Skip to main content

What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study)

Adaptive servo-ventilation in real-life conditions



As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions.


The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal.


177/214 patients were analysed (87.57% male) with a median (IQ25–75) age of 71 (65–77) years, an ASV-treatment duration of 2.88 (1.76–4.96) years, an ASV-usage of 6.52 (5.13–7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6–13.5) to 6 (3–9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38–62)/h to a residual device index of 1.9 (0.7–3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05).


In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management.

Trial registration

The OTRLASV study is registered on (Identifier: NCT02429986) on 1 April 2015.


Adaptive Servo-Ventilation (ASV) is a partially automated treatment modality used to correct various types of sleep-disordered breathing (SDB), including periodic breathing [1, 2], but also central and obstructive apnea and hypopnea [3,4,5]. Current proposed indications for ASV are Treatment-Emergent Central Sleep Apnea (TECSA), Central Sleep Apnea (CSA) associated with stroke, renal failure or other etiologies such as drug induced CSA, co-existing CSA with obstructive sleep apnea (OSA), and idiopathic CSA [5]. For patients with preserved LVEF (left ventricular ejection fraction, i.e. LVEF > 45%) and moderate-to-severe predominant CSA, ASV is an “Option level recommendation” according to the American Academy of Sleep Medicine (AASM) [6], whereas the European Respiratory Society Task Force proposed ASV in this clinical situation (but only after a Continuous Positive Airway Pressure (CPAP) trial failure) [5]. Based on the results of the SERVE-HF study [7], current recommendations underline a consensus against the use of ASV in Chronic Heart Failure (CHF) patients with both reduced LVEF (i.e. LVEF ≤45%) and moderate-to-severe predominant CSA [5, 6].

ASV was initially developed for the treatment of central sleep apnea and Cheyne-Stokes breathing associated with CHF and reduced LVEF [2]. Studies dedicated to these patients are somewhat relatively numerous as compared with other potential indications for ASV [4, 5, 8, 9] and in particular, the only large randomized study in the ASV field concerns these patients (SERVE-HF study, [7]). Paradoxicaly, the prevalence of related comorbidities/etiologies and sleep apnea patterns for real-life ASV populations has rarely been evaluated [8, 10,11,12,13]. Recently, in an unselected monocentric study concerning 293 ASV-treated patients, Randerath et al. reported that only 9.6% of the patients fulfilled the SERVE-HF criteria subtype, thus bringing into question the representativity of the patients included in previously published ASV-studies [13]. As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged [14].

With the aim of filling the literature gap characterized by a lack of studies describing associated comorbidities/etiologies for all types of ASV patients, we report here the clinical characteristics of the patients included in the Observational Transversal Real-life Study of ASV (OTRLASV) study. OTRLASV is a multicentric study aimed at describing the clinical characteristics of patients who have undergone ASV for over a year in real-life conditions.


Study design and study population

The OTRLSAV study is an observational prospective five-expert-centre study (see Additional file 1 for centres) conducted in a exhaustive cohort of consecutive patients treated for at least 1 year with ASV for sleep apnea (SA) ( Identifier: NCT02429986). The protocol complied with the Declaration of Helsinki and was reviewed and approved by an independent ethics committee (Comité de Protection des Personnes “Sud Méditérannée III”; reference number 2014.11.04).

SA was defined according to the French Social Security rules required for the reimbursement of ASV costs: 1) an Apnea Hypopnea Index (AHI) ≥ 30/h (or AHI ≥ 15/h and more than 10/h respiratory-effort-related arousal), and 2) associated with sleepiness and at least three symptoms from among snoring, headaches, hypertension, reduced vigilance, libido disorders, nycturia). In order to be reimbursed, the ASV-treated patient needs to be examined each year. Participating investigators enroled eligible patients (see Additional file 2 for inclusions/exclusion criteria) during this annual visit. Each investigative center was open for 14 months, starting in March 2015. The safety annoucement for the SERVE-HF study happened on May 13th, 2015. Prior to this, we included 8 patients (4.5%), and the remaing 169 patients (95.5%) were included after this date, with a last inclusion in January 2017).

Collected data

The clinical information collected for the analysis included age, sex, anthropometry, smoking status, blood pressure, initial polysomnography (PSG) or respiratory polygraphy (PG) AHI, Epworth Sleepiness Scale (ESS), number of hospitalizations during the last year (with aetiology), presence of cardiomyopathy (with aetiology and treatment), especially an altered LVEF, cardiological monitoring, and whether or not the patient knew his/her drug prescription by rote.

