(Circulation. 2000;101:392.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Continuous Positive Airway Pressure on Sleep Apnea and Ventricular Irritability in Patients With Heart Failure
From the Sleep Disorders Laboratory, Department of Veterans Affairs Medical Center, and Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
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Abstract |
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Background—Patients with heart failure and systolic dysfunction may develop disordered breathing during sleep. Repeated episodes of apnea and hypopnea may result in desaturation and arousals, which could adversely affect left ventricular function. The purpose of this study was to determine the short-term effects of continuous positive airway pressure (CPAP) on sleep-disordered breathing and its consequences in heart failure patients.
Methods and Results—The author prospectively studied 29 male patients whose initial polysomnograms showed 15 or more episodes of apnea and hypopnea per hour (apnea-hypopnea index, AHI). Twenty-one patients had predominately central and 8 patients obstructive sleep apnea. All were treated with CPAP during the subsequent night. In 16 patients, CPAP resulted in virtual elimination of disordered breathing. In these patients, the mean AHI (36±12 [SD] versus 4±3 per hour, P=0.0001), arousal index due to disordered breathing (16±9 versus 2±2 per hour, P=0.0001), and percent of total sleep time below saturation of 90% (20±23% to 0.3±0.7%, P=0.0001) decreased, and lowest saturation (76±8% versus 90±3%, P=0.0001) increased with CPAP. In 13 patients who did not respond to CPAP, these values did not change significantly. In patients whose sleep apnea responded to CPAP, the number of hourly episodes of nocturnal premature ventricular contractions (66±117 versus 18±20, P=0.055) and couplets (3.2±6 versus 0.2±0.21, P=0.031) decreased. In contrast, in patients whose sleep apnea did not respond to CPAP, ventricular arrhythmias did not change significantly.
Conclusions—In 55% of patients with heart failure and sleep apnea, first-night nasal CPAP eliminates disordered breathing and reduces ventricular irritability.
Key Words: nervous system, sympathetic • heart failure • respiration • hypoxia
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Heart failure is a highly prevalent disorder with considerable morbidity and mortality despite advancements in its therapy. A recent systematic study in patients with treated, stable heart failure with left ventricular systolic dysfunction reported that
50% had periodic breathing during
sleep.1 Periodic breathing (defined as a pattern of
breathing consisting of periodically recurring cycles of apnea or
hypopnea followed by hyperpnea) may result in arterial
oxyhemoglobin desaturation, excessive arousals, and changes in
intrathoracic pressure.1 2 3 If left untreated, the
pathophysiological consequences of periodic
breathing could affect cardiac function adversely, contributing to an
increase in morbidity and mortality of patients with heart
failure.4 In a study reported from this
laboratory,1 we found that heart failure patients with
sleep apnea had a lower left ventricular ejection fraction
and a higher prevalence of atrioventricular
arrhythmias than patients without periodic breathing; the cause
and effect, however, could not be determined. Nasal continuous positive airway pressure (CPAP) devices are well known to prevent upper airway occlusion, which occurs in obstructive sleep apnea (OSA).5 6 7 These devices have been successfully used to treat OSA in patients without heart failure. More recently, CPAP devices have been used for treatment of sleep apnea in patients with heart failure and systolic dysfunction.8 9 10 With regard to treatment of central sleep apnea (CSA), the most common form of disordered breathing in heart failure, although the results from one center have been promising,8 2 other centers9 10 reported no significant beneficial effects of CPAP on CSA.
During the past few years, we have been involved in studies of
periodic breathing in a relatively large number of patients with heart
failure resulting from systolic dysfunction.1 11
We have studied patients who were ambulatory and stable on standard
therapy for heart failure, with no other major disorders (eg, chronic
obstructive lung disease). Patients who were found to have an
apnea-hypopnea index (AHI) of 
15 per hour were subsequently treated
with CPAP and are the subject of this report.
