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Original Research |

Long-term Auto-Servoventilation or Constant Positive Pressure in Heart Failure and Coexisting Central With Obstructive Sleep ApneaLong-term Efficacy of Auto-Servoventilation FREE TO VIEW

Winfried J. Randerath, MD, FCCP; Gregor Nothofer; Christina Priegnitz, MD; Norbert Anduleit; Marcel Treml, PhD; Victoria Kehl, PhD; Wolfgang Galetke, MD
Author and Funding Information

From the Institute of Pneumology at the University Witten/Herdecke, Clinic for Pneumology and Allergology, Center of Sleep Medicine and Respiratory Care, Bethanien Hospital (Drs Randerath, Priegnitz, and Treml and Messrs Nothofer and Anduleit), Solingen; Institute of Medical Statistics and Epidemiology (Dr Kehl), Study Centre Munich, Hospital Klinikum rechts der Isar, Technical University of Munich, Munich; and Krankenhaus der Augustinerinnen (Dr Galetke), Cologne, Germany.

Correspondence to: Winfried J. Randerath, MD, FCCP, Institute of Pneumology at the University Witten/Herdecke, Clinic for Pneumology and Allergology, Center of Sleep Medicine and Respiratory Care, Bethanien Hospital, Aufderhöherstraße 169-175, 42699 Solingen, Germany; e-mail: randerath@klinik-bethanien.de


Funding/Support: This study was supported in part by Philips Respironics (Murrysville, PA).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(2):440-447. doi:10.1378/chest.11-2089
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Background:  The coexistence of obstructive sleep apnea (OSA) and central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) is common in patients with heart failure (HF). While CPAP improves CSA/CSR by about 50%, maximal suppression is crucial in improving clinical outcomes. Auto-servoventilation (ASV) effectively suppresses CSA/CSR in HF, but few trials have been performed in patients with coexisting OSA and CSA/CSR. Our objective was to evaluate a randomized, controlled trial to compare the efficacy of ASV and CPAP in reducing breathing disturbances and improving cardiac parameters in patients with HF and coexisting sleep-disordered breathing.

Methods:  Both modes were delivered using the BiPAP autoSV (Philips Respironics) over a 12-month period. Seventy patients (63 men, 66.3 ± 9.1 y, BMI 31.3 ± 6.0 kg/m2) had coexisting OSA and CSA/CSR, arterial hypertension, coronary heart disease, or cardiomyopathy and clinical signs of heart failure New York Heart Association classes II-III. Polysomnography, brain natriuretic peptide (BNP), spiroergometry, and echocardiography were performed at baseline and after 3 and 12 months of treatment.

Results:  Both modes of therapy significantly improved respiratory disturbances, oxygen desaturations, and arousals over the study period. ASV reduced the central apnea hypopnea index (baseline CPAP, 21.8 ± 11.7; ASV, 23.1 ± 13.2; 12 months CPAP, 10.7 ± 8.7; ASV, 6.1 ± 7.8, P < .05) and BNP levels (baseline CPAP, 686.7 ± 978.7 ng/mL; ASV, 537.3 ± 891.8; 12 months CPAP, 847.3 ± 1848.1; ASV, 230.4 ± 297.4; P < .05) significantly more effectively as compared with CPAP. There were no relevant differences in exercise performance and echocardiographic parameters between the groups.

Conclusions:  ASV improved CSA/CSR and BNP over a 12-month period more effectively than CPAP.