The patient status for CHF and LVEF, neurological and renal comorbidities/etiologies, opioid prescriptions were systematically collected. An idiopathic CSA was defined when none of the above causes for CSA applied. ASV treatment modalities were also collected using the manufacturer’s software: usage reported in hours/night for the last 6 months, reported residual AHI by the device (AHIflow), auto-adjusted level of expiratory pressure use versus fixed expiratory pressure, inspiratory and expiratory pressure levels, duration of pressurization, backup frequency, leak level, interface type, use of humidifier, use of heated circuit, and use of a chinstrap. In addition, we collected the treatment initiation time and modality of initiation (hospital or ambulatory conditions), device and interface manufacturer, history of the devices used before ASV, history of the interfaces used. Whether or not night monitoring (a polygraphy / polysomnography / oximetry during ASV for 1 night) had been performed in the last 6 months was also collected, as well as any subsequent changes to device settings and interface choice.

Initial polygraphy (PG) or polysomnography (PSG) diagnosis and definition of SDB groups

In line with a recent published real-life study [12], we chose to differentiate central versus obstructive groups using the predominant apnea pattern. Patients with more than 50% of central apneas were classified in the central sleep apnea (CSA) group, while patients with more than 50% of obstructives apneas were classified in the obstructive sleep apnea (OSA) group. Patients with an initial diagnosis of OSA treated with CPAP but secondarily treated with ASV were classified in the Treatment-Emergent Central Sleep Apnea (TECSA) group. Central apnea was scored if respiratory effort was absent. This latter criteria was chosen because it represented a consensus between the different centers and recommendations for scoring (see Additional file 3 for details).


All echocardiograms were performed by senior cardiologists. LVEF was calculated using the Simpson’s and/or Teichholz’s methods. For patients with multiple measures, only the most recent was kept for analysis, and a threshold of a LVEF ≤45% was used to categorize the patient as “reduced” versus “preserved” LVEF, as in the SERVE-HF study [7].

Statistical analyses

Data distributions were assessed for normality and continuous data are expressed as means with their standard deviations (SD) or medians and interquartile ranges (IQ25–75) accordingly. Qualitative parameters were expressed as numbers and percentages. Comparisons between the three SDB-groups (CSA, OSA and TECSA) were performed using ANOVA or Kruskal-Wallis test for quantitative data. Qualitative variables were compared using Chi-square or Fisher test. For significant global comparison, pairwise comparisons were performed using Holm correction for multiple comparison.

The relationship between the date of ASV initiation and delays (since last echocardiography or the last echocardiography) was studied with the Cochran Armitage test. The relationship between the date of ASV initiation and a CPAP trial or a night monitoring in the 6 months preceding the inclusion of the patient in the study was studied using the Jonckheere-Terpstra test. ASV-usage groups were compared by Student’s test or Wilcoxon Mann Withney test for quantitative parameters and Chi-square or Fisher test for qualitative ones. A two-sided p value of < 0.05 was considered as indicating statistical significance.

Multivariable logistic regression analysis was used to study associations between ASV-adherence (≤4 h versus > 4 h) and collected data. Using backward selection, pertinent covariates with a univariable p-value < 0.15 were fed into the multivariable analysis. The α -to-exit was set at 0.05. Odds-ratios with their 95% Wald CI were reported. Model goodness-of-fit was assessed using the Hosmer-Lemeshow test. Missing data have not been replaced. All analyses were conducted by the Department of Research and Medical Information at the Montpellier University Hospitals using statistical software (SAS, V.9.3; SAS Institute; Cary, North Carolina, USA).


The flow chart for the study is depicted in Fig. 1. General and sleep characteristics of the population are summarised in Table 1. Briefly, the 177 patients (87.6% male) analysed had a median age of 71 (IQ25–75: 65–77) years, a median body mass index of 29.9 (26.6–34.0) kg/m2, and 12% were active smokers (35% had never smoked). The majority of patients was classified in the CSA group (59.3%), whereas the remaining 40.7% were evenly divided into an OSA group (20.3%) and a TECSA group (20.3%) (see Additional file 1 for SDB-group prevalence depending of the enrolment center). SDB-diagnosis was performed by PSG or PG in respectively 42.9 and 57.1% of cases. The median initial AHI for the whole population (WP) was 50/h (38–62), with no difference associated with the diagnosis method (AHIPG of 50/h (39–57) versus AHIPSG of 50/h (37–68), p = 0.729).

Fig. 1
figure 1

Flow chart of the study. ASV: Adaptive Servo-Ventilation; AHI: Apnea Hypopnea Index; TECSA: Treatment Emergent Central Sleep Apnea; SA: Sleep Apnea, SDB: Sleep Disordered Breathing

Table 1 General and sleep characteristics of the population


A CPAP trial was performed before ASV initiation for 37.1% of the CSA group, 57.6% of the OSA group and 100% of the TECSA group (p < 0.001). The delay between the date of ASV initiation and the existence of a CPAP trial before ASV initiation is depicted in Additional file 4 (p = 0.37). No other mode of ventilation than ASV and CPAP was used.

