problem because of steadily increasing prevalence, high morbidity, early mortality, and significant health care and quality of life costs.1 In spite of advancements in the medical treatment of HF, morbidity and mortality among adults with HF continues to escalate and the overall prevalence of HF is increasing in the U.S. 2, 3, 4 HF is commonly accompanied by sleep-related breathing disorders (SRBD); it is estimated that at least 45% of adults who have a LVEF of less than 45% also have SRBD.5
SRBD are characterized by abnormal respiratory patterns during sleep, including obstructive sleep apnea (OSA) and two centrally-mediated disorders of respiratory control, central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR).6 Approximately 25–50% of patients with HF have CSR-CSA,7, 8 a cyclic breathing pattern characterized by a crescendo-decrescendo pattern of tidal volume interposed with periods of 20–30 s of hyperventilation followed by 10–40 s hypopneas or apneas.9 The presence of CSR-CSA in HF indicates respiratory instability, observed as hyperventilation that results from pulmonary vagal irritant receptor stimulation due to pulmonary congestion in combination with prolonged circulation time and enhanced chemoreceptor sensitivity.10, 11 The physiologic pathway of CSR-CSA in HF is an adverse prognostic indicator.12
The detrimental sequelae of CSR-CSA in HF include sympathetic over-activity, hemodynamic impairment, and poor event-free survival.13, 14, 15, 16 CSR-CSA increases the risk of sudden cardiac death in adults with HF.13, 17 Previous studies show that mortality or cardiac transplantation is positively correlated with CSR-CSA, the apnea-hypopnea index (AHI), arousal index (ArI), and the amount of stage N1 and N2 sleep and adversely related to total sleep time.18 When compared to HF without CSR-CSA, HF with CSR-CSA is also associated with lower LVEF, higher brain natriuretic peptide (BNP), higher urinary and plasma norepinephrine concentration, and increased sympathetic activation.19, 20, 21, 22
Although excessive daytime sleepiness and decrements in health-related quality of life (HRQoL) may be consequences of SRBD in HF (Fig. 1), evidence to data about these relationships is inconsistent. Several studies reported that subjective daytime sleepiness had no relationship with CSR-CSA,23, 24 whereas in other studies CSR-CSA was related to daytime sleepiness and poorer HRQoL among patients with HF.25, 26 Although treatment trials are often aimed at addressing non-inferiority or superiority in terms of biophysiologic responses, it is also important to address patient-centered outcomes of treating CSR-CSA in HF (Table 1).
The treatment options for CSR-CSA in HF include: 1) positive airway pressure such as adaptive servo ventilation (ASV), bilevel positive pressure ventilation (bilevel PPV), and continuous positive airway pressure (CPAP); 2) oxygen therapy; and 3) and respiratory stimulant therapy such as 3% CO2 inhalation and theophylline.9, 27 ASV is a novel therapy that provides expiratory positive airway pressure (EPAP) and inspiratory positive airway pressure (IPAP), that is servo-controlled based on the detection of CSR-CSA. ASV adjusts the IPAP in response to the patient's respiratory effort and EPAP eliminates upper airway collapse during the hyperventilation phase of CSR-CSA.18 Bilevel PPV provides assisted ventilation with a fixed lower level of EPAP and a higher level of IPAP during spontaneous breathing and a preset respiratory rate, or backup respiratory rate, can be set for apneic phases.28 CPAP provides a single level of air pressure above atmospheric pressure.29
Evidence suggests that ASV treatment of CSR-CSA is efficacious for eliminating CSR-CSA in HF.30, 31 Previously published systematic reviews and meta-analyses of ASV for CSR-CSA in HF have predominantly included cardiac function (e.g., LVEF) and objectively measured CSR-CSA (e.g., measured by apnea-hypopnea index [AHI]); yet, subjective daytime sleepiness and HRQoL of ASV in CSR-CSA in HF have been less well-described in prior reviews and meta-analyses. Previous systematic reviews of ASV in HF have not specifically focused on CSR-CSA, but have focused more broadly on measures of the apnea-hypopnea index rather than more specific measures of central apnea (e.g., the central apnea index) and CSR.32 Therefore, a systematic evaluation of studies that have examined specific measures of CSR-CSA and subjective outcomes of ASV treatment of CSR-CSA in HF is necessary to better define opportunities for future inquiries, and develop clinical recommendations for the management of CSR-CSA in HF. The objectives of this study are to examine the effects of ASV on (1) subjective outcomes, including daytime sleepiness and HRQoL, and (2) sleep-related breathing disorder outcomes, cardiovascular function, polysomnography defined sleep quality outcomes, and event-free survival among adults who have chronic HF and CSR-CSA.