Trial registry:  ISRCTN Registry; No: ISRCTN70594408; URL: www.controlled-trials.com

Figures in this Article

In recent years, the complexity of sleep-related breathing disorders (SRBDs) has been acknowledged, especially in patients with cardiovascular disease.1,2 Aside from the distinct entities of obstructive sleep apnea (OSA), central sleep apnea (CSA), and Cheyne-Stokes respiration (CSR), combinations of these breathing disorders may also manifest in some patients.3 The definition of CSA has also been expanded to include patients with CPAP-resistant CSA, CPAP-emergent CSA, and opioid-induced sleep apnea.1

The diagnosis and treatment of SRBD in patients with heart failure (HF) is of crucial importance. First, SRBD often remains unobserved in this population because the typical symptoms of sleep apnea can be masked by the symptoms of their underlying heart disease. Second, patients with HF and SRBD are characterized by a reduced left ventricular function, increased malignant arrhythmias, and poor prognosis.4,5 Last, patients with OSA have been shown to have a reduced survival rate due to cardiovascular events.6,7

If SRBDs remain unresolved after optimizing medical and interventional cardiac treatment,8 oxygen therapy, CPAP, and bilevel therapy are often evaluated in trials. While there is only limited evidence to recommend oxygen or bilevel therapy, CPAP has proven to reduce breathing disorders by approximately 50% and improve left ventricular function.9,10 However, CPAP does not normalize SRBD in all of these patients or improve survival.9

The optimal suppression of respiratory disturbances in HF may be of major importance for the prognosis.11 The results of the Canadian Positive Airway Pressure Trial for Heart Failure Patients with Central Sleep Apnea post hoc analysis suggested that an improved survival may only manifest in patients whose apnea hypopnea index (AHI) is reduced to < 15/h. Accordingly, treatments which suppress the AHI in those patients who are not optimally controlled by CPAP may be of clinical importance.

Auto-servoventilation (ASV) effectively reduces OSA and CSA/CSR. ASV devices provide a fixed or automatic expiratory positive airway pressure (EPAP) to eliminate upper airway obstruction and modulate the inspiratory positive airway pressure (IPAP) to overcome CSR.8 Thus, the algorithms prevent hypoxia and hypocapnia, eliminate ventilatory overshoot, and stabilize respiration. Short-term studies have demonstrated that ASV is superior to subtherapeutic ASV, CPAP, or bilevel in improving sleep quality, daytime performance, respiratory disturbances, and cardiovascular and sympathetic markers.1214 More recent studies have focused on patients with comorbid OSA and CSA.3,15,16 However, they were of short follow-up and limited sample size.

Based on previous findings, we hypothesized that ASV would improve CSA/CSR more effectively than CPAP in patients with mild to moderate HF and coexisting OSA and CSA over the long term.

Patients

Seventy consecutive patients ≥ 18 years with clinically diagnosed HF (left ventricular ejection fraction ≥ 20%, New York Heart Association [NYHA] class II-III) under optimal medical treatment and coexisting OSA and CSA (AHI ≥ 15/h, central proportion ≤ 80% and obstructive proportion between 20% and 50%) were included. Underlying cardiac disorders included arterial hypertension, coronary artery disease, and dilated cardiomyopathy. Cardiac medication did not differ between the groups and was not significantly changed during the course of the study. Exclusion criteria included myocardial infarction, unstable angina pectoris, or cardiac surgery within the last 3 months, and pregnancy. All patients gave their written informed consent. The study was approved by the ethical committee of the University of Witten/Herdecke (Institutional Review Board No. 53/2006).

Treatment Device

Both treatment modes (CPAP and ASV) were delivered using the same device (BiPAP autoSV; Philips Respironics). When used in CPAP mode, the IPAP and EPAP were set at the same level. When delivering ASV therapy, the EPAP pressure was fixed according to the CPAP titration and the IPAP varied between the EPAP pressure and maximum IPAP, which was set by the physician according to the requirements of the patient within the range of 4-30 cm H2O. The device automatically applied mandatory breaths during periods of central apnea.

Design

This was a randomized, parallel-group design, operator- and patient-blinded, single-center clinical study. After a full-night, inpatient polysomnography, eligible patients were randomized (lots were drawn by a person not involved in the study) to receive CPAP or ASV therapy for a 1-year period (Table 1). Patients and data analysts were blinded to therapy allocation. All patients underwent three additional consecutive nights in the sleep laboratory; two for titration purposes and one under optimal settings (treatment night 1, Fig 1, e-Appendix 1).