For the WP, AHI indices significantly improved according to machine-derived values for the ASV treatment group (AHIflow = 1.9/h (0.7–3.8)) versus pre-treatment PG/PSG-derived values (AHIPG/PSG = 50.00 (38.30–62.30)], p < 0.001; Table 1). Significantly decreased final AHIflow values were observed for each SDB group (versus initial AHIPG/PSG, p < 0.001). The median initial Epworth Scale Score (ESS) for the WP was 10 (6–13.5); the final ESS was 6 (3–9). The difference between initial and final ESS was significant for the CSA (p < 0.001) and TECSA groups (p = 0.009), but not for the OSA group (p = 0.068).

ASV initiation was performed at home for 35.3% of the WP, under hospital ambulatory conditions for 19.7 and 45.1% were admitted for continuous hospitalization (no differences were found between SDB groups, p = 0.162).

The median duration of ASV treatment was 2.88 years (1.76–4.96) with no difference between groups. The median ASV-usage for the WP was 6.5 h/day (5.1–7.7). 87.0% of the WP were adherent to ASV for more than 4 h/day. Table 2 depicts the comparison between sub-groups of ASV-adherence (≤4 h versus > 4 h) for clinical, ASV or monitoring data. Statistically significant differences existed (1) between SDB groups (p < 0.001), (2) for the presence of PG- or oximetry-based ASV monitoring in the last 6 months (p = 0.014), and (3) for the initial (p = 0.012) and final (p = 0.034) ESS scores.

Table 2 Comparison between ASV-adherence sub-groups (≤4 h versus > 4 h) for clinical, ASV and monitoring data

Multivariable logistic regression analysis was used to study associations between collected data and ASV-adherence (≤4 h versus > 4 h). The following variables (with a p < 0.15 value in the univariate analysis) were included in the multivariable model: SDB-groups, initial ESS, a PG- or oximetry-based ASV monitoring in the last 6 months, a CPAP trial before ASV initiation, an ASV initiation during continuous hospitalization, a neurological comorbidity, and patient treatment knowledge (whether or not the patient knew their treatment). Multivariable logistic regression demonstrated that (1) TECSA group versus CSA group, (2) absence of a PG- or oximetry-based ASV monitoring in the last 6 months and (3) a high initial EES score were associated with a ≤ 4 h ASV-adherence (Table 3). In order to rule out a possible confounding effect for the comorbidity variables, each “comorbidity/etiology” variable was forced into the multivariable analysis but the results were unchanged and “comorbidity/etiology” variables remained statistically non-significant.

Table 3 Logistic regression analysis with adherence (≤ 4 h /day) as the dependent variable. Summary of significant explicative variables

Comorbidities/etiologies reported for ASV-treated patients

Associated comorbidities/etiologies are depicted in Fig. 2. Comorbidities/etiologies are strictly cardiological in nature for 62% of the patients, only neurological for 4%, and only renal failure for 0.5%. No patient had more than two comorbidities/etiologies and the vast majority (24/25) had at least one cardiological comorbidity. No comorbidities/etiologies were reported for 33 patients (18.6%), 51.5% of whom belonged to the CSA group. Thus, 9.6% of the WP can be defined as idiopathic CSA.

Fig. 2
figure 2

Comorbidities/etiologies associated with ASV prescription. The number and percentages of the total population are presented (1 patient = 0.6%). For 33 patients (18.6%), no comorbidity was related to SA

Cardiological characteristic

Table 4 depicted the cardiological data of the population. Ischaemic heart failure was present in 34.9% of the WP, 24.6% presented with non-ischaemic heart failure, 30.5% with atrial fibrillation, and 7.3% were diagnosed with a reduced LVEF. For the 147 patients for whom the date of the last cardiological consultation was known, the median delay was 183 days (70–365). Similarly, the median delay since last echocardiography (n = 145) was 263 days (116–529) and appeared to differ between SDB groups (p = 0.015), with a shorter delay for the OSA group (175 days (28–356)). These delays were not dependent on the year of ASV initiation (Additional files 5 and 6, p = 0.19 and p = 0.77, respectively, for consultations and echocardiographic exams). 20.9% of patients were hospitalized the year preceding inclusion, but only 6.2% for cardiological reasons (in detail, six patients were hospitalized for acute (3) or chronic (3) coronary syndrome requiring revascularization by stent (5) or angioplasty (1), 3 patients for acute heart failure, 1 patient for acute atrioventricular block requiring implantation of a pacemaker and 1 patient for a stroke).