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Methods |
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The patients in the current study belonged to the pool of 81 patients with stable heart failure and left ventricular systolic dysfunction (left ventricular ejection fraction <45%) who have been described in detail previously.1 11 Twenty-nine of these patients whose initial polysomnograms showed an AHI of
15 per hour were subsequently
treated with CPAP. All patients were clinically stable (no change in symptoms of heart failure or their medications within the previous 4 weeks) and on standard therapy, including an angiotensin-converting enzyme inhibitor (23 patients), hydralazine (4 patients), digoxin (23 patients), isosorbide dinitrate (12 patients), and diuretics (26 patients).
Exclusion criteria have been detailed previously1 11 and included major comorbid disorders (such as chronic obstructive pulmonary disease and known intrinsic liver and renal disorders) and use of morphine derivatives, benzodiazepines, theophylline, and acetazolamide. For uniformity, only male patients were studied: female patients are seldom referred to this center.
Polysomnography
On the first night, the patients slept in the sleep laboratory
after electrodes had been placed, with the intention of familiarizing
them with the environment of the sleep laboratory. On the second night,
polysomnography was performed using standard techniques as detailed
previously.12 13 For staging sleep, we recorded
electroencephalogram (2 channels), chin electromyogram (1 channel), and
electro-oculogram (2 channels). Thoracoabdominal excursions and
naso-oral airflow (measured by a thermocouple) were measured
qualitatively. Arterial blood oxyhemoglobin saturation was
recorded using an oximeter. The output of pulse oximeter at 0 V was
considered 0% saturation and at 1 V, 100% saturation. The voltage
calibration was performed several times throughout each study. The
variables were recorded on a multichannel polygraph (Model 78D;
Grass Instrument Company).1 11 12 13
An apnea was defined as cessation of inspiratory airflow for 10
seconds. All such events were counted irrespective of the degree of
desaturation or presence of an arousal. An obstructive apnea was
defined as the absence of airflow in the presence of rib cage and/or
abdominal excursions. A central apnea was defined as the absence of rib
cage and abdominal excursions with absence of airflow. It is noted,
however, that in the absence of measurements of esophageal pressure, it
is sometimes difficult to truly distinguish a central apnea from an
obstructive apnea. Hypopnea was defined as a discernible reduction in
airflow or thoracoabdominal excursions lasting 10 seconds and
resulting in an arousal14 or at least a 4% drop in
arterial oxyhemoglobin saturation. The author classified
hypopnea as obstructive if paradoxical thoracoabdominal excursions
occurred or if the airflow decreased out of proportion to the reduction
in the thoracoabdominal excursions. The number of episodes of apnea and
hypopnea per hour of sleep is referred to as the AHI. Similarly, the
number of episodes of arousal per hour of sleep is referred to as the
arousal index. The patients were classified to have predominately
OSA- or CSA-hypopnea as defined earlier.1 In
patients with predominately CSA, the obstructive AHI had to be <10 per
hour; at least 50% of the disordered breathing events were classified
as central. In these patients, the obstructive AHI varied from 0.0 to
9.1 per hour. In patients with predominately OSA, obstructive AHI had
to be 10 per hour, and it represented at least 50% of
the disordered breathing events. In these patients the obstructive AHI
varied from 19.9 to 35.3 per hour. All polysomnograms were scored
blindly.
CPAP Titration
Patients who had an AHI 15 were studied during the third night
in the sleep laboratory with CPAP. Titration began with 5 cm
H2O, and the pressure was progressively and
gradually increased by 1 cm H2O every 15 minutes,
to eliminate episodes of apnea, hypopnea, desaturation, and arousal.
Pressure was decreased, at the patient’s request if awakening
occurred, and titration was resumed as the patients fell asleep. We had
the intention to discontinue CPAP if patients complained of dizziness
or chest discomfort.