Figure Jump LinkFigure 1. Diagram of the study design. ASV = auto-servoventilation; BR = breathing rate; EPAP = expiratory positive airway pressure; IPAP = inspiratory positive airway pressure; ITT = intention to treat; PP = per protocol; PSG = polysomnography.Grahic Jump Location
Table Graphic Jump Location
Table 1 —Anthropometric and Polysomnographic Parameters of the Complete Study Group

AHI periodic is a subgroup of AHI central. AHI = apnea hypopnea index; AHI central, /h = number of central apneas and hypopneas per hour of total sleep time; AHI mixed, /h = number of mixed apneas and hypopneas per hour of total sleep time; AHI obstructive, /h = number of obstructive apneas and hypopneas per hour of total sleep time; AHI periodic, /h = number of periodic apneas and hypopneas per hour of total sleep time (the periodic breathing disturbances are a subgroup of the central AHI); AHI total, /h = total number of apneas and hypopneas per hour of total sleep time; AI central = number of central apneas per hour of total sleep time; AI obstructive = number of obstructive apneas per hour of total sleep time; Arousal resp, /h = number of respiration-associated EEG arousals per hour of total sleep time; Arousal total, /h = total number of EEG arousals per hour of total sleep time; ASV = auto-servoventilation; % TST = proportion of rapid eye movement sleep per hour of total sleep time; REM = rapid eye movement; REM, S1/S2, % TST = proportion of sleep stages 1 and 2 per hour of total sleep time; S3/S4, % TST = proportion of sleep stages 3 and 4 and per hour of total sleep time; Time < 90% Sao2, min = time with oxygen saturation below 90%; TST = total sleep time; WASO = wake after sleep onset.

a 

Baseline vs treatment (Wilcoxon test): P < .001.

b 

ASV vs CPAP (Mann-Whitney U test): P < .05.

c 

ASV vs CPAP (Mann-Whitney U test): P < .001.

d 

Baseline vs treatment (Wilcoxon test): P < .01.

e 

ASV vs CPAP (Mann-Whitney U test): P < .01.

f 

Baseline vs treatment (Wilcoxon test): P < .05.

At baseline and at 3 and 12 months, patients underwent echocardiography, cardiopulmonary exercise testing, measurement of brain natriuretic protein (BNP), and self-administered a series of questionnaires, including the Minnesota Living with Heart Failure self-administered questionnaire (e-Appendix 1).17 Patients were contacted by telephone after 6 and 9 months to collect data on quality of life.

Polysomnography

Polysomnography was performed using an Alice 4 Sleep Diagnostic System (Philips Respironics). The analysis of sleep stages and arousals was carried out according to Rechtschaffen and Kales.18

We classified hypopneas as central if there was a reduction in respiratory flow and effort without flattening of the flow curve or paradoxical breathing. Events with a central and obstructive proportion were classified as mixed. Central apneas were scored if respiratory effort was absent. Periodic breathing was scored if the pattern of waxing and waning of flow and effort was present19 (e-Appendix 1).

Statistics

The primary end point of the study was the central AHI on treatment at 12 months. The sample size was calculated as 35 patients per treatment group. All analyses were performed on the intention-to-treat (ITT) data set (e-Appendix 1). The per-protocol (PP) data set, which contained all patients with 12-month data, was also analyzed.

Between-group comparisons were performed using an adjusted linear regression with the 12-month value as the dependent variable and the baseline value and treatment group as the independent variables. In addition, changes in each parameter between baseline and 12 months were compared between the treatment groups using an independent sample t test. In case of non-normality, the Mann-Whitney U test was used.