Table 4 Cardiovascular data

Polygraphy and oximetry-based ASV monitoring data

Data for PG- or oximetry-based ASV monitoring performed in the 6 months preceding inclusion are summarised in Table 5. PG on ASV was performed in 31/173 patients, whereas 24/160 patients had overnight oximeter recording on ASV; one patient has both types of control. These controls were associated with a consecutive change in settings for 7 patients in either group (ASV-PG n = 7 and ASV-oximetry n = 7). These changes consisted in a modification of the pressure level for 9 patients, with a modification of the back-up frequency rate for one patient, and a modification of the interface for 5 patients. The cases where a PG- or oximetry-based ASV monitoring was performed in the last 6 months were not linked with the ASV-initiation date (p = 0.12, see Fig. 3).

Table 5 Data from polygraphy- or oximetry-based ASV quality monitoring performed in the last 6 months preceding the inclusion in the study
Fig. 3
figure 3

Exams (polygraphy (PG) or oximetry) performed in the 6 months preceding study inclusion, depending of the ASV-initiation date


In the context of the SERVE-HF study [7], a trial that has raised serious concerns about the effect and safety of ASV, physicians are waiting for new related studies [15]. Our study provides new data on ASV-use in real-life conditions and new insights for future trials. We report that: 1) the major comorbidity associated with ASV-treated patients after SERVE-HF study remains cardiologic in nature, and concerns 75.7% of patients (but, only 6.2% of the latter were hospitalized for cardiological reasons during the preceding year); 2) 54.8% of the ASV-treated patients previously received a CPAP treatment; 3) 87.0% of the patients were adherent to their ASV for more than 4 h/day; 4) more than a third of the patients included in our study had polygraphy- or oximetry-based monitoring to verify ASV quality in the 6 months preceding inclusion and a consecutive change (device settings or mask type) was performed for 25.9% of them. Interestingly, this monitoring was positively associated with an ASV-adherence > 4 h/jour.

Conditions associated with ASV

This prospective, real-life study on a non-selected ASV population from five French centers is the first to give data on the related comorbidities/etiologies in “post-SERVE-HF” conditions (see Table 6 to compare with other, similar, real-life studies). In our study, the more prevalent associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (59.5% of the WP present with CHF and 30.5% present with atrial fibrillation). In the Rochester Epidemiology Project (REP) database, a similar high prevalence for cardiac comorbidities/etiologies (78%) and atrial fibrillation (35.9%) was reported, but with less heart failure (34%) [14].

Table 6 Data from the published ASV-real-life and non comparative studies (only studies with more than 70 patients were included; data concern the whole population)

To date, the prevalence of idiopathic CSA is unknown [5]. The 9.6% prevalence of idiopathic CSA found in our study is close to the 10% reported by the recent study from Malfertheiner et al. [12], but differs from the 28% given by the only previous report in 2011 [10]. In the REP database, the prevalence of idiopathic CSA was only 4.9% [14]. It is impossible to determine if these differences between studies are the consequence of a recruitment bias related to the investigative centers, the absence of collected data or a real change in the prevalence of the comorbidities/etiologies associated with the prescription of ASV. In particular, the prevalence of idiopathic CSA is conditioned by the exhaustively aetiologic screening performed, which is not always specified in real-life studies (e.g. cerebral screening with magnetic resonance imaging). Surprisingly, there are no recent recommendations concerning the aetiological screening to be carried out as a prerequisite for ASV prescription, except for a cardiac evaluation to rule out the possibility of a reduced LVEF in CSA patients [5].

CPAP trials as a prerequisite for ASV therapy

For patients with CSA and failure of a recommended first-line CPAP trial, the 2017 European Respiratory Society Task Force systematically proposed ASV therapy as a second line of therapy (except for SERVE-HF pattern patients for whom ASV is contraindicated) [5]. The same recommendation exists for OSA patients [5] (and is a defining characteristic of TECSA patients). In contrast, in 2012, CPAP treatment for CSA patients was only an “Option level” recommendation for the American Academy of Sleep Medicine [7].

Here, we report that only 37.1% of the patients in the CSA group and 57.6% of the OSA group had a CPAP trial prior to ASV therapy. The percentage of CPAP trials occurring before ASV intiation remains stable over time, and therefore appears to not be influenced by the different recommendations. In other, similar, published real-life studies (Table 6), the required pre-ASV CPAP trial was not always performed, and when performed, lacked important specifications and/or appropriate duration.

In a recent, large, manufacturer-maintained database, it was surprising to observe that only 3.6% of the 9295 patients treated with ASV were previously treated with CPAP, thus questioning the true prevalence of TECSA-patients treated with ASV [16]. However, this type of manufacturer-database cannot rule out the possibility of a previous CPAP treatment with a different manufacturer, and thus underestimating the TECSA-prevalence. In contrast, the prevalence of TECSA was 75.5% of the ASV-treated patients in the REP database [14]. The exact role CPAP screening among patients eligible for ASV treatment should be detailed in future studies.