For the purpose of this study, we defined individuals whose AHI on CPAP decreased to <15 per hour, "CPAP-responsive." This was the threshold we used to define presence of clinically significant sleep apnea.1 In all these patients, the AHI decreased by >50%.
Other Studies
To determine the prevalence of arrhythmia and its
response to CPAP, Holter monitoring was performed during
polysomnography, as detailed previously.14 In this study,
16 patients had paired Holter recordings.
Ventricular tachycardia was defined as the
presence of 3 ventricular premature beats in a row. Right
and left ventricular ejection fractions were calculated
from gated first pass and multigated radionuclide ventriculograms,
respectively, using standard techniques. Pulmonary function
tests and arterial blood samples were obtained as detailed
previously.1 13 These studies were approved by the
Institutional Review Board at the University of Cincinnati, and
written informed consent of each patient was obtained.
Statistical Analysis
We used the Wilcoxon rank sum test for paired and
Mann-Whitney U statistic for unpaired data, because our data
were not normally distributed; 
2 was used for
comparison of proportions. A 2-tail P value 
0.05 was
considered significant. Values are reported as mean±SD. Calculations
were done using GraphPad Instat V2.03.
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Results |
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There were 29 heart failure patients, 8 with OSA and 21 with CSA. Fifty-five percent (16 of 29) patients responded to CPAP, 7 with OSA and 9 with CSA.
Patients with OSA were significantly heavier and had a higher
prevalence of habitual snoring than patients with CSA (Table 1
). In patients with OSA, application of
nasal CPAP resulted in significant improvement in disordered breathing
and arterial oxyhemoglobin desaturation, with a significant
drop in arousals due to periodic breathing (Figure 1). These arousals decreased from
22±10 to 3±3 per hour and accounted for most of the decrease in
overall arousal index from 42±31 to 14±9 per hour
(P=0.008). Sleep stages did not change significantly. CPAP
values varied from 5 to 18 cm H2O, with a mean of
8±5 cm H2O.
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In one patient with predominate OSA (AHI 54 per hour, obstructive AHI 35 per hour, and central apnea index 14 per hour), CPAP resulted in elimination of all obstructive episodes (index=0.0 per hour), but episodes of central apnea increased (central apnea index increased to 21 per hour with CPAP). This patient was considered nonresponsive to CPAP.
There were 21 patients with CSA, 9 of whom responded to CPAP (43% of
patients with CSA). CPAP significantly improved disordered breathing
and arterial oxyhemoglobin desaturation with a significant
decrease in the number of arousals due to periodic breathing (Figure 2). These arousals decreased from
12±8 to 2±2 per hour (Figure 2) and accounted for the decrease
in the overall arousal index from 21±16 to 11±9 per hour
(P=0.098). There were no significant changes in sleep
stages, however. The CPAP values varied from 5 to 12 cm
H2O and the mean was 7±2 cm
H2O.
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In the 12 heart failure patients with CSA who did not respond to CPAP, the mean values for AHI (62±22 versus 62±29 per hour, baseline versus CPAP, respectively), central apnea index (43±21 versus 49±21 per hour), total dark time (397±21 versus 383±43 minutes), total sleep time (255+51 versus 212±83 minutes), most sleep stages, and arousal index (40±27 versus 40±31 per hour) did not change significantly. However, CPAP modestly improved arterial oxyhemoglobin desaturation with percent total sleep time below 90% decreasing from 30±17% to 9±15%, P=0.02). Values for CPAP varied from 5 to 18 cm H2O, and the mean was 13±4 cm H2O.
Although there were significant differences in demographics of patients
with OSA versus CSA (Table 1
), demographics of heart failure
patients with CSA who did not respond to CPAP did not differ from those
who did (Table 1). However, the AHI was significantly higher in
nonresponsive than responsive patients (Table 1).