All statistical tests were performed two-sided with a significance level of 5%. Results from the primary endpoint are confirmatory. All other analyses are explanatory, and the P values are not adjusted for multiplicity. All statistical analyses were performed with the software package PASW 18.0 (SPSS, Inc). Data are presented as mean and SD (e-Appendix 1).

Seventy patients (63 men; mean age, 66.3 ± 9.1 years; and mean BMI, 31.3 ± 6.0 kg/m2) were enrolled into the study (Table 1). One patient withdrew consent before initiation, and nine patients discontinued the study early in each group, leaving 51 patients who completed the study (Fig 1).

The total AHI in the whole study population was 43.9 ± 20.7/h with 54.7% CSA/CSR (CPAP 56.0%, ASV 53.4%, not significant). There were no significant differences between the CPAP and ASV groups in anthropometric, echocardiographic, and polysomnographic parameters at baseline (Tables 1, 2).

Table Graphic Jump Location
Table 2 —Cardiac Parameters (PP Analysis)

IVSTd = interventricular septal thickness, diastolic; IVSTs = interventricular septal thickness, systolic; LVEDD = left ventricular end-diastolic diameter; LVEDV = left ventricular end-diastolic volume; LVEDWT = left ventricular end-diastolic wall thickness; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic diameter; LVESV = left ventricular end-systolic volume; LVESWT = left ventricular end-systolic wall thickness; LVTX = left ventricular Tei index; NT-proBNP = N-terminal brain natriuretic peptide; PP = per protocol; o2max/HR = maximal oxygen consumption per heart beat; V˙ o2max/kg = maximal oxygen consumption per kilogram of body weight. See Table 1 legend for expansion of other abbreviations.

a 

ASV vs CPAP (Mann-Whitney U test): P < .05.

b 

Baseline vs treatment (Wilcoxon test): P < .01.

c 

Baseline vs treatment (Wilcoxon test): P < .05.

d 

ASV vs CPAP (Mann-Whitney U test): P < .01.

Both methods significantly improved the total AHI. CPAP reduced the central breathing disturbances by about 50%. However, ASV improved the central AHI significantly better than CPAP, reaching a mean level below 10/h (Fig 2, e-Fig 1). Thus, the primary outcome parameter was reached (P = .023). ASV also significantly reduced periodic and mixed breathing disturbances as compared with CPAP at 12 months (Table 1, e-Table 1). In addition, the BNP level significantly improved in the ASV group in the PP analysis (Table 2).

Figure Jump LinkFigure 2. A-C, Tukey plots of the respiratory disturbances. The Tukey plots of the (A) total, (B) central, and (C) obstructive AHI under CPAP (open bars) and ASV (hatched bars). The boxes present the interquartile distances, the horizontal lines the median, the whiskers the maximum and minimum values within 1.5 times the interquartile range. Both treatment options significantly improve all types of respiratory disturbances as compared with baseline. However, ASV significantly improved the central AHI at 3 and 12 months and in terms of the total AHI at 3 months as compared with CPAP. AHI = apnea hypopnea index. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location

Both modes of therapy significantly normalized OSA. Mean and minimal oxygen saturation, total and respiratory associated arousals, and snoring similarly improved with both modes. There was no significant difference between the modes in terms of sleep stages and other sleep parameters (Table 1, e-Table 1).

The maximum oxygen consumption was significantly higher in the ASV group at all times. However, there was no significant change over time between the groups. The echocardiographic parameters did not differ substantially between the two groups (Table 2).

The overall compliance was > 4 h/d over the study period in both groups with no significant differences between them (CPAP, 4.3 ± 2.3 h/d; ASV, 5.2 ± 2.0 h/d). The self-assessed questionnaire showed significant improvements of daytime sleepiness, witnessed snoring and apneas with both modes, and additional improvement of attention under ASV. Furthermore, ASV significantly improved the level of dyspnea and fatigue, but there were no significant differences between the groups (e-Appendix 2, e-Tables 2, 3).