One of the major criticisms of the SERVE-HF study was the weak ASV-adherence of the patients. Indeed, only 47% of the patients were adherent for more than 4 h/day at 1 year (with a mean of only 3.4 h/day). The data presented for the CAT-HF study were even worse, with 2.7/h/day at 6 months [17]). In contrast, 87% of our patients were adherent for more than 4 h/day. This high adherence was also reported by the French study from Carnevale et al. [10], and is likely linked to the reimbursement rules imposed by the French single-payer national insurance system. Unfortunately, ASV-adherence or usage was rarely reported in the other, similar, real-life studies, except for the Oldenburg et al. study (65.9% of patients > 4 h/day at 24 months, see Table 6) [8]. A recent analysis of a large database from the United States confirms a 73.2% ASV-adherence at 3 months for 8957 patients without previous CPAP trials in real-life conditions (ASV-adherence defined by an ASV usage ≥4 h per night, > 70% of nights during the consecutive 30-day period preceding the collection of the data). In the same study, the ASV-adherence at 3 months was 76% for the 209 patients who were previously CPAP treated [16], which is similar to the 69.4% reported in our study.

However, to date, an ASV-usage dependent effect on quality of life has not been demonstrated, as was the case for CPAP [11, 18, 19]. In the CAT-HF trial, the relationship between ASV-adherence (> 3 h) and the burden associated with atrial fibrillation does not reach significance despite a beneficial effect of combined optimal medical treatment (OMT) plus ASV-treatment versus OMT alone [20].

ASV-adherence is of crucial meaning because it is difficult to imagine a potential effect of ASV on strong outcomes (such as quality of life or cardiovascular mobility or mortality) without greater adherence than those reported in the recent ASV-trials [7, 17]. Of course ASV-adherence is a complex parameter, underlined by the on-treatment analysis of the SERVE-HF study. Indeed, Woehrle et al. reported that patients randomised to control who voluntarily switched to ASV had lower cardiovascular mortality than those initially randomised to ASV [21]. In addition, if the increase in cardiovascular mortality is associated with ASV, the risk did not appear to be proportional to the duration of ASV-use [21]. ASV-adherence may not be only a marker of ASV-therapy, but also a marker of a wide-range of patient behaviours toward health and disease. In this regard, it was suggested that ASV usage may be linked to oral medication compliance [22]. For CPAP therapy and OSA patients, two previous studies have reported conflicting results [23, 24]. In our study, we failed to demonstrate a link between the ASV-adherence and the number of cardiological medications or patient knowledge concerning his/her drug treatments. In the REP database, the adherence to ASV at any time was not associated with the rate of change of medication pre-ASV versus post-ASV [14]. Future ASV-randomized studies should assess oral medication compliance in order take to rule out possible bias when interpreting ASV effects [22]. This is one of the major criticisms against the SERVE-HF design study [22].

Polygraphy and oximetry-based ASV monitoring

One of the interesting insights from our study concerns the PG- and oximetry-based ASV quality monitoring and the subsequent consequences on settings and ASV-adherence. 34.4% of patients were so monitored, and a consecutive setting change was then performed among 25.9% of them. ASV quality monitoring was not linked to the ASV initiation date, but was favourably associated with ASV-adherence. During ASV therapy, few studies report the correlation and concordance of the AHI measured by PG or PSG and the simultaneous AHI results given by the ASV device (AHIflow) (i.e. real versus device-provided measures). For CPAP, it was underlined that AHIflow was not always correlated or concordant with PG/PSG measures, especially when a 3% versus a 4% threshold of oxygen desaturation is used (results were worse when a PSG was used because of the additive impact of arousals (which cannot be diagnosed by the device) on the scoring) [18, 25,26,27]. Equivalent, exhaustive data are lacking for ASV therapy, whereas preliminary [28] or final data [8, 29, 30] are in favour of a similar discrepancy between AHIflow and AHIPSG. In the Silveira study, the Bland and Altman plot of the difference between PSG-AHI and ASV-AHIflow against the mean of both measurements, reports a mean difference of 11.9 ± 9.6 (95% limits of agreement − 6.90, 30.71) [30]. In a recent editorial, Thomas and Bianchi have underlined the existing concern that the efficacy of CPAP and ASV therapies can be overestimated by the reported AHIflow [27]. Future randomized ASV-studies must take into account these considerations by including several PSG controls for ASV quality in the study design. The latter should rule out the consequences of non-optimised ASV therapy on mechanistic parameters such as arousal and desaturation, which are innately underestimated by ASV AHIflow. This is of crucial importance considering the potential ineffectiveness of the device suggested by the literature and the possible consequences on ASV-adherence suggested by our study.

Limits of the study

Our prospective study is a non-randomized observational study with potential unknown sources of bias. Large randomized controlled studies are needed, but a preliminary step is a careful assessment of patients currently treated or potentially eligible for ASV treatment. Observational studies must be multicenter to eliminate bias related to patient recruitment (cf. Additional file 2).