Section snippets
Search strategy
The search strategy included publicly-available, online databases which are repositories of scientific publications that address life sciences and biomedical topics (PubMed) and nursing, allied health, biomedicine and health care (CINAHL). ProQuest, Web of Science, and ScienceDirect were also searched. Database searches were carried out using medical subject headings (MeSH) or key words. Search terms were selected to focus on the population and intervention (Table 2). Ancestry searching, or the
Quality of evidence
Of the ten papers included in the review, seven were randomized parallel-group trials35, 36, 37, 38, 39, 40, 41 and three were randomized cross-over trials.42, 43, 44 Four studies were considered as high quality,35, 38, 39, 40 whereas six studies were considered as good quality (Table 3, Table 4).36, 37, 41, 42, 43, 44 None of the studies initially included were later excluded with methodological and quality assessments. Methodological concerns that reduced level and/or quality ratings of the
Discussion
The major findings of the systematic review include that ASV has a beneficial effect on the reduction of CSR-CSA in both the short- and long-term period of treatment. Secondly, there is no consistent beneficial effect of ASV on sleep quality, defined by polysomnography, in terms of arousals, TST, SWS, and REM sleep. Third, ASV may improve LVEF, BNP, and catecholamine, but due to inconsistent results, the evidence does not support the superiority of the effects of ASV compared to other
Conclusion
ASV improves CSR-CSA but the evidence does not support improvement of other outcomes, such as cardiovascular, objective sleep quality or subjective outcomes. With the recently released findings of the SERVE-HF Trial, combined with the current systematic review findings, treatment of CSR-CSA in HF with ASV is not recommended. It is important to continue to clinically screen for SRBD in HF adults and refer patients for sleep evaluation to clearly discern OSA from CSR-CSA.
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Cited by (10)
Individual and socioeconomic impact of sleep related breathing disorders
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second EditionSleep Deficiency: A Symptoms Perspective: Exemplars from Chronic Heart Failure, Inflammatory Bowel Disease, and Breast Cancer
2022, Clinics in Chest MedicineCitation Excerpt :However, the data are somewhat conflicting. Among people with HF and central sleep apnea, adaptive servoventilation did not improve daytime sleepiness,48 whereas both exercise and continuous positive airway pressure (CPAP) improved the apnea-hypopnea index and daytime sleepiness in people with HF and obstructive sleep apnea. However, the effects of exercise were larger than CPAP on function.49
Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020
2022, Respiratory InvestigationCitation Excerpt :In a randomized controlled trial of patients suffering from chronic heart failure with LVEF ≤45% in a small single center, it was indicated that the prognosis was good in the subgroup with CPAP adherence, while in a post-hoc analysis of the CANPAP trial, which is a randomized controlled trial in which patients suffering from chronic heart failure with AHI ≥15 and LVEF ≤45% were assigned to a CPAP group and a control group, prognosis was evaluated with predominance of central respiratory events, where it was found to be better in the CPAP case with AHI <15 than that of the control group [195,197,203–206]. With regards to the prognosis improvement effect of ASV, in addition to the results of multiple observational studies in which the prognosis of patients suffering from chronic heart failure with LVEF ≤45% who were introduced with ASV was relatively good [195,197,203–206], small single-center randomized controlled trials of patients with LVEF >45% of chronic heart failure indicated improved prognosis [197]. However, the SERVE-HF trial, a multicenter randomized controlled trial of patients suffering from chronic heart failure with LVEF ≤45%, indicated that the primary endpoint was not significantly different between the two groups, with the secondary endpoints indicating a significant increase in all-cause mortality and cardiovascular mortality in ASV [197,204].
Sleep duration and architecture during ASV for central sleep apnoea in systolic heart failure
2020, Respiratory Physiology and NeurobiologySleep-Disordered Breathing and Excessive Daytime Sleepiness
2017, Sleep Medicine ClinicsObstructive sleep apnea: effect of comorbidities and positive airway pressure on all-cause mortality
2017, Sleep MedicineCitation Excerpt :However, a positive effect was noted on subjective reports and quality of life. Coexisting heart failure and central, obstructive sleep apnea are associated with worse prognosis [12,13], although controlled trials treatment of central sleep apnea (CSA) with auto-adjusted servo-ventilation (ASV) have raised significant concerns because mortality rates were not reduced, but instead were associated with significantly greater mortality and no improvement in hospitalization due to HF or in quality of life [14]. This raises the problem that CSA may be a consequence of severe cardiovascular disease rather than its cause.