In patients whose sleep apnea responded to CPAP, the number of
premature ventricular contractions, couplets, and
ventricular tachycardias decreased with CPAP
(Table 2). In contrast, CPAP had no
significant effect on ventricular irritability in patients
whose disordered breathing did not improve (Table 2).
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Discussion |
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This is the largest study of the effects of CPAP on sleep-disordered breathing in patients with stable, treated heart failure and systolic dysfunction. There were 29 heart failure patients with sleep apnea, 55% of whom (16 of 29 patients) responded significantly to CPAP. In these patients, AHI, arousal index, and arterial oxyhemoglobin saturation improved. Ventricular arrhythmias also improved in patients whose disordered breathing responded to CPAP; there was no significant change in nonresponders.
Effects of CPAP in Heart Failure Patients With OSA
In 8 patients with OSA, application of nasal CPAP (8±5 cm
H2O) resulted in a significant reduction in AHI
from 37 to 5 per hour (Figure 1). As a result, arousal index due
to sleep apnea and hypopnea decreased significantly from 22 to 3 per
hour, and time below saturation of 90% decreased from 31% of the
total sleep time to 1% (Figure 1).
Continuous positive airway pressure is known to maintain upper airway patency by increasing transmural pressure of upper airways.5 6 7 The relief of upper airway occlusion in heart failure patients with OSA should be similar to OSA patients without heart failure. However, therapeutic implications of improvement in obstructive apnea-hypopnea in the setting of heart failure with established left ventricular systolic dysfunction and/or coronary artery disease could be different from those in OSA without heart failure. These may include several factors,3 4 such as improved myocardial oxygen delivery, decreased sympathetic activity, left ventricular transmural pressure, and afterload.
Effects of CPAP on Heart Failure Patients With CSA
In 43% (9 of 21) of the patients with CSA, application of
CPAP (7±2 cm H2O) resulted in virtual
normalization of disordered breathing (Figure 2). In these
patients, the average AHI decreased from 36 to 4 per hour and central
apnea index decreased from 23 to 2 per hour. As a result,
arterial oxyhemoglobin desaturation was virtually
eliminated and arousal index decreased considerably from 21 to 11 per
hour. The latter was due to reduction in disordered breathing–related
arousal index, which decreased from 12 to 2 per hour
(P=0.008).
Despite considerable improvement in periodic breathing, CPAP failed to improve sleep efficiency and wakefulness after sleep onset. This appears to be unique to patients with heart failure, both with OSA and CSA even after long-term use.8 In contrast, even short-term application of CPAP in OSA without heart failure usually improves sleep characteristics.5
The majority of patients with heart failure and CSA failed to acutely respond to CPAP. We progressively increased CPAP level to eliminate central apnea. However, the number of episodes of central apnea remained relatively unchanged (see Results). Upper airway occlusion is known to occur in patients with CSA,15 and Issa and Sullivan16 showed that high level (9 to 16.5 cm H2O) CPAP was required to eliminate CSA in patients without known left ventricular systolic dysfunction. In the present study in heart failure patients with CSA, we increased the pressure hoping to prevent CSA, but high level CPAP failed to eliminate these apneas in 57% of the patients and the mean AHI and central apnea index remained unchanged. These data suggest that even if upper airway collapse occurred in CSA, elimination of occlusion by CPAP did not eliminate CSA, indicating that pathogenesis of CSA and OSA differs at least in most patients with heart failure. This conclusion is further supported by the only patient with predominant episodes of OSA, which were completely eliminated by CPAP (obstructive AHI was zero); episodes of CSA increased (see Results).
We can only speculate why in 57% of patients with heart failure, CSA
does not respond to CPAP. We found no significant differences in any of
the demographics between CPAP-responsive and nonresponsive (Table 1). The only significant difference, however, was that
nonresponsive patients had a more severe sleep apnea than responsive
patients (AHI=62±22 versus 36±15 per hour). In the face of severe
CSA, during the periods of repetitive cyclical hyperventilation after
episodes of central apnea, CPAP may result in arousability that
promotes ventilatory instability.17 Irrespective of the
mechanism, however, severe CSA could be an important predictor of
long-term CPAP nonresponsiveness in heart failure patients.