These data demonstrate that ASV is advantageous as compared with CPAP in patients with clinically diagnosed mild to moderate HF and coexisting OSA and CSA. While both methods normalize obstructive apneas and hypopneas similarly, ASV was significantly more effective in suppressing central and mixed breathing disturbances, including periodic breathing, over the long term. This finding was accompanied by an improvement of the level of BNP as a marker of HF prognosis under ASV as compared with CPAP.

We focused on a group of patients with both coexisting OSA and CSA because it was clinically relevant to our practice. Although OSA can be sufficiently treated with CPAP, the central portion is reduced only by approximately 50%.9 Furthermore, CSA may even emerge or be unmasked by CPAP therapy.1,2 Optimal suppression of respiratory disturbances may be of crucial importance for the long-term outcome of patients with and without HF.6,7,11 For these reasons, optimal treatment of both OSA and CSA/CSR appears to be essentially relevant.

The proportion of obstructive and mixed breathing disturbances and CSA/CSR was 50% each. Not surprisingly, CPAP and ASV both normalized OSA; however, the study confirmed earlier results that CPAP reduces CSA/CSR by approximately 50%. Thus, the room of further improvement of central breathing disturbances that could be achieved by ASV was 50% and of the total AHI, 25%. Nevertheless, ASV reduced central breathing disturbances significantly more effectively than CPAP both in the ITT and PP analysis at 3 and 12 months. Furthermore, the improvement in CSA/CSR on ASV led to a significant improvement in the total AHI at 3 months and a clear trend toward an improvement at 12 months as compared with CPAP.

While there were no differences in the exercise performance tests between the modes, the reduction of the BNP level indicates an improvement of heart function when using ASV. This finding was supported by the self-assessed reductions of dyspnea and fatigue under this mode of therapy.

The data presented in this study are in agreement with previous studies looking at the respiratory and cardiologic effects of ASV therapy, although these have only investigated the effects of this treatment over the short to mid term. Teschler and colleagues20 compared one night of oxygen, CPAP, bi-level therapy, and ASV in a group of 14 patients with stable cardiac failure and predominant CSA/CSR. Similar to our data, CPAP reduced the central apnea index by only 50%. While bi-level led to a better improvement of the mean central apnea index, there was a huge variation in individual results in Teschler et al’s20 study. In contrast, ASV normalized the central apnea index in almost all the patients.20 Arzt et al14 showed that ASV reduced the AHI < 15 in a group of patients insufficiently treated with bilevel and CPAP. However, this article included patients with almost pure CSA/CSR. Pepperell et al12 studied ASV and subtherapeutic ASV for 1 month. Effective ASV improved respiratory disturbances, daytime functioning, and cardiovascular and sympathetic markers significantly better than subtherapeutic ASV. This study differed from our design due to the more severe HF and shorter duration. Philippe et al13 assigned 25 patients with CSA and CSR, and stable HF (NYHA stages II-IV), to ASV or CPAP for 6 months. The authors found a significantly better improvement in respiratory disturbances, heart function, quality of life, and compliance in the patients using ASV. In contrast, our data do not show differences in patient compliance or self-assessment of quality of life. However, one might assume that the smaller margin of improvement in the central and total AHI and the lower severity of HF in our trial were the most important reasons for the differences. Morgenthaler et al21 compared ASV and noninvasive positive pressure ventilation (NIV) in central, mixed, and complex sleep apnea over the short term. Both treatment options improved respiration but ASV was superior over NIV. More recently, Koyama and colleagues16 treated 10 patients with HF NYHA II-III with ASV and seven patients without ASV. They found a significant improvement in the treated patients in NYHA class, BNP, ejection fraction, and CRP after 6 weeks. While our results on BNP agree with Koyama’s findings, the difference in the additional parameters may result from the differences in the study populations and the different treatment in the control group (CPAP vs no positive pressure treatment).