In constrast with recent, similar, real-life studies, our study was not specifically designed to assess the prevalence of SERVE-HF pattern patients in the ASV-treated population. Prevalences of 9 and 12% for SERVE-HF pattern patients were respectively reported in retrospective studies by Randerath et al. [13] and Malfertheiner et al. [12], whereas we report only a 5.8% prevalence. The chronology of our study and the release-date for the SERVE-HF safety notice explains this apparent discrepancy. Our first inclusion occurred in March 2015; the safety notice was released in May 2015. Therefore, our prospective study probably underestimated the prevalence of these patients, because most of the patients stopped their ASV treatment after the safety notice (in this regard, no SERVE-HF pattern patients were included in the 3 centers that joined the study after October 2015). An additional limitation of our study arises from one of the inclusion criteria. Indeed, we were unable to collect the occurrence of spontaneous improvement in central sleep apnea because only patients presenting at the annual control consultation for the continuation of the ASV treatment were included in the study.

Of course, our data may be less relevant to other countries mainly because of governmental policy rules governing ASV-costs. In France, ASV reimbursement at the time of this study was based on a combination of associated clinical symptoms, an AHI-threshold (regardless of apnea and hypopnea patterns) and an ASV-usage > 3 h/day. As a consequence, patients with a diagnostic AHI < 15/h were not treated with ASV, unlike patients included in other real-life studies [11, 12].

The major problem we faced was to classify patients into the CSA and OSA groups according to the results of their PV or PSG exams. As in Malfertheiner et al. [12], we chose to differentiate central versus obstructive SDB groups using the predominant apnea pattern. This choice helped overcome problems caused by changes in scoring recommendations for respiratory events. Indeed, in our study, patient initial diagnoses spanned from 2002 to 2016. During this period, the definition of apnea remained stable, whereas the definition of hypopnea went through major changes, including not only decreased thresholds for the percentage of flow, but also 3% or 4% oxygen desaturation thresholds, and central versus obstructive pattern definitions [31, 32].

In contrast to the consequences of not performing PG- or oximetry-based ASV-night monitoring, we failed to report the consequences of the cardiologic consultation and echocardiography (in particular in terms of cardiological therapy or ASV-setting changes). Future trials must record these data because modifications in the cardiologic treatment can bias the evaluation of ASV-therapy.


Real-life studies inherently have many biases, but they can help us to better construct randomized studies. Our study reports the updated prevalence of cardiological, neurological, renal and opioid comorbidities/etiologies associated with ASV prescriptions. It emphasizes the need to better define CPAP as a prerequisite for ASV, and emphasizes the need for iterative night-monitoring and cardiological assessments in ASV-treated patients.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.



American Academy of Sleep Medicine


Angiotensin-converting enzyme


Atrial fibrillation


Apnea Hypopnea Index

AHIflow :

Residual Apnea–Hypopnea-Index measured by the ASV device

APH Marseille:

Assistance Publique Hopitaux de Marseille

APHP Paris:

Assistance Publique Hopitaux de Paris


Angiotensin-receptor blocker


Adaptive Servo-Ventilation


Body mass index


Blood pressure


Central Apnea Index


Chronic Heart Failure

CHU Dijon:

Centre Hospitalier Universitaire de Dijon

CHU Montpellier:

Centre Hospitalier Universitaire de Montpellier (CHU Montpellier)


Continuous Positive Airway Pressure


Central Sleep Apnea


Epworth Sleepiness Scale


Hypopnea Index


Implanted cardiac defibrillator

IQ25–75 :

Medians and interquartile ranges


Left ventricular ejection fraction


Mixed Apnea Index


Obstructive Apnea Index


Obstructive sleep apnea

PC Boujan:

Polyclinique Saint Privat Boujan sur Libron


Respiratory polygraphy




Sleep Apnea


Standard deviations


Sleep-disordered breathing


Treatment Emergent Central Sleep Apnea


Whole population


  1. Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146:514–23.

    Article  Google Scholar 

  2. Teschler H, Döhring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;164:614–9.

    Article  CAS  Google Scholar 

  3. Aurora RN, Chowdhuri S, Ramar K, Bista SR, Casey KR, Lamm CI, et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep. 2012;35:17–40.

    Article  Google Scholar 

  4. Javaheri S, Brown LK, Randerath WJ. Clinical applications of adaptive servoventilation devices: part 2. Chest. 2014;146:858–68.

    Article  Google Scholar 

  5. Randerath W, Verbraecken J, Andreas S, Arzt M, Bloch KE, Brack T, et al. Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep. Eur Respir J. 2017;49.

  6. Aurora RN, Bista SR, Casey KR, Chowdhuri S, Kristo DA, Mallea JM, et al. Updated adaptive servo-ventilation recommendations for the 2012 AASM guideline: “The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses.”. J Clin Sleep Med Med. 2016;12:757–61.