Effects of CPAP on Ventricular Irritability During
Sleep
Comparing baseline to CPAP, there were no significant changes in
the hourly rates of various ventricular arrhythmias
in CPAP nonresponders (Table 2). However, in heart failure
patients whose disordered breathing improved with CPAP,
ventricular arrhythmias decreased. The hourly rate
(during sleep) of premature ventricular contractions
decreased from 66 to 18 (P=0.055), couplets from 3.2 to 0.2
per hour (P=0.031), and ventricular
tachycardias from 1.1 to 0.05 per hour. We acknowledge that
the number of patients was small (n=8 in each group) and normally there
is considerable intra-individual variability in ventricular
arrhythmias, yet the mean values of the various
ventricular arrhythmias did not change
significantly in CPAP nonresponders (Table 2).
There are at least 2 explanations for reduction in
ventricular irritability in CPAP-responsive patients. CPAP
improved arterial oxyhemoglobin desaturation and the number
of arousals (Table 2), both of which are associated with
sympathetic overactivity.18 19 20 21 22 23 In addition, improved
saturation may have also improved myocardial oxygen delivery.
Although we did not measure sympathetic activity, this has been shown repeatedly in various studies and under a variety of circumstances. The studies of Somers and colleagues have shown increased sympathetic activity with arousals in normal men18 and men with central19 and OSA.20 Studies by Naughton and associates23 have shown increased plasma norepinephrine concentration in heart failure patients with CSA when compared with heart failure patients without CSA; and application of nasal CPAP decreased both norepinephrine plasma concentration and urinary excretion. Furthermore, it has been shown that major ventricular arrhythmias are associated with and potentially caused by cardiac sympathetic overactivity.24 Therefore, it is perhaps reasonable to speculate that the decrease in ventricular arrhythmias by CPAP was mediated by decreased sympathetic activity secondary to decrease in the number of arousals and improved saturation.
Decreased sympathetic activity by CPAP also decreases systemic vascular resistance and transmural left ventricular pressure, the latter in part due to changes in intrathoracic pressure as well.25 Thus, CPAP decreases left ventricular afterload resulting in an increase in left ventricular ejection fraction and improved pump failure.8 Because sudden death, presumably caused by ventricular arrhythmias, and pump failure are the 2 major causes of death in heart failure patients, CPAP by decreasing ventricular arrhythmias, as noted in the present study, and improving ejection fraction8 may improve survival in heart failure.
Decreased cardiac output and hypotension are potential complications of CPAP. We did not monitor hemodynamics during sleep; however, in our study none of the patients complained of chest discomfort or dizziness with use of CPAP. Regarding safety of CPAP in heart failure patients, 2 points are emphasized. Our patients were ambulatory and stable, and no one was in class IV of New York Heart Association classification. Most importantly, CPAP was increased gradually by increments of 1 cm H2O. In contrast, in studies which have reported decreased cardiac output, CPAP was used at predetermined high pressures, eg, 10 cm H2O. One study using the latter approach reported that heart failure patients with atrial fibrillation were particularly sensitive to CPAP.26 In our study, there were 5 patients with atrial fibrillation, and no one reported any adverse effects with gradual titration. Heart failure patients with low intravascular volume, receiving vasodilators or ß-blockers may not be able to increase venous return to compensate for the sudden increases in intrathoracic pressure. Our data in 29 heart failure patients suggest that gradual titration of CPAP is a safe procedure. We avoid application of CPAP at a predetermined pressure of >5 cm H2O to patients with heart failure.
Limitations of This Study
As noted in Methods, for uniformity only male subjects were
studied. We therefore acknowledge that the results of this study may
not necessarily be applicable to female patients with heart
failure.