Recently, some studies focused on patients with coexisting OSA and CSA. Our group performed a prospective pilot study on the efficacy of ASV in 10 male consecutive patients with coexisting OSAS and CSA/CSR with and without HF over 8 weeks. ASV proved to effectively suppress all types of respiratory disturbances and to improve sleep quality.3 These results were further confirmed by Kasai et al22 in 31 patients with HF who were treated for 3 months with CPAP or ASV. Similarly to Philippe et al,13 our data show improvement of some aspects of quality of life under ASV while they did not change under CPAP.

The current study showed similar daily compliance rates with both CPAP and ASV treatment and a similar number of patients discontinued treatment in each treatment arm. These compliance levels are in line with previous studies investigating compliance with CPAP in patients with OSA23 and CPAP and ASV compliance in patients with HF.22 These compliance levels are also clinically relevant given the limited amount of sleep apnea symptoms observed in patients with HF and the long-term design used in this study.

Some limitations should be discussed. The effects on cardiac parameters might have been more distinct in patients with more severely limited heart function. However, we focused on patients with mild to moderate HF for several reasons: Although about 50% of patients with stable HF in NYHA stages ≥ II suffer from SRBD, most studies on ASV focused on more severely ill patients with overwhelming CSR rather than coexisting OSA and CSA/CSR. However, ASV has especially been designed for those with coexisting breathing disturbances which required clinical verification. Moreover, due to the high prevalence of less severe HF in daily practice, it seemed reasonable to search for sufficient treatment options for this population. In addition, it was important to present long-term data from less severely affected patients prior to performing a randomized controlled study over 1 year in patients with a left-ventricular ejection fraction < 20%. Finally, changes in treatment and other confounding factors might limit the interpretation of data from severely affected patients.

As a consequence, the results cannot be generalized to other patient populations, for example, patients with HF NYHA IV, patients suffering from CPAP-emerging CSA, or opioid-induced sleep apnea. However, the results encourage one to perform long-term trials in these and other groups.

This study was performed using the ASV version with fixed EPAP and varying IPAP. The first short-term data on algorithms with additional automatic adaptation of the EPAP have been presented,24 showing a slightly better suppression of respiratory disturbances as compared with the algorithm tested here. However, long-term studies on this technique are lacking.

In conclusion, ASV has proven to suppress central, periodic, and mixed respiratory disturbances more effectively, and obstructive events equally effectively as compared with CPAP over a period of 12 months in patients with mild to moderate HF. This was accompanied by an improvement of the level of BNP as a marker of HF.

Author contributions: Dr Randerath had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Randerath: contributed to the conception and design of this study; acquisition, analysis, and interpretation of data; and manuscript preparation.

Mr Nothofer: contributed to the acquisition and interpretation of data and revision of the manuscript.

Dr Priegnitz: contributed to the acquisition and interpretation of data and manuscript preparation.

Mr Anduleit: contributed to the analysis and interpretation of data and manuscript preparation.

Dr Treml: contributed to the analysis and interpretation of data and manuscript preparation.

Dr Kehl: contributed to the analysis and interpretation of data and preparation of the manuscript.

Dr Galetke: contributed to the conception and design of this study and manuscript preparation.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Randerath has received travel grants and speaking fees from Philips Respironics. Dr Kehl has received fees as a contract statistician for Philips Respironics. The remaining authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: We thank Carla Miltz for her effort and support in completing this manuscript. Furthermore, we thank Ilona Kietzmann and Kerstin Richter for their support in analyzing and evaluating the data collected in this study.

Additional information: The e-Appendixes, e-Tables, and e-Figure can be found in the “Supplemental Materials” area of the online article.