    Article  Google Scholar 

  7. Cowie MR, Woehrle H, Wegscheider K, Angermann C, d’Ortho M-P, Erdmann E, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med. 2015;373:1095–105.

    Article  CAS  Google Scholar 

  8. Oldenburg O, Wellmann B, Bitter T, Fox H, Buchholz A, Freiwald E, et al. Adaptive servo-ventilation to treat central sleep apnea in heart failure with reduced ejection fraction: the Bad Oeynhausen prospective ASV registry. Clin Res. 2018;107:719–28.

    Google Scholar 

  9. Oldenburg O. Cheyne-stokes respiration in chronic heart failure. Treatment with adaptive servoventilation therapy. Circ J. 2012;76:2305–17.

    Article  Google Scholar 

  10. Carnevale C, Georges M, Rabec C, Tamisier R, Levy P, Pépin J-L. Effectiveness of adaptive servo ventilation in the treatment of hypocapnic central sleep apnea of various etiologies. Sleep Med. 2011;12:952–8.

    Article  Google Scholar 

  11. Momomura S-I, Seino Y, Kihara Y, Adachi H, Yasumura Y, Yokoyama H. Adaptive servo-ventilation therapy using an innovative ventilator for patients with chronic heart failure: a real-world, multicenter, retrospective, observational study (SAVIOR-R). Heart Vessel. 2015;30:805–17.

    Article  Google Scholar 

  12. Malfertheiner MV, Lerzer C, Kolb L, Heider K, Zeman F, Gfüllner F, et al. Whom are we treating with adaptive servo-ventilation? A clinical post hoc analysis. Clin Res. 2017;106:702–10.

    Google Scholar 

  13. Randerath W, Schumann K, Treml M, Herkenrath S, Castrogiovanni A, Javaheri S, et al. Adaptive servoventilation in clinical practice: beyond SERVE-HF? ERJ Open Res. 2017;3(4):00078–2017.

    Article  Google Scholar 

  14. Mansukhani MP, Kolla BP, Naessens JM, Gay PC, Morgenthaler TI. Effects of adaptive servoventilation therapy for central sleep apnea on health care utilization and mortality: a population-based study. J Clin Sleep Med. 2019;15:119–28.

    Article  Google Scholar 

  15. Jaffuel D, Molinari N, Berdague P, Pathak A, Galinier M, Dupuis M, et al. Impact of sacubitril-valsartan combination in patients with chronic heart failure and sleep apnoea syndrome: the ENTRESTO-SAS study design. ESC Heart Fail. 2018;5:222–30.

    Article  Google Scholar 

  16. Pépin J-LD, Woehrle H, Liu D, Shao S, Armitstead JP, Cistulli PA, et al. Adherence to positive airway therapy after switching from CPAP to ASV: a big data analysis. J Clin Sleep Med. 2018;14:57–63.

    Article  Google Scholar 

  17. O’Connor CM, Whellan DJ, Fiuzat M, Punjabi NM, Tasissa G, Anstrom KJ, et al. Cardiovascular outcomes with minute ventilation-targeted adaptive servo-ventilation therapy in heart failure: the CAT-HF trial. J Am Coll Cardiol. 2017;69:1577–87.

    Article  Google Scholar 

  18. Huang H-CC, Hillman DR, McArdle N. Control of OSA during automatic positive airway pressure titration in a clinical case series: predictors and accuracy of device download data. Sleep. 2012;35:1277–1283A.

    Article  Google Scholar 

  19. Weaver TE, Maislin G, Dinges DF, Bloxham T, George CFP, Greenberg H, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007;30:711–9.

    Article  Google Scholar 

  20. Piccini JP, Pokorney SD, Anstrom KJ, Oldenburg O, Punjabi NM, Fiuzat M, et al. Adaptive servo-ventilation reduces atrial fibrillation burden in patients with heart failure and sleep apnea. Heart Rhythm. 2019;16:91–7.

    Article  Google Scholar 

  21. Woehrle H, Cowie MR, Eulenburg C, Suling A, Angermann C, d’Ortho M-P, et al. Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis. Eur Respir J. 2017;50.

  22. Lee C-H, Barbé F. Adaptive servoventilation for central sleep apnoea in heart failure: a broken dream. Lancet Respir Med. 2016;4:846–7.

    Article  Google Scholar 

  23. Platt AB, Kuna ST, Field SH, Chen Z, Gupta R, Roche DF, et al. Adherence to sleep apnea therapy and use of lipid-lowering drugs: a study of the healthy-user effect. Chest. 2010;137:102–8.

    Article  CAS  Google Scholar 

  24. Villar I, Izuel M, Carrizo S, Vicente E, Marin JM. Medication adherence and persistence in severe obstructive sleep apnea. Sleep. 2009;32:623–8.