As also noted in Methods, in the absence of esophageal pressure, classification of central versus obstructive disordered breathing events might have not been always accurate and some misclassification might have occurred. However, independent of the kind of sleep apnea, the results of this study show that CPAP virtually eliminated sleep-disordered breathing in 55% of the heart failure patients and improved ventricular arrhythmias. Therefore, the impact of this finding in a typical patient with heart failure and sleep apnea cannot be overemphasized.
Meanwhile, regarding classification of disordered breathing into
central versus obstructive disordered breathing, the results of our
studies and others suggest that misclassification of events should be
limited. In all our studies, polysomnograms were scored blindly.
Afterward, when the disordered breathing events were matched with
demographics of patients, we have consistently observed that
those patients classified as OSA are significantly heavier and have a
higher prevalence of snoring1 than those classified as CSA
(Table 1). Furthermore, with our pharmacological studies, eg,
theophylline,12 13 as expected, only disordered breathing
events classified central in nature decreased, with episodes of
obstructive apnea remaining unchanged. Finally, in a study using
esophageal balloon, it was concluded that thoracoabdominal excursions
(measured qualitatively by mercury strain gauges) alone had a positive
predictive value of 0.96 for classifying central or obstructive
apneas.27
In summary, the results of this study show that CPAP is effective in eliminating sleep apnea in the majority of heart failure patients. As a result, arterial oxyhemoglobin saturation improves and the number of arousals and nocturnal ventricular irritability decrease. We speculate that long-term CPAP may favorably influence the natural history of heart failure and its morbidity and mortality.
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Acknowledgments |
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This work was supported by Merit Review Grants from the Department of Veterans Affairs.
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Footnotes |
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Reprint requests to S. Javaheri, MD, Pulmonary Section (111F), VA Medical Center, Cincinnati, OH 45220.
Received June 9, 1999; revision received August 18, 1999; accepted August 31, 1999.
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V. K. Somers, D. P. White, R. Amin, W. T. Abraham, F. Costa, A. Culebras, S. Daniels, J. S. Floras, C. E. Hunt, L. J. Olson, et al. Sleep Apnea and Cardiovascular Disease: An American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health) J. Am. Coll. Cardiol., August 19, 2008; 52(8): 686 - 717. [Full Text] [PDF]
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A. Garcia-Touchard, V. K. Somers, L. J. Olson, and S. M. Caples Central Sleep Apnea: Implications for Congestive Heart Failure Chest, June 1, 2008; 133(6): 1495 - 1504. [Abstract] [Full Text] [PDF]
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C. M. Ryan, S. Juvet, R. Leung, and T. D. Bradley Timing of Nocturnal Ventricular Ectopy in Heart Failure Patients With Sleep Apnea Chest, April 1, 2008; 133(4): 934 - 940. [Abstract] [Full Text] [PDF]
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J. S. Allam, E. J. Olson, P. C. Gay, and T. I. Morgenthaler Efficacy of Adaptive Servoventilation in Treatment of Complex and Central Sleep Apnea Syndromes Chest, December 1, 2007; 132(6): 1839 - 1846. [Abstract] [Full Text] [PDF]
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 O. Oldenburg, L. Faber, J. Vogt, A. Dorszewski, F. Szabados, D. Horstkotte, and B. Lamp Influence of cardiac resynchronisation therapy on different types of sleep disordered breathing Eur J Heart Fail, August 1, 2007; 9(8): 820 - 826. [Abstract] [Full Text] [PDF]
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S. Garrigue, J.-L. Pepin, P. Defaye, F. Murgatroyd, Y. Poezevara, J. Clementy, and P. Levy High Prevalence of Sleep Apnea Syndrome in Patients With Long-Term Pacing: The European Multicenter Polysomnographic Study Circulation, April 3, 2007; 115(13): 1703 - 1709. [Abstract] [Full Text] [PDF]
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 E. N. Simantirakis and P. E. Vardas Cardiac pacing in sleep apnoea: diagnostic and therapeutic implications. Europace, November 1, 2006; 8(11): 984 - 987. [Abstract] [Full Text] [PDF]
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B. Shivalkar, C. Van De Heyning, M. Kerremans, D. Rinkevich, J. Verbraecken, W. De Backer, and C. Vrints Obstructive Sleep Apnea Syndrome: More Insights on Structural and Functional Cardiac Alterations, and the Effects of Treatment With Continuous Positive Airway Pressure J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1433 - 1439. [Abstract] [Full Text] [PDF]
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 E. N. Simantirakis, S. E. Schiza, S. I. Chrysostomakis, G. I. Chlouverakis, N. C. Klapsinos, N. M. Siafakas, and P. E. Vardas Atrial Overdrive Pacing for the Obstructive Sleep Apnea-Hypopnea Syndrome N. Engl. J. Med., December 15, 2005; 353(24): 2568 - 2577. [Abstract] [Full Text] [PDF]
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 A D Staniforth, S C Sporton, M J Early, J A Wedzicha, A W Nathan, and R J Schilling Ventricular arrhythmia, Cheyne-Stokes respiration, and death: observations from patients with defibrillators Heart, November 1, 2005; 91(11): 1418 - 1422. [Abstract] [Full Text] [PDF]
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K. Ferrier, A. Campbell, B. Yee, M. Richards, T. O'Meeghan, M. Weatherall, and A. Neill Sleep-Disordered Breathing Occurs Frequently in Stable Outpatients With Congestive Heart Failure Chest, October 1, 2005; 128(4): 2116 - 2122. [Abstract] [Full Text] [PDF]
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 C M Ryan, K Usui, J S Floras, and T D Bradley Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea Thorax, September 1, 2005; 60(9): 781 - 785. [Abstract] [Full Text] [PDF]
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E. Skobel, C. Norra, A. Sinha, C. Breuer, P. Hanrath, and C. Stellbrink Impact of sleep-related breathing disorders on health-related quality of life in patients with chronic heart failure Eur J Heart Fail, June 1, 2005; 7(4): 505 - 511. [Abstract] [Full Text] [PDF]
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 G. E. Meadows, D. M. O'Driscoll, A. K. Simonds, M. J. Morrell, and D. R. Corfield Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness J Appl Physiol, October 1, 2004; 97(4): 1343 - 1348. [Abstract] [Full Text] [PDF]
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A.-M. Sinha, E. C. Skobel, O.-A. Breithardt, C. Norra, K. U. Markus, C. Breuer, P. Hanrath, and C. Stellbrink Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure J. Am. Coll. Cardiol., July 7, 2004; 44(1): 68 - 71. [Abstract] [Full Text] [PDF]
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A. Chen and F. M. Kusumoto QT Dispersion: Much Ado About Something? Chest, June 1, 2004; 125(6): 1974 - 1977. [Full Text] [PDF]
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 J. C. T. Pepperell, N. A. Maskell, D. R. Jones, B. A. Langford-Wiley, N. Crosthwaite, J. R. Stradling, and R. J. O. Davies A Randomized Controlled Trial of Adaptive Ventilation for Cheyne-Stokes Breathing in Heart Failure Am. J. Respir. Crit. Care Med., November 1, 2003; 168(9): 1109 - 1114. [Abstract] [Full Text] [PDF]
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R. Wolk, T. Kara, and V. K. Somers Sleep-Disordered Breathing and Cardiovascular Disease Circulation, July 8, 2003; 108(1): 9 - 12. [Full Text] [PDF]
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J. o-D. L. Lattimore, D. S. Celermajer, and I. Wilcox Obstructive sleep apnea and cardiovascular disease J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1429 - 1437. [Abstract] [Full Text] [PDF]
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 P. V. Tishler, E. K. Larkin, M. D. Schluchter, and S. Redline Incidence of Sleep-Disordered Breathing in an Urban Adult Population: The Relative Importance of Risk Factors in the Development of Sleep-Disordered Breathing JAMA, May 7, 2003; 289(17): 2230 - 2237. [Abstract] [Full Text] [PDF]
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A. Malhotra, V. V. Muse, and E. J. Mark Case 12-2003 - An 82-Year-Old Man with Dyspnea and Pulmonary Abnormalities N. Engl. J. Med., April 17, 2003; 348(16): 1574 - 1585. [Full Text] [PDF]
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T. D. Bradley and J. S. Floras Sleep Apnea and Heart Failure: Part II: Central Sleep Apnea Circulation, April 8, 2003; 107(13): 1822 - 1826. [Full Text] [PDF]
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P. A. Lanfranchi, V. K. Somers, A. Braghiroli, U. Corra, E. Eleuteri, and P. Giannuzzi Central Sleep Apnea in Left Ventricular Dysfunction: Prevalence and Implications for Arrhythmic Risk Circulation, February 11, 2003; 107(5): 727 - 732. [Abstract] [Full Text] [PDF]
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S. Javaheri Pembrey's Dream: The Time Has Come for a Long-term Trial of Nocturnal Supplemental Nasal Oxygen to Treat Central Sleep Apnea in Congestive Heart Failure Chest, February 1, 2003; 123(2): 322 - 325. [Full Text] [PDF]
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 T. Kohnlein, T. Welte, L.B. Tan, and M.W. Elliott Assisted ventilation for heart failure patients with Cheyne-Stokes respiration Eur. Respir. J., October 1, 2002; 20(4): 934 - 941. [Abstract] [Full Text] [PDF]
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T Kohnlein, T Welte, L B Tan, and M W Elliott Central sleep apnoea syndrome in patients with chronic heart disease: a critical review of the current literature Thorax, June 1, 2002; 57(6): 547 - 554. [Abstract] [Full Text] [PDF]
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S. Garrigue, P. Bordier, P. Jais, D. C. Shah, M. Hocini, C. Raherison, M. Tunon De Lara, M. Haissaguerre, and J. Clementy Benefit of Atrial Pacing in Sleep Apnea Syndrome N. Engl. J. Med., February 7, 2002; 346(6): 404 - 412. [Abstract] [Full Text] [PDF]
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J. W. H. Fung, T. S. T. Li, D. K. L. Choy, G. W. K. Yip, F. W. S. Ko, J. E. Sanderson, and D. S. C. Hui Severe Obstructive Sleep Apnea Is Associated With Left Ventricular Diastolic Dysfunction Chest, February 1, 2002; 121(2): 422 - 429. [Abstract] [Full Text] [PDF]
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H. TESCHLER, J. DOHRING, Y.-M. WANG, and M. BERTHON-JONES Adaptive Pressure Support Servo-Ventilation . A Novel Treatment for Cheyne-Stokes Respiration in Heart Failure Am. J. Respir. Crit. Care Med., August 15, 2001; 164(4): 614 - 619. [Abstract] [Full Text] [PDF]
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R. M. Mehta, M. L. Groth, T. D. Bradley, F. S. Fitzgerald, D. D. Sin, P. P. Liu, and A. G. Logan Continuous Positive Airway Pressure in Patients With Congestive Heart Failure and Cheyne-Stokes Respiration With Central Sleep Apnea Response Circulation, June 12, 2001; 103 (23): e121 - e121. [Full Text] [PDF]
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D. M. Kaye, D. Mansfield, A. Aggarwal, M. T. Naughton, and M. D. Esler Acute Effects of Continuous Positive Airway Pressure on Cardiac Sympathetic Tone in Congestive Heart Failure Circulation, May 15, 2001; 103(19): 2336 - 2338. [Abstract] [Full Text] [PDF]
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