AHI

apnea hypopnea index

ASV

auto-servoventilation

BNP

brain natriuretic peptide

CSA

central sleep apnea

CSR

Cheyne-Stokes respiration

EPAP

expiratory positive airway pressure

HF

heart failure

IPAP

inspiratory positive airway pressure

ITT

intention to treat

NIV

noninvasive positive pressure ventilation

NYHA

New York Heart Association

OSA

obstructive sleep apnea

PP

per protocol

SRBD

sleep-related breathing disorder

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Figures

Figure Jump LinkFigure 1. Diagram of the study design. ASV = auto-servoventilation; BR = breathing rate; EPAP = expiratory positive airway pressure; IPAP = inspiratory positive airway pressure; ITT = intention to treat; PP = per protocol; PSG = polysomnography.Grahic Jump Location
Figure Jump LinkFigure 2. A-C, Tukey plots of the respiratory disturbances. The Tukey plots of the (A) total, (B) central, and (C) obstructive AHI under CPAP (open bars) and ASV (hatched bars). The boxes present the interquartile distances, the horizontal lines the median, the whiskers the maximum and minimum values within 1.5 times the interquartile range. Both treatment options significantly improve all types of respiratory disturbances as compared with baseline. However, ASV significantly improved the central AHI at 3 and 12 months and in terms of the total AHI at 3 months as compared with CPAP. AHI = apnea hypopnea index. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Anthropometric and Polysomnographic Parameters of the Complete Study Group

AHI periodic is a subgroup of AHI central. AHI = apnea hypopnea index; AHI central, /h = number of central apneas and hypopneas per hour of total sleep time; AHI mixed, /h = number of mixed apneas and hypopneas per hour of total sleep time; AHI obstructive, /h = number of obstructive apneas and hypopneas per hour of total sleep time; AHI periodic, /h = number of periodic apneas and hypopneas per hour of total sleep time (the periodic breathing disturbances are a subgroup of the central AHI); AHI total, /h = total number of apneas and hypopneas per hour of total sleep time; AI central = number of central apneas per hour of total sleep time; AI obstructive = number of obstructive apneas per hour of total sleep time; Arousal resp, /h = number of respiration-associated EEG arousals per hour of total sleep time; Arousal total, /h = total number of EEG arousals per hour of total sleep time; ASV = auto-servoventilation; % TST = proportion of rapid eye movement sleep per hour of total sleep time; REM = rapid eye movement; REM, S1/S2, % TST = proportion of sleep stages 1 and 2 per hour of total sleep time; S3/S4, % TST = proportion of sleep stages 3 and 4 and per hour of total sleep time; Time < 90% Sao2, min = time with oxygen saturation below 90%; TST = total sleep time; WASO = wake after sleep onset.

a 

Baseline vs treatment (Wilcoxon test): P < .001.

b 

ASV vs CPAP (Mann-Whitney U test): P < .05.

c 

ASV vs CPAP (Mann-Whitney U test): P < .001.

d 

Baseline vs treatment (Wilcoxon test): P < .01.

e 

ASV vs CPAP (Mann-Whitney U test): P < .01.

f 

Baseline vs treatment (Wilcoxon test): P < .05.

Table Graphic Jump Location
Table 2 —Cardiac Parameters (PP Analysis)

IVSTd = interventricular septal thickness, diastolic; IVSTs = interventricular septal thickness, systolic; LVEDD = left ventricular end-diastolic diameter; LVEDV = left ventricular end-diastolic volume; LVEDWT = left ventricular end-diastolic wall thickness; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic diameter; LVESV = left ventricular end-systolic volume; LVESWT = left ventricular end-systolic wall thickness; LVTX = left ventricular Tei index; NT-proBNP = N-terminal brain natriuretic peptide; PP = per protocol; o2max/HR = maximal oxygen consumption per heart beat; V˙ o2max/kg = maximal oxygen consumption per kilogram of body weight. See Table 1 legend for expansion of other abbreviations.

a 

ASV vs CPAP (Mann-Whitney U test): P < .05.

b 

Baseline vs treatment (Wilcoxon test): P < .01.

c 

Baseline vs treatment (Wilcoxon test): P < .05.

d 

ASV vs CPAP (Mann-Whitney U test): P < .01.

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