    Article  Google Scholar 

  25. Reiter J, Zleik B, Bazalakova M, Mehta P, Thomas RJ. Residual events during use of CPAP: prevalence, predictors, and detection accuracy. J Clin Sleep Med. 2016;12:1153–8.

    Article  Google Scholar 

  26. Schwab RJ, Badr SM, Epstein LJ, Gay PC, Gozal D, Kohler M, et al. An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults. Am J Respir Crit Care Med. 2013;188:613–20.

    Article  Google Scholar 

  27. Thomas RJ, Bianchi MT. Urgent need to improve PAP management: the devil is in two (fixable) details. J Clin Sleep Med. 2017;13:657–64.

    Article  Google Scholar 

  28. Tomita Y, Kasai T, Kasuga S, Morimoto K, Takaya H, Maeno K, et al. Evaluation of the apnea-hypopnea index determined by adaptive-servo ventilation devices in heart failure patients with sleep disordered breathing. Eur Respir J. 2014;44:P2008.

    Google Scholar 

  29. Gunn S, Naik S, Bianchi MT, Thomas RJ. Estimation of adaptive ventilation success and failure using polysomnogram and outpatient therapy biomarkers. Sleep. 2018;41(9).

  30. Silveira M-G, Sampol G, Cambrodi R, Ferre À, Lloberes P. Adaptive servoventilation device software in the assessment of residual respiratory events in patients with central or complex apnoeas. Arch Bronconeumol. 2017;53:455–7.

    Article  Google Scholar 

  31. The report of an American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep. 1999;22:667–89.

  32. Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the sleep apnea definitions task force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2012;8:597–619.

    PubMed  PubMed Central  Google Scholar 

Download references


The OTRLASV investigators gratefully recognise the vital input and support of the home care providers: Agevie (José Suarez), APARD Adene Group (Julien Bauchu, Frédéric Bousquet), ARARD Group (Florian Varielle), Home Air Agiradom Group (Frédéric Gil), LVL medical (Thierry Lefort)).


The authors have no support nor funding to report in relation with the present study.

Author information

Authors and Affiliations



DJ access to the data and takes responsibility for the integrity and accuracy of the analysis. CP and CR have equally contributed to this work. All authors contributed to and approved the final submitted manuscript. DJ: study design, data collection, analysis, and manuscript preparation; CP: data collection, manuscript preparation; CR: data collection, manuscript preparation; JPM: data collection, analysis, manuscript preparation; MG: data collection, manuscript preparation; SR: data collection, manuscript preparation; AP: data collection, manuscript preparation; CMS: data analysis and manuscript preparation, EN: data analysis; NM: study design, data analysis, manuscript preparation; AB: study design, data analysis and manuscript preparation.

Corresponding author

Correspondence to Dany Jaffuel.

Ethics declarations

Ethics approval and consent to participate

The OTRLASV study is registered on (Identifier: NCT02429986). The protocol complied with the Declaration of Helsinki and was reviewed and approved by an independent ethics committee (Comité de Protection des Personnes “Sud Méditérannée III”; reference number 2014.11.04).

Consent for publication

Not applicable.

Competing interests

Dr. Dany Jaffuel has performed lecturing at sponsored meetings for the following companies in the last 5 years: Apard, Bastide, Loewenstein Medical, Philips, SEFAM. He has sat on advisory boards for the following companies in the last 5 years: Lowenstein Medical, SEFAM. He has received sponsorship support to attend academic meetings in the last 5 years from Lowenstein Medical, Resmed, Philips and SEFAM.

- Dr. Alain Palot has performed lecturing at sponsored meetings for the following companies in the last 5 years: ARARD, Resmed, Philips. He has sat on advisory boards for the following company in the last 5 years: Resmed

- Dr. Claudio Rabec has performed lecturing at sponsored meetings and/or participated in boards for the following companies in the last 5 years: Resmed, Philips, Lowenstein, Air Liquide Medical Systems

AB, CMS, CP, EN, JPM, NM, MG, SR report no conflicts of interest in relation to the present work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Additional file 1.

SDB patient groups and enrolment center.

Additional file 2.

Inclusion and exclusion criteria.

Additional file 3.

Definition of the Central Sleep Apnea Group, the Obstructive Sleep Apnea group, and the Treatment Emergent Central Sleep Apnea Group.

Additional file 4.

Relationship between the existence of a CPAP trial before ASV initiation and the date of ASV initiation (p = 0.37).

Additional file 5.

Date of the last cardiological consultation depending on the year of ASV initiation (p = 0.19).

Additional file 6.

Date of the last cardiological echocardiography depending on the year of ASV initiation (p = 0.77).

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jaffuel, D., Philippe, C., Rabec, C. et al. What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study). Respir Res 20, 235